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1.  Development of the N1–P2 auditory evoked response to amplitude rise time and rate of formant transition of speech sounds 
Neuroscience letters  2013;544:56-61.
We investigated the development of weighting strategies for acoustic cues by examining the morphology of the N1–P2 auditory evoked potential (AEP) to changes in amplitude rise time (ART) and rate of formant transition (RFT) of consonant–vowel (CV) pairsin4–6-year olds and adults. In the AEP session, individuals listened passively to the CVs /ba/, /wa/, and a /ba/ with a superimposed slower-rising /wa/ envelope (/ba/wa). In the behavioral session, individuals listened to the same stimuli and judged whether they heard a /ba/ or /wa/. We hypothesized that a developmental shift in weighting strategies should be reflected in a change in the morphology of the N1–P2 AEP. In 6-year olds and adults, the N1–P2 amplitude at the vertex reflected a change in RFT but not in ART. In contrast, in the 4–5-year olds, the vertex N1–P2 did not show specificity to changes in ART or RFT. In all groups, the N1–P2 amplitude at channel C4 (right hemisphere) reflected a change in ART but not in RFT. Behaviorally, 6-year olds and adults predominately utilized RFT cues (classified /ba/wa as /ba/) during phonetic judgments, as opposed to 4–5-year olds which utilized both cues equally. Our findings suggest that both ART and RFT are encoded in the auditory cortex, but an N1–P2 shift toward the vertex following age 4–5 indicates a shift toward an adult-like weighting strategy, such that, to utilize RFT to a greater extent.
PMCID: PMC3756151  PMID: 23570734
Auditory evoked potential; Consonant–vowel; Development; Speech; Amplitude rise time; Formant transition
2.  Do adults with cochlear implants rely on different acoustic cues for phoneme perception than adults with normal hearing? 
Several acoustic cues specify any single phonemic contrast. Nonetheless, adult, native speakers of a language share weighting strategies, showing preferential attention to some properties over others. Cochlear implant (CI) signal processing disrupts the salience of some cues: in general, amplitude structure remains readily available, but spectral structure less so. This study asked how well speech recognition is supported if CI users shift attention to salient cues not weighted strongly by native speakers.
20 adults with CIs participated. The /bɑ/-/wɑ/ contrast was used because spectral and amplitude structure varies in correlated fashion for this contrast. Normal-hearing adults weight the spectral cue strongly, but the amplitude cue negligibly. Three measurements were made: labeling decisions, spectral and amplitude discrimination, and word recognition.
Outcomes varied across listeners: some weighted the spectral cue strongly, some weighted the amplitude cue, and some weighted neither. Spectral discrimination predicted spectral weighting. Spectral weighting explained the most variance in word recognition. Age of onset of hearing loss predicted spectral weighting, but not unique variance in word recognition.
The weighting strategies of listeners with normal hearing likely support speech recognition best, so efforts in implant design, fitting, and training should focus on developing those strategies.
PMCID: PMC4008700  PMID: 24686722
3.  Visual context due to speech-reading suppresses the auditory response to acoustic interruptions in speech 
Speech reading enhances auditory perception in noise. One means by which this perceptual facilitation comes about is through information from visual networks reinforcing the encoding of the congruent speech signal by ignoring interfering acoustic signals. We tested this hypothesis neurophysiologically by acquiring EEG while individuals listened to words with a fixed portion of each word replaced by white noise. Congruent (meaningful) or incongruent (reversed frames) mouth movements accompanied the words. Individuals judged whether they heard the words as continuous (illusion) or interrupted (illusion failure) through the noise. We hypothesized that congruent, as opposed to incongruent, mouth movements should further enhance illusory perception by suppressing the auditory cortex's response to interruption onsets and offsets. Indeed, we found that the N1 auditory evoked potential (AEP) to noise onsets and offsets was reduced when individuals experienced the illusion during congruent, but not incongruent, audiovisual streams. This N1 inhibitory effect was most prominent at noise offsets, suggesting that visual influences on auditory perception are instigated to a greater extent during noisy periods. These findings suggest that visual context due to speech-reading disengages (inhibits) neural processes associated with interfering sounds (e.g., noisy interruptions) during speech perception.
PMCID: PMC4078912  PMID: 25053937
audiovisual integration; auditory evoked potentials; degraded speech; illusory filling-in; phonemic restoration
4.  Larval nutrition differentially affects adult fitness and Plasmodium development in the malaria vectors Anopheles gambiae and Anopheles stephensi 
Parasites & Vectors  2013;6:345.
Mosquito fitness is determined largely by body size and nutritional reserves. Plasmodium infections in the mosquito and resultant transmission of malaria parasites might be compromised by the vector’s nutritional status. We studied the effects of nutritional stress and malaria parasite infections on transmission fitness of Anopheles mosquitoes.
Larvae of Anopheles gambiae sensu stricto and An. stephensi were reared at constant density but with nutritionally low and high diets. Fitness of adult mosquitoes resulting from each dietary class was assessed by measuring body size and lipid, protein and glycogen content. The size of the first blood meal was estimated by protein analysis. Mosquitoes of each dietary class were fed upon a Plasmodium yoelii nigeriensis-infected mouse, and parasite infections were determined 5 d after the infectious blood meal by dissection of the midguts and by counting oocysts. The impact of Plasmodium infections on gonotrophic development was established by dissection.
Mosquitoes raised under low and high diets emerged as adults of different size classes comparable between An. gambiae and An. stephensi. In both species low-diet females contained less protein, lipid and glycogen upon emergence than high-diet mosquitoes. The quantity of larval diet impacted strongly upon adult blood feeding and reproductive success. The prevalence and intensity of P. yoelii nigeriensis infections were reduced in low-diet mosquitoes of both species, but P. yoelii nigeriensis impacted negatively only on low-diet, small-sized An. gambiae considering survival and egg maturation. There was no measurable fitness effect of P. yoelii nigeriensis on An. stephensi.
Under the experimental conditions, small-sized An. gambiae expressed high mortality, possibly caused by Plasmodium infections, the species showing distinct physiological concessions when nutrionally challenged in contrast to well-fed, larger siblings. Conversely, An. stephensi was a robust, successful vector regardless of its nutrional status upon emergence. The data suggest that small-sized An. gambiae, therefore, would contribute little to malaria transmission, whereas this size effect would not affect An. stephensi.
PMCID: PMC4029273  PMID: 24326030
Anopheles gambiae sensu stricto; Anopheles stephensi; Mosquito; Plasmodium yoelii nigeriensis; Blood-feeding; Body size; Fitness
5.  Neural restoration of degraded audiovisual speech 
Neuroimage  2011;60(1):530-538.
When speech is interrupted by noise, listeners often perceptually “fill-in” the degraded signal, giving an illusion of continuity and improving intelligibility. This phenomenon involves a neural process in which the auditory cortex (AC) response to onsets and offsets of acoustic interruptions is suppressed. Since meaningful visual cues behaviorally enhance this illusory filling-in, we hypothesized that during the illusion, lip movements congruent with acoustic speech should elicit a weaker AC response to interruptions relative to static (no movements) or incongruent visual speech. AC response to interruptions was measured as the power and inter-trial phase consistency of the auditory evoked theta band (4-8 Hz) activity of the electroencephalogram (EEG) and the N1 and P2 auditory evoked potentials (AEPs). A reduction in the N1 and P2 amplitudes and in theta phase-consistency reflected the perceptual illusion at the onset and/or offset of interruptions regardless of visual condition. These results suggest that the brain engages filling-in mechanisms throughout the interruption, which repairs degraded speech lasting up to ~250 ms following the onset of the degradation. Behaviorally, participants perceived greater speech continuity over longer interruptions for congruent compared to incongruent or static audiovisual streams. However, this specific behavioral profile was not mirrored in the neural markers of interest. We conclude that lip-reading enhances illusory perception of degraded speech not by altering the quality of the AC response, but by delaying it during degradations so that longer interruptions can be tolerated.
PMCID: PMC3288427  PMID: 22178454
Audiovisual integration; Auditory Evoked Potentials; EEG; Illusory filling-in; phase-locking; Theta band
6.  Antibodies to metabotropic glutamate receptor 5 in the Ophelia syndrome 
Neurology  2011;77(18):1698-1701.
To report the metabotropic glutamate receptor 5 (mGluR5) as the autoantigen of antibodies from 2 patients with Hodgkin lymphoma (HL) and limbic encephalopathy (Ophelia syndrome).
Immunohistochemistry with brain tissue and cultures of rat hippocampal neurons were used to demonstrate antibodies. Immunoprecipitation, mass spectrometry, and mGluR5-null mice served to identify the antigen. HEK293 cells transfected with mGluR5 or mGluR1 were used to determine immunologic crossreactivity.
Both patients developed symptoms consistent with limbic encephalopathy; one had MRI findings typical of this disorder and the other had more extensive radiologic involvement, including parietal and occipital cortex. Patients' sera had antibodies that predominantly reacted with the neuropil of hippocampus and cell surface of live hippocampal neurons. Immunoprecipitation from cultured neurons and mass spectrometry demonstrated that the antigen was mGluR5, a receptor involved in processes of learning and memory. The reactivity of patients' sera was abrogated in brain of mGluR5-null mice, further confirming the antibody specificity. Studies with a large number of controls including 2 patients with cerebellar ataxia and mGluR1 antibodies showed that mGluR5 was only identified by sera of the 2 patients with the Ophelia syndrome, and that despite the homology of this receptor with mGluR1 each autoantigen was specific for a distinct syndrome.
Antibodies to mGluR5 should be considered in patients with symptoms of limbic encephalitis and HL (Ophelia syndrome). Recognition of this disorder is important because it can affect young individuals and is reversible.
PMCID: PMC3208954  PMID: 22013185
7.  Etomidate and mortality in cirrhotic patients with septic shock 
Clinical effects and outcomes of a single dose etomidate prior to intubation in the intensive care setting is controversial. The aim of this study is to evaluate the association of a single dose effect of etomidate prior to intubation on the mortality of septic cirrhotic patients and the impact of the subsequent use of low dose hydrocortisone.
This is a nested-cohort study within a randomized double blind placebo controlled study evaluating the use of low dose hydrocortisone in cirrhotic septic patients. Cirrhotic septic patients ≥ 18 years were included in the study. Patients who received etomidate prior to intubation were compared to those who did not receive etomidate for all cause 28-day mortality as a primary outcome.
Sixty two intubated patients out of the 75 patients randomized in the initial trial were eligible for this study. Twenty three of the 62 intubated patients received etomidate dose prior to intubation. Etomidate use was not associated with all cause 28-day mortality or hospital mortality but was associated with significantly higher ICU mortality (91% vs. 64% for etomidate and controls groups, respectively; p = 0.02). Etomidate patients who received subsequent doses of hydrocortisone required lower doses of vasopressors and had more vasopressor-free days but no improvement in mortality.
In this group of septic cirrhotic patients with very high mortality, etomidate increased ICU mortality. Subsequent use of hydrocortisone appears to have no benefit beyond decreasing vasopressor requirements. The lowest mortality was observed in patients who did not receive etomidate but received hydrocortisone.
PMCID: PMC3295685  PMID: 22208901
8.  Neurophysiological Influence of Musical Training on Speech Perception 
Does musical training affect our perception of speech? For example, does learning to play a musical instrument modify the neural circuitry for auditory processing in a way that improves one's ability to perceive speech more clearly in noisy environments? If so, can speech perception in individuals with hearing loss (HL), who struggle in noisy situations, benefit from musical training? While music and speech exhibit some specialization in neural processing, there is evidence suggesting that skills acquired through musical training for specific acoustical processes may transfer to, and thereby improve, speech perception. The neurophysiological mechanisms underlying the influence of musical training on speech processing and the extent of this influence remains a rich area to be explored. A prerequisite for such transfer is the facilitation of greater neurophysiological overlap between speech and music processing following musical training. This review first establishes a neurophysiological link between musical training and speech perception, and subsequently provides further hypotheses on the neurophysiological implications of musical training on speech perception in adverse acoustical environments and in individuals with HL.
PMCID: PMC3115576  PMID: 21716639
auditory cortex; speech perception; musical training; hearing loss; speech in noise; EEG; MEG; neuroplasticity
9.  Timeliness of syndromic influenza surveillance through work and school absenteeism 
Archives of Public Health  2010;68(3):115-120.
In this paper, we investigate the usefulness of work and school absenteeism surveillance as an early warning system for influenza. In particular, time trends in daily absenteeism rates collected during the A(H1N1)2009 pandemic are compared with weekly incidence rates of influenza-like illness (ILI) obtained from the Belgian Sentinel General Practitioner (SGP) network. The results indicate a rise in absenteeism rates prior to the onset of the influenza epidemic, suggesting that absenteeism surveillance is a promising tool for early warning of influenza epidemics. To convincingly conclude on the usefulness of absenteeism data for early warning, additional data covering several influenza seasons is needed.
PMCID: PMC3463027
School absenteeism; worker absenteeism; influenza; influenza A virus; H1N1 subtype
10.  Influenza vaccination recording system in Belgium 
Archives of Public Health  2010;68(3):109-114.
PMCID: PMC3463028
11.  Influenza surveillance in children: first experiences with the Belgian Paediatric Surveillance system 'PediSurv' 
Archives of Public Health  2010;68(3):94-99.
PMCID: PMC3463030
Influenza; paediatrics; A(H1N1)2009; epidemiology
12.  Clinical surveillance of the influenza A(H1N1)2009 pandemic through the network of sentinel general practitioners 
Archives of Public Health  2010;68(2):62-67.
PMCID: PMC3463021
Sentinel surveillance; family practice; Influenza; Influenza A virus; H1N1 Subtype
13.  Neural timecourse of echo suppression in humans 
In reverberant environments, the brain can suppress echoes so that auditory perception is dominated by the primary or leading sounds. Echo suppression comprises at least two distinct phenomena whose neural bases are unknown: spatial translocation of an echo toward the primary sound, and object capture to combine echo and primary sounds into a single event. In an electroencephalography (EEG) study, we presented subjects with primary-echo (leading-lagging) click pairs in virtual acoustic space, with inter-click delay at the individual's 50% suppression threshold. On each trial, subjects reported both click location (one or both hemi-fields) and the number of clicks they heard (1 or 2). Thus, the threshold stimulus led to two common percepts: Suppressed and Not Suppressed. On some trials, a subset of subjects reported an Intermediate percept, in which two clicks were perceived in the same hemi-field as the leading click, providing a dissociation between spatial translocation and object capture. We conducted time-frequency and event-related potential (ERP) analyses to examine the timecourse of the neural mechanisms mediating echo suppression. Enhanced gamma band phase synchronization (peaking at ~40 Hz) specific to successful echo suppression was evident from 20 – 60 ms post-stimulus. N1 latency provided a categorical neural marker of spatial translocation, while N1 amplitude still reflected the physical presence of a second (lagging) click. These results provide evidence that: 1) echo suppression begins early, at the latest when the acoustic signal first reaches cortex, and 2) the brain spatially translocates a perceived echo before the primary sound captures it.
PMCID: PMC2835501  PMID: 20130199
auditory; EEG; binaural hearing; spatial perception; gamma; Hearing
14.  Brain oscillations during semantic evaluation of speech 
Brain and cognition  2009;70(3):259-266.
Changes in oscillatory brain activity have been related to perceptual and cognitive processes such as selective attention and memory matching. Here we examined brain oscillations, measured with electroencephalography (EEG), during a semantic speech processing task that required both lexically mediated memory matching and selective attention. Participants listened to nouns spoken in male and female voices, and detected an animate target (p = 20%) in a train of inanimate standards or vice versa. For a control task, subjects listened to the same words and detected a target male voice in standards of a female voice or vice versa. The standard trials of the semantic task showed enhanced upper beta (25–30 Hz) and gamma band (GBA, 30-60 Hz) activity compared to the voice task. Upper beta and GBA enhancement was accompanied by a suppression of alpha (8–12 Hz) and lower to mid beta (13–20 Hz) activity mainly localized to posterior electrodes. Enhancement of phase-locked theta activity peaking near 275 ms also occurred over the midline electrodes. Theta, upper beta, and gamma band enhancement may reflect lexically mediated template matching in auditory memory, whereas the alpha and beta suppression likely indicate increased attentional processes and memory demands.
PMCID: PMC2683907  PMID: 19324486
EEG; Gamma band activity; Theta activity; Alpha activity; Beta activity; Semantic; Speech
15.  Attentional Gain Control of Ongoing Cortical Speech Representations in a “Cocktail Party” 
Normal listeners possess the remarkable perceptual ability to select a single speech stream among many competing talkers. However, few studies of selective attention have addressed the unique nature of speech as a temporally extended and complex auditory object. We hypothesized that sustained selective attention to speech in a multi-talker environment would act as gain control on the early auditory cortical representations of speech. Using high-density electroencephalography and a template-matching analysis method, we found selective gain to the continuous speech content of an attended talker, greatest at a frequency of 4–8 Hz, in auditory cortex. In addition, the difference in alpha power (8–12 Hz) at parietal sites across hemispheres indicated the direction of auditory attention to speech, as has been previously found in visual tasks. The strength of this hemispheric alpha lateralization, in turn, predicted an individual’s attentional gain of the cortical speech signal. These results support a model of spatial speech stream segregation, mediated by a supramodal attention mechanism, enabling selection of the attended representation in auditory cortex.
PMCID: PMC2832933  PMID: 20071526
auditory cortex; speech; selective attention; EEG; spatial attention; oscillations
16.  Treating Octogenarian and Nonagenarian Acute Myeloid Leukemia Patients — Predictive Prognostic Models 
Cancer  2009;115(11):2472-2481.
Treating the octogenarian and nonagenarian acute myeloid leukemia (AML) patients with intensive chemotherapy is controversial. Several models to predict outcome were proposed including the use of a co-morbidity index. However, it is unclear whether Charlson Co-morbidity Index (CCI) or Hematopoietic Cell Transplant Co-morbidity Index (HCTCI) is more sensitive.
We analyzed our experience with 92 AML patients ≥80 years old. We recorded the patients’ pretreatment characteristics and their treatment outcome.
All patients were offered intensive treatment; 59 (64%) were treated intensively with a variety of regimens while 33 (36%) elected to receive supportive care. CCI and HCTCI had similar predictive ability for outcome in both groups. Multivariate analyses of the prognostic factors identified near-normal albumin (48% of the patients; 1-year survival rate >27%) as a favorable factor for the whole cohort, age <83 (47% of the patients; 1-year survival rate >25%) and non-monocytic morphology (75% of the patients; 1-year survival rate >26%) for the intensively-treated cohort and bone marrow blasts <46% (50% of the patients; 1-year survival rate >19%) for those who received supportive care.
This retrospective analysis was developed to assist in treatment decisions for octogenarian and nonagenarian AML patients. These findings will need validation in a prospective study.
PMCID: PMC2688783  PMID: 19322894
17.  Clinical experience with alteplase in the management of intracardiac and major cardiac vessels thrombosis in pediatrics: a case series 
Annals of Saudi Medicine  2010;30(3):227-232.
Experience with alteplase in pediatric patients is limited and recommendations are extrapolated from adult data. Comprehensive guidelines on the management of thromboembolic events in this group are lacking. We assessed the efficacy and safety of alteplase (recombinant tissue plasminogen activator) in the management of intracardiac and major cardiac vessel thrombosis in pediatric patients.
All pediatric patients, 14 years of age and younger, with intracardiac or major cardiac vessel thrombus who were treated with alteplase from 1997 to 2004 at our tertiary care institute were identified through the pharmacy database. Patient data were retrospectively evaluated for the efficacy and safety of altepase.
Five cases were eligible out of nineteen who received alteplase. Patient ages ranged from 40 days to 13 years. The initial dose of alteplase ranged from 0.3 to 0.6 mg/kg followed by a continuous infusion in three patients with a dosage range between 0.05 and 0.5 mg/kg/hr, while intermittent infusion was used in the other two patients. The duration of therapy ranged from 2 to 4 days. By the end of the treatment, two patients had complete resolution of thrombus and one had partial resolution. Two patients failed to respond and had “old” thrombus. Major bleeding events were reported in three patients. The rest had minor bleeding events.
Alteplase may effectively dissolve intracardiac thrombi, particularly when freshly formed. Continuous infusion for a long duration appears to be associated with an increased risk of major bleeding. Optimal dose and duration of infusion are still unknown.
PMCID: PMC2886874  PMID: 20427940
18.  Neural mechanisms for illusory filling-in of degraded speech 
NeuroImage  2008;44(3):1133-1143.
The brain uses context and prior knowledge to repair degraded sensory inputs and improve perception. For example, listeners hear speech continuing uninterrupted through brief noises, even if the speech signal is artificially removed from the noisy epochs. In a functional MRI study, we show that this temporal filling-in process is based on two dissociable neural mechanisms: the subjective experience of illusory continuity, and the sensory repair mechanisms that support it. Areas mediating illusory continuity include the left posterior angular gyrus (AG) and superior temporal sulcus (STS) and the right STS. Unconscious sensory repair occurs in Broca’s area, bilateral anterior insula, and pre-supplementary motor area. The left AG/STS and all the repair regions show evidence for word-level template matching and communicate more when fewer acoustic cues are available. These results support a two-path process where the brain creates coherent perceptual objects by applying prior knowledge and filling-in corrupted sensory information.
PMCID: PMC2653101  PMID: 18977448
Auditory induction; Continuity illusion; fMRI; Perceptual filling-in; Phonemic restoration; Speech
19.  Auditory training alters the physiological detection of stimulus-specific cues in humans 
Auditory training alters neural activity in humans but it is unknown if these alterations are specific to the trained cue. The objective of this study was to determine if enhanced cortical activity was specific to the trained voice-onset-time (VOT) stimuli ‘mba’ and ’ba’, or whether it generalized to the control stimulus ‘a’ that did not contain the trained cue.
Thirteen adults were trained to identify a 10 ms VOT cue that differentiated the two experimental stimuli. We recorded event-related potentials (ERPs) evoked by three different speech sounds ‘ba’ ‘mba’ and ‘a’ before and after six days of VOT training.
The P2 wave increased in amplitude after training for both control and experimental stimuli, but the effects differed between stimulus conditions. Whereas the effects of training on P2 amplitude were greatest in the left hemisphere for the trained stimuli, enhanced P2 activity was seen in both hemispheres for the control stimulus. In addition, subjects with enhanced pre-training N1 amplitudes were more responsive to training and showed the most perceptual improvement.
Both stimulus-specific and general effects of training can be measured in humans. An individual’s pre-training N1 response might predict their capacity for improvement.
N1 and P2 responses can be used to examine physiological correlates of human auditory perceptual learning.
PMCID: PMC2654261  PMID: 19028139
Auditory learning; Auditory Plasticity; Auditory training; P2; Speech training
20.  Differences in flooding tolerance between species from two wetland habitats with contrasting hydrology: implications for vegetation development in future floodwater retention areas 
Annals of Botany  2008;103(2):341-351.
Background and Aims
Plants need different survival strategies in habitats differing in hydrological regimes. This probably has consequences for vegetation development when former floodplain areas that are currently confronted with soil flooding only, will be reconnected to the highly dynamical river bed. Such changes in river management are increasingly important, especially at locations where increased water retention can prevent flooding events in developed areas. It is therefore crucial to determine the responses of plant species from relatively low-dynamic wetlands to complete submergence, and to compare these with those of species from river forelands, in order to find out what the effects of such landscape-scale changes on vegetation would be.
To compare the species' tolerance to complete submergence and their acclimation patterns, a greenhouse experiment was designed with a selection of 19 species from two contrasting sites: permanently wet meadows in a former river foreland, and frequently submerged grasslands in a current river foreland. The plants were treated with short (3 weeks) and long (6 weeks) periods of complete submergence, to evaluate if survival, morphological responses, and changes in biomass differed between species of the two habitats.
Key Results
All tested species inhabiting river forelands were classified as tolerant to complete submergence, whereas species from wet meadows showed either relatively intolerant, intermediate or tolerant responses. Species from floodplains showed in all treatments stronger shoot elongation, as well as higher production of biomass of leaves, stems, fine roots and taproots, compared with meadow species.
There is a strong need for the creation of temporary water retention basins during high levels of river discharge. However, based on the data presented, it is concluded that such reconnection of former wetlands (currently serving as meadows) to the main river bed will strongly influence plant species composition and abundance.
PMCID: PMC2707312  PMID: 18836190
Acclimation; biomass allocation; climate; complete submergence; flooding tolerance; retention areas; shoot elongation; soil flooding; waterlogging; wetland species
21.  Multisensory integration enhances phonemic restoration 
Phonemic restoration occurs when speech is perceived to be continuous through noisy interruptions, even when the speech signal is artificially removed from the interrupted epochs. This temporal filling-in illusion helps maintain robust comprehension in adverse environments and illustrates how contextual knowledge through the auditory modality (e.g. lexical) can improve perception. This study investigated how one important form of context, visual speech, affects phonemic restoration. The hypothesis was that audiovisual integration of speech should improve phonemic restoration, allowing the perceived continuity to span longer temporal gaps. Subjects listened to tri-syllabic words with a portion of each word replaced by white noise while watching lip-movement that was either congruent, temporally reversed (incongruent), or static. For each word, subjects judged whether the utterance sounded continuous or interrupted, where a “continuous” response indicated an illusory percept. Results showed that illusory filling-in of longer white noise durations (longer missing segments) occurred when the mouth movement was congruent with the spoken word compared to the other conditions, with no differences occurring between the static and incongruent conditions. Thus, phonemic restoration is enhanced when applying contextual knowledge through multisensory integration.
PMCID: PMC2663900  PMID: 19275331
23.  Recommended diagnostic criteria for paraneoplastic neurological syndromes 
Background: Paraneoplastic neurological syndromes (PNS) are defined by the presence of cancer and exclusion of other known causes of the neurological symptoms, but this criterion does not separate "true" PNS from neurological syndromes that are coincidental with a cancer.
Objective: To provide more rigorous diagnostic criteria for PNS.
Methods: An international panel of neurologists interested in PNS identified those defined as "classical" in previous studies. The panel reviewed the existing diagnostic criteria and recommended new criteria for those in whom no clinical consensus was reached in the past. The panel reviewed all reported onconeural antibodies and established the conditions to identify those that would be labelled as "well characterised". The antibody information was obtained from published work and from unpublished data from the different laboratories involved in the study.
Results: The panel suggest two levels of evidence to define a neurological syndrome as paraneoplastic: "definite" and "possible". Each level can be reached combining a set of criteria based on the presence or absence of cancer and the definitions of "classical" syndrome and "well characterised" onconeural antibody.
Conclusions: The proposed criteria should help clinicians in the classification of their patients and the prospective and retrospective analysis of PNS cases.
PMCID: PMC1739186  PMID: 15258215
24.  Effect of CPOE User Interface Design on User-Initiated Access to Educational and Patient Information during Clinical Care 
Objective: Authors evaluated whether displaying context sensitive links to infrequently accessed educational materials and patient information via the user interface of an inpatient computerized care provider order entry (CPOE) system would affect access rates to the materials.
Design: The CPOE of Vanderbilt University Hospital (VUH) included “baseline” clinical decision support advice for safety and quality. Authors augmented this with seven new primarily educational decision support features. A prospective, randomized, controlled trial compared clinicians' utilization rates for the new materials via two interfaces. Control subjects could access study-related decision support from a menu in the standard CPOE interface. Intervention subjects received active notification when study-related decision support was available through context sensitive, visibly highlighted, selectable hyperlinks.
Measurements: Rates of opportunities to access and utilization of study-related decision support materials from April 1999 through March 2000 on seven VUH Internal Medicine wards.
Results: During 4,466 intervention subject-days, there were 240,504 (53.9/subject-day) opportunities for study-related decision support, while during 3,397 control subject-days, there were 178,235 (52.5/subject-day) opportunities for such decision support, respectively (p = 0.11). Individual intervention subjects accessed the decision support features at least once on 3.8% of subject-days logged on (278 responses); controls accessed it at least once on 0.6% of subject-days (18 responses), with a response rate ratio adjusted for decision support frequency of 9.17 (95% confidence interval 4.6–18, p < 0.0005). On average, intervention subjects accessed study-related decision support materials once every 16 days individually and once every 1.26 days in aggregate.
Conclusion: Highlighting availability of context-sensitive educational materials and patient information through visible hyperlinks significantly increased utilization rates for study-related decision support when compared to “standard” VUH CPOE methods, although absolute response rates were low.
PMCID: PMC1174891  PMID: 15802487
25.  Prevalence of visual impairment in relation to the number of ophthalmologists in a given area: a nationwide approach 
Sociological and economic risk factors of visual impairment have never been described in France at a national level as the association between the number of ophthalmologists per inhabitant and visual impairment prevalence.
Two national surveys were pooled. First, 2075 institutions were selected at random from the French Health Ministry files. Second, a random, stratified sample of 356,208 citizens living in the community was selected. Blindness and low vision (LV) prevalence rates were estimated by age and gender. Geographical equities were estimated by logistic regression adjusted on age and occupational category. The association between ophthalmologist density and visual impairment prevalence rate was estimated per region. Interviews were completed with 14,603 (94.9%) of 15,403 randomly selected subjects in institutions, and 16,945 (77.8%) of 21,760 randomly selected subjects in the community. Three groups were defined from the interviews: low vision, blind, and control.
Prevalence rates were LV 2.08% and blindness 0.12%. Both rates increased exponentially with age. No major difference was found with gender. Injury was the declared reason for both LV (12%) and blindness (12%). Large regional differences in prevalence persisted for LV after adjustment on age and occupation (ORs: 0.35 to 2.10), but not for blindness. Regions with ophthalmologists below the national per capita average were usually those with higher LV prevalence.
An inverse correlation was found between ophthalmologist number and LV prevalence rates for subjects of similar age and socio-professional category. This denoted possible inequity in the provision of healthcare.
PMCID: PMC1500999  PMID: 16756661

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