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.
Audiovisual integration; Auditory Evoked Potentials; EEG; Illusory filling-in; phase-locking; Theta band
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.
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.
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.
auditory cortex; speech perception; musical training; hearing loss; speech in noise; EEG; MEG; neuroplasticity
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.
School absenteeism; worker absenteeism; influenza; influenza A virus; H1N1 subtype
Influenza; paediatrics; A(H1N1)2009; epidemiology
Sentinel surveillance; family practice; Influenza; Influenza A virus; H1N1 Subtype
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.
auditory; EEG; binaural hearing; spatial perception; gamma; Hearing
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.
EEG; Gamma band activity; Theta activity; Alpha activity; Beta activity; Semantic; Speech
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.
auditory cortex; speech; selective attention; EEG; spatial attention; oscillations
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.
BACKGROUND AND OBJECTIVES:
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.
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.
Auditory induction; Continuity illusion; fMRI; Perceptual filling-in; Phonemic restoration; Speech
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.
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.
Acclimation; biomass allocation; climate; complete submergence; flooding tolerance; retention areas; shoot elongation; soil flooding; waterlogging; wetland species
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.
Auditory learning; Auditory Plasticity; Auditory training; P2; Speech training
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.
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.
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.
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.
suspect a paraneoplastic disorder is a puzzling problem that has not
recently been studied in a large series of patients referred for
METHODS—From 422 consecutive patients with peripheral neuropathy, 26 were analysed who
concomitantly had carcinoma but no tumorous infiltration, drug
toxicity, or cachexia. Their clinical, pathological, and
electrophysiological data were analysed according to the presence of
anti-onconeural antibodies, the latency between presentation and cancer
diagnosis, and the incidence of carcinoma in the corresponding types of
neuropathy of the population of 422patients.
(group I) had anti-onconeural antibodies (six anti-Hu, one anti-CV2)
and 19 did not (groups IIA and B). In group I, subacute sensory
neuropathy (SSN) was the most frequent but other neuropathies including
demyelinating neuropathies were present. Patients in group II A had a
short latency (mean 7.88months), and a rapidly and usually severe
neuropathy which corresponded in 11/14 to an established inflammatory
disorder including neuropathy with encephalomyelitis, mononeuritis
multiplex, and acute or chronic inflammatory demyelinating
polyneuropathy (CIDP). Patients in group IIB had a long latency (mean
8.4 years) and a very chronic disorder corresponding in four of five to
an axonal non-inflammatory polyneuropathy. In this population, the
incidence of carcinoma occurring with a short latency was 47% in
sensory neuronopathy, 1.7% in Guillain-Barré syndrome, 10% in
mononeuritis multiplex and CIDP, and 4.5% in axonal polyneuropathy.
neuropathies associated with carcinoma are heterogeneous disorders.
Neuropathies occurring with a long latency with tumours probably
resulted from a coincidental association. Neuropathies which occurred
within a few years of the tumour evolved rapidly and corresponded
mostly to inflammatory disorders. As dysimmune neuropathies are
probably paraneoplastic in a limited number of cases, patients with
these disorders should probably not be investigated systematically for
carcinoma in the absence of anti-onconeural antibodies, except when the
neuropathy is associated with encephalomyelitis and probably with
vasculitis. Questions remain concerning CIDP.
OBJECTIVE--To evaluate the outcome of patients with remitting seronegative symmetrical synovitis with pitting oedema (RS3PE). METHODS--In a retrospective chart review study, we identified all the patients presenting with polyarthritis and pitting oedema in the past 20 years. We tried to recall the 24 patients with characteristics of RS3PE according to McCarty et al. Two patients had died and four could not be traced. Five could not be seen after the initial period of follow up; relevant data were obtained from their practitioner. For the remaining 13 patients, clinical, radiological, and biological evaluation was performed in our department, with the last assessment in 1993. RESULTS--The follow up period was from one to 18 years (mean 4.6 (SD 4.5) years). Eleven patients developed one or several recurrences of articular manifestations consisting of mild oligoarthritis (n = 8), definite spondyloarthropathy (n = 2), and rheumatoid arthritis (n = 1). The delay of the first recurrence was 18 months to 12 years after the first attack. Thirteen patients had no recurrence, but three of them developed remarkable features: rheumatoid factor, antinuclear antibodies (1/2000), Sjögren's syndrome. HLA B typing was performed in nine patients and revealed B7 (n = 2), B27 (n = 2) and B22 (n = 2). Isolated HLA B27 typing was performed in two other patients and was positive in one. CONCLUSION--The long term outcome of RS3PE can lead to different rheumatic diseases. RS3PE appears to be a syndrome related to the elderly onset of the rheumatic diseases, including spondyloarthropathy and rheumatoid arthritis, rather than a specific entity.