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Biomedical subjects

J Townsend

Publications and source records attributed to J Townsend.

At least 19 recordsLinked to original sources

Auditory semantic networks for words and natural sounds.

Does lexical processing rely on a specialized semantic network in the brain, or does it draw on more general semantic resources? The primary goal of this study was to compare behavioral and electrophysiological responses evoked during the processing of words, environmental sounds, and non-meaningful sounds in semantically matching or mismatching visual contexts. A secondary goal was to characterize the dynamic relationship between the behavioral and neural activities related to semantic integration using a novel analysis technique, ERP imaging. In matching trials, meaningful-sound ERPs were characterized by an extended positivity (200-600 ms) that in mismatching trials partly overlapped with centro-parietal N400 and frontal N600 negativities. The mismatch word-N400 peaked later than the environmental sound-N400 and was only slightly more posterior in scalp distribution. Single-trial ERP imaging revealed that for meaningful stimuli, the match-positivity consisted of a sensory P2 (200 ms), a semantic positivity (PS, 300 ms), and a parietal response-related positivity (PR, 500-800 ms). The magnitudes (but not the timing) of the N400 and PS activities correlated with subjects' reaction times, whereas both the latency and magnitude of the PR was correlated with subjects' reaction times. These results suggest that largely overlapping neural networks process verbal and non-verbal semantic information. In addition, it appears that semantic integration operates across different time scales: earlier processes (indexed by the PS and N400) utilize the established meaningful, but not necessarily lexical, semantic representations, whereas later processes (indexed by the PR and N600) are involved in the explicit interpretation of stimulus semantics and possibly of the required response.

Acoustic Stimulation↗

Medical, surgical, and health outcomes of gastrostomy feeding.

A prospective controlled study with repeated measures before and after surgery examined the medical, surgical, and health outcomes of gastrostomy for children with disabilities at a tertiary paediatric referral centre in the North Thames area, UK. Anthropometric measures included weight, mid-upper-arm and head circumference. Five-day prospective food diaries were completed and data on physical health and surgical outcomes recorded. Seventy-six children participated and underwent gastrostomy (44 males, 32 females; median age 3 y 4 mo, range 4 mo-17 y 5 mo), and 35/76 required an anti-reflux procedure. Categories of disability were: cerebral palsy (32/76), syndrome of chromosomal or other genetic origin (25/76), slowly progressive degenerative disease (11/76), and unconfirmed diagnosis (8/76). Most children had gross motor difficulties (99%) and were non-ambulant (83%). Oromotor problems were identified in 78% of children, 69% aspirated, and 65% were fed nasogastrically before surgery. The mean weight before surgery was -2.84 standard deviation score (SDS; SD 2.21, range -9.8 to 3.4). Two-thirds of children achieved catch-up growth postoperatively: weight-for-age (mean difference 0.51 SDS, 95% CI 0.23-0.79, p=0.001) and mid-upper arm circumference (mean difference 1.12 cm, 95% confidence interval 0.50-1.75, p=0.001). Health gains included a reduction in drooling, secretions, vomiting, and constipation. Major surgical complications were found in 13/74 children. The study provides evidence that catch-up growth and health gains are possible following gastrostomy.

Adolescent↗

Price and cigarette consumption in Europe.

OBJECTIVE: To analyse the variation in demand for tobacco according to price of cigarettes across the European region. DESIGN: Cross-sectional study. SETTING: All the 52 countries of the European region. PARTICIPANTS: For each European country, data were collected on annual per adult cigarette consumption (2000), smoking prevalence (most recent), retail price of a pack of local and foreign brand cigarettes (around 2000), the gross domestic product adjusted by purchasing power parities, and the adult population (2000). MAIN OUTCOME MEASURE: Price elasticity of demand for cigarettes (that is, the change in cigarette consumption according to a change in tobacco price) across all the European countries, estimated by double-log multiple linear regression. RESULTS: Controlling for male to female prevalence ratio, price elasticities for consumption were -0.46 (95% confidence interval (CI) -0.74 to -0.17) and -0.74 (95% CI -1.13 to -0.35) for local and foreign brand, respectively. The inverse relation between cigarette price and consumption was stronger in countries not in the European Union (price elasticity for foreign brand cigarettes of -0.8) as compared to European Union countries (price elasticity of -0.4). CONCLUSIONS: The result that, on average, in Europe smoking consumption decreases 5-7% for a 10% increase in the real price of cigarettes strongly supports an inverse association between price and cigarette smoking.

Adolescent↗

Hospital at home for chronic obstructive pulmonary disease: an integrated hospital and community based generic intermediate care service for prevention and early discharge.

Recent randomized controlled studies have reported success for hospital at home for prevention and early discharge of chronic obstructive pulmonary disease (COPD) patients using hospital based respiratory nurse specialists. This observational study reports results using an integrated hospital and community based generic intermediate care service. The length of care, readmission within 60 days and death within 60 days in the early discharge (9.37 days, 21.1%, 7%) and the prevention of admission (five to six days, 34.1%, 3.8%) are similar to previous studies. We suggest that this generic community model of service may allow hospital at home services for COPD to be introduced in more areas.

Aged↗

ERPs differentiate syllable and nonphonetic sound processing in children and adults.

We examined maturation of speech-sound-related indices of auditory event-related brain potentials (ERPs). ERPs were elicited by syllables and nonphonetic correlates in children and adults. Compared with syllables, nonphonetic stimuli elicited larger N1 and P2 in adults and P1 in children. Because the nonphonetics were more perceptually salient, this N1 effect was consistent with known N1 sensitivity to sound onset features. Based on stimulus dependence and independent component structure, children's P1 appeared to contain overlapping P2-like activity. In both subject groups, syllables elicited larger N2/N4 peaks. This might reflect sound content feature processing, more extensive for speech than nonspeech sounds. Therefore, sound detection mechanisms (N1, P2) still develop whereas sound content processing (N2, N4) is largely mature during mid-childhood; in children and adults, speech sounds are processed more extensively than nonspeech sounds 200-400 ms poststimulus.

Acoustic Stimulation↗

An evaluation of the costs, effectiveness and quality of renal replacement therapy provision in renal satellite units in England and Wales.

OBJECTIVES: To survey of the structure, processes and organisation of renal satellite units (RSUs) in England and Wales (Phase 1), and to compare the effectiveness, acceptability, accessibility and economic impact of chronic haemodialysis performed in RSUs compared to main renal units (MRUs) (Phase 2). DATA SOURCES: Phase 1: all renal satellite units in England and Wales. Phase 2: haemodialysis patients in a representative sample (based on geography, site, private--public ownership, medical input) of 12 RSUs and their MRUs. REVIEW METHODS: Phase 1 consisted of a questionnaire survey. Semi-structured interviews were held in a representative sample of 24 RSUs with the senior clinician, senior nurse and manager. Phase 2 consisted of a cross-sectional comparison of patients in these RSUs and patients in the parent MRUs deemed suitable for satellite care by senior staff. Clinical information was obtained from medical notes and unit computer systems. Generic and disease specific health-related quality of life (HRQoL) measures were used. Co-morbidity was assessed by the Wright/Khan Index, the Lister/Chandna score, the Modified Charlson Index, and the Karnofsky Performance Score. Statistical analyses compared RSU versus MRU patients and took account of the paired and clustered nature of the data. RESULTS: In Phase 1, responses were received from 74/80 (93%) of RSUs; 2600 patients were being treated in these RSUs. The interviews were generally positive about the impact of RSUs in terms of improved accessibility and a better environment for chronic haemodialysis (HD) patients, and in expanding renal replacement therapy patients (RRT) capacity. In Phase 2, some 82% of eligible patients took part, 394 patients in the 12 RSUs and 342 in the parent MRUs. The response rate was similar in both groups. There were no significant differences in clinical processes of care. Most clinical outcomes were similar, especially after pooled analysis, although a few parameters were statistically significantly different -- notably the proportion achieving Renal Association Standards for adequacy of dialysis as measured by the urea reduction ratio (URR) was higher in the RSU patients. Patient-specific quality of life did not differ except on the patient satisfaction questions from the KDQOL, which were scored higher by the RSU sample. Strength of preference for health status on and off dialysis was very similar between the groups, as were EQ-5D utilities. Major adverse events were not common in the RSU patients, although there were many hypotensive episodes on HD, a proportion of which affected the duration of the HD session. Of the costs measured, the only difference that was statistically significant was for District Nurse visits. Of particular note was that despite the MRU group having a higher proportion of patients hospitalised, this did not translate into a statistically significant budgetary impact in terms of the total cost per patient of hospitalisations or mean cost per patient per hospitalisation. CONCLUSIONS: This study has shown that RSUs are an effective alternative to MRU HD for a wide spectrum of patients. They improve geographic access for more dispersed areas and reduce patients' travel time, and are generally more acceptable to patients on several criteria. There does not seem to be an adverse impact of care in the RSUs although comparative long-term prospective data are lacking. The evidence suggests that satellite development could be successfully expanded; not all MRUs have any satellites and many have only a few. No single RSU model can be recommended but key factors would include local geography, the likely catchment population and the type of patients to be treated. There is a need for more basic budgetary information linking activity and expenditure to be available and more transparent, to perform at least an insightful top-down costing of the two care settings. Other areas suggested for further research include: a comparison of adverse events occurring in MRUs and RSUs with longer duration and larger numbers to identify more severe events, along with the more research into the scope for preventing such events, and a study into the patients deemed ineligible for satellite care. International comparisons of satellite care would also be useful.

Adult↗

Price and consumption of tobacco in Spain over the period 1965-2000.

Changes in cigarette price have had an appreciable impact on smoking prevalence in several countries. We analysed the price elasticity of demand for cigarettes (effect of price of cigarettes on tobacco consumption) between 1965 and 2000 in Spain. For total consumption of cigarettes, a 1% increase in price is associated with a 0.19% decrease of consumption (price elasticity of -0.19; P<0.01). The real price of blond cigarettes was significantly and inversely associated with blond cigarette consumption: on average, smoking prevalence decreased 1.25% for a 1% increase in the real price of cigarettes (significant price elasticity of -1.25). For black cigarettes we found a lower but still high and significant elasticity of -0.61. There is an inverse relation between price and consumption of cigarettes in Spain, indicating that interventions at the economic level (such as real increases in prices) may have an important public health impact in tobacco control.

Adult↗

Gonadotroph heterogeneity, density and distribution, and gonadotroph-lactotroph associations in the pars distalis of the male equine pituitary gland.

The intrapituitary mechanisms regulating gonadotrophin secretion in the horse remain unclear. Here, we examined seasonal and gonadal effects on the gonadotroph and lactotroph populations of male horses with the aim of defining a possible morphological basis for the differential release of gonadotrophins. Pituitaries were collected from: (i) gonadal-intact horses in the breeding season (GBS); (ii) orchidectomized horses in the breeding season (OBS); and (iii) orchidectomized horses in the nonbreeding season (ONBS). Immunohistochemistry was performed using antibodies to the luteinizing hormone (LH) beta subunit, follicle-stimulating hormone (FSH) beta subunit and prolactin. In all groups, gonadotrophs were distributed throughout the pars distalis, with dense populations detected near the borders with the pars tuberalis and pars intermedia. The numbers of LH-monohormonal, FSH-monohormonal and bihormonal cells/field were greater in GBS than in OBS and ONBS horses. Similarly, the proportion of gonadotrophs in relation to all pituitary cells was larger in gonadal-intact than orchidectomized horses. In the absence of the gonads, no effects of season were observed on these variables. Interestingly, the relative proportions of gonadotroph subtypes and the LH/FSH gonadotroph ratio were similar among groups. Furthermore, while specific gonadotroph-lactotroph associations were identified in all groups, significant gonadal effects within the breeding season and direct effects of season within orchidectomized horses were detected for the number of lactotrophs. This study reveals a gonadal-independent effect of season on the lactotroph, but not the gonadotroph population of the equine pituitary, and a clear gonadal stimulation of both cell types within the breeding season. We suggest that alterations in intercellular arrangements, rather than changes in the incidence of gonadotroph subtypes, may contribute to the differential release of gonadotrophins and, accordingly, to the intrapituitary control of fertility throughout the male equine annual reproductive cycle.

Animals↗

Routine examination of the newborn: the EMREN study. Evaluation of an extension of the midwife role including a randomised controlled trial of appropriately trained midwives and paediatric senior house officers.

OBJECTIVES: To assess the implications and cost-effectiveness of extending the role of midwives to include the routine (24-hour) examination of the healthy newborn usually carried out by junior doctors. DESIGN: The study included a prospective randomised controlled trial (RCT) with mother and baby dyads randomised to either senior house officer (SHO) or midwife for the routine examination of the newborn. Midwives and SHOs were also videoed while performing the examinations and the videos were rated by an independent consultant and senior midwife. In addition extensive interviews, surveys, consultations and assessments were carried out. SETTING: A District General Hospital (for the RCT), a London Teaching Hospital, general practices and mothers' homes (for interviews); questionnaires were sent to all maternity units in England (for the National Survey). PARTICIPANTS: A total of 826 mother and baby dyads in a District General Hospital in south-east England. Midwives and SHOs, as well as midwifery managers, paediatric consultants; general practitioners (GPs) and representatives of key organisations. INTERVENTIONS: A routine examination of a newborn baby was carried out at about 24 hours from birth and a further examination for half the babies in each group, at 10-days at home by the community midwife. MAIN OUTCOME MEASURES: Referrals assessed as appropriate and as major or minor by three independent consultants. Problems identified during the first year of life assessed as identifiable at 24 hours. Quality assessment by video against an agreed written proforma. Maternal satisfaction. Opinion of professionals and mothers about aspects of the examination. RESULTS: There was no statistical difference between SHO and midwife examinations in appropriate referral rates to hospital or community or in inappropriate referral rates to hospital. Videoed assessments were assessed as carried out more appropriately by the midwives than by the SHOs. Overall maternal satisfaction was high and higher when a midwife rather than an SHO examined. Few new health problems were identified at the 10-day examination. From the National Survey, it was estimated that about 2% of babies in England are examined by a midwife. If midwives were to examine all babies where there were no complications of birth or antenatal history, there would be savings of about 2 pounds per baby born, equivalent to savings of 1.2 pounds million nationally. Were midwives to examine all babies on normal wards savings would increase to about 4.30 pounds per baby born or 2.5 million pounds nationally. Representatives of the professional bodies were of the opinion that having trained midwives carrying out the examination would be valuable. CONCLUSIONS: All component aspects of the study were consistent in showing benefits or at least no significant barriers to suitably qualified, trained midwives carrying out the examinations. Developing the role of the midwife to include examination of the newborn is likely to result in improved quality of examinations and higher satisfaction from mothers. It would slightly reduce overall health service costs, with some increased resources needed by midwifery departments, and some decrease in resource needs of paediatric departments. There is a need for further research into the value of the examination being carried out at home rather than in hospital; the overall unsatisfactory quality of the examination of the hips; and appropriate inclusion criteria for which babies' midwives should examine.

Adult↗

A multicentre, randomized, double-blind, placebo-controlled, 1-year study of bupropion SR for smoking cessation.

BACKGROUND: Bupropion sustained release (bupropion SR) has been shown to increase smoking cessation success rates in the US studies. OBJECTIVE: To determine whether bupropion SR, in combination with counselling, is effective for smoking cessation in a multi-country study. METHODS: This randomized, double-blind, placebo-controlled trial enrolled 707 smokers. A total of 527 received bupropion SR 300 mg daily for 7 weeks and 180 received placebo. A total of 11 clinic visits and 10 telephone contacts were scheduled, during the course of 1 year. Seven-week and 12-month abstinence rates were the study outcomes. RESULTS: Both continuous and weekly point prevalence smoking abstinence rates were significantly higher in the bupropion SR group compared with placebo. The continuous abstinence rate from weeks 4 to 7 was 46% in the bupropion SR group compared with 23% in the placebo group [odds ratio (OR) = 2.82; 95% confidence interval (CI) 1.89-4.28; P < 0.001). At month 12, the continuous abstinence rates were 21% for the bupropion SR group and 11% for the placebo group (OR = 2.19; 95% CI 1.29-3.86, P = 0.002). For most nicotine-withdrawal symptoms small changes were measured. Adverse events were higher for the bupropion SR group compared with placebo (insomnia 24% vs. 15%; dry mouth 13% vs. 5%). CONCLUSION: Bupropion SR in combination with counselling increased the abstinence rate compared with placebo, and was well tolerated.

Adult↗

Toxic potential of dietary genistein isoflavone and beta-lapachone on capacitation and acrosome reaction of epididymal spermatozoa.

We determined if acrosomal reaction was influenced by exposure of sperm cells to two dietary phytochemicals, genistein isoflavone and beta-lapachone, using the rat model. Spermatozoa were capacitated in capacitating medium with or without genistein isoflavone and beta-lapachone, and the percentage of posttreatment acrosome reaction compared with controls was assessed with two fluorescent probes, chlortetracycline (CTC) and fluorescein isothiocyanate- Pisum sativum ag-glutinin conjugate (FITC-PSA). Spermatozoa were permeabilized in ethanol and labeled with the FITC-PSA or CTC to determine the acrosome status. The results revealed that calcium ionophore could induce acrosome reaction in spermatozoa and that acrosome-reacted sperm cells showed obvious darkness in the head region, whereas acrosome-intact sperm displayed bright fluorescence over the entire sperm head. The basic response and pattern of acrosome reaction status were significantly similar in both CTC and FITC assays and in both treatment (genistein and beta-lapachone) groups. It was observed that higher doses of both genistein and beta-lapachone significantly suppressed acrosome reaction and that this inhibitory effect was both dose- and time-dependent. It was stipulated that the observed genistein inhibition of acrosome reaction could be due to suppression of protein kinase C, and that beta-lapachone could inhibit acrosome reaction through direct cytotoxic effects on sperm cell membrane at higher doses. However, light microscopic examination indicated that both phytochemicals had no significant effect on sperm morphology. It is concluded that, in view of the fact that acrosome reaction is a physiological prerequisite for fertilization of most mammalian eggs, both genistein and beta-lapachone could potentially suppress male fertility via suppression of acrosome reaction at higher doses, but could enhance fertility by promoting acrosome reaction at lower doses. This bimodal mode of action of both phytochemicals could offer a potentially new dimension in the search for causes of male infertility and possibly for male contraceptive development.

Acrosome Reaction↗

Price and consumption of tobacco in Italy over the last three decades.

Changes in cigarette price have had an appreciable impact on smoking consumption in several countries. We analysed the price elasticity of demand for cigarettes in Italy over the period 1970-2001. A 1% increase in price of cigarettes led to a 0.30% decline in smoking prevalence and to a 0.43% decline in cigarette consumption. The present analyses confirm the existence of an inverse association between price and prevalence/consumption of cigarettes in Italy, and indicate that economic aspects may have important public health implications in tobacco control.

Commerce↗

The quality of routine examinations of the newborn performed by midwives and SHOs; an evaluation using video recordings.

OBJECTIVE: To evaluate the quality of the routine examination of the newborn as carried out by senior house officers (SHOs) and midwives. DESIGN: Randomised controlled trial set in a district general hospital in Southeast England. Eligible babies were randomised to a midwife (11) or an SHO (8) who were then video recorded undertaking the routine newborn examination. MAIN OUTCOME MEASURES: Quality of 62 observed technical and communication components of the newborn examination, as agreed between independent consultant paediatrician and senior midwife raters. RESULTS: Major differences were found in the rated quality of examinations between midwives and SHOs for the examinations of the heart and lungs, for the overall quality of the examination, and in areas of communication skills. Quality of examination of the hips was assessed as poor for both professional groups. Where there were significant differences between examiners, the quality of the midwives' examinations was higher. Inter-rater agreement between the consultant paediatricians and senior midwives ranged from excellent to poor for different items of the examination with a mean kappa value of 0.42 across all items indicating moderate agreement. CONCLUSIONS: The quality of midwife examinations exceeded that of SHOs. All midwives who examine receive formalized training in the examination of the newborn; SHOs may benefit from similar specific training. Training for both professional groups may need to be reviewed, particularly in relation to agreement on 'gold standards' for the screening of developmental dysplasia of the hip.

England↗

Prioritisation of health technology assessment. The PATHS model: methods and case studies.

OBJECTIVES: To develop a method of economic evaluation and triage for research prioritisation, before the funding decision. DATA SOURCES: Existing models were researched focusing on MEDLINE, HealthSTAR, IBSS and HEED. REVIEW METHODS: Papers of primary relevance that included a proposed model were reviewed in detail, and their models appraised using criteria adapted from the EUR-ASSESS project and the authors' previous experience. From this the PATHS model was developed. It assumes three or more possible alternative outcomes or scenarios in terms of research results: 'favourable' to the technology being assessed, 'unfavourable' or 'inconclusive'. An associated flow of benefits or disbenefits, costs or savings is identified for each potential research outcome depending on the likely implementation of the results as judged by experts. These benefits and costs are weighted and discounted in the model to give an expected incremental cost-effectiveness ratio (EICER). EICERS could be estimated for any number of research areas or proposals to inform funding prioritisation. The model was tested and evaluated on three case studies identified in liaison with the NHS R&D HTA programme and the UK Medical Research Council. These case studies were funded research projects, where full evaluation was underway and where results would be reported during the PATHS project. The studies were selected to include surgery or other invasive procedures, and non-invasive health services projects (a fourth case study did not complete during the course of the study). The three case studies included randomised controlled trials of early surgery or observation for small abdominal aortic aneurysms, infusion protocols for adult pre-hospital care, and postnatal midwifery support. RESULTS: Each of the three assessments indicated net clinical benefit or no clinical loss of benefit, in addition to health service cost savings in excess of the cost of the trial. For two case studies, the value of the proposed trial, as evaluated by the model in the prediction, was consistent with the ex post evaluation, thus providing positive tests of the value of the model. In the third case meaningful ex post analysis was not possible as very poor compliance with the trial protocol (indicated in the ex ante evaluation) seriously undermined its conclusions. During the study, at the request of the UK HTA programme, the model was also applied to a funding request for a large randomised trial of beta-interferon for multiple sclerosis treatment. CONCLUSION: The PATHS model has a useful part to play in the research prioritisation process. Its strengths lie in its emphasis on the impact of research results on policy and practice (the keystone for NHS research) and net effects on health benefits and costs. It assesses the cost-effectiveness of the research and may identify ways to enhance the research design, endpoints relevant to implementation, analytical methods and dissemination. Further research is recommended to investigate the scope for synthesising the strengths of the PATHS model with other approaches including value of information; to compare ex ante and immediate ex post assessments of implementation with long term follow-up of actual implementation; and to assess the robustness of such approaches to the choice and number of experts used.

Decision Support Techniques↗

Dynamic brain sources of visual evoked responses.

It has been long debated whether averaged electrical responses recorded from the scalp result from stimulus-evoked brain events or stimulus-induced changes in ongoing brain dynamics. In a human visual selective attention task, we show that nontarget event-related potentials were mainly generated by partial stimulus-induced phase resetting of multiple electroencephalographic processes. Independent component analysis applied to the single-trial data identified at least eight classes of contributing components, including those producing central and lateral posterior alpha, left and right mu, and frontal midline theta rhythms. Scalp topographies of these components were consistent with their generation in compact cortical domains.

Adult↗

Routine examination of the newborn and maternal satisfaction: a randomised controlled trial.

OBJECTIVE: To determine whether the routine examination of the newborn by a midwife compared with a junior paediatrician (SHO) affects maternal satisfaction with this examination. METHODS: Randomised controlled trial: 826 mother and baby pairs in a district general hospital in south east England were randomised to a paediatric SHO or a midwife for the routine newborn examination. Maternal satisfaction with the examination was analysed in relation to intervention group, process, and background variables. RESULTS: Some 81% of mothers reported that they were satisfied or very satisfied with the newborn examination. Mothers assigned to a midwife were more satisfied with the newborn examination (crude odds ratio (OR) 0.54 (95% confidence interval (CI) 0.39 to 0.75), p < 0.001). However, after provision of health education during the examination, continuity of care provided, and history of miscarriage had been controlled for, status of examiner was no longer related to maternal satisfaction (adjusted OR 0.82 (95% CI 0.57-1.20), NS). The discussion of healthcare issues by the examiner (adjusted OR 0.49 (95% CI 0.34 to 0.70), p < 0.001) and continuity of care (adjusted OR 0.43 (95% CI 0.23 to 0.81), p < 0.01) were both related to enhanced satisfaction, and history of miscarriage (adjusted OR 1.61 (1.08 to 2.40), p < 0.05) was associated with lower maternal satisfaction with the newborn examination. Midwives (61%) were more likely than SHOs (33%) to discuss healthcare issues, such as feeding, sleeping, and skin care. CONCLUSIONS: Mothers were more likely to be satisfied with the newborn examination by a midwife than an SHO because midwives were more likely to discuss healthcare issues during the examination and were able to provide continuity of care. However, midwife examinations according to exclusion criteria agreed with trial midwives excluded half of all newborns, and criteria may have to be reconsidered for practice implementation.

Clinical Competence↗

Association of ataxin-7 with the proteasome subunit S4 of the 19S regulatory complex.

Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disorder characterized by ataxia and selective neuronal cell loss caused by the expansion of a translated CAG repeat encoding a polyglutamine tract in ataxin-7, the SCA7 gene product. To gain insight into ataxin-7 function and to decipher the molecular mechanisms of neurodegeneration in SCA7, a two-hybrid assay was performed to identify ataxin-7 interacting proteins. Herein, we show that ataxin-7 interacts with the ATPase subunit S4 of the proteasomal 19S regulatory complex. The ataxin-7/S4 association is modulated by the length of the polyglutamine tract whereby S4 shows a stronger association with the wild-type allele of ataxin-7. We demonstrate that endogenous ataxin-7 localizes to discrete nuclear foci that also contain additional components of the proteasomal complex. Immunohistochemical analyses suggest alterations either of the distribution or the levels of S4 immunoreactivity in neurons that degenerate in SCA7 brains. Immunoblot analyses demonstrate reduced levels of S4 in SCA7 cerebella without evident alterations in the levels of other proteasome subunits. These results suggest a role for S4 and ubiquitin-mediated proteasomal proteolysis in the molecular pathogenesis of SCA7.

Adenosine Triphosphatases↗

Analysis and visualization of single-trial event-related potentials.

In this study, a linear decomposition technique, independent component analysis (ICA), is applied to single-trial multichannel EEG data from event-related potential (ERP) experiments. Spatial filters derived by ICA blindly separate the input data into a sum of temporally independent and spatially fixed components arising from distinct or overlapping brain or extra-brain sources. Both the data and their decomposition are displayed using a new visualization tool, the "ERP image," that can clearly characterize single-trial variations in the amplitudes and latencies of evoked responses, particularly when sorted by a relevant behavioral or physiological variable. These tools were used to analyze data from a visual selective attention experiment on 28 control subjects plus 22 neurological patients whose EEG records were heavily contaminated with blink and other eye-movement artifacts. Results show that ICA can separate artifactual, stimulus-locked, response-locked, and non-event-related background EEG activities into separate components, a taxonomy not obtained from conventional signal averaging approaches. This method allows: (1) removal of pervasive artifacts of all types from single-trial EEG records, (2) identification and segregation of stimulus- and response-locked EEG components, (3) examination of differences in single-trial responses, and (4) separation of temporally distinct but spatially overlapping EEG oscillatory activities with distinct relationships to task events. The proposed methods also allow the interaction between ERPs and the ongoing EEG to be investigated directly. We studied the between-subject component stability of ICA decomposition of single-trial EEG epochs by clustering components with similar scalp maps and activation power spectra. Components accounting for blinks, eye movements, temporal muscle activity, event-related potentials, and event-modulated alpha activities were largely replicated across subjects. Applying ICA and ERP image visualization to the analysis of sets of single trials from event-related EEG (or MEG) experiments can increase the information available from ERP (or ERF) data.

Alpha Rhythm↗