Search PubMed⌕ Search

Biomedical subjects

J Clarke

Publications and source records attributed to J Clarke.

At least 37 records · Page 2Linked to original sources
PubMed2004

Pilot scheme for performance assessment of HIV-1 genotypic resistance testing in the UK.

HIV-1 drug susceptibility testing by genotypic methods is now widespread in the UK and it is thus important to determine the reproducibility of such investigations. A pilot study was carried out to determine the reproducibility between laboratories of genotypic testing by nucleotide sequencing of patient samples, and to compare the interpretations of the results provided to the clinicians. Samples were distributed between the participating laboratories. Eight laboratories, using three different methods, sequenced four samples. Nucleotide sequence and reports were collated and compared by one laboratory. Where sequencing data were obtained > 99% concordance was observed for nucleotide designations. No discordances in nucleotide sequencing were found in positions associated with drug resistance. However, there were considerable differences between the laboratories in the interpretation of some of the mutations with respect to their effect on drug susceptibility. This study emphasises the variability in the available interpretation systems, and the importance of joint laboratory-clinical discussion in making decisions about treatment options.

Data Interpretation, Statistical↗
PubMed2003

Management of return-to-work programs for workers with musculoskeletal disorders: a qualitative study in three Canadian provinces.

In this qualitative research project, researchers in three Canadian provinces explored the perceptions of many different actors involved in return-to-work (RTW) programs for injured workers, studying their views on successful RTW strategies and barriers to/facilitators of the RTW process, then analyzing the underlying dynamics driving their different experiences. Each research team recruited actors in a variety of different workplaces and key informants in the RTW system, and used a combination of in-depth, semi-structured interviews and focus groups to collect data, which were coded using an open coding system. Analysis took a social constructionist perspective. The roles and mandates of the different groups of actors (injured workers; other workplace actors; actors outside the workplace), while sometimes complementary, could also differ, leading to tension and conflict. Characteristics of injured workers described as influencing RTW success included personal and sociodemographic factors, beliefs and attitudes, and motivation. Human resources managers and health care professionals tended to attribute workers' motivation to their individual characteristics, whereas injured workers, worker representatives and health and safety managers described workplace culture and the degree to which workers' well-being was considered as having a strong influence on workers' motivation. Some supervisors experienced role conflict when responsible for both production quotas and RTW programs, but difficulties were alleviated by innovations such as consideration of RTW program responsibilities in the determination of production quotas and in performance evaluations. RTW program success seemed related to labor-management relations and top management commitment to Health and Safety. Non-workplace issues included confusion stemming from the compensation system itself, communication difficulties with some treating physicians, and role conflict on the part of physicians wishing to advocate for patients whose problems were non-compensable. Several common themes emerged from the experiences related by the wide range of actors including the importance of trust, respect, communication and labor relations in the failure or success of RTW programs for injured workers.

Accidents, Occupational↗
PubMed2003

The topography of metabolic deficits in posterior cortical atrophy (the visual variant of Alzheimer's disease) with FDG-PET.

BACKGROUND: The term "posterior cortical atrophy" (PCA) refers to a clinical syndrome in which higher order visual processing is disrupted owing to a neurodegenerative disorder, the most commonly associated pathology being Alzheimer's disease. OBJECTIVE: To map the topography of hypometabolic brain regions in a group of subjects with PCA who had undergone detailed neuropsychological characterisation. METHODS: Resting cerebral metabolism was measured with ((18)F)fluorodeoxyglucose-positron emission tomography (FDG-PET) in patients with PCA (n = 6), typical Alzheimer's disease (n = 10), and healthy controls (n = 10). The data were analysed using statistical parametric mapping (SPM99) and region of interest techniques. RESULTS: Clinically, the PCA subjects showed predominant visuospatial deficits (including features of Balint's syndrome) consistent with damage to the dorsal stream of visual processing. Compared with the controls, the PCA group showed marked glucose hypometabolism primarily affecting the posterior cerebral hemispheres (right worse than left). In addition, the PCA group showed two symmetrical areas of hypometabolism in the region of the frontal eye fields. Compared with typical Alzheimer's disease, the PCA group had selective hypometabolism in the occipito-parietal region (right much worse than left). CONCLUSIONS: The neuropsychological and PET findings are consistent with damage predominantly to the dorsal stream of visual processing. Frontal eye field hypometabolism secondary to loss of input from the occipito-parietal region may be the mechanism for the ocular apraxia seen in Balint's syndrome.

Aged↗
PubMed2003

Primary human parvovirus B19 infection in an HIV infected patient on highly active antiretroviral therapy.

Adults developing primary human parvovirus B19 (B19) infection may present with arthralgia, fever, and maculopapular rash. Recovery is linked to the development of specific neutralising antibodies. In immunosuppressed patients, including those with HIV infection, such humoral responses are impaired and severe chronic bone marrow suppression and arthritis may occur.

AIDS-Related Opportunistic Infections↗
PubMed2002

Dosimetry of a low-kV intra-operative X-ray source using basic analytical beam models.

The low energy (30-50 kVp) beams from an intra-operative X-ray source are modelled using a basic analytical model considering just primary beam attenuation and absorption. Spatial dosimetry at such low energies is difficult due to the rapid changes in dose-rate from the radiation source. The purpose of the model was to determine the variation with distance in water of coefficients required for beam dosimetry and to validate beam measurements performed in water of high-gradient dose distributions. The model predicts a change in mean mass-energy absorption coefficient of up to 3 % over the range of clinically-relevant distances in water. Distance-dose distributions (variation in dose with distance in water) for the X-ray source were calculated with the model and found to be in agreement with measurement (at clinically-relevant distances), to within a spatial distance comparable to the dimensions and positional accuracy of the ionization chamber used, and comparable to the expected dosimetric anisotropy of the radiation source. Measured and calculated distance-doses begin to diverge at relatively large distances from the radiation source, which is where dose-rates are so low that detector signal levels are comparable with noise.

Absorption↗
PubMed2002

Assessing the dietetic needs of different patient groups receiving enteral tube feeding in primary care.

AIM: To examine the nature of all contacts between adult tube-fed patients and the dietetic service and to refine the current dietetic protocols to reflect the findings of the study with a view to improving patient care. METHODS: All adult patients referred to the Community Nutrition and Dietetic Service within a 6-month period were included in the study. Using a proforma developed from a retrospective case-note analysis, data were collected on the complications that prompted more frequent contacts than the department protocol. Data were analysed using the Statistical Package for the Social Sciences. RESULTS: The most common indication for home enteral feeding in this group of adult patients was a swallowing disorder resulting from a cerebrovascular accident (59.5%) followed by cancer (21.5%). There was a trend for cancer patients to need more intervention compared with those patients with other medical conditions. A significant difference was observed in the total contacts and telephone calls given to those patients in there own homes (P=0.019) and there was a trend towards more domicilary visits with this group. CONCLUSIONS: The department protocols have been revised to include a planned review within 2-6 weeks of initial dietetic assessment in the community for those patients who were identified to have the greatest need. More intensive dietetic monitoring has clear implications for dietetic services in the community.

Adolescent↗
PubMed2002

Rapid distributed fronto-parieto-occipital processing stages during working memory in humans.

Cortical potentials were recorded from implanted electrodes during a difficult working memory task requiring rapid storage, modification and retrieval of multiple memoranda. Synchronous event-related potentials were generated in distributed occipital, parietal, Rolandic and prefrontal sites beginning approximately 130 ms after stimulus onset and continuing for >500 ms. Coherent phase-locked, event-related oscillations supported interaction between these dorsal stream structures throughout the task period. The Rolandic structures generated early as well as sustained potentials to sensory stimuli in the absence of movement. Activation peaks and phase lags between synaptic populations suggested that perceptual processing occurred exclusively in the visual association cortex from approximately 90 to 130 ms, with its results projected to fronto-parietal areas for interpretation from approximately 130 to 280 ms. The direction of interaction then appeared to reverse from approximately 300 to 400 ms, consistent with mental arithmetic being performed by fronto-parietal areas operating upon a visual scratch pad in the dorsolateral occipital cortex. A second reversal, from approximately 420 to 600 ms, may have represented an updating of memoranda stored in fronto-parietal sites. Lateralized perisylvian oscillations suggested an articulatory loop. Anterior cingulate activity was evoked by feedback signals indicating errors. These results indicate how a fronto-centro-parietal 'central executive' might interact with an occipital visual scratch pad, perisylvian articulatory loop and limbic monitor to implement the sequential stages of a complex mental operation.

Adolescent↗
PubMed2002

Outcome of ventilatory support for acute respiratory failure in motor neurone disease.

OBJECTIVES: To review the outcome of acute ventilatory support in patients presenting acutely with respiratory failure, either with an established diagnosis of motor neurone disease (MND) or with a clinical event where the diagnosis of MND has not yet been established. METHODS: Outcome was reviewed in 24 patients with respiratory failure due to MND who received endotracheal intubation and intermittent positive pressure ventilation either at presentation or as a result of the unexpected development of respiratory failure. Patients presenting to local hospitals with acute respiratory insufficiency and requiring tracheal intubation, ventilatory support, and admission to an intensive therapy unit (ITU) before transfer to a regional respiratory care unit were selected. Clinical features of presentation, management, and outcome were studied. RESULTS: 24 patients with MND were identified, all being intubated and ventilated acutely within hours of presentation. 17 patients (71%) were admitted in respiratory failure before the diagnosis of MND had been made; the remaining seven patients (29%) were already known to have MND but deteriorated rapidly such that intubation and ventilation were initiated acutely. Seven patients (29%) died on ITU (between seven and 54 days after admission). 17 patients (71%) were discharged from ITU. 16 patients (67%) received long term respiratory support and one patient required no respiratory support following tracheal extubation. The daily duration of support that was required increased gradually with time. CONCLUSION: When a patient with MND is ventilated acutely, with or without an established diagnosis, independence from the ventilator is rarely achieved. Almost all of these patients need long term ventilatory support and the degree of respiratory support increases with time as the disease progresses. The aim of management should be weaning the patient to the minimum support compatible with symptomatic relief and comfort. Respiratory failure should be anticipated in patients with MND when the diagnosis has been established.

Acute Disease↗
PubMed2001

Community care.

Explore the source record for details and available documents.

Adult↗
PubMed2001

Effects of dissipation on a superconducting single electron transistor.

We measure the effect of dissipation on the minimum zero-bias conductance, G(min)0, of a superconducting single electron transistor (sSET) capacitively coupled to a two-dimensional electron gas (2DEG) in a GaAs/AlGaAs heterostructure. Depleting the 2DEG with a back gate voltage decreases the dissipation experienced by the sSET in situ. We find that G(min)0 increases as the dissipation is increased or the temperature is reduced; the functional forms of these dependences are compared with the model of Wilhelm et al. in which the leads coupled to the sSET are represented by lossy transmission lines.

Journal Article↗
PubMed2001

Mapping the folding pathway of an immunoglobulin domain: structural detail from Phi value analysis and movement of the transition state.

BACKGROUND: Do proteins that have the same structure fold by the same pathway even when they are unrelated in sequence? To address this question, we are comparing the folding of a number of different immunoglobulin-like proteins. Here, we present a detailed protein engineering phi value analysis of the folding pathway of TI I27, an immunoglobulin domain from human cardiac titin. RESULTS: TI I27 folds rapidly via a kinetic intermediate that is destabilized by most mutations. The transition state for folding is remarkably native-like in terms of solvent accessibility. We use phi value analysis to map this transition state and show that it is highly structured; only a few residues close to the N-terminal region of the protein remain completely unfolded. Interestingly, most mutations cause the transition state to become less native-like. This anti-Hammond behavior can be used as a novel means of obtaining additional structural information about the transition state. CONCLUSIONS: The residues that are involved in nucleating the folding of TI I27 are structurally equivalent to the residues that form the folding nucleus in an evolutionary unrelated fibronectin type III protein. These residues form part of the common structural core of Ig-like domains. The data support the hypothesis that interactions essential for defining the structure of these beta sandwich proteins are also important in nucleation of folding.

Connectin↗
PubMed2001

A critical review of reviews on the treatment of chronic low back pain.

STUDY DESIGN: Systematic literature review. OBJECTIVE: To critically appraise the methodology of systematic reviews of conservative therapies for chronic nonspecific low back pain and to study the relation between the methodologic quality and other characteristics of these reviews. SUMMARY OF BACKGROUND DATA: Systematic reviews offer a concise summary of the evidence on treatment effectiveness, but flaws in their methodology can lead to invalid conclusions with serious implications for quality of patient care. METHODS: Searches of MEDLINE, EMBASE, Psychinfo, and the Cochrane Library were conducted. Titles, abstracts, and articles were reviewed by two blinded authors using three inclusion criteria: 1) chronic nonspecific low back pain, 2) systematic review, and 3) conservative treatment intervention. Data were extracted from each review by three authors. RESULTS: The search strategy retrieved 1102 titles and abstracts; 109 met inclusion criteria. A review of the full text of these articles excluded an additional 73 articles. Data abstraction and methodologic assessment were conducted on 36 articles reviewing 19 discrete interventions. The average quality score was 4.1, ranging from 1 (low) to 7 (high). There was a trend for recent reviews to be of higher quality. Fifty-six percent of the reviews had positive conclusions, but they had lower quality scores compared with those that had negative or uncertain conclusions. There were 27 (73%) qualitative and 10 (27%) quantitative summaries of results. CONCLUSIONS: Although the overall quality of systematic reviews was satisfactory, the quality of the individual papers included in the reviews varied considerably. The reviews often provided contradictory evidence on the effectiveness of a wide range of commonly used conservative interventions for chronic nonspecific low back pain. These findings illustrate the pitfalls of systematic reviews where there are a number of low-quality trials and underscore the need for high-quality primary trials that will allow for more conclusive reviews.

Adolescent↗
PubMed2001

The folding nucleus of a fibronectin type III domain is composed of core residues of the immunoglobulin-like fold.

To identify the contacts that stabilise the rate-limiting transition state for folding of FNfn10 (the tenth fnIII domain of human fibronectin), 42 mutants have been analysed at 29 positions across this domain. An anomalous response to mutation means that structure formation in the A, B and G strands cannot be evaluated by this method. In all the residues analysed, phi-values are fractional and no completely structured region is observed. The analysis reveals that hydrophobic residues from the central strands of the beta-sandwich form a large core of interactions in the transition state. Brønsted analysis shows that the stabilisation energy from the amino acid side-chains in the transition state is approximately 40 % of that in the native state. The protein folds by a nucleation-condensation mechanism, and tertiary interactions within the core make up the folding nucleus. Local interactions, in turns and loops, are apparently much less significant. Comparison with an homologous domain from human tenascin (TNfn3), shows that FNfn10 has a more extended, structured transition state spanning three different "layers" of the beta-sandwich. The results support the hypothesis that interactions in the common structural core guide the folding of these domains.

Fibronectins↗