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Biomedical subjects

Richard Newton

Publications and source records attributed to Richard Newton.

17 recordsLinked to original sources

A Hidden Markov model web application for analysing bacterial genomotyping DNA microarray experiments.

Whole genome DNA microarray genomotyping experiments compare the gene content of different species or strains of bacteria. A statistical approach to analysing the results of these experiments was developed, based on a Hidden Markov model (HMM), which takes adjacency of genes along the genome into account when calling genes present or absent. The model was implemented in the statistical language R and applied to three datasets. The method is numerically stable with good convergence properties. Error rates are reduced compared with approaches that ignore spatial information. Moreover, the HMM circumvents a problem encountered in a conventional analysis: determining the cut-off value to use to classify a gene as absent. An Apache Struts web interface for the R script was created for the benefit of users unfamiliar with R. The application may be found at http://hmmgd.cryst.bbk.ac.uk/hmmgd. The source code illustrating how to run R scripts from an Apache Struts-based web application is available from the corresponding author on request. The application is also available for local installation if required.

Algorithms↗

Islet autoimmunity in children with Down's syndrome.

There is an unexplained excess of type 1 diabetes and other organ-specific autoimmune diseases in children with Down's syndrome, but the immunogenetic characteristics of diabetes in Down's syndrome have not been investigated. We studied the frequency of islet autoantibodies in 106 children with Down's syndrome and no history of autoimmunity and analyzed HLA class II genotypes in 222 children with Down's syndrome, 40 children with Down's syndrome and type 1 diabetes, 120 age- and sex-matched children with type 1 diabetes, and 621 healthy control subjects. Co-occurrence of at least two islet autoantibody markers was observed in 6 of 106 nondiabetic children with Down's syndrome compared with 13 of 2,860 healthy age-matched children (P < 0.001). There was an excess of diabetes-associated HLA class II genotypes in children with Down's syndrome and type 1 diabetes compared with age- and sex-matched healthy control subjects (P < 0.001). Down's syndrome children with type 1 diabetes were, however, less likely to carry the highest risk genotype DR4-DQ8/DR3-DQ2 than children with type 1 diabetes from the general population (P = 0.01) but more likely to carry low-risk genotypes (P < 0.0001). The frequency of subclinical islet autoimmunity is increased in Down's syndrome, and susceptibility to type 1 diabetes in Down's syndrome is partially HLA mediated. Other factors, possibly including genes on chromosome 21, may increase the penetrance of type 1 diabetes in Down's syndrome.

Adolescent↗

Nutritional intervention to prevent weight gain in patients commenced on olanzapine: a randomized controlled trial.

OBJECTIVE: Olanzapine is the most commonly prescribed atypical antipsychotic medication in Australia. Research reports an average weight gain of between 4.5 and 7 kg in the 3 months following its commencement. Trying to minimize this weight gain in a population with an already high prevalence of obesity, mortality and morbidity is of clinical and social importance. This randomized controlled trial investigated the impact of individual nutrition education provided by a dietitian on weight gain in the 3 and 6 months following the commencement of olanzapine. METHOD: Fifty-one individuals (29 females, 22 males) who had started on olanzapine in the previous 3 months (mean length of 27 days +/- 20) were recruited through Peninsula Health Psychiatric Services and were randomly assigned to either the intervention (n = 29) or the control group (n = 22). Individuals in the intervention group received six 1 hour nutrition education sessions over a 3-month period. Weight, waist circumference, body mass index (BMI) and qualitative measures of exercise levels, quality of life, health and body image were collected at baseline at 3 and 6 months. RESULTS: After 3 months, the control group had gained significantly more weight than the treatment group (6.0 kg vs 2.0 kg, p < or = 0.002). Weight gain of more than 7% of initial weight occurred in 64% of the control group compared to 13% of the treatment group. The control group's BMI increased significantly more than the treatment group's (2 kg/m(2)vs 0.7 kg/m(2), p < or = 0.03). The treatment group reported significantly greater improvements in moderate exercise levels, quality of life, health and body image compared to the controls. At 6 months, the control group continued to show significantly more weight gain since baseline than the treatment group (9.9 kg vs 2.0 kg, p < or = 0.013) and consequently had significantly greater increases in BMI (3.2 kg/m(2)vs 0.8 kg/m(2), p < or = 0.017). CONCLUSION: Individual nutritional intervention provided by a dietitian is highly successful at preventing olanzapine-induced weight gain.

Adult↗

Development of an inner urban homeless mental health service.

OBJECTIVES: The aim is to describe the development, principles and practices of the Waratah Area Homeless Outreach Psychiatric Service (WAHOPS) and place these in the context of international developments in homeless psychiatric services. METHODS: Information on the development of the service was collected from current and past staff. Reference is made to the relevant literature. RESULTS: WAHOPS has developed a unique model of practice based on local and international experience. CONCLUSIONS: Specialized mental health services for the homeless, by working in close collaboration with existing homeless services, can successfully engage and manage patients. The application of homeless practices may need to become more widespread in public mental health services as patterns of accommodation change within the Australian population.

Australia↗

Intra-arterial tumor necrosis factor-alpha impairs endothelium-dependent vasodilatation and stimulates local tissue plasminogen activator release in humans.

OBJECTIVE: Inflammation contributes to the pathogenesis of cardiovascular disease, potentially through the actions of proinflammatory cytokines. We assessed the direct effects of local intra-arterial tumor necrosis factor-alpha (TNF-alpha), interleukin-6, and endotoxin on blood flow and endogenous tissue plasminogen activator (t-PA) release in vivo in humans. METHODS AND RESULTS: In a double-blind, randomized, placebo-controlled trial, blood flow, plasma cytokine, and fibrinolytic parameters were measured using venous occlusion plethysmography and blood sampling. Ten subjects received intrabrachial TNF-alpha, interleukin-6, and endotoxin infusions, and 8 additional subjects received intrabrachial infusions of bradykinin, acetylcholine, and sodium nitroprusside after pretreatment with TNF-alpha. TNF-alpha but not interleukin-6, endotoxin, or placebo caused a gradual and sustained approximately 20-fold increase in plasma t-PA concentrations (P<0.001) that was associated with elevated plasma interleukin-6 concentrations (P<0.05) but without an effect on blood flow or plasminogen activator inhibitor type 1 antigen. Compared with placebo, TNF-alpha pretreatment impaired bradykinin- and acetylcholine-induced vasodilatation (P<0.03) and resulted in a doubling of bradykinin-induced t-PA release (P<0.05). CONCLUSIONS: Intra-arterial TNF-alpha causes an acute local vascular inflammation that is associated with impaired endothelium-dependent vasomotion as well as a sustained and substantial increase in endothelial t-PA release. TNF-alpha has potentially both adverse vasomotor and beneficial profibrinolytic effects on endothelial function.

Acetylcholine↗

Sensory and electrophysiological properties of guinea-pig sensory neurones expressing Nav 1.7 (PN1) Na+ channel alpha subunit protein.

The TTX-sensitive Na(v)1.7 (PN1) Na(+) channel alpha subunit protein is expressed mainly in small dorsal root ganglion (DRG) neurones. This study examines immunocytochemically whether it is expressed exclusively or preferentially in nociceptive primary afferent DRG neurones, and determines the electrophysiological properties of neurones that express it. Intracellular somatic action potentials (APs) evoked by dorsal root stimulation were recorded in L6/S1 DRG neurones at 30 +/- 2 degrees C in vivo in deeply anaesthetised young guinea-pigs. Each neurone was classified, from its dorsal root conduction velocity (CV) as a C-, Adelta- or Aalpha/beta-fibre unit and from its response to mechanical and thermal stimuli, as a nociceptive, low threshold mechanoreceptive (LTM) or unresponsive unit. Fluorescent dye was injected into the soma and Na(v)1.7-like immunoreactivity (Na(v)1.7-LI) was examined on sections of dye-injected neurones. All C-, 90 % of Adelta- and 40 % of Aalpha/beta-fibre units, including both nociceptive and LTM units, showed Na(v)1.7-LI. Positive units included 1/1 C-LTM, 6/6 C-nociceptive, 4/4 C-unresponsive (possible silent nociceptive) units, 5/6 Adelta-LTM (D hair), 13/14 Adelta-nociceptive, 2/9 Aalpha/beta-nociceptive, 10/18 Aalpha/beta-LTM cutaneous and 0/9 Aalpha/beta-muscle spindle afferent units. Overall, a higher proportion of nociceptive than of LTM neurones was positive, and the median relative staining intensity was greater in nociceptive than LTM units. Na(v)1.7-LI intensity was clearly positively correlated with AP duration and (less strongly) negatively correlated with CV and soma size. Since nociceptive units tend overall to have longer duration APs, slower CVs and smaller somata, these correlations may be related to the generally greater expression of Na(v)1.7 in nociceptive units.

Action Potentials↗

Minimizing adverse effects on patients of involuntary relocation from long-stay wards to community residences.

OBJECTIVES: This study examined the incidence of, and variables associated with, relocation trauma among 85 patients who moved from long-stay psychiatric wards to community care units as part of a hospital closure in Melbourne, Australia. METHODS: Some participants moved directly from wards and some moved first to transitional units on the hospital grounds. Preparation for the transition, such as visits to the community care unit before the move, was documented, and severity of symptoms, aggressive behaviors, and preferences for living environments one month before and one month after the move were compared. Relocation trauma was measured one month after the move. After significant factors associated with trauma were determined, additional tests further discriminated these factors. RESULTS: Although 66 percent of participants were happy with community care units one month after the move, 18 percent preferred hospital living. Of 81 participants who had data on relocation trauma, 20, or 25 percent, met relocation trauma criteria. Preparation in a transitional unit reduced the likelihood of trauma, as did making six or more premove visits to the new facility and having a preparation period of more than 16 weeks. When preparation in a transitional unit, number of premove visits, and duration of preparation were considered together, only the number of premove visits and duration of preparation remained significantly associated with relocation trauma. CONCLUSIONS: Adverse effects of relocation on long-stay psychiatric patients may be minimized by the preparation of patients over a period of four months or more, with inclusion of six or more visits to the new facility. Moving via a transitional environment is not essential.

Adolescent↗

Epilepsy--giving the diagnosis. A survey of British paediatric neurologists.

Adult-centred studies continue to show poor information provision and understanding in people with epilepsy. This study explores whether paediatric neurologists work within a consultation framework designed to meet information needs. A questionnaire on how to give the diagnosis was sent to 32 UK Paediatric Neurologists. Consultation content was largely determined intuitively rather than on a shared knowledge of the process involved. Little consensus was identified in relation to analogy and the usefulness or awareness of available unevaluated literature; but most acknowledged the value of a specialist epilepsy nurse. Most responses were based on a typical medical agenda but less than 20% addressed emotional responses and adaptation. Three approaches were identified-'pro-active' (running the risk of overload but recognising the right of parents to information), 'reactive' (more individually tailored, but assumes doctors can judge parental reactions) and 'drip-feed' (protective and pre-selecting topics to meet the situation). Our aim to establish a guideline proved impossible. Further study should develop more detailed models of the disclosure process, and identify epilepsy explanations that can be consumer-tested.

Adult↗