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Biomedical subjects

R O'Connell

Publications and source records attributed to R O'Connell.

At least 19 recordsLinked to original sources

Observation of weak impact of a stochastic magnetic field on fast-ion confinement.

Fast ions are observed to be very well confined in the Madison Symmetric Torus reversed field pinch despite the presence of stochastic magnetic field. The fast-ion energy loss is consistent with the classical slowing down rate, and their confinement time is longer than expected by stochastic estimates. Fast-ion confinement is measured from the decay of d-d neutrons following a short pulse of a 20 keV atomic deuterium beam. Ion confinement agrees with computation of particle trajectories in the stochastic magnetic field, and is understood through consideration of ion guiding center islands.

Journal Article↗

Forms that Inform.

OBJECTIVES: Sound medical decisions are easier for clinicians who have essential patient data in the right place at the right time. Our goal was to develop a usable form to guide clinical decisions and then test it using actual cases. METHODS: The authors designed a form to represent data from patients with chest pain; it was revised several times. We incorporated opinions from clinician-users as well as evidence from the literature to improve usability. To test the design, we filled out forms with actual patient data derived from Emergency Department charts of patients who presented with chest pain. We then validated the design by having house officer reviewers make the decision to admit, observe in the ER for one day, or discharge subjects based entirely on a one-page form. RESULTS: Thirty-three house officers reviewed our initial design and made suggestions. Our literature search yielded a number of factors discriminating ischemic from non-ischemic chest pain. Sixteen factors were included on a finalized form in the rank order assigned by reviewing physicians. Over 4 days, data from 29 subjects were used to fill out copies of the form. Based purely on the completed forms, house officers made decisions to admit, discharge, or observe all 29 subjects in less than 30 minutes. CONCLUSIONS: Forms have traditionally been employed to record and organize data. Here we show how principles of usability engineering can be used to create a form to meet the needs of users and even encourage evidence-based practice.

Chest Pain↗

Observation of velocity-independent electron transport in the reversed field pinch.

Confinement of runaway electrons has been observed for the first time in a reversed field pinch during improved-confinement plasmas in the Madison Symmetric Torus. Energy-resolved hard-x-ray flux measurements have been used to determine the velocity dependence of the electron diffusion coefficient, utilizing computational solutions of the Fokker-Planck transport equation. With improved-confinement, the fast electron diffusivity drops by 2 orders of magnitude and is independent of velocity. This suggests a change in the transport mechanism away from stochastic magnetic field diffusion.

Journal Article↗

Sibling pairs with affective disorders: resemblance of demographic and clinical features.

BACKGROUND: As part of a collaborative linkage study, the authors obtained clinical and demographic data on 160 families in which more than one sibling was affected with a bipolar illness. The aim of the study was to identify clinical characteristics that had a high degree of familiality. METHOD: Data on age at onset, gender, frequency of illness-episodes and proportion of manic to depressive episodes were examined to determine intra-pair correlations in affected sibling pairs. Dimension scales were developed measuring frequency and severity of lifetime mania, depression, psychosis and mood-incongruence of psychotic symptoms; degree of familial aggregation for scores on these dimensions was calculated. RESULTS: Sibling pairs correlated significantly for age at onset (p = 0.293, P < 0 001); dimension scores for psychosis (p = 0.332, P < 0.001); and proportion of manic to depressive episodes (p = 0.184, P = 0.002). These findings remained significant when correcting for multiple testing. Of the other test variables; mania (p = 0.171, P = 0.019); incongruence dimensions (p = 0.242, P = 0.042); .frequency of manic episodes (p = 0.152, P = 0.033); and frequency of depressive episodes (p = 0.155, P = 0.028) were associated with modest correlations but these were not significant after correction. Degree of familial aggregation was not significant for sex (kappa = 0.084) or dimension scores for depression (p = 0.078, P = 0.300). CONCLUSIONS: Significant but modest familial resemblance has been shown for some specific features of bipolar illness, particularly age at onset and degree of psychosis. Further research may establish the extent to which these findings are mediated by genetic and/or environmental factors.

Bipolar Disorder↗

The Wellcome trust UK-Irish bipolar affective disorder sibling-pair genome screen: first stage report.

We have completed the first stage of a two-stage genome wide screen designed to identify chromosomal regions that may harbour susceptibility genes for bipolar affective disorder. The first stage screening sample included 509 subjects from 151 nuclear families recruited within the United Kingdom and Republic of Ireland. This sample contained 154 narrowly defined affected sibling pairs (DSM-IV BPI) and 258 broadly defined affected sibling pairs (DSM-IV BPI, SABP, BPII, BPNOS or MDD(R)), approximately two thirds of all families contained at least one other additional typed individual. All individuals were genotyped using 398 highly polymorphic microsatellite markers from Applied Biosystems's Linkage Mapping Set Version 2. The average inter-marker distance was 9.6 cM and the mean heterozygosity was 0.78. Analysis of these data using non-parametric linkage methods (MAPMAKER/SIBS) found no evidence for loci of major effect and no regions reached genome-wide significance for either suggestive or significant linkage. We identified 19 points across the genome where the MLS exceeded a value set for follow up in our second stage screen (MLS > or = 0.74 (equivalent to a nominal pointwise significance of 5%) under the narrowest diagnostic model). These points were on chromosomes 2, 3, 4, 6, 7, 9, 10, 12, 17, 18 & X. Some of these points overlapped with previous linkage reports both within bipolar affective disorder and other psychiatric illnesses. Under the narrowest diagnostic model, the single most significant multipoint linkage was on chromosome 18 at marker D18S452 (MLS=1.54). Overall the highest MLS was 1.70 on chromosome 2 at marker D2S125, under the broadest diagnostic model.

Adult↗

Isolation and characterization of the activated B-cell factor 1 homolog in Caenorhabditis elegans.

Members of the basic helix-loop-helix (bHLH) family of transcription factors regulate a wide array of developmental processes in many cell types, including cell fate specification, differentiation and morphogenesis. Our studies describe the cloning of a gene from the nematode Caenorhabditis elegans that is closely related to the vertebrate-activated B-cell factor (ABF) gene. The nematode gene product CeABF-1 was detected by northern blot analysis from RNA isolated from pooled nematodes representing different developmental stages. The developmental expression profile of CeABF-1 was shown by RT-PCR analysis to be predominantly expressed in the larval stages L3 and L4, with lower levels observed in the L2 larval stage and adult. We also show that CeABF-1 is capable of forming heterodimers with E2A proteins and binding E-box target sites. Mammalian cells transfected with CeABF-1 expression plasmids were capable of blocking E2A-mediated gene transcription, but full repression activity required the presence of two conserved amino acid residues found within the first helix of the CeABF-1 bHLH domain. These results suggest a conserved mechanism of gene repression between certain class II bHLH and class I bHLH proteins found in vertebrates and invertebrates.

Amino Acid Sequence↗

Characterization of a basic helix-loop-helix protein, ABF-1: nuclear localization, transcriptional properties, and interaction with Id-2.

The activated B-cell factor (ABF)-1 cDNA was initially isolated from Epstein-Barr virus (EBV)-infected B cells and codes for a DNA-binding protein belonging to the basic helix-loop-helix (bHLH) family of transcription factors. In this study, we characterized the nuclear localization signal of ABF-1, mapped two distinct transcriptional repression domains, and identified one ABF-1-interacting protein, Id-2. By examining the subcellular location of deletion mutants of ABF-1 fused to green fluorescent protein (GFP), critical regions involved in nuclear localization were determined. Analysis of GFP-tagged ABF-1 deletion mutants revealed two separate regions capable of directing nuclear localization. One region mapped to the N-terminal amino acids 71 to 103, whereas the second region localized to the C-terminal bHLH domain. Transient transfection of ABF-1 deletion mutants demonstrated that the N-terminal amino acids 1 to 40 and the bHLH domain function together to achieve maximum repression of E2A activity. Taken together, these results indicate that ABF-1 is a nuclear transcriptional repressor with two distinct regions that function in a synergistic fashion to attenuate E2A-mediated gene activation.

Basic Helix-Loop-Helix Proteins↗

Cigarette smoking and psychotic symptoms in bipolar affective disorder.

BACKGROUND: An association exists between smoking and schizophrenia, independent of other factors and related to psychotic symptomatology. AIMS: To determine whether smoking is associated with psychosis in bipolar affective disorder. METHOD: Smoking data were collected from 92 unrelated patients with bipolar affective disorder. An ordinal logistic regression analysis tested the relationship between smoking severity and psychotic symptomatology, allowing for potential confounders. RESULTS: A significant relationship was detected between smoking/heavy smoking and history of psychosis (68.7%, n=44). Smoking was less prevalent in patients who were less symptomatic (56.5%, n=13) than in patients with a more severe psychosis (75.7, n=31). Prevalence and severity of smoking predicted severity of psychotic symptoms (P=0.001), a relationship independent of other variables (P=0.0272). CONCLUSION: A link between smoking and psychosis exists in bipolar affective disorder and may be independent of categorical diagnosis.

Adult↗

Variation in in-patient stroke management in ten centres in different countries: the INCLEN multicentre stroke collaboration.

BACKGROUND AND PURPOSE: Large within-country variations have been described in stroke management and there have been a few studies of between-country variation (in the USA and the UK). We designed a study to examine stroke management across a wide range of countries representing different stages of economic development. Large variations would suggest the need to explore methods of increasing the uptake of evidence-based stroke practice. METHODS: Members of the International Clinical Epidemiology Network (INCLEN) from 14 centres in ten countries agreed to review the records of the last 50 patients admitted to hospital with a clinical diagnosis of stroke. Information on demographic variables, the clinical diagnosis of stroke type, investigations performed and treatments given and the discharge destination of the patient were recorded and sent to the coordinating centre in Australia for analysis. RESULTS: There were statistically significant between-centre differences in the proportions of patients cared for by a neurologist, staying in hospital for at least ten days and having CT or MRI scans. Significant between-centre differences were also seen for treatment, for example, the use of aspirin in non-haemorrhagic stroke varied from 11 to 79%. The variation (for all interventions studied) was no longer statistically significant when examined within strata according to availability of facilities. CONCLUSIONS: The large variation between centres in the management of stroke is largely 'explained' by the availability of resources, even for interventions that do not depend on resource availability. It will be important to develop management guidelines that reflect evidence-based practice of relevance across a range of economic settings.

Age Factors↗

Standardisation of subjectively scored HIV immunoassays: developing a quality assurance program to assist in reproducible interpretation of results using an anti-HIV particle agglutination assay as a model.

Immunoassays such as particle agglutination assays, rapid tests and western or line blots are scored or read subjectively. These readings display intra- and inter-reader variability, as well as intra- and inter-laboratory variability. In the present study the consistency of scoring was assessed between readers both within and between two groups of scientists using the Serodia anti-HIV particle agglutination assay as an example of an assay scored subjectively. An anti-HIV positive sample in eight serial dilutions made to yield a full range of results expected for the assay was presented 12 times (96 test wells). Each dilution was placed randomly in a plate and tested with the Serodia anti-HIV particle agglutination assay then photographed. Participants in the two groups each scored the photographed plate independently and twice, 2 h apart. Each well was assigned a status (the consensus result of the four most experienced Australian readers) and each participant's results were compared with this status. The average percentage of wells assessed as 'correct' for the Group A participants was 86% (range 56-98%) and for the Group B participants was 67% 'correct' (range 46-88%). In general, strongly positive and negative wells were scored 'correctly'. The highest variations between scores were seen in the borderline positive dilutions +/- region. A quality assessment program based on the method used to obtain these results will be instituted in order to improve the consistency of scoring assays read subjectively.

AIDS Serodiagnosis↗

Carcinoma of the hypopharynx, esophagus and cardia.

In a series of 230 patients with carcinoma of the hypopharynx, esophagus and cardia, 114 patients with squamous cell tumors and 86 patients with adenocarcinomas were resected (rate of restability, 87 per cent). Mortality at 30 days was 17.5 per cent. Over-all hospital mortality was 22.0 per cent. The one year survival rate was 40.0 per cent and the five year survival rate was 19.5 per cent. Reflux esophagitis occurred in 26 per cent of survivors, benign stricture in 9 per cent and local recurrence in 7 per cent. Eighty-two per cent of patients were permanently free of dysphagia postoperatively. Aggressive surgical procedures provide effective palliation and a worthwhile proportion of long term survivors.

Adenocarcinoma↗

Surgical treatment of squamous cell carcinoma of the oesophagus.

During the period 1976-1983, a total of 72 patients with squamous cell carcinoma of the oesophagus were seen. Exploration was undertaken in 62 patients and all those explored had their tumours resected. The overall operative mortality rate was 12.9 per cent. Overall survival rates were 49 per cent at 1 year, 31 per cent at 2 years and 11.5 per cent at 5 years.

Adult↗

The relationship between technetium 99m pertechnetate gastric scanning and gastric contents.

In order to elucidate the gastric handling of 99Tcm, we performed scintiscanning under basal and stimulated conditions while simultaneously monitoring gastric outputs of water and sodium, hydrogen and 99Tcm pertechnetate ions in six healthy fasting volunteers. Our results showed that gastric scintiscanning correlated well with gastric luminal 99Tcm activity (r = 0.99). However, clearance of 99Tcm from plasma into the gastric lumen showed only a poor correlation with hydrogen ion output (r = 0.68) and no correlation with sodium output. Explanation of these results on a cellular basis can be achieved by assuming a two-component mechanism for 99Tcm secretion, with both the parietal cells (H+ ion secretory) and non-parietal cells (Na+ ion secretory) contributing to 99Tcm gastric output. The relative contribution of each cell type to total 99Tcm secretion is dependent on the degree of gastric stimulation, with non-parietal 99Tcm secretion dominating in the basal state and parietal 99Tcm secretion dominating in the stimulated state. It is concluded therefore, that gastric scintiscanning with 99Tcm pertechnetate should stand only as an empirical test of gastric function and not as a means of measuring acid output.

Adult↗