199 research outputs found

    Robert Milton Zollinger, M.D., teacher, surgeon, soldier, and farmer.

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    From Humble roots, Dr. Robert Milton Zollinger worked his way to a position in history among the giants of American surgery. He was born on September 4, 1903, in the central Ohio town of Millersport, the son of Elmira and William Zollinger. Neither of his parents had a high school education, but they supported education and always expressed a confidence that young Robert would be successful at anything he attempted.1 He had aspirations of attending West Point, a dream that was never fulfilled when he decided to be a surgeon. On being informed of his son’s intentions, Zollinger’s father bestowed on him advice that he ostensibly adhered to throughout his career: ‘‘If you are going to be a doctor, be a good one.’

    Risk and protective factors for suicide and suicidal behaviour: a literature review

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    The Scottish Development Centre for Mental Health, in partnership with the University of Edinburgh (Research Unit in Health, Behaviour and Change and General Practice Section) and the University of Stirling (Department of Applied Social Science and Department of Nursing and Midwifery), were commissioned by the then Scottish Executive to undertake a review of the literature on risk and protective factors for suicide and suicidal behaviour. The review had two overarching aims: first, to describe and assess current knowledge regarding the societal and cultural factors associated with increased incidence of suicide (risk factors), and to delineate the population subgroups that are at increased risk of suicidal behaviour; and second, to describe and assess current knowledge regarding factors that promote resilience and healthy survival against suicidal behaviour amongst people who are exposed to known suicidal risk conditions (protective factors)

    A realist evaluation of a normal birth programme

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    Background. Complex programmes are characterised by multiple components, acting independently and interdependently, at multiple levels, within diverse and dynamic systems. High-quality evaluation of such programmes is imperative for optimising their development, implementation and effectiveness, but is often challenging. There is debate about whether the traditional outcome-focused approaches are feasible or appropriate for evaluations of large-scale, complex programmes as they often fall short of explaining how and why they do or do not work. Theory-driven approaches offer a more appropriate alternative as they attempt to uncover the black-box between the programme's inputs and the resulting complex pattern of outcomes. Aim. This paper illustrates drawing upon a realist evaluation to assess a complex programme to support normal birth. Method. Firstly, the programme theories - the ideas about how the programme would bring about change - were elicited from programme developers and key stakeholders. Secondly, these initial hypotheses were tested out by collecting data on how the programme worked in different contexts, using a multiple case study design. Thirdly, the data were analysed and interpreted to refine the programme theories in light of evidence on how the programme unfolded in practice. Findings. Described in detail are the process of conducting a realist evaluation, methods used, steps in data analyses, challenges encountered and the approach adopted to overcome them. The usefulness of this approach and some limitations are discussed

    The complexity of selection at the major primate β-defensin locus

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    BACKGROUND: We have examined the evolution of the genes at the major human β-defensin locus and the orthologous loci in a range of other primates and mouse. For the first time these data allow us to examine selective episodes in the more recent evolutionary history of this locus as well as the ancient past. We have used a combination of maximum likelihood based tests and a maximum parsimony based sliding window approach to give a detailed view of the varying modes of selection operating at this locus. RESULTS: We provide evidence for strong positive selection soon after the duplication of these genes within an ancestral mammalian genome. Consequently variable selective pressures have acted on β-defensin genes in different evolutionary lineages, with episodes both of negative, and more rarely positive selection, during the divergence of primates. Positive selection appears to have been more common in the rodent lineage, accompanying the birth of novel, rodent-specific β-defensin genes. These observations allow a fuller understanding of the evolution of mammalian innate immunity. In both the rodent and primate lineages, sites in the second exon have been subject to positive selection and by implication are important in functional diversity. A small number of sites in the mature human peptides were found to have undergone repeated episodes of selection in different primate lineages. Particular sites were consistently implicated by multiple methods at positions throughout the mature peptides. These sites are clustered at positions predicted to be important for the specificity of the antimicrobial or chemoattractant properties of β-defensins. Surprisingly, sites within the prepropeptide region were also implicated as being subject to significant positive selection, suggesting previously unappreciated functional significance for this region. CONCLUSIONS: Identification of these putatively functional sites has important implications for our understanding of β-defensin function and for novel antibiotic design

    Survey to identify research priorities for primary care in Scotland during and following the COVID-19 pandemic.

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    Objectives To identify research priorities for primary care in Scotland following the COVID-19 pandemic. Design Modified James Lind Alliance methodology; respondents completed an online survey to make research suggestions and rank research themes in order of priority. Setting Scotland primary care. Participants Healthcare professionals in primary care in Scotland and members of primary care patient and public involvement groups. 512 respondents provided research suggestions; 8% (n=40) did not work in health or social care; of those who did work, 68.8% worked in primary care, 16.3% community care, 11.7% secondary care, 4.5% third sector, 4.2% university (respondents could select multiple options). Of those respondents who identified as healthcare professionals, 33% were in nursing and midwifery professions, 25% were in allied health professions (of whom 45% were occupational therapists and 35% were physiotherapists), 20% were in the medical profession and 10% were in the pharmacy profession. Main outcomes Suggestions for research for primary care made by respondents were categorised into themes and subthemes by researchers and ranked in order of priority by respondents. Results There were 1274 research suggestions which were categorised under 12 themes and 30 subthemes. The following five themes received the most suggestions for research: disease and illness (n=461 suggestions), access (n=202), workforce (n=164), multidisciplinary team (MDT; n=143) and integration (n=108). One hundred and three (20%) respondents to the survey participated in ranking the list of 12 themes in order of research priority. The five most highly ranked research priorities were disease and illness, health inequalities, access, workforce and MDTs. The disease and illness theme had the greatest number of suggestions for research and was scored the most highly in the ranking exercise. The subtheme ranked as the most important research priority in the disease and illness theme was 'mental health'. Conclusions The themes and subthemes identified in this study should inform research funders so that the direction of primary healthcare is informed by evidence

    eIF4A RNA Helicase Associates with Cyclin-Dependent Protein Kinase A in Proliferating Cells and is Modulated by Phosphorylation

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    Eukaryotic initiation factor 4A (eIF4A) is a highly conserved RNA-stimulated ATPase and helicase involved in the initiation of messenger RNA translation. Previously, we found that eIF4A interacts with cyclin-dependent kinase A (CDKA), the plant ortholog of mammalian CDK1. Here, we show that this interaction occurs only in proliferating cells where the two proteins coassociate with 5′-cap-binding protein complexes, eIF4F or the plant-specific eIFiso4F. CDKA phosphorylates eIF4A on a conserved threonine residue (threonine-164) within the RNA-binding motif 1b TPGR. In vivo, a phospho-null (APGR) variant of the Arabidopsis (Arabidopsis thaliana) eIF4A1 protein retains the ability to functionally complement a mutant (eif4a1) plant line lacking eIF4A1, whereas a phosphomimetic (EPGR) variant fails to complement. The phospho-null variant (APGR) rescues the slow growth rate of roots and rosettes, together with the ovule-abortion and late-flowering phenotypes. In vitro, wild-type recombinant eIF4A1 and its phospho-null variant both support translation in cell-free wheat germ extracts dependent upon eIF4A, but the phosphomimetic variant does not support translation and also was deficient in ATP hydrolysis and helicase activity. These observations suggest a mechanism whereby CDK phosphorylation has the potential to down-regulate eIF4A activity and thereby affect translation
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