1,043 research outputs found

    Are routinely collected NHS administrative records suitable for endpoint identification in clinical trials? Evidence from the West of Scotland coronary prevention study

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    Background: Routinely collected electronic patient records are already widely used in epidemiological research. In this work we investigated the potential for using them to identify endpoints in clinical trials.<p></p> Methods: The events recorded in the West of Scotland Coronary Prevention Study (WOSCOPS), a large clinical trial of pravastatin in middle-aged hypercholesterolaemic men in the 1990s, were compared with those in the record-linked deaths and hospitalisations records routinely collected in Scotland.<p></p> Results: We matched 99% of fatal study events by date. We showed excellent matching (97%) of the causes of fatal endpoint events and good matching (.80% for first events) of the causes of nonfatal endpoint events with a slightly lower rate of mismatching of record linkage than study events (19% of first study myocardial infarctions (MI) and 4% of first record linkage MIs not matched as MI). We also investigated the matching of non-endpoint events and showed a good level of matching, with .78% of first stroke/TIA events being matched as stroke/TIA. The primary reasons for mismatches were record linkage data recording readmissions for procedures or previous events, differences between the diagnoses in the routinely collected data and the conclusions of the clinical trial expert adjudication committee, events occurring outside Scotland and therefore being missed by record linkage data, miscoding of cardiac events in hospitalisations data as ‘unspecified chest pain’, some general miscoding in the record linkage data and some record linkage errors.<p></p> Conclusions: We conclude that routinely collected data could be used for recording cardiovascular endpoints in clinical trials and would give very similar results to rigorously collected clinical trial data, in countries with unified health systems such as Scotland. The endpoint types would need to be carefully thought through and an expert endpoint adjudication committee should be involved.<p></p&gt

    Ultracold Fermions in a Graphene-Type Optical Lattice

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    Some important features of the graphene physics can be reproduced by loading ultracold fermionic atoms in a two-dimensional optical lattice with honeycomb symmetry and we address here its experimental feasibility. We analyze in great details the optical lattice generated by the coherent superposition of three coplanar running laser waves with respective angles 2π/32\pi/3. The corresponding band structure displays Dirac cones located at the corners of the Brillouin zone and close to half-filling this system is well described by massless Dirac fermions. We characterize their properties by accurately deriving the nearest-neighbor hopping parameter t0t_0 as a function of the optical lattice parameters. Our semi-classical instanton method proves in excellent agreement with an exact numerical diagonalization of the full Hamilton operator in the tight-binding regime. We conclude that the temperature range needed to access the Dirac fermions regime is within experimental reach. We also analyze imperfections in the laser configuration as they lead to optical lattice distortions which affect the Dirac fermions. We show that the Dirac cones do survive up to some critical intensity or angle mismatches which are easily controlled in actual experiments. In the tight-binding regime, we predict, and numerically confirm, that these critical mismatches are inversely proportional to the square-root of the optical potential strength. We also briefly discuss the interesting possibility of fine-tuning the mass of the Dirac fermions by controlling the laser phase in an optical lattice generated by the incoherent superposition of three coplanar independent standing waves with respective angles 2π/32\pi/3

    Phenylpyrrole fungicides act on triosephosphate isomerase to induce methylglyoxal stress and alter hybrid histidine kinase activity.

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    Fludioxonil, a natural product of pyrrolnitrin, is a potent fungicide used on crops worldwide. Drug action requires the presence of a group III hybrid histidine kinase (HHK) and the high osmolarity glycerol (HOG) pathway. We have reported that the drug does not act directly on HHK, but triggers the conversion of the kinase to a phosphatase, which dephosphorylates Ypd1 to constitutively activate HOG signaling. Still, the direct drug target remains unknown and mode of action ill defined. Here, we heterologously expressed a group III HHK, dimorphism-regulating kinase 1 (Drk1) in Saccharomyces cerevisae to delineate fludioxonil's target and action. We show that the drug interferes with triosephosphate isomerase (TPI) causing release of methylglyoxal (MG). MG activates the group III HHK and thus the HOG pathway. Drug action involved Drk1 cysteine 392, as a C392S substitution increased drug resistance in vivo. Drug sensitivity was reversed by dimedone treatment, indicating Drk1 responds in vivo to an aldehydic stress. Fludioxonil treatment triggered elevated cytosolic methylglyoxal. Likewise, methylglyoxal treatment of Drk1-expressing yeast phenocopied treatment with fludioxonil. Fludioxonil directly inhibited TPI and also caused it to release methylglyoxal in vitro. Thus, TPI is a drug target of the phenylpyrrole class of fungicides, inducing elevated MG which alters HHK activity, likely converting the kinase to a phosphatase that acts on Ypd1 to trigger HOG pathway activation and fungal cell death

    The effects of changes in the order of verbal labels and numerical values on children's scores on attitude and rating scales

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    Research with adults has shown that variations in verbal labels and numerical scale values on rating scales can affect the responses given. However, few studies have been conducted with children. The study aimed to examine potential differences in children’s responses to Likert-type rating scales according to their anchor points and scale direction, and to see whether or not such differences were stable over time. 130 British children, aged 9 to 11, completed six sets of Likert-type rating scales, presented in four different ways varying the position of positive labels and numerical values. The results showed, both initially and 8-12 weeks later, that presenting a positive label or a high score on the left of a scale led to significantly higher mean scores than did the other variations. These findings indicate that different arrangements of rating scales can produce different results which has clear implications for the administration of scales with children

    A randomized trial of prenatal n-3 fatty acid supplementation and preterm delivery

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    Background: Previous studies have suggested that maternal supplementation with n−3 long-chain polyunsaturated fatty acids may reduce the incidence of preterm delivery but may also prolong gestation beyond term; however, more data are needed regarding the role of n−3 long-chain polyunsaturated fatty acids in pregnancy. Methods: We performed a multicenter, double-blind, randomized trial in which women who were pregnant with single or multiple fetuses were assigned to receive either fish-oil capsules that contained 900 mg of n−3 long-chain polyunsaturated fatty acids (n−3 group) or vegetable-oil capsules that contained trace n−3 long-chain polyunsaturated fatty acids (control group) daily, beginning before 20 weeks of gestation and continuing to 34 weeks of gestation or delivery, whichever occurred first. The primary outcome was early preterm delivery, defined as delivery before 34 completed weeks of gestation. Other pregnancy and neonatal outcomes were also assessed. Results: A total of 5544 pregnancies in 5517 women were randomly assigned at six centers in Australia; 5486 pregnancies were included in the primary analysis. Early preterm delivery occurred in the case of 61 of 2734 pregnancies (2.2%) in the n−3 group and 55 of 2752 pregnancies (2.0%) in the control group; the between-group difference was not significant (adjusted relative risk, 1.13; 95% confidence interval [CI], 0.79 to 1.63; P=0.50). There were no significant differences between the groups in the incidence of interventions in post-term (\u3e41 weeks of gestation) deliveries, in adverse events, or in other pregnancy or neonatal outcomes, except that a higher percentage of infants born to women in the n−3 group than in the control group were very large for gestational age at birth (adjusted relative risk, 1.30; 95% CI, 1.02 to 1.65). Percentages of serious adverse events did not differ between the groups. Minor gastrointestinal disturbances were more commonly reported in the n−3 group than in the control group. Conclusions: Supplementation with n−3 long-chain polyunsaturated fatty acids from early pregnancy (\u3c20 weeks of gestation) until 34 weeks of gestation did not result in a lower incidence of early preterm delivery or a higher incidence of interventions in post-term deliveries than control. (Funded by the Australian National Health and Medical Research Council and the Thyne Reid Foundation; ORIP Australian New Zealand Clinical Trials Registry number, ACTRN12613001142729.

    A Generic Framework for Implicate Generation Modulo Theories

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    International audienceThe clausal logical consequences of a formula are called its implicates. The generation of these implicates has several applications, such as the identification of missing hypotheses in a logical specification. We present a procedure that generates the implicates of a quantifier-free formula modulo a theory. No assumption is made on the considered theory, other than the existence of a decision procedure. The algorithm has been implemented (using the solvers MiniSAT, CVC4 and Z3) and experimental results show evidence of the practical relevance of the proposed approach

    An integrative review of the continuing professional development needs for nurse educators

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    Objectives: The study aimed at describing the field of research in continuing professional development for nurse educators and the continuous education and development needs of nurse educators by asking: What research has been done in the field of continuing professional development of nurse educators? What are the continuing education and development needs and requirements reported for and by nurse educators?Design: An integrative review of peer-reviewed academic literature following a systematic search design.Data sources: Qualitative, quantitative, and mixed methods publications in CINAHL, Cochrane Library, Web of Science, Embase, ERIC, and PubMed.Review methods: Search results were screened for full text and assessed for quality using the Mixed Methods Assessment Tool. Full texts were then thematic analysed using an inductive and reflective process.Results: The number of published academic articles about the continuing professional development for nurse educators is small (n = 13). The themes produced from the articles identify heterogenous development needs for nurse educators, clustered around four themes: (1) professional competencies (2) management and resources, (3) communication and collaboration, and (4) agency. The findings of this review show that nurse educators have multiple roles which have specific and multiple personal and institutional needs.Conclusions: The results of this review show that the continuing professional development needs are heterogenous between nurse educators, yet share commonalities across departmental teams as a whole, and across different countries. This raises the issue of how these needs can or should be, focused on the sustainable development of nurse educators.</div

    Anthropogenic drivers of variation in concentrations of perfluoroalkyl substances in otters (Lutra lutra) from England and Wales

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    Per- and polyfluoroalkyl substances (PFASs) are ubiquitous environmental contaminants that have been linked to adverse health effects in wildlife and humans. Here, we report the presence of PFASs in Eurasian otters (Lutra lutra) in England and Wales and their association with anthropogenic sources. The following 15 compounds were analyzed: 10 perfluoroalkyl carboxylic acids (PFCAs), 4 perfluoroalkyl sulfonic acids (PFSAs), and perfluorooctane sulfonamide, in livers of 50 otters which died between 2007 and 2009. PFASs were detected in all otters analyzed, with 12/15 compounds detected in ≥80% of otters. Perfluorooctane sulfonate (PFOS) accounted for 75% of the ΣPFAS profile, with a maximum concentration of 6800 μg/kg wet weight (ww). Long-chain (≥C8) PFCAs accounted for 99.9% of the ΣPFCA profile, with perfluorodecanoic acid and perfluorononanoic acid having the highest maxima (369 μg/kg ww and 170 μg/kg ww, respectively). Perfluorooctanoic acid (PFOA) concentrations were negatively associated with the distance from a factory that used PFOA in polytetrafluoroethylene manufacture. Most PFAS concentrations in otters were positively associated with load entering wastewater treatment works (WWTW) and with arable land, suggesting that WWTW effluent and sewage sludge-amended soils are significant pathways of PFASs into freshwaters. Our results reveal the widespread pollution of British freshwaters with PFASs and demonstrate the utility of otters as effective sentinels for spatial variation in PFAS concentrations
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