1,922 research outputs found

    Evidence of methodological bias in hospital standardised mortality ratios: retrospective database study of English hospitals

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    Objective To assess the validity of case mix adjustment methods used to derive standardised mortality ratios for hospitals, by examining the consistency of relations between risk factors and mortality across hospitals

    Vascular endothelial growth factor-A165b restores normal glomerular water permeability in a diphtheria-toxin mouse model of glomerular injury

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    BACKGROUND/AIMS:Genetic cell ablation using the human diphtheria toxin receptor (hDTR) is a new strategy used for analysing cellular function. Diphtheria toxin (DT) is a cytotoxic protein that leaves mouse cells relatively unaffected, but upon binding to hDTR it ultimately leads to cell death. We used a podocyte-specific hDTR expressing (Pod-DTR) mouse to assess the anti-permeability and cyto-protective effects of the splice isoform vascular endothelial growth factor (VEGF-A165b). METHODS:The Pod-DTR mouse was crossed with a mouse that over-expressed VEGF-A165b specifically in the podocytes (Neph-VEGF-A165b). Wild type (WT), Pod-DTR, Neph-VEGF-A165b and Pod-DTR X Neph-VEGF-A165b mice were treated with several doses of DT (1, 5, 100, and 1,000 ng/g bodyweight). Urine was collected and the glomerular water permeability (LpA/Vi) was measured ex vivo after 14 days. Structural analysis and podocyte marker expression were also assessed. RESULTS: Pod-DTR mice developed an increased glomerular LpA/Vi 14 days after administration of DT (all doses), which was prevented when the mice over-expressed VEGF-A165b. No major structural abnormalities, podocyte ablation or albuminuria was observed in Pod-DTR mice, indicating this to be a mild model of podocyte disease. However, a change in expression and localisation of nephrin within the podocytes was observed, indicating disruption of the slit diaphragm in the Pod-DTR mice. This was prevented in the Pod-DTR X Neph-VEGF-A165b mice. CONCLUSION: Although only a mild model of podocyte injury, over-expression of the anti-permeability VEGF-A165b isoform in the podocytes of Pod-DTR mice had a protective effect. Therefore, this study further highlights the therapeutic potential of VEGF-A165b in glomerular disease

    Can Inflation be Falsified?

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    Despite its central role in modern cosmology, doubts are often expressed as to whether cosmological inflation is really a falsifiable theory. We distinguish two facets of inflation, one as a theory of initial conditions for the hot big bang and the other as a model for the origin of structure in the Universe. We argue that the latter can readily be excluded by observations, and that there are also a number of ways in which the former can find itself in conflict with observational data. Both aspects of the theory are indeed falsifiable.Comment: 7 pages LaTeX file with two figures incorporated by epsf. Fifth Prize in Gravity Research Foundation Essay Competition. To appear, General Relativity and Gravitatio

    The Dilemma of Using Sward Height as a Management Tool for Intensively Grazed Sheep Pasture in Spring

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    Sward height is often used as a tool for both animal and pasture management, especially when continuously grazing pasture. For example, sward height has been used to define the conditions for optimal feed intake of multiple-bearing ewes, both before and after lambing (Everett-Hincks et al.2005; Morris and Kenyon 2004). Sward height is easily applied by the grazier and so becomes an effective tool. However, changes in the leaf distribution and relative species makeup of the sward both seasonally (Thomson et al. 2001) and in response to grazing management (Webby and Pengelly 1986) mean that the amount of pasture per unit height will change. When these changes occur a dilemma is presented to the grazier. How do they manage the trade-off between a simple indicator for management decisions and the lost opportunity of harvesting pasture mass that may be accumulating below the assigned sward height? This paper presents data from an experiment that investigated the impacts of defoliation strategies on sward of differing starting masses, with defoliation management based on height rather than mass. The paper quantifies the accumulation of herbage below defoliation height and highlights the dilemma of using sward height as a management tool when aiming to maximise the utilisation of our pasture resource

    Performance of point-of-care HbA1c test devices: implications for use in clinical practice – a systematic review and meta-analysis

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    Regular monitoring of glycated hemoglobin subfraction A1c (HbA1c) in people with diabetes and treatment with glucose-lowering medications to improve glycaemic control can reduce the risk of developing complications [1]. In 2011, a World Health Organization consultation concluded that HbA1cat a threshold of 6.5% (48 mmol/mol) can be used as a diagnostic test for diabetes [2]. HbA1c monitoring often requires the patient to attend the health center twice: once to have blood taken and then returning to get test results and receive adjustments to medication. Point-of-care (POC) analysers are bench-top instruments that use a finger-prick blood sample and are designed for use in a treatment room or at the bed-side. They provide a test result within a few minutes allowing clinical decisions and medication changes to take place immediately. The suitability of many of these devices for the accurate measurement of HbA1c has been questioned, with some POC HbA1c test devices reported not to meet accepted accuracy and precision criteria [3]. Ideal imprecision goals for HbA1c should be coefficient of variation (CV) of <2% for HbA1c reported in % units (or <3% in SI units, mmol/mol) [4], [5], [6]. Most evaluations of POC HbA1c devices have taken place in laboratory settings [7], [8]; fewer studies have assessed device performance in a POC setting or with clinicians performing the tests [9], [10]. The only published review that has attempted to combine data from accuracy studies identified five studies covering three devices and compared correlation coefficients [11]. Systematically reporting and pooling data estimates of bias and precision between POC HbA1c devices and laboratory measurements would enable end users to assess which analysers best meet their analytical performance needs. This may be of particular importance for clinicians in primary care settings where much of the management of diabetes patients takes place. The comparison of accuracy between devices over the entire therapeutic range would need to be carried out by combining data on measurement error (bias) between POC and laboratory tests [12]. The aim of this study was to compare accuracy and precision of POC HbA1c devices with the local laboratory method based on data from published studies and discuss the clinical implications of the findings
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