3,284 research outputs found

    Cardiovascular mortality and oral antidiabetic drugs: protocol for a systematic review and network meta-analysis

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    Introduction Cardiovascular diseases are the leading cause of morbidity and mortality among individuals with diabetes. Despite the beneficial effects of antidiabetic drugs (ADDs) in terms of lowering haemoglobin A1c, several ADDs have been shown to increase the risk of cardiovascular events. Given the high prevalence of cardiovascular disease among individuals with diabetes, it is important to weigh the benefits of ADDs against their cardiovascular safety. Therefore, the objective of the current study is to conduct a systematic review with network meta-analysis to compare the effects of different oral pharmacological classes of ADDs on cardiovascular safety. Methods and analysis Randomised clinical trials (RCTs) and observational studies published in English up to 31 January 2017, and which include direct and/or indirect evidence, will be included. Studies will be retrieved by searching four electronic databases and cross-referencing. Dual selection and abstraction of data will occur. The primary outcome will be cardiovascular mortality. Secondary outcomes will include all-cause mortality, new event of acute myocardial infarction, stroke (haemorrhagic and ischaemic), hospitalisation for acute coronary syndrome and urgent revascularisation procedures. Risk of bias will be assessed using the Cochrane Risk of Bias assessment instrument for RCTs and the Strengthening the Reporting of Observational Studies in Epidemiology instrument for observational studies. Network meta-analysis will be performed using multivariate random-effects meta-regression models. The surface under the cumulative ranking curve will be used to provide a hierarchy of ADDs that increase cardiovascular mortality. Dissemination The results of this study will be presented at a professional conference and submitted to a peer-reviewed journal. PROSPERO registration number CRD42017051220

    Generation, characterization, and use of EKLF(Klf1)/CRE knock-in mice for cell-restricted analyses

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    IntroductionEKLF/Klf1 is a tissue-restricted transcription factor that plays a critical role in all aspects of erythropoiesis. Of particular note is its tissue-restricted pattern of expression, a property that could prove useful for expression control of a linked marker or enzymatic gene.Methods and resultsWith this in mind, we fused the CRE recombinase to the genomic EKLF coding region and established mouse lines. We find by FACS analyses that CRE expression driven by the EKLF transcription unit recapitulates erythroid-restricted expression with high penetrance in developing embryos. We then used this line to test its properties in the adult, where we found EKLF/CRE is an active and is a robust mimic of normal EKLF expression in the adult bone marrow. EKLF/CRE is also expressed in erythroblastic island macrophage in the fetal liver, and we demonstrate for the first time that, as seen during embryonic development, EKLF is also expressed in adult BM-derived erythroblastic island macrophage. Our data also support lineage studies showing EKLF expression at early stages of hematopoiesis.DiscussionThe EKLF/CRE mouse lines are novel reagents whose availability will be of great utility for future experiments by investigators in the red cell field

    Urinary ATP and visualization of intracellular bacteria: a superior diagnostic marker for recurrent UTI in renal transplant recipients?

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    Renal transplant recipients (RTR) are highly susceptible to urinary tract infections (UTIs) with over 50% of patients having at least one UTI within the first year. Yet it is generally acknowledged that there is considerable insensitivity and inaccuracy in routine urinalysis when screening for UTIs. Thus a large number of transplant patients with genuine urine infections may go undiagnosed and develop chronic recalcitrant infections, which can be associated with graft loss and morbidity. Given a recent study demonstrating ATP is released by urothelial cells in response to bacteria exposure, possibly acting at metabotropic P2Y receptors mediating a proinflammatory response, we have investigated alternative, and possibly more appropriate, urinalysis techniques in a cohort of RTRs.Mid-stream urine (MSU) samples were collected from 53 outpatient RTRs. Conventional leukocyte esterase and nitrite dipstick tests, and microscopic pyuria counts (in 1 ?l), ATP concentration measurements, and identification of intracellular bacteria in shed urothelial cells, were performed on fresh unspun samples and compared to ‘gold-standard’ bacterial culture results.Of the 53 RTRs, 22% were deemed to have a UTI by ‘gold-standard’ conventional bacteria culture, whereas 87%, 8% and 4% showed evidence of UTIs according to leukocyte esterase dipstick, nitrite dipstick, and a combination of both dipsticks, respectively. Intracellular bacteria were visualized in shed urothelial cells of 44% of RTRs, however only 1 of the 23 RTRs (44%) was deemed to have a UTI by conventional bacteria culture. A significant association of the ‘gold-standard’ test with urinary ATP concentration combined with visualization of intracellular bacteria in shed urothelial cells was determined using the Fisher’s exact test.It is apparent that standard bedside tests for UTIs give variable results and that seemingly quiescent bacteria in urothelial cells are very common in RTRs and may represent a focus of subclinical infection. Furthermore, our results suggest urinary ATP concentration combined with detection of intracellular bacteria in shed urinary epithelial cells may be a sensitive means by which to detect ‘occult’ infection in RTRs

    Recommendation of computer systems for operation of the Habitability data base

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    "Prepared for the U. S. Army Construction Engineering Research Laboratory."Bibliography: p. 48-52

    Challenges Faced by the Clayton County, Georgia Public Defender’s Office

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    While the Sixth Amendment to the U.S. Constitution guarantees indigent defendant’s legal representation in state and federal courts, public defenders’ offices are challenged by the lack of resources to represent an endless flow of clients, attract and retain talented counsel, enlist the help of expert witnesses, as well as deliver the best quality defense. This study addresses the daily strain of defending clients who are not always the most cooperative in helping their own defense, but it also reveals the struggles and challenges faced by an urban southern public defender’s office and what changes need to be implemented to improve the public defender system. In the end, this study finds that public defender programs need adequate funding to fully deliver a quality legal defense

    Thermal Transport Model for Heat Sink Design

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    A document discusses the development of a finite element model for describing thermal transport through microcalorimeter arrays in order to assist in heat-sinking design. A fabricated multi-absorber transition edge sensor (PoST) was designed in order to reduce device wiring density by a factor of four. The finite element model consists of breaking the microcalorimeter array into separate elements, including the transition edge sensor (TES) and the silicon substrate on which the sensor is deposited. Each element is then broken up into subelements, whose surface area subtends 10 10 microns. The heat capacity per unit temperature, thermal conductance, and thermal diffusivity of each subelement are the model inputs, as are the temperatures of each subelement. Numerical integration using the Finite in Time Centered in Space algorithm of the thermal diffusion equation is then performed in order to obtain a temporal evolution of the subelement temperature. Thermal transport across interfaces is modeled using a thermal boundary resistance obtained using the acoustic mismatch model. The document concludes with a discussion of the PoST fabrication. PoSTs are novel because they enable incident x-ray position sensitivity with good energy resolution and low wiring density
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