473 research outputs found

    Aerodynamic investigations of ventilated brake discs.

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    The heat dissipation and performance of a ventilated brake disc strongly depends on the aerodynamic characteristics of the flow through the rotor passages. The aim of this investigation was to provide an improved understanding of ventilated brake rotor flow phenomena, with a view to improving heat dissipation, as well as providing a measurement data set for validation of computational fluid dynamics methods. The flow fields at the exit of four different brake rotor geometries, rotated in free air, were measured using a five-hole pressure probe and a hot-wire anemometry system. The principal measurements were taken using two-component hot-wire techniques and were used to determine mean and unsteady flow characteristics at the exit of the brake rotors. Using phase-locked data processing, it was possible to reveal the spatial and temporal flow variation within individual rotor passages. The effects of disc geometry and rotational speed on the mean flow, passage turbulence intensity, and mass flow were determined. The rotor exit jet and wake flow were clearly observed as characterized by the passage geometry as well as definite regions of high and low turbulence. The aerodynamic flow characteristics were found to be reasonably independent of rotational speed but highly dependent upon rotor geometry

    Discrete Choice Experiments: A Guide to Model Specification, Estimation and Software

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    We provide a user guide on the analysis of data (including best–worst and best–best data) generated from discrete-choice experiments (DCEs), comprising a theoretical review of the main choice models followed by practical advice on estimation and post-estimation. We also provide a review of standard software. In providing this guide, we endeavour to not only provide guidance on choice modelling but to do so in a way that provides a β€˜way in’ for researchers to the practicalities of data analysis. We argue that choice of modelling approach depends on the research questions, study design and constraints in terms of quality/quantity of data and that decisions made in relation to analysis of choice data are often interdependent rather than sequential. Given the core theory and estimation of choice models is common across settings, we expect the theoretical and practical content of this paper to be useful to researchers not only within but also beyond health economics

    Ξ³-Catenin is overexpressed in acute myeloid leukemia and promotes the stabilization and nuclear localization of Ξ²-catenin

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    Canonical Wnt signaling regulates the transcription of T-cell factor (TCF)-responsive genes through the stabilization and nuclear translocation of the transcriptional co-activator, Ξ²-catenin. Overexpression of Ξ²-catenin features prominently in acute myeloid leukemia (AML) and has previously been associated with poor clinical outcome. Overexpression of Ξ³-catenin mRNA (a close homologue of Ξ²-catenin) has also been reported in AML and has been linked to the pathogenesis of this disease, however, the relative roles of these catenins in leukemia remains unclear. Here we report that overexpression and aberrant nuclear localization of Ξ³-catenin is frequent in AML. Significantly, Ξ³-catenin expression was associated with Ξ²-catenin stabilization and nuclear localization. Consistent with this, we found that ectopic Ξ³-catenin expression promoted the stabilization and nuclear translocation of Ξ²-catenin in leukemia cells. Ξ²-Catenin knockdown demonstrated that both Ξ³- and Ξ²-catenin contribute to TCF-dependent transcription in leukemia cells. These data indicate that Ξ³-catenin expression is a significant factor in the stabilization of Ξ²-catenin in AML. We also show that although normal cells exclude nuclear translocation of both Ξ³- and Ξ²-catenin, this level of regulation is lost in the majority of AML patients and cell lines, which allow nuclear accumulation of these catenins and inappropriate TCF-dependent transcription

    Neoadjuvant chemotherapy in breast cancer-response evaluation and prediction of response to treatment using dynamic contrast-enhanced and diffusion-weighted MR imaging

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    Objective To explore the predictive value of MRI parameters and tumour characteristics before neoadjuvant chemotherapy (NAC) and to compare changes in tumour size and tumour apparent diffusion coefficient (ADC) during treatment, between patients who achieved pathological complete response (pCR) and those who did not. Methods Approval by the Regional Ethics Committee and written informed consent were obtained. Thirty-one patients with invasive breast carcinoma scheduled for NAC were enrolled (mean age, 50.7; range, 37–72). Study design included MRI before treatment (Tp0), after four cycles of NAC (Tp1) and before surgery (Tp2). Data in pCR versus non-pCR groups were compared and cut-off values for pCR prediction were evaluated. Results Before NAC, HER2 overexpression was the single significant predictor of pCR (p=0.006). At Tp1 ADC, tumour size and changes in tumour size were all significantly different in the pCR and non-pCR groups. Using 1.42Γ—10βˆ’3 mm2/s as the cut-off value for ADC, pCR was predicted with sensitivity and specificity of 88% and 80%, respectively. Using a cut-off value of 83% for tumour volume reduction, sensitivity and specificity for pCR were 91% and 80%. Conclusion ADC, tumour size and tumour size reduction at Tp1 were strong independent predictors of pCR

    Dialysis initiation, modality choice, access, and prescription: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

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    Globally, the number of patients undergoing maintenance dialysis is increasing, yet throughout the world there is significant variability in the practice of initiating dialysis. Factors such as availability of resources, reasons for starting dialysis, timing of dialysis initiation, patient education and preparedness, dialysis modality and access, as well as varied \u201ccountry-specific\u201d factors significantly affect patient experiences and outcomes. As the burden of end-stage kidney disease (ESKD) has increased globally, there has also been a growing recognition of the importance of patient involvement in determining the goals of care and decisions regarding treatment. In January 2018, KDIGO (Kidney Disease: Improving Global Outcomes) convened a Controversies Conference focused on dialysis initiation, including modality choice, access, and prescription. Here we present a summary of the conference discussions, including identified knowledge gaps, areas of controversy, and priorities for research. A major novel theme represented during the conference was the need to move away from a \u201cone-size-fits-all\u201d approach to dialysis and provide more individualized care that incorporates patient goals and preferences while still maintaining best practices for quality and safety. Identifying and including patient-centered goals that can be validated as quality indicators in the context of diverse health care systems to achieve equity of outcomes will require alignment of goals and incentives between patients, providers, regulators, and payers that will vary across health care jurisdictions

    Live Imaging of Innate Immune Cell Sensing of Transformed Cells in Zebrafish Larvae: Parallels between Tumor Initiation and Wound Inflammation

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    Live imaging and genetic studies of the initial interactions between leukocytes and transformed cells in zebrafish larvae indicate an attractant role for H2O2 and suggest that blocking these early interactions reduces expansion of transformed cell clones

    The use of discrete choice experiments to inform health workforce policy: a systematic review.

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    BACKGROUND: Discrete choice experiments have become a popular study design to study the labour market preferences of health workers. Discrete choice experiments in health, however, have been criticised for lagging behind best practice and there are specific methodological considerations for those focused on job choices. We performed a systematic review of the application of discrete choice experiments to inform health workforce policy. METHODS: We searched for discrete choice experiments that examined the labour market preferences of health workers, including doctors, nurses, allied health professionals, mid-level and community health workers. We searched Medline, Embase, Global Health, other databases and grey literature repositories with no limits on date or language and contacted 44 experts. Features of choice task and experimental design, conduct and analysis of included studies were assessed against best practice. An assessment of validity was undertaken for all studies, with a comparison of results from those with low risk of bias and a similar objective and context. RESULTS: Twenty-seven studies were included, with over half set in low- and middle-income countries. There were more studies published in the last four years than the previous ten years. Doctors or medical students were the most studied cadre. Studies frequently pooled results from heterogeneous subgroups or extrapolated these results to the general population. Only one third of studies included an opt-out option, despite all health workers having the option to exit the labour market. Just five studies combined results with cost data to assess the cost effectiveness of various policy options. Comparison of results from similar studies broadly showed the importance of bonus payments and postgraduate training opportunities and the unpopularity of time commitments for the uptake of rural posts. CONCLUSIONS: This is the first systematic review of discrete choice experiments in human resources for health. We identified specific issues relating to this application of which practitioners should be aware to ensure robust results. In particular, there is a need for more defined target populations and increased synthesis with cost data. Research on a wider range of health workers and the generalisability of results would be welcome to better inform policy
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