139 research outputs found

    Can we import quality tools? a feasibility study of European practice assessment in a country with less organised general practice

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    <p>Abstract</p> <p>Background</p> <p>Quality is on the agenda of European general practice (GP). European researchers have, in collaboration, developed tools to assess quality of GPs. In this feasibility study, we tested the European Practice Assessment (EPA) in a one-off project in Belgium, where general practice has a low level of GP organisation.</p> <p>Methods</p> <p>A framework for feasibility analysis included describing the recruiting of participants, a brief telephone study survey among non-responders, organisational and logistic problems. Using field notes and focus groups, we studied the participants' opinions.</p> <p>Results</p> <p>In this study, only 36 of 1000 invited practices agreed to participate. Co-ordination, administrative work, practice visits and organisational problems required several days per practice. The researchers further encountered technical problems, for instance when entering the data and uploading to the web-based server. In subsequent qualitative analysis using two focus groups, most participant GPs expressed a positive feeling after the EPA procedure. In the short period of follow-up, only a few GPs reported improvements after the visit. The participant GPs suggested that follow-up and coaching would probably facilitate the implementation of changes.</p> <p>Conclusion</p> <p>This feasibility study shows that prior interest in EPA is low in the GP community. We encountered a number of logistic and organisational problems. It proved attractive to participants, but it can be augmented by coaching of participants in more than a one-off project to identify and achieve targets for quality improvement. In the absence of commitment of the government, a network of universities and one scientific organisation will offer EPA as a service to training practices.</p

    LPMLE3 : a novel 1-D approach to study water flow in streambeds using heat as a tracer

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    We introduce LPMLE3, a new 1-D approach to quantify vertical water flow components at streambeds using temperature data collected in different depths. LPMLE3 solves the partial differential equation for coupled water flow and heat transport in the frequency domain. Unlike other 1-D approaches it does not assume a semi-infinite halfspace with the location of the lower boundary condition approaching infinity. Instead, it uses local upper and lower boundary conditions. As such, the streambed can be divided into finite subdomains bound at the top and bottom by a temperature-time series. Information from a third temperature sensor within each subdomain is then used for parameter estimation. LPMLE3 applies a low order local polynomial to separate periodic and transient parts (including the noise contributions) of a temperature-time series and calculates the frequency response of each subdomain to a known temperature input at the streambed top. A maximum-likelihood estimator is used to estimate the vertical component of water flow, thermal diffusivity, and their uncertainties for each streambed subdomain and provides information regarding model quality. We tested the method on synthetic temperature data generated with the numerical model STRIVE and demonstrate how the vertical flow component can be quantified for field data collected in a Belgian stream. We show that by using the results in additional analyses, nonvertical flow components could be identified and by making certain assumptions they could be quantified for each subdomain. LPMLE3 performed well on both simulated and field data and can be considered a valuable addition to the existing 1-D methods

    Zebrafish usp39 Mutation Leads to rb1 mRNA Splicing Defect and Pituitary Lineage Expansion

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    Loss of retinoblastoma (Rb) tumor suppressor function is associated with human malignancies. Molecular and genetic mechanisms responsible for tumorigenic Rb downregulation are not fully defined. Through a forward genetic screen and positional cloning, we identified and characterized a zebrafish ubiquitin specific peptidase 39 (usp39) mutation, the yeast and human homolog of which encodes a component of RNA splicing machinery. Zebrafish usp39 mutants exhibit microcephaly and adenohypophyseal cell lineage expansion without apparent changes in major hypothalamic hormonal and regulatory signals. Gene expression profiling of usp39 mutants revealed decreased rb1 and increased e2f4, rbl2 (p130), and cdkn1a (p21) expression. Rb1 mRNA overexpression, or antisense morpholino knockdown of e2f4, partially reversed embryonic pituitary expansion in usp39 mutants. Analysis of pre-mRNA splicing status of critical cell cycle regulators showed misspliced Rb1 pre-mRNA resulting in a premature stop codon. These studies unravel a novel mechanism for rb1 regulation by a neuronal mRNA splicing factor, usp39. Zebrafish usp39 regulates embryonic pituitary homeostasis by targeting rb1 and e2f4 expression, respectively, contributing to increased adenohypophyseal sensitivity to these altered cell cycle regulators. These results provide a mechanism for dysregulated rb1 and e2f4 pathways that may result in pituitary tumorigenesis

    Zeb2 is essential for Schwann cell differentiation, myelination and nerve repair

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    Schwann cell development and peripheral nerve myelination require the serial expression of transcriptional activators, such as Sox10, Oct6 (also called Scip or Pou3f1) and Krox20 (also called Egr2). Here we show that transcriptional repression, mediated by the zinc-finger protein Zeb2 (also known as Sip1), is essential for differentiation and myelination. Mice lacking Zeb2 in Schwann cells develop a severe peripheral neuropathy, caused by failure of axonal sorting and virtual absence of myelin membranes. Zeb2-deficient Schwann cells continuously express repressors of lineage progression. Moreover, genes for negative regulators of maturation such as Sox2 and Ednrb emerge as Zeb2 target genes, supporting its function as an inhibitor of inhibitors in myelination control. When Zeb2 is deleted in adult mice, Schwann cells readily dedifferentiate following peripheral nerve injury and become repair cells. However, nerve regeneration and remyelination are both perturbed, demonstrating that Zeb2, although undetectable in adult Schwann cells, has a latent function throughout life
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