75 research outputs found

    Continuous, Semi-discrete, and Fully Discretized Navier-Stokes Equations

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    The Navier--Stokes equations are commonly used to model and to simulate flow phenomena. We introduce the basic equations and discuss the standard methods for the spatial and temporal discretization. We analyse the semi-discrete equations -- a semi-explicit nonlinear DAE -- in terms of the strangeness index and quantify the numerical difficulties in the fully discrete schemes, that are induced by the strangeness of the system. By analyzing the Kronecker index of the difference-algebraic equations, that represent commonly and successfully used time stepping schemes for the Navier--Stokes equations, we show that those time-integration schemes factually remove the strangeness. The theoretical considerations are backed and illustrated by numerical examples.Comment: 28 pages, 2 figure, code available under DOI: 10.5281/zenodo.998909, https://doi.org/10.5281/zenodo.99890

    Preponderance of the oncogenic V599E and V599K mutations in B-raf kinase domain is enhanced in melanoma cutaneous/subcutaneous metastases

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    BACKGROUND: Downstream of Ras, the serine/threonine kinase B-raf has been reported to be mutated, among other carcinomas, in a substantial subset of primary melanomas with a preponderance of mutations within the kinase domain including the activating V599E and V599K transitions. METHODS: We here investigated a representative series of 60 resection specimens of cutaneous and subcutaneous melanoma metastases for the presence of mutations within the activation segment (exon 15) of the B-raf kinase domain by polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) gel electrophoresis. RESULTS: Sequencing of cloned PCR-SSCP amplicons resulted in 24 (40%) samples harbouring somatic mutations which is not exceeding the mutation frequency in recently investigated primary melanomas. The activating mutation T1796A was present in 24/60 (40%) resection specimens, followed in frequency by the oncogenic g1795A mutation in 8/60 (13%) cases. As to the B-raf protein sequence, the acidic amino acid transitions V599E and V599K were predicted in 19/60 (32%) and 6/60 (10%) cases, resepectively, but were not associated with enhanced risk for subsequent metastasis in patients' follow up. In comparison to the primary melanomas that we recently investigated, the spectrum of predicted B-raf protein mutations narrowed significantly in the cutaneous/subcutaneous metastases. Unexpectedly, V599 and V599E mutations were absent in cutaneous/subcutaneous metastases derived from acrolentiginous melanomas as preceding primary tumours. CONCLUSION: During transition from primary melanomas towards cutaneous/subcutaneous metastases, the spectrum of predicted B-raf mutations narrows significantly. Focusing on the V599E and V599K, these oncogenic mutations are likely to affect melanocyte-specific pathways controlling proliferation and differentiation

    Does the routine use of global coronary heart disease risk scores translate into clinical benefits or harms? A systematic review of the literature

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    <p>Abstract</p> <p>Background</p> <p>Guidelines now recommend routine assessment of global coronary heart disease (CHD) risk scores. We performed a systematic review to assess whether global CHD risk scores result in clinical benefits or harms.</p> <p>Methods</p> <p>We searched MEDLINE (1966 through June 13, 2007) for articles relevant to our review. Using predefined inclusion and exclusion criteria, we included studies of any design that provided physicians with global risk scores or allowed them to calculate scores themselves, and then measured clinical benefits and/or harms. Two reviewers reviewed potentially relevant studies for inclusion and resolved disagreement by consensus. Data from each article was then abstracted into an evidence table by one reviewer and the quality of evidence was assessed independently by two reviewers.</p> <p>Results</p> <p>11 studies met criteria for inclusion in our review. Six studies addressed clinical benefits and 5 addressed clinical harms. Six studies were rated as "fair" quality and the others were deemed "methodologically limited". Two fair quality studies showed that physician knowledge of global CHD risk is associated with increased prescription of cardiovascular drugs in high risk (but not all) patients. Two additional fair quality studies showed no effect on their primary outcomes, but one was underpowered and the other focused on prescribing of lifestyle changes, rather than drugs whose prescribing might be expected to be targeted by risk level. One of these aforementioned studies showed improved blood pressure in high-risk patients, but no improvement in the proportion of patients at high risk, perhaps due to the high proportion of participants with baseline risks significantly exceeding the risk threshold. Two fair quality studies found no evidence of harm from patient knowledge of global risk scores when they were accompanied by counseling, and optional or scheduled follow-up. Other studies were too methodologically limited to draw conclusions.</p> <p>Conclusion</p> <p>Our review provides preliminary evidence that physicians' knowledge of global CHD risk scores may translate into modestly increased prescribing of cardiovascular drugs and modest short-term reductions in CHD risk factors without clinical harm. Whether these results are replicable, and translate across other practice settings or into improved long-term CHD outcomes remains to be seen.</p

    Impaired PASAT performance in multiple sclerosis correlates with reduced diffusion anisotropy in white matter pathways of the working memory network

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    Perceptions of a simulated general dental practice facility - reported experiences from past students at the Maurice Wohl General Dental Practice Centre 2001-2008

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    UNLABELLED: This article assesses the perceived value of a simulated general dental practice centre as reported by past undergraduates over five years. Various aspects of teaching and related outcomes are explored based on responses received from anonymous questionnaires. A team based approach to cooperative learning led by current practitioners experienced in primary dental care was seen as pivotal to the huge success of the teaching model. Moreover the role of cooperative learning and its influence on building individual clinical confidence and acumen was considered highly beneficial as part of the transition from novice to expert. METHODOLOGY: An anonymous questionnaire was distributed to students six months after qualification for a period of five years. The last registered postal address held by the Institute was used for this purpose. The years surveyed were: 2001-2002, 2002-2003, 2003-2004, 2005-2006 and 2007-2008. The questionnaire provided for both qualitative aspects of feedback and a quantitative representation of the overall perception of effectiveness of the General Dental Practice Centre, as expressed by a visual analogue scale. RESULTS: In total 135 questionnaires were returned representing a return rate of 53%. From the responses received 99% of the students reported that they enjoyed their sessions at the Centre with 96% expressing satisfaction with the teaching regime. The mean visual analogue scale rating the centre overall was reported as 83%, with a year on year increase ranging from 76-92%. Rich qualitative data were derived from free text responses. CONCLUSION: A simulated general dental practice centre was highly rated by past dental students in terms of the overall learning experience received and its relevance to later vocational training. By far the most consistently reported attribute was the opportunity to practise close support four handed dentistry with a nurse. Training in practice management and organisational skills were viewed as important with effective teamwork and a friendly environment seen as conducive to building up knowledge and confidence. The role of experienced current primary care practitioners as teachers was seen to be very effective in this setting
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