226 research outputs found

    Prophylaxis is the new standard of care in patients with haemophilia

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    Randomised controlled clinical trial evidence on prophylaxis as optimal care for patients with haemophilia was generated more than a decade ago. However, this knowledge has not translated into clinical practice in South Africa (SA) owing to many barriers to prophylaxis. These include the high treatment burden imposed by prophylaxis (frequent injections two to four times a week), the need for intravenous access to administer replacement clotting factor therapies, and the higher volume of clotting factor required compared with episodic treatment. The recently introduced non-factor therapies in haemophilia care have addressed many of these barriers. For example, emicizumab, which is currently the only globally approved non-factor therapy, can be administered subcutaneously less frequently (weekly, fortnightly or every 4 weeks) and has led to global adoption of prophylaxis as the standard of care in haemophilia by the bleeding disorders community. Haemophilia A is the most prevalent clotting factor deficiency in SA, with >2 000 people diagnosed to date. However, only a few of these patients are currently on prophylaxis. In this ‘In Practice’ article, we review the rationale for prophylaxis, outline its goals and benefits, and provide evidence-based guidance on which haemophilia patients should be prioritised for emicizumab prophylaxis. This consensus guidance facilitates the adoption of prophylaxis as a national policy and the new standard of care in haemophilia in SA.http://www.samj.org.zadm2022HaematologyPaediatrics and Child Healt

    A review of mid-frequency vibro-acoustic modelling for high-speed train extruded aluminium panels as well as the most recent developments in hybrid modelling techniques

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    Tumour cells sustain their high proliferation rate through metabolic reprogramming, whereby cellular metabolism shifts from oxidative phosphorylation to aerobic glycolysis, even under normal oxygen levels. Hypoxia-inducible factor 1A (HIF1A) is a major regulator of this process, but its activation under normoxic conditions, termed pseudohypoxia, is not well documented. Here, using an integrative approach combining the first genome-wide mapping of chromatin binding for an endocytic adaptor, ARRB1, both in vitro and in vivo with gene expression profiling, we demonstrate that nuclear ARRB1 contributes to this metabolic shift in prostate cancer cells via regulation of HIF1A transcriptional activity under normoxic conditions through regulation of succinate dehydrogenase A (SDHA) and fumarate hydratase (FH) expression. ARRB1-induced pseudohypoxia may facilitate adaptation of cancer cells to growth in the harsh conditions that are frequently encountered within solid tumours. Our study is the first example of an endocytic adaptor protein regulating metabolic pathways. It implicates ARRB1 as a potential tumour promoter in prostate cancer and highlights the importance of metabolic alterations in prostate cancer

    Expenditure Reform in Industrialised Countries: A Case Study Approach

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    This study examines reforms of public expenditure in industrialised countries over the past two decades. We distinguish ambitious and timid reformers and analyse in detail reform experiences in eight case studies of ambitious reform episodes. We find that ambitious reform countries reduce spending on transfers, subsidies and public consumption while largely sparing education spending. Such expenditure retrenchment is also typically part of a comprehensive reform package that includes improvements in fiscal institutions as well as structural and other macroeconomic reforms. The study finds that ambitious expenditure retrenchment and reform coincides with large improvements in fiscal and economic growth indicators

    Do nuclei go pear-shaped? Coulomb excitation of Rn-220 and Ra-224 at REX-ISOLDE (CERN)

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    Volume: 93The IS475 collaboration conducted Coulomb-excitation experiments with post-accelerated radioactive Rn-220 and Ra-224 beams at the REX-ISOLDE facility. The beam particles (E-beam: 2.83 MeV/u) were Coulomb excited using Ni-60, Cd-14, and Sn-120 scattering targets. De-excitation gamma-rays were detected employing the Miniball array and scattered particles were detected in a silicon detector. Exploiting the Coulomb-excitation code GOSIA for each nucleus several matrix elements could be obtained from the measured gamma-ray yields. The extracted matrix element allows for the conclusion that, while Rn-220 represents an octupole vibrational system, Ra-224 has already substantial octupole correlations in its ground state. This finding has i(m)plications for the search of CP-violating Schiff moments in the atomic systems of the adjacent odd-mass nuclei.Peer reviewe

    Effectiveness of a Multidisciplinary Occupational Training Program for Chronic Low Back Pain

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    Objective: To evaluate the effectiveness of a 12-wk multidisciplinary occupational training program for patients with chronic low back pain and to identify prognostic factors for treatment success. Design: A total of 51 participants were evaluated at baseline, at discharge, and at 1 yr after conclusion of the program. The evaluation included a physical examination and assessment of functional disability, psychological factors, and coping styles. The main target of the program is full work resumption. The central outcome measures therefore are three variables on return to work. Results: Analysis of variance for repeated measures revealed significant beneficial changes during the program for all measures except for several coping-style variables. The acquired level of maximum oxygen uptake, trunk flexibility, functional disability, and catastrophizing were maintained at 1-yr follow-up. At 1-yr follow-up, >60% of the participants had fully returned to work, which is an increase of >40% compared with baseline. Regression analyses showed that sex, age, the baseline values of reinterpretation of pain sensations, and functional disability and changes in trunk flexibility scores during the program are important prognostic factors for complete return to work. Conclusions: Based on the current findings, the program seems to be efficacious in the short term. Future attention must be directed toward maintaining these results, although work resumption rates improved considerably 1 yr after conclusion of the program

    Bulk and surface rheology of Aculyn™ 22 and Aculyn™ 33 polymeric solutions and kinetics of foam drainage

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    This paper was accepted for publication in the journal Colloids and Surfaces A: Physicochemical and Engineering Aspects and the definitive published version is available at http://dx.doi.org/10.1016/j.colsurfa.2013.05.072Experimental investigations of both bulk and surface rheology of solutions of commercially available polymers AculynTM 22 and AculynTM 33 in presence of sodium chloride are performed in a wide range of the polymer and salt concentrations. It is shown that the bulk viscosity and the surface viscoelastic modulus of solutions of both polymers increases with the increase of polymer concentration and the decrease of the salt concentration. Solutions of both polymers demonstrate very good foamability and form stable foams. Foam drainage is governed mainly by the bulk viscosity when the latter is in the range of 100-500 mPa·s
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