Effective Feedback to Improve Primary Care Prescribing Safety (EFIPPS) a pragmatic three-arm cluster randomised trial:designing the intervention (ClinicalTrials.gov registration NCT01602705)

Peer reviewedPublisher PD

Maternal Malaria Induces a Procoagulant and Antifibrinolytic State That Is Embryotoxic but Responsive to Anticoagulant Therapy

Low birth weight and fetal loss are commonly attributed to malaria in endemic areas, but the cellular and molecular mechanisms that underlie these poor birth outcomes are incompletely understood. Increasing evidence suggests that dysregulated hemostasis is important in malaria pathogenesis, but its role in placental malaria (PM), characterized by intervillous sequestration of Plasmodium falciparum, proinflammatory responses, and excessive fibrin deposition is not known. To address this question, markers of coagulation and fibrinolysis were assessed in placentae from malaria-exposed primigravid women. PM was associated with significantly elevated placental monocyte and proinflammatory marker levels, enhanced perivillous fibrin deposition, and increased markers of activated coagulation and suppressed fibrinolysis in placental plasma. Submicroscopic PM was not proinflammatory but tended to be procoagulant and antifibrinolytic. Birth weight trended downward in association with placental parasitemia and high fibrin score. To directly assess the importance of coagulation in malaria-induced compromise of pregnancy, Plasmodium chabaudi AS-infected pregnant C57BL/6 mice were treated with the anticoagulant, low molecular weight heparin. Treatment rescued pregnancy at midgestation, with substantially decreased rates of active abortion and reduced placental and embryonic hemorrhage and necrosis relative to untreated animals. Together, the results suggest that dysregulated hemostasis may represent a novel therapeutic target in malaria-compromised pregnancies

Diabetes self-management arrangements in Europe: a realist review to facilitate a project implemented in six countries

Background: Self-management of long term conditions can promote quality of life whilst delivering benefits to the financing of health care systems. However, rarely are the meso-level influences, likely to be of direct relevance to these desired outcomes, systematically explored. No specific international guidelines exist suggesting the features of the most appropriate structure and organisation of health care systems within which to situate self-management approaches and practices. This review aimed to identify the quantitative literature with regard to diabetes self-management arrangements currently in place within the health care systems of six countries (The United Kingdom, The Netherlands, Norway, Spain, Bulgaria, and Greece) and explore how these are integrated into the broader health care and welfare systems in each country. Methods: The methodology for a realist review was followed. Publications of interest dating from 2000 to 2013 were identified through appropriate MeSH terms by a systematic search in six bibliographic databases. A search diary was maintained and the studies were assessed for their quality and risk of bias. Results: Following the multi-step search strategy, 56 studies were included in the final review (the majority from the UK) reporting design methods and findings on 21 interventions and programmes for diabetes and chronic disease self-management. Most (11/21, 52%) of the interventions were designed to fit within the context of primary care. The majority (11/21, 52%) highlighted behavioural change as an important goal. Finally, some (5/21, 24%) referred explicitly to Internet-based tools. Conclusions: This review is based on results which are derived from a total of at least 5,500 individuals residing in the six participating countries. It indicates a policy shift towards patient-centred self-management of diabetes in a primary care context. The professional role of diabetes specialist nurses, the need for multidisciplinary approaches and a focus on patient education emerge as fundamental principles in the design of relevant programmes. Socio-economic circumstances are relevant to the capacity to self-manage and suggest that any gains and progress will be hard to maintain during economic austerity. This realist review should be interpreted within the wider context of a whole systems approach regarding self-care support and chronic illness management

Measurement of the prompt J/psi and psi(2S) polarizations in pp collisions at sqrt(s) = 7 TeV

The polarizations of prompt J/psi and psi(2S) mesons are measured in proton-proton collisions at sqrt(s) = 7 TeV, using a dimuon data sample collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 4.9 inverse femtobarns. The prompt J/psi and psi(2S) polarization parameters lambda[theta], lambda[phi], and lambda[theta, phi], as well as the frame-invariant quantity lambda(tilde), are measured from the dimuon decay angular distributions in three different polarization frames. The J/psi results are obtained in the transverse momentum range 14 < pt < 70 GeV, in the rapidity intervals abs(y) < 0.6 and 0.6 < abs(y) < 1.2. The corresponding psi(2S) results cover 14 < pt < 50 GeV and include a third rapidity bin, 1.2 < abs(y) < 1.5. No evidence of large transverse or longitudinal polarizations is seen in these kinematic regions, which extend much beyond those previously explored

Schadevergoeding bij overlijden: een stoel die een soort tafeltje is

In het aansprakelijkheidsrecht heeft een benadeelde in beginsel recht op volledige vergoeding van zijn schade. De gevolgen van de schadetoebrengende gebeurtenis dienen zoveel als mogelijk te worden weggenomen of te worden gecompenseerd. Daarbij wordt gekeken naar de situatie waarin de benadeelde zou hebben verkeerd indien de schadetoebrengende gebeurtenis niet zou hebben plaatsgevonden. Dat is bij overlijden per definitie problematisch. Er is iemand weggevallen, wat vele gevolgen heeft. De schade als gevolg van het overlijden komt maar beperkt voor vergoeding in aanmerking. In artikel 6:108 BW is een drietal beperkingen te vinden. Het gaat hier om beperkingen ten aanzien van de aard van de schade, de kring van gerechtigden en de omvang van de schade. Daarbij hinkt het recht op schadevergoeding bij overlijden op twee gedachten. Aan de ene kant is er het aansprakelijkheidsrecht, maar de geleden schade komt niet volledig voor vergoeding in aanmerking. Aan de andere kant is er het recht op alimentatie uit het familierecht, maar dat wordt bij overlijden niet consequent toegepast. De motieven voor de beperkingen van het recht op schadevergoeding zijn achterhaald en niet (langer) overtuigend. Het recht is niet bij de tijd, het sluit niet aan bij de maatschappelijke ontwikkelingen. De beperkingen die het recht op schadevergoeding bij overlijden in de huidige samenleving met zich meebrengt zorgen voor complexe methoden om de nabestaanden tegemoet te komen en oogsten daardoor veel kritiek. In deze bijdrage wordt die kritiek besproken. De bijdrage wordt afgesloten met enkele denkrichtingen voor nader onderzoek

Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization

Alignment of the CMS tracker with LHC and cosmic ray data

© CERN 2014 for the benefit of the CMS collaboration, published under the terms of the Creative Commons Attribution 3.0 License by IOP Publishing Ltd and Sissa Medialab srl. Any further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation and DOI.The central component of the CMS detector is the largest silicon tracker ever built. The precise alignment of this complex device is a formidable challenge, and only achievable with a significant extension of the technologies routinely used for tracking detectors in the past. This article describes the full-scale alignment procedure as it is used during LHC operations. Among the specific features of the method are the simultaneous determination of up to 200 000 alignment parameters with tracks, the measurement of individual sensor curvature parameters, the control of systematic misalignment effects, and the implementation of the whole procedure in a multi-processor environment for high execution speed. Overall, the achieved statistical accuracy on the module alignment is found to be significantly better than 10μm

Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.Peer reviewe