Stabilisation of BGK modes by relativistic effects

Context. We examine plasma thermalisation processes in the foreshock region of astrophysical shocks within a fully kinetic and self-consistent treatment. We concentrate on proton beam driven electrostatic processes, which are thought to play a key role in the beam relaxation and the particle acceleration. Our results have implications for the effectiveness of electron surfing acceleration and the creation of the required energetic seed population for first order Fermi acceleration at the shock front. Aims. We investigate the acceleration of electrons via their interaction with electrostatic waves, driven by the relativistic Buneman instability, in a system dominated by counter-propagating proton beams. Methods. We adopt a kinetic Vlasov-Poisson description of the plasma on a fixed Eulerian grid and observe the growth and saturation of electrostatic waves for a range of proton beam velocities, from 0.15c to 0.9c. Results. We can report a reduced stability of the electrostatic wave (ESW) with increasing non-relativistic beam velocities and an improved wave stability for increasing relativistic beam velocities, both in accordance with previous findings. At the highest beam speeds, we find the system to be stable again for a period of ≈160 plasma periods. Furthermore, the high phase space resolution of the Eulerian Vlasov approach reveals processes that could not be seen previously with PIC simulations. We observe a, to our knowledge, previously unreported secondary electron acceleration mechanism at low beam speeds. We believe that it is the result of parametric couplings to produce high phase velocity ESW’s which then trap electrons, accelerating them to higher energies. This allows electrons in our simulation study to achieve the injection energy required for Fermi acceleration, for beam speeds as low as 0.15c in unmagnetised plasma

Programme cantonal diabète dans le canton de Vaud indicateurs pour le suivi et le baromètre : rapport final

Le Programme cantonal Diabète souhaite collecter des indicateurs afin d'objectiver son suivi et produire un Baromètre Diabète Vaud qui serait publié et distribué périodiquement à un public large. Ce rapport présente les indicateurs suggérés par l'IUMSP, mandaté afin d'établir une liste raisonnée d'indicateurs sur le diabète pour le canton de Vaud. La sélection d'indicateurs s'est faite d'après plusieurs critères, parmi lesquels la disponibilité des indicateurs actuelle et à long terme, ainsi que leur pertinence avérée par la littérature. Ce rapport décrit les résultats pour les indicateurs sélectionnés, ainsi que les informations nécessaires à leur compréhension : source, fréquence de mise à disposition, méthode de calcul, limites, références éventuelles. Parmi les indicateurs décrits dans ce rapport, certains sont proposés comme spécialement pertinents à inclure dans le futur Baromètre Diabète Vaud. Aussi, une suggestion de présentation de ces indicateurs (fiches descriptives) est articulée pour ce dernier

Quasi-periodic modulation of solar and stellar flaring emission by magnetohydrodynamic oscillations in a nearby loop

We propose a new model for quasi-periodic modulation of solar and stellar flaring emission. Fast magnetoacoustic oscillations of a non-flaring loop can interact with a nearby flaring active region. This interaction occurs when part of the oscillation situated outside the loop reaches the regions of steep gradients in magnetic field within an active region and produces periodic variations of electric current density. The modulation depth of these variations is a few orders of magnitude greater than the amplitude of the driving oscillation. The variations of the current can induce current-driven plasma micro-instabilities and thus anomalous resistivity. This can periodically trigger magnetic reconnection, and hence acceleration of charged particles, producing quasi-periodic pulsations of X-ray, optical and radio emission at the arcade footpoints

Computational design of dynamic receptor-peptide signaling complexes applied to chemotaxis.

Engineering protein biosensors that sensitively respond to specific biomolecules by triggering precise cellular responses is a major goal of diagnostics and synthetic cell biology. Previous biosensor designs have largely relied on binding structurally well-defined molecules. In contrast, approaches that couple the sensing of flexible compounds to intended cellular responses would greatly expand potential biosensor applications. Here, to address these challenges, we develop a computational strategy for designing signaling complexes between conformationally dynamic proteins and peptides. To demonstrate the power of the approach, we create ultrasensitive chemotactic receptor-peptide pairs capable of eliciting potent signaling responses and strong chemotaxis in primary human T cells. Unlike traditional approaches that engineer static binding complexes, our dynamic structure design strategy optimizes contacts with multiple binding and allosteric sites accessible through dynamic conformational ensembles to achieve strongly enhanced signaling efficacy and potency. Our study suggests that a conformationally adaptable binding interface coupled to a robust allosteric transmission region is a key evolutionary determinant of peptidergic GPCR signaling systems. The approach lays a foundation for designing peptide-sensing receptors and signaling peptide ligands for basic and therapeutic applications

Comparative assessment of onabotulinumtoxinA and mirabegron for overactive bladder: an indirect treatment comparison

CONTEXT: OnabotulinumtoxinA and mirabegron have recently gained marketing authorisation to treat symptoms of overactive bladder (OAB). OBJECTIVE: To evaluate the relative efficacy of mirabegron and onabotulinumtoxinA in patients with idiopathic OAB. DESIGN: Network meta-analysis. DATA SOURCES: A search of 9 electronic databases, review documents, guidelines and websites. METHODS: Randomised trials comparing any licensed dose of onabotulinumtoxinA or mirabegron with each other, anticholinergic drugs or placebo were eligible (19 randomised trials were identified). 1 reviewer extracted data from the studies and a second reviewer checked the data. Candidate trials were assessed for similarity and networks were developed for each outcome. Bayesian network meta-analysis was conducted using both fixed-effects and random-effects models. When there were differences in mean baseline values between mirabegron and onabotulinumtoxinA trials they were adjusted for using network meta-regression (NMR). RESULTS: No studies directly comparing onabotulinumtoxinA to mirabegron were identified. A network was created for each of the 7 outcomes, with 3-9 studies included in each individual network. The trials included in the networks were broadly similar. Patients in the onabotulinumtoxinA trials had more urinary incontinence and urgency episodes at baseline than patients in the mirabegron trials and these differences were adjusted for using NMR. Both onabotulinumtoxinA and mirabegron were more efficacious than placebo at reducing the frequency of urinary incontinence, urgency, urination and nocturia. OnabotulinumtoxinA was more efficacious than mirabegron (50 and 25 mg) in completely resolving daily episodes of urinary incontinence and urgency and in reducing the frequency of urinary incontinence, urgency and urination. NMR supported the results of the network meta-analysis. CONCLUSIONS: In the absence of head-to-head trials comparing onabotulinumtoxinA to mirabegron, this indirect comparison indicates that onabotulinumtoxinA may be superior to mirabegron in improving symptoms of urinary incontinence, urgency and urinary frequency in patients with idiopathic OAB

Chlamydia control activities in Europe: cross-sectional survey

Background: Chlamydia is the most commonly reported bacterial sexually transmitted infection in Europe. The objective of the Screening for Chlamydia in Europe (SCREen) project was to describe current and planned chlamydia control activities in Europe. Methods: The authors sent a questionnaire asking about different aspects of chlamydia epidemiology and control to public health and clinical experts in each country in 2007. The principles of sexually transmitted infection control were used to develop a typology comprising five categories of chlamydia control activities. Each country was assigned to a category, based on responses to the questionnaire. Results: Experts in 29 of 33 (88%) invited countries responded. Thirteen of 29 countries (45%) had no current chlamydia control activities. Six countries in this group stated that there were plans to introduce chlamydia screening programmes. There were five countries (17%) with case management guidelines only. Three countries (10%) also recommended case finding amongst partners of diagnosed chlamydia cases or people with another sexually transmitted infection. Six countries (21%) further specified groups of asymptomatic people eligible for opportunistic chlamydia testing. Two countries (7%) reported a chlamydia screening programme. There was no consistent association between the per capita gross domestic product of a country and the intensity of chlamydia control activities (P = 0.816). Conclusion: A newly developed classification system allowed the breadth of ongoing national chlamydia control activities to be described and categorized. Chlamydia control strategies should ensure that clinical guidelines to optimize chlamydia diagnosis and case management have been implemented before considering the appropriateness of screening programmes

Social inequalities in self-rated health by age: Cross-sectional study of 22 457 middle-aged men and women

<p>Abstract</p> <p>Background</p> <p>We investigate the association between occupational social class and self-rated health (SRH) at different ages in men and women.</p> <p>Methods</p> <p>Cross sectional population study of 22 457 men and women aged 39–79 years living in the general community in Norfolk, United Kingdom, recruited using general practice age-sex registers in 1993–1997. The relationship between self-rated health and social class was examined using logistic regression, with a poor or moderate rating as the outcome.</p> <p>Results</p> <p>The prevalence of poor or moderate (lower) self-rated health increased with increasing age in both men and women. There was a strong social class gradient: in manual classes, men and women under 50 years of age had a prevalence of lower self-rated health similar to that seen in men and women in non-manual social classes over 70 years old. Even after adjustment for age, educational status, and lifestyle factors (body mass index (BMI), smoking, physical activity and alcohol consumption) there was still strong evidence of a social gradient in self-rated health, with unskilled men and women approximately twice as likely to report lower self-rated health as professionals (OR_men= 2.44 (95%CI 1.69, 3.50); OR_women= 1.97 (95%CI 1.45, 2.68).</p> <p>Conclusion</p> <p>There was a strong gradient of decreased SRH with age in both men and women. We found a strong cross-sectional association between SRH and social class, which was independent of education and major health related behaviors. The social class differential in SRH was similar with age. Prospective studies to confirm this association should explore social and emotional as well as physical pathways to inequalities in self reported health.</p

Discourses of antagonism and desire : marketing for international students in neighbourhood schools

This paper explores the consequences of these discourses for the ways that international students are identified and positioned within school communities. My argument is developed in four sections. The first describes my ongoing exploration into the impact of international student programmes in Australia. The second exemplifies my argument: exploring the day-to-day experiences of vice principals in two Victorian government state secondary schools as they market their schools, and examining the systemic and ontological discourses played out within those conversations. The third interrogates discourses of identity and difference, neo-liberalism and nave cosmopolitanism which I find shape teacher conversations about international student programmes. In the final section, I argue that the impact of the discourse formations implicit in teacher talk about international student programmes has been the objectification of international students and their ambivalent inclusion within the school community.<br /

Elevated 4R-tau in astrocytes from asymptomatic carriers of the MAPT 10+16 intronic mutation

The microtubule-associated protein tau gene (MAPT) 10+16 intronic mutation causes frontotemporal lobar degeneration (FTLD) by increasing expression of four-repeat (4R)-tau isoforms. We investigated the potential role for astrocytes in the pathogenesis of FTLD by studying the expression of 4R-tau. We derived astrocytes and neurons from induced pluripotent stem cells from two asymptomatic 10+16 carriers which, compared to controls, showed persistently increased 4R:3R-tau transcript and protein ratios in both cell types. However, beyond 300 days culture, 10+16 neurons showed less marked increase of this 4R:3R-tau transcript ratio compared to astrocytes. Interestingly, throughout maturation, both 10+16 carriers consistently displayed different 4R:3R-tau transcript and protein ratios. These elevated levels of 4R-tau in astrocytes implicate glial cells in the pathogenic process and also suggests a cell-type-specific regulation and may inform and help on treatment of pre-clinical tauopathies

Post-trial follow-up methodology in large randomised controlled trials: a systematic review.

BACKGROUND: Randomised controlled clinical trials typically have a relatively brief in-trial follow-up period which can underestimate safety signals and fail to detect long-term hazards, which may take years to appear. Extended follow-up after the scheduled closure of the trial allows detection of both persistent or enhanced beneficial effects following cessation of study treatment (i.e. a legacy effect) and the emergence of possible adverse effects (e.g. development of cancer). METHODS: A systematic review was conducted following PRISMA guidelines to qualitatively compare post-trial follow-up methods used in large randomised controlled trials. Five bibliographic databases, including Medline and the Cochrane Library, and one trial registry were searched. All large randomised controlled trials (more than 1000 adult participants) published from March 2006 to April 2017 were evaluated. Two reviewers screened and extracted data attaining > 95% concordance of papers checked. Assessment of bias in the trials was evaluated using the Cochrane Risk of Bias tool. RESULTS: Fifty-seven thousand three hundred and fifty-two papers were identified and 65 trials which had post-trial follow-up (PTFU) were included in the analysis. The majority of trials used more than one type of follow-up. There was no evidence of an association between the retention rates of participants in the PTFU period and the type of follow-up used. Costs of PTFU varied widely with data linkage being the most economical. It was not possible to assess associations between risk of bias during the in-trial period and proportions lost to follow-up during the PTFU period. DISCUSSION: Data captured during the post-trial follow-up period can add scientific value to a trial. However, there are logistical and financial barriers to overcome. Where available, data linkage via electronic registries and records is a cost-effective method which can provide data on a range of endpoints. SYSTEMATIC REVIEW REGISTRATION: Not applicable for PROSPERO registration