Prevalence, correlates and clinical usefulness of antibodies to RNA polymerase III in systemic sclerosis: a cross-sectional analysis of data from an Australian cohort

Extent: 13p.INTRODUCTION: The prevalence of antibodies to RNA polymerase III (anti-RNAP) differs among systemic sclerosis (SSc) cohorts worldwide. Previously reported associations of anti-RNAP include diffuse cutaneous disease, tendon friction rubs and renal crisis, with recent reports suggesting a close temporal association between malignancy and SSc disease onset among patients with anti-RNAP. METHODS: Patients with SSc were tested for the presence of anti-RNAP at recruitment into the Australian Scleroderma Cohort Study. We used univariate and multivariable methods to identify and quantify clinical and laboratory correlates of anti-RNAP in SSc. Diagnostic testing procedures were used to determine the usefulness of these antibodies in estimating the likelihood of clinically important outcomes. RESULTS: There were 451 patients with mean ± standard deviation age and disease duration at recruitment of 58.1 ± 12.4 and 11.6 ± 10.0 years, respectively; 151 (33.5%) patients were recruited within 5 years of diagnosis of SSc. Overall, 69 (15.3%) patients had anti-RNAP. Univariate associations of anti-RNAP were diffuse disease (75.4% vs. 20.9%, P < 0.0001), joint contractures (73.9% vs. 30.1%, P < 0.0001), greater highest-recorded modified Rodnan skin score (20.6 ± 12.4 vs. 10.1 ± 7.9, P < 0.0001), synovitis (31.9% vs. 19.9%, P = 0.03), myositis (2.9% vs. 0.5%, P = 0.05), systemic hypertension (59.4% vs. 39.7%, P = 0.002), renal crisis (24.6% vs. 1.8%, P < 0.0001) and malignancy diagnosed within 5 years of onset of SSc skin disease (13.3% vs. 3.9%, P = 0.01). In multiple regression analysis, after adjustment for other covariates, anti-RNAP were independently associated with renal crisis (odds ratio (OR) 3.8, 95% confidence interval (CI) 1.2 to 11.5, P = 0.02; positive predictive value (PPV) 24.6%, negative predictive value (NPV) 98.2%), diffuse disease (OR 6.4, 95% CI 2.9 to 13.8, P < 0.0001; PPV 75.4%, NPV 20.9%), joint contractures (OR 2.5, 95% CI 1.2 to 5.3, P = 0.02; PPV 73.9%, NPV 69.9%) and malignancy diagnosed within 5 years of onset of SSc skin disease (OR 4.2, 95% CI 1.3 to 13.4, P = 0.01; PPV 13.3%, NPV 96.1%). CONCLUSIONS: Anti-RNAP status is a clinically useful prognostic marker in SSc and enables clinicians to identify patients at high risk of developing renal crisis, synovitis, myositis and joint contractures. Patients with anti-RNAP also have an increased risk of malignancy within a 5-year timeframe before or after onset of SSc skin changes.Mandana Nikpour, Pravin Hissaria, Jillian Byron, Joanne Sahhar, Maree Micallef, William Paspaliaris, Janet Roddy, Peter Nash, Alan Sturgess, Susanna Proudman and Wendy Steven

Sustainable Undernutrition Reduction in Ethiopia (SURE) evaluation study: a protocol to evaluate impact, process and context of a large-scale integrated health and agriculture programme to improve complementary feeding in Ethiopia.

INTRODUCTION: Improving complementary feeding in Ethiopia requires special focus on dietary diversity. The Sustainable Undernutrition Reduction in Ethiopia (SURE) programme is a government-led multisectoral intervention that aims to integrate the work of the health and agriculture sectors to deliver a complex multicomponent intervention to improve child feeding and reduce stunting. The Federal Ministries of Health and Agriculture and Natural Resources implement the intervention. The evaluation aims to assess a range of processes, outcomes and impacts. METHODS AND ANALYSIS: The SURE evaluation study is a theory-based, mixed methods study comprising impact and process evaluations. We hypothesise that the package of SURE interventions, including integrated health and agriculture behaviour change communication for nutrition, systems strengthening and multisectoral coordination, will result in detectable differences in minimum acceptable diet in children 6-23 months and stunting in children 24-47 months between intervention and comparison groups. Repeated cross-sectional household surveys will be conducted at baseline and endline to assess impact. The process will be assessed using observations, key informant interviews and focus group discussions to investigate the fidelity and dose of programme implementation, behavioural pathways of impact and contextual factors interacting with the intervention. Pathways of impact will also be explored through statistical analyses. ETHICS AND DISSEMINATION: The study has received ethics approval from the scientific and ethical review committees at the Ethiopian Public Health Institute and the London School of Hygiene and Tropical Medicine. The findings will be disseminated collaboratively with stakeholders at specified time points and through peer-reviewed publications and presentations

Can selenium deficiency in Malawi be alleviated through consumption of agro-biofortified maize flour? Study protocol for a randomised, double-blind, controlled trial

Micronutrient deficiencies including selenium (Se) are widespread in Malawi and potentially underlie a substantial disease burden, particularly among poorer and marginalised populations. Concentrations of Se in staple cereal crops can be increased through application of Se fertilisers – a process known as agronomic biofortification (agro-biofortification) – and this may contribute to alleviating deficiencies. The Addressing Hidden Hunger with Agronomy (AHHA) trial aims to establish the efficacy of this approach for improving Se status in rural Malawi

Relapse prevention for addictive behaviors

The Relapse Prevention (RP) model has been a mainstay of addictions theory and treatment since its introduction three decades ago. This paper provides an overview and update of RP for addictive behaviors with a focus on developments over the last decade (2000-2010). Major treatment outcome studies and meta-analyses are summarized, as are selected empirical findings relevant to the tenets of the RP model. Notable advances in RP in the last decade include the introduction of a reformulated cognitive-behavioral model of relapse, the application of advanced statistical methods to model relapse in large randomized trials, and the development of mindfulness-based relapse prevention. We also review the emergent literature on genetic correlates of relapse following pharmacological and behavioral treatments. The continued influence of RP is evidenced by its integration in most cognitive-behavioral substance use interventions. However, the tendency to subsume RP within other treatment modalities has posed a barrier to systematic evaluation of the RP model. Overall, RP remains an influential cognitive-behavioral framework that can inform both theoretical and clinical approaches to understanding and facilitating behavior change

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Measurement of the very rare K+→π+ννˉK^+ \to \pi^+ \nu \bar\nu decay

The decay K+→π+νν¯ , with a very precisely predicted branching ratio of less than 10−10 , is among the best processes to reveal indirect effects of new physics. The NA62 experiment at CERN SPS is designed to study the K+→π+νν¯ decay and to measure its branching ratio using a decay-in-flight technique. NA62 took data in 2016, 2017 and 2018, reaching the sensitivity of the Standard Model for the K+→π+νν¯ decay by the analysis of the 2016 and 2017 data, and providing the most precise measurement of the branching ratio to date by the analysis of the 2018 data. This measurement is also used to set limits on BR(K+→π+X ), where X is a scalar or pseudo-scalar particle. The final result of the BR(K+→π+νν¯ ) measurement and its interpretation in terms of the K+→π+X decay from the analysis of the full 2016-2018 data set is presented, and future plans and prospects are reviewed

A study of the amplification of laser and VLF waves using a simple pendulum model

The Lorentz force equation governing the interaction between radiation and charged particles in the presence of a static magnetic field can be reduced to the form of the simple pendulum equation, when applied to the Free Electron Laser (FEL) and to the amplification of whistler waves in the magnetosphere. The first topic in this thesis is the start-up of an FEL with a compact design having a small, spatial undulator period, many periods, and a small undulator field strength. Under these conditions, the number of photons spontaneously emitted into the resonator mode each pass is so small that a classical field cannot be established. Quantum fluctuations affect the wave- particle interaction and therefore diminish weak field gain. An FEL start-up condition, several orders of magnitude more restrictive than determined by quantum recoil alone, is derived from the photon rate equation. The next topic is the evolution of a weak, classical radiation field driven by a long electron pulsehttp://archive.org/details/studyofamplifica00sturCaptain, United States ArmyApproved for public release; distribution is unlimited

Evaluating open and distance education at Central Queensland University: three sites of evidence-based practice and reflection

This seminar articulates with the recent publication of Evaluation in Open and Distance Education: Retrospects and Prospects (Nouwens, Erdinc & Danaher, 2004a), a special theme issue of the Turkish Online Journal of Distance Education, five of whose eight articles were co-written by twelve CQU staff members from three Faculties and one Division. http://tojde.anadolu.edu.tr/tojde15/index.htm The seminar takes up three of the sites of evidence-based practice and reflection around evaluating open and distance education at Central Queensland University canvassed in the theme issue: • an online discussion list as promoting students’ attitudinal change (Bradshaw & Hinton, 2004); • a philosophically informed framework for identifying multiple interests of evaluating open and distance education (Nouwens, Ross, Harreveld, Thomson & Danaher, 2004); • the selection of CQU’s designated online learning management system (Sturgess & Nouwens, 2004). Each site is examined for what it highlighted about the nature, purposes and effects of evaluating open and distance education and also for its potential utility in contributing to ongoing discussions about understanding and enhancing the effectiveness of teaching and learning at CQU