34 research outputs found

    Abstracts from the NIHR INVOLVE Conference 2017

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    Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

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    Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30‚Äď50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1¬∑30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10‚Äą793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1¬∑5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1¬∑6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4¬∑6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5¬∑9 events per 100 person-years in the placebo group (hazard ratio 0¬∑78, 95% CI 0¬∑68‚Äď0¬∑90), which indicated that albiglutide was superior to placebo (p<0¬∑0001 for non-inferiority; p=0¬∑0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

    RS 301 Oral History: Interview with Karen Mueller

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    In this text, student Erin Kate Ewart interviews Karen Mueller, a local community member in her seventies, who has been a practicing Zen Buddhist for twenty years. Before the pandemic, Karen attended the Arcata Zen group for meditation and sitting, as well as numerous other Zen retreats throughout the state. Topics covered include the transition of her practice to virtual, her likes and dislikes of Zoom, how her practice may change in the future, and her personal relationship with meditation over her decades of life

    Topically applied recombinant chemokine analogues fully protect macaques from vaginal simian-human immunodeficiency virus challenge

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    Effective strategies for preventing human immunodeficiency virus infection are urgently needed, but recent failures in key clinical trials of vaccines and microbicides highlight the need for new approaches validated in relevant animal models. Here, we show that 2 new chemokine (C-C motif) receptor 5 inhibitors, 5P12-RANTES (regulated on activation, normal T cell expressed and secreted) and 6P4-RANTES, fully protect against infection in the rhesus vaginal challenge model. These highly potent molecules, which are amenable to low-cost production, represent promising new additions to the microbicides pipeline

    Global Health Impacts for Economic Models of Climate Change: A Systematic Review and Meta-Analysis

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    RATIONALE: Avoiding excess health damages attributable to climate change is a primary motivator for policy interventions to reduce greenhouse gas emissions. However, the health benefits of climate mitigation, as included in the policy assessment process, have been estimated without much input from health experts. OBJECTIVES: In accordance with recommendations from the National Academies in a 2017 report on approaches to update the social cost of greenhouse gases (SC-GHG), an expert panel of 26 health researchers and climate economists gathered for a virtual technical workshop in May 2021 to conduct a systematic review and meta-analysis and recommend improvements to the estimation of health impacts in economic-climate models. METHODS: Regionally-resolved effect estimates of unit increases in temperature on net all-cause mortality risk were generated through random-effects pooling of studies identified through a systematic review. RESULTS: Effect estimates, and associated uncertainties, varied by global region, but net increases in mortality risk associated with increased average annual temperatures (ranging from 0.1-1.1% per 1 degree C) was estimated for all global regions. Key recommendations for the development and utilization of health damage modules were provided by the expert panel, and include: not relying on individual methodologies in estimating health damages; incorporating a broader range of cause-specific mortality impacts; improving the climate parameters available in economic models; accounting for socio-economic trajectories and adaptation factors when estimating health damages; and carefully considering how air pollution impacts should be incorporated in economic-climate models. CONCLUSIONS: This work provides an example for how subject-matter experts can work alongside climate economists in making continued improvements to SC-GHG estimates

    Deep Underground Neutrino Experiment (DUNE) Near Detector Conceptual Design Report

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    International audienceThe Deep Underground Neutrino Experiment (DUNE) is an international, world-class experiment aimed at exploring fundamental questions about the universe that are at the forefront of astrophysics and particle physics research. DUNE will study questions pertaining to the preponderance of matter over antimatter in the early universe, the dynamics of supernovae, the subtleties of neutrino interaction physics, and a number of beyond the Standard Model topics accessible in a powerful neutrino beam. A critical component of the DUNE physics program involves the study of changes in a powerful beam of neutrinos, i.e., neutrino oscillations, as the neutrinos propagate a long distance. The experiment consists of a near detector, sited close to the source of the beam, and a far detector, sited along the beam at a large distance. This document, the DUNE Near Detector Conceptual Design Report (CDR), describes the design of the DUNE near detector and the science program that drives the design and technology choices. The goals and requirements underlying the design, along with projected performance are given. It serves as a starting point for a more detailed design that will be described in future documents