Evidence of the effectiveness and patient experience of formalised social support for people with a diagnosis of heart failure.

Final report to Chest, Heart & Stroke Scotland. This systematic review was undertaken during December 2014 to June 2015, andwas commissioned by Chest, Heart and Stroke Scotland (CHSS). The review teamcomprised of systematic review experts, and experts in heart failure and/orloneliness

Evidence of the effectiveness and patient experience of formalised social support for people with a diagnosis of heart failure.

Final report to Chest, Heart & Stroke Scotland. This systematic review was undertaken during December 2014 to June 2015, andwas commissioned by Chest, Heart and Stroke Scotland (CHSS). The review teamcomprised of systematic review experts, and experts in heart failure and/orloneliness

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

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 (30–50 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. 10 793 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 0·68–0·90), 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

Natural Language Processing Methods for Enhancing Geographic Metadata for Phylogeography of Zoonotic Viruses

Zoonotic viruses, viruses that are trans-mittable between animals and humans, represent emerging or re-emerging patho-gens that pose significant public health threats throughout the world. It is there-fore crucial to advance current surveil-lance mechanisms for these viruses through outlets such as phylogeography. Phylogeographic techniques may be ap-plied to trace the origins and geographical distribution of these viruses using se-quence and location data, which are often obtained from publicly available data-bases such as GenBank. Despite the abun-dance of zoonotic viral sequence data in GenBank records, phylogeographic anal-ysis of these viruses is greatly limited by the lack of adequate geographic metadata. Although more detailed information may often be found in the related articles refer-enced in these records, manual extraction of this information presents a severe bot-tleneck. In this work, we propose an auto-mated system for extracting this infor

Coordination of DNA replication and histone modification by the Rik1-Dos2 complex

Histone modification marks have an important role in many chromatin processes(1,2). During DNA replication, both heterochromatin and euchromatin are disrupted ahead of the replication fork and are then reassembled into their original epigenetic states behind the fork(3,4). How histone marks are accurately inherited from generation to generation is still poorly understood. In fission yeast (Schizosaccharomyces pombe), RNA interference (RNAi)-mediated histone methylation is cell cycle regulated. Centromeric repeats are transiently transcribed in the S phase of the cell cycle and are processed into short interfering RNAs (siRNAs) by the complexes RITS (RNA-induced initiation of transcriptional gene silencing) and RDRC (RNA-directed RNA polymerase complex)(5-7). The small RNAs together with silencing factors-including Dos1 (also known as Clr8 and Raf1), Dos2 (also known as Clr7 and Raf2), Rik1 and Lid2-promote heterochromatic methylation of histone H3 at lysine 9 (H3K9) by a histone methyltransferase, Clr4 (refs 8-13). The methylation of H3K9 provides a binding site for Swi6, a structural and functional homologue of metazoan heterochromatin protein 1 (HP1)(14). Here we characterize a silencing complex in fission yeast that contains Dos2, Rik1, Mms19 and Cdc20 (the catalytic subunit of DNA polymerase-e). This complex regulates RNA polymerase II (RNA Pol II) activity in heterochromatin and is required for DNA replication and heterochromatin assembly. Our findings provide a molecular link between DNA replication and histone methylation, shedding light on how epigenetic marks are transmitted during each cell cycle