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

Historical changes in the riparian habitats of Labrador's Churchill River due to flow regulation: The imperative of cumulative effects assessment.

Extensive hydroelectric facilities were constructed in the upper watershed of Labrador's Churchill River during the 1960's and 70's. Two additional dams and generating stations are now planned for the lower reaches of the river. Despite the fact that cumulative effects assessment is a legal requirement under Canadian law, and is expected by people who hold aboriginal title to the land and wish to take a highly precautionary approach to further industrial development, environmental research to date has been restricted to a very narrow temporal and spatial scope, virtually ignoring changes that have already occurred throughout watershed.River shorelines and their ecosystems are important parts of ecological and cultural landscapes and are always considerably changed by large-scale river regulation. The objective of this study is to demonstrate that despite the lack of formal data collection in the past, a rich understanding of patterns of change in the hydrological regimes and riparian vegetation communities of the Churchill River can be attained, and can contribute to a meaningful understanding of the cumulative effects of hydroelectric development.Labrador Innu and Inuit/Metis shared empirical observations of changes in the river shorelines, and offered personal opinions about the significance of these changes. They also participated in botanical survey work in several reaches of the main stem of the river to collect data on riparian plant communities. Existing hydrological records were analyzed to relate pre-and post-development flow patterns to plant species richness and cover. Historical observations by travelers and scientists, time series air and ground photography, and research on the effects of flow regulation on riparian habitats in other boreal regions also informed the study.Hydroelectric development has already had extensive and severe effects on the riparian zones of the river. It has reduced biodiversity, especially in the reservoirs, and has destroyed places of cultural value. Land use along several affected river corridors, as well as the traditional knowledge that developed within these riverine landscapes has been eroded. The river valley riparian zones downstream of the existing power stations have been altered, but continue to maintain substantial ecological and cultural integrity. The construction of additional dams on the lower Churchill River would further decrease the structural complexity and species richness of riparian zones, and flood almost all remaining sites of cultural significance along the main stem shores of the river.Thesis (Ph.D.)--Dalhousie University (Canada), 2007

VRML History: Storing and Browsing Temporal 3DWorlds

Spatio-temporal data are presented and explored by VR-based visualization systems which offer 3D-navigation and time-navigation for better immersion and analysis. If the visualization results are disseminated on the WWW, they are mostly transformed into videos or, recently, into animated VRML-files which neither support 3D-navigation nor time navigation nor a time-referenced data representation. In this paper, the script language VRML History is proposed which supports the description of spatio-temporal worlds on the internet by conceptually extending VRML with a new time dimension. This is realized by a set of new nodes representing temporal geometries and time references, and a set of Java-classes extending standard VRML-browsers to perform time navigation

Genetic Determinants for Virulence and Transmission of the Panzootic Avian Influenza Virus H5N8 Clade 2.3.4.4 in Pekin Ducks

Since 2014, several waves of avian influenza virus (AIV) H5N8 of clade 2.3.4.4 occurred globally on unprecedented levels. Unlike viruses in the first wave in 2014–2015 (H5N8-A), viruses in 2015–2016 (H5N8-B) exhibited unusually high pathogenicity (HP) in wild and domestic ducks.</jats:p

Preface

Prefac

German corporate governance in international and European context: Third edition

German corporate governance in international and European context: Third editio