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

Wearable Light-and-Motion Dataloggers for Sleep/Wake Research: A Review

Long-term recording of a person’s activity (actimetry or actigraphy) using devices typically worn on the wrist is increasingly applied in sleep/wake, chronobiological, and clinical research to estimate parameters of sleep and sleep-wake cycles. With the recognition of the importance of light in influencing these parameters and with the development of technological capabilities, light sensors have been introduced into devices to correlate physiological and environmental changes. Over the past two decades, many such new devices have appeared from different manufacturers. One of the aims of this review is to help researchers and clinicians choose the data logger that best fits their research goals. Seventeen currently available light-and-motion recorders entered the analysis. They were reviewed for appearance, dimensions, weight, mounting, battery, sensors, features, communication interface, and software. We found that all devices differed from each other in several features. In particular, six devices are equipped with a light sensor that can measure blue light. It is noteworthy that blue light most profoundly influences the physiology and behavior of mammals. As the wearables market is growing rapidly, this review helps guide future developments and needs to be updated every few years

Wearable Light-and-Motion Dataloggers for Sleep/Wake Research: A Review

Long-term recording of a person’s activity (actimetry or actigraphy) using devices typically worn on the wrist is increasingly applied in sleep/wake, chronobiological, and clinical research to estimate parameters of sleep and sleep-wake cycles. With the recognition of the importance of light in influencing these parameters and with the development of technological capabilities, light sensors have been introduced into devices to correlate physiological and environmental changes. Over the past two decades, many such new devices have appeared from different manufacturers. One of the aims of this review is to help researchers and clinicians choose the data logger that best fits their research goals. Seventeen currently available light-and-motion recorders entered the analysis. They were reviewed for appearance, dimensions, weight, mounting, battery, sensors, features, communication interface, and software. We found that all devices differed from each other in several features. In particular, six devices are equipped with a light sensor that can measure blue light. It is noteworthy that blue light most profoundly influences the physiology and behavior of mammals. As the wearables market is growing rapidly, this review helps guide future developments and needs to be updated every few years

Structural changes of erythrocyte membrane revealed by 3D confocal optical profilometer

We examined hematological changes influenced by the experimental hypervitaminosis A. The 3D confocal optical profilometer was applied for assessment of the erythrocytes’ membrane structural changes influenced by an overdose of vitamin A. The blood smears were evaluated in terms of alterations of geometrical and optical parameters of erythrocytes for two groups of animals: oil base and retinol palmitate (n=9 animals for each group). The results demonstrate that an overdose of retinol palmitate causes changes in the torus curvature and pallor of discocytes, their surface area and volume. The observed structural malformations of the shape of red blood cells become visible at the earlier pre-clinical stage of changes in animal state and behaviour. With this in mind, the results of the study open a new area of research in the certain dysfunction diagnosis of red blood cells and has a great potential in the further development of new curative protocols

Structural changes of erythrocyte membrane revealed by 3D confocal optical profilometer

Abstract We examined hematological changes influenced by the experimental hypervitaminosis A. The 3D confocal optical profilometer was applied for assessment of the erythrocytes’ membrane structural changes influenced by an overdose of vitamin A. The blood smears were evaluated in terms of alterations of geometrical and optical parameters of erythrocytes for two groups of animals: oil base and retinol palmitate (n = 9 animals for each group). The results demonstrate that an overdose of retinol palmitate causes changes in the torus curvature and pallor of discocytes, their surface area and volume. The observed structural malformations of the shape of red blood cells become visible at the earlier preclinical stage of changes in animal state and behavior. With this in mind, the results of the study open a new area of research in the certain dysfunction diagnosis of red blood cells and have a great potential in the further development of new curative protocols

Improved Λ p Elastic Scattering Cross Sections between 0.9 and 2.0 GeV/c as a Main Ingredient of the Neutron Star Equation of State

Strange matter is believed to exist in the cores of neutron stars based on simple kinematics. If this is true, then hyperon-nucleon interactions will play a significant part in the neutron star equation of state. Yet, compared to other elastic scattering processes, there is very little data on Λ−N scattering. This experiment utilized the CEBAF Large Acceptance Spectrometer (CLAS) detector to study the Λp→Λp elastic scattering cross section in the incident Λ momentum range 0.9–2.0  GeV/c. These are the first data on this reaction since the 1970s. The new cross sections have significantly better accuracy and precision than the existing world data, and the techniques developed here can also be used in future experiments

Measurement of the proton spin structure at long distances

Measuring the spin structure of protons and neutrons tests our understanding of how they arise from quarks and gluons, the fundamental building blocks of nuclear matter. At long distances, the coupling constant of the strong interaction becomes large, requiring non-perturbative methods to calculate quantum chromodynamics processes, such as lattice gauge theory or effective field theories. Here we report proton spin structure measurements from scattering a polarized electron beam off polarized protons. The spin-dependent cross-sections were measured at large distances, corresponding to the region of low momentum transfer squared between 0.012 and 1.0 GeV2. This kinematic range provides unique tests of chiral effective field theory predictions. Our results show that a complete description of the nucleon spin remains elusive, and call for further theoretical works, for example, in lattice quantum chromodynamics. Finally, our data extrapolated to the photon point agree with the Gerasimov–Drell–Hearn sum rule, a fundamental prediction of quantum field theory that relates the anomalous magnetic moment of the proton to its integrated spin-dependent cross-sections