Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)

Durability of carbon-supported manganese oxide nanoparticles for the oxygen reduction reaction (ORR) in alkaline medium

International audienceMnOx/C-based electrocatalysts, prepared by the chemical deposition of manganese oxide nanoparticles on carbon, were tested towards the Oxygen Reduction Reaction (ORR) in their as-synthesized state and after ageing, either in ambient air for a year (mild ageing) or in an O2-saturated molar KOH solution at 80 °C for three weeks (premature ageing). For each electrocatalyst, the morphology and composition were characterised using TEM, XRD and chemical analysis. ORR kinetic parameters were evaluated using the Rotating Disk Electrode (RDE) and Rotating Ring Disk Electrode (RRDE) setups. Whilst the oxygen reduction activity of the electrocatalysts barely changes after mild ageing, it decreases after premature ageing following dramatic modifications to both the chemical and crystalline structures of the carbon-supported MnOx nanoparticles. The peroxide yield also sharply increases after premature ageing. Doping MnOx/C with nickel or magnesium divalent cations is beneficial since it improves both the catalytic activity and selectivity towards the 4-electron ORR pathway, even after ageing

The Cosmic Dawn and Epoch of Reionisation with SKA

Concerted effort is currently ongoing to open up the Epoch of Reionization (EoR) ($z\sim$15-6) for studies with IR and radio telescopes. Whereas IR detections have been made of sources (Lyman-$\alpha$ emitters, quasars and drop-outs) in this redshift regime in relatively small fields of view, no direct detection of neutral hydrogen, via the redshifted 21-cm line, has yet been established. Such a direct detection is expected in the coming years, with ongoing surveys, and could open up the entire universe from $z\sim$6-200 for astrophysical and cosmological studies, opening not only the EoR, but also its preceding Cosmic Dawn ($z\sim$30-15) and possibly even the later phases of the Dark Ages ($z\sim$200-30). All currently ongoing experiments attempt statistical detections of the 21-cm signal during the EoR, with limited signal-to-noise. Direct imaging, except maybe on the largest (degree) scales at lower redshifts, as well as higher redshifts will remain out of reach. The Square Kilometre Array(SKA) will revolutionize the field, allowing direct imaging of neutral hydrogen from scales of arc-minutes to degrees over most of the redshift range $z\sim$6-28 with SKA1-LOW, and possibly even higher redshifts with the SKA2-LOW. In this SKA will be unique, and in parallel provide enormous potential of synergy with other upcoming facilities (e.g. JWST). In this chapter we summarize the physics of 21-cm emission, the different phases the universe is thought to go through, and the observables that the SKA can probe, referring where needed to detailed chapters in this volume (Abridged)