Optimising cosmic shear surveys to measure modifications to gravity on cosmic scales

We consider how upcoming photometric large scale structure surveys can be optimized to measure the properties of dark energy and possible cosmic scale modifications to General Relativity in light of realistic astrophysical and instrumental systematic uncertainities. In particular we include flexible descriptions of intrinsic alignments, galaxy bias and photometric redshift uncertainties in a Fisher Matrix analysis of shear, position and position-shear correlations, including complementary cosmological constraints from the CMB. We study the impact of survey tradeoffs in depth versus breadth, and redshift quality. We parameterise the results in terms of the Dark Energy Task Force figure of merit, and deviations from General Relativity through an analagous Modified Gravity figure of merit. We find that intrinsic alignments weaken the dependence of figure of merit on area and that, for a fixed observing time, a fiducial Stage IV survey plateaus above roughly 10,000deg2 for DE and peaks at about 5,000deg2 as the relative importance of IAs at low redshift penalises wide, shallow surveys. While reducing photometric redshift scatter improves constraining power, the dependence is shallow. The variation in constraining power is stronger once IAs are included and is slightly more pronounced for MG constraints than for DE. The inclusion of intrinsic alignments and galaxy position information reduces the required prior on photometric redshift accuracy by an order of magnitude for both the fiducial Stage III and IV surveys, equivalent to a factor of 100 reduction in the number of spectroscopic galaxies required to calibrate the photometric sample.Comment: 13 pages, 6 figures. Fixed an error in equation 19 which changes the right hand panels of figures 1 and 2, and modifies conclusions on the results for fixed observing tim

Induction of Endothelial Cell Injury by Cigarette Smoke

Cigarette smoke contains different populations of free radicals which may be responsible for endothelial cell (EC) injury of smokers. The purpose of this study was to examine the effects of gas-phase cigarette smoke on EC endothelium-derived relaxing factor (EDRF)/NO-guanylate cyclase (GC)-cGMP pathway and on EC detatchment-type injury after incubation with smoke. Furthermore, we examined whether different kind of antioxidants can prevent smoke-caused EC injury. We measured cGMP pathway using direct (sodium nitroprusside, SNP) and indirect (A23187, the calcium ionophore and bradykinin, BK) activators of GC. Directly and indirectly stimulated EC cGMP production dose-dependently decreased and EC detatchment increased after incubation with smoke. Externally added thiols (glutathione, GSH; D-Penicillamine, DP; N-acetylcysteine, NAC) protected EC from damage of cGMP production and cell detatchment. Other antioxidants (catalase, deferoxamine and superoxide dismutase) were ineffective. These results suggest that the thiol containing GC in EC is destroyed or inactivated or thiol like species responsible for activation of GC is incomplete in EC after incubation with smoke. It is also possible that externally added thiols bind an unknown component of smoke and this way, EC is protected. EC injury may contribute to vascular diseases associated with cigarette smoking

Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes

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