Hypermultiplets and Topological Strings

The c-map relates classical hypermultiplet moduli spaces in compactifications of type II strings on a Calabi-Yau threefold to vector multiplet moduli spaces via a further compactification on a circle. We give an off-shell description of the c-map in N=2 superspace. The superspace Lagrangian for the hypermultiplets is a single function directly related to the prepotential of special geometry, and can therefore be computed using topological string theory. Similarly, a class of higher derivative terms for hypermultiplets can be computed from the higher genus topological string amplitudes. Our results provide a framework for studying quantum corrections to the hypermultiplet moduli space, as well as for understanding the black hole wave-function as a function of the hypermultiplet moduli.Comment: 21 pages, references adde

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Human impact erodes chimpanzee behavioral diversity

Chimpanzees possess a large number of behavioral and cultural traits among non-human species. The ‘disturbance hypothesis’ predicts that human impact depletes resources and disrupts social learning processes necessary for behavioral and cultural transmission. We used an unprecedented data set of 144 chimpanzee communities, with information on 31 behaviors, to show that chimpanzees inhabiting areas with high human impact have a mean probability of occurrence reduced by 88%, across all behaviors, compared to low impact areas. This behavioral diversity loss was evident irrespective of the grouping or categorization of behaviors. Therefore, human impact may not only be associated with the loss of populations and genetic diversity, but also affects how animals behave. Our results support the view that ‘culturally significant units’ should be integrated into wildlife conservation

The International Network for Evaluating Outcomes (iNeo) of neonates: evolution, progress and opportunities

Neonates born very preterm (before 32 weeks’ gestational age), are a significant public health concern because of their high-risk of mortality and life-long disability. In addition, caring for very preterm neonates can be expensive, both during their initial hospitalization and their long-term cost of permanent impairments. To address these issues, national and regional neonatal networks around the world collect and analyse data from their constituents to identify trends in outcomes, and conduct benchmarking, audit and research. Improving neonatal outcomes and reducing health care costs is a global problem that can be addressed using collaborative approaches to assess practice variation between countries, conduct research and implement evidence-based practices. The International Network for Evaluating Outcomes (iNeo) of neonates was established in 2013 with the goal of improving outcomes for very preterm neonates through international collaboration and comparisons. To date, 10 national or regional population-based neonatal networks/datasets participate in iNeo collaboration. The initiative now includes data on >200,000 very preterm neonates and has conducted important epidemiological studies evaluating outcomes, variations and trends. The collaboration has also surveyed >320 neonatal units worldwide to learn about variations in practices, healthcare service delivery, and physical, environmental and manpower related factors and support services for parents. The iNeo collaboration serves as a strong international platform for Neonatal-Perinatal health services research that facilitates international data sharing, capacity building, and global efforts to improve very preterm neonate care

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

BACKGROUN

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin- kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. RESULTS At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P = 0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P = 0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P = 0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). CONCLUSIONS In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients