Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Annual trends in catchability and fish stock assessments

A key assumption of many fish stock assessment models is that catchability is constant over time. We assume here that trends in catchability may occur through fishing power creeping. The tuning fleets, which are prone to fishing power development, may be identified using the Hybrid method. A range of catchability trends, including values derived from the Hybrid method, is then implemented to standardise the fishing effort of some tuning fleets used in the stock assessments performed by XSA (eXtended Survivors Analysis). Stocks being assessed are the North Sea cod, saithe, plaice and sole. The performances of the new and traditional XSA assessments are compared using criteria based on the precision of catchability estimates, stationarity of Log-catchability residuals and retrospective patterns relative to fishing mortality, spawning stock biomass and recruitment estimates. The performances of the North Sea cod, plaice and sole assessments could be enhanced by accounting for an overall annual increase in the catchability of some of the tuning fleets. No significant trends could be detected in the catchability of the tuning fleets relative to the assessment of the North Sea saithe. By contrast with the traditional assessment, the spawning biomass of cod is expected not to have increased between 1997 and 1998, while the fishing mortality of sole is expected to have increased over the same period.No disponibl

Distribution–abundance relationships for North Sea Atlantic cod (Gadus morhua): Observation versus theory

Density-dependent habitat selection has implications for fisheries management and for the recovery of depleted fish populations. According to ideal free distribution theory, populations contract into areas of highest habitat suitability as their abundance decreases. This can increase their vulnerability to fishing and predation. We detected density-dependent habitat selection by juvenile Atlantic cod (Gadus morhua) (ages 1 and 2) in the North Sea and compared the observed distribution-abundance relationships with those predicted from a model based on ideal free distribution theory and knowledge of optimal temperatures for growth, where temperature was used as a measure of suitability. As predicted by the model, in years when stock size was low, the catches were largely confined to regions with near-optimal bottom temperatures. Conversely, when population size was high, catches were spread across a larger area including regions with suboptimal temperatures. The spatial extent of optimal habitat appears to have decreased from 1977 to 2002, reflecting a gradual warming of the North Sea. The combined negative effects of increased temperature on recruitment rates and the reduced availability of optimal habitat may have increased the vulnerability of the cod population to fishing mortality

Glutathione/thioredoxin systems modulate mitochondrial H2O2 emission: An experimental-computational study

none7openAon M.A.; Stanley B.A.; Sivakumaran V.; Kembro J.M.; O'Rourke B.; Paolocci N.; Cortassa S.Aon, M. A.; Stanley, B. A.; Sivakumaran, V.; Kembro, J. M.; O'Rourke, B.; Paolocci, N.; Cortassa, S