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BackgroundElevated lipoprotein-associated phospholipase A 2 activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A 2 . MethodsIn a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization). ResultsDuring a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P = 0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P = 0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P = 0.02). ConclusionsIn patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke. (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.)The Darapladib is a potent and reversible oral inhibitor of lipoprotein-associated phospholipase A 2 . 10 In a swine model of atherosclerosis, darapladib reduced levels of lipoprotein-associated phospholipase A 2 in plaque, reduced the necrotic core area, and inhibited the development of lesions in coronary arteries. 11 Darapladib has also been shown to reduce lipoprotein-associated phospholipase A 2 activity in human carotid plaque. 12 In the Integrated Biomarker and Imaging Study 2 (IBIS-2) involving patients with coronary heart disease, darapladib, as compared with placebo, halted the progression in the volume of the necrotic core of coronary-artery plaques (a secondary end point), as determined by intravascular ultrasonographic virtual histologic analysis during a 12-month period. 13 These findings suggest that darapladib could reduce the risk of events associated with coronary heart disease by altering the composition of atherosclerotic plaques to a less vulnerable state. 1 In the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy (STABILITY) trial, we evaluated the clini...

The early development of the Atlantic cod, Gadus morhua was studied from fertilization until first-feeding. Multiple families were reared at 7 degrees C and a developmental staging series was prepared using morphological landmarks visible with the light microscope. Stages were named rather than numbered to allow for future additions and broadly grouped into larger time intervals called periods. The most useful staging features were found to be initially cell number, and later in development, somite number. The mean cell cycle time for the first six cleavages was 135 min and the linear regression equation for development of somites(s) over time (t) was s = 0.29t - 18.14. The segmentation period began at 220 h postfertilization (hpf), and unlike some other teleosts, the addition of new somites continued throughout the majority of embryonic development, until just prior to hatching. Hatching occurred at 256 hpf, after which individuals remained motionless at the water's surface, undergoing negative phototaxis only after the first day posthatch. The first-feeding stage was reached at the end of the third day posthatch, subsequent to development of a functional jaw and hindgut. This staging series provides an essential baseline reference for future experiments involving developing cod embryos and for the aquaculture industry.

Egg quality, those characteristics of the egg that determine its capacity to survive, is a significant problem for many species of fish currently being farmed. Little is known about the determinants of egg quality and there is little agreement regarding reliable methods for its assessment. To be of practical benefit, assessments should be simple to perform and should be carried out as early in development as is possible. Fertilization rates are often used as measures of quality. For the Atlantic halibut Hippoglossus hippoglossus, fertilization rate and assessments of cell symmetry at early cleavage stages provide reasonable indicators of quality. Regardless of assessment method, it is strongly recommended that performance data from all batches of each broodfish be examined when surveying the overall quality of a stock. The misleading effects of pooling such information are demonstrated for a rainbow trout Oncorhynchus mykiss broodstock. Although a large number of factors have been implicated as possible determinants of egg quality, only 1) bacterial colonization of the eggs, 2) nutritional status of the broodfish and, 3) overripening, the process of aging that occurs when eggs are retained within the broodfish after ovulation, have been clearly shown to affect egg quality.The effect of overripening on fish egg quality is discussed in detail. Species-specific differences in the time scale of overripening are pointed out and related to spawning strategy and water temperature. Rainbow trout eggs and those of other salmonids should be fertilized within approximately one week of ovulation. Overripening proceeds much more rapidly in warm water species, e.g., tilapia eggs must be fertilized within an hour or so of ovulation. Egg viability also decreases rapidly for batch spawning species. Fertilization data are presented for Atlantic halibut demonstrating that egg quality decreases 4-6 h after ovulation. The rate of overripening was comparable for eggs held in vitro in ovarian fluid to those retained within the ovarian lumen. These halibut data, combined with information from other marine and freshwater fish, indicate that overripening is a significant determinant of egg quality for many if not all fish. . 1991.Broodstock management, fecundity, egg quality and the timing of egg production in the rainbow trout Oncorhynchus mykiss. Aquaculture 100: 141-166.

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A mild elevation (130-149 micromol. L(-1)) in the preoperative serum creatinine level significantly increases the need for mechanical renal support, the duration of special care and total postoperative stay, and the in-hospital mortality. As the preoperative serum creatinine level increases further (> or =150 micromol. L(-1)), this effect is more pronounced. No significant difference in outcome was observed between the use of cardioplegia or crossclamp fibrillation for myocardial protection.

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