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We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls. We carried out replication in an independent sample with an effective sample size of up to 19,492. SNPs at nine loci reached genome-wide(More)
Increased lipoprotein-associated phospholipase A2 (Lp-PLA2) activity is associated with increased risk of cardiac events, but it is not known whether Lp-PLA2 is a causative agent. Here we show that selective inhibition of Lp-PLA2 with darapladib reduced development of advanced coronary atherosclerosis in diabetic and hypercholesterolemic swine. Darapladib(More)
OBJECTIVES We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD). BACKGROUND Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers. METHODS The KIF6 Trp719Arg(More)
Upregulation of low-density lipoprotein receptor (LDLr) is a key mechanism to control elevated plasma LDL-cholesterol levels. Here we identify a new class of compounds that directly binds to the sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP). We show that a 14C-labeled, photo-activatable analog specifically labeled both(More)
Peroxisome proliferator-activated receptor delta (PPARdelta) agonism increases HDL cholesterol and has therefore the potential to stimulate macrophage-to-feces reverse cholesterol transport (RCT). To test whether PPARdelta activation promotes RCT in mice, in vivo macrophage RCT was assessed using cholesterol-loaded/3H-cholesterol-labeled macrophages(More)
We propose a new set of browser security indicators, based on user research and an understanding of the design challenges faced by browsers. To motivate the need for new security indicators, we critique existing browser security indicators and survey 1,329 people about Google Chrome’s indicators. We then evaluate forty icons and seven complementary strings(More)
Five adolescents with transverse myelitis were reviewed. All presented with a rapid onset paralysis of the lower limbs and impairment of bladder control. The maximum disability developed between 10 minutes and six hours. There was no history of trauma, asthma, or prodromal illness. Investigations failed to demonstrate a vascular cause. Extensive spinal cord(More)
OBJECTIVE To apply genetic analysis of genome-wide association data to study the extent and nature of a shared biological basis between migraine and coronary artery disease (CAD). METHODS Four separate methods for cross-phenotype genetic analysis were applied on data from 2 large-scale genome-wide association studies of migraine (19,981 cases, 56,667(More)
Because cholesteryl ester transfer protein (CETP) inhibition is a potential HDL-raising therapy, interest has been raised in the mechanisms and consequences of CETP activity. To explore these mechanisms and the dynamics of CETP in vitro, a mechanistic mathematical model was developed based upon the shuttle mechanism for lipid transfer. Model parameters were(More)
A postprandial ammonia tolerance test (PPATT) was performed on normal dogs and dogs with signs that suggested they may have liver disease. All dogs underwent transcolonic scintigraphy, liver biopsy, or both and were assigned to extrahepatic disease, primary hepatocellular, and congenital portosystemic vascular anomalies (PSVA) groups. Each dog was fed a(More)