Independent susceptibility markers for atrial fibrillation on chromosome 4q25

Background-: Genetic variants on chromosome 4q25 are associated with atrial fibrillation (AF). We sought to determine whether there is more than 1 susceptibility signal at this locus. Methods and results-: Thirty-four haplotype-tagging single-nucleotide polymorphisms (SNPs) at the 4q25 locus were genotyped in 790 case and 1177 control subjects from Massachusetts General Hospital and tested for association with AF. We replicated SNPs associated with AF after adjustment for the most significantly associated SNP in 5066 case and 30 661 referent subjects from the German Competence Network for Atrial Fibrillation, Atherosclerosis Risk In Communities Study, Cleveland Clinic Lone AF Study, Cardiovascular Health Study, and Rotterdam Study. All subjects were of European ancestry. A multimarker risk score composed of SNPs that tagged distinct AF susceptibility signals was constructed and tested for association with AF, and all results were subjected to meta-analysis. The previously reported SNP, rs2200733, was most significantly associated with AF (minor allele odds ratio 1.80, 95% confidence interval 1.50 to 2.15, P=1.2×10) in the discovery sample. Adjustment for rs2200733 genotype revealed 2 additional susceptibility signals marked by rs17570669 and rs3853445. A graded risk of AF was observed with an increasing number of AF risk alleles at SNPs that tagged these 3 susceptibility signals. Conclusions-: We identified 2 novel AF susceptibility signals on chromosome 4q25. Consideration of multiple susceptibility signals at chromosome 4q25 identifies individuals with an increased risk of AF and may localize regulatory elements at the locus with biological relevance in the pathogenesis of AF

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

Dynamics of the Earth's particle radiation environment

The physical processes affecting the dynamics of the Earth's particle radiation environment are reviewed along with scientific and engineering models developed for its description. The emphasis is on models that are either operational engineering models or models presently under development for this purpose. Three components of the radiation environment, i.e., galactic cosmic rays (GCRs), solar energetic particles (SEPs) and trapped radiation, are considered separately. In the case of SEP models, we make a distinction between statistical flux/fluence models and those aimed at forecasting events. Models of the effects of particle radiation on the atmosphere are also reviewed. Further, we summarize the main features of the models and discuss the main outstanding issues concerning the models and their possible use in operational space weather forecasting. We emphasize the need for continuing the development of physics-based models of the Earth's particle radiation environment, and their validation with observational data, until the models are ready to be used for nowcasting and/or forecasting the dynamics of the environment