Background-Because of the higher radiosensitivity of infants and children compared with adults, there is a need to evaluate the doses delivered to pediatric patients who undergo interventional cardiac procedures. However, knowledge of the effective dose in pediatric interventional cardiology is very limited. Methods and Results-For an accurate risk estimation, a patient-specific Monte Carlo simulation of the effective dose was set up in 60 patients with congenital heart disease who underwent diagnostic (nϭ28) or therapeutic (nϭ32) cardiac catheterization procedures. The dose-saving effect of using extra copper filtration in the x-ray beam was also investigated. For diagnostic cardiac catheterizations, a median effective dose of 4.6 mSv was found. Therapeutic procedures resulted in a higher median effective dose of 6.0 mSv because of the prolonged use of fluoroscopy. The overall effect of inserting extra copper filtration into the x-ray beam was a total effective dose reduction of 18% with no detrimental effect on image quality. An excellent correlation between the dose-area product and effective patient dose was found (rϭ0.95). Hence, dose-area product is suitable for online estimation of the effective dose with good accuracy. With all procedures included, the resulting median lifetime risk for stochastic effects was 0.08%.
Conclusions-Because
Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.
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