Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

Combined use of ionophore and virginiamycin for finishing Nellore steers fed high concentrate diets

Zebu cattle fed high concentrate diets may present inconsistent performance due to the occurrence of metabolic disorders, like acidosis. The isolated use of ionophores and virginiamycin in high grain diets can improve animal performance and reduce the incidence of such disorders, but recent studies suggested that their combination may have an additive effect. Thus, 72 Nellore steers, 389 ± 15 kg initial body weight (BW), were confined and fed for 79 days to evaluate the combination of virginiamycin and salinomycin on performance and carcass traits. Animals were allocated to a randomized complete block design by BW, in a 2 × 2 factorial arrangement of treatments, with two concentrate levels (73 and 91 %) and two virginiamycin levels (0 and 15 mg kg-1), and salinomycin (13 mg kg-1) included in all diets. The interaction was not significant (p > 0.05). Dry matter intake (DMI), average daily gain (ADG), gain-to-feed ratio (G:F), starch consumed, and fecal starch content were higher (p 0.05) between treatments. Starch consumed and estimated dietary net energy for maintenance (NEm) and gain (NEg) were higher (p < 0.05) for virginiamycin-treated animals, with no substantial effects on carcass traits. The inclusion of virginiamycin in finishing diets containing salinomycin reduced DMI while maintaining ADG and improving NEm and NEg, suggesting an additive effect of virginiamycin and ionophores, but without affecting carcass quality

Consensus Recommendations for RBC Transfusion Practice in Critically Ill Children From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative

Intensive Car