Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs

Divaricate patterns in Cambro-Ordovician obolid brachiopods from Gondwana

A new brachiopod species, Westonia mardini, from the Furongian of Turkey and a new occurrence of Westonia urbiona from the Cambrian Series 3 of Iberian Peninsula are reported. These new finds of 'westoniids' collected in Gondwana allow the discussion of the functional morphology of their terrace ridges. This structure enabled an effective and rapid reburrowing and allowed the occupation of the shallow marine unstable sands and silts in the shoreface environments. This burrowing mechanism, with their pedicle directed downwards, was unknown before the Cambrian Series 2 and was abandoned chiefly in the Early Ordovician. Here we also review the distribution of 'westoniids' in space and time to analyse the diversification, decline and replacement of this important group of brachiopods. They became a significant part of the semi-infaunal marine associations beginning with the Cambrian Series 2 and proliferated in shallow arenaceous shelves during the Cambrian Series 3 and during the Furongian in most palaeocontinents. The acme of 'Westoniid' obolids associations was in the Furongian, but locally relict associations were present in high-latitude Gondwana until the Tremadocian. Decline of westoniid associations began during the Tremadocian, being replaced by very diverse smooth-shelled obolid associations with a novel burrowing mechanism and deeper lifestyle

Search for nu(mu) -> nu(tau) oscillation with the OPERA experiment in the CNGS beam

The OPERA neutrino experiment in the underground Gran Sasso Laboratory (LNGS) was designed to perform the first detection of neutrino oscillations in direct appearance mode in the nu(mu) -> nu(tau) channel, the nu(tau) signature being the identification of the tau-lepton created in its charged current interaction. The hybrid apparatus consists of a large mass emulsion film/lead target complemented by electronic detectors. Placed in the LNGS, it is exposed to the high-energy long-baseline CERN Neutrino beam to Gran Sasso (CNGS) 730 km away from the neutrino source. The observation of a first nu(tau) candidate event was reported in 2010. In this paper, we discuss the result of the analysis of the data taken during the first two years of operation (2008-2009) underlining the major improvements brought to the analysis chain and to the Monte Carlo simulations. The statistical significance of the one event observed so far is then evaluated to 95%