Background Several germline single nucleotide polymorphisms (SNPs) have been consistently associated with prostate cancer (PCa) risk. Objective To determine whether there is an improvement in PCa risk prediction by adding these SNPs to existing predictors of PCa. Design, setting, and participants Subjects included men in the placebo arm of the randomized Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial in whom germline DNA was available. All men had an initial negative prostate biopsy and underwent study-mandated biopsies at 2 yr and 4 yr. Predictive performance of baseline clinical parameters and/or a genetic score based on 33 established PCa risk-associated SNPs was evaluated. Outcome measurements and statistical analysis Area under the receiver operating characteristic curves (AUC) were used to compare different models with different predictors. Net reclassification improvement (NRI) and decision curve analysis (DCA) were used to assess changes in risk prediction by adding genetic markers. Results and limitations Among 1654 men, genetic score was a significant predictor of positive biopsy, even after adjusting for known clinical variables and family history (p = 3.41 × 10−8). The AUC for the genetic score exceeded that of any other PCa predictor at 0.59. Adding the genetic score to the best clinical model improved the AUC from 0.62 to 0.66 (p < 0.001), reclassified PCa risk in 33% of men (NRI: 0.10; p = 0.002), resulted in higher net benefit from DCA, and decreased the number of biopsies needed to detect the same number of PCa instances. The benefit of adding the genetic score was greatest among men at intermediate risk (25th percentile to 75th percentile). Similar results were found for high-grade (Gleason score ≥7) PCa. A major limitation of this study was its focus on white patients only. Conclusions Adding genetic markers to current clinical parameters may improve PCa risk prediction. The improvement is modest but may be helpful for better determining the need for repeat prostate biopsy. The clinical impact of these results requires further study.

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Thermal gradients of 24°–36°C/km have been found in the slope cover sediments of the accretionary prism off northeast Japan (Deep Sea Drilling Project (DSDP) sites 438A, 439, and 440). These gradients lead to the prediction of temperatures in excess of 400°C at depths of 15 km using an increase in thermal conductivity with depth due to the decrease in porosity. Such temperatures conflict with the predictions of temperatures of 150°C at even greater depths from conductive thermal models and petrologic studies of low‐temperature blueschists at similar ancient margins. One‐dimensional, steady state conduction and advection via Darcian water flow, of heat, up through the prism was simulated numerically. The measured thermal gradients can be reconciled with temperatures less than 125°C at the prism base by water flowing upward at rates of the order of 10−10 m/s. Such velocities imply that the total volume of water available from compaction of sediments subducted beneath the northeast Japan prism would flow up through a <10 km width of the prism (perpendicular to the trench) and would require the DSDP sites to have been located fortuitously over the localized zone(s) of water flow. Smaller velocities will reproduce the measured gradients, and thus greater widths through which water flow occurs are predicted, if the temperature at the prism base is higher and/or if the prism is thinner and a subduction channel several kilometers high separates the accreted sediments from the descending plate. Where water flow is significant, as likely wherever abundant, water‐rich sediments are subducted, thermal gradients below a few kilometers in accretionary prisms may be much lower than near‐surface values. This has profound implications for the thermal structure of the prism off northeast Japan and elsewhere.

We present the most comprehensive comparison to date of the predictive benefit of genetics in addition to currently used clinical variables, using genotype data for 33 single-nucleotide polymorphisms (SNPs) in 1,547 Caucasian men from the placebo arm of the REduction by DUtasteride of prostate Cancer Events (REDUCE®) trial. Moreover, we conducted a detailed comparison of three techniques for incorporating genetics into clinical risk prediction. The first method was a standard logistic regression model, which included separate terms for the clinical covariates and for each of the genetic markers. This approach ignores a substantial amount of external information concerning effect sizes for these Genome Wide Association Study (GWAS)-replicated SNPs. The second and third methods investigated two possible approaches to incorporating meta-analysed external SNP effect estimates – one via a weighted PCa ‘risk’ score based solely on the meta analysis estimates, and the other incorporating both the current and prior data via informative priors in a Bayesian logistic regression model. All methods demonstrated a slight improvement in predictive performance upon incorporation of genetics. The two methods that incorporated external information showed the greatest receiver-operating-characteristic AUCs increase from 0.61 to 0.64. The value of our methods comparison is likely to lie in observations of performance similarities, rather than difference, between three approaches of very different resource requirements. The two methods that included external information performed best, but only marginally despite substantial differences in complexity.

Two identical LVADs were equipped with different types of heart valve prostheses (Björk-Shiley disk and PU-valves) and tested in two simultaneous calf experiments for 28 days each. Noise levels, accelerations of the pump housing and thrombus formation were higher for the mechanical valve pump.

Materials and methods:Since the use of conventional prosthetic heart valves in LVAD and TAH applications i s still associated with thomboembolic events and other complications, the purpose of this study was the comparative evaluation of an alternative valve for the above purpose. Based on the original design of the Taguchi LVAD, two modified identical LVADs were manufactured from PU-solutions by dipcoating techniques. The blood-contacting surfaces D were made from Cardiomat 610 . One LVAD was equipped with Björk-Shiley Monostrut valves, the other with a stented PU-valve in inlet position and an integrated PU-valve in the outlet cannula. Fig. l shows a crosssection of the used LVAD, on the left half the PU-valve version, on the right half the BjÖrk-Shiley valve version. Both LVADs were paracorporeally implanted in atrial-aortic mode in 70 kg Jersey calves, driven in parallel for 4 weeks ( fig. 2), and explanted.

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