Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Bose Polaron Interactions in a Cavity-Coupled Monolayer Semiconductor

The interaction between a mobile quantum impurity and a bosonic bath leads to the formation of quasiparticles, termed Bose polarons. The elementary properties of Bose polarons, such as their mutual interactions, can differ drastically from those of the bare impurities. Here, we explore Bose polaron physics in a two-dimensional nonequilibrium setting by injecting σ − polarized exciton-polariton impurities into a bath of coherent σ + polarized polaritons generated by resonant laser excitation of monolayer MoSe 2 embedded in an optical cavity. By exploiting a biexciton Feshbach resonance between the impurity and the bath polaritons, we tune the interacting system to the strong-coupling regime and demonstrate the coexistence of two new quasiparticle branches. Using time-resolved pump-probe measurements, we observe how polaron dressing modifies the interaction between impurity polaritons. Remarkably, we find that the interactions between high-energy polaron quasiparticles, which are repulsive for small bath occupancy, can become attractive in the strong impurity-bath coupling regime. Our experiments provide the first direct measurement of Bose polaron-polaron interaction strength in any physical system and pave the way for exploration and control of many-body correlations in driven-dissipative settings.ISSN:2160-330

Bose Polaron Interactions in a Cavity-Coupled Monolayer Semiconductor

The interaction between a mobile quantum impurity and a bosonic bath leads to the formation of quasiparticles, termed Bose polarons. The elementary properties of Bose polarons, such as their mutual interactions, can differ drastically from those of the bare impurities. Here, we explore Bose polaron physics in a two-dimensional nonequilibrium setting by injecting σ^{-} polarized exciton-polariton impurities into a bath of coherent σ^{+} polarized polaritons generated by resonant laser excitation of monolayer MoSe_{2} embedded in an optical cavity. By exploiting a biexciton Feshbach resonance between the impurity and the bath polaritons, we tune the interacting system to the strong-coupling regime and demonstrate the coexistence of two new quasiparticle branches. Using time-resolved pump-probe measurements, we observe how polaron dressing modifies the interaction between impurity polaritons. Remarkably, we find that the interactions between high-energy polaron quasiparticles, which are repulsive for small bath occupancy, can become attractive in the strong impurity-bath coupling regime. Our experiments provide the first direct measurement of Bose polaron-polaron interaction strength in any physical system and pave the way for exploration and control of many-body correlations in driven-dissipative settings

The Use of Transperineal Sector Biopsy as A First-Line Biopsy Strategy:A Multi-Institutional Analysis of Clinical Outcomes and Complications

PURPOSE: Systematic transrectal ultrasound biopsies have been the first-line biopsy strategy in men with suspected prostate cancer for over 30 years. Transperineal biopsy is an alternative approach but has been predominately reserved as a repeat biopsy strategy and not widely used as a first-line approach. This study evaluates the diagnostic and clinical outcomes of transperineal sector biopsy (TPSB) as a first-line biopsy strategy in the diagnosis and management of prostate cancer. MATERIALS AND METHODS: A multi-institutional review of 402 consecutive patients who underwent primary transperineal sector biopsy. All patients had no prior history of prostate biopsy. TPSB was carried out as a day-case procedure under general or regional anaesthesia. The cancer detection rate, location and complications for all cases were evaluated. RESULTS: Prostate cancer was identified in 249 patients (61.9%) and was comparably sited across anterior, middle and posterior sectors. The disease was clinically significant (Gleason 3+4 or > 4mm maximum cancer length) in 187 patients (47%). Post biopsy urinary retention occurred in 6 patients (1.5%). Hematuria requiring overnight hospital admission occurred in 4 patients (1.0%). There were no cases of urosepsis. CONCLUSIONS: As a primary diagnostic strategy, TPSB is a safe and effective technique with high cancer detection rates. It also offers an attractive compromise to more extensive transperineal protocols, which can be more time-consuming and associated with higher morbidity.&nbsp

Structured and Modular Training Pathway for Robot-assisted Radical Prostatectomy (RARP):Validation of the RARP Assessment Score and Learning Curve Assessment

none12Background: Use of robot-assisted radical prostatectomy (RARP) for prostate cancer is increasing. Structured surgical training and objective assessment are critical for outcomes. Objective: To develop and validate a modular training and assessment pathway via Healthcare Failure Mode and Effect Analysis (HFMEA) for trainees undertaking RARP and evaluate learning curves (LCs) for procedural steps. Design, setting, and participants: This multi-institutional (Europe, Australia, and United States) observational prospective study used HFMEA to identify the high-risk steps of RARP. A specialist focus group enabled validation. Fifteen trainees who underwent European Association of Urology robotic surgery curriculum training performed RARP and were assessed by mentors using the tool developed. Results produced LCs for each step. A plateau above score 4 indicated competence. Outcome measurements and statistical analysis: We used a modular training and assessment tool (RARP Assessment Score) to evaluate technical skills. LCs were constructed. Multivariable Kruskal-Wallis, Mann-Whitney U, and k coefficient analyses were used. Results and limitations: Five surgeons were observed for 42 console hours to map steps of RARP. HFMEA identified 84 failure modes and 46 potential causes with a hazard score >8. Content validation created the RARP Assessment Score: 17 stages and 41 steps. The RARP Assessment Score was acceptable (56.67%), feasible (96.67%), and had educational impact (100%). Fifteen robotic surgery trainees were assessed for 8 mo. In 426 RARP cases (range: 4-79), all procedural steps were attempted by trainees. Trainees were assessed with the RARP Assessment Score by their expert mentors, and LCs for individual steps were plotted. LCs demonstrated plateaus for anterior bladder neck transection (16 cases), posterior bladder neck transection (18 cases), posterior dissection (9 cases), dissection of prostatic pedicle and seminal vesicles (15 cases), and anastomosis (17 cases). Other steps did not plateau during data collection. Conclusions: The RARP Assessment Score based on HFMEA methodology identified critical steps for focused RARP training and assessed surgeons. LCs demonstrate the experience necessary to reach a level of competence in technical skills to protect patients. Patient summary: We developed a safety and assessment tool to gauge the technical skills of surgeons performing robot-assisted radical prostatectomy. Improvement was monitored, and measures of progress can be used in future to guide mentors when training surgeons to operate safely. (C) 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.mixedLovegrove, Catherine; Novara, Giacomo; Mottrie, Alex; Guru, Khurshid A.; Brown, Matthew; Challacombe, Ben; Popert, Richard; Raza, Johar; Van Der Poel, Henk; Peabody, James; Dasgupta, Prokar; Ahmed, KamranLovegrove, Catherine; Novara, Giacomo; Mottrie, Alex; Guru, Khurshid A.; Brown, Matthew; Challacombe, Ben; Popert, Richard; Raza, Johar; Van Der Poel, Henk; Peabody, James; Dasgupta, Prokar; Ahmed, Kamra