The use of biomarkers for prostate cancer (PCa) screening, detection, and prognostication have revolutionized the diagnosis and management of the disease. Current clinical practice has been driven largely by the utilization of prostate-specific antigen (PSA). The lack of specificity of PSA for PCa has led to both unnecessary biopsies and overdiagnosis of indolent cancers. The recent controversial recommendation by the United States Preventive Services Task Force against PCa screening has highlighted the need for novel clinically useful biomarkers. We review the literature on PCa biomarkers in serum, urine, and tissue. While these markers show promise, none seems poised to replace PSA, but rather may augment it. Further validation and consideration of how these novel markers improve clinical outcome is necessary. The discovery of new genetic markers shows promise in stratifying men with aggressive PCa.

The relative importance of separation by distance and by environment to population genetic diversity can be conveniently tested in river networks, where these two drivers are often independently distributed over space. To evaluate the importance of dispersal and environmental conditions in shaping microbial population structures, we performed genome-resolved metagenomic analyses of benthic Microcoleus-dominated cyanobacterial mats collected in the Eel and Russian River networks (California, USA). The 64 Microcoleus genomes were clustered into three species that shared >96.5% average nucleotide identity (ANI). Most mats were dominated by one strain, but minor alleles within mats were often shared, even over large spatial distances (>300 km). Within the most common Microcoleus species, the ANI between the dominant strains within mats decreased with increasing spatial separation. However, over shorter spatial distances (tens of kilometres), mats from different subwatersheds had lower ANI than mats from the same subwatershed, suggesting that at shorter spatial distances environmental differences between subwatersheds in factors like canopy cover, conductivity, and mean annual temperature decreases ANI. Since mats in smaller creeks had similar levels of nucleotide diversity (π) as mats in larger downstream subwatersheds, within-mat genetic diversity does not appear to depend on the downstream accumulation of upstream-derived strains. The four-gamete test and sequence length bias suggest recombination occurs between almost all strains within each species, even between populations separated by large distances or living in different habitats. Overall, our results show that, despite some isolation by distance and environmental conditions, sufficient gene-flow occurs among cyanobacterial strains to prevent either driver from producing distinctive population structures across the watershed.

Tetra-amelia syndrome is a congenital disorder associated with near or complete absence of all 4 limbs. Noninvasive hemodynamic monitoring may be difficult or impossible in such patients. We describe the use of a finger cuff blood pressure system for continuous noninvasive blood pressure monitoring in an infant with near-complete tetra-amelia undergoing laparoscopic gastrostomy tube placement. This case suggests the potential use of such a blood pressure monitoring system for other patients with comparable deformities.

Objective

This study compared admission rates to a United States anesthesiology residency program for applicants completing face-to-face versus web-based interviews during the admissions process. We also explored factors driving applicants to select each interview type.

Methods

The 211 applicants invited to interview for admission to our anesthesiology residency program during the 2014-2015 application cycle were participants in this pilot observational study. Of these, 141 applicants selected face-to-face interviews, 53 applicants selected web-based interviews, and 17 applicants declined to interview. Data regarding applicants' reasons for selecting a particular interview type were gathered using an anonymous online survey after interview completion. Residency program admission rates and survey answers were compared between applicants completing face-to-face versus web-based interviews.

Results

One hundred twenty-seven (75.1%) applicants completed face-to-face and 42 (24.9%) completed web-based interviews. The admission rate to our residency program was not significantly different between applicants completing face-to-face versus web-based interviews. One hundred eleven applicants completed post-interview surveys. The most common reasons for selecting web-based interviews were conflict of interview dates between programs, travel concerns, or financial limitations. Applicants selected face-to-face interviews due to a desire to interact with current residents, or geographic proximity to the residency program.

Conclusions

These results suggest that completion of web-based interviews is a viable alternative to completion of face-to-face interviews, and that choice of interview type does not affect the rate of applicant admission to the residency program. Web-based interviews may be of particular interest to applicants applying to a large number of programs, or with financial limitations.

Background

Active surveillance (AS) is an accepted means of managing low-risk prostate cancer. Because of the rarity of downstream events, data from existing AS cohorts cannot yet address how differences in surveillance intensity affect metastasis and mortality. This study projected the comparative benefits of different AS schedules in men diagnosed with prostate cancer who had Gleason score (GS) ≤6 disease and risk profiles similar to those in North American AS cohorts.

Methods

Times of GS upgrading were simulated based on AS data from the University of Toronto, Johns Hopkins University, the University of California at San Francisco, and the Canary Pass Active Surveillance Cohort. Times to metastasis and prostate cancer death, informed by models from the Scandinavian Prostate Cancer Group 4 trial, were projected under biopsy surveillance schedules ranging from watchful waiting to annual biopsies. Outcomes included the risk of metastasis, the risk of death, remaining life-years (LYs), and quality-adjusted LYs.

Results

Compared with watchful waiting, AS biopsies reduced the risk of prostate cancer metastasis and prostate cancer death at 20 years by 1.4% to 3.3% and 1.0% to 2.4%, respectively; and 5-year biopsies reduced the risk of metastasis and prostate cancer death by 1.0% to 2.4% and 0.6% to 1.6%, respectively. There was little difference between annual and 5-year biopsy schedules in terms of LYs (range of differences, 0.04-0.16 LYs) and quality-adjusted LYs (range of differences, -0.02 to 0.09 quality-adjusted LYs).

Conclusions

Among men diagnosed with GS ≤6 prostate cancer, obtaining a biopsy every 3 or 4 years appears to be an acceptable alternative to more frequent biopsies. Reducing surveillance intensity for those who have a low risk of progression reduces the number of biopsies while preserving the benefit of more frequent schedules.

The Hamamatsu R5912-HQE photomultiplier-tube (PMT) is a novel high-quantum efficiency PMT. It is currently used in the DEAP-3600 dark matter detector and is of significant interest for future dark matter and neutrino experiments where high signal yields are needed. We report on the methods developed for in-situ characterization and monitoring of DEAP's 255 R5912-HQE PMTs. This includes a detailed discussion of typical measured single-photoelectron charge distributions, correlated noise (afterpulsing), dark noise, double, and late pulsing characteristics. The characterization is performed during the detector commissioning phase using laser light injected through a light diffusing sphere and during normal detector operation using LED light injected through optical fibres.

The Dark matter Experiment using Argon Pulse-shape discrimination (DEAP) has been designed for a direct detection search for particle dark matter using a single-phase liquid argon target. The projected cross section sensitivity for DEAP-3600 to the spin-independent scattering of Weakly Interacting Massive Particles (WIMPs) on nucleons is 10−46cm2 for a 100 GeV/c2 WIMP mass with a fiducial exposure of 3 tonne-years. This paper describes the physical properties and construction of the DEAP-3600 detector.

Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities. During the acute phase of disease, a higher respiratory SARS-CoV-2 viral burden and lower Receptor Binding Domain and Spike antibody titers were associated with both the physical predominant and the multidomain deficit clusters. A lower frequency of circulating B lymphocytes by mass cytometry (CyTOF) was observed in the multidomain deficit cluster. Circulating fibroblast growth factor 21 (FGF21) was significantly elevated in the mental/cognitive predominant and the multidomain clusters. Future efforts to link PASC to acute anti-viral host responses may help to better target treatment and prevention of PASC.

The glycosylation of IgG plays a critical role during human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, activating immune cells and inducing cytokine production. However, the role of IgM N-glycosylation has not been studied during human acute viral infection. The analysis of IgM N-glycosylation from healthy controls and hospitalized coronavirus disease 2019 (COVID-19) patients reveals increased high-mannose and sialylation that correlates with COVID-19 severity. These trends are confirmed within SARS-CoV-2-specific immunoglobulin N-glycan profiles. Moreover, the degree of total IgM mannosylation and sialylation correlate significantly with markers of disease severity. We link the changes of IgM N-glycosylation with the expression of Golgi glycosyltransferases. Lastly, we observe antigen-specific IgM antibody-dependent complement deposition is elevated in severe COVID-19 patients and modulated by exoglycosidase digestion. Taken together, this work links the IgM N-glycosylation with COVID-19 severity and highlights the need to understand IgM glycosylation and downstream immune function during human disease.