Prospective Study of Antibiotic Prophylaxis for Prostate Biopsy Involving >1100 Men

We aimed to compare infection rates for two 3-day antibiotic prophylaxis regimens for transrectal ultrasound-guided prostate biopsy (TRUSgbp) and demonstrate local microbiological trends. In 2008, 558 men and, in 2009, 625 men had TRUSgpb. Regimen 1 (2008) comprised 400 mg Ofloxacin immediately before biopsy and 200 mg 12-hourly for 3 days. Regimen 2 (2009) comprised Ofloxacin 200 mg 12-hourly for 3 days commencing 24 hours before biopsy. 20/558 (3.6%) men had febrile episodes with regimen 1 and 10/625 (1.6%) men with regimen 2 (P = 0.03). E. coli was the most frequently isolated organism. Overall, 7/13 (54%) of positive urine cultures were quinolone resistant and (5/13) 40% were multidrug resistant. Overall, 5/9 (56%) patients with septicaemia were quinolone resistant. All patients were sensitive to Meropenem. There was 1 (0.2%) death with regimen 1. Commencing Ofloxacin 24 hours before TRUSgpb reduced the incidence of febrile episodes significantly. We observed the emergence of quinolone and multidrug-resistant E. coli. Meropenem should be considered for unresolving sepsis

Lepton Fluxes from Atmospheric Charm

We reexamine the charm contribution to atmospheric lepton fluxes in the context of perturbative QCD. We include next-to-leading order corrections and discuss theoretical uncertainties due to the extrapolations of the gluon distributions at small-x. We show that the charm contribution to the atmospheric muon flux becomes dominant over the conventional contribution from pion and kaon decays at energies of about 10^5 GeV. We compare our fluxes with previous calculations.Comment: 19 pages, latex, revtex, psfi

A Canadian approach to the regionalization of testis cancer: A review

At the Canadian Testis Cancer Workshop, the rationale and feasibility of regionalization of testis cancer care were discussed. The two-day workshop involved urologists, medical and radiation oncologists, pathologists, radiologists, physician’s assistants, residents and fellows, and nurses, as well as patients and patient advocacy groups. This review summarizes the discussion and recommendations of one of the central topics of the workshop — the centralization of testis cancer in Canada. It was acknowledged that non-guideline-concordant care in testis cancer occurs frequently, in the range of 18–30%. The National Health Service in the U.K. stipulates various testis cancer care modalities be delivered through supra-regional network. All cases are reviewed at a multidisciplinary team meeting and aspects of care can be delivered locally through the network. In Germany, no such network exists, but an insurance-supported online second opinion network was developed that currently achieves expert case review in over 30% of cases. There are clear benefits to regionalization in terms of survival, treatment morbidity, and cost. There was agreement at the workshop that a structured pathway for diagnosis and treatment of testis cancer patients is required. Regionalization may be challenging in Canada because of geography; independent administration of healthcare by each province; physicians fearing loss of autonomy and revenue; patient unwillingness to travel long distances from home; and the inability of the larger centers to handle the ensuing increase in volume. We feel the first step is to identify the key performance indicators and quality metrics to track the quality of care received. After identifying these metrics, implementation of a “networks of excellence” model, similar to that seen in sarcoma care in Ontario, could be effective, coupled with increased use of health technology, such as virtual clinics and telemedicine

Heavy quarkonium: progress, puzzles, and opportunities

A golden age for heavy quarkonium physics dawned a decade ago, initiated by the confluence of exciting advances in quantum chromodynamics (QCD) and an explosion of related experimental activity. The early years of this period were chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in 2004, which presented a comprehensive review of the status of the field at that time and provided specific recommendations for further progress. However, the broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles could only be partially anticipated. Since the release of the YR, the BESII program concluded only to give birth to BESIII; the $B$-factories and CLEO-c flourished; quarkonium production and polarization measurements at HERA and the Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the deconfinement regime. All these experiments leave legacies of quality, precision, and unsolved mysteries for quarkonium physics, and therefore beg for continuing investigations. The plethora of newly-found quarkonium-like states unleashed a flood of theoretical investigations into new forms of matter such as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the spectroscopy, decays, production, and in-medium behavior of c\bar{c}, b\bar{b}, and b\bar{c} bound states have been shown to validate some theoretical approaches to QCD and highlight lack of quantitative success for others. The intriguing details of quarkonium suppression in heavy-ion collisions that have emerged from RHIC have elevated the importance of separating hot- and cold-nuclear-matter effects in quark-gluon plasma studies. This review systematically addresses all these matters and concludes by prioritizing directions for ongoing and future efforts.Comment: 182 pages, 112 figures. Editors: N. Brambilla, S. Eidelman, B. K. Heltsley, R. Vogt. Section Coordinators: G. T. Bodwin, E. Eichten, A. D. Frawley, A. B. Meyer, R. E. Mitchell, V. Papadimitriou, P. Petreczky, A. A. Petrov, P. Robbe, A. Vair

A Single Mutation in the Carboxy Terminus of Reovirus Outer-Capsid Protein σ3 Confers Enhanced Kinetics of σ3 Proteolysis, Resistance to Inhibitors of Viral Disassembly, and Alterations in σ3 Structure

Mammalian reoviruses undergo acid-dependent proteolytic disassembly within endosomes, resulting in formation of infectious subvirion particles (ISVPs). ISVPs are obligate intermediates in reovirus disassembly that mediate viral penetration into the cytoplasm. The initial biochemical event in the reovirus disassembly pathway is the proteolysis of viral outer-capsid protein σ3. Mutant reoviruses selected during persistent infection of murine L929 cells (PI viruses) demonstrate enhanced kinetics of viral disassembly and resistance to inhibitors of endocytic acidification and proteolysis. To identify sequences in σ3 that modulate acid-dependent and protease-dependent steps in reovirus disassembly, the σ3 proteins of wild-type strain type 3 Dearing; PI viruses L/C, PI 2A1, and PI 3-1; and four novel mutant σ3 proteins were expressed in insect cells and used to recoat ISVPs. Treatment of recoated ISVPs (rISVPs) with either of the endocytic proteases cathepsin L or cathepsin D demonstrated that an isolated tyrosine-to-histidine mutation at amino acid 354 (Y354H) enhanced σ3 proteolysis during viral disassembly. Yields of rISVPs containing Y354H in σ3 were substantially greater than those of rISVPs lacking this mutation after growth in cells treated with either acidification inhibitor ammonium chloride or cysteine protease inhibitor E64. Image reconstructions of electron micrographs of virus particles containing wild-type or mutant σ3 proteins revealed structural alterations in σ3 that correlate with the Y354H mutation. These results indicate that a single mutation in σ3 protein alters its susceptibility to proteolysis and provide a structural framework to understand mechanisms of σ3 cleavage during reovirus disassembly

Rates of primary and secondary treatments for patients on active surveillance for localized prostate cancer—A population‐based cohort study

Abstract Background The rate of primary and secondary treatment while on active surveillance (AS) for localized prostate cancer at the general population level is unknown. Our objective was to determine the patterns of secondary treatments after primary surgery or radiation for patients who undergo AS. Methods This was a population‐based retrospective cohort study of men aged 50‐80 years old in Ontario, Canada, between 2008 and 2016. We identified 26 742 patients with prostate cancer, a Gleason grade score ≤7, and an index prostate‐specific antigen ≤10 ng/mL. Patients were categorized as undergoing AS with or without delayed primary treatment (DT; treatment >6 months after diagnosis) versus immediate treatment (IT; treatment ≤6 months). Patients receiving DT and IT were propensity score matched and the rate of secondary treatment (surgery or radiation ± androgen deprivation treatment) was compared using Cox proportional hazards models. Results We identified 10 214 patients who underwent AS and 11 884 patients who underwent IT. Among patients undergoing AS, 3724 (36.5%) eventually underwent DT and among them, 406 (10.9%) underwent secondary treatment. The median time to DT was 1.2 years (IQR 0.5‐8.1 years). The relative rate of undergoing secondary treatment was similar in the DT vs IT group (HR 0.92; 95% CI: 0.79‐1.08). The risk of death in the DT group was higher compared to patients who did not undergo treatment (HR 1.23, 95% CI: 1.01‐1.49). Conclusions Among patients with localized prostate cancer on AS, one third undergo DT. The rate of secondary treatment was similar between the DT and IT groups. Patients in the DT group may experience a higher risk of mortality compared to those who remained on AS