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Take Home Message Intervention-related deaths were rare in the ERSPC trial, but relatively large differences in the number of intervention-related deaths were observed among centers. Standardized cause-of-death reviews are important in identifying intervention-related deaths and should be used in screening trials., Background Identification of intervention-related deaths is important for an accurate assessment of the ratio of benefit to harm in screening trials. Objective To investigate intervention-related deaths by study arm in the European Randomized Study of Prostate Cancer Screening (ERSPC). Design, setting, and participants ERSPC is a multicenter trial initiated in the 1990s to investigate whether screening on the basis of prostate-specific antigen (PSA) can decrease prostate cancer mortality. The present study included men in the core age group (55–69 yr: screening group n = 112 553, control group n = 128 681) with 16-yr follow-up. Outcome measurements and statistical analysis Causes of death among men with prostate cancer in ERSPC were predominantly evaluated by independent national committees via review of medical records according to a predefined algorithm. Intervention-related deaths were defined as deaths caused by complications during the screening procedure, treatment, or follow-up. Descriptive statistics were used for the results. Results and limitations In total, 34 deaths were determined to be intervention-related, of which 21 were in the screening arm and 13 in the control arm. The overall risk of intervention-related death was 1.41 (95% confidence interval 0.99–1.99) per 10 000 randomized men for both arms combined and varied among centers from 0 to 7.0 per 10 000 randomized men. A limitation of this study is that differences in procedures among centers decreased the comparability of the results. Conclusions Intervention-related deaths were rare in ERSPC. Monitoring of intervention-related deaths in screening trials is important for assessment of harms. Patient summary We investigated deaths due to screening or treatment to assess harm in a trial of prostate cancer screening. Few such deaths were identified.

MRI-targeted prostate biopsy improves detection of clinically significant prostate cancer (PCa). However, up to 70% of PCa lesions display intralesional tumor heterogeneity. Current target sampling strategies do not yet adequately account for this finding. This prospective study included 118 patients who underwent transperineal robotic assisted biopsy of the prostate. We identified a total of 58 PCa-positive PI-RADS lesions. We compared diagnostic accuracy of a target-saturation biopsy strategy to accuracy of single, two, or three randomly selected targeted biopsy cores and analysed potential clinical implications. Intralesional detection of clinically significant cancer (ISUP ≥ 2) was 78.3% for target-saturation biopsy and 39.1%, 52.2%, and 67.4% for one, two, and three targeted cores, respectively. Target-saturation biopsies led to a more accurate characterization of PCa in terms of Gleason score and reduced rates of significant cancer missed. Compared to one, two, and three targeted biopsy cores, target-saturation biopsies led to intensified staging procedures in 21.7%, 10.9, and 8.7% of patients, and ultimately to a potential change in therapy in 39.1%, 26.1%, and 10.9% of patients. This work presents the concept of robotic-assisted target saturation biopsy. This technique has the potential to improve diagnostic accuracy and thus individual staging procedures and treatment decisions.

Introduction: Active surveillance (AS) strategies were established to avoid overtreatment of low-risk prostate cancer (PCa) patients. Low tumor volume represents one indication criteria; however, applying this criterion after MRI-targeted prostate biopsies may lead to overestimation of tumor volume; wherefore, patients suitable for AS would be exposed to the risk of overtreatment. Methods: This retrospective analysis included 318 patients in which PCa was detected by MRI-TRUS fusion prostate biopsy. Classic and extended indication for AS included Gleason 6 and Gleason 3 + 4 cancer, respectively. We assessed the effect of targeted biopsies and temporary rating strategies on eligibility for AS and developed new “composite” algorithms to more accurately assess eligibility for AS. Results: Forty-four (13.8%) and 60 (18.9%) of the 318 patients qualified for AS according to “classic” and “extended” criteria, respectively. Application of the “composite 1” definition led to AS eligibility of 52 of 248 patients (20.97%) in the classic and of 77 of 248 patients (31.05%) in the “extended” group. Conclusions: We could demonstrate that classic algorithms led to ineligibility of patients for AS. We propose a new rating algorithm to improve tumor assessment for a more accurate indication for AS.

Alumina is one of the most popular ceramic materials widely used in both tooling and construction applications due to its low production cost, and high properties. However, the final properties of the product depend not only on the purity of the powder, but also, e.g., on its particle size, specific surface area, and the production technology used. These parameters are particularly important in the case of choosing additive techniques for the production of details. Therefore, the article presents the results of comparing five grades of Al2O3 ceramic powder. Their specific surface area (via Brunauer–Emmett–Teller (BET) and Barrett–Joyner–Halenda (BJH) methods), particle size distribution, and phase composition by X-ray diffraction (XRD) were determined. Moreover, the surface morphology was characterized by the scanning electron microscopy (SEM) technique. The discrepancy between generally available data and the results obtained from measurements has been indicated. Moreover, the method of spark plasma sintering (SPS), equipped with the registration system of the position of the pressing punch during the process, was used to determine the sinterability curves of each of the tested grades of Al2O3 powder. Based on the obtained results, a significant influence of the specific surface area, particle size, and the width of their distribution at the beginning of the Al2O3 powder sintering process was confirmed. Furthermore, the possibility of using the analyzed variants of powders for binder jetting technology was assessed. The dependence of the particle size of the powder used on the quality of the printed parts was demonstrated. The procedure presented in this paper, which involves analyzing the properties of alumina varieties, was used to optimize the Al2O3 powder material for binder jetting printing. The selection of the best powder in terms of technological properties and good sinterability makes it possible to reduce the number of 3D printing processes, which makes it more economical and less time-consuming.

Holmium laser enucleation of the prostate (HoLEP) is a valid treatment option to relieve bladder outlet obstruction in patients with large prostate volumes (PV). Its efficacy, tolerability, and safety are comparable to the ones of other laser treatments of the prostate and resection techniques. However, safety and efficacy of HoLEP have not been compared between patients with and without preoperative urinary retention. We included 350 patients (mean age 71.2 years) who had undergone HoLEP due to lower urinary tract symptoms (LUTS) or urinary retention caused by prostatic hyperplasia. We evaluated the differences in peri- and postoperative outcomes and complications between patients with and patients without preoperative urinary retention. The mean PV was 115 cm3. PV was > 100 cm3 in 61.9% and < 100 cm3 in 38.1% of the patients. Perioperative complications occurred in 23 patients (6.6%), 15 of which (4.3%) required operative revision. We found no significant differences in terms of complication rates between patients with PV > 100 cm3 and patients with PV < 100 cm3. Mean catheterization-duration was 3.3 days. Preoperatively, 140 patients (40%) had a suprapubic or transurethral indwelling catheter; they did not differ from patients without preoperative catheter regarding postoperative catheter removal success rate, early postoperative complications, and functional outcomes. Prostate cancer was diagnosed in 43 patients (12.3%). Median postoperative PSA-decline was 6.1 ug/l (89.8% drop). HoLEP is a safe and effective treatment for patients with LUTS or urinary retention and large PV. PV > 100 cm3 was not associated with higher complication rates or successful catheter-removal. Furthermore, functional outcomes were independent of preoperative catheterization.

BACKGROUND VPM1002BC is a genetically modified Mycobacterium bovis bacillus Calmette-Guérin (BCG) strain with potentially improved immunogenicity and attenuation. OBJECTIVE To report on the efficacy, safety, tolerability and quality of life of intravesical VPM1002BC for the treatment of non-muscle-invasive bladder cancer (NMIBC) recurrence after conventional BCG therapy. DESIGN, SETTING, AND PARTICIPANTS We designed a phase 1/2 single-arm trial (NCT02371447). Patients with recurrent NMIBC after BCG induction ± BCG maintenance therapy and intermediate to high risk for cancer progression were eligible. INTERVENTION Patients were scheduled for standard treatment of six weekly instillations with VPM1002BC followed by maintenance for 1 yr. Treatment was stopped in cases of recurrence. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary endpoint was defined as the recurrence-free rate (RFR) in the bladder 60 wk after trial registration. The sample size was calculated based on the assumption that ≥30% of the patients would be without recurrence at 60 wk after registration. RESULTS AND LIMITATIONS After exclusion of two ineligible patients, 40 patients remained in the full analysis set. All treated tumours were of high grade and 27 patients (67.5%) presented with carcinoma in situ. The recurrence-free rate in the bladder at 60 wk after trial registration was 49.3% (95% confidence interval [CI] 32.1-64.4%) and remained at 47.4% (95% CI 30.4-62.6%] at 2 yr and 43.7% (95% CI 26.9-59.4%) at 3 yr after trial registration. At the same time, progression to muscle-invasive disease had occurred in three patients and metastatic disease in four patients. Treatment-related grade 1, 2, and 3 adverse events (AEs) were observed in 14.3%, 54.8%, and 4.8% of the patients, respectively. No grade ≥4 AEs occurred. Two of the 42 patients did not tolerate five or more instillations during induction. Limitations include the single-arm trial design and the low number of patients for subgroup analysis. CONCLUSIONS At 1 yr after treatment start, almost half of the patients remained recurrence-free after therapy with VPM100BC. The primary endpoint of the study was met and the therapy is safe and well tolerated. PATIENT SUMMARY We conducted a trial of VPM100BC, a genetically modified bacillus Calmette-Guérin (BCG) strain for treatment of bladder cancer not invading the bladder muscle. At 1 year after the start of treatment, almost half of the patients with a recurrence after previous conventional BCG were free from non-muscle-invasive bladder cancer (NMIBC). The results are encouraging and VPM1002BC merits further evaluation in randomised studies for patients with NMIBC.

The extent of variation in urinary and sexual functional outcomes after radical prostatectomy (RPE) between prostate cancer (PC) operating sites remains unknown. Therefore, this analysis aims to compare casemix-adjusted functional outcomes (EPIC-26 scores incontinence, irritative/obstructive function and sexual function) between operating sites 12 months after RPE.Analysis of a cohort of 7065 men treated with RPE at 88 operating sites (prostate cancer centers, "PCCs") between 2016 and 2019. Patients completed EPIC-26 and sociodemographic information surveys at baseline and 12 months after RPE. Survey data were linked to clinical data. EPIC-26 domain scores at 12 months after RPE were adjusted for relevant confounders (including baseline domain score, clinical and sociodemographic information) using regression analysis. Differences between sites were described using minimal important differences (MIDs) and interquartile ranges (IQR). The effects of casemix adjustment on the score results were described using Cohen's d and MIDs.Adjusted domain scores at 12 months varied between sites, with IQRs of 66-78 (incontinence), 89-92 (irritative/obstructive function), and 20-29 (sexual function). Changes in domain scores after casemix adjustment for sites ≥ 1 MID were noted for the incontinence domain (six sites). Cohen's d ranged between - 0.07 (incontinence) and - 0.2 (sexual function), indicating a small to medium effect of casemix adjustment.Variation between sites was greatest in the incontinence and sexual function domains for RPE patients. Future research will need to identify the factors contributing to this variation.The study is registered at the German Clinical Trial Registry ( https://www.drks.de/drks_web/ ) with the following ID: DRKS00010774.

INTRODUCTION AND OBJECTIVE:MRI-targeted prostate biopsy improves the detection of clinically significant prostate cancer (PCa) and reduces overdetection of clinically insignificant cancer. However,...

INTRODUCTION AND OBJECTIVE:With a median follow–up of 16 years the European Randomized Study of Screening for Prostate Cancer (ERSPC) shows a relative reduction of prostate cancer (PCa) specific mo...

The sand lances (also known as sand-eels) are small fish belonging to family Ammodytidae that consists of 31 species belonging to 7 genera. Despite world-wide distribution, key role in the ...

Background Differential treatment between trial arms has been suggested to bias prostate cancer (PC) mortality in the European Randomized Study of Screening for Prostate Cancer (ERSPC). Objective To quantify the contribution of treatment differences to the observed PC mortality reduction between the screening arm (SA) and the control arm (CA). Design, setting, and participants A total of 14 136 men with PC (SA: 7310; CA: 6826) in the core age group (55–69 yr) at 16 yr of follow-up. Outcome measurements and statistical analysis The outcomes measurements were observed and estimated numbers of PC deaths by treatment allocation in the SA and CA, respectively. Primary treatment allocation was modeled using multinomial logistic regression adjusting for center, age, year, prostate-specific antigen, grade group, and tumor-node-metastasis stage. For each treatment, logistic regression models were fitted for risk of PC death, separately for the SA and CA, and using the same covariates as for the treatment allocation model. Treatment probabilities were multiplied by estimated PC death risks for each treatment based on one arm, and then summed and compared with the observed number of deaths. Results and limitations The difference between the observed and estimated treatment distributions (hormonal therapy, radical prostatectomy, radiotherapy, and active surveillance/watchful waiting) in the two arms ranged from −3.3% to 3.3%. These figures, which represent the part of the treatment differences between arms that cannot be explained by clinicopathological differences, are small compared with the observed differences between arms that ranged between 7.2% and 10.1%. The difference between the observed and estimated numbers of PC deaths among men with PC was 0.05% (95% confidence interval [CI] −0.1%, 0.2%) when applying the CA model to the SA, had the two groups received identical primary treatment, given their clinical characteristics. When instead applying the SA model to the CA, the difference was, as expected, very similar—0.01% (95% CI −0.3%, 0.2%). Consistency of the results of the models demonstrates the robustness of the modeling approach. As the observed difference between trial arms was 4.2%, our findings suggest that differential treatment explains only a trivial proportion of the main findings of ERSPC. A limitation of the study is that only data on primary treatment were available. Conclusions Use of prostate-specific antigen remains the predominant explanation for the reduction in PC mortality seen in the ERSPC trial and is not attributable to differential treatment between trial arms. Patient summary This study shows that prostate cancer deaths in the European screening trial (European Randomized Study of Screening for Prostate Cancer) were prevented because men were diagnosed and treated earlier through prostate-specific antigen screening, and not because of different, or better, treatment in the screening arm compared with the control arm.

MRI-targeted prostate biopsy improves detection of clinically significant prostate cancer (PCa). However, up to 70% of PCa lesions display intralesional tumor heterogeneity. Current target sampling strategies do not yet adequately account for this finding. This prospective study included 118 patients who underwent transperineal robotic assisted biopsy of the prostate. We identified a total of 58 PCa-positive PI-RADS lesions. We compared diagnostic accuracy of a target-saturation biopsy strategy to accuracy of single, two, or three randomly selected targeted biopsies and analysed potential clinical implications. Intralesional detection of clinically significant cancer (ISUP ≥ 2) was 78.3% for target-saturation biopsy and 39.1%, 52.2%, and 67.4% for one, two, and three targeted cores, respectively. Target-saturation biopsies led to a more accurate characterization of PCa in terms of Gleason score and reduced rates of missed cancer. Compared to one, two, and three targeted biopsies, target-saturation biopsies led to intensified staging procedures in 21.7%, 10.9, and 8.7% of patients, and ultimately to a potential change in therapy in 39.1%, 26.1%, and 10.9% of patients. This work presents the concept of robotic-assisted target saturation biopsy. This technique has the potential to improve diagnostic accuracy and thus individual staging procedures and treatment decisions.

The volume Credit scoring in context of interpretable machine learning presents a unique, and simultaneously balanced, combination of explanation of theoretical concepts and contemporary scoring practices rooted in these concepts. We assume that the reader has a working analytical knowledge in fields of finance, mathematics, applied statistics and data processing algorithms. This monograph is prepared for one of the three main target groups: 1) finance and economics students (graduate or postgraduate levels), 2) risk practitioners (e.g., risk managers, data scientists, risk modelers, regulators, consultants) and 3) independent researchers (including academics, freelancing risk specialists, and machine-learning experts). This monograph’s primary purpose and the ambition we had while writing it, were to present the development and maintenance of the creditworthiness assessment process, emphasizing the applicability of the state of the art data analytics methods (i.e., machine learning). The modern transformation allowing big data driven decision-making, especially in credits coring, is present not only in universal banks but also in many other entities that offer solutions based on trade credit. Today’s standards and business practices require full transparency and audibility of the analytical methods used. The era of black boxes, the actions of which could not be understood and decision-making processes in which stakeholders are not able to precisely explain the impact of individual factors, has already ended in many industries and in banking itself probably never came. For this reason, in this monograph so many pages are devoted not only to the machine-learning methods themselves (supported by the Explainable Artificial Intelligence - XAI) but also to other aspects of building robust and trustworthy quantitative models supporting business processes.

The article focus on problematic associated with beggining of rap music. Studying oldest songs from genre showing, that in most instances, people rapping for fun or to encourage other in participation in it. Author probe not only first rap songs and rap artists, but also music extraction, which arise from inspiration some type of music, like blues, funk, or jazz. Analise few singles from 70. and 80. trying answer on question, why some tracks were so popular. By specyfic of subject, text vicariously keeping on city culture of New York, previous century in United States.

Background Trials of cancer screening present results in terms of deaths prevented, but metastasis is also a key endpoint that screening seeks to prevent. We developed a framework for projecting overall (de novo and progressive) metastases prevented in a screening trial using prostate cancer screening as a case study. Methods Mechanistic simulation model in which screening shifts a fraction of cases that would be metastatic at diagnosis to being non-metastatic. This shift increases the incidence of non-overdiagnosed, organ-confined cases. We use estimates of the risk of metastatic progression for these cases to project how many progress to metastasis after diagnosis and tally the projected de novo and progressive metastatic cases with and without screening. We use data on stage shift from the European Randomized Study of Screening for Prostate Cancer (ERSPC) and data on the risk of metastatic progression from the Scandinavian Prostate Cancer Group-4 trial. We estimate the relative risk and absolute risk reductions in metastatic disease at diagnosis and compare these with reductions in overall metastases. Results Assuming no effect of screening beyond initial stage shift at diagnosis, the model projects a 43% reduction in metastasis at diagnosis but a 22% reduction in the cumulative probability of metastasis over 12 years in favor of screening. These results are consistent with the empirical findings from the ERSPC. Conclusion Any reduction in metastatic disease at diagnosis under screening is likely to be an overly optimistic predictor of the impact of screening on overall metastasis and disease-specific mortality.

Inducing reproduction during periods of the year when spawning typically does not occur is an important goal for the feasibility of commercial fish farming. Pre-seasonal propagation of pikeperch generally occurs about 3 months before the natural spawning season. The objective of this study was to assess effects of imposing a thermal schedule for control of water temperature and differing salmon gonadotropin releasing hormone analogue (sGnRHa) dosages on final stages of oocyte growth, and egg quality by optimizing protocol duration and synchronizing spawning time. In Experiment 1, there was analysis of thermal schedule effects for water temperature control when hormonal administrations occurred before or after water warming (WARMING and STABLE, respectively). In Experiment 2, there was assessment of the sGnRHa dosage effects during the warming schedule. In both experiments there was analysis of oocyte diameter from time of sGnRHa administration until the late stages of maturation. There was greater synchrony in time of spawning in specimens of the WARMING group with lesser variability in time from sGnRHa administration to spawning. In Experiment 2, values for reproductive variables were variable among the different groups, without any differences between treatments. Oocyte diameter at the time of sGnRHa administration was correlated with embryo survival. For effective pre-seasonal pikeperch propagation, the selection of breeders based on oocyte diameter, and administration of 5 μg/kg sGnRHa immediately upon transport to hatchery, followed by a 1 °C/d temperature increase to 10 °C, are effective methods for induction of spawning during periods when spawning does not naturally occur.

Background: The European Randomized study of Screening for Prostate Cancer (ERSPC) has previously demonstrated that prostate-specific antigen (PSA) screening decreases prostate cancer (PCa) mortality. Objective: To determine whether PSA screening decreases PCa mortality for up to 16 yr and to assess results following adjustment for nonparticipation and the number of screening rounds attended. Design, setting, and participants: This multicentre population-based randomised screening trial was conducted in eight European countries. Report includes 182 160 men, followed up until 2014 (maximum of 16 yr), with a predefined core age group of 162 389 men (55-69 yr), selected from population registry. Outcome measurements and statistical analysis: The outcome was PCa mortality, also assessed with adjustment for nonparticipation and the number of screening rounds attended. Results and limitations: The rate ratio of PCa mortality was 0.80 (95% confidence interval [CI] 0.72-0.89, p 20 ng/ml (9.9% compared with 4.1% in the second round, p

This case report describes a unique manifestation of a primary urethral squamous cell carcinoma (SCC) as the underlying pathology in an 80-year-old male patient who underwent partial penectomy due to an enlarging penile mass. Persistent pain in the right knee was discovered to be a pathologic fracture using magnetic resonance imaging. Computed tomography-guided biopsy confirmed metastatic SCC. Whole-body positron emission tomography revealed systemic dissemination to multiple sites. Orthopedic knee replacement was performed in combination with local radiotherapy. Palliative chemotherapy was rejected due to poor performance status. Primary urethral SCC is rare and an uncommon cause of advanced penile cancer. These findings could be of great interest to clinicians for two reasons. First, a tumor’s appearance can be misleading. Consequently, histological work-up in accordance with clinical guidelines is necessary for accurate diagnosis. Second, a more comprehensive investigation is required when clinical symptoms persist despite the use of conventional treatment. Our case is an instance in which persistent pain masked the presence of downstream metastasis. We believe that these aforementioned points are of significant clinical importance and present a salient learning opportunity.

Background The European Randomized Study of Screening for Prostate Cancer (ERSPC) demonstrated that prostate-specific antigen (PSA) screening significantly reduced prostate cancer mortality (rate ratio, 0.79; 95% confidence interval, 0.69-0.91). The US Prostate, Lung, Colorectal, and Ovarian (PLCO) trial indicated no such reduction but had a wide 95% CI (rate ratio for prostate cancer mortality, 1.09; 95% CI, 0.87-1.36). Standard meta-analyses are unable to account for key differences between the trials that can impact the estimated effects of screening and the trials' point estimates. Methods The authors calibrated 2 microsimulation models to individual-level incidence and mortality data from 238,936 men participating in the ERSPC and PLCO trials. A cure parameter for the underlying efficacy of screening was estimated by the models separately for each trial. The authors changed step-by-step major known differences in trial settings, including enrollment and attendance patterns, screening intervals, PSA thresholds, biopsy receipt, control arm contamination, and primary treatment, to reflect a more ideal protocol situation and differences between the trials. Results Using the cure parameter estimated for the ERSPC, the models projected 19% to 21% and 6% to 8%, respectively, prostate cancer mortality reductions in the ERSPC and PLCO settings. Using this cure parameter, the models projected a reduction of 37% to 43% under annual screening with 100% attendance and biopsy compliance and no contamination. The cure parameter estimated for the PLCO trial was 0. Conclusions The observed cancer mortality reduction in screening trials appears to be highly sensitive to trial protocol and practice settings. Accounting for these differences, the efficacy of PSA screening in the PLCO setting is not necessarily inconsistent with ERSPC results. Cancer 2018;124:1197-206. © 2017 American Cancer Society.

The composites consisting of ITO-supported ZnO nanorods covered with TiO2 shell were doped with nitrogen and decorated with gold nanoparticles in order to improve their photocatalytic activity under visible light. N-doped TiO2 (TiO2(N)) was prepared under mild conditions through a simple sol-gel synthesis in the presence of NH4Cl. Such procedure results in formation of a highly porous shell of TiO2(N) on the ZnO nanorods. The gold nanoparticles (AuNPs) of the size 7–25 nm were grafted onto the surface of TiO2 as well as TiO2(N) by a photodeposition method from aqueous solution of [AuCl(4-x)(OH)x]− precursor at pH 6.7. The composition and microstructure of the prepared samples were characterized by SEM, HR-TEM, HAADF-STEM, XRD, XPS and UV–vis spectroscopy. The photocatalytic properties of ZnO/TiO2/Au and ZnO/TiO2(N)/Au composites were studied under illumination with Xe lamp equipped with a 400 nm cut-off filter. It was found that low AuNPs loading (0.37% at.) resulted in 60% enhancement of photocatalytic decolorization of methylene blue (MB) under visible light with respect to Au-free sample owing to Au-plasmonic effect. Also, a simultaneous N-doping and AuNPs-decoration allows to multiply by three the photocurrent in photoelectrochemical water oxidation at the potential of 0.8 V vs. Ag/AgCl. We also showed that the elaborated Au-loaded composites possess a strong catalytic activity in O2 reduction under a small negative bias (−0.25 V vs. Ag/AgCl) in dark. We proved that illumination of the polarized sample with visible light enhances oxygen reduction and the produced active oxygen species (O2 −, H2O2 and OH) improve significantly degradation of MB, which was confirmed by total organic carbon (TOC) measurements. We demonstrated that rapid decomposition of MB is possible even in the presence of Na2SO4 which completely inhibits the process on the non-polarized catalyst.

ZnO/TiO2 composites were prepared by sol-gel deposition of TiO2 on ZnO nanorods hydrothermally grown on electrically conductive indium tin oxide substrate (ITO). It has been shown that the ZnO/TiO2 interface plays a key role in enhancement of photodecomposition of methylene blue (MB) used as a model test pollutant, under monochromatic light irradiation (400 nm). The increase of photocatalytic activity was attributed to the shift of absorption edge of ZnO/TiO2 towards visible light in comparison with bare TiO2. Further enhancement of photocatalytic activity of ZnO/TiO2 was achieved through its additional calcination at 450 °C for 3 h. This treatment brings 40% increase in the rate of MB decomposition and a two-fold rise of the photocurrent in H2O oxidation. Measurements of open circuit potential (Voc) showed that the improved properties of additionally calcined ZnO/TiO2 composites stem from decrease of the electron-hole recombination rate. Scanning transmission electron microscopy (STEM) studies showed that the additional calcination resulted in formation of voids at the ZnO/TiO2 interface. Energy dispersive X-ray (EDX) and X-ray photoelectron (XPS) spectroscopies proved that formation of voids is accompanied by the outward diffusion of Zn ions into TiO2 layer and allowed to conclude about the existence of the Kirkendall effect at ZnO/TiO2 interface. Occurrence of this effect observed for the first time at such moderate temperature (450 °C) is attributed to a highly defective nature of the surface layer of the ZnO nanorods.

Transrectal (TR) ultrasound-guided prostate biopsy is one of the most commonly performed urologic procedures worldwide. The major drawback of this approach is the associated risk for infectious complications. Sepsis rates are increasing due to rising antibiotic resistance, representing a global issue. The transperineal (TP) approach for prostate biopsy has recently been adopted at many centres as an alternative to the TR biopsy, and it was shown to be associated with a lower risk for sepsis. The aim of this study was to assess safety and tolerability of TP prostate biopsy performed in local anaesthesia. We retrospectively analysed data of patients who had undergone office-based TP prostate biopsy in local anaesthesia, performed by a single surgeon between January 2015 and May 2019. We evaluated the patients’ acceptance of the procedure by a pain score, as well as its safety and diagnostic performance. Four hundred patients were included. Median age was 66 years [range, 49–86]. Median prostate-specific antigen (PSA) concentration was 6.4 ng/ml [range, 0.3–1400], median PSA density was 0.15 ng/ml2 [range, 0–31.1] and median prostate volume was 40 ml [range, 6–150]. A total of 118 (29.5%) and 105 (26.2%) patients had orally received two and one doses of 500 mg fluoroquinolone, respectively, and 177 (44.3%) patients did not receive any antibiotic prophylaxis. No infectious complications occurred. Median pain score was 2.0 (range, 0–8). Overall cancer detection rate was 64.5% (258/400). Freehand TP prostate biopsy in local anaesthesia is a safe, effective and well-tolerated outpatient procedure with a high cancer detection rate. The elimination of infectious complications and its high accuracy make this technique a feasible alternative to the TR approach for the urological office. We assume that the single puncture and our trocar-like access sheath introduction technique diminish tissue trauma and bacterial exposition, and thus contribute to these promising results.

INTRODUCTION AND OBJECTIVES:Chemoprevention of prostate cancer (PCa) has been extensively investigated in the last decades. So far only 5-alpha-reductase-inhibitors (5-ARI) are supported by clinica...

BACKGROUND: Prostate-specific antigen (PSA) screening and concomitant treatment can be implemented in several ways. The authors investigated how the net benefit of PSA screening varies between common practice versus “good practice.”. METHODS: Microsimulation screening analysis (MISCAN) was used to evaluate the effect on quality-adjusted life-years (QALYs) if 4 recommendations were followed: limited screening in older men, selective biopsy in men with elevated PSA, active surveillance for low-risk tumors, and treatment preferentially delivered at high-volume centers. Outcomes were compared with a base model in which annual screening started at ages 55 to 69 years and were simulated using data from the European Randomized Study of Screening for Prostate Cancer. RESULTS: In terms of QALYs gained compared with no screening, for 1000 screened men who were followed over their lifetime, recommended good practice led to 73 life-years (LYs) and 74 QALYs gained compared with 73 LYs and 56 QALYs for the base model. In contrast, common practice led to 78 LYs gained but only 19 QALYs gained, for a greater than 75% relative reduction in QALYs gained from unadjusted LYs gained. The poor outcomes for common practice were influenced predominantly by the use of aggressive treatment for men with low-risk disease, and PSA testing in older men also strongly reduced potential QALY gains. CONCLUSIONS: Commonly used PSA screening and treatment practices are associated with little net benefit. Following a few straightforward clinical recommendations, particularly greater use of active surveillance for low-risk disease and reducing screening in older men, would lead to an almost 4-fold increase in the net benefit of prostate cancer screening. Cancer 2016;122:3386–3393. © 2016 American Cancer Society.

The aim of the paper is to present the philosophy of Lean Management as an instrument of improving sustainable management of enterprises. The article presents the origins, characteristics of the broadly understood concept of Lean Management and describes the idea of Sustainable Development (SD). At the same time implications for the application and development of the instruments which operationalize the assumptions of SD at the level of enterprises are discussed. The paper specifies those areas of functioning of contemporary companies in which Lean Management can be implemented and compares them with the features of traditional management in particular subjects.

Introduction VPM1002BC is a genetically modified Mycobacterium bovis Bacillus Calmette Guerin (BCG) strain with potentially improved immunogenicity and attenuation. Here, we report on efficacy, safety and tolerability of intravesical VPM1002BC for the treatment of non-muscle invasive bladder cancer (NMIBC). Methods We designed a phase I/II single arm trial (NCT02371447). Patients were eligible with BCG failure (2008 EAU definition) and intermediate to high risk for NMIBC progression after conventional BCG therapy. The primary endpoint of the phase II part was defined as recurrence free survival (RFS) in the bladder 60 weeks after the first VPM1002BC instillation. From September 2015 to April 2018, a total of 40 patients (6 from phase I and 34 from phase II) were included into the trial. Patients were scheduled for a standard treatment of 6 weekly instillations with VPM1002BC followed by a maintenance regimen of 1 year. Results The study population consisted of 4 female and 36 male patients (median age 72 years). Previous maintenance BCG therapy was conducted in 14/40 patients. All recurrent tumours were high grade (2004 WHO definition) and 27 (67.5%) patients presented with carcinoma in situ (CIS). RFS in the bladder at 60 weeks after the first instillation was 49.3 % [95% CI 32.1%, 64.4%]. At the same time, progression in stage, grade or new occurrence of CIS had occurred in 12 (30%) patients, 3 of which had progression to muscle-invasive disease. Two patients died from bladder cancer (> 60 weeks after start of therapy). Over the whole course of therapy, treatment related grade 1, 2 and 3 AEs were observed in 15%, 52.5%, and 5% of the patients, respectively. No adverse events (AEs) grade ≥4 occurred. Two (5%) out of the 40 patients did not tolerate ≥ 5 instillations during induction. Fifteen patients (37.5%) received all scheduled instillations. Conclusion One year after start of treatment, therapy with VPM100BC resulted in freedom from NMIBC recurrence in the bladder in almost half of the patients with recurrence after previous BCG exposure. The treatment is safe and well tolerated.

Many of the existing stochastic models of gene expression contain the first-order decay reaction term that may describe active protein degradation or dilution. If the model variable is interpreted as the molecule number, and not concentration, the decay term may also approximate the loss of protein molecules due to cell division as a continuous degradation process. The seminal model of that kind leads to gamma distributions of protein levels, whose parameters are defined by the mean frequency of protein bursts and mean burst size. However, such models (whether interpreted in terms of molecule numbers or concentrations) do not correctly account for the noise due to protein partitioning between daughter cells. We present an exactly solvable stochastic model of gene expression in cells dividing at random times, where we assume description in terms of molecule numbers with a constant mean protein burst size. The model is based on a population balance equation supplemented with protein production in random bursts. If protein molecules are partitioned equally between daughter cells, we obtain at steady state the analytical expressions for probability distributions similar in shape to gamma distribution, yet with quite different values of mean burst size and mean burst frequency than would result from fitting of the classical continuous-decay model to these distributions. For random partitioning of protein molecules between daughter cells, we obtain the moment equations for the protein number distribution and thus the analytical formulas for the squared coefficient of variation., Comment: 14 pages, 4 figures, accepted in Physical Review E

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A 21% prostate cancer (PCa) mortality reduction was observed in the European Randomized Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. A direct correlation between stage shift and changes in PCa-mortality would support earlier detection through screening as the main reason for this reduction. In this study we empirically estimate how changes in the risk of being diagnosed with (advanced) PCa are related to the changes in PCa death in the ERSPC using a meta-regression approach. In total 81% and 89% of the changes in PCa mortality could be explained by changes in PCa incidence. Although this analysis cannot show direct causal relations, results support the hypothesis that PSA screening reduced PCa mortality by detecting cancer at an earlier stage while still curable. These findings do however not open the way to unrestricted PSA based screening for PCa. A balance between harm and benefit needs to be found.

Purpose: The balance of benefits and harms in prostate cancer screening has not been sufficiently characterized. We related indicators of mortality reduction and overdetection by center within the European Randomized Study of Prostate Cancer Screening (ERSPC). Experimental Design: We analyzed the absolute mortality reduction expressed as number needed to invite (NNI = 1/absolute risk reduction; indicating how many men had to be randomized to screening arm to avert a prostate cancer death) for screening and the absolute excess of prostate cancer detection as number needed for overdetection (NNO = 1/absolute excess incidence; indicating the number of men invited per additional prostate cancer case), and compared their relationship across the seven ERSPC centers. Results: Both absolute mortality reduction (NNI) and absolute overdetection (NNO) varied widely between the centers: NNI, 200–7,000 and NNO, 16–69. Extent of overdiagnosis and mortality reduction was closely associated [correlation coefficient, r = 0.76; weighted linear regression coefficient, β = 33; 95% confidence interval (CI), 5–62; R2 = 0.72]. For an averted prostate cancer death at 13 years of follow-up, 12 to 36 excess cases had to be detected in various centers. Conclusions: The differences between the ERSPC centers likely reflect variations in prostate cancer incidence and mortality, as well as in screening protocol and performance. The strong interrelation between the benefits and harms suggests that efforts to maximize the mortality effect are bound to increase overdiagnosis and might be improved by focusing on high-risk populations. The optimal balance between screening intensity and risk of overdiagnosis remains unclear. Clin Cancer Res; 22(1); 243–9. ©2015 AACR.

Objective To assess the value of a positive family history (FH) as a risk factor for prostate cancer incidence and grade among men undergoing organised prostate-specific antigen (PSA) screening in a population-based study. Subjects and Methods The study cohort comprised all attendees of the Swiss arm of the European Randomised Study of Screening for Prostate Cancer (ERSPC) with systematic PSA level tests every 4 years. Men reporting first-degree relative(s) diagnosed with prostate cancer were considered to have a positive FH. Biopsy was exclusively PSA triggered at a PSA level threshold of 3 ng/mL. The primary endpoint was prostate cancer diagnosis. Kaplan–Meier and Cox regression analyses were used. Results Of 4 932 attendees with a median (interquartile range, IQR) age of 60.9 (57.6–65.1) years, 334 (6.8%) reported a positive FH. The median (IQR) follow-up duration was 11.6 (10.3–13.3) years. Cumulative prostate cancer incidence was 60/334 (18%, positive FH) and 550/4 598 (12%, negative FH) [odds ratio 1.6, 95% confidence interval (CI) 1.2–2.2, P = 0.001). In both groups, most prostate cancer diagnosed was low grade. There were no significant differences in PSA level at diagnosis, biopsy Gleason score or Gleason score on pathological specimen among men who underwent radical prostatectomy between both groups. On multivariable analysis, age (hazard ratio [HR] 1.04, 95% CI 1.02–1.06), baseline PSA level (HR 1.13, 95% CI 1.12–1.14), and FH (HR 1.6, 95% CI 1.24–2.14) were independent predictors for overall prostate cancer incidence (all P < 0.001). Only baseline PSA level (HR 1.14, 95% CI 1.12–1.16, P < 0.001) was an independent predictor of Gleason score ≥7 prostate cancer on prostate biopsy. The proportion of interval prostate cancer diagnosed in-between the screening rounds was not significantly different. Conclusion Irrespective of the FH status, the current PSA-based screening setting detects the majority of aggressive prostate cancers and missed only a minority of interval cancers with a 4-year screening algorithm. Our results suggest that men with a positive FH are at increased risk of low-grade but not aggressive prostate cancer.