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The Normal Quantile Transform (NQT) has been used in many hydrological and meteorological applications in order to make the Cumulated Density Function (CDF) of the observed, simulated and forecast river discharge, water level or precipitation data Gaussian. It is also the heart of the meta-Gaussian model for assessing the total predictive uncertainty of the Hydrological Uncertainty Processor (HUP) developed by Krzysztofowicz. In the field of geo-statistics this transformation is better known as Normal-Score Transform. In this paper some possible problems caused by small sample sizes for the applicability in flood forecasting systems will be discussed and illustrated by examples. For the practical implementation commands and examples from the freely available and widely used statistical computing language R (R Development Core Team, 2011) will be given (represented in Courier font) and possible solutions are suggested by combining extreme value analysis and non-parametric regression methods. [ABSTRACT FROM AUTHOR]

Safety is an essential part of the evaluation of new medications and competing risks that occur in most clinical trials are a well identified challenge in the analysis of adverse events. Two statistical frameworks exist to consider competing risks: the cause-specific and the subdistribution framework. To date, the application of the cause-specific framework is the standard practice in safety analyses. Here we analyze how the safety analysis results of new medications would be affected if instead of the cause-specific the subdistribution framework was chosen. We conducted a simulation study with 600 participants, equally allocated to verum and control groups and a 30 months follow-up period. Simulated trials were analyzed for safety in a competing risk (death) setting using both the cause-specific and subdistribution frameworks. Results show that comparing safety profiles in a subdistribution setting is always more pessimistic than in a cause-specific setting. For the group with the longest survival and a safety advantage in a cause-specific setting, the advantage either disappeared or a disadvantage was found in the subdistribution analysis setting. These observations are not contradictory but show different perspectives. To evaluate the safety of a new medication over its comparator, one needs to understand the origin of both the risks and the benefits associated with each therapy. These requirements are best met with a cause-specific framework. The subdistribution framework seems better suited for clinical prediction, and therefore more relevant for providers or payers, for example., (© 2023. The Author(s).)

Purpose: To evaluate the validity of PI-RADS categories 1 and 2 version 2.1 (V2.1) as predictors of the absence of carcinoma and to reevaluate lesions that were analysed as suspicious prior to PI-RADS or according to PI-RADS versions 1 and 2 and classified as PI-RADS 1 or 2 in V2.1., Methods: Retrospective evaluation of 1170 multiparametric MRIs performed at one academic teaching hospital (2012-2019). Study cohort comprised 188 men that achieved PI-RADS scores 1 or 2 (V2.1) and underwent systematic and targeted biopsy, split into one group with suspect findings in the original reports that were created prior to PI-RADS or with version 1 and 2, and another group with unremarkable reports. Differences in presence of prostate cancer and PSA density were assessed by Chi-square and Fisher's exact test, and the negative predictive value (NPV) for both groups was conducted., Results: The NPV for clinically significant carcinoma (csCa) was 89.1% for 55 men with suspect findings in the original report and 93.2% for 133 men with negative MRI. There was no difference between the groups regarding the detection of csCa (p = 0.103). PSA density was significantly higher in the group with suspect original reports (p = 0.015)., Conclusion: A PI-RADS score 1 or 2 appears less likely to miss existing prostate cancer, although a small amount of csCa can be overlooked. In case of clinical suspicion or elevated PSA density and PI-RADS score 1 or 2, an individual decision has to be taken if biopsy is necessary or if monitoring is sufficient., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

As a microcosm for future challenges, the COVID-19 pandemic exhibits increasingly transboundary dynamics, causing interconnected problems across multiple societal systems. To examine the role of innovations as a social mechanism to reconcile these arising challenges, we view the unfolding of the pandemic through the lens of a content analysis of 707 innovation projects that address the fundamental human needs of consumers and businesses. This study proposes a novel procedure to characterize large-scale innovative activities via text mining and employs a theoretical framework for identifying the pressing societal needs amidst crises. Our typology of rapid-response COVID-19 innovations exhibits a diverse set of domains ranging from technological innovations to what may be described as frugal and social innovations. We provide evidence for the growing prevalence of social needs beyond the basic notion of safety during the early months of the crisis. Our contributions show that a structural model of innovation activities and their latent drivers may help policy makers and innovators to move toward achieving a systemic reaction to such crises., (© 2021 The Authors.)

Objectives: Following an exploratory approach, we examined cardiovascular disease risk factors at baseline and the 5-year incidence proportion of self-reported doctor-diagnosed cardiovascular diseases (CVD) in teachers and other occupational groups of the Gutenberg Health Study., Methods: Study participants lived in the region of Mainz, Germany. Data from 6510 working participants without prevalent CVD at baseline (2007-2012) were analyzed. Participants were teachers (n = 215), other professionals from the health, social or educational (HSE) fields (n = 1061) or worked outside the HSE fields (n = 5234). For occupational comparisons, we estimated prevalence ratios (PR) for each CVD risk factor at baseline with robust Poisson regression analyses. We calculated crude CVD incidence rates based on the observed 5-year CVD cumulative incidence at follow-up and estimated age-weighted incidence proportions. All analyses were stratified by sex., Results: Male non-HSE workers showed a higher prevalence of smoking and physical inactivity than male teachers (PR 2.26; 95%-CI: 1.06-4.82/PR 1.89; 95%-CI: 1.24-2.87). In contrast, non-HSE workers and other HSE professionals were less likely to have reported an unhealthy alcohol intake than teachers. Differences were attenuated after SES-adjustment. We did not detect occupational group-specific differences in CVD incidence. However, there were only two cases of CVD among the teachers., Conclusion: Particularly male teachers showed a healthier lifestyle regarding physical inactivity and smoking. Nevertheless, occupational-medical care practitioners and researchers need to be aware of the relatively heightened prevalence of unhealthy alcohol intake in female and male teachers, and in absolute terms, the high hypertension prevalence in male teachers.

Objective: The aim of this study was to determine the tumour detection rate of magnetic resonance-guided biopsy (MRGB) in the supine position for significant prostate cancer in an inhomogeneous patient cohort., Materials and Methods: Thirty-two consecutive patients with a total prostate-specific antigen > 4 ng/ml and/or a tumour-suspicious palpable lesion upon digital rectal examination and a cancer-suspicious region in multiparametric magnetic resonance imaging (MRI) underwent MRGB in a standard 1.5 T magnet. Diagnostic MRI was performed in 20 patients at the authors' institute and 12 men at another location. Eight patients were investigated at 3 T and 24 at 1.5 T. Twenty men had prior negative biopsies and 12 were biopsy naïve. All biopsies were performed in the supine position using a table-mounted device and an 18 G biopsy gun., Results: The overall tumour detection rate was 53% (17/32). Two cores (median; range 1-4) were extracted. Clinically significant cancers were found in 94% (16/17). None of the patients showed any postbiopsy complications. The prostate volumes of patients with cancer were significantly lower (39.3 ml) than those of men without cancer (49.7 ml). No significant differences were found between the numbers of tumour-positive and tumour-negative collected cores. In a median follow-up of 14 months, no cancer was detected in the negative biopsy group., Conclusion: MRGB in the supine position can be a valuable tool to detect significant prostate cancer, even in a patient cohort with different prebiopsy pathways. The biopsy method could be a reasonable alternative to MRGB in the prone position.

Objective: The aim of this study was to evaluate the accuracy of multiparametric endorectal magnetic resonance imaging (mp-MRI) in detecting and characterising the largest tumour lesion, which is defined as the index tumour of prostate cancer., Material and Methods: A total of 55 patients with proven histological prostate cancer underwent post-biopsy MRI at 1.5 T and subsequent radical prostatectomy. The maximum tumour diameter (MTD) of the index lesion was determined independently by MRI and histopathology in a prospective manner. The detection rate of the index lesion, the MTD and volume by pathology, and the pathological tumour (pT) stage were correlated with the MTD by MRI using Pearson's correlation., Results: Pathohistology revealed 158 cancer foci. MRI detected 55 foci. The sensitivity, specificity, accuracy, and negative and positive predictive values of mp-MRI for index lesion detection were 89%, 100%, 90%, 44% and 100%, respectively. Three positive correlations were found: one between the MTD of the index lesion by MRI and the MTD by pathology (Pearson coefficient = 0.890, p < 0.01), a second between the MTD by MRI and the index tumour volume at pathology (Pearson coefficient = 0.786, p < 0.01), and a third between the MTD and the pT stage (Pearson coefficient = 0.678, p < 0.01)., Conclusion: mp-MRI can accurately detect the index lesion and estimate the TVP of localised prostate cancer.

Recent identification of genetic variants in iron storage disease has changed the classification system and diagnostic algorithms for hemochromatosis. Clinical diagnosis of the disease requires phenotypic evidence of iron overload because the commonly disease-associated HFE genotypes have an incomplete penetrance. Furthermore, approximately 20% of patients with a clinical diagnosis of hemochromatosis have no disease-associated genotype, which underlines the importance of clear phenotypic criteria of hemochromatosis. A diagnosis of hemochromatosis cannot be made even in patients with liver cirrhosis simply on the basis of genetic testing that indicates that iron overload is the cause of the disease and not its consequence. Proper diagnosis requires integration of clinical presentation, family history, and the results of biochemical and histopathologic tests. Here we propose a rational diagnostic algorithm for hepatic iron overload syndromes and illustrate potential pitfalls by presenting a family study in a pedigree with rare HFE variants (H63D and E168Q), in cis on the same chromosome. Although the clinical suspicion of hemochromatosis was confirmed by histology, chemical analysis of liver tissue revealed a normal hepatic iron concentration, which is compatible with the genetic finding of 1 normal and 1 doubly mutated allele. In conclusion, clinical suspicion of hemochromatosis and elevated serum iron parameters should prompt HFE genotyping for C282Y and H63D. Should they be uninformative, further genetic tests should be recommended only if iron overload in liver tissue has been confirmed chemically.