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Purpose: The congenital Long QT Syndrome (LQTS) and Brugada Syndrome (BrS) are Mendelian autosomal dominant diseases that frequently precipitate fatal cardiac arrhythmias. Incomplete penetrance is a barrier to clinical management of heterozygotes harboring variants in the major implicated disease genes KCNQ1, KCNH2, and SCN5A. We apply and evaluate a Bayesian penetrance estimation strategy that accounts for this phenomenon. Methods: We generated Bayesian penetrance models for KCNQ1-LQT1 and SCN5A-LQT3 using variant-specific features and clinical data from the literature, international arrhythmia genetic centers, and population controls. We analyzed the distribution of posterior penetrance estimates across 4 genotype-phenotype relationships and compared continuous estimates with ClinVar annotations. Posterior estimates were mapped onto protein structure. Results: Bayesian penetrance estimates of KCNQ1-LQT1 and SCN5A-LQT3 are empirically equivalent to 10 and 5 clinically phenotype heterozygotes, respectively. Posterior penetrance estimates were bimodal for KCNQ1-LQT1 and KCNH2-LQT2, with a higher fraction of missense variants with high penetrance among KCNQ1 variants. There was a wide distribution of variant penetrance estimates among identical ClinVar categories. Structural mapping revealed heterogeneity among “hot spot” regions and featured high penetrance estimates for KCNQ1 variants in contact with calmodulin and the S6 domain. Conclusions: Bayesian penetrance estimates provide a continuous framework for variant interpretation.

Background: The proliferation of genetic profiling has revealed many associations between genetic variations and disease. However, large-scale phenotyping efforts in largely healthy populations, coupled with DNA sequencing, suggest variants currently annotated as pathogenic are more common in healthy populations than previously thought. In addition, novel and rare variants are frequently observed in genes associated with disease both in healthy individuals and those under suspicion of disease. This raises the question of whether these variants can be useful predictors of disease. To answer this question, we assessed the degree to which the presence of a variant in the cardiac potassium channel gene KCNH2 was diagnostically predictive for the autosomal dominant long QT syndrome. Methods: We estimated the probability of a long QT diagnosis given the presence of each KCNH2 variant using Bayesian methods that incorporated variant features such as changes in variant function, protein structure, and in silico predictions. We call this estimate the posttest probability of disease. Our method was applied to over 4000 individuals heterozygous for 871 missense or in-frame insertion/deletion variants in KCNH2 and validated against a separate international cohort of 933 individuals heterozygous for 266 missense or in-frame insertion/deletion variants. Results: Our method was well-calibrated for the observed fraction of heterozygotes diagnosed with long QT syndrome. Heuristically, we found that the innate diagnostic information one learns about a variant from 3-dimensional variant location, in vitro functional data, and in silico predictors is equivalent to the diagnostic information one learns about that same variant by clinically phenotyping 10 heterozygotes. Most importantly, these data can be obtained in the absence of any clinical observations. Conclusions: We show how variant-specific features can inform a prior probability of disease for rare variants even in the absence

Background: The proliferation of genetic profiling has revealed many associations between genetic variations and disease. However, large-scale phenotyping efforts in largely healthy populations, coupled with DNA sequencing, suggest variants currently annotated as pathogenic are more common in healthy populations than previously thought. In addition, novel and rare variants are frequently observed in genes associated with disease both in healthy individuals and those under suspicion of disease. This raises the question of whether these variants can be useful predictors of disease. To answer this question, we assessed the degree to which the presence of a variant in the cardiac potassium channel gene KCNH2 was diagnostically predictive for the autosomal dominant long QT syndrome. Methods: We estimated the probability of a long QT diagnosis given the presence of each KCNH2 variant using Bayesian methods that incorporated variant features such as changes in variant function, protein structure, and in silico predictions. We call this estimate the posttest probability of disease. Our method was applied to over 4000 individuals heterozygous for 871 missense or in-frame insertion/deletion variants in KCNH2 and validated against a separate international cohort of 933 individuals heterozygous for 266 missense or in-frame insertion/deletion variants. Results: Our method was well-calibrated for the observed fraction of heterozygotes diagnosed with long QT syndrome. Heuristically, we found that the innate diagnostic information one learns about a variant from 3-dimensional variant location, in vitro functional data, and in silico predictors is equivalent to the diagnostic information one learns about that same variant by clinically phenotyping 10 heterozygotes. Most importantly, these data can be obtained in the absence of any clinical observations. Conclusions: We show how variant-specific features can inform a prior probability of disease for rare variants even in the absence

Collaborative writing (CW) activities have captured the attention of second language instructors and researchers over the past two decades, reporting their potential benefits for the second language (L2) learners. With the growing interest in web 2.0 tools and their affordance for collaboration, online collaborative writing tools (e.g., Google Docs) have been increasingly implemented in second language classrooms. To date, most of the studies that examined the nature of students’ interaction and collaboration in online collaborative writing mode have been conducted in English as L2 classes or European languages over a short period of time. This longitudinal study aimed to investigate the nature of students’ online interaction when completing CW tasks in Arabic as a second language (ASL) classes in Saudi Arabia. This study was conducted in two Arabic language institutes in Saudi Arabian universities. Thirty-one ASL students participated in this study which was implemented online outside the regular classrooms over a 15-week semester. The participants formed eight pairs and five triads and jointly completed four collaborative writing tasks (two argumentative and two descriptive). The participants were required to complete each task over two weeks using Google Docs for writing their texts, supplemented with WhatsApp chat for their discussion. The study used a convergent mixed methods design that involved the collection of qualitative and quantitative data from online and offline sources (comments, history revision, texts in Google Docs, WhatsApp chat, interviews, questionnaire, observation notes, DocuViz). Drawing on Storch’s (2002) model of dyadic interaction, I investigated patterns of interaction that the ASL students formed during their online collaborative writing activities. Data analysis identified five patterns of interaction: cooperative, collaborative, active/passive (active/passive/passive for triads), facilitator/contributor (facilitator/contributor/contrib

OBJECTIVE: Although remdesivir (GS-5734) has recently demonstrated clinical benefits against the pandemic outbreak of coronavirus disease 2019 (COVID-19), neuropsychological adverse reactions (ADRs) remain to be examined in real-world settings. Therefore, we aimed to identify and characterize the neuropsychological ADRs associated with remdesivir use. MATERIALS AND METHODS: We obtained data for this international pharmacovigilance cohort study from individual case safety reports (ICSRs) in a World Health Organization database (VigiBase) from the first report on remdesivir on February 17, 2020, until August 30, 2020 (n=1,403,532). ADRs reported to be relevant to remdesivir were compared with the full database by using a Bayesian neural network method to calculate the information component (IC). RESULTS: A total of 2,107 reported cases of neuropsychological ADRs suspected to be associated with remdesivir were identified from among all ICSRs in the database during the observation period. Although 108 neuropsychological ADRs (64 neurologic events and 44 psychologic events) were reported in association with the medication, no statistically significant pharmacovigilance signal could be detected; the ICO25 value was negative for all of the neuropsychological dysfunctions (anxiety [n=13, 0.62%], seizures [n=12, 0.57%], lethargy [n=6, 0.28%], agitation [n=5, 0.25%], cerebral infarction [n=3, 0.14%]. ischemic stroke [n=3, 0.14%], and hemiparesis [n=3, 0.14%]). CONCLUSIONS: Our study demonstrates that remdesivir, a novel drug applied to the treatment of COVID-19, does not have a significant association with adverse neurologic or psychiatric reactions in the real-world setting., Funding Agencies: National Research Foundation of Korea (NRF) - Korean government [NRF2019R1G1A109977912]

The current version of the urology training program will concentrate on the mediation of competences and skills in various fields of action for outpatient urology instead of persisting on the minimum and reference numbers of surgical and diagnostic procedures. However, the following fields of action must be fulfilled: microbiology, andrology and systemic cancer therapy. There is justifiable concern that various institutions will lose their permission for a complete 5-year residency program based on the above-mentioned demands since not all institutions have all subspecialties in urology. Those institutions need to define new ways of residency training such as interdisciplinary programs within their own institution between disciplines like pediatric surgery, gynecology and medical oncology. Other options are combined training programs between regional urology departments with different main focuses or training programs between institutions and urologists in private practice. There is an unmet need to improve residency training as well as board examinations by new structures and a reliable curriculum. Based on the changed main focuses of the new version of urology training, we need to discuss the future of residency programs. It might be helpful to discuss two different types of urology training with a common trunk for the first three years followed by a more outpatient-based residency training for the general urologist and a more specialized training for the inpatient urologist to be educated in complex treatment modalities. An open mind to broadening our own horizon, respectful discussion with other departments and the development of common, reliable and interdisciplinary contents represent indispensable prerequisites to realize such an innovative future training program.

Due to demographic changes, the proportion of people requiring urological treatment will continue to rise. In order to better address this development, we need a well-trained and motivated urological medical community. Not only is continued education in urology an integral part of this, but it must also be embedded into future-oriented, flexible work-hour models, taking into account the German Work Time Act. Thus, in order to obtain a better assessment of the current situation of urological physicians undergoing specialist training, work -hour models currently used in urological clinics must be evaluated. This should allow conclusions to be drawn to find future-oriented solutions in order to do justice to the Future Offensive-Urology in 2025. Transparency, openness, and cooperation should be top priority between the DGU (German Association for Urology) working groups active in this field and the working groups of the BvDU (German Professional Association for Urologists).

Background The working and continued training conditions of assistant physicians in urology in Germany have already been analyzed. But what about senior urologists in Germany? Under which conditions do they have to work? As far as we know no published data currently exist which illuminate the conditions of this special urological professional group, therefore, the results of this survey are presented. Objective To survey and evaluate the current working conditions of certified and senior urologists in Germany as comprehensively as possible. Material and methods The working group of employed physicians of the Professional Association of German Urologists (BvDU) carried out a survey within the framework of the urological senior physician forum 2016 and on-line via the e-mail distributor of the German Society for Urology (DGU). The questions involved the workload, working conditions and satisfaction, overtime performed, working hours and opt out regulations. Results A total of 176 senior physicians participated in the survey of which 88% were male and 12% female. In Germany there are 1125 senior physicians. The average age of the responders was 44.9 years. In more than 80% of the participants the average weekly working hours were over 50h and 70% signed an opt out regulation. An association between an increasing job dissatisfaction above a working week over 55h and an average attendance in on-call service over 4h could be established. The number of on-call services had no influence on job satisfaction. A total of 43% (70 out of 162) of the participants stated that overtime hours were regularly forfeited and 12% (20 out of 162) that all overtime hours were forfeited. Approximately 30% of senior physicians in German urology were dissatisfied with the current working conditions in the present form. Conclusion Based on the acquired data, adaptation and improvements in the working conditions of senior urologists are necessary in order to maintain the attractiveness of the o

Due to demographic changes, the proportion of people requiring urological treatment will continue to rise. In order to better address this development, we need a well-trained and motivated urological medical community. Not only is continued education in urology an integral part of this, but it must also be embedded into future-oriented, flexible work-hour models, taking into account the German Work Time Act. Thus, in order to obtain a better assessment of the current situation of urological physicians undergoing specialist training, work -hour models currently used in urological clinics must be evaluated. This should allow conclusions to be drawn to find future-oriented solutions in order to do justice to the Future Offensive-Urology in 2025. Transparency, openness, and cooperation should be top priority between the DGU (German Association for Urology) working groups active in this field and the working groups of the BvDU (German Professional Association for Urologists).

The current version of the urology training program will concentrate on the mediation of competences and skills in various fields of action for outpatient urology instead of persisting on the minimum and reference numbers of surgical and diagnostic procedures. However, the following fields of action must be fulfilled: microbiology, andrology and systemic cancer therapy. There is justifiable concern that various institutions will lose their permission for a complete 5-year residency program based on the above-mentioned demands since not all institutions have all subspecialties in urology. Those institutions need to define new ways of residency training such as interdisciplinary programs within their own institution between disciplines like pediatric surgery, gynecology and medical oncology. Other options are combined training programs between regional urology departments with different main focuses or training programs between institutions and urologists in private practice. There is an unmet need to improve residency training as well as board examinations by new structures and a reliable curriculum. Based on the changed main focuses of the new version of urology training, we need to discuss the future of residency programs. It might be helpful to discuss two different types of urology training with a common trunk for the first three years followed by a more outpatient-based residency training for the general urologist and a more specialized training for the inpatient urologist to be educated in complex treatment modalities. An open mind to broadening our own horizon, respectful discussion with other departments and the development of common, reliable and interdisciplinary contents represent indispensable prerequisites to realize such an innovative future training program.

Background The working and continued training conditions of assistant physicians in urology in Germany have already been analyzed. But what about senior urologists in Germany? Under which conditions do they have to work? As far as we know no published data currently exist which illuminate the conditions of this special urological professional group, therefore, the results of this survey are presented. Objective To survey and evaluate the current working conditions of certified and senior urologists in Germany as comprehensively as possible. Material and methods The working group of employed physicians of the Professional Association of German Urologists (BvDU) carried out a survey within the framework of the urological senior physician forum 2016 and on-line via the e-mail distributor of the German Society for Urology (DGU). The questions involved the workload, working conditions and satisfaction, overtime performed, working hours and opt out regulations. Results A total of 176 senior physicians participated in the survey of which 88% were male and 12% female. In Germany there are 1125 senior physicians. The average age of the responders was 44.9 years. In more than 80% of the participants the average weekly working hours were over 50h and 70% signed an opt out regulation. An association between an increasing job dissatisfaction above a working week over 55h and an average attendance in on-call service over 4h could be established. The number of on-call services had no influence on job satisfaction. A total of 43% (70 out of 162) of the participants stated that overtime hours were regularly forfeited and 12% (20 out of 162) that all overtime hours were forfeited. Approximately 30% of senior physicians in German urology were dissatisfied with the current working conditions in the present form. Conclusion Based on the acquired data, adaptation and improvements in the working conditions of senior urologists are necessary in order to maintain the attractiveness of the o

De-Hua Chang,1 Karin Slebocki,2 Ekaterina Khristenko,1 Jan Herden,3 Johannes Salem,3 Nils Große Hokamp,2 Kamal Mammadov,2 Martin Hellmich,4 Christoph Kabbasch21Department of Diagnostic and Interventional Radiology, University Medical Center Heidelberg, Heidelberg, Germany; 2Department of Diagnostic and Interventional Radiology, University Hospital of Cologne, Cologne, Germany; 3Department of Urology, University Hospital of Cologne, Cologne, Germany; 4Institute of Medical Statistics and Computational Biology (IMSB), Medical Faculty, University of Cologne, Cologne, GermanyPurpose: Retrospective evaluation and comparison of image quality generated by low-dose computed tomography (LDCT) from obese patients with urolithiasis using alternative reconstruction algorithms.Materials and methods: Twenty-five obese patients (body mass index [BMI]>25 kg/m2,) underwent LDCT scans for suspected urolithiasis. The scans were recompiled using filtered-back projection (FBP), statistical iterative reconstruction (iDose) and iterative model-based reconstruction (IMR). Dose-length product (DLP) and patient details were obtained from the CT dose report and clinical charts, respectively. Objective image noise was assessed by measuring the SD of Hounsfield units (HUs) in defined locations. Additionally, subjective image evaluation was independently performed by two radiologists using a 3-point Likert scale. The inter-reviewer agreement of image quality was calculated.Results: Ureteral concretions were observed in all CT scans, two of which revealed bilateral stones. The assessed patients’ mean BMI was 29.29±3.74 kg/m,2 and the DLP of the CT scans was 100.04±10.00 mGy*cm. All scans were rated diagnostic with the iDose and iterative model-based reconstructions, whereas 41% of the scans performed with FBP reconstruction were nondiagnostic. With respect to image quality, IMR was superior to iDose and FBP, both in the objective (P<0.001) an

The Internet is an important source of health information with relevant impact on the physician-patient relationship. The German urological associations host one of the most comprehensive platforms for patient information on urological diseases. The aim of the study was to characterise its users and their specific needs. We invited users of the website via pop-up to complete a 26-item online survey to evaluate health-related behaviour, distress and decision-making preferences. We received n=551 complete responses. The most frequently requested topics were from the field of andrology (45.4%, n=250). Of these, the most popular topics were circumcision (28.9%, n=159) and erectile dysfunction (18.1%; n=100). Overall, 216 users (39.2%) searched for information prior to their first doctor's appointment, and 89.3% (n=492) preferred autonomous or shared decision-making. Users seeking information on circumcision were less frequently under urological treatment (p<.001), and more self-determined regarding healthcare decisions (p=.01). Circumcision was the only information on the website, which received relevant critical comments. Andrology was the most frequently requested urological topic. The vast majority of patients wanted to take self-determined healthcare decisions and searched for information prior to a doctor's appointment. This might have an impact on the physician-patient relationship and causes a high demand for good-quality health information websites.

To measure the usage rate of social media (SoMe) resources in the prostate cancer community, we performed a comprehensive quantitative and qualitative assessment of SoMe activity on the topic of PCa on the four most frequented platforms. We scanned the SoMe platforms Facebook, Twitter, YouTube, and Instagram for prostate cancer as a cross-sectional analysis or during a defined time period. Sources were included if their communication centered on PCa by title and content. We assessed activity measurements for each SoMe source and classified the sources into six functional categories. We identified 99 PCa-related Facebook groups that amassed 31,262 members and 90 Facebook pages with 283,996 likes. On YouTube, we found 536 PCa videos accounting for 43,966,634 views, 52,655 likes, 8597 dislikes, and 12,393 comments. During a 1-year time period, 32,537 users generated 110,971 tweets on #ProstateCancer on Twitter, providing over 544 million impressions. During a 1-month time period, 638 contributors posted 1081 posts on Instagram, generating over 22,000 likes and 4,748,159 impressions. Among six functional categories, general information/support dominated the SoMe landscape on all SoMe platforms. SoMe activity on the topic of PCa on the four most frequented platforms is high. Facebook groups, YouTube videos, and Twitter tweets are mainly used for giving general information on PCa and education. High SoMe utilization in the PCa community underlines its future role for communication of PCa.

The Internet is an important source of health information with relevant impact on the physician-patient relationship. The German urological associations host one of the most comprehensive platforms for patient information on urological diseases. The aim of the study was to characterise its users and their specific needs. We invited users of the website via pop-up to complete a 26-item online survey to evaluate health-related behaviour, distress and decision-making preferences. We received n=551 complete responses. The most frequently requested topics were from the field of andrology (45.4%, n=250). Of these, the most popular topics were circumcision (28.9%, n=159) and erectile dysfunction (18.1%; n=100). Overall, 216 users (39.2%) searched for information prior to their first doctor's appointment, and 89.3% (n=492) preferred autonomous or shared decision-making. Users seeking information on circumcision were less frequently under urological treatment (p<.001), and more self-determined regarding healthcare decisions (p=.01). Circumcision was the only information on the website, which received relevant critical comments. Andrology was the most frequently requested urological topic. The vast majority of patients wanted to take self-determined healthcare decisions and searched for information prior to a doctor's appointment. This might have an impact on the physician-patient relationship and causes a high demand for good-quality health information websites.

To measure the usage rate of social media (SoMe) resources in the prostate cancer community, we performed a comprehensive quantitative and qualitative assessment of SoMe activity on the topic of PCa on the four most frequented platforms. We scanned the SoMe platforms Facebook, Twitter, YouTube, and Instagram for prostate cancer as a cross-sectional analysis or during a defined time period. Sources were included if their communication centered on PCa by title and content. We assessed activity measurements for each SoMe source and classified the sources into six functional categories. We identified 99 PCa-related Facebook groups that amassed 31,262 members and 90 Facebook pages with 283,996 likes. On YouTube, we found 536 PCa videos accounting for 43,966,634 views, 52,655 likes, 8597 dislikes, and 12,393 comments. During a 1-year time period, 32,537 users generated 110,971 tweets on #ProstateCancer on Twitter, providing over 544 million impressions. During a 1-month time period, 638 contributors posted 1081 posts on Instagram, generating over 22,000 likes and 4,748,159 impressions. Among six functional categories, general information/support dominated the SoMe landscape on all SoMe platforms. SoMe activity on the topic of PCa on the four most frequented platforms is high. Facebook groups, YouTube videos, and Twitter tweets are mainly used for giving general information on PCa and education. High SoMe utilization in the PCa community underlines its future role for communication of PCa.

This Consensus Statement summarizes recommendations for clinical diagnosis, investigation and management of patients with Silver-Russell syndrome (SRS), an imprinting disorder that causes prenatal and postnatal growth retardation. Considerable overlap exists between the care of individuals born small for gestational age and those with SRS. However, many specific management issues exist and evidence from controlled trials remains limited. SRS is primarily a clinical diagnosis; however, molecular testing enables confirmation of the clinical diagnosis and defines the subtype. A 'normal' result from a molecular test does not exclude the diagnosis of SRS. The management of children with SRS requires an experienced, multidisciplinary approach. Specific issues include growth failure, severe feeding difficulties, gastrointestinal problems, hypoglycaemia, body asymmetry, scoliosis, motor and speech delay and psychosocial challenges. An early emphasis on adequate nutritional status is important, with awareness that rapid postnatal weight gain might lead to subsequent increased risk of metabolic disorders. The benefits of treating patients with SRS with growth hormone include improved body composition, motor development and appetite, reduced risk of hypoglycaemia and increased height. Clinicians should be aware of possible premature adrenarche, fairly early and rapid central puberty and insulin resistance. Treatment with gonadotropin-releasing hormone analogues can delay progression of central puberty and preserve adult height potential. Long-term follow up is essential to determine the natural history and optimal management in adulthood.