Anterior deflected urinary stream in female children: description of a unique clinical entity and surgical management

ObjectivesTo investigate the clinical presentation and outcomes for a series of female pediatric patients with severe anterior deflection of the urinary stream (ADUS) who were managed via urethromeatoplasty.MethodsThis single institution retrospective cohort study used the institutional billing database to identify female patients ≤18 years who received a urethromeatoplasty (CPT 53450) from 2007 to 2022. Patients were included if a substantial anterior deflection of their urinary stream was the primary indication for surgery. Patients were excluded if they were >18 years of age, had a history of prior genital trauma, or underwent surgery for an indication other than a deflected urinary stream.ResultsTwenty female patients underwent urethromeatoplasty between 2007 and 2022, with a median age of 3 years old. All patients presented with difficulty aiming the urinary stream during toilet training and demonstrated a web of tissue along the posterior aspect of the urethral orifice. 19/20 patients noted immediate response (i.e., normal, non-deflected urinary stream) after the urethromeatoplasty with no further urinary complaints. There were no post-operative complications within a 90-day period.ConclusionsADUS is a clinical entity characterized by a web of deflecting tissue at the female posterior urethral meatus that causes severe urinary deflection without other urologic symptoms. This is not well-described in the literature. Surgical correction via urethromeatoplasty is safe and effective

Design of a Bovine Low-Density SNP Array Optimized for Imputation

The Illumina BovineLD BeadChip was designed to support imputation to higher density genotypes in dairy and beef breeds by including single-nucleotide polymorphisms (SNPs) that had a high minor allele frequency as well as uniform spacing across the genome except at the ends of the chromosome where densities were increased. The chip also includes SNPs on the Y chromosome and mitochondrial DNA loci that are useful for determining subspecies classification and certain paternal and maternal breed lineages. The total number of SNPs was 6,909. Accuracy of imputation to Illumina BovineSNP50 genotypes using the BovineLD chip was over 97% for most dairy and beef populations. The BovineLD imputations were about 3 percentage points more accurate than those from the Illumina GoldenGate Bovine3K BeadChip across multiple populations. The improvement was greatest when neither parent was genotyped. The minor allele frequencies were similar across taurine beef and dairy breeds as was the proportion of SNPs that were polymorphic. The new BovineLD chip should facilitate low-cost genomic selection in taurine beef and dairy cattle

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

An Interdisciplinary Approach to Cybersecurity Curriculum

Today’s global information systems are inter-related and inter-dependent. Attacks on a single institution in one country can have major impacts throughout the world. Collaborative efforts by the United States Government and private sector led to the development of a voluntary risk-based Cybersecurity Framework, a set of broad standards and best practices that work across industries. The Framework avoids placing additional regulatory requirements on businesses. The Framework can serve a model for designing curriculum and developing cybersecurity courses. It provides a good vehicle for bringing interdisciplinary aspects into the curriculu

Protection against symptomatic SARS-CoV-2 BA.5 infection conferred by the Pfizer-BioNTech Original/BA.4-5 bivalent vaccine compared to the mRNA Original (ancestral) monovalent vaccines – a matched cohort study in France

AbstractThis cohort study aimed to evaluate the protection against symptomatic SARS-CoV-2 infection conferred by the Pfizer-BioNTech Original/BA.4-5 bivalent vaccine compared to mRNA Original (ancestral) monovalent vaccines. Individuals of ≥60 years old who received a booster dose between 03/10/2022 and 06/11/2022, when both the bivalent and monovalent vaccines were used in France, were included. Individuals who received a booster dose with (1) a monovalent Original mRNA vaccine (Pfizer- BioNTech or Moderna) or (2) the bivalent Pfizer-BioNTech Original/BA.4-5 vaccine were matched. The outcome of interest was a positive SARS-CoV-2 RT-PCR or antigenic test associated to self-reported symptoms, at least seven days after receiving the booster dose. Data were analysed with a Cox Proportional-Hazards model adjusted for the presence of previous infection, age, sex, and the presence of medium risk comorbidities. A total of 136,852 individuals were included and followed for a median period of 77 days. The bivalent vaccine conferred an additional protection of 8% [95% CI: 0% - 16%, p=0.045] against symptomatic SARS-CoV-2 infection compared to the monovalent vaccines.</jats:p