Observations on Animal and Human Health During the Outbreak of \u3ci\u3eMycobacterium bovis \u3c/i\u3ein Game Farm Wapiti in Alberta

This report describes and discusses the history, clinical, pathologic, epidemiologic, and human health aspects of an outbreak of Mycobacterium bovis infection in domestic wapiti in Alberta between 1990 and 1993, shortly after legislative changes allowing game farming. The extent and seriousness of the outbreak of M. bovis in wapiti in Alberta was not fully known at its onset. The clinical findings in the first recognized infected wapiti are presented and the postmortem records for the herd in which the animal resided are summarized. Epidemiologic findings from the subsequent field investigation are reviewed, the results of recognition and investigation of human exposure are updated, and recommendations for reduction of human exposure are presented

Melt-under-cutting and buoyancy-driven calving from tidewater glaciers: new insights from discrete element and continuum model simulations

This work was funded by the ConocoPhillips Northern Area Program (CRIOS: Calving Rates and Impact on Sea Level) and the Nordic Research Council (SVALI: Stability and Variation of Arctic Land Ice and eSTICC: eScience Tools for Investigating Climate Change in northern high latitudes).The simple calving laws currently used in ice sheet models do not adequately reflect the complexity and diversity of calving processes. To be effective, calving laws must be grounded in a sound understanding of how calving actually works. Here, we develop a new strategy for formulating calving laws, using a) the Helsinki Discrete Element Model (HiDEM) to explicitly model fracture and calving processes, and b) the continuum model Elmer/Ice to identify critical stress states associated with HiDEM calving events. A range of observed calving processes emerges spontaneously from HiDEM in response to variations in ice-front buoyancy and the size of subaqueous undercuts. Calving driven by buoyancy and melt undercutting is under-predicted by existing calving laws, but we show that the location and magnitude of HiDEM calving events can be predicted in Elmer/Ice from characteristic stress patterns. Our results open the way to developing calving laws that properly reflect the diversity of calving processes, and provide a framework for a unified theory of the calving process continuum.Publisher PDFPeer reviewe

Analysis of the uncertainty in microbubble characterization

There is increasing interest in the use of microbubble contrast agents for quantitative imaging applications such as perfusion and blood pressure measurement. The response of a microbubble to ultrasound excitation is, however, extremely sensitive to its size, the properties of its coating and the characteristics of the sound field and surrounding environment. Hence the results of microbubble characterization experiments can be significantly affected by experimental uncertainties, and this can limit their utility in predictive modelling. The aim of this study was to attempt to quantify these uncertainties and their influence upon measured microbubble characteristics. Estimates for the parameters characterizing the microbubble coating were obtained by fitting model data to numerical simulations of microbubble dynamics. The effect of uncertainty in different experimental parameters was gauged by modifying the relevant input values to the fitting process. The results indicate that even the minimum expected uncertainty in, for example, measurements of microbubble radius using conventional optical microscopy, leads to variations in the estimated coating parameters of ~20%. This should be taken into account in designing microbubble characterization experiments and in the use of data obtained from them

Clinically actionable mutation profiles in patients with cancer identified by whole-genome sequencing

Next-generation sequencing (NGS) efforts have established catalogs of mutations relevant to cancer development. However, the clinical utility of this information remains largely unexplored. Here, we present the results of the first eight patients recruited into a clinical whole-genome sequencing (WGS) program in the United Kingdom. We performed PCR-free WGS of fresh frozen tumors and germline DNA at 75× and 30×, respectively, using the HiSeq2500 HTv4. Subtracted tumor VCFs and paired germlines were subjected to comprehensive analysis of coding and noncoding regions, integration of germline with somatically acquired variants, and global mutation signatures and pathway analyses. Results were classified into tiers and presented to a multidisciplinary tumor board. WGS results helped to clarify an uncertain histopathological diagnosis in one case, led to informed or supported prognosis in two cases, leading to de-escalation of therapy in one, and indicated potential treatments in all eight. Overall 26 different tier 1 potentially clinically actionable findings were identified using WGS compared with six SNVs/indels using routine targeted NGS. These initial results demonstrate the potential of WGS to inform future diagnosis, prognosis, and treatment choice in cancer and justify the systematic evaluation of the clinical utility of WGS in larger cohorts of patients with cancer

UK Joint Advisory Group consensus statements for training and certification in endoscopic retrograde cholangiopancreatography

© 2022 The Authors. Published by Thieme Open. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-1629-7540Introduction: Despite the high-risk nature of endoscopic retrograde cholangiopancreatography (ERCP), a robust and standardised credentialing process to ensure competency before independent practice is lacking worldwide. On behalf of the Joint Advisory Group (JAG), we aimed to develop evidence-based recommendations to form the framework of ERCP training and certification in the UK. Methods: Under the oversight of the JAG, a modified Delphi process was conducted with stakeholder representation from the British Society of Gastroenterology, Association of Upper Gastrointestinal Surgeons, trainees and trainers. Recommendations on ERCP training and certification were formulated after formal literature review and appraised using the GRADE tool. These were subjected to electronic voting to achieve consensus. Accepted statements were peer-reviewed by JAG and relevant Specialist Advisory Committees before incorporation into the ERCP certification pathway. Results: In total, 27 recommendation statements were generated for the following domains: definition of competence (9 statements), acquisition of competence (8 statements), assessment of competence (6 statements) and post-certification support (4 statements). The consensus process led to the following criteria for ERCP certification: 1) performing ≥300 hands-on procedures; 2) attending a JAG-accredited ERCP skills course; 3) in modified Schutz 1-2 procedures: achieving native papilla cannulation rate ≥80%, complete bile duct clearance ≥70%, successful stenting of distal biliary strictures ≥75%, physically unassisted in ≥80% of cases; 4) 30-day post-ERCP pancreatitis rates ≤5%; 5) satisfactory performance in formative and summative direct observation of procedural skills (DOPS) assessments. Conclusion: JAG certification in ERCP has been developed following evidence-based consensus to quality assure training and to ultimately improve future standards of ERCP practice

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure