Optimisation of Surgical Timing in Rheumatic Mitral Valve Disease

Rheumatic heart disease is a consequence of Group A streptococcal infections, and disproportionately affects the world’s most disadvantaged people. Whilst the disease has been essentially eradicated from nonindigenous populations in Australia, Indigenous Australians continue to have some of the highest rates of rheumatic heart disease in the world. The mortality and morbidity associated with rheumatic heart disease primarily results from complications of valvular heart disease which include heart failure and stroke. Valvular surgery can reduce the risk of these, however it comes with its own short-term increase in risk and long-term sequelae. Guidelines for the management of valvular heart disease primarily focus on North American and European populations which are generally older and with mainly single valve disease. Given the unique pathophysiology and demographics of rheumatic valvular disease, this may prove problematic. Rheumatic heart disease is epitomised by progressive mixed and multivalvular disease in children and young adults. Early intervention provides improved long-term outcomes following valvular surgery, especially in young adults. This thesis focuses on surgical delays, screening, and echocardiographic predictors as methods to reduce long-term risk in patients with rheumatic heart disease and optimise timing of tertiary intervention. Chapter 1 reviews the current management of rheumatic heart disease and the pitfalls of existing international guidelines in patients with rheumatic heart disease including current evidence for timing and replacement of valves. Chapter 2 reports on current surgical management of rheumatic heart disease in Australia and compares that to current guidelines. Given most patients come from remote communities, it further looks at delayed referrals and further, delayed surgery for those referred. It illustrates that there are many patients with guideline indications for surgery who fail to be referred or have surgery performed. Chapter 3 examines the prevalence of rheumatic heart disease in Indigenous populations across different regions of South Australia. This provides guidance to the tailoring of screening programs as well as defining the prevalence of echocardiographic confirmed RHD in South Australia. This study shows the prevalence of RHD in remote areas are significantly higher than metropolitan or rural areas. Chapter 4 quantifies sonographer sensitivity and accuracy using the World Heart Federation rheumatic heart disease echocardiographic screening criteria, as well as examining sonographer views of the echocardiographic parameters to enable further refinement of existing criteria. It confirms that sonographers have an extremely high sensitivity and reasonable specificity for RHD screening. Chapter 5 demonstrates the potential role of the left atrium in the management of rheumatic mitral valve disease. It finds that left atrial ejection fraction is the strongest and most reliable predictor for developing a guideline indication for valve intervention in the subsequent two-years. Finally, the insights gained in current management, screening, and echocardiographic assessment are placed in the context of previous literature in Chapter 6, before possible directions for future studies on optimising surgical outcomes and longevity of patients with rheumatic heart disease are discussed in Chapter 7.Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 202

Experiences of forecasting the magnetic storms of March and June 2015 and analysis of the resulting ground effects in the UK

Since the 1990’s the British Geological Survey (BGS) have issued a daily (Monday to Friday) three-day geomagnetic activity forecast. Recipients of this service have included the Met Office, as part of the UK’s ‘National Hazards Partnership’ that provides government with data and analysis, and power companies concerned about geomagnetic induced currents (GIC). The St. Patrick’s Day storm of 17th March 2015 was the first magnetic storm since August 2005 with a daily Ap > 100. By this measure it could be considered to be the largest magnetic storm of solar cycle 24 (so far). The magnitude of the geomagnetic activity was surprising as the solar event signatures preceding it were not considered that remarkable. The magnetic storms of 21st – 24th June, caused by a series of Earth-directed coronal mass ejections, resulted in further significant geomagnetic activity. This time daily Ap reached a peak of 73 on the 23rd June 2015. In each case the magnetic storms reached a peak of G4 in the NOAA Space Weather scale for geomagnetic storms. Both these events are described from the viewpoint of BGS operational space weather forecasters. In the UK BGS operate three magnetic observatories continuously recording the Earth’s magnetic field. Additionally since 2013, BGS also monitor changes to the geo-electric field at all three observatories. These geomagnetic and geo-electric data are used to model and research the impact of GIC on the UK power grid. Observational and modeling results from both the March and June storms are presented and discussed

Observatory Data Products for Space Weather Applications

With the inclusion of space weather on the UK government’s national risk register, continuous monitoring of geomagnetic activity levels and real-time dissemination of the information is essential. BGS, as a long-term operator of magnetic observatories carries out this role and provides advice on geomagnetic hazard on a daily basis. This includes human-derived predictions of geomagnetic activity levels for up to three days ahead made on a daily basis, as well as more continuous computer-based predictions of 3-hourly and daily activity indices. These local and global activity forecasts and the associated nowcasts, whether they are of well-established, IAGA endorsed, indices or other purpose-built parameters, all rely on good quality, accurate and reliable real-time observatory data as the primary essential ingredient for derivation. Near real-time processing of data from the BGS observatories can be supplemented by data from other INTERMAGNET standard observatories for the derivation of global parameters. This poster includes a summary of this work and highlights scientific developments behind some of these space weather products, such as forecast evaluation and the value of machine learning prediction algorithms. Difficulties in finding the most suitable parameter and cadence of that parameter for given specific applications are discussed. For example this might be for the monitoring of geomagnetically induced currents for the power industry or for the establishment of a meaningful and useful local alert system for aurorae enthusiasts

Experimental evolution, genetic analysis and genome re-sequencing reveal the mutation conferring artemisinin resistance in an isogenic lineage of malaria parasites

<p>Abstract</p> <p>Background</p> <p>Classical and quantitative linkage analyses of genetic crosses have traditionally been used to map genes of interest, such as those conferring chloroquine or quinine resistance in malaria parasites. Next-generation sequencing technologies now present the possibility of determining genome-wide genetic variation at single base-pair resolution. Here, we combine <it>in vivo </it>experimental evolution, a rapid genetic strategy and whole genome re-sequencing to identify the precise genetic basis of artemisinin resistance in a lineage of the rodent malaria parasite, <it>Plasmodium chabaudi</it>. Such genetic markers will further the investigation of resistance and its control in natural infections of the human malaria, <it>P. falciparum</it>.</p> <p>Results</p> <p>A lineage of isogenic <it>in vivo </it>drug-selected mutant <it>P. chabaudi </it>parasites was investigated. By measuring the artemisinin responses of these clones, the appearance of an <it>in vivo </it>artemisinin resistance phenotype within the lineage was defined. The underlying genetic locus was mapped to a region of chromosome 2 by Linkage Group Selection in two different genetic crosses. Whole-genome deep coverage short-read re-sequencing (Illumina^®Solexa) defined the point mutations, insertions, deletions and copy-number variations arising in the lineage. Eight point mutations arise within the mutant lineage, only one of which appears on chromosome 2. This missense mutation arises contemporaneously with artemisinin resistance and maps to a gene encoding a de-ubiquitinating enzyme.</p> <p>Conclusions</p> <p>This integrated approach facilitates the rapid identification of mutations conferring selectable phenotypes, without prior knowledge of biological and molecular mechanisms. For malaria, this model can identify candidate genes before resistant parasites are commonly observed in natural human malaria populations.</p

Family medicine trainees' clinical experience of chronic disease during training: a cross-sectional analysis from the registrars' clinical encounters in training study

Background: A broad case-mix in family physicians’ (general practitioners’, GPs’) vocational trainee experience is deemed essential in producing competent independent practitioners. It is suggested that the patient-mix should include common and significant conditions and be similar to that of established GPs. But the content of contemporary GP trainees’ clinical experience in training is not well-documented. In particular, how well trainees’ experience reflects changing general practice demographics (with an increasing prevalence of chronic disease) is unknown. We aimed to establish levels of trainees’ clinical exposure to chronic disease in training (and associations of this exposure) and to establish content differences in chronic disease consultations (compared to other consultations), and differences in trainees’ actions arising from these consultations. Methods: A cross-sectional analysis from the Registrars’ Clinical Encounters in Training (ReCEnT) study, a cohort study of GP registrars’ (trainees’) consultations in four Australian GP training organisations. Trainees record detailed data from 60 consecutive consultations per six-month training term. Diagnoses/problems encountered are coded using the International Classification of Primary Care-2 PLUS (ICPC-2 PLUS). A classification system derived from ICPC-2 PLUS was used to define diagnoses/problems as chronic/non-chronic disease. The outcome factor for analyses was trainees’ consultations in which chronic disease was encountered. Independent variables were a range of patient, trainee, practice, consultation and educational factors. Results: Of 48,112 consultations (of 400 individual trainees), 29.5% included chronic disease problems/diagnoses. Associations of a consultation including chronic disease were the patient being older, male, and having consulted the trainee previously, and the practice routinely bulk-billing (not personally charging) patients. Consultations involving a chronic disease lasted longer, dealt with more problems/diagnoses, and were more likely to result in specialist referrals and trainees generating a personal learning goal. They were associated with less pathology tests being ordered. Conclusions: Trainees saw chronic disease less frequently than have established GPs in comparable studies. The longer duration and more frequent generation of learning goals in chronic disease-containing consultations suggest trainees may find these consultations particularly challenging. Our findings may inform the design of measures aimed at increasing the chronic disease component of trainees’ patient-mix.Parker Magin, Simon Morgan, Kim Henderson, Amanda Tapley, Patrick McElduff, James Pearlman, Susan Goode, Neil Spike, Caroline Laurence, John Scott, Allison Thomson and Mieke van Drie

The relationship between buildings and health: A systematic review

© 2018 The Author(s). Published by Oxford University Press on behalf of Faculty of 268 Public Health. All rights reserved. Background The built environment exerts one of the strongest directly measurable effects on physical and mental health, yet the evidence base underpinning the design of healthy urban planning is not fully developed. Method This study provides a systematic review of quantitative studies assessing the impact of buildings on health. In total, 7127 studies were identified from a structured search of eight databases combined with manual searching for grey literature. Only quantitative studies conducted between January 2000 and November 2016 were eligible for inclusion. Studies were assessed using the quality assessment tool for quantitative studies. Results In total, 39 studies were included in this review. Findings showed consistently that housing refurbishment and modifications, provision of adequate heating, improvements to ventilation and water supply were associated with improved respiratory outcomes, quality of life and mental health. Prioritization of housing for vulnerable groups led to improved wellbeing. However, the quality of the underpinning evidence and lack of methodological rigour in most of the studies makes it difficult to draw causal links. Conclusion This review identified evidence to demonstrate the strong association between certain features of housing and wellbeing such as adequate heating and ventilation. Our findings highlight the need for strengthening of the evidence base in order for meaningful conclusions to be drawn

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

GTOSat: Radiation Belt Dynamics from the Inside

GTOSat, a 6U SmallSat integrated and tested at NASA Goddard Space Flight Center (GSFC), has a scheduled launch date of July 31st, 2022, on an Atlas V. From a low inclination geosynchronous transfer orbit (GTO), GTOSat has the primary science goal of advancing our quantitative understanding of acceleration and loss of relativistic electrons in the Earth’s outer radiation belt. It will measure energy spectra and pitch angles of both the seed and the energized electron populations simultaneously using a compact, high-heritage Relativistic Electron Magnetic Spectrometer (REMS) built by The Aerospace Corporation. A boom-mounted Fluxgate Magnetometer (FMAG), developed by NASA GSFC, will provide 3-axis knowledge of the ambient local magnetic field. The spacecraft bus uses a combination of commercial and in-house/custom designed components. Design, integration, and testing of the spacecraft bus was performed by a small, dedicated team at GSFC. Throughout development GTOSat has encountered numerous challenges, expected and unexpected, that we’re ready to share with the community

British literature in transmission : writing and wireless

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