An entropy stable discontinuous Galerkin method for the shallow water equations on curvilinear meshes with wet/dry fronts accelerated by GPUs

We extend the entropy stable high order nodal discontinuous Galerkin spectral element approximation for the non-linear two dimensional shallow water equations presented by Wintermeyer et al. [N. Wintermeyer, A. R. Winters, G. J. Gassner, and D. A. Kopriva. An entropy stable nodal discontinuous Galerkin method for the two dimensional shallow water equations on unstructured curvilinear meshes with discontinuous bathymetry. Journal of Computational Physics, 340:200-242, 2017] with a shock capturing technique and a positivity preservation capability to handle dry areas. The scheme preserves the entropy inequality, is well-balanced and works on unstructured, possibly curved, quadrilateral meshes. For the shock capturing, we introduce an artificial viscosity to the equations and prove that the numerical scheme remains entropy stable. We add a positivity preserving limiter to guarantee non-negative water heights as long as the mean water height is non-negative. We prove that non-negative mean water heights are guaranteed under a certain additional time step restriction for the entropy stable numerical interface flux. We implement the method on GPU architectures using the abstract language OCCA, a unified approach to multi-threading languages. We show that the entropy stable scheme is well suited to GPUs as the necessary extra calculations do not negatively impact the runtime up to reasonably high polynomial degrees (around $N=7$). We provide numerical examples that challenge the shock capturing and positivity properties of our scheme to verify our theoretical findings

Recreational Physical Activity as an Independent Predictor of Multivariable Cardiovascular Disease Risk

The role of physical activity in preventing CVD has been highlighted by Professor Jerry Morris in the 1950’s. We report outcome of a 15-year prospective study with the aim to identify whether physical activity showed cardiovascular benefit independent of common risk factors and of central obesity. Baseline data of 8662 subjects, with no previous history of heart disease, diabetes or stroke, were obtained from an age- and gender- stratified sample of adults in Australian capital cities and were linked with the National Death Index to determine the causes of death of 610 subjects who had died to 31 December 2004. The study consisted of 4175 males (age 42.3±13.1 years) and 4487 females (age 42.8±13.2 years). Fasting serum lipid levels, systolic and diastolic blood pressure and smoking habits at baseline were recorded. The Framingham Risk Scores of 15-year mortality due to CHD and CVD were calculated using established equations. Subjects were also asked if they engaged in vigorous exercise, less vigorous exercise or walk for recreation and exercise in the past 2 weeks. Subjects in the high recreational physical activity category were 0.16 (0.06–0.43; p<0.001) and 0.12 (0.03–0.48; p = 0.003) times as likely as subjects in the low category for CVD and CHD mortality respectively. After adjusting for both the Framingham Risk Score and central obesity (Waist circumference to Hip circumference Ratio), those in the high recreational physical activity group were 0.35 (0.13–0.98) times less likely compared to the low category for CVD mortality. Recreational physical activity independently predicted reduced cardiovascular mortality over fifteen years. A public health focus on increased physical activity and preventing obesity is required to reduce the risk of CVD and CHD

Differences in genotype and virulence among four multidrug-resistant <i>Streptococcus pneumoniae</i> isolates belonging to the PMEN1 clone

We report on the comparative genomics and characterization of the virulence phenotypes of four &lt;i&gt;S. pneumoniae&lt;/i&gt; strains that belong to the multidrug resistant clone PMEN1 (Spain&lt;sup&gt;23F&lt;/sup&gt; ST81). Strains SV35-T23 and SV36-T3 were recovered in 1996 from the nasopharynx of patients at an AIDS hospice in New York. Strain SV36-T3 expressed capsule type 3 which is unusual for this clone and represents the product of an in vivo capsular switch event. A third PMEN1 isolate - PN4595-T23 - was recovered in 1996 from the nasopharynx of a child attending day care in Portugal, and a fourth strain - ATCC700669 - was originally isolated from a patient with pneumococcal disease in Spain in 1984. We compared the genomes among four PMEN1 strains and 47 previously sequenced pneumococcal isolates for gene possession differences and allelic variations within core genes. In contrast to the 47 strains - representing a variety of clonal types - the four PMEN1 strains grouped closely together, demonstrating high genomic conservation within this lineage relative to the rest of the species. In the four PMEN1 strains allelic and gene possession differences were clustered into 18 genomic regions including the capsule, the blp bacteriocins, erythromycin resistance, the MM1-2008 prophage and multiple cell wall anchored proteins. In spite of their genomic similarity, the high resolution chinchilla model was able to detect variations in virulence properties of the PMEN1 strains highlighting how small genic or allelic variation can lead to significant changes in pathogenicity and making this set of strains ideal for the identification of novel virulence determinant

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

The Ergogenic Effect of Recombinant Human Erythropoietin on V̇O2max Depends on the Severity of Arterial Hypoxemia

Treatment with recombinant human erythropoietin (rhEpo) induces a rise in blood oxygen-carrying capacity (CaO2) that unequivocally enhances maximal oxygen uptake (V̇O2max) during exercise in normoxia, but not when exercise is carried out in severe acute hypoxia. This implies that there should be a threshold altitude at which V̇O2max is less dependent on CaO2. To ascertain which are the mechanisms explaining the interactions between hypoxia, CaO2 and V̇O2max we measured systemic and leg O2 transport and utilization during incremental exercise to exhaustion in normoxia and with different degrees of acute hypoxia in eight rhEpo-treated subjects. Following prolonged rhEpo treatment, the gain in systemic V̇O2max observed in normoxia (6–7%) persisted during mild hypoxia (8% at inspired O2 fraction (FIO2) of 0.173) and was even larger during moderate hypoxia (14–17% at FIO2 = 0.153–0.134). When hypoxia was further augmented to FIO2 = 0.115, there was no rhEpo-induced enhancement of systemic V̇O2max or peak leg V̇O2. The mechanism highlighted by our data is that besides its strong influence on CaO2, rhEpo was found to enhance leg V̇O2max in normoxia through a preferential redistribution of cardiac output toward the exercising legs, whereas this advantageous effect disappeared during severe hypoxia, leaving augmented CaO2 alone insufficient for improving peak leg O2 delivery and V̇O2. Finally, that V̇O2max was largely dependent on CaO2 during moderate hypoxia but became abruptly CaO2-independent by slightly increasing the severity of hypoxia could be an indirect evidence of the appearance of central fatigue

Baseline factors associated with early and late death in intracerebral haemorrhage survivors

Background and purpose: The aim of this study was to determine whether early and late death are associated with different baseline factors in intracerebral haemorrhage (ICH) survivors. Methods: This was a secondary analysis of the multicentre prospective observational CROMIS‐2 ICH study. Death was defined as ‘early’ if occurring within 6 months of study entry and ‘late’ if occurring after this time point. Results: In our cohort (n = 1094), there were 306 deaths (per 100 patient‐years: absolute event rate, 11.7; 95% confidence intervals, 10.5–13.1); 156 were ‘early’ and 150 ‘late’. In multivariable analyses, early death was independently associated with age [per year increase; hazard ratio (HR), 1.05, P = 0.003], history of hypertension (HR, 1.89, P = 0.038), pre‐event modified Rankin scale score (per point increase; HR, 1.41, P &lt; 0.0001), admission National Institutes of Health Stroke Scale score (per point increase; HR, 1.11, P &lt; 0.0001) and haemorrhage volume &gt;60 mL (HR, 4.08, P &lt; 0.0001). Late death showed independent associations with age (per year increase; HR, 1.04, P = 0.003), pre‐event modified Rankin scale score (per point increase; HR, 1.42, P = 0.001), prior anticoagulant use (HR, 2.13, P = 0.028) and the presence of intraventricular extension (HR, 1.73, P = 0.033) in multivariable analyses. In further analyses where time was treated as continuous (rather than dichotomized), the HR of previous cerebral ischaemic events increased with time, whereas HRs for Glasgow Coma Scale score, National Institutes of Health Stroke Scale score and ICH volume decreased over time. Conclusions: We provide new evidence that not all baseline factors associated with early mortality after ICH are associated with mortality after 6 months and that the effects of baseline variables change over time. Our findings could help design better prognostic scores for later death after ICH

New broad-spectrum resistance to septoria tritici blotch derived from synthetic hexaploid wheat

Septoria tritici blotch (STB), caused by the ascomycete Mycosphaerella graminicola, is one of the most devastating foliar diseases of wheat. We screened five synthetic hexaploid wheats (SHs), 13 wheat varieties that represent the differential set of cultivars and two susceptible checks with a global set of 20 isolates and discovered exceptionally broad STB resistance in SHs. Subsequent development and analyses of recombinant inbred lines (RILs) from a cross between the SH M3 and the highly susceptible bread wheat cv. Kulm revealed two novel resistance loci on chromosomes 3D and 5A. The 3D resistance was expressed in the seedling and adult plant stages, and it controlled necrosis (N) and pycnidia (P) development as well as the latency periods of these parameters. This locus, which is closely linked to the microsatellite marker Xgwm494, was tentatively designated Stb16q and explained from 41 to 71% of the phenotypic variation at seedling stage and 28–31% in mature plants. The resistance locus on chromosome 5A was specifically expressed in the adult plant stage, associated with SSR marker Xhbg247, explained 12–32% of the variation in disease, was designated Stb17, and is the first unambiguously identified and named QTL for adult plant resistance to M. graminicola. Our results confirm that common wheat progenitors might be a rich source of new Stb resistance genes/QTLs that can be deployed in commercial breeding programs

Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2):a multicentre observational cohort study

Background: Cerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack. Methods: Our observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316. Findings: Between Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0–20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1–5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27–10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29–0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53–0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60–0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07–0·43, p=0·0065; and 0·33, 0·14–0·51, p=0·00059, respectively). Interpretation: In patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from oral anticoagulation. Funding: The Stroke Association and the British Heart Foundation