Association between continuity of provider-adjusted regularity of general practitioner contact and unplanned diabetes-related hospitalisation: A data linkage study in New South Wales, Australia, using the 45 and Up Study cohort

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Objective To assess the association between continuity of provider-adjusted regularity of general practitioner (GP) contact and unplanned diabetes-related hospitalisation or emergency department (ED) presentation. Design Cross-sectional study. Setting Individual-level linked self-report and administrative health service data from New South Wales, Australia. Participants 27 409 survey respondents aged ≥45 years with a prior history of diabetes and at least three GP contacts between 1 July 2009 and 30 June 2015. Main outcome measures Unplanned diabetes-related hospitalisations or ED presentations, associated costs and bed days. Results Twenty-one per cent of respondents had an unplanned diabetes-related hospitalisation or ED presentation. Increasing regularity of GP contact was associated with a lower probability of hospitalisation or ED presentation (19.9% for highest quintile, 23.5% for the lowest quintile). Conditional on having an event, there was a small decrease in the number of hospitalisations or ED presentations for the low (-6%) and moderate regularity quintiles (-8%), a reduction in bed days (ranging from -30 to -44%) and a reduction in average cost of between -23% and -41%, all relative to the lowest quintile. When probability of diabetes-related hospitalisation or ED presentation was included, only the inverse association with cost remained significant (mean of A3798 to A6350 less per individual, compared with the lowest regularity quintile). Importantly, continuity of provider did not significantly modify the effect of GP regularity for any outcome. Conclusions Higher regularity of GP contact - that is more evenly dispersed, not necessarily more frequent care - has the potential to reduce secondary healthcare costs and, conditional on having an event, the time spent in hospital, irrespective of continuity of provider. These findings argue for the advocacy of regular care, as distinct from solely continuity of provider, when designing policy and financial incentives for GP-led primary care

Transverse Fivebranes in Matrix Theory

M-theory on the maximally supersymmetric plane wave background of eleven-dimensional supergravity admits spherical BPS transverse M5-branes with zero light-cone energy. We give direct evidence that the single M5-brane state corresponds to the trivial (X=0) classical vacuum in the large N limit of the plane wave matrix theory. In particular, we show that the linear fluctuation spectrum of the spherical fivebrane matches exactly with the set of exactly protected excited states about the X=0 vacuum in the matrix model. These states include geometrical fluctuations of the sphere, excitations of the worldvolume two-form field, and fermion excitations. In addition, we propose a description of multiple fivebrane states in terms of matrix model vacua. Finally, we discuss how to obtain the continuum D2/M2 and NS5/M5 theories on spheres from the matrix model. The matrix model can be viewed as a regularization for these theories.Comment: Latex file, 2 eps figures, 22 pages; v2: typo correcte

Calibration of Smearing and Cooling Algorithms in SU(3)-Color Gauge Theory

The action and topological charge are used to determine the relative rates of standard cooling and smearing algorithms in pure SU(3)-color gauge theory. We consider representative gauge field configurations on $16^3\times 32$ lattices at $\beta=5.70$ and $24^3\times 36$ lattices at $\beta=6.00$. We find the relative rate of variation in the action and topological charge under various algorithms may be succinctly described in terms of simple formulae. The results are in accord with recent suggestions from fat-link perturbation theory.Comment: RevTeX, 25 pages, 22 figures, full resolution jpeg version of Fig. 22 can be obtained from http://www.physics.adelaide.edu.au/cssm/papers_etc/SmearingComp.jp

A Perturbative Calculation of the Electromagnetic Form Factors of the Deuteron

Making use of the effective field theory expansion recently developed by the authors, we compute the electromagnetic form factors of the deuteron analytically to next-to-leading order (NLO). The computation is rather simple, and involves calculating several Feynman diagrams, using dimensional regularization. The results agree well with data and indicate that the expansion is converging. They do not suffer from any ambiguities arising from off-shell versus on-shell amplitudes.Comment: 22 pages, 8 figures. Discussion of effective range theory added, typos correcte

Cost effectiveness of thrombolytic therapy with tissue plasminogen activator as compared with streptokinase for acute myocardial infarction

BACKGROUND. Patients with acute myocardial infarction who were treated with accelerated tissue plasminogen activator (t-PA) (given over a period of 1 1/2 hours rather than the conventional 3 hours, and with two thirds of the dose given in the first 30 minutes) had a 30-day mortality that was 15 percent lower than that of pati

Benchmarking Taxonomic and Genetic Diversity After the Fact: Lessons Learned From the Catastrophic 2019–2020 Australian Bushfires

Environmental catastrophes are increasing in frequency and severity under climate change, and they substantially impact biodiversity. Recovery actions after catastrophes depend on prior benchmarking of biodiversity and that in turn minimally requires critical assessment of taxonomy and species-level diversity. Long-term recovery of species also requires an understanding of within-species diversity. Australia’s 2019–2020 bushfires were unprecedented in their extent and severity and impacted large portions of habitats that are not adapted to fire. Assessments of the fires’ impacts on vertebrates identified 114 species that were a high priority for management. In response, we compiled explicit information on taxonomic diversity and genetic diversity within fire-impacted vertebrates to provide to government agencies undertaking rapid conservation assessments. Here we discuss what we learned from our effort to benchmark pre-fire taxonomic and genetic diversity after the event. We identified a significant number of candidate species (genetic units that may be undescribed species), particularly in frogs and mammals. Reptiles and mammals also had high levels of intraspecific genetic structure relevant to conservation management. The first challenge was making published genetic data fit for purpose because original publications often focussed on a different question and did not provide raw sequence read data. Gaining access to analytical files and compiling appropriate individual metadata was also time-consuming. For many species, significant unpublished data was held by researchers. Identifying which data existed was challenging. For both published and unpublished data, substantial sampling gaps prevented areas of a species’ distribution being assigned to a conservation unit. Summarising sampling gaps across species revealed that many areas were poorly sampled across taxonomic groups. To resolve these issues and prepare responses to future catastrophes, we recommend that researchers embrace open data principles including providing detailed metadata. Governments need to invest in a skilled taxonomic workforce to document and describe biodiversity before an event and to assess its impacts afterward. Natural history collections should also target increasing their DNA collections based on sampling gaps and revise their collection strategies to increasingly take population-scale DNA samples in order to document within-species genetic diversity.Funding for this project was provided by the National Environmental Science Programme Threatened Species Recovery Hub, Theme 8: Post bushfire recovery support, and the Centre for Biodiversity Analysis (https://biology.anu.edu.au/research/centres-units/centre-biodiv ersity-analysis)

Structural Requirements for Dihydrobenzoxazepinone Anthelmintics:Actions against Medically Important and Model Parasites: Trichuris muris, Brugia malayi, Heligmosomoides polygyrus, and Schistosoma mansoni

Nine hundred million people are infected with the soil-transmitted helminths Ascaris lumbricoides (roundworm), hookworm, and Trichuris trichiura (whipworm). However, low single-dose cure rates of the benzimidazole drugs, the mainstay of preventative chemotherapy for whipworm, together with parasite drug resistance, mean that current approaches may not be able to eliminate morbidity from trichuriasis. We are seeking to develop new anthelmintic drugs specifically with activity against whipworm as a priority and previously identified a hit series of dihydrobenzoxazepinone (DHB) compounds that block motility of ex vivo Trichuris muris. Here, we report a systematic investigation of the structure–activity relationship of the anthelmintic activity of DHB compounds. We synthesized 47 analogues, which allowed us to define features of the molecules essential for anthelmintic action as well as broadening the chemotype by identification of dihydrobenzoquinolinones (DBQs) with anthelmintic activity. We investigated the activity of these compounds against other parasitic nematodes, identifying DHB compounds with activity against Brugia malayi and Heligmosomoides polygyrus. We also demonstrated activity of DHB compounds against the trematode Schistosoma mansoni, a parasite that causes schistosomiasis. These results demonstrate the potential of DHB and DBQ compounds for further development as broad-spectrum anthelmintics

Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium.

BACKGROUND: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. METHODS: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. FINDINGS: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. INTERPRETATION: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies. FUNDING: EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research