Independent external validation of cardiovascular disease mortality in women utilising Framingham and SCORE risk models: a mortality follow-up study

Background - We conducted an independent external validation of three cardiovascular risk score models (Framingham risk score model and SCORE risk charts developed for low-risk regions and high-risk regions in Europe) on a prospective cohort of 4487 Australian women with no previous history of heart disease, diabetes or stroke. External validation is an important step to evaluate the performance of risk score models using discrimination and calibration measures to ensure their applicability beyond the settings in which they were developed. Methods - Ten year mortality follow-up of 4487 Australian adult women from the National Heart Foundation third Risk Factor Prevalence Study with no baseline history of heart disease, diabetes or stroke. The 10-year risk of cardiovascular mortality was calculated using the Framingham and SCORE models and the predictive accuracy of the three risk score models were assessed using both discrimination and calibration. Results - The discriminative ability of the Framingham and SCORE models were good (area under the curve>0.85). Although all models overestimated the number of cardiovascular deaths by greater than 15%, the Hosmer-Lemeshow test indicated that the Framingham and SCORE-Low models were calibrated and hence suitable for predicting the 10-year cardiovascular mortality risk in this Australian population. An assessment of the treatment thresholds for each of the three models in identifying participants recommended for treatment were found to be inadequate, with low sensitivity and high specificity resulting from the high recommended thresholds. Lower treatment thresholds of 8.7% for the Framingham model, 0.8% for the SCORE-Low model and 1.3% for the SCORE-High model were identified for each model using the Youden index, at greater than 78% sensitivity and 80% specificity. Conclusions - Framingham risk score model and SCORE risk chart for low-risk regions are recommended for use in the Australian women population for predicting the 10-year cardiovascular mortality risk. These models demonstrate good discrimination and calibration performance. Lower treatment thresholds are proposed for better identification of individuals for treatment

Anthropometric measurements of general and central obesity and the prediction of cardiovascular disease risk in women: a cross-sectional study

Objectives: It is important to ascertain which anthropometric measurements of obesity, general or central, are better predictors of cardiovascular disease (CVD) risk in women. 10-year CVD risk was calculated from the Framingham risk score model, SCORE risk chart for high-risk regions, general CVD and simplified general CVD risk score models. Increase in CVD risk associated with 1 SD increment in each anthropometric measurement above the mean was calculated, and the diagnostic utility of obesity measures in identifying participants with increased likelihood of being above the treatment threshold was assessed. Design: Cross-sectional data from the National Heart Foundation Risk Factor Prevalence Study. Setting: Population-based survey in Australia. Participants: 4487 women aged 20–69 years without heart disease, diabetes or stroke. Outcome measures: Anthropometric obesity measures that demonstrated the greatest increase in CVD risk as a result of incremental change, 1 SD above the mean, and obesity measures that had the greatest diagnostic utility in identifying participants above the respective treatment thresholds of various risk score models.Results: Waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-stature ratio had larger effects on increased CVD risk compared with body mass index (BMI). These central obesity measures also had higher sensitivity and specificity in identifying women above and below the 20% treatment threshold than BMI. Central obesity measures also recorded better correlations with CVD risk compared with general obesity measures. WC and WHR were found to be significant and independent predictors of CVD risk, as indicated by the high area under the receiver operating characteristic curves (>0.76), after controlling for BMI in the simplified general CVD risk score model. Conclusions: Central obesity measures are better predictors of CVD risk compared with general obesity measures in women. It is equally important to maintain a healthy weight and to prevent central obesity concurrently

Molecular-Level Insights into Oxygen Reduction Catalysis by Graphite-Conjugated Active Sites

Using a combination of experimental and computational investigations, we assemble a consistent mechanistic model for the oxygen reduction reaction (ORR) at molecularly well-defined graphite-conjugated catalyst (GCC) active sites featuring aryl-pyridinium moieties $(N^+-GCC)$. ORR catalysis at glassy carbon surfaces modified with $N^+-GCC$ fragments displays near-first-order dependence in $O_2$ partial pressure and near-zero-order dependence on electrolyte pH. Tafel analysis suggests an equilibrium one-electron transfer process followed by a rate-limiting chemical step at modest overpotentials that transitions to a rate-limiting electron transfer sequence at higher overpotentials. Finite-cluster computational modeling of the $N^+-GCC$ active site reveals preferential $O_2$ adsorption at electrophilic carbons alpha to the pyridinium moiety. Together, the experimental and computational data indicate that ORR proceeds via a proton-decoupled $O_2$ activation sequence involving either concerted or stepwise electron transfer and adsorption of $O_2$, which is then followed by a series of electron/proton transfer steps to generate water and turn over the catalytic cycle. The proposed mechanistic model serves as a roadmap for the bottom-up synthesis of highly active N-doped carbon ORR catalysts

Gravitational Waves From Known Pulsars: Results From The Initial Detector Era

We present the results of searches for gravitational waves from a large selection of pulsars using data from the most recent science runs (S6, VSR2 and VSR4) of the initial generation of interferometric gravitational wave detectors LIGO (Laser Interferometric Gravitational-wave Observatory) and Virgo. We do not see evidence for gravitational wave emission from any of the targeted sources but produce upper limits on the emission amplitude. We highlight the results from seven young pulsars with large spin-down luminosities. We reach within a factor of five of the canonical spin-down limit for all seven of these, whilst for the Crab and Vela pulsars we further surpass their spin-down limits. We present new or updated limits for 172 other pulsars (including both young and millisecond pulsars). Now that the detectors are undergoing major upgrades, and, for completeness, we bring together all of the most up-to-date results from all pulsars searched for during the operations of the first-generation LIGO, Virgo and GEO600 detectors. This gives a total of 195 pulsars including the most recent results described in this paper.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyAustralian Research CouncilInternational Science Linkages program of the Commonwealth of AustraliaCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Economia y CompetitividadConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsNetherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFOCUS Programme of Foundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space AdministrationOTKA of HungaryLyon Institute of Origins (LIO)National Research Foundation of KoreaIndustry CanadaProvince of Ontario through the Ministry of Economic Development and InnovationNational Science and Engineering Research Council CanadaCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationAstronom

A First Search for coincident Gravitational Waves and High Energy Neutrinos using LIGO, Virgo and ANTARES data from 2007

We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.Comment: 19 pages, 8 figures, science summary page at http://www.ligo.org/science/Publication-S5LV_ANTARES/index.php. Public access area to figures, tables at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p120000

Swift follow-up observations of candidate gravitational-wave transient events

We present the first multi-wavelength follow-up observations of two candidate gravitational-wave (GW) transient events recorded by LIGO and Virgo in their 2009-2010 science run. The events were selected with low latency by the network of GW detectors and their candidate sky locations were observed by the Swift observatory. Image transient detection was used to analyze the collected electromagnetic data, which were found to be consistent with background. Off-line analysis of the GW data alone has also established that the selected GW events show no evidence of an astrophysical origin; one of them is consistent with background and the other one was a test, part of a "blind injection challenge". With this work we demonstrate the feasibility of rapid follow-ups of GW transients and establish the sensitivity improvement joint electromagnetic and GW observations could bring. This is a first step toward an electromagnetic follow-up program in the regime of routine detections with the advanced GW instruments expected within this decade. In that regime multi-wavelength observations will play a significant role in completing the astrophysical identification of GW sources. We present the methods and results from this first combined analysis and discuss its implications in terms of sensitivity for the present and future instruments.Comment: Submitted for publication 2012 May 25, accepted 2012 October 25, published 2012 November 21, in ApJS, 203, 28 ( http://stacks.iop.org/0067-0049/203/28 ); 14 pages, 3 figures, 6 tables; LIGO-P1100038; Science summary at http://www.ligo.org/science/Publication-S6LVSwift/index.php ; Public access area to figures, tables at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p110003

Search for gravitational waves associated with the InterPlanetary Network short gamma ray bursts

We outline the scientific motivation behind a search for gravitational waves associated with short gamma ray bursts detected by the InterPlanetary Network (IPN) during LIGO's fifth science run and Virgo's first science run. The IPN localisation of short gamma ray bursts is limited to extended error boxes of different shapes and sizes and a search on these error boxes poses a series of challenges for data analysis. We will discuss these challenges and outline the methods to optimise the search over these error boxes.Comment: Methods paper; Proceedings for Eduardo Amaldi 9 Conference on Gravitational Waves, July 2011, Cardiff, U

Influence of Calendar Period on the Association Between BMI and Coronary Heart Disease: A Meta-Analysis of 31 Cohorts

Objective: The association between obesity and coronary heart disease (CHD) may have changed over time, for example due to improved pharmacological treatment of CHD risk factors. This meta-analysis of 31 prospective cohort studies explores the influence of calendar period on CHD risk associated with body mass index (BMI). Design and Methods: The relative risks (RRs) of CHD for a five-BMI-unit increment and BMI categories were pooled by means of random effects models. Meta-regression analysis was used to examine the influence of calendar period (>1985 v 1985) in univariate and multivariate analyses (including mean population age as a covariate). Results: The age, sex, and smoking adjusted RR (95% confidence intervals) of CHD for a five-BMI-unit increment was 1.28(1.22:1.34). For underweight, overweight and obesity, the RRs (compared to normal weight) were 1.11(0.91:1.36), 1.31(1.22:1.41), and 1.78(1.55:2.04), respectively. The univariate analysis indicated 31% (95%CI: 56:0) lower RR of CHD associated with a five-BMI-unit increment and a 51% (95%CI: 78: 14)) lower RR associated with obesity in studies starting after 1985 (n ¼ 15 and 10, respectively) compared to studies starting in or before 1985 (n ¼ 16 and 10). However, in the multivariate analysis, only mean population age was independently associated with the RRs for a five-BMI-unit increment and obesity ( 29(95%CI: 55: 5)) and 31(95%CI: 66:3), respectively) per 10-year increment in mean age). Conclusion: This study provides no consistent evidence for a difference in the association between BMI and CHD by calendar period. The mean population age seems to be the most important factor that modifies the association between the risk of CHD and BMI, in which the RR decreases with increasing age