1,312 research outputs found
Adiposity has differing associations with incident coronary heart disease and mortality in the Scottish population: cross-sectional surveys with follow-up
Objective:
Investigation of the association of excess adiposity with three different outcomes: all-cause mortality, coronary heart disease (CHD) mortality and incident CHD.
Design:
Cross-sectional surveys linked to hospital admissions and death records.
Subjects:
19 329 adults (aged 18–86 years) from a representative sample of the Scottish population.
Measurements:
Gender-stratified Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause mortality, CHD mortality and incident CHD. Separate models incorporating the anthropometric measurements body mass index (BMI), waist circumference (WC) or waist–hip ratio (WHR) were created adjusted for age, year of survey, smoking status and alcohol consumption.
Results:
For both genders, BMI-defined obesity (greater than or equal to30 kg m−2) was not associated with either an increased risk of all-cause mortality or CHD mortality. However, there was an increased risk of incident CHD among the obese men (hazard ratio (HR)=1.78; 95% confidence interval=1.37–2.31) and obese women (HR=1.93; 95% confidence interval=1.44–2.59). There was a similar pattern for WC with regard to the three outcomes; for incident CHD, the HR=1.70 (1.35–2.14) for men and 1.71 (1.28–2.29) for women in the highest WC category (men greater than or equal to102 cm, women greater than or equal to88 cm), synonymous with abdominal obesity. For men, the highest category of WHR (greater than or equal to1.0) was associated with an increased risk of all-cause mortality (1.29; 1.04–1.60) and incident CHD (1.55; 1.19–2.01). Among women with a high WHR (greater than or equal to0.85) there was an increased risk of all outcomes: all-cause mortality (1.56; 1.26–1.94), CHD mortality (2.49; 1.36–4.56) and incident CHD (1.76; 1.31–2.38).
Conclusions:
In this study excess adiposity was associated with an increased risk of incident CHD but not necessarily death. One possibility is that modern medical intervention has contributed to improved survival of first CHD events. The future health burden of increased obesity levels may manifest as an increase in the prevalence of individuals living with CHD and its consequences
New tools for evaluating protein tyrosine sulfation: tyrosylprotein sulfotransferases (TPSTs) are novel targets for RAF protein kinase inhibitors
Protein tyrosine sulfation is a post-translational modification best known for regulating extracellular protein–protein interactions. Tyrosine sulfation is catalysed by two Golgi-resident enzymes termed tyrosylprotein sulfotransferases (TPSTs) 1 and 2, which transfer sulfate from the cofactor PAPS (3′-phosphoadenosine 5′-phosphosulfate) to a context-dependent tyrosine in a protein substrate. A lack of quantitative tyrosine sulfation assays has hampered the development of chemical biology approaches for the identification of small-molecule inhibitors of tyrosine sulfation. In the present paper, we describe the development of a non-radioactive mobility-based enzymatic assay for TPST1 and TPST2, through which the tyrosine sulfation of synthetic fluorescent peptides can be rapidly quantified. We exploit ligand binding and inhibitor screens to uncover a susceptibility of TPST1 and TPST2 to different classes of small molecules, including the anti-angiogenic compound suramin and the kinase inhibitor rottlerin. By screening the Published Kinase Inhibitor Set, we identified oxindole-based inhibitors of the Ser/Thr kinase RAF (rapidly accelerated fibrosarcoma) as low-micromolar inhibitors of TPST1 and TPST2. Interestingly, unrelated RAF inhibitors, exemplified by the dual BRAF/VEGFR2 inhibitor RAF265, were also TPST inhibitors in vitro. We propose that target-validated protein kinase inhibitors could be repurposed, or redesigned, as more-specific TPST inhibitors to help evaluate the sulfotyrosyl proteome. Finally, we speculate that mechanistic inhibition of cellular tyrosine sulfation might be relevant to some of the phenotypes observed in cells exposed to anionic TPST ligands and RAF protein kinase inhibitors
Bartonella species detection in captive, stranded and free-ranging cetaceans
We present prevalence of Bartonella spp. for multiple cohorts of wild and captive cetaceans. One hundred and six cetaceans including 86 bottlenose dolphins (71 free-ranging, 14 captive in a facility with a dolphin experiencing debility of unknown origin, 1 stranded), 11 striped dolphins, 4 harbor porpoises, 3 Risso's dolphins, 1 dwarf sperm whale and 1 pygmy sperm whale (all stranded) were sampled. Whole blood (n = 95 live animals) and tissues (n = 15 freshly dead animals) were screened by PCR (n = 106 animals), PCR of enrichment cultures (n = 50 animals), and subcultures (n = 50 animals). Bartonella spp. were detected from 17 cetaceans, including 12 by direct extraction PCR of blood or tissues, 6 by PCR of enrichment cultures, and 4 by subculture isolation. Bartonella spp. were more commonly detected from the captive (6/14, 43%) than from free-ranging (2/71, 2.8%) bottlenose dolphins, and were commonly detected from the stranded animals (9/21, 43%; 3/11 striped dolphins, 3/4 harbor porpoises, 2/3 Risso's dolphins, 1/1 pygmy sperm whale, 0/1 dwarf sperm whale, 0/1 bottlenose dolphin). Sequencing identified a Bartonella spp. most similar to B. henselae San Antonio 2 in eight cases (4 bottlenose dolphins, 2 striped dolphins, 2 harbor porpoises), B. henselae Houston 1 in three cases (2 Risso's dolphins, 1 harbor porpoise), and untyped in six cases (4 bottlenose dolphins, 1 striped dolphin, 1 pygmy sperm whale). Although disease causation has not been established, Bartonella species were detected more commonly from cetaceans that were overtly debilitated or were cohabiting in captivity with a debilitated animal than from free-ranging animals. The detection of Bartonella spp. from cetaceans may be of pathophysiological concern
Search for the Standard Model Higgs Boson with the OPAL Detector at LEP
This paper summarises the search for the Standard Model Higgs boson in e+e-
collisions at centre-of-mass energies up to 209 GeV performed by the OPAL
Collaboration at LEP. The consistency of the data with the background
hypothesis and various Higgs boson mass hypotheses is examined. No indication
of a signal is found in the data and a lower bound of 112.7GeV/C^2 is obtained
on the mass of the Standard Model Higgs boson at the 95% CL.Comment: 51 pages, 21 figure
Colour reconnection in e+e- -> W+W- at sqrt(s) = 189 - 209 GeV
The effects of the final state interaction phenomenon known as colour
reconnection are investigated at centre-of-mass energies in the range sqrt(s) ~
189-209 GeV using the OPAL detector at LEP. Colour reconnection is expected to
affect observables based on charged particles in hadronic decays of W+W-.
Measurements of inclusive charged particle multiplicities, and of their angular
distribution with respect to the four jet axes of the events, are used to test
models of colour reconnection. The data are found to exclude extreme scenarios
of the Sjostrand-Khoze Type I (SK-I) model and are compatible with other
models, both with and without colour reconnection effects. In the context of
the SK-I model, the best agreement with data is obtained for a reconnection
probability of 37%. Assuming no colour reconnection, the charged particle
multiplicity in hadronically decaying W bosons is measured to be (nqqch) =
19.38+-0.05(stat.)+-0.08 (syst.).Comment: 30 pages, 9 figures, Submitted to Euro. Phys. J.
Deep Learning for Detection and Localization of B-Lines in Lung Ultrasound
Lung ultrasound (LUS) is an important imaging modality used by emergency
physicians to assess pulmonary congestion at the patient bedside. B-line
artifacts in LUS videos are key findings associated with pulmonary congestion.
Not only can the interpretation of LUS be challenging for novice operators, but
visual quantification of B-lines remains subject to observer variability. In
this work, we investigate the strengths and weaknesses of multiple deep
learning approaches for automated B-line detection and localization in LUS
videos. We curate and publish, BEDLUS, a new ultrasound dataset comprising
1,419 videos from 113 patients with a total of 15,755 expert-annotated B-lines.
Based on this dataset, we present a benchmark of established deep learning
methods applied to the task of B-line detection. To pave the way for
interpretable quantification of B-lines, we propose a novel "single-point"
approach to B-line localization using only the point of origin. Our results
show that (a) the area under the receiver operating characteristic curve ranges
from 0.864 to 0.955 for the benchmarked detection methods, (b) within this
range, the best performance is achieved by models that leverage multiple
successive frames as input, and (c) the proposed single-point approach for
B-line localization reaches an F1-score of 0.65, performing on par with the
inter-observer agreement. The dataset and developed methods can facilitate
further biomedical research on automated interpretation of lung ultrasound with
the potential to expand the clinical utility.Comment: 10 pages, 4 figure
Search for R-Parity Violating Decays of Scalar Fermions at LEP
A search for pair-produced scalar fermions under the assumption that R-parity
is not conserved has been performed using data collected with the OPAL detector
at LEP. The data samples analysed correspond to an integrated luminosity of
about 610 pb-1 collected at centre-of-mass energies of sqrt(s) 189-209 GeV. An
important consequence of R-parity violation is that the lightest supersymmetric
particle is expected to be unstable. Searches of R-parity violating decays of
charged sleptons, sneutrinos and squarks have been performed under the
assumptions that the lightest supersymmetric particle decays promptly and that
only one of the R-parity violating couplings is dominant for each of the decay
modes considered. Such processes would yield final states consisting of
leptons, jets, or both with or without missing energy. No significant
single-like excess of events has been observed with respect to the Standard
Model expectations. Limits on the production cross- section of scalar fermions
in R-parity violating scenarios are obtained. Constraints on the supersymmetric
particle masses are also presented in an R-parity violating framework analogous
to the Constrained Minimal Supersymmetric Standard Model.Comment: 51 pages, 24 figures, Submitted to Eur. Phys. J.
Measurement of the Hadronic Photon Structure Function F_2^gamma at LEP2
The hadronic structure function of the photon F_2^gamma is measured as a
function of Bjorken x and of the factorisation scale Q^2 using data taken by
the OPAL detector at LEP. Previous OPAL measurements of the x dependence of
F_2^gamma are extended to an average Q^2 of 767 GeV^2. The Q^2 evolution of
F_2^gamma is studied for average Q^2 between 11.9 and 1051 GeV^2. As predicted
by QCD, the data show positive scaling violations in F_2^gamma. Several
parameterisations of F_2^gamma are in agreement with the measurements whereas
the quark-parton model prediction fails to describe the data.Comment: 4 pages, 2 figures, to appear in the proceedings of Photon 2001,
Ascona, Switzerlan
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