Associations between blood sex steroid concentrations and risk of major adverse cardiovascular events in healthy older women in Australia: a prospective cohort substudy of the ASPREE trial

Background: Blood testosterone concentrations in women decline during the reproductive years and reach a nadir in the seventh decade, after which concentrations increase and are restored to those of reproductive-aged women early in the eighth decade. We aimed to establish the association between the concentration of testosterone in the blood and risk of major adverse cardiovascular events (MACE) and all-cause mortality in healthy older women. Methods: SHOW was a prospective cohort substudy of the longitudinal randomised ASPREE trial. Eligible participants were women aged at least 70 years from Australia with unimpaired cognition, no previous MACE, and a life expectancy of at least 5 years. Participants who were receiving hormonal or steroid therapy were ineligible for inclusion. We measured serum concentrations of sex steroids with liquid chromatography–tandem mass spectrometry and of SHBG with immunoassay. We compared lower concentrations of sex hormones with higher concentrations using four quartiles. Primary endpoints were risk of MACE and all-cause mortality, the associations of which with sex steroid concentrations were assessed using Cox proportional hazards regression that included age, body-mass index, smoking status, alcohol consumption, diabetes, hypertension, dyslipidaemia, impaired renal function, and treatment allocation in the ASPREE trial (aspirin vs placebo). ASPREE is registered with ClinicalTrials.gov, NCT01038583. Findings: Of the 9180 women recruited to the ASPREE trial between March 10, 2010, and Dec 31 2014, 6358 participants provided sufficient biobank samples at baseline and 5535 were included in the final analysis. Median age at entry was 74·0 years (IQR 71·7–77·7). During a median 4·4 years of follow-up (24 553 person-years), 144 (2·6%) women had a first MACE (incidence 5·9 per 1000 person-years). During a median 4·6 years of follow-up (3·8–5·6), 200 women died (7·9 per 1000 person-years). In the fully adjusted models, higher concentrations of testosterone were associated with a lower incidence of MACE (quartile 4 vs quartile 1: hazard ratio 0·57 [95% CI 0·36–0·91]; p=0·02), as were higher concentrations of DHEA (quartile 4 vs quartile 1: 0·61 [0·38–0·97]; p=0·04). For oestrone, a lower risk of MACE was seen for concentrations in quartile 2 only, compared with quartile 1 (0·55 [0·33–0·92]; p=0·02). In fully adjusted models, no association was seen between SHBG and MACE, or between any hormone or SHBG and all-cause mortality. Interpretation: Blood concentrations of testosterone and DHEA above the lowest quartile in older women were associated with a reduced risk of a first-ever MACE. Given that the physiological effects of DHEA are mediated through its steroid metabolites, if the current findings were to be replicated, trials investigating testosterone therapy for the primary prevention of ischaemic cardiovascular disease events in older women would be warranted. Funding: The National Health and Medical Research Council of Australia, US National Institute on Aging, the Victorian Cancer Agency, the Commonwealth Scientific and Industrial Research Organisation, and Monash University

Quantum saturation and condensation of excitons in Cu2_2O: a theoretical study

Recent experiments on high density excitons in Cu$_2$O provide evidence for degenerate quantum statistics and Bose-Einstein condensation of this nearly ideal gas. We model the time dependence of this bosonic system including exciton decay mechanisms, energy exchange with phonons, and interconversion between ortho (triplet-state) and para (singlet-state) excitons, using parameters for the excitonic decay, the coupling to acoustic and low-lying optical phonons, Auger recombination, and ortho-para interconversion derived from experiment. The single adjustable parameter in our model is the optical-phonon cooling rate for Auger and laser-produced hot excitons. We show that the orthoexcitons move along the phase boundary without crossing it (i.e., exhibit a ``quantum saturation''), as a consequence of the balance of entropy changes due to cooling of excitons by phonons and heating by the non-radiative Auger two-exciton recombination process. The Auger annihilation rate for para-para collisions is much smaller than that for ortho-para and ortho-ortho collisions, explaining why, under the given experimental conditions, the paraexcitons condense while the orthoexcitons fail to do so.Comment: Revised to improve clarity and physical content 18 pages, revtex, figures available from G. Kavoulakis, Physics Department, University of Illinois, Urban

Potential role of the posterior cruciate ligament synovio-entheseal complex in joint effusion in early osteoarthritis: a magnetic resonance imaging and histological evaluation of cadaveric tissue and data from the Osteoarthritis Initiative

Objective: This study explored posterior cruciate ligament (PCL) synovio-entheseal complex (SEC) microanatomy to determine whether it may participate in the early osteoarthritis (OA) disease process. Methods: SEC microanatomy and OA features were evaluated in 14 non-arthritic cadaveric knees (mean age = 69.9) using magnetic resonance imaging (MRI) and histology. MRI images of 49 subjects selected from the progression cohort of the Osteoarthritis Initiative (OAI) were evaluated by a musculoskeletal radiologist using an original semi-quantitative method for features associated with OA at the PCL tibial enthesis. Statistical analysis was performed using chi-square and Wilcoxon signed-rank tests to evaluate associations between SEC configuration and OA features. Results: The PCL formed a SEC-like structure encompassing bone- and ligament-lining intra-articular cartilages to which the posterior root of the medial meniscus contributed. Degenerative features at the PCL-SEC included: neovascularisation (44%), enthesis chondrocyte clustering (44%), collagen matrix fissuring at the enthesis (56%) and in the PCL itself (67%), tidemark duplication (44%), bone remodelling (44%) and microscopic inflammatory changes (33%). In the OAI cohort, SEC-related pathology included bone marrow lesions (BMLs) (69%) and osteophytosis (94%) at locations that corresponded to SEC-related cartilages. Posterior joint recess effusion (49%) was linked to MRI abnormalities at PCL-SEC cartilages (χ2 = 7.27, P = 0.007). Conclusions: The PCL has a prominent SEC configuration that is associated with microscopic OA changes in aged clinically non-diseased joints. MRI determined knee OA commonly exhibited pathological features at this site which was associated with adjacent joint effusion. Thus, the PCL-SEC could play a hitherto unappreciated role in the early OA disease process

Contribution of Color Information in Visual Saliency Model for Videos

International audienceMuch research has been concerned with the contribution of the low level features of a visual scene to the deployment of visual attention. Bottom-up saliency models have been developed to predict the location of gaze according to these features. So far, color besides to brightness, contrast and motion is considered as one of the primary features in computing bottom-up saliency. However, its contribution in guiding eye movements when viewing natural scenes has been debated. We investigated the contribution of color information in a bottom-up visual saliency model. The model efficiency was tested using the experimental data obtained on 45 observers who were eye tracked while freely exploring a large data set of color and grayscale videos. The two datasets of recorded eye positions, for grayscale and color videos, were compared with a luminance-based saliency model. We incorporated chrominance information to the model. Results show that color information improves the performance of the saliency model in predicting eye positions

Astroparticle Physics with a Customized Low-Background Broad Energy Germanium Detector

The MAJORANA Collaboration is building the MAJORANA DEMONSTRATOR, a 60 kg array of high purity germanium detectors housed in an ultra-low background shield at the Sanford Underground Laboratory in Lead, SD. The MAJORANA DEMONSTRATOR will search for neutrinoless double-beta decay of 76Ge while demonstrating the feasibility of a tonne-scale experiment. It may also carry out a dark matter search in the 1-10 GeV/c^2 mass range. We have found that customized Broad Energy Germanium (BEGe) detectors produced by Canberra have several desirable features for a neutrinoless double-beta decay experiment, including low electronic noise, excellent pulse shape analysis capabilities, and simple fabrication. We have deployed a customized BEGe, the MAJORANA Low-Background BEGe at Kimballton (MALBEK), in a low-background cryostat and shield at the Kimballton Underground Research Facility in Virginia. This paper will focus on the detector characteristics and measurements that can be performed with such a radiation detector in a low-background environment.Comment: Submitted to NIMA Proceedings, SORMA XII. 9 pages, 4 figure