Extracellular Hsp72 concentration relates to a minimum endogenous criteria during acute exercise-heat exposure

Extracellular heat-shock protein 72 (eHsp72) concentration increases during exercise-heat stress when conditions elicit physiological strain. Differences in severity of environmental and exercise stimuli have elicited varied response to stress. The present study aimed to quantify the extent of increased eHsp72 with increased exogenous heat stress, and determine related endogenous markers of strain in an exercise-heat model. Ten males cycled for 90 min at 50% O2peak in three conditions (TEMP, 20°C/63% RH; HOT, 30.2°C/51%RH; VHOT, 40.0°C/37%RH). Plasma was analysed for eHsp72 pre, immediately post and 24-h post each trial utilising a commercially available ELISA. Increased eHsp72 concentration was observed post VHOT trial (+172.4%) (P<0.05), but not TEMP (-1.9%) or HOT (+25.7%) conditions. eHsp72 returned to baseline values within 24hrs in all conditions. Changes were observed in rectal temperature (Trec), rate of Trec increase, area under the curve for Trec of 38.5°C and 39.0°C, duration Trec ≥ 38.5°C and ≥ 39.0°C, and change in muscle temperature, between VHOT, and TEMP and HOT, but not between TEMP and HOT. Each condition also elicited significantly increasing physiological strain, described by sweat rate, heart rate, physiological strain index, rating of perceived exertion and thermal sensation. Stepwise multiple regression reported rate of Trec increase and change in Trec to be predictors of increased eHsp72 concentration. Data suggests eHsp72 concentration increases once systemic temperature and sympathetic activity exceeds a minimum endogenous criteria elicited during VHOT conditions and is likely to be modulated by large, rapid changes in core temperature

The Large UV/Optical/Infrared Surveyor (LUVOIR): Decadal Mission Concept Study Update

In preparation for the 2020 Decadal Survey in Astronomy and Astrophysics, NASA commissioned the study of four large mission concepts: the Large UV/Optical/Infrared Surveyor (LUVOIR), the Habitable Exoplanet Imager (HabEx), the far-infrared surveyor Origins Space Telescope (OST), and the X-ray surveyor Lynx. The LUVOIR Science and Technology Definition Team (STDT) has identified a broad range of science objectives for LUVOIR that include the direct imaging and spectral characterization of habitable exoplanets around sun-like stars, the study of galaxy formation and evolution, the exchange of matter between galaxies, star and planet formation, and the remote sensing of Solar System objects. The LUVOIR Study Office, located at NASA's Goddard Space Flight Center (GSFC), is developing two mission concepts to achieve the science objectives. LUVOIR-A is a 15-meter segmented-aperture observatory that would be launched in an 8.4-m extended fairing on the Space Launch System (SLS) Block 2 configuration. LUVOIR-B is an 8-meter unobscured segmented aperture telescope that fits in a smaller, conventional 5-meter fairing, but still requires the lift capacity of the SLS Block 1B Cargo vehicle. Both concepts include a suite of serviceable instruments: the Extreme Coronagraph for Living Planetary Systems (ECLIPS), an optical/near-infrared coronagraph capable of delivering 10 (sup minus10) contrast at inner working angles as small as 2 lambda divided by D; the LUVOIR UV Multi-object Spectrograph (LUMOS), which will provide low- and medium-resolution UV (100-400 nanometer) multi-object imaging spectroscopy in addition to far-UV imaging; the High Definition Imager (HDI), a high-resolution wide-field-of-view NUV-Optical-NIR imager. LUVOIR-A also has a fourth instrument, Pollux, a high-resolution UV spectro-polarimeter being contributed by Centre National d'Etudes Spatiales (CNES). This paper provides an overview of the LUVIOR science objectives, design drivers, and mission concepts

The Large UV/Optical/Infrared Surveyor (LUVOIR): Decadal Mission Study Update

NASA commissioned the study of four large mission concepts, including the Large Ultraviolet / Optical / Infrared (LUVOIR) Surveyor, to be evaluated by the 2020 Decadal Survey in Astrophysics. In response, the Science and Technology Definition Team (STDT) identified a broad range of science objectives for LUVOIR that include the direct imaging and spectral characterization of habitable exoplanets around sun-like stars, the study of galaxy formation and evolution, the exchange of matter between galaxies, star and planet formation, and the remote sensing of Solar System objects. To meet these objectives, the LUVOIR Study Office, located at NASA's Goddard Space Flight Center (GSFC), completed the first design iteration of a 15-m segmented-aperture observatory that would be launched by the Space Launch System (SLS) Block 2 configuration. The observatory includes four serviceable instruments: the Extreme Coronagraph for Living Planetary Systems (ECLIPS), an optical / near-infrared coronagraph capable of delivering 10(exp -10) contrast at inner working angles as small as 2 lambda/D; the LUVOIR UV Multi-object Spectrograph (LUMOS), which will provide low- and medium-resolution UV (100 - 400 nm) multi-object imaging spectroscopy in addition to far-UV imaging; the High Definition Imager (HDI), a high-resolution wide-field-of-view NUV-Optical-NIR imager; and Pollux, a high-resolution UV spectro-polarimeter being contributed by Centre National d'Etudes Spatiales (CNES). The study team has executed a second design iteration to further improve upon the 15-m concept, while simultaneously studying an 8-m concept. In these proceedings, we provide an update on these two architectures

Dense sampling of ethnic groups within African countries reveals fine-scale genetic structure and extensive historical admixture

Previous studies have highlighted how African genomes have been shaped by a complex series of historical events. Despite this, genome-wide data have only been obtained from a small proportion of present-day ethnolinguistic groups. By analyzing new autosomal genetic variation data of 1333 individuals from over 150 ethnic groups from Cameroon, Republic of the Congo, Ghana, Nigeria, and Sudan, we demonstrate a previously underappreciated fine-scale level of genetic structure within these countries, for example, correlating with historical polities in western Cameroon. By comparing genetic variation patterns among populations, we infer that many northern Cameroonian and Sudanese groups share genetic links with multiple geographically disparate populations, likely resulting from long-distance migrations. In Ghana and Nigeria, we infer signatures of intermixing dated to over 2000 years ago, corresponding to reports of environmental transformations possibly related to climate change. We also infer recent intermixing signals in multiple African populations, including Congolese, that likely relate to the expansions of Bantu language-speaking peoples

Comparing measures of overall and central obesity in relation to cardiometabolic risk factors among US Hispanic/Latino adults: Obesity and Cardiometabolic Risk in Hispanics

US Hispanics/Latinos have high prevalence of obesity and related comorbidities. We compared overall and central obesity measures in associations with cardiometabolic outcomes among US Hispanics/Latinos

Objectively Measured Sedentary Time and Cardiometabolic Biomarkers in US Hispanic/Latino AdultsCLINICAL PERSPECTIVE: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Sedentary behavior is recognized as a distinct construct from lack of moderate-vigorous physical activity and is associated with deleterious health outcomes. Previous studies have primarily relied on self-reported data, while data on the relationship between objectively-measured sedentary time and cardiometabolic biomarkers are sparse, especially among U.S. Hispanics/Latinos

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function

Cost effectiveness of endovascular ultrasound renal denervation in patients with resistant hypertension

Background Resistant hypertension (rHTN) is defined as blood pressure (BP) of ≥ 140/90 mmHg despite treatment with at least three antihypertensive medications, including a diuretic. Endovascular ultrasound renal denervation (uRDN) aims to control BP alongside conventional BP treatment with antihypertensive medication. This analysis assesses the cost effectiveness of the addition of the Paradise uRDN System compared with standard of care alone in patients with rHTN from the perspective of the United Kingdom (UK) health care system. Methods Using RADIANCE-HTN TRIO trial data, we developed a state-transition model. Baseline risk was calculated using Framingham and Prospective Cardiovascular Münster (PROCAM) risk equations to estimate the long-term cardiovascular risks in patients treated with the Paradise uRDN System, based on the observed systolic BP (SBP) reduction following uRDN. Relative risks sourced from a meta-analysis of randomised controlled trials were then used to project cardiovascular events in patients with baseline SBP (‘control’ patients); utility and mortality inputs and costs were derived from UK data. Costs and outcomes were discounted at 3.5% per annum. Modelled outcomes were validated against trial meta-analyses and the QRISK3 algorithm and real-world evidence of RDN effectiveness. One-way and probabilistic sensitivity analyses were conducted to assess the uncertainty surrounding the model inputs and sensitivity of the model results to changes in parameter inputs. Results were reported as incremental cost-effectiveness ratios (ICERs). Results A mean reduction in office SBP of 8.5 mmHg with uRDN resulted in an average improvement in both absolute life-years (LYs) and quality-adjusted life-years (QALYs) gained compared with standard of care alone (0.73 LYs and 0.67 QALYs). The overall base-case ICER with uRDN was estimated at £5600 (€6500) per QALY gained (95% confidence interval £5463–£5739 [€6341–€6661]); modelling demonstrated &gt; 99% probability that the ICER is below the £20,000–£30,000 (€23,214–€34,821) per QALYs gained willingness-to-pay threshold in the UK. Results were consistent across sensitivity analyses and validation checks. Conclusions Endovascular ultrasound RDN with the Paradise system offers patients with rHTN, clinicians, and healthcare systems a cost-effective treatment option alongside antihypertensive medication

The Dynamic X-ray Sky of the Local Universe

Over the next decade, we can expect time domain astronomy to flourish at optical and radio wavelengths. In parallel with these efforts, a dedicated transient "machine" operating at higher energies (X-ray band through soft gamma-rays) is required to reveal the unique subset of events with variable emission predominantly visible above 100 eV. Here we focus on the transient phase space never yet sampled due to the lack of a sensitive, wide-field and triggering facility dedicated exclusively to catching high energy transients and enabling rapid coordinated multi-wavelength follow-up. We first describe the advancements in our understanding of known X-ray transients that can only be enabled through such a facility and then focus on the classes of transients theoretically predicted to be out of reach of current detection capabilities. Finally there is the exciting opportunity of revealing new classes of X-ray transients and unveiling their nature through coordinated follow-up observations at longer wavelengths.Comment: 8 pages, 2 figures; White Paper submitted to the Astro2010 SSE pane

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis