The genetic case for cardiorespiratory fitness as a clinical vital sign and the routine prescription of physical activity in healthcare

Background: Cardiorespiratory fitness (CRF) and physical activity (PA) are well-established predictors of morbidity and all-cause mortality. However, CRF is not routinely measured and PA not routinely prescribed as part of standard healthcare. The American Heart Association (AHA) recently presented a scientific case for the inclusion of CRF as a clinical vital sign based on epidemiological and clinical observation. Here, we leverage genetic data in the UK Biobank (UKB) to strengthen the case for CRF as a vital sign and make a case for the prescription of PA. / Methods: We derived two CRF measures from the heart rate data collected during a submaximal cycle ramp test: CRF-vo2max, an estimate of the participants' maximum volume of oxygen uptake, per kilogram of body weight, per minute; and CRF-slope, an estimate of the rate of increase of heart rate during exercise. Average PA over a 7-day period was derived from a wrist-worn activity tracker. After quality control, 70,783 participants had data on the two derived CRF measures, and 89,683 had PA data. We performed genome-wide association study (GWAS) analyses by sex, and post-GWAS techniques to understand genetic architecture of the traits and prioritise functional genes for follow-up. / Results: We found strong evidence that genetic variants associated with CRF and PA influenced genetic expression in a relatively small set of genes in the heart, artery, lung, skeletal muscle and adipose tissue. These functionally relevant genes were enriched among genes known to be associated with coronary artery disease (CAD), type 2 diabetes (T2D) and Alzheimer’s disease (three of the top 10 causes of death in high-income countries) as well as Parkinson’s disease, pulmonary fibrosis, and blood pressure, heart rate, and respiratory phenotypes. Genetic variation associated with lower CRF and PA was also correlated with several disease risk factors (including greater body mass index, body fat and multiple obesity phenotypes); a typical T2D profile (including higher insulin resistance, higher fasting glucose, impaired beta-cell function, hyperglycaemia, hypertriglyceridemia); increased risk for CAD and T2D; and a shorter lifespan. / Conclusions: Genetics supports three decades of evidence for the inclusion of CRF as a clinical vital sign. Given the genetic, clinical and epidemiological evidence linking CRF and PA to increased morbidity and mortality, regular measurement of CRF as a marker of health and routine prescription of PA could be a prudent strategy to support public health

Exoplanet phase curves: observations and theory

Phase curves are the best technique to probe the three dimensional structure of exoplanets' atmospheres. In this chapter we first review current exoplanets phase curve observations and the particular challenges they face. We then describe the different physical mechanisms shaping the atmospheric phase curves of highly irradiated tidally locked exoplanets. Finally, we discuss the potential for future missions to further advance our understanding of these new worlds.Comment: Fig.5 has been updated. Table 1 and corresponding figures have been updated with new values for WASP-103b and WASP-18b. Contains a table sumarizing phase curve observation

Impact of Scottish smoke-free legislation on smoking quit attempts and prevalence

<p><b>Objectives:</b> In Scotland, legislation was implemented in March 2006 prohibiting smoking in all wholly or partially enclosed public spaces. We investigated the impact on attempts to quit smoking and smoking prevalence.</p> <p><b>Methods:</b> We performed time series models using Box-Jenkins autoregressive integrated moving averages (ARIMA) on monthly data on the gross ingredient cost of all nicotine replacement therapy (NRT) prescribed in Scotland in 2003–2009, and quarterly data on self-reported smoking prevalence between January 1999 and September 2010 from the Scottish Household Survey.</p> <p><b>Results:</b> NRT prescription costs were significantly higher than expected over the three months prior to implementation of the legislation. Prescription costs peaked at £1.3 million in March 2006; £292,005.9 (95% CI £260,402.3, £323,609, p<0.001) higher than the monthly norm. Following implementation of the legislation, costs fell exponentially by around 26% per month (95% CI 17%, 35%, p<0.001). Twelve months following implementation, the costs were not significantly different to monthly norms. Smoking prevalence fell by 8.0% overall, from 31.3% in January 1999 to 23.7% in July–September 2010. In the quarter prior to implementation of the legislation, smoking prevalence fell by 1.7% (95% CI 2.4%, 1.0%, p<0.001) more than expected from the underlying trend.</p> <p><b>Conclusions:</b> Quit attempts increased in the three months leading up to Scotland's smoke-free legislation, resulting in a fall in smoking prevalence. However, neither has been sustained suggesting the need for additional tobacco control measures and ongoing support.</p&gt

A geometric network model of intrinsic grey-matter connectivity of the human brain

Network science provides a general framework for analysing the large-scale brain networks that naturally arise from modern neuroimaging studies, and a key goal in theoretical neuro- science is to understand the extent to which these neural architectures influence the dynamical processes they sustain. To date, brain network modelling has largely been conducted at the macroscale level (i.e. white-matter tracts), despite growing evidence of the role that local grey matter architecture plays in a variety of brain disorders. Here, we present a new model of intrinsic grey matter connectivity of the human connectome. Importantly, the new model incorporates detailed information on cortical geometry to construct ‘shortcuts’ through the thickness of the cortex, thus enabling spatially distant brain regions, as measured along the cortical surface, to communicate. Our study indicates that structures based on human brain surface information differ significantly, both in terms of their topological network characteristics and activity propagation properties, when compared against a variety of alternative geometries and generative algorithms. In particular, this might help explain histological patterns of grey matter connectivity, highlighting that observed connection distances may have arisen to maximise information processing ability, and that such gains are consistent with (and enhanced by) the presence of short-cut connections

Allele-specific miRNA-binding analysis identifies candidate target genes for breast cancer risk

Most breast cancer (BC) risk-associated single-nucleotide polymorphisms (raSNPs) identified in genome-wide association studies (GWAS) are believed to cis-regulate the expression of genes. We hypothesise that cis-regulatory variants contributing to disease risk may be affecting microRNA (miRNA) genes and/or miRNA binding. To test this, we adapted two miRNA-binding prediction algorithms-TargetScan and miRanda-to perform allele-specific queries, and integrated differential allelic expression (DAE) and expression quantitative trait loci (eQTL) data, to query 150 genome-wide significant ( P≤5×10-8 ) raSNPs, plus proxies. We found that no raSNP mapped to a miRNA gene, suggesting that altered miRNA targeting is an unlikely mechanism involved in BC risk. Also, 11.5% (6 out of 52) raSNPs located in 3'-untranslated regions of putative miRNA target genes were predicted to alter miRNA::mRNA (messenger RNA) pair binding stability in five candidate target genes. Of these, we propose RNF115, at locus 1q21.1, as a strong novel target gene associated with BC risk, and reinforce the role of miRNA-mediated cis-regulation at locus 19p13.11. We believe that integrating allele-specific querying in miRNA-binding prediction, and data supporting cis-regulation of expression, improves the identification of candidate target genes in BC risk, as well as in other common cancers and complex diseases.Funding Agency Portuguese Foundation for Science and Technology CRESC ALGARVE 2020 European Union (EU) 303745 Maratona da Saude Award DL 57/2016/CP1361/CT0042 SFRH/BPD/99502/2014 CBMR-UID/BIM/04773/2013 POCI-01-0145-FEDER-022184info:eu-repo/semantics/publishedVersio

The more things change ... the more things change: developmental plasticity of tumor-initiating mammary epithelial cells

In our haste to find and eliminate breast cancer stem cells, it appears as though we may have missed something. Contrary to current thought, a recent paper by Meyer and colleagues demonstrates developmental plasticity of breast cancer cells with respect to the CD24 cell surface marker, such that CD44pos; CD24pos and CD44pos; CD24low/- cells are able to give rise to one another in an activin/nodal-dependent manner, and that cells derived from single cells of either phenotype are capable of forming tumors as xenografts. If confirmed clinically, these data imply that simply targeting the CD44pos; CD24low/- breast cancer stem cell for breast cancer treatment may be destined to fail unless this plasticity is taken into account and prevented

Into the UV: The Atmosphere of the Hot Jupiter HAT-P-41b Revealed

For solar system objects, ultraviolet spectroscopy has been critical in identifying sources of stratospheric heating and measuring the abundances of a variety of hydrocarbon and sulfur-bearing species, produced via photochemical mechanisms, as well as oxygen and ozone. To date, fewer than 20 exoplanets have been probed in this critical wavelength range (0.2–0.4 μm). Here we use data from Hubble's newly implemented WFC3 UVIS G280 grism to probe the atmosphere of the hot Jupiter HAT-P-41b in the ultraviolet through optical in combination with observations at infrared wavelengths. We analyze and interpret HAT-P-41b's 0.2–5.0 μm transmission spectrum using a broad range of methodologies including multiple treatments of data systematics as well as comparisons with atmospheric forward, cloud microphysical, and multiple atmospheric retrieval models. Although some analysis and interpretation methods favor the presence of clouds or potentially a combination of Na, VO, AlO, and CrH to explain the ultraviolet through optical portions of HAT-P-41b's transmission spectrum, we find that the presence of a significant H− opacity provides the most robust explanation. We obtain a constraint for the abundance of H−, $\mathrm{log}({{\rm{H}}}^{-})=-8.65\pm 0.62$, in HAT-P-41b's atmosphere, which is several orders of magnitude larger than predictions from equilibrium chemistry for a ~1700–1950 K hot Jupiter. We show that a combination of photochemical and collisional processes on hot hydrogen-dominated exoplanets can readily supply the necessary amount of H− and suggest that such processes are at work in HAT-P-41b and the atmospheres of many other hot Jupiters

Crack formation and prevention in colloidal drops

Crack formation is a frequent result of residual stress release from colloidal films made by the evaporation of colloidal droplets containing nanoparticles. Crack prevention is a significant task in industrial applications such as painting and inkjet printing with colloidal nanoparticles. Here, we illustrate how colloidal drops evaporate and how crack generation is dependent on the particle size and initial volume fraction, through direct visualization of the individual colloids with confocal laser microscopy. To prevent crack formation, we suggest use of a versatile method to control the colloid-polymer interactions by mixing a nonadsorbing polymer with the colloidal suspension, which is known to drive gelation of the particles with short-range attraction. Gelation-driven crack prevention is a feasible and simple method to obtain crack-free, uniform coatings through drying-mediated assembly of colloidal nanoparticlesopen0

Computer-Based Interventions for Problematic Alcohol Use:a Review of Systematic Reviews

PURPOSE: The aim of this review is to provide an overview of knowledge and knowledge gaps in the field of computer-based alcohol interventions by (1) collating evidence on the effectiveness of computer-based alcohol interventions in different populations and (2) exploring the impact of four specified moderators of effectiveness: therapeutic orientation, length of intervention, guidance and trial engagement.  METHODS: A review of systematic reviews of randomized trials reporting on effectiveness of computer-based alcohol interventions published between 2005 and 2015.  RESULTS: Fourteen reviews met the inclusion criteria. Across the included reviews, it was generally reported that computer-based alcohol interventions were effective in reducing alcohol consumption, with mostly small effect sizes. There were indications that longer, multisession interventions are more effective than shorter or single session interventions. Evidence on the association between therapeutic orientation of an intervention, guidance or trial engagement and reductions in alcohol consumption is limited, as the number of reviews addressing these themes is low. None of the included reviews addressed the association between therapeutic orientation, length of intervention or guidance and trial engagement.  CONCLUSIONS: This review of systematic reviews highlights the mostly positive evidence supporting computer-based alcohol interventions as well as reveals a number of knowledge gaps that could guide future research in this field

Mapping Exoplanets

The varied surfaces and atmospheres of planets make them interesting places to live, explore, and study from afar. Unfortunately, the great distance to exoplanets makes it impossible to resolve their disk with current or near-term technology. It is still possible, however, to deduce spatial inhomogeneities in exoplanets provided that different regions are visible at different times---this can be due to rotation, orbital motion, and occultations by a star, planet, or moon. Astronomers have so far constructed maps of thermal emission and albedo for short period giant planets. These maps constrain atmospheric dynamics and cloud patterns in exotic atmospheres. In the future, exo-cartography could yield surface maps of terrestrial planets, hinting at the geophysical and geochemical processes that shape them.Comment: Updated chapter for Handbook of Exoplanets, eds. Deeg & Belmonte. 17 pages, including 6 figures and 4 pages of reference