Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

The choice for EU theorists: Establishing a common framework for analysis

European Union (EU) studies have entered a highly contentious and, arguably, creative phase. A range of theoretical perspectives, seemingly quite highly differentiated from one another, now compete for influence and lsquospacersquo. However, the questions remain: is EU studies developing theories which are truly competing theories? Or is it developing theories that do not compete so much as they aim to explain distinctly different pieces of the EU puzzle? This paper responds directly to these two questions, while reviewing recent literature on EU governance. It argues, first, that we lack theories of EU governance that are true rivals; and, second, that leading models explain different outcomes at different levels in a multi-level system of governance. The result is somewhat phoney debates between compatible theories masquerading as rivals, and between lsquocomparative politicsrsquo and lsquointernational relationsrsquo approaches. Above all, perhaps, we find middle range theories posing as general or lsquometa-theoriesrsquo. In the absence of a plausible general theory of EU governance, theorists must choose precisely which type of outcome theywish to explain

Open data from the third observing run of LIGO, Virgo, KAGRA, and GEO

The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in 2019 April and lasting six months, O3b starting in 2019 November and lasting five months, and O3GK starting in 2020 April and lasting two weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main data set, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages

Dasar-dasar analisis geoteknik

XVI+426hlm.;23c

Effects of chronic herbivory and historic land use on population structure of a forest perennial, Trillium catesbaei

Question: How have long-term herbivory and past land use impacted the population structure of Trillium catesbaei, a long-lived rhizomatous herb? Location: Western Great Smoky Mountains National Park, Tennessee, USA. Methods: We examined T. catesbaei populations at three sites: (1) Cades Cove (CC), an area of intensive historic land use that has been maintained as open fields and woodlots with a history of chronic deer herbivory, (2) Whiteoak Sink (WOS), a reference area with similar land-use history, geology, and soils that has succeeded to closed-canopy forest with relatively low levels of deer herbivory, and (3) Leadbetter Ridge (LBR), an area of primary forest that has never received significant anthropogenic disturbance. Trillium catesbaei is the most common Trillium species at the three study sites, but smaller in stature, shorter lived, and more of a habitat generalist. Results: Chronic herbivory in CC has created a highly-truncated age structure with no plants older than 9 years, while plant ages at the other sites were more evenly distributed. Compared to WOS, plants in CC were younger at a given height and more likely to flower when younger. Across all life stages, populations at CC contained 68 x fewer plants than WOS. The age structures of WOS and LBR were similar. Compared to published age estimates for other Trillium species, our results suggest that T. catesbaei is relatively short lived within the genus. Conclusions: Chronic herbivory had pronounced effects on the population structure of a perennial herb. Other long-lived herbaceous species may exhibit similar truncated age structures and flowering by younger and smaller plants. Habitat generalist species within a genus, such as T. catesbaei, that are able to reproduce more quickly may persist longer under chronic herbivory. However, chronic herbivory has likely caused the loss of herbaceous species from CC and may eventually cause the local extirpation of T. catesbaei populations. © IAVS; Opulus Press