Twelve loci provide insights into the genetic basis of lacunar stroke and small vessel disease: a meta-analysis of genome-wide association studies

We did a pooled analysis of data from newly recruited patients with an MRI-confirmed diagnosis of lacunar stroke and existing genome-wide association studies (GWAS). Patients were recruited from hospitals in the UK as part of the UK DNA Lacunar Stroke studies 1 and 2 and from collaborators within the International Stroke Genetics Consortium. Cases and controls were stratified by ancestry and two meta-analyses were done: a European ancestry analysis, and a transethnic analysis that included all ancestry groups. We also did a multi-trait analysis of GWAS, in a joint analysis with a study of cerebral white matter hyperintensities (an aetiologically related radiological trait), to find additional genetic associations. We did a transcriptome-wide association study (TWAS) to detect genes for which expression is associated with lacunar stroke; identified significantly enriched pathways using multi-marker analysis of genomic annotation; and evaluated cardiovascular risk factors causally associated with the disease using mendelian randomisation

An investigation of wing buffeting response at subsonic and transonic speeds. Phase 2: F-111A flight data analysis. Volume 1: Summary of technical approach, results and conclusions

A detailed investigation of the flight buffeting response of the F-111A was performed in two phases. In Phase 1 stochastic analysis techniques were applied to wing and fuselage responses for maneuvers flown at subsonic speeds and wing leading edge sweep of 26 degrees. Power spectra and rms values were obtained. This report gives results of Phase 2 where the analyses were extended to include maneuvers flown at wing leading edge sweep values of 50 and 75.5 degrees at subsonic and supersonic speeds and the responses examined were expanded to include vertical shear, bending moment, and hingeline torque of the left and right horizontal tails. Power spectra, response time histories, variations of rms response with angle of attack and effects of wing sweep and Mach number are presented and discussed. Some Phase 1 results are given for comparison purposes

Groundwater Availability of the Northern High Plains Aquifer in Colorado, Kansas, Nebraska, South Dakota, and Wyoming

The Northern High Plains aquifer underlies about 93,000 square miles of Colorado, Kansas, Nebraska, South Dakota, and Wyoming and is the largest subregion of the nationally important High Plains aquifer. Irrigation, primarily using groundwater, has supported agricultural production since before 1940, resulting in nearly $50 billion in sales in 2012. In 2010, the High Plains aquifer had the largest groundwater withdrawals of any major aquifer system in the United States.Nearly one-half of those withdrawals were from the Northern High Plains aquifer, which has little hydrologic interaction with parts of the aquifer farther south. Land-surface elevation ranges from more than 7,400 feet (ft) near the western edge to less than 1,100 ft near the eastern edge. Major streams primarily flow west to east and include the Big Blue River, Elkhorn River, Loup River, Niobrara River, Republican Riverand Platte River with its two forks—the North Platte River and South Platte River. Population in the Northern High Plains aquifer area is sparse with only 2 cities having a population greater than 30,000.Droughts across much of the area from 2001 to 2007, combined with recent (2004–18) legislation, have heightened concerns regarding future groundwater availability and highlighted the need for science-based water-resource management. Groundwater models with the capability to provide forecasts of groundwater availability and related stream base flows from the Northern High Plains aquifer were published recently (2016) and were used to analyze groundwater avail-ability. Stream base flows are generally the dominant component of total streamflow in the Northern High Plains aquifer, and total streamflows or shortages thereof define conjunctive management triggers, at least in Nebraska. Groundwater availability was evaluated through comparison of aquifer-scale water budgets compared for periods before and after major groundwater development and across selected future fore-casts. Groundwater-level declines and the forecast amount of groundwater in storage in the aquifer also were examined

Initial Acoustoelastic Measurements in Olivine: Investigating the Effect of Stress on P- and S-Wave Velocities

It is well known that elasticity is a key physical property in the determination of the structure and composition of the Earth and provides critical information for the interpretation of seismic data. This study investigates the stress-induced variation in elastic wave velocities, known as the acoustoelastic effect, in San Carlos olivine. A recently developed experimental ultrasonic acoustic system, the Directly Integrated Acoustic System Combined with Pressure Experiments (DIASCoPE), was used with the D-DIA multi-anvil apparatus to transmit ultrasonic sound waves and collect the reflections. We use the DIASCoPE to obtain longitudinal (P) and shear (S) elastic wave velocities from San Carlos olivine at pressures ranging from 3.2–10.5 GPa and temperatures from 450–950°C which we compare to the stress state in the D-DIA derived from synchrotron X-ray diffraction. We use elastic-plastic self-consistent (EPSC) numerical modeling to forward model X-ray diffraction data collected in D-DIA experiments to obtain the macroscopic stress on our sample. We can observe the relationship between the relative elastic wave velocity change (ΔV/V) and macroscopic stress to determine the acoustoelastic constants, and interpret our observations using the linearized first-order equation based on the model proposed by Hughes and Kelly (1953), https://doi.org/10.1103/physrev.92.1145. This work supports the presence of the acoustoelastic effect in San Carlos olivine, which can be measured as a function of pressure and temperature. This study will aid in our understanding of the acoustoelastic effect and provide a new experimental technique to measure the stress state in elastically deformed geologic materials at high pressure conditions

Direct imaging of short-range order and its impact on deformation in Ti-6Al.

Chemical short-range order (SRO) within a nominally single-phase solid solution is known to affect the mechanical properties of alloys. While SRO has been indirectly related to deformation, direct observation of the SRO domain structure, and its effects on deformation mechanisms at the nanoscale, has remained elusive. Here, we report the direct observation of SRO in relation to deformation using energy-filtered imaging in a transmission electron microscope (TEM). The diffraction contrast is enhanced by reducing the inelastically scattered electrons, revealing subnanometer SRO-enhanced domains. The destruction of these domains by dislocation planar slip is observed after ex situ and in situ TEM mechanical testing. These results confirm the impact of SRO in Ti-Al alloys on the scale of angstroms. The direct confirmation of SRO in relationship to dislocation plasticity in metals can provide insight into how the mechanical behavior of concentrated solid solutions by the material's thermal history

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

Helping or Hurting?: Understanding Women’s Perceptions of Male Allies

In the past decade, organizational scholars have begun to explore the role of allies in mitigating workplace discrimination toward women and members of minority groups. However, this nascent literature has, to this point, failed to consider the perspective of targets of ally behavior. That is, we do not yet know how targets of discrimination experience others’ intervention or advocacy. To begin to understand these issues, we examine target perceptions of allyship through a qualitative critical incident approach, asking women to describe experiences in which a man has effectively and ineffectively acted as an ally to them in the workplace. Our findings from surveying 100 women provide new insights regarding who engages in ally behaviors, what behaviors these allies enact, when and where the behaviors take place, and why participants believed their male ally engaged in this behavior