Robust, flexible, and scalable tests for Hardy-Weinberg Equilibrium across diverse ancestries

Traditional Hardy-Weinberg equilibrium (HWE) tests (the χ2 test and the exact test) have long been used as a metric for evaluating genotype quality, as technical artifacts leading to incorrect genotype calls often can be identified as deviations from HWE. However, in datasets comprised of individuals from diverse ancestries, HWE can be violated even without genotyping error, complicating the use of HWE testing to assess genotype data quality. In this manuscript, we present the Robust Unified Test for HWE (RUTH) to test for HWE while accounting for population structure and genotype uncertainty, and evaluate the impact of population heterogeneity and genotype uncertainty on the standard HWE tests and alternative methods using simulated and real sequence datasets. Our results demonstrate that ignoring population structure or genotype uncertainty in HWE tests can inflate false positive rates by many orders of magnitude. Our evaluations demonstrate different tradeoffs between false positives and statistical power across the methods, with RUTH consistently amongst the best across all evaluations. RUTH is implemented as a practical and scalable software tool to rapidly perform HWE tests across millions of markers and hundreds of thousands of individuals while supporting standard VCF/BCF formats. RUTH is publicly available at https://www.github.com/statgen/ruth

Far Infrared Prperties of M Dwarfs

We report the mid- and far-infrared properties of nearby M dwarfs. Spitzer/MIPS measurements were obtained for a sample of 62 stars at 24 um, with subsamples of 41 and 20 stars observed at 70 um and 160 um respectively. We compare the results with current models of M star photospheres and look for indications of circumstellar dust in the form of significant deviations of K-[24 um] colors and 70 um / 24 um flux ratios from the average M star values. At 24 um, all 62 of the targets were detected; 70 um detections were achieved for 20 targets in the subsample observed; and no detections were seen in the 160 um subsample. No clear far-infrared excesses were detected in our sample. The average far infrared excess relative to the photospheric emission of the M stars is at least four times smaller than the similar average for a sample of solar-type stars. However, this limit allows the average fractional infrared luminosity in the M-star sample to be similar to that for more massive stars. We have also set low limits for the maximum mass of dust possible around our stars.Comment: 28 pages, 4 figures, to be published in The Astrophysical Journa

The Chemical Composition of Carbon-Rich, Very Metal-Poor Stars: A New Class of Mildly Carbon-Rich Objects Without Excess of Neutron-Capture Elements

We report on an analysis of the chemical composition of five carbon-rich, very metal-poor stars based on high-resolution spectra. One star, CS22948-027, exhibits very large overabundances of carbon, nitrogen, and the neutron-capture elements, as found in the previous study of Hill et al.. This result may be interpreted as a consequence of mass transfer from a binary companion that previously evolved through the asymptotic giant branch stage. By way of contrast, the other four stars we investigate exhibit no overabundances of barium ([Ba/Fe]<0), while three of them have mildly enhanced carbon and/or nitrogen ([C+N]+1). We have been unable to determine accurate carbon and nitrogen abundances for the remaining star (CS30312-100). These stars are rather similar to the carbon-rich, neutron-capture-element-poor star CS22957-027 discussed previously by Norris et al., though the carbon overabundance in this object is significantly larger ([C/Fe]=+2.2). Our results imply that these carbon-rich objects with ``normal'' neutron-capture element abundances are not rare among very metal-deficient stars. One possible process to explain this phenomenon is as a result of helium shell flashes near the base of the AGB in very low-metallicity, low-mass (M~< 1M_sun) stars, as recently proposed by Fujimoto et al.. The moderate carbon enhancements reported herein ([C/Fe]+1) are similar to those reported in the famous r-process-enhanced star CS22892-052. We discuss the possibility that the same process might be responsible for this similarity, as well as the implication that a completely independent phenomenon was responsible for the large r-process enhancement in CS22892-052.Comment: 53 pages, 8 figures, to appear in Ap

Expansion of the calcium hypothesis of brain aging and Alzheimer&apos;s disease: minding the store

-dependent processes and, through somewhat different pathways, in accelerated functional decline during aging and AD

Remote Sensing and Estimation

Contains table of contents for Section 4, and reports on six research projects.MIT Lincoln Laboratory Agreement CX-19383MIT Lincoln Laboratory Agreement BX-6178MIT Lincoln Laboratory Agreement BX-6433National Aeronautics and Space Administration/Goddard Space Flight Center Grant NAS5-31376National Aeronautics and Space Administration/Goddard Space Flight Center Grant NAG5-10MIT Leaders for Manufacturing Progra

Effect of an 860-m thick, cold, freshwater aquifer on geothermal potential along the axis of the eastern Snake River Plain, Idaho

A 1912-m exploration corehole was drilled along the axis of the eastern Snake River Plain, Idaho. Two temperature logs run on the corehole display an obvious inflection point at about 960 m. Such behavior is indicative of downward fluid flow in the wellbore. The geothermal gradient above 935 m is 4.5 °C/km, while the gradient is 72–75 °C/km from 980 to 1440 m. Projecting the higher gradients upward to where they intersect the lower gradient on the temperature logs places the bottom of the cold, freshwater Snake River Plain aquifer, which suppresses the geothermal gradient at this location, at least 860 m below the surface. The average heat flow for the corehole between 983 and 1550 m is 132 mW/m2. Although the maximum bottom-hole temperature extrapolated from a measured time–temperature curve was only 59.3 °C, geothermometers suggest an equilibrium temperature on the order of 125–140 °C based on a single fluid sample from 1070 m. Furthermore, below 960 m the basalt core shows obvious signs of alteration, including a distinct color change, the formation of smectite clay, and the presence of secondary minerals filling vesicles and fracture zones. This alteration boundary could act as an effective cap or seal for a hot-water geothermal system

Evaluation of the Geothermal Potential of the Western Snake River Plain Based on a Deep Corehole on the Mountain Home AFB Near Mountain Home, Idaho

A geothermal exploration corehole was drilled to a total depth of 1821.5 m on the Mountain Home Air Force Base near Mountain Home, Idaho. The corehole was used to collect an unusually large amount of data, including uniaxial compressive stress (UCS) experiments on core samples, to evaluate the geothermal potential of the western Snake River Plain. In addition, unlike many exploration holes in this region, a fluid entry was encountered at 1745.3 m and flowed artesian to the surface. A maximum temperature of 149.4 °C was calculated for the entry. A temperature log run on the corehole from 3 to 1675 m is nearly linear with little variation. The average geothermal gradient is 73 °C/km, and the average heat flow between 200 and 1500 m is 102 ± 15 mW/m2. Chemical analyses of a sample from the fluid entry suggest that a significant proportion of the water is not meteoric. Five geothermometers show equilibrium temperature in the range of 133–157 °C. Furthermore, based on the unconfined UCS experiments on basalt core samples, a brittle unit was found to comprise the fractured reservoir that the geothermal water flows from, while an overlying ductile unit acts as a hydrothermal caprock. This implies that the reservoir/caprock pair may be a target for future exploration wells drilled to delineate the extent of the potential resource and the boundaries of the connected fracture network

In vitro modeling of nonhypoxic cold ischemia–reperfusion simulating lung transplantation

Although anoxia/reoxygenation of cultured cells has been employed to model lung ischemia-reperfusion injury (IRI), this does not accurately mimic events experienced by lung cells while a lung is retrieved from a donor, stored, and transplanted. We developed an in vitro model of non-hypoxic IRI to simulate these events

Anaesthetists stress is induced by patient ASA grade and may impair non-technical skills during intubation

BackgroundThe aims of this study were to determine if patient ASA grade was associated with increased stress in anaesthetists with a subsequent effect on non-technical skills.MethodsStress was measured using a validated objective (heart rate variability or heart rate) and subjective tool. We studied eight consultant anaesthetists at baseline (rest) and during 16 episodes of intubation with an ASA 1 or 2 patient vs. an ASA 3 or 4 patient. The primary outcome for the study was objective and subjective stress between both patient groups. Secondary outcomes were non-technical skill ratings and the association between stress measurements.ResultsASA 3 or 4 patients were associated with increases in objective stress when compared to baseline (mean 4.6 vs. 6.7; P = 0.004). However, ASA 1 or 2 patients were not associated with increases in stress when compared to baseline (mean 4.6 vs. 4.7; P = 1). There was no significant difference in subjective stress between the groups (P = 0.18). Objective stress negatively affected situational awareness (P = 0.03) and decision-making (P = 0.03); however, these did not decline to a clinically significant threshold. Heart rate variability (r = 0.60; P = 0.002) better correlated with subjective stress when compared to heart rate (r = 0.30; P = 0.15). Agreement between raters for Anaesthetic Non-Technical Skills (ANTS) scores was acceptable (ICC = 0.51; P = 0.003).ConclusionThis study suggests that higher patient ASA grade can increase stress in anaesthetists, which may impair non-technical skills