Alzheimer's disease is a debilitating and highly heritable neurological condition. As such, genetic studies have sought to understand the genetic architecture of Alzheimer's disease since the 1990s, ...with successively larger genome-wide association studies (GWAS) and meta-analyses. These studies started with a small sample size of 1086 individuals in 2007, which was able to identify only the APOE locus. In 2013, the International Genomics of Alzheimer's Project (IGAP) did a meta-analysis of all existing GWAS using data from 74 046 individuals, which stood as the largest Alzheimer's disease GWAS until 2018. This meta-analysis discovered 19 susceptibility loci for Alzheimer's disease in populations of European ancestry.
Three new Alzheimer's disease GWAS published in 2018 and 2019, which used larger sample sizes and proxy phenotypes from biobanks, have substantially increased the number of known susceptibility loci in Alzheimer's disease to 40. The first, an updated GWAS from IGAP, included 94 437 individuals and discovered 24 susceptibility loci. Although IGAP sought to increase sample size by recruiting additional clinical cases and controls, the two other studies used parental family history of Alzheimer's disease to define proxy cases and controls in the UK Biobank for a genome-wide association by proxy, which was meta-analysed with data from GWAS of clinical Alzheimer's disease to attain sample sizes of 388 324 and 534 403 individuals. These two studies identified 27 and 29 susceptibility loci, respectively. However, the three studies were not independent because of the large overlap in their participants, and interpretation can be challenging because different variants and genes were highlighted by each study, even in the same locus. Furthermore, neither the variant with the strongest Alzheimer's disease association nor the nearest gene are necessarily causal. This situation presents difficulties for experimental studies, drug development, and other future research.
The ultimate goal of understanding the genetic architecture of Alzheimer's disease is to characterise novel biological pathways that underly Alzheimer's disease pathogenesis and to identify novel drug targets. GWAS have successfully contributed to the characterisation of the genetic architecture of Alzheimer's disease, with the identification of 40 susceptibility loci; however, this does not equate to the discovery of 40 Alzheimer's disease genes. To identify Alzheimer's disease genes, these loci need to be mapped to variants and genes through functional genomics studies that combine annotation of variants, gene expression, and gene-based or pathway-based analyses. Such studies are ongoing and have validated several genes at Alzheimer's disease loci, but greater sample sizes and cell-type specific data are needed to map all GWAS loci.
In the past five years, the number of known double neutron stars (DNSs) in the Milky Way has roughly doubled. We argue that the observed sample can be split into three distinct subpopulations based ...on their orbital characteristics: (i) short-period, low-eccentricity binaries; (ii) wide binaries; and (iii) short-period, high-eccentricity binaries. These subpopulations also exhibit distinct spin period and spindown rate properties. We focus on subpopulation (iii), which contains the Hulse-Taylor binary. Contrary to previous analysis, we demonstrate that, if they are the product of isolated binary evolution, the Porb and e distribution of these systems requires that the second-born NSs must have been formed with small natal kicks ( 25 km s−1) and have pre-SN masses narrowly distributed around 3.2 M . These constraints challenge binary evolution theory and further predict closely aligned spin and orbital axes, inconsistent with the Hulse-Taylor binary's measured spin-orbit misalignment angle of 20°. Motivated by the similarity of these DNSs to B2127+11C, a DNS residing in the globular cluster M15, we argue that this subpopulation is consistent with being formed in, and then ejected from, globular clusters. This scenario provides a pathway for the formation and merger of DNSs in stellar environments without recent star formation, as observed in the host galaxy population of short gamma-ray bursts and the recent detection by LIGO of a merging DNS in an old stellar population.
In patients with traumatic brain injury, hypothermia can reduce intracranial hypertension. The benefit of hypothermia on functional outcome is unclear.
We randomly assigned adults with an ...intracranial pressure of more than 20 mm Hg despite stage 1 treatments (including mechanical ventilation and sedation management) to standard care (control group) or hypothermia (32 to 35°C) plus standard care. In the control group, stage 2 treatments (e.g., osmotherapy) were added as needed to control intracranial pressure. In the hypothermia group, stage 2 treatments were added only if hypothermia failed to control intracranial pressure. In both groups, stage 3 treatments (barbiturates and decompressive craniectomy) were used if all stage 2 treatments failed to control intracranial pressure. The primary outcome was the score on the Extended Glasgow Outcome Scale (GOS-E; range, 1 to 8, with lower scores indicating a worse functional outcome) at 6 months. The treatment effect was estimated with ordinal logistic regression adjusted for prespecified prognostic factors and expressed as a common odds ratio (with an odds ratio <1.0 favoring hypothermia).
We enrolled 387 patients at 47 centers in 18 countries from November 2009 through October 2014, at which time recruitment was suspended owing to safety concerns. Stage 3 treatments were required to control intracranial pressure in 54% of the patients in the control group and in 44% of the patients in the hypothermia group. The adjusted common odds ratio for the GOS-E score was 1.53 (95% confidence interval, 1.02 to 2.30; P=0.04), indicating a worse outcome in the hypothermia group than in the control group. A favorable outcome (GOS-E score of 5 to 8, indicating moderate disability or good recovery) occurred in 26% of the patients in the hypothermia group and in 37% of the patients in the control group (P=0.03).
In patients with an intracranial pressure of more than 20 mm Hg after traumatic brain injury, therapeutic hypothermia plus standard care to reduce intracranial pressure did not result in outcomes better than those with standard care alone. (Funded by the National Institute for Health Research Health Technology Assessment program; Current Controlled Trials number, ISRCTN34555414.).
Context. Various binary black hole formation channels have been proposed since the first gravitational event GW150914 was discovered by the Advanced Laser Interferometer Gravitational-Wave ...Observatory (AdLIGO). The immediate progenitor of the binary black hole is a close binary system composed of a black hole and a helium star, which can be the outcome of the classical isolated binary evolution through the common envelope, or alternatively of the massive close evolution through chemically homogeneous channel. Aims. We study the spin angular momentum evolution of the helium star in order to constrain the spin of the second-born black hole. This work focuses on the common envelope formation channel, however, some of our conclusions are also relevant for the chemically homogeneous evolution channel. Methods. We perform detailed stellar structure and binary evolution calculations that take into account, mass-loss, internal differential rotation, and tidal interactions between the helium star and the black hole companion, where we also calculate the strength of the tidal interactions from first principles based on the structure of the helium stars. We systematically explore the parameter space of initial binary properties, including initial black hole and helium star masses, initial rotation of the helium star as well as metallicity. Results. We argue that the natal spin of the first-born black hole through the common envelope scenario is negligible (≲0.1), and therefore the second-born black hole’s spin dominates the measured effective spin, χeff, from gravitational wave events of double black hole mergers. We find that tides can be only important when orbital periods are shorter than 2 days. Upon core collapse, the helium star produces a black hole (the second-born black hole in the system) with a spin that can span the entire range from zero to maximally spinning. We show that the bimodal distribution of the spin of the second-born black hole obtained in recent papers is mainly due to oversimplifying assumptions. We find an anti-correlation between the merging timescale of the two black holes, Tmerger, and the effective spin χeff. Finally, we provide new prescriptions for the tidal coefficient E2 for both H-rich and the He-rich stars. Conclusions. To understand the spin of the second-born black hole, careful treatment of both tides and stellar winds is needed. We predict that, with future improvements to AdLIGO’s sensitivity, the sample of merging binary black hole systems will show an overdensity of sources with positive but small χeff originating from lower-mass black hole mergers born at low redshift.
The African American Policy Forum and the Center for Intersectionality and Social Policy Studies states, "The risks that Black and other girls of color confront rarely receive the full attention of ...researchers, advocates, policymaker and funders." The limited awareness of the challenges that Black girls face perpetuates the mischaracterization of their attitudes, abilities, and achievement. Thus, school becomes an inhospitable place where Black girls receive mixed messages about femininity and goodness and are held to unreasonable standards. This study explores how Black girls describe and understand their school experiences as racialized and gendered and the ways a conversation space allows Black girls' meaning making about and critical examination of individual and collective schooling experiences.
Abstract
The gravitational pull of an unseen companion to a luminous star is well known to cause deviations to the parallax and proper motion of a star. In a previous paper in this series, we argue ...that the astrometric mission Gaia can identify long-period binaries by precisely measuring these arcs. An arc in a star’s path can also be caused by a flyby: a hyperbolic encounter with another massive object. We quantify the apparent acceleration over time induced by a companion star as a function of the impact parameter, velocity of interaction, and companion mass. In principle, Gaia could be used to astrometrically identify the contribution of massive compact halo objects to the local dark matter potential of the Milky Way. However, after quantifying their rate and Gaia’s sensitivity, we find that flybys are so rare that Gaia will probably never observe one. Therefore, every star in the Gaia database exhibiting astrometric acceleration is likely in a long-period binary with another object. Nevertheless, we show how intermediate-mass black holes, if they exist in the local stellar neighborhood, can induce anomalously large accelerations on stars.
In astrometric binaries, the presence of a dark, unseen star can be inferred from the gravitational pull it induces on its luminous binary companion. While the orbit of such binaries can be ...characterized with precise astrometric measurements, constraints made from astrometry alone are not enough to measure the component masses. In this work, we determine the precision with which Gaia can astrometrically measure the orbits and-with additional observations-the component masses, for luminous stars hosting hidden companions. Using realistic mock Gaia observations, we find that Gaia can precisely measure the orbits of binaries hosting hidden brown dwarfs out to tens of parsecs and hidden white dwarf and neutron star companions at distances as far as several hundred parsecs. Heavier black hole companions may be measured out to 1 kpc or farther. We further determine how orbital period affects this precision, finding that Gaia can characterize orbits with periods as short as 10 days and as long as a few 103 days, with the best measured orbits having periods just short of Gaia's mission lifetime. Extending Gaia's nominal five-year mission lifetime by an additional five years not only allows for the measurement of longer period orbits, but those longer period binaries can be seen at even greater distances.
Abstract
Filaments in Herschel molecular cloud images are found to exhibit a ‘characteristic width’. This finding is in tension with spatial power spectra of the data, which show no indication of ...this characteristic scale. We demonstrate that this discrepancy is a result of the methodology adopted for measuring filament widths. First, we perform the previously used analysis technique on artificial scale-free data, and obtain a peaked width distribution of filament-like structures. Next, we repeat the analysis on three Herschel maps and reproduce the narrow distribution of widths found in previous studies – when considering the average width of each filament. However, the distribution of widths measured at all points along a filament spine is broader than the distribution of mean filament widths, indicating that the narrow spread (interpreted as a ‘characteristic’ width) results from averaging. Furthermore, the width is found to vary significantly from one end of a filament to the other. Therefore, the previously identified peak at 0.1 pc cannot be understood as representing the typical width of filaments. We find an alternative explanation by modelling the observed width distribution as a truncated power-law distribution, sampled with uncertainties. The position of the peak is connected to the lower truncation scale and is likely set by the choice of parameters used in measuring filament widths. We conclude that a ‘characteristic’ width of filaments is not supported by the available data.
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