Regolith of the crater floor units, Jezero crater, Mars: textures, composition, and implications for provenance

A multi-instrument study of the regolith of Jezero crater floor units by the Perseverance rover has identified three types of regolith: fine-grained, coarse-grained, and mixed-type. Mastcam-Z, Wide Angle Topographic Sensor for Operations and eNgineering, and SuperCam Remote Micro Imager were used to characterize the regolith texture, particle size, and roundedness where possible. Mastcam-Z multispectral and SuperCam laser-induced breakdown spectroscopy data were used to constrain the composition of the regolith types. Fine-grained regolith is found surrounding bedrock and boulders, comprising bedforms, and accumulating on top of rocks in erosional depressions. Spectral and chemical data show it is compositionally consistent with pyroxene and a ferric-oxide phase. Coarse-grained regolith consists of 1–2 mm well-sorted gray grains that are found concentrated around the base of boulders and bedrock, and armoring bedforms. Its chemistry and spectra indicate it is olivine-bearing, and its spatial distribution and roundedness indicate it has been transported, likely by saltation-induced creep. Coarse grains share similarities with the olivine grains observed in the Séítah formation bedrock, making that unit a possible source for these grains. Mixed-type regolith contains fine- and coarse-grained regolith components and larger rock fragments. The rock fragments are texturally and spectrally similar to bedrock within the Máaz and Séítah formations, indicating origins by erosion from those units, although they could also be a lag deposit from erosion of an overlying unit. The fine- and coarse-grained types are compared to their counterparts at other landing sites to inform global, regional, and local inputs to regolith formation within Jezero crater. The regolith characterization presented here informs the regolith sampling efforts underway by Perseverance

The Women's international study of long-duration oestrogen after menopause (WISDOM): a randomised controlled trial

BACKGROUND: At the time of feasibility work and final design of the trial there was no randomised control trial evidence for the long-term risks and benefits of hormone replacement therapy. Observational studies had suggested that long term use of estrogen was likely to be associated, amongst other things, with reduced risks of osteoporosis and ischaemic heart disease and increased risks of breast and endometrial cancer. Concomitant use of progestogens had been shown to protect against endometrial cancer, but there were few data showing how progestogen might affect estrogen actions on other conditions. Disease specific risks from observational studies suggested that, overall, long-term HRT was likely to be beneficial. Several studies showed that mortality from all causes was lower in HRT users than in non-users. Some secondary cardiovascular prevention trials were ongoing but evidence was also required for a range of outcomes in healthy women. The WISDOM trial was designed to compare combined estrogen and progestogen versus placebo, and estrogen alone versus combined estrogen and progestogen. During the development of WISDOM the Women's Health Initiative trial was designed, funded and started in the US. DESIGN: Randomised, placebo, controlled, trial. METHODS: The trial was set in general practices in the UK (384), Australia (94), and New Zealand (24). In these practices 284175 women aged 50–69 years were registered with 226282 potentially eligible. We sought to randomise 22300 postmenopausal women aged 50 – 69 and treat for ten years. The interventions were: conjugated equine estrogens, 0.625 mg orally daily; conjugated equine estrogens plus medroxyprogesterone acetate 2.5/5.0 mg orally daily; matched placebo. Primary outcome measures were: major cardiovascular disease, osteoporotic fractures, breast cancer and dementia. Secondary outcomes were: other cancers, all cause death, venous thromboembolism and cerebro-vascular disease. RESULTS: The trial was prematurely closed during recruitment following publication of early results from the Women's Health Initiative. At the time of closure, 56583 had been screened, 8980 entered run-in, and 5694 (26% of target of 22,300) randomised. Those women randomised had received a mean of one year of therapy, mean age was 62.8 years and total follow-up time was 6491 person years. DISCUSSION: The WISDOM experience leads to some simple messages. The larger a trial is the more simple it needs to be to ensure cost effective and timely delivery. When a trial is very costly and beyond the resources of one country, funders and investigators should make every effort to develop international collaboration with joint funding

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Hot atmospheres of galaxies, groups, and clusters of galaxies

Most of the ordinary matter in the local Universe has not been converted into stars but resides in a largely unexplored diffuse, hot, X-ray emitting plasma. It pervades the gravitational potentials of massive galaxies, groups and clusters of galaxies, as well as the filaments of the cosmic web. The physics of this hot medium, such as its dynamics, thermodynamics and chemical composition can be studied using X-ray spectroscopy in great detail. Here, we present an overview of the basic properties and discuss the self similarity of the hot "atmospheres" permeating the gravitational halos from the scale of galaxies, through groups, to massive clusters. Hot atmospheres are stabilised by the activity of supermassive black holes and, in many ways, they are of key importance for the evolution of their host galaxies. The hot plasma has been significantly enriched in heavy elements by supernovae during the period of maximum star formation activity, probably more than 10 billion years ago. High resolution X-ray spectroscopy just started to be able to probe the dynamics of atmospheric gas and future space observatories will determine the properties of the currently unseen hot diffuse medium throughout the cosmic web.Comment: Accepted for publication in the book "Reviews in Frontiers of Modern Astrophysics: From Space Debris to Cosmology" (eds Kabath, Jones and Skarka; publisher Springer Nature) funded by the European Union Erasmus+ Strategic Partnership grant "Per Aspera Ad Astra Simul" 2017-1-CZ01-KA203-03556

A saturated map of common genetic variants associated with human height.

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries

Body size in early life and risk of lymphoid malignancies and histological subtypes in adulthood

Abstract Risk of adult lymphoid malignancy is associated with recent adiposity. Some have reported apparent associations with adiposity in childhood or early adulthood, but whether these associations are independent of recent adiposity is unknown. Birth weight, body size at age 10 years, clothes size at age 20 years, and recent body mass index (BMI) were recorded in 745,273 UK women, mean age 60.1 (SD 4.9) at baseline, without prior cancer. They were followed for 11 years, during which time 5,765 lymphoid malignancies occurred. Using Cox regression, a higher risk of lymphoid malignancy was strongly associated with higher recent BMI (RR=1.33, 95%CI 1.17-1.51, for BMI 35+ vs <22.5 kg/m(2)), and this association remained essentially unchanged after adjustment for birth weight and body size at 10. Higher lymphoid malignancy risk was also associated with large size at birth, at age 10, and at age 20 years, but after adjustment for recent BMI, the significance of the associations with large size at birth and at age 10 years was sufficiently reduced that residual confounding by adult BMI could not be excluded; a weak association with large size at 20 years remained (adjusted RR =1.17, 95%CI 1.10-1.24 for large size at age 20 vs. medium or small size). We found no strong evidence of histological specificity in any of these associations. In conclusion, our findings suggest a possible role of adiposity throughout adulthood in the risk of lymphoid malignancy, but the independent contribution of body size at birth and during childhood appears to be small.We thank all the women who participated in the Million Women Study. The Million Women Study Collaborators are: Hayley Abbiss, Simon Abbott, Rupert Alison, Naomi Allen, Miranda Armstrong, Krys Baker, Angela Balkwill, Emily Banks, Isobel Barnes, Valerie Beral, Judith Black, Roger Blanks, Kathryn Bradbury, Anna Brown, Benjamin Cairns, Karen Canfell, Dexter Canoy, Andrew Chadwick, Francesca Crowe, Dave Ewart, Sarah Ewart, Lee Fletcher, Sarah Floud, Toral Gathani, Laura Gerrard, Adrian Goodill, Jane Green, Lynden Guiver, Michal Hozak, Isobel Lingard, Sau Wan Kan, Nicky Langston, Bette Liu, Kath Moser, Kirstin Pirie, Gillian Reeves, Keith Shaw, Emma Sherman, Helena Strange, Sian Sweetland, Sarah Tipper, Ruth Travis, Lyndsey Trickett, Lucy Wright, Owen Yang, Heather Young

Alcohol drinking, tobacco smoking and subtypes of haematological malignancy in the UK Million Women Study

ABSTRACT Background: Previous research suggests associations of lower alcohol intake and higher tobacco consumption with increased risks of haematological malignancy. The prospective Million Women Study provides sufficient power for reliable estimates of subtype-specific associations in women. Methods: Approximately 1.3 million middle-aged women were recruited in the United Kingdom during 1996–2001 and followed for death, emigration and cancer registration until 2009 (mean 10.3 years per woman); potential risk factors were assessed by questionnaire. Adjusted relative risks were estimated by Cox regression. Results: During follow-up, 9162 incident cases of haematological malignancy were recorded, including 7047 lymphoid and 2072 myeloid cancers. Among predominantly moderate alcohol drinkers, higher intake was associated with lower risk of lymphoid malignancies, in particular diffuse large B-cell lymphoma (relative risk 0.85 per 10 g alcohol per day (95% confidence interval 0.75–0.96)), follicular lymphoma (0.86 (0.76–0.98)) and plasma cell neoplasms (0.86 (0.77–0.96)). Among never- and current smokers, higher cigarette consumption was associated with increased risk of Hodgkin lymphoma (1.45 per 10 cigarettes per day (1.22–1.72)), mature T-cell malignancies (1.38 (1.10–1.73)) and myeloproliferative/myelodysplastic disease (1.42 (1.31–1.55)). Conclusion: These findings confirm and extend existing evidence for associations of subtypes of haematological malignancy with two common exposures in women

Age at menarche and risks of coronary heart and other vascular diseases in a large UK cohort

BACKGROUND: Early menarche has been associated with increased risk of coronary heart disease (CHD), but most studies were relatively small and could not assess risk across a wide range of menarcheal ages; few have examined associations with other vascular diseases. We examined CHD, cerebrovascular disease, and hypertensive disease risks by age at menarche in a large prospective study of UK women. METHODS AND RESULTS: In 1.2 million women (mean±SD age, 56±5 years) without previous heart disease, stroke, or cancer, menarcheal age was reported to be 13 years by 25%, ≤10 years by 4%, and ≥17 years by 1%. After 11.6 years of follow-up, 73 378 women had first hospitalization for or death from CHD, 25 426 from cerebrovascular disease, and 249 426 from hypertensive disease. Using Cox regression, we calculated relative risks for each vascular outcome by single year of menarcheal age. The relationship was U-shaped for CHD. Compared with women with menarche at 13 years, the adjusted relative risk for CHD for menarche at ≤10 years of age was 1.27 (95% confidence interval, 1.22-1.31; P<0.0001) and for menarche at ≥17 years of age was 1.23 (95% confidence interval, 1.16-1.30; P<0.0001). U-shaped relationships were also seen for cerebrovascular and hypertensive disease, although the magnitudes of these risks for early and late menarche were smaller than those for CHD. CONCLUSIONS: In this cohort, the relation of age at menarche to vascular disease risk was U shaped, with both early and late menarche being associated with increased risk. Associations were weaker for cerebrovascular and hypertensive disease than for CHD.This research was supported by Cancer Research UK (grant C570/A11692), the Medical Research Council (grant MR/K02700X/1), and the NHS Cancer Screening Program (reference No. R19220/CN002). Dr Cairns acknowledges support from the BHF Center of Research Excellence, Oxford, UK (British Heart Foundation grant RE/13/1/30181)

Body mass index and physical activity in relation to the incidence of hip fracture in postmenopausal women.

Hip fracture risk increases with physical inactivity and decreases with obesity but there is little information on their combined effects. We report on the separate and combined effects of body mass index (BMI) and physical activity on hospital admissions for hip fracture among postmenopausal women in a large prospective study of UK women. Self-reported information on body size, physical activity, and other relevant factors was collected in 1996-2001 and participants were followed for incident hip fractures by record linkage to NHS hospital admission data. Cox regression was used to calculate adjusted relative risks of hip fracture. Among 925 345 postmenopausal women followed for an average of 6.2 years, 2582 were admitted to hospital with an incident hip fracture. Hip fracture risk increased with decreasing BMI: compared to obese women (BMI 30+) relative risks were 1.71 (95%CI 1.47-1.97) for BMI 25.0-29.9kg/m(2) and 2.55 (95%CI 2.22-2.94) for BMI 20.0-24.9kg/m(2). The increase in fracture risk per unit decrease in BMI was significantly greater among lean women than among overweight women (p&lt;0.001). For women in every category of BMI, physical inactivity was associated with increased risk of hip fracture. There was no significant interaction between the relative effects of BMI and physical activity. For women who reported that they took any exercise versus no exercise the adjusted relative risk of hip fracture was 0.68 (95%CI 0.62-0.75), with similar results for strenuous exercise. In this large cohort of postmenopausal women BMI and physical activity had independent effects on hip fracture risk. © 2010 American Society for Bone and Mineral Research