We introduce a new framework for quantifying correlated uncertainties of the infinite-matter equation of state derived from chiral effective field theory (χEFT). Bayesian machine learning via ...Gaussian processes with physics-based hyperparameters allows us to efficiently quantify and propagate theoretical uncertainties of the equation of state, such as χEFT truncation errors, to derived quantities. We apply this framework to state-of-the-art many-body perturbation theory calculations with nucleon-nucleon and three-nucleon interactions up to fourth order in the χEFT expansion. This produces the first statistically robust uncertainty estimates for key quantities of neutron stars. We give results up to twice nuclear saturation density for the energy per particle, pressure, and speed of sound of neutron matter, as well as for the nuclear symmetry energy and its derivative. At nuclear saturation density, the predicted symmetry energy and its slope are consistent with experimental constraints.
We analyze the power counting of two-body currents in nuclear effective field theories (EFTs). We find that the existence of nonperturbative physics at low energies, which is manifest in the ...existence of the deuteron and the ^{1}S_{0} NN virtual bound state, combined with the appearance of singular potentials in versions of nuclear EFT that incorporate chiral symmetry, modifies the renormalization-group flow of the couplings associated with contact operators that involve nucleon-nucleon pairs and external fields. The order of these couplings is thereby enhanced with respect to the naive-dimensional-analysis estimate. Consequently, short-range currents enter at a lower order in the chiral EFT than has been appreciated up until now, and their impact on low-energy observables is concomitantly larger. We illustrate the changes in the power counting with a few low-energy processes involving external probes and few-nucleon systems, including electron-deuteron elastic scattering and radiative neutron capture by protons.
Summary Background Proper assessment of the harms caused by the misuse of drugs can inform policy makers in health, policing, and social care. We aimed to apply multicriteria decision analysis (MCDA) ...modelling to a range of drug harms in the UK. Methods Members of the Independent Scientific Committee on Drugs, including two invited specialists, met in a 1-day interactive workshop to score 20 drugs on 16 criteria: nine related to the harms that a drug produces in the individual and seven to the harms to others. Drugs were scored out of 100 points, and the criteria were weighted to indicate their relative importance. Findings MCDA modelling showed that heroin, crack cocaine, and metamfetamine were the most harmful drugs to individuals (part scores 34, 37, and 32, respectively), whereas alcohol, heroin, and crack cocaine were the most harmful to others (46, 21, and 17, respectively). Overall, alcohol was the most harmful drug (overall harm score 72), with heroin (55) and crack cocaine (54) in second and third places. Interpretation These findings lend support to previous work assessing drug harms, and show how the improved scoring and weighting approach of MCDA increases the differentiation between the most and least harmful drugs. However, the findings correlate poorly with present UK drug classification, which is not based simply on considerations of harm. Funding Centre for Crime and Justice Studies (UK).
Summary Background Although trastuzumab plus chemotherapy is the standard of care for first-line treatment of HER2-positive advanced gastric cancer, there is no established therapy in the second-line ...setting. In GATSBY, we examined the efficacy and tolerability of trastuzumab emtansine in patients previously treated for HER2-positive advanced gastric cancer (unresectable, locally advanced, or metastatic gastric cancer, including adenocarcinoma of the gastro-oesophageal junction). Methods This is the final analysis from GATSBY, a randomised, open-label, adaptive, phase 2/3 study, done at 107 centres (28 countries worldwide). Eligible patients had HER2-positive advanced gastric cancer and progressed during or after first-line therapy. In stage one of the trial, patients were randomly assigned to treatment groups (2:2:1) to receive intravenous trastuzumab emtansine (3·6 mg/kg every 3 weeks or 2·4 mg/kg weekly) or physician's choice of a taxane (intravenous docetaxel 75 mg/m2 every 3 weeks or intravenous paclitaxel 80 mg/m2 weekly). In stage two, patients were randomly assigned to treatment groups (2:1) to receive the independent data monitoring committee (IDMC)-selected dose of trastuzumab emtansine (2·4 mg/kg weekly) or a taxane (same regimen as above). We used permuted block randomisation, stratified by world region, previous HER2-targeted therapy, and previous gastrectomy. The primary endpoint (overall survival) was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov , number NCT01641939. Findings Between Sept 3, 2012, and Oct 14, 2013, 70 patients were assigned to receive trastuzumab emtansine 3·6 mg/kg every 3 weeks, 75 to receive trastuzumab emtansine 2·4 mg/kg weekly, and 37 to receive a taxane in the stage 1 part of the trial. At the pre-planned interim analysis (Oct 14, 2013), the IDMC selected trastuzumab emtansine 2·4 mg/kg weekly as the dose to proceed to stage 2. By Feb 9, 2015, a further 153 patients had been randomly assigned to receive trastuzumab emtansine 2·4 mg/kg weekly and a further 80 to receive a taxane. At data cutoff, median follow-up was 17·5 months (IQR 12·1–23·0) for the trastuzumab emtansine 2·4 mg/kg weekly group and 15·4 months (9·2–18·1) in the taxane group. Median overall survival was 7·9 months (95% CI 6·7–9·5) with trastuzumab emtansine 2·4 mg/kg weekly and 8·6 months (7·1–11·2) with taxane treatment (hazard ratio 1·15, 95% CI 0·87–1·51, one-sided p=0·86). The trastuzumab emtansine 2·4 mg/kg group had lower incidences of grade 3 or more adverse events (134 60% of 224 patients treated with trastuzumab emtansine vs 78 70% of 111 patients treated with a taxane), and similar incidences of adverse events leading to death (eight 4% vs four 4%), serious adverse events (65 29% vs 31 28%), and adverse events leading to treatment discontinuation (31 14% vs 15 14%) than did taxane treatment. The most common grade 3 or more adverse events in the trastuzumab emtansine 2·4 mg/kg weekly group were anaemia (59 26%) and thrombocytopenia (25 11%) compared with neutropenia (43 39%), and anaemia (20 18%), in the taxane group. The most common serious adverse events were anaemia (eight 4%), upper gastrointestinal haemorrhage (eight 4%), pneumonia (seven 3%), gastric haemorrhage (six 3%), and gastrointestinal haemorrhage (five 2%) in the trastuzumab emtansine 2·4 mg/kg weekly group compared with pneumonia (four 4%), febrile neutropenia (four 4%), anaemia (three 3%), and neutropenia (three 3%) in the taxane group. Interpretation Trastuzumab emtansine was not superior to taxane in patients with previously treated, HER2-positive advanced gastric cancer. There is still an unmet need in this patient group and therapeutic options remain limited. Funding F Hoffmann-La Roche.
Given the exceptional diversity of orchids (26 000+ species), improving strategies for the conservation of orchids will benefit a vast number of taxa. Furthermore, with rapidly increasing numbers of ...endangered orchids and low success rates in orchid conservation translocation programmes worldwide, it is evident that our progress in understanding the biology of orchids is not yet translating into widespread effective conservation.
We highlight unusual aspects of the reproductive biology of orchids that can have important consequences for conservation programmes, such as specialization of pollination systems, low fruit set but high seed production, and the potential for long-distance seed dispersal. Further, we discuss the importance of their reliance on mycorrhizal fungi for germination, including quantifying the incidence of specialized versus generalized mycorrhizal associations in orchids. In light of leading conservation theory and the biology of orchids, we provide recommendations for improving population management and translocation programmes.
Major gains in orchid conservation can be achieved by incorporating knowledge of ecological interactions, for both generalist and specialist species. For example, habitat management can be tailored to maintain pollinator populations and conservation translocation sites selected based on confirmed availability of pollinators. Similarly, use of efficacious mycorrhizal fungi in propagation will increase the value of ex situ collections and likely increase the success of conservation translocations. Given the low genetic differentiation between populations of many orchids, experimental genetic mixing is an option to increase fitness of small populations, although caution is needed where cytotypes or floral ecotypes are present. Combining demographic data and field experiments will provide knowledge to enhance management and translocation success. Finally, high per-fruit fecundity means that orchids offer powerful but overlooked opportunities to propagate plants for experiments aimed at improving conservation outcomes. Given the predictions of ongoing environmental change, experimental approaches also offer effective ways to build more resilient populations.
The Human Gene Mutation Database (HGMD
®
) constitutes a comprehensive collection of published germline mutations in nuclear genes that underlie, or are closely associated with human inherited ...disease. At the time of writing (March 2017), the database contained in excess of 203,000 different gene lesions identified in over 8000 genes manually curated from over 2600 journals. With new mutation entries currently accumulating at a rate exceeding 17,000 per annum, HGMD represents de facto the central unified gene/disease-oriented repository of heritable mutations causing human genetic disease used worldwide by researchers, clinicians, diagnostic laboratories and genetic counsellors, and is an essential tool for the annotation of next-generation sequencing data. The public version of HGMD (
http://www.hgmd.org
) is freely available to registered users from academic institutions and non-profit organisations whilst the subscription version (HGMD Professional) is available to academic, clinical and commercial users under license via QIAGEN Inc.
The enslaved population of medieval Iberia composed only a small percentage of the general populace at any given point, and slave labor was not essential to the regional economy during the period. ...Yet slaves were present in Iberia from the beginning of recorded history until the early modern era, and the regulations and norms for slavery and servitude shifted as time passed and kingdoms rose and fell. The Romans brought their imperially sanctioned forms of slavery to the Iberian peninsula, and these were adapted by successive Christian kingdoms during the Middle Ages. The Muslim conquest of Iberia introduced new ideas about slavery and effected an increase in slave trade. During the later Middle Ages and the early modern period, slave owners in Christian Spain and Portugal maintained slaves at home, frequently captives taken in wars and sea raids, and exported their slave systems to colonies across the Atlantic.Slavery in Medieval and Early Modern Iberiaprovides a magisterial survey of the many forms of bound labor in Iberia from ancient times to the decline of slavery in the eighteenth century. William D. Phillips, Jr., examines the pecuniary and legal terms of slavery from purchase to manumission. He pays particular attention to the conditions of life for the enslaved, which, in a religiously diverse society, differed greatly for Muslims and Christians as well as for men and women. This sweeping narrative will become the definitive account of slavery in a place and period that deeply influenced the forms of forced servitude that shaped the New World.
The Human Gene Mutation Database (HGMD
®
) constitutes a comprehensive collection of published germline mutations in nuclear genes that are thought to underlie, or are closely associated with human ...inherited disease. At the time of writing (June 2020), the database contains in excess of 289,000 different gene lesions identified in over 11,100 genes manually curated from 72,987 articles published in over 3100 peer-reviewed journals. There are primarily two main groups of users who utilise HGMD on a regular basis; research scientists and clinical diagnosticians. This review aims to highlight how to make the most out of HGMD data in each setting.
The Human Gene Mutation Database (HGMD
®
) is a comprehensive collection of germline mutations in nuclear genes that underlie, or are associated with, human inherited disease. By June 2013, the ...database contained over 141,000 different lesions detected in over 5,700 different genes, with new mutation entries currently accumulating at a rate exceeding 10,000 per annum. HGMD was originally established in 1996 for the scientific study of mutational mechanisms in human genes. However, it has since acquired a much broader utility as a central unified disease-oriented mutation repository utilized by human molecular geneticists, genome scientists, molecular biologists, clinicians and genetic counsellors as well as by those specializing in biopharmaceuticals, bioinformatics and personalized genomics. The public version of HGMD (
http://www.hgmd.org
) is freely available to registered users from academic institutions/non-profit organizations whilst the subscription version (HGMD Professional) is available to academic, clinical and commercial users under license via BIOBASE GmbH.
Context: The prevalence of obesity among women of childbearing age is increasing. Emerging evidence suggests that this has long-term adverse influences on offspring health.
Objective: The aim was to ...examine whether maternal body composition and gestational weight gain have persisting effects on offspring adiposity in early adulthood.
Design and Setting: The Motherwell birth cohort study was conducted in a general community in Scotland, United Kingdom.
Participants: We studied 276 men and women whose mothers’ nutritional status had been characterized in pregnancy. Four-site skinfold thicknesses, waist circumference, and body mass index (BMI), were measured at age 30 yr; sex-adjusted percentage body fat and fat mass index were calculated.
Main Outcome Measure: Indices of offspring adiposity at age 30 yr were measured.
Results: Percentage body fat was greater in offspring of mothers with a higher BMI at the first antenatal visit (rising by 0.35%/kg/m2; P < 0.001) and in offspring whose mothers were primiparous (difference, 1.5% in primiparous vs. multiparous; P = 0.03). Higher offspring percentage body fat was also independently associated with higher pregnancy weight gain (7.4%/kg/wk; P = 0.002). There were similar significant associations of increased maternal BMI, greater pregnancy weight gain, and parity with greater offspring waist circumference, BMI, and fat mass index.
Conclusions: Adiposity in early adulthood is influenced by prenatal influences independently of current lifestyle factors. Maternal adiposity, greater gestational weight, and parity all impact on offspring adiposity. Strategies to reduce the impact of maternal obesity and greater pregnancy weight gain on offspring future health are required.
Adiposity in early adulthood is influenced by prenatal influences including greater maternal pregnancy body mass index, gestational weight gain, and primiparity, independent of current lifestyle factors.
PDF
