Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data

This study was supported by a grant from the National Institute for Health Research (NIHR) under its Health Technology Assessment programme (reference No 13/03/25, to ARM

Neurophysiology

Contains research objectives and reports on one research project.U. S. Air Force Cambridge Research Laboratories under Contract AF19(628)-4147Bell Telephone Laboratories, Inc.National Institutes of Health (Grant MH-04737-04)National Science Foundation (Grant GP-2495)National Institutes of Health (Grant NB-04987-02)The Teagle Foundation, Inc.National Aeronautics and Space Administration (Grant NsG-496)U. S. Air Force (Aeronautical Systems Division) under Contract AF 33(615)-1747National Institutes of Health (Grant NB-04985-01

Ethical principles in machine learning and artificial intelligence: cases from the field and possible ways forward

Decision-making on numerous aspects of our daily lives is being outsourced to machine-learning algorithms and artificial intelligence (AI), motivated by speed and efficiency in the decision process. Machine learning (ML) approaches - one of the typologies of algorithms underpinning artificial intelligence - are typically developed as black boxes. The implication is that ML code scripts are rarely scrutinised; interpretability is usually sacrificed in favour of usability and effectiveness. Room for improvement in practices associated with programme development have also been flagged along other dimensions, including inter alia fairness, accuracy, accountability, and transparency. In this contribution, the production of guidelines and dedicated documents around these themes is discussed. The following applications of AI-driven decision making are outlined: a) Risk assessment in the criminal justice system, and b) autonomous vehicles, highlighting points of friction across ethical principles. Possible ways forward towards the implementation of governance on AI are finally examined

The Impact of Climate Change on Virginia\u27s Coastal Areas

As part of HJ47/SJ47 (2020), the Virginia General Assembly directed the Joint Commission on Technology and Science (JCOTS) to study the “safety, quality of life, and economic consequences of weather and climate-related events on coastal areas in Virginia.” In pursuit of this goal, the commission was to “accept any scientific and technical assistance provided by the nonpartisan, volunteer Virginia Academy of Science, Engineering, and Medicine (VASEM). VASEM convened an expert study board with representation from the Office of the Governor, planning district commissions in coastal Virginia, The Port of Virginia, the Virginia Economic Development Partnership, state universities, private industry, and law firms. In producing the report, the board followed methods similar to those used by the National Academies of Science, Engineering, and Medicine by convening an expert committee tasked with studying and reporting on the topic. As a result, the report represents the views and perspectives of the study board members but was not submitted for public review or comment. This report is the product of those efforts. It finds that climate change will have an increasingly disruptive effect on people living in Virginia’s coastal areas during the 21st century — and that these disruptions will have repercussions across the Commonwealth. It includes an explanation of the physical forces driving climate change, an analysis of the current and projected effects of climate change on the Commonwealth, perspectives that legislators might consider as they face these challenges, and recommendations that could help Virginia implement more productive and effective strategies to address them

Chimpanzees Share Forbidden Fruit

The sharing of wild plant foods is infrequent in chimpanzees, but in chimpanzee communities that engage in hunting, meat is frequently used as a ‘social tool’ for nurturing alliances and social bonds. Here we report the only recorded example of regular sharing of plant foods by unrelated, non-provisioned wild chimpanzees, and the contexts in which these sharing behaviours occur. From direct observations, adult chimpanzees at Bossou (Republic of Guinea, West Africa) very rarely transferred wild plant foods. In contrast, they shared cultivated plant foods much more frequently (58 out of 59 food sharing events). Sharing primarily consists of adult males allowing reproductively cycling females to take food that they possess. We propose that hypotheses focussing on ‘food-for-sex and -grooming’ and ‘showing-off’ strategies plausibly account for observed sharing behaviours. A changing human-dominated landscape presents chimpanzees with fresh challenges, and our observations suggest that crop-raiding provides adult male chimpanzees at Bossou with highly desirable food commodities that may be traded for other currencies

Biochemical and genetic analysis of butyrylcholinesterase (BChE) in a family, due to prolonged neuromuscular blockade after the use of succinylcholine

Butyrylcholinesterase (BChE) is a plasma enzyme that catalyzes the hydrolysis of choline esters, including the muscle-relaxant succinylcholine and mivacurium. Patients who present sustained neuromuscular blockade after using succinylcholine usually carry BChE variants with reduced enzyme activity or an acquired BChE deficiency. We report here the molecular basis of the BCHE gene underlying the slow catabolism of succinylcholine in a patient who underwent endoscopic nasal surgery. We measured the enzyme activity of BChE and extracted genomic DNA in order to study the promoter region and all exons of the BCHE gene of the patient, her parents and siblings. PCR products were sequenced and compared with reference sequences from GenBank. We detected that the patient and one of her brothers have two homozygous mutations: nt1615 GCA > ACA (Ala539Thr), responsible for the K variant, and nt209 GAT > GGT (Asp70Gly), which produces the atypical variant A. Her parents and two of her brothers were found to be heterozygous for the AK allele, and another brother is homozygous for the normal allele. Sequence analysis of exon 1 including 5′UTR showed that the proband and her brother are homozygous for –116GG. The AK/AK genotype is considered the most frequent in hereditary hypocholinesterasemia (44%). This work demonstrates the importance of defining the phenotype and genotype of the BCHE gene in patients who are subjected to neuromuscular block by succinylcholine, because of the risk of prolonged neuromuscular paralysis

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz

Evidence for Reduced Drug Susceptibility without Emergence of Major Protease Mutations following Protease Inhibitor Monotherapy Failure in the SARA Trial

Background Major protease mutations are rarely observed following failure with protease inhibitors (PI), and other viral determinants of failure to PI are poorly understood. We therefore characterized Gag-Protease phenotypic susceptibility in subtype A and D viruses circulating in East Africa following viral rebound on PIs. Methods Samples from baseline and treatment failure in patients enrolled in the second line LPV/r trial SARA underwent phenotypic susceptibility testing. Data were expressed as fold-change in susceptibility relative to a LPV-susceptible reference strain. Results We cloned 48 Gag-Protease containing sequences from seven individuals and performed drug resistance phenotyping from pre-PI and treatment failure timepoints in seven patients. For the six patients where major protease inhibitor resistance mutations did not emerge, mean fold-change EC50 to LPV was 4.07 fold (95% CI, 2.08–6.07) at the pre-PI timepoint. Following viral failure the mean fold-change in EC50 to LPV was 4.25 fold (95% CI, 1.39–7.11, p = 0.91). All viruses remained susceptible to DRV. In our assay system, the major PI resistance mutation I84V, which emerged in one individual, conferred a 10.5-fold reduction in LPV susceptibility. One of the six patients exhibited a significant reduction in susceptibility between pre-PI and failure timepoints (from 4.7 fold to 9.6 fold) in the absence of known major mutations in protease, but associated with changes in Gag: V7I, G49D, R69Q, A120D, Q127K, N375S and I462S. Phylogenetic analysis provided evidence of the emergence of genetically distinct viruses at the time of treatment failure, indicating ongoing viral evolution in Gag-protease under PI pressure. Conclusions Here we observe in one patient the development of significantly reduced susceptibility conferred by changes in Gag which may have contributed to treatment failure on a protease inhibitor containing regimen. Further phenotype-genotype studies are required to elucidate genetic determinants of protease inhibitor failure in those who fail without traditional resistance mutations whilst PI use is being scaled up globally

Sex differences in the movement patterns of free-ranging chimpanzees (Pan troglodytes schweinfurthii): foraging and border checking

Most social primates live in cohesive groups, so travel paths inevitably reflect compromise: decision processes of individuals are obscured. The fission-fusion social organisation of the chimpanzee, however, allows an individual’s movements to be investigated independently. We followed 15 chimpanzees (8 male and 7 female) through the relatively flat forest of Budongo, Uganda, plotting the path of each individual over periods of 1-3 days. Chimpanzee movement was parsed into phases ending with halts of more than 20 minutes, during which individuals fed, rested or engaged in social activities. Males, lactating or pregnant females, and sexually receptive females all travelled similar average distances between halts, at similar speeds, and along similarly direct beeline paths. Compared to lactating or pregnant females, males did travel for a significantly longer time each day and halted more often, but the most striking sex differences appeared in the organisation of movement phases into a day’s path. After a halt, males tended to continue in the same direction as before. Lactating or pregnant females showed no such strategy and often retraced the preceding phase, returning to previously visited food patches. We suggest that female chimpanzee movements approximate an optimal solution to feeding requirements, whereas the paths of males allow integration of foraging with territorial defence. The ‘continually moving forwards’ strategy of males enables them to monitor their territory boundaries – border checking – whilst foraging, generally avoiding the explicit boundary patrols observed at other chimpanzee study sites