Measurements of total alkalinity and inorganic dissolved carbon in the Atlantic Ocean and adjacent Southern Ocean between 2008 and 2010

Water column dissolved inorganic carbon and total alkalinity were measured during five hydrographic sections in the Atlantic Ocean and Drake Passage. The work was funded through the Strategic Funding Initiative of the UK's Oceans2025 programme, which ran from 2007 to 2012. The aims of this programme were to establish the regional budgets of natural and anthropogenic carbon in the North Atlantic, the South Atlantic, and the Atlantic sector of the Southern Ocean, as well as the rates of change of these budgets. This paper describes in detail the dissolved inorganic carbon and total alkalinity data collected along east–west sections at 47° N to 60° N, 24.5° N, and 24° S in the Atlantic and across two Drake Passage sections. Other hydrographic and biogeochemical parameters were measured during these sections, and relevant standard operating procedures are mentioned here. Over 95% of dissolved inorganic carbon and total alkalinity samples taken during the 24.5° N, 24° S, and the Drake Passage sections were analysed onboard and subjected to a first-level quality control addressing technical and analytical issues. Samples taken along 47° N to 60° N were analysed and subjected to quality control back in the laboratory. Complete post-cruise second-level quality control was performed using cross-over analysis with historical data in the vicinity of measurements, and data were submitted to the CLIVAR and Carbon Hydrographic Data Office (CCHDO), the Carbon Dioxide Information Analysis Center (CDIAC) and and will be included in the Global Ocean Data Analyses Project, version 2 (GLODAP 2), the upcoming update of Key et al. (2004)

A high-affinity antibody against the CSP N-terminal domain lacks Plasmodium falciparum inhibitory activity

Malaria is a global health concern and research efforts are ongoing to develop a superior vaccine to RTS,S/AS01. To guide immunogen design, we seek a comprehensive understanding of the protective humoral response against Plasmodium falciparum circumsporozoite protein (PfCSP). In contrast to the well-studied responses to the repeat region and the C-terminus, the antibody response against the N-terminal domain of PfCSP (N-CSP) remains obscure. Here, we characterized the molecular recognition and functional efficacy of the N-CSP-specific monoclonal antibody 5D5. The crystal structure at 1.85 Åresolution revealed that 5D5 binds an α-helical epitope in N-CSP with high affinity through extensive shape and charge complementarity, and the unusual utilization of an N-linked glycan. Nevertheless, functional studies indicated low 5D5 binding to live Pf sporozoites, and lack of sporozoite inhibition in vitro and in mosquitoes. Overall, our data on low recognition and inhibition of sporozoites do not support the inclusion of the 5D5 epitope into the next generation of CSP-based vaccines.Summary Statement The Plasmodium falciparum sporozoite surface protein, PfCSP, is an attractive vaccine target, but the antibody response against the CSP N-terminal domain has remained understudied. Here, to guide immunogen design, Thai et al. provide insights into the binding motif and functional efficacy of the N-terminal domain-specific monoclonal antibody, 5D5

Disruption of a Proto-Planetary Disk by the Black Hole at the Milky Way Centre

Recently, an ionized cloud of gas was discovered plunging toward the supermassive black hole, SgrA*, at the centre of the Milky Way. The cloud is being tidally disrupted along its path to closest approach at ~3100 Schwarzschild radii from the black hole. Here, we show that the observed properties of this cloud of gas can naturally be produced by a proto-planetary disk surrounding a low-mass star, which was scattered from the observed ring of young stars orbiting SgrA*. As the young star approaches the black hole, its disk experiences both photo-evaporation and tidal disruption, producing a cloud. Our model implies that planets form in the Galactic centre, and that tidal debris from proto-planetary disks can flag low mass stars which are otherwise too faint to be detected.Comment: Accepted to Nature Communications; new Figure 4b provides predicted Br-gamma emission as a function of tim

The use of history to identify anterior cruciate ligament injuries in the acute trauma setting: the 'LIMP index'

YesObjective To identify the injury history features reported by patients with ACL injuries and determine whether history may be used to identify patients requiring follow-up appointments from acute trauma services. Multi-site cross-sectional service evaluation using a survey questionnaire design conducted in the UK. The four injury history features investigated (LIMP) were ‘Leg giving way at the time of injury’, ‘Inability to continue activity immediately following injury’, ‘Marked effusion’ and ‘Pop (heard or felt) at the time of injury’. 194 patients with ACL injury were identified of which 165 (85.5%) attended an acute trauma service. Data on delay was available for 163 (98.8%) of these patients of which 120 (73.6%) had a follow-up appointment arranged. Patients who had a follow-up appointment arranged waited significantly less time for a correct diagnosis (geometric mean 29 vs 198 days; p<0.001) and to see a specialist consultant (geometric mean 61 vs 328 days; p<0.001). Using a referral threshold of any 2 of the 4 LIMP injury history features investigated, 95.8% of patients would have had a follow-up appointment arranged. Findings support the value of questioning patients on specific injury history features in identifying patients who may have suffered ACL injury. Using a threshold of 2 or more of the 4 LIMP history features investigated would have reduced the percentage of patients inappropriately discharged by 22.2%. Evidence presented suggests that this would significantly reduce the time to diagnosis and specialist consultation minimising the chance of secondary complications

What works in managing young people who offend? A summary of the international evidence

This review was commissioned by the Ministry of Justice and considers international literature concerning the management of young people who have offended. It was produced to inform youth justice policy and practice. The review focuses on the impact and delivery of youth justice supervision, programmes and interventions within the community, secure settings, and during transition into adult justice settings or into mainstream society

Blood ties: ABO is a trans-species polymorphism in primates

The ABO histo-blood group, the critical determinant of transfusion incompatibility, was the first genetic polymorphism discovered in humans. Remarkably, ABO antigens are also polymorphic in many other primates, with the same two amino acid changes responsible for A and B specificity in all species sequenced to date. Whether this recurrence of A and B antigens is the result of an ancient polymorphism maintained across species or due to numerous, more recent instances of convergent evolution has been debated for decades, with a current consensus in support of convergent evolution. We show instead that genetic variation data in humans and gibbons as well as in Old World Monkeys are inconsistent with a model of convergent evolution and support the hypothesis of an ancient, multi-allelic polymorphism of which some alleles are shared by descent among species. These results demonstrate that the ABO polymorphism is a trans-species polymorphism among distantly related species and has remained under balancing selection for tens of millions of years, to date, the only such example in Hominoids and Old World Monkeys outside of the Major Histocompatibility Complex.Comment: 45 pages, 4 Figures, 4 Supplementary Figures, 5 Supplementary Table

Evidence-informed capacity building for setting health priorities in low- and middle-income countries: : A framework and recommendations for further research

Priority-setting in health is risky and challenging, particularly in resource-constrained settings. It is not simply a narrow technical exercise, and involves the mobilisation of a wide range of capacities among stakeholders – not only the technical capacity to “do” research in economic evaluations. Using the Individuals, Nodes, Networks and Environment (INNE) framework, we identify those stakeholders, whose capacity needs will vary along the evidence-to-policy continuum. Policymakers and healthcare managers require the capacity to commission and use relevant evidence (including evidence of clinical and cost-effectiveness, and of social values); academics need to understand and respond to decision-makers’ needs to produce relevant research. The health system at all levels will need institutional capacity building to incentivise routine generation and use of evidence. Knowledge brokers, including priority-setting agencies (such as England’s National Institute for Health and Care Excellence, and Health Interventions and Technology Assessment Program, Thailand) and the media can play an important role in facilitating engagement and knowledge transfer between the various actors. Especially at the outset but at every step, it is critical that patients and the public understand that trade-offs are inherent in priority-setting, and careful efforts should be made to engage them, and to hear their views throughout the process. There is thus no single approach to capacity building; rather a spectrum of activities that recognises the roles and skills of all stakeholders. A range of methods, including formal and informal training, networking and engagement, and support through collaboration on projects, should be flexibly employed (and tailored to specific needs of each country) to support institutionalisation of evidence-informed priority-setting. Finally, capacity building should be a two-way process; those who build capacity should also attend to their own capacity development in order to sustain and improve impact

Recombination dynamics of a human Y-chromosomal palindrome:rapid GC-biased gene conversion, multi-kilobase conversion tracts, and rare inversions

The male-specific region of the human Y chromosome (MSY) includes eight large inverted repeats (palindromes) in which arm-to-arm similarity exceeds 99.9%, due to gene conversion activity. Here, we studied one of these palindromes, P6, in order to illuminate the dynamics of the gene conversion process. We genotyped ten paralogous sequence variants (PSVs) within the arms of P6 in 378 Y chromosomes whose evolutionary relationships within the SNP-defined Y phylogeny are known. This allowed the identification of 146 historical gene conversion events involving individual PSVs, occurring at a rate of 2.9-8.4×10(-4) events per generation. A consideration of the nature of nucleotide change and the ancestral state of each PSV showed that the conversion process was significantly biased towards the fixation of G or C nucleotides (GC-biased), and also towards the ancestral state. Determination of haplotypes by long-PCR allowed likely co-conversion of PSVs to be identified, and suggested that conversion tract lengths are large, with a mean of 2068 bp, and a maximum in excess of 9 kb. Despite the frequent formation of recombination intermediates implied by the rapid observed gene conversion activity, resolution via crossover is rare: only three inversions within P6 were detected in the sample. An analysis of chimpanzee and gorilla P6 orthologs showed that the ancestral state bias has existed in all three species, and comparison of human and chimpanzee sequences with the gorilla outgroup confirmed that GC bias of the conversion process has apparently been active in both the human and chimpanzee lineages