49 research outputs found

    The impact of electronic monitoring on fleet wide discarding of small cod in Scottish demersal fisheries

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    Acknowledgments The authors of this paper would like to acknowledge the fishers, fisheries inspectors, and video reviewers who participated in or supported the Scottish cod catch quota management scheme. Additionally, we thank two anonymous reviewers for their encouraging and insightful comments and suggestions.Peer reviewedPublisher PD

    Doing cold smarter

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    Cold has been much neglected in the energy debate. Governments are developing strategies and policies to green everything from electricity to transport to heat, but the energy and environmental impacts of cooling have so far been largely ignored. This is a serious oversight, since making things cold is energy intensive and can be highly polluting, and demand for cooling in all its forms is booming worldwide – especially in developing countries. According to one projection, by the end of this century global demand for air conditioning alone could consume the equivalent of half our worldwide electricity generation today – and most of the increase will come in developing markets. The ‘greening’ of cold is clearly an urgent global problem – but it may also offer Britain a massive business opportunity. Cold may have been ignored but is vitally important to many aspects of modern life. An effective cold chain, for example, is essential for tackling problems such as food waste, food security, water conservation and public health. Cooling is also critical for many less obvious but essential functions: data centres couldn’t operate without it, nor for example MRI scanners in medicine or superconductors in power electronics. Cooling also provides modern levels of comfort in hot countries – and can make the difference between some regions being habitable or not. At the same time, vast amounts of cold are wasted – for instance during the regasification of LNG – which could in principle be recycled to satisfy some of this demand and start to reduce the environmental damage caused by cooling. Such a system-level approach – which starts by asking what energy services we need, and what is the least damaging way to provide them, rather than accepting existing practices as a fait accompli – has recently been coined the ‘Cold Economy’. It is clear the Cold Economy could unleash a wide range of innovative clean cold technologies and provide energy resilience, economic growth and environmental benefits, but there is an urgent need to develop a system-level analysis of this problem and the potential solutions to inform both industry and policymakers. The Birmingham Policy Commission: Doing Cold Smarter was convened to start this work

    A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment.

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    Through the combined use of (18)F-fallypride positron emission tomography and magnetic resonance imaging this study examined the neural mechanisms underlying the attentional deficits associated with attention deficit/hyperactivity disorder and their potential reversal with a single therapeutic dose of methylphenidate. Sixteen adult patients with attention deficit/hyperactivity disorder and 16 matched healthy control subjects were positron emission tomography and magnetic resonance imaging scanned and tested on a computerized sustained attention task after oral methylphenidate (0.5 mg/kg) and placebo administration in a within-subject, double-blind, cross-over design. Although patients with attention deficit/hyperactivity disorder as a group showed significant attentional deficits and reduced grey matter volume in fronto-striato-cerebellar and limbic networks, they had equivalent D2/D3 receptor availability and equivalent increases in endogenous dopamine after methylphenidate treatment to that observed in healthy control subjects. However, poor attentional performers drawn from both the attention deficit/hyperactivity disorder and the control groups had significantly reduced left caudate dopamine activity. Methylphenidate significantly increased dopamine levels in all nigro-striatal regions, thereby normalizing dopamine levels in the left caudate in low performers. Behaviourally, methylphenidate improved sustained attention in a baseline performance-dependent manner, irrespective of diagnosis. This finding was accompanied by an equally performance-dependent effect of the drug on dopamine release in the midbrain, whereby low performers showed reduced dopamine release in this region. Collectively, these findings support a dimensional model of attentional deficits and underlying nigro-striatal dopaminergic mechanisms of attention deficit/hyperactivity disorder that extends into the healthy population. Moreover, they confer midbrain dopamine autoreceptors a hitherto neglected role in the therapeutic effects of oral methylphenidate in attention deficit/hyperactivity disorder. The absence of significant case-control differences in D2/D3 receptor availability (despite the observed relationships between dopamine activity and attention) suggests that dopamine dysregulation per se is unlikely to be the primary cause underlying attention deficit/hyperactivity disorder pathology in adults. This conclusion is reinforced by evidence of neuroanatomical changes in the same set of patients with attention deficit/hyperactivity disorder

    Modelling the Spread of HIV Immune Escape Mutants in a Vaccinated Population

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    Because cytotoxic T-lymphocytes (CTLs) have been shown to play a role in controlling human immunodeficiency virus (HIV) infection and because CTL-based simian immunodeficiency virus (SIV) vaccines have proved effective in non-human primates, one goal of HIV vaccine design is to elicit effective CTL responses in humans. Such a vaccine could improve viral control in patients who later become infected, thereby reducing onwards transmission and enhancing life expectancy in the absence of treatment. The ability of HIV to evolve mutations that evade CTLs and the ability of these ‘escape mutants’ to spread amongst the population poses a challenge to the development of an effective and robust vaccine. We present a mathematical model of within-host evolution and between-host transmission of CTL escape mutants amongst a population receiving a vaccine that elicits CTL responses to multiple epitopes. Within-host evolution at each epitope is represented by the outgrowth of escape mutants in hosts who restrict the epitope and their reversion in hosts who do not restrict the epitope. We use this model to investigate how the evolution and spread of escape mutants could affect the impact of a vaccine. We show that in the absence of escape, such a vaccine could markedly reduce the prevalence of both infection and disease in the population. However the impact of such a vaccine could be significantly abated by CTL escape mutants, especially if their selection in hosts who restrict the epitope is rapid and their reversion in hosts who do not restrict the epitope is slow. We also use the model to address whether a vaccine should span a broad or narrow range of CTL epitopes and target epitopes restricted by rare or common HLA types. We discuss the implications and limitations of our findings

    Upper mantle electrical resistivity structure beneath the central Mariana subduction system

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    Author Posting. © American Geophysical Union, 2010. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 11 (2010): Q09003, doi:10.1029/2010GC003101.This paper reports on a magnetotelluric (MT) survey across the central Mariana subduction system, providing a comprehensive electrical resistivity image of the upper mantle to address issues of mantle dynamics in the mantle wedge and beneath the slow back-arc spreading ridge. After calculation of MT response functions and their correction for topographic distortion, two-dimensional electrical resistivity structures were generated using an inversion algorithm with a smoothness constraint and with additional restrictions imposed by the subducting slab. The resultant isotropic electrical resistivity structure contains several key features. There is an uppermost resistive layer with a thickness of up to 150 km beneath the Pacific Ocean Basin, 80–100 km beneath the Mariana Trough, and 60 km beneath the Parece Vela Basin along with a conductive mantle beneath the resistive layer. A resistive region down to 60 km depth and a conductive region at greater depth are inferred beneath the volcanic arc in the mantle wedge. There is no evidence for a conductive feature beneath the back-arc spreading center. Sensitivity tests were applied to these features through inversion of synthetic data. The uppermost resistive layer is the cool, dry residual from the plate accretion process. Its thickness beneath the Pacific Ocean Basin is controlled mainly by temperature, whereas the roughly constant thickness beneath the Mariana Trough and beneath the Parece Vela Basin regardless of seafloor age is controlled by composition. The conductive mantle beneath the uppermost resistive layer requires hydration of olivine and/or melting of the mantle. The resistive region beneath the volcanic arc down to 60 km suggests that fluids such as melt or free water are not well connected or are highly three-dimensional and of limited size. In contrast, the conductive region beneath the volcanic arc below 60 km depth reflects melting and hydration driven by water release from the subducting slab. The resistive region beneath the back-arc spreading center can be explained by dry mantle with typical temperatures, suggesting that any melt present is either poorly connected or distributed discontinuously along the strike of the ridge. Evidence for electrical anisotropy in the central Mariana upper mantle is weak.Japanese participation in the Marianas experiment was supported by Japan Society for the Promotion of Science for Grant-In-Aid for Scientific Research (15340149 and 12440116), Japan-U.S. Integrated Action Program and the 21st Century COE Program of Origin and Evolution of Planetary Systems, and by the Ministry of Education, Culture, Sports, Science, and Technology for the Stagnant Slab Project, Grant-in Aid for Scientific Research on Priority Areas (17037003 and 16075204). U.S. participation was supported by NSF grant OCE0405641. Australian support came from Flinders University. T. M. is supported by the Postdoctoral Scholar Program at the Woods Hole Oceanographic Institution, with funding provided by the Deep Ocean Exploration Institute

    Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

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    Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

    Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

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    The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

    SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

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    Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

    Cleaned and processed input data and summary results for the 2022 OSPAR CEMP Assessment

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    These dataset files contains the cleaned and processed input data and summary results for the 2022 OSPAR CEMP Assessment of contaminants and biological effects in biota, sediment and water.  See read_me.txt for further information.</p
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