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Showing papers by "University of Exeter published in 2019"


Journal ArticleDOI
27 Sep 2019-Gut
TL;DR: Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care.
Abstract: Ulcerative colitis and Crohn’s disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn’s and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn’s disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn’s disease, including patients, their families and friends.

1,140 citations


Journal ArticleDOI
Pierre Friedlingstein1, Pierre Friedlingstein2, Matthew W. Jones3, Michael O'Sullivan1, Robbie M. Andrew, Judith Hauck4, Glen P. Peters, Wouter Peters5, Wouter Peters6, Julia Pongratz7, Julia Pongratz8, Stephen Sitch1, Corinne Le Quéré3, Dorothee C. E. Bakker3, Josep G. Canadell9, Philippe Ciais10, Robert B. Jackson11, Peter Anthoni12, Leticia Barbero13, Leticia Barbero14, Ana Bastos8, Vladislav Bastrikov10, Meike Becker15, Meike Becker16, Laurent Bopp2, Erik T. Buitenhuis3, Naveen Chandra17, Frédéric Chevallier10, Louise Chini18, Kim I. Currie19, Richard A. Feely20, Marion Gehlen10, Dennis Gilfillan21, Thanos Gkritzalis22, Daniel S. Goll23, Nicolas Gruber24, Sören B. Gutekunst25, Ian Harris26, Vanessa Haverd9, Richard A. Houghton27, George C. Hurtt18, Tatiana Ilyina7, Atul K. Jain28, Emilie Joetzjer10, Jed O. Kaplan29, Etsushi Kato, Kees Klein Goldewijk30, Kees Klein Goldewijk31, Jan Ivar Korsbakken, Peter Landschützer7, Siv K. Lauvset15, Nathalie Lefèvre32, Andrew Lenton33, Andrew Lenton34, Sebastian Lienert35, Danica Lombardozzi36, Gregg Marland21, Patrick C. McGuire37, Joe R. Melton, Nicolas Metzl32, David R. Munro38, Julia E. M. S. Nabel7, Shin-Ichiro Nakaoka39, Craig Neill34, Abdirahman M Omar15, Abdirahman M Omar34, Tsuneo Ono, Anna Peregon10, Anna Peregon40, Denis Pierrot13, Denis Pierrot14, Benjamin Poulter41, Gregor Rehder42, Laure Resplandy43, Eddy Robertson44, Christian Rödenbeck7, Roland Séférian10, Jörg Schwinger15, Jörg Schwinger31, Naomi E. Smith6, Naomi E. Smith45, Pieter P. Tans20, Hanqin Tian46, Bronte Tilbrook33, Bronte Tilbrook34, Francesco N. Tubiello47, Guido R. van der Werf48, Andy Wiltshire44, Sönke Zaehle7 
University of Exeter1, École Normale Supérieure2, Norwich Research Park3, Alfred Wegener Institute for Polar and Marine Research4, University of Groningen5, Wageningen University and Research Centre6, Max Planck Society7, Ludwig Maximilian University of Munich8, Commonwealth Scientific and Industrial Research Organisation9, Centre national de la recherche scientifique10, Stanford University11, Karlsruhe Institute of Technology12, Atlantic Oceanographic and Meteorological Laboratory13, Cooperative Institute for Marine and Atmospheric Studies14, Bjerknes Centre for Climate Research15, Geophysical Institute, University of Bergen16, Japan Agency for Marine-Earth Science and Technology17, University of Maryland, College Park18, National Institute of Water and Atmospheric Research19, National Oceanic and Atmospheric Administration20, Appalachian State University21, Flanders Marine Institute22, Augsburg College23, ETH Zurich24, Leibniz Institute of Marine Sciences25, University of East Anglia26, Woods Hole Research Center27, University of Illinois at Urbana–Champaign28, University of Hong Kong29, Utrecht University30, Netherlands Environmental Assessment Agency31, University of Paris32, University of Tasmania33, Hobart Corporation34, University of Bern35, National Center for Atmospheric Research36, University of Reading37, Cooperative Institute for Research in Environmental Sciences38, National Institute for Environmental Studies39, Russian Academy of Sciences40, Goddard Space Flight Center41, Leibniz Institute for Baltic Sea Research42, Princeton University43, Met Office44, Lund University45, Auburn University46, Food and Agriculture Organization47, VU University Amsterdam48
TL;DR: In this article, the authors describe data sets and methodology to quantify the five major components of the global carbon budget and their uncertainties, including emissions from land use and land use change, and show that the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere is a measure of imperfect data and understanding of the contemporary carbon cycle.
Abstract: . Accurate assessment of anthropogenic carbon dioxide ( CO2 ) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere – the “global carbon budget” – is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and methodology to quantify the five major components of the global carbon budget and their uncertainties. Fossil CO2 emissions ( EFF ) are based on energy statistics and cement production data, while emissions from land use change ( ELUC ), mainly deforestation, are based on land use and land use change data and bookkeeping models. Atmospheric CO2 concentration is measured directly and its growth rate ( GATM ) is computed from the annual changes in concentration. The ocean CO2 sink ( SOCEAN ) and terrestrial CO2 sink ( SLAND ) are estimated with global process models constrained by observations. The resulting carbon budget imbalance ( BIM ), the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere, is a measure of imperfect data and understanding of the contemporary carbon cycle. All uncertainties are reported as ±1σ . For the last decade available (2009–2018), EFF was 9.5±0.5 GtC yr −1 , ELUC 1.5±0.7 GtC yr −1 , GATM 4.9±0.02 GtC yr −1 ( 2.3±0.01 ppm yr −1 ), SOCEAN 2.5±0.6 GtC yr −1 , and SLAND 3.2±0.6 GtC yr −1 , with a budget imbalance BIM of 0.4 GtC yr −1 indicating overestimated emissions and/or underestimated sinks. For the year 2018 alone, the growth in EFF was about 2.1 % and fossil emissions increased to 10.0±0.5 GtC yr −1 , reaching 10 GtC yr −1 for the first time in history, ELUC was 1.5±0.7 GtC yr −1 , for total anthropogenic CO2 emissions of 11.5±0.9 GtC yr −1 ( 42.5±3.3 GtCO2 ). Also for 2018, GATM was 5.1±0.2 GtC yr −1 ( 2.4±0.1 ppm yr −1 ), SOCEAN was 2.6±0.6 GtC yr −1 , and SLAND was 3.5±0.7 GtC yr −1 , with a BIM of 0.3 GtC. The global atmospheric CO2 concentration reached 407.38±0.1 ppm averaged over 2018. For 2019, preliminary data for the first 6–10 months indicate a reduced growth in EFF of +0.6 % (range of −0.2 % to 1.5 %) based on national emissions projections for China, the USA, the EU, and India and projections of gross domestic product corrected for recent changes in the carbon intensity of the economy for the rest of the world. Overall, the mean and trend in the five components of the global carbon budget are consistently estimated over the period 1959–2018, but discrepancies of up to 1 GtC yr −1 persist for the representation of semi-decadal variability in CO2 fluxes. A detailed comparison among individual estimates and the introduction of a broad range of observations shows (1) no consensus in the mean and trend in land use change emissions over the last decade, (2) a persistent low agreement between the different methods on the magnitude of the land CO2 flux in the northern extra-tropics, and (3) an apparent underestimation of the CO2 variability by ocean models outside the tropics. This living data update documents changes in the methods and data sets used in this new global carbon budget and the progress in understanding of the global carbon cycle compared with previous publications of this data set (Le Quere et al., 2018a, b, 2016, 2015a, b, 2014, 2013). The data generated by this work are available at https://doi.org/10.18160/gcp-2019 (Friedlingstein et al., 2019).

981 citations


Journal ArticleDOI
08 May 2019-Nature
TL;DR: An optical version of a brain-inspired neurosynaptic system, using wavelength division multiplexing techniques, is presented that is capable of supervised and unsupervised learning.
Abstract: Software implementations of brain-inspired computing underlie many important computational tasks, from image processing to speech recognition, artificial intelligence and deep learning applications. Yet, unlike real neural tissue, traditional computing architectures physically separate the core computing functions of memory and processing, making fast, efficient and low-energy computing difficult to achieve. To overcome such limitations, an attractive alternative is to design hardware that mimics neurons and synapses. Such hardware, when connected in networks or neuromorphic systems, processes information in a way more analogous to brains. Here we present an all-optical version of such a neurosynaptic system, capable of supervised and unsupervised learning. We exploit wavelength division multiplexing techniques to implement a scalable circuit architecture for photonic neural networks, successfully demonstrating pattern recognition directly in the optical domain. Such photonic neurosynaptic networks promise access to the high speed and high bandwidth inherent to optical systems, thus enabling the direct processing of optical telecommunication and visual data. An optical version of a brain-inspired neurosynaptic system, using wavelength division multiplexing techniques, is presented that is capable of supervised and unsupervised learning.

862 citations


Journal ArticleDOI
TL;DR: The 2019 report of The Lancet Countdown on health and climate change : ensuring that the health of a child born today is not defined by a changing climate is ensured.

794 citations


Journal ArticleDOI
TL;DR: It is shown how ecosystem service assessments can be expanded to include mental health, and a heuristic, conceptual model for doing so is provided.
Abstract: A growing body of empirical evidence is revealing the value of nature experience for mental health. With rapid urbanization and declines in human contact with nature globally, crucial decisions must be made about how to preserve and enhance opportunities for nature experience. Here, we first provide points of consensus across the natural, social, and health sciences on the impacts of nature experience on cognitive functioning, emotional well-being, and other dimensions of mental health. We then show how ecosystem service assessments can be expanded to include mental health, and provide a heuristic, conceptual model for doing so.

736 citations


Journal ArticleDOI
TL;DR: In this paper, the authors presented a paper on the African Climate and Development Initiative (ACDI) in South Africa, focusing on the effects of climate change on the local environment.
Abstract: 1 Department of Forest Ecosystems and Society, Oregon State University, Corvallis, OR 97331, USA 2 School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia 3 Conservation Biology Institute, 136 SW Washington Avenue, Suite 202, Corvallis, OR 97333, USA 4 African Climate and Development Initiative, University of Cape Town, Cape Town, 7700, South Africa. 5 The Fletcher School and Global Development and Environment Institute, Tufts University, Medford, MA, USA

609 citations


Journal ArticleDOI
TL;DR: The results highlight that the impacts of VPD on vegetation growth should be adequately considered to assess ecosystem responses to future climate conditions.
Abstract: Atmospheric vapor pressure deficit (VPD) is a critical variable in determining plant photosynthesis. Synthesis of four global climate datasets reveals a sharp increase of VPD after the late 1990s. In response, the vegetation greening trend indicated by a satellite-derived vegetation index (GIMMS3g), which was evident before the late 1990s, was subsequently stalled or reversed. Terrestrial gross primary production derived from two satellite-based models (revised EC-LUE and MODIS) exhibits persistent and widespread decreases after the late 1990s due to increased VPD, which offset the positive CO2 fertilization effect. Six Earth system models have consistently projected continuous increases of VPD throughout the current century. Our results highlight that the impacts of VPD on vegetation growth should be adequately considered to assess ecosystem responses to future climate conditions.

605 citations


Journal ArticleDOI
TL;DR: A genome‐wide association study meta‐analysis of body fat distribution, measured by waist‐to‐hip ratio (WHR) adjusted for body mass index (WHRadjBMI), and identified 463 signals in 346 loci found heritability and variant effects were generally stronger in women than men, and one‐third of all signals to be sexually dimorphic.
Abstract: More than one in three adults worldwide is either overweight or obese. Epidemiological studies indicate that the location and distribution of excess fat, rather than general adiposity, are more informative for predicting risk of obesity sequelae, including cardiometabolic disease and cancer. We performed a genome-wide association study meta-analysis of body fat distribution, measured by waist-to-hip ratio (WHR) adjusted for body mass index (WHRadjBMI), and identified 463 signals in 346 loci. Heritability and variant effects were generally stronger in women than men, and we found approximately one-third of all signals to be sexually dimorphic. The 5% of individuals carrying the most WHRadjBMI-increasing alleles were 1.62 times more likely than the bottom 5% to have a WHR above the thresholds used for metabolic syndrome. These data, made publicly available, will inform the biology of body fat distribution and its relationship with disease.

580 citations


Journal ArticleDOI
TL;DR: It is argued that implementation of agreed-upon standards for models in biodiversity assessments would promote transparency and repeatability, eventually leading to higher quality of the models and the inferences used in assessments.
Abstract: Demand for models in biodiversity assessments is rising, but which models are adequate for the task? We propose a set of best-practice standards and detailed guidelines enabling scoring of studies based on species distribution models for use in biodiversity assessments. We reviewed and scored 400 modeling studies over the past 20 years using the proposed standards and guidelines. We detected low model adequacy overall, but with a marked tendency of improvement over time in model building and, to a lesser degree, in biological data and model evaluation. We argue that implementation of agreed-upon standards for models in biodiversity assessments would promote transparency and repeatability, eventually leading to higher quality of the models and the inferences used in assessments. We encourage broad community participation toward the expansion and ongoing development of the proposed standards and guidelines.

519 citations


Journal ArticleDOI
TL;DR: Patients and surgeons can expect a hip replacement to last 25 years in around 58% of patients, assuming that estimates from national registries are less likely to be biased.

516 citations


Journal ArticleDOI
TL;DR: H2 O2 oxidizes specific cysteine residues of target proteins to the sulfenic acid form and, similar to other organisms, this modification could initiate thiol-based redox relays and modify target enzymes, receptor kinases and transcription factors.
Abstract: Contents Summary 1197 I Introduction 1198 II Measurement and imaging of H2 O2 1198 III H2 O2 and O2 ·- toxicity 1199 IV Production of H2 O2 : enzymes and subcellular locations 1200 V H2 O2 transport 1205 VI Control of H2 O2 concentration: how and where? 1205 VII Metabolic functions of H2 O2 1207 VIII H2 O2 signalling 1207 IX Where next? 1209 Acknowledgements 1209 References 1209 SUMMARY: Hydrogen peroxide (H2 O2 ) is produced, via superoxide and superoxide dismutase, by electron transport in chloroplasts and mitochondria, plasma membrane NADPH oxidases, peroxisomal oxidases, type III peroxidases and other apoplastic oxidases Intracellular transport is facilitated by aquaporins and H2 O2 is removed by catalase, peroxiredoxin, glutathione peroxidase-like enzymes and ascorbate peroxidase, all of which have cell compartment-specific isoforms Apoplastic H2 O2 influences cell expansion, development and defence by its involvement in type III peroxidase-mediated polymer cross-linking, lignification and, possibly, cell expansion via H2 O2 -derived hydroxyl radicals Excess H2 O2 triggers chloroplast and peroxisome autophagy and programmed cell death The role of H2 O2 in signalling, for example during acclimation to stress and pathogen defence, has received much attention, but the signal transduction mechanisms are poorly defined H2 O2 oxidizes specific cysteine residues of target proteins to the sulfenic acid form and, similar to other organisms, this modification could initiate thiol-based redox relays and modify target enzymes, receptor kinases and transcription factors Quantification of the sources and sinks of H2 O2 is being improved by the spatial and temporal resolution of genetically encoded H2 O2 sensors, such as HyPer and roGFP2-Orp1 These H2 O2 sensors, combined with the detection of specific proteins modified by H2 O2 , will allow a deeper understanding of its signalling roles

Journal ArticleDOI
16 May 2019-Cell
TL;DR: An ∼12-fold expanded global ocean DNA virome dataset is established of 195,728 viral populations, now including the Arctic Ocean, and it is validated that these populations form discrete genotypic clusters.

Journal ArticleDOI
TL;DR: This analysis is written with the dual aim of helping clinical safety professionals to critically appraise current medical AI research from a quality and safety perspective, and supporting research and development in AI by highlighting some of the clinical safety questions that must be considered if medical application of these exciting technologies is to be successful.
Abstract: In medicine, artificial intelligence (AI) research is becoming increasingly focused on applying machine learning (ML) techniques to complex problems, and so allowing computers to make predictions from large amounts of patient data, by learning their own associations.1 Estimates of the impact of AI on the wider economy globally vary wildly, with a recent report suggesting a 14% effect on global gross domestic product by 2030, half of which coming from productivity improvements.2 These predictions create political appetite for the rapid development of the AI industry,3 and healthcare is a priority area where this technology has yet to be exploited.2 3 The digital health revolution described by Duggal et al 4 is already in full swing with the potential to ‘disrupt’ healthcare. Health AI research has demonstrated some impressive results,5–10 but its clinical value has not yet been realised, hindered partly by a lack of a clear understanding of how to quantify benefit or ensure patient safety, and increasing concerns about the ethical and medico-legal impact.11 This analysis is written with the dual aim of helping clinical safety professionals to critically appraise current medical AI research from a quality and safety perspective, and supporting research and development in AI by highlighting some of the clinical safety questions that must be considered if medical application of these exciting technologies is to be successful. Clinical decision support systems (DSS) are in widespread use in medicine and have had most impact providing guidance on the safe prescription of medicines,12 guideline adherence, simple risk screening13 or prognostic scoring.14 These systems use predefined rules, which have predictable behaviour and are usually shown to reduce clinical error,12 although sometimes inadvertently introduce safety issues themselves.15 16 Rules-based systems have also been developed to address diagnostic uncertainty17–19 …

Journal ArticleDOI
TL;DR: Positive associations between recreational nature contact in the last seven days and self-reported health and well-being were consistent across key groups including older adults and those with long-term health issues.
Abstract: Spending time in natural environments can benefit health and well-being, but exposure-response relationships are under-researched. We examined associations between recreational nature contact in the last seven days and self-reported health and well-being. Participants (n = 19,806) were drawn from the Monitor of Engagement with the Natural Environment Survey (2014/15–2015/16); weighted to be nationally representative. Weekly contact was categorised using 60 min blocks. Analyses controlled for residential greenspace and other neighbourhood and individual factors. Compared to no nature contact last week, the likelihood of reporting good health or high well-being became significantly greater with contact ≥120 mins (e.g. 120–179 mins: ORs [95%CIs]: Health = 1.59 [1.31–1.92]; Well-being = 1.23 [1.08–1.40]). Positive associations peaked between 200–300 mins per week with no further gain. The pattern was consistent across key groups including older adults and those with long-term health issues. It did not matter how 120 mins of contact a week was achieved (e.g. one long vs. several shorter visits/week). Prospective longitudinal and intervention studies are a critical next step in developing possible weekly nature exposure guidelines comparable to those for physical activity.

Journal ArticleDOI
01 Mar 2019-Science
TL;DR: Advances in the understanding of pantropical interbasin climate interactions are reviewed and their implications for both climate prediction and future climate projections are reviewed.
Abstract: The El Nino-Southern Oscillation (ENSO), which originates in the Pacific, is the strongest and most well-known mode of tropical climate variability. Its reach is global, and it can force climate variations of the tropical Atlantic and Indian Oceans by perturbing the global atmospheric circulation. Less appreciated is how the tropical Atlantic and Indian Oceans affect the Pacific. Especially noteworthy is the multidecadal Atlantic warming that began in the late 1990s, because recent research suggests that it has influenced Indo-Pacific climate, the character of the ENSO cycle, and the hiatus in global surface warming. Discovery of these pantropical interactions provides a pathway forward for improving predictions of climate variability in the current climate and for refining projections of future climate under different anthropogenic forcing scenarios.

Journal ArticleDOI
TL;DR: The United Kingdom Earth System Model UKESM1 as discussed by the authors was developed and tuned to achieve acceptable performance in key physical and Earth system quantities, and discuss the challenges involved in mitigating biases in a model with complex connections between its components.
Abstract: We document the development of the first version of the United Kingdom Earth System Model UKESM1. The model represents a major advance on its predecessor HadGEM2‐ES, with enhancements to all component models and new feedback mechanisms. These include: a new core physical model with a well‐resolved stratosphere; terrestrial biogeochemistry with coupled carbon and nitrogen cycles and enhanced land management; tropospheric‐stratospheric chemistry allowing the holistic simulation of radiative forcing from ozone, methane and nitrous oxide; two‐moment, five‐species, modal aerosol; and ocean biogeochemistry with two‐way coupling to the carbon cycle and atmospheric aerosols. The complexity of coupling between the ocean, land and atmosphere physical climate and biogeochemical cycles in UKESM1 is unprecedented for an Earth system model. We describe in detail the process by which the coupled model was developed and tuned to achieve acceptable performance in key physical and Earth system quantities, and discuss the challenges involved in mitigating biases in a model with complex connections between its components. Overall the model performs well, with a stable pre‐industrial state, and good agreement with observations in the latter period of its historical simulations. However, global mean surface temperature exhibits stronger‐than‐observed cooling from 1950 to 1970, followed by rapid warming from 1980 to 2014. Metrics from idealised simulations show a high climate sensitivity relative to previous generations of models: equilibrium climate sensitivity (ECS) is 5.4 K, transient climate response (TCR) ranges from 2.68 K to 2.85 K, and transient climate response to cumulative emissions (TCRE) is 2.49 K/TtC to 2.66 K/TtC.

Journal ArticleDOI
TL;DR: The authors discusses newly developed tools that facilitate a more rapid and comprehensive evaluation of model simulations with observations, process-based emergent constraints that are a promising way to focus evaluation on the observations most relevant to climate projections, and advanced methods for model weighting.
Abstract: Earth system models are complex and represent a large number of processes, resulting in a persistent spread across climate projections for a given future scenario. Owing to different model performances against observations and the lack of independence among models, there is now evidence that giving equal weight to each available model projection is suboptimal. This Perspective discusses newly developed tools that facilitate a more rapid and comprehensive evaluation of model simulations with observations, process-based emergent constraints that are a promising way to focus evaluation on the observations most relevant to climate projections, and advanced methods for model weighting. These approaches are needed to distil the most credible information on regional climate changes, impacts, and risks for stakeholders and policy-makers.

Proceedings ArticleDOI
Matej Kristan1, Amanda Berg2, Linyu Zheng3, Litu Rout4  +176 moreInstitutions (43)
01 Oct 2019
TL;DR: The Visual Object Tracking challenge VOT2019 is the seventh annual tracker benchmarking activity organized by the VOT initiative; results of 81 trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in the recent years.
Abstract: The Visual Object Tracking challenge VOT2019 is the seventh annual tracker benchmarking activity organized by the VOT initiative. Results of 81 trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in the recent years. The evaluation included the standard VOT and other popular methodologies for short-term tracking analysis as well as the standard VOT methodology for long-term tracking analysis. The VOT2019 challenge was composed of five challenges focusing on different tracking domains: (i) VOTST2019 challenge focused on short-term tracking in RGB, (ii) VOT-RT2019 challenge focused on "real-time" shortterm tracking in RGB, (iii) VOT-LT2019 focused on longterm tracking namely coping with target disappearance and reappearance. Two new challenges have been introduced: (iv) VOT-RGBT2019 challenge focused on short-term tracking in RGB and thermal imagery and (v) VOT-RGBD2019 challenge focused on long-term tracking in RGB and depth imagery. The VOT-ST2019, VOT-RT2019 and VOT-LT2019 datasets were refreshed while new datasets were introduced for VOT-RGBT2019 and VOT-RGBD2019. The VOT toolkit has been updated to support both standard shortterm, long-term tracking and tracking with multi-channel imagery. Performance of the tested trackers typically by far exceeds standard baselines. The source code for most of the trackers is publicly available from the VOT page. The dataset, the evaluation kit and the results are publicly available at the challenge website.

Journal ArticleDOI
TL;DR: Clinical and pharmacokinetic factors that predict primary non-response at week 14 after starting treatment, non-remission at week 54, and adverse events leading to drug withdrawal are identified.

Journal ArticleDOI
TL;DR: It is shown that being a morning person is causally associated with better mental health but does not affect BMI or risk of Type 2 diabetes, and the chronotype loci associate with sleep timing.
Abstract: Being a morning person is a behavioural indicator of a person's underlying circadian rhythm. Using genome-wide data from 697,828 UK Biobank and 23andMe participants we increase the number of genetic loci associated with being a morning person from 24 to 351. Using data from 85,760 individuals with activity-monitor derived measures of sleep timing we find that the chronotype loci associate with sleep timing: the mean sleep timing of the 5% of individuals carrying the most morningness alleles is 25 min earlier than the 5% carrying the fewest. The loci are enriched for genes involved in circadian regulation, cAMP, glutamate and insulin signalling pathways, and those expressed in the retina, hindbrain, hypothalamus, and pituitary. Using Mendelian Randomisation, we show that being a morning person is causally associated with better mental health but does not affect BMI or risk of Type 2 diabetes. This study offers insights into circadian biology and its links to disease in humans.

Journal ArticleDOI
TL;DR: Pesticide resistance provides an interesting case of rapid evolution under strong selective pressures, which can be used to address fundamental questions concerning the evolutionary origins of adaptations to novel conditions, and lessons learnt from pesticide resistance should be applied in the deployment of novel, non‐chemical pest‐control methods.
Abstract: Durable crop protection is an essential component of current and future food security. However, the effectiveness of pesticides is threatened by the evolution of resistant pathogens, weeds and insect pests. Pesticides are mostly novel synthetic compounds, and yet target species are often able to evolve resistance soon after a new compound is introduced. Therefore, pesticide resistance provides an interesting case of rapid evolution under strong selective pressures, which can be used to address fundamental questions concerning the evolutionary origins of adaptations to novel conditions. We ask: (i) whether this adaptive potential originates mainly from de novo mutations or from standing variation; (ii) which pre-existing traits could form the basis of resistance adaptations; and (iii) whether recurrence of resistance mechanisms among species results from interbreeding and horizontal gene transfer or from independent parallel evolution. We compare and contrast the three major pesticide groups: insecticides, herbicides and fungicides. Whilst resistance to these three agrochemical classes is to some extent united by the common evolutionary forces at play, there are also important differences. Fungicide resistance appears to evolve, in most cases, by de novo point mutations in the target-site encoding genes; herbicide resistance often evolves through selection of polygenic metabolic resistance from standing variation; and insecticide resistance evolves through a combination of standing variation and de novo mutations in the target site or major metabolic resistance genes. This has practical implications for resistance risk assessment and management, and lessons learnt from pesticide resistance should be applied in the deployment of novel, non-chemical pest-control methods.

Journal ArticleDOI
TL;DR: A taxonomy of different data driven evolutionary optimization problems is provided, main challenges in data-driven evolutionary optimization with respect to the nature and amount of data, and the availability of new data during optimization are discussed.
Abstract: Most evolutionary optimization algorithms assume that the evaluation of the objective and constraint functions is straightforward. In solving many real-world optimization problems, however, such objective functions may not exist. Instead, computationally expensive numerical simulations or costly physical experiments must be performed for fitness evaluations. In more extreme cases, only historical data are available for performing optimization and no new data can be generated during optimization. Solving evolutionary optimization problems driven by data collected in simulations, physical experiments, production processes, or daily life are termed data-driven evolutionary optimization. In this paper, we provide a taxonomy of different data driven evolutionary optimization problems, discuss main challenges in data-driven evolutionary optimization with respect to the nature and amount of data, and the availability of new data during optimization. Real-world application examples are given to illustrate different model management strategies for different categories of data-driven optimization problems.

Journal ArticleDOI
06 Aug 2019-JAMA
TL;DR: Among older adults without cognitive impairment or dementia, both an unfavorable lifestyle and high genetic risk were significantly associated with higher dementia risk, while a favorable lifestyle was associated with a lower dementia risk among participants with high Genetic risk.
Abstract: Importance Genetic factors increase risk of dementia, but the extent to which this can be offset by lifestyle factors is unknown. Objective To investigate whether a healthy lifestyle is associated with lower risk of dementia regardless of genetic risk. Design, Setting, and Participants A retrospective cohort study that included adults of European ancestry aged at least 60 years without cognitive impairment or dementia at baseline. Participants joined the UK Biobank study from 2006 to 2010 and were followed up until 2016 or 2017. Exposures A polygenic risk score for dementia with low (lowest quintile), intermediate (quintiles 2 to 4), and high (highest quintile) risk categories and a weighted healthy lifestyle score, including no current smoking, regular physical activity, healthy diet, and moderate alcohol consumption, categorized into favorable, intermediate, and unfavorable lifestyles. Main Outcomes and Measures Incident all-cause dementia, ascertained through hospital inpatient and death records. Results A total of 196 383 individuals (mean [SD] age, 64.1 [2.9] years; 52.7% were women) were followed up for 1 545 433 person-years (median [interquartile range] follow-up, 8.0 [7.4-8.6] years). Overall, 68.1% of participants followed a favorable lifestyle, 23.6% followed an intermediate lifestyle, and 8.2% followed an unfavorable lifestyle. Twenty percent had high polygenic risk scores, 60% had intermediate risk scores, and 20% had low risk scores. Of the participants with high genetic risk, 1.23% (95% CI, 1.13%-1.35%) developed dementia compared with 0.63% (95% CI, 0.56%-0.71%) of the participants with low genetic risk (adjusted hazard ratio, 1.91 [95% CI, 1.64-2.23]). Of the participants with a high genetic risk and unfavorable lifestyle, 1.78% (95% CI, 1.38%-2.28%) developed dementia compared with 0.56% (95% CI, 0.48%-0.66%) of participants with low genetic risk and favorable lifestyle (hazard ratio, 2.83 [95% CI, 2.09-3.83]). There was no significant interaction between genetic risk and lifestyle factors (P = .99). Among participants with high genetic risk, 1.13% (95% CI, 1.01%-1.26%) of those with a favorable lifestyle developed dementia compared with 1.78% (95% CI, 1.38%-2.28%) with an unfavorable lifestyle (hazard ratio, 0.68 [95% CI, 0.51-0.90]). Conclusions and Relevance Among older adults without cognitive impairment or dementia, both an unfavorable lifestyle and high genetic risk were significantly associated with higher dementia risk. A favorable lifestyle was associated with a lower dementia risk among participants with high genetic risk.

Journal ArticleDOI
TL;DR: An expanded GWAS of birth weight and subsequent analysis using structural equation modeling and Mendelian randomization decomposes maternal and fetal genetic contributions and causal links between birth weight, blood pressure and glycemic traits.
Abstract: Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.

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TL;DR: The MIUViG (Minimum Information about an Uncultivated Virus Genome) as mentioned in this paper standard was developed within the Genomic Standards Consortium framework and includes virus origin, genome quality, genome annotation, taxonomic classification, biogeographic distribution and in silico host prediction.
Abstract: We present an extension of the Minimum Information about any (x) Sequence (MIxS) standard for reporting sequences of uncultivated virus genomes. Minimum Information about an Uncultivated Virus Genome (MIUViG) standards were developed within the Genomic Standards Consortium framework and include virus origin, genome quality, genome annotation, taxonomic classification, biogeographic distribution and in silico host prediction. Community-wide adoption of MIUViG standards, which complement the Minimum Information about a Single Amplified Genome (MISAG) and Metagenome-Assembled Genome (MIMAG) standards for uncultivated bacteria and archaea, will improve the reporting of uncultivated virus genomes in public databases. In turn, this should enable more robust comparative studies and a systematic exploration of the global virosphere.

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TL;DR: Nielsen et al. as discussed by the authors presented a statistical analysis of the first 300 stars observed by the Gemini Planet Imager Exoplanet Survey (GPEES) to infer the underlying distributions of substellar companions with respect to their mass, semimajor axis, and host stellar mass.
Abstract: Author(s): Nielsen, EL; De Rosa, RJ; Macintosh, B; Wang, JJ; Ruffio, JB; Chiang, E; Marley, MS; Saumon, D; Savransky, D; Mark Ammons, S; Bailey, VP; Barman, T; Blain, C; Bulger, J; Burrows, A; Chilcote, J; Cotten, T; Czekala, I; Doyon, R; Duchene, G; Esposito, TM; Fabrycky, D; Fitzgerald, MP; Follette, KB; Fortney, JJ; Gerard, BL; Goodsell, SJ; Graham, JR; Greenbaum, AZ; Hibon, P; Hinkley, S; Hirsch, LA; Hom, J; Hung, LW; Ilene Dawson, R; Ingraham, P; Kalas, P; Konopacky, Q; Larkin, JE; Lee, EJ; Lin, JW; Maire, J; Marchis, F; Marois, C; Metchev, S; Millar-Blanchaer, MA; Morzinski, KM; Oppenheimer, R; Palmer, D; Patience, J; Perrin, M; Poyneer, L; Pueyo, L; Rafikov, RR; Rajan, A; Rameau, J; Rantakyro, FT; Ren, B; Schneider, AC; Sivaramakrishnan, A; Song, I; Soummer, R; Tallis, M; Thomas, S; Ward-Duong, K; Wolff, S | Abstract: We present a statistical analysis of the first 300 stars observed by the Gemini Planet Imager Exoplanet Survey. This subsample includes six detected planets and three brown dwarfs; from these detections and our contrast curves we infer the underlying distributions of substellar companions with respect to their mass, semimajor axis, and host stellar mass. We uncover a strong correlation between planet occurrence rate and host star mass, with stars M ∗ g1.5 M o more likely to host planets with masses between 2 and 13M Jup and semimajor axes of 3-100 au at 99.92% confidence. We fit a double power-law model in planet mass (m) and semimajor axis (a) for planet populations around high-mass stars (M ∗ g1.5 M o) of the form , finding α = -2.4 +0.8 and β = -2.0 +0.5, and an integrated occurrence rate of % between 5-13M Jup and 10-100 au. A significantly lower occurrence rate is obtained for brown dwarfs around all stars, with % of stars hosting a brown dwarf companion between 13-80M Jup and 10-100 au. Brown dwarfs also appear to be distributed differently in mass and semimajor axis compared to giant planets; whereas giant planets follow a bottom-heavy mass distribution and favor smaller semimajor axes, brown dwarfs exhibit just the opposite behaviors. Comparing to studies of short-period giant planets from the radial velocity method, our results are consistent with a peak in occurrence of giant planets between ∼1 and 10 au. We discuss how these trends, including the preference of giant planets for high-mass host stars, point to formation of giant planets by core/pebble accretion, and formation of brown dwarfs by gravitational instability.

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TL;DR: Cardiac rehabilitation may make little or no difference in all-cause mortality over the short term, but may improve all- Cause mortality in the long term (> 12 months follow-up) and downgraded results using the GRADE tool for all but one outcome.
Abstract: Background Chronic heart failure (HF) is a growing global health challenge. People with HF experience substantial burden that includes low exercise tolerance, poor health-related quality of life (HRQoL), increased risk of mortality and hospital admission, and high healthcare costs. The previous (2014) Cochrane systematic review reported that exercise-based cardiac rehabilitation (CR) compared to no exercise control shows improvement in HRQoL and hospital admission among people with HF, as well as possible reduction in mortality over the longer term, and that these reductions appear to be consistent across patient and programme characteristics. Limitations noted by the authors of this previous Cochrane Review include the following: (1) most trials were undertaken in patients with HF with reduced (< 45%) ejection fraction (HFrEF), and women, older people, and those with preserved (≥ 45%) ejection fraction HF (HFpEF) were under-represented; and (2) most trials were undertaken in the hospital/centre-based setting. Objectives To determine the effects of exercise-based cardiac rehabilitation on mortality, hospital admission, and health-related quality of life of people with heart failure. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and three other databases on 29 January 2018. We also checked the bibliographies of systematic reviews and two trial registers. Selection criteria We included randomised controlled trials that compared exercise-based CR interventions with six months’ or longer follow-up versus a no exercise control that could include usual medical care. The study population comprised adults (> 18 years) with evidence of HF - either HFrEF or HFpEF. Data collection and analysis Two review authors independently screened all identified references and rejected those that were clearly ineligible for inclusion in the review. We obtained full papers of potentially relevant trials. Two review authors independently extracted data from the included trials, assessed their risk of bias, and performed GRADE analyses. Main results We included 44 trials (5783 participants with HF) with a median of six months’ follow-up. For this latest update, we identified 11 new trials (N = 1040), in addition to the previously identified 33 trials. Although the evidence base includes predominantly patients with HFrEF with New York Heart Association classes II and III receiving centre-based exercise-based CR programmes, a growing body of studies include patients with HFpEF and are undertaken in a home-based setting. All included studies included a no formal exercise training intervention comparator. However, a wide range of comparators were seen across studies that included active intervention (i.e. education, psychological intervention) or usual medical care alone. The overall risk of bias of included trials was low or unclear, and we downgraded results using the GRADE tool for all but one outcome. Cardiac rehabilitation may make little or no difference in all-cause mortality over the short term (≤ one year of follow-up) (27 trials, 28 comparisons (2596 participants): intervention 67/1302 (5.1%) vs control 75/1294 (5.8%); risk ratio (RR) 0.89, 95% confidence interval (CI) 0.66 to 1.21; low-quality GRADE evidence) but may improve all-cause mortality in the long term (> 12 months follow up) (6 trials/comparisons (2845 participants): intervention 244/1418 (17.2%) vs control 280/1427 (19.6%) events): RR 0.88, 95% CI 0.75 to 1.02; high-quality evidence). Researchers provided no data on deaths due to HF. CR probably reduces overall hospital admissions in the short term (up to one year of follow-up) (21 trials, 21 comparisons (2182 participants): (intervention 180/1093 (16.5%) vs control 258/1089 (23.7%); RR 0.70, 95% CI 0.60 to 0.83; moderate-quality evidence, number needed to treat: 14) and may reduce HF-specific hospitalisation (14 trials, 15 comparisons (1114 participants): (intervention 40/562 (7.1%) vs control 61/552 (11.1%) RR 0.59, 95% CI 0.42 to 0.84; low-quality evidence, number needed to treat: 25). After CR, a clinically important improvement in shortterm disease-specific health-related quality of life may be evident (Minnesota Living With Heart Failure questionnaire - 17 trials, 18 comparisons (1995 participants): mean difference (MD) -7.11 points, 95% CI -10.49 to -3.73; low-quality evidence). Pooling across all studies, regardless of the HRQoL measure used, shows there may be clinically important improvement with exercise (26 trials, 29 comparisons (3833 participants); standardised mean difference (SMD) -0.60, 95% CI -0.82 to -0.39; I² = 87%; Chi² = 215.03; lowquality evidence). ExCR effects appeared to be consistent different models of ExCR delivery: centre vs. home-based, exercise dose, exercise only vs. comprehensive programmes, and aerobic training alone vs aerobic plus resistance programmes. Authors’ conclusions This updated Cochrane Review provides additional randomised evidence (11 trials) to support the conclusions of the previous version (2014) of this Cochane Review. Compared to no exercise control, CR appears to have no impact on mortality in the short term (< 12 months’ follow-up). Low- to moderate-quality evidence shows that CR probably reduces the risk of all-cause hospital admissions and may reduce HF-specific hospital admissions in the short term (up to 12 months). CR may confer a clinically important improvement in health-related quality of life, although we remain uncertain about this because the evidence is of low quality. Future ExCR trials need to continue to consider the recruitment of traditionally less represented HF patient groups including older, female, and HFpEF patients, and alternative CR delivery settings including home- and using technology-based programmes.

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TL;DR: The visual component of VCs offers distinct advantages over telephone consultations, and when integrated with current systems VCs can provide a time-saving alternative to face-to-face consultations when formal physical examination is not required.
Abstract: Background People increasingly communicate online, using visual communication mediums such as Skype and FaceTime. Growing demands on primary care services mean that new ways of providing patient care are being considered. Video consultation (VC) over the internet is one such mode. Aim To explore patients’ and clinicians’ experiences of VC. Design and setting Semi-structured interviews in UK primary care. Method Primary care clinicians were provided with VC equipment. They invited patients requiring a follow-up consultation to an online VC using the Attend Anywhere web-based platform. Participating patients required a smartphone, tablet, or video-enabled computer. Following VCs, semi-structured interviews were conducted with patients (n = 21) and primary care clinicians (n = 13), followed by a thematic analysis. Results Participants reported positive experiences of VC, and stated that VC was particularly helpful for them as working people and people with mobility or mental health problems. VCs were considered superior to telephone consultations in providing visual cues and reassurance, building rapport, and improving communication. Technical problems, however, were common. Clinicians felt, for routine use, VCs must be more reliable and seamlessly integrated with appointment systems, which would require upgrading of current NHS IT systems. Conclusion The visual component of VCs offers distinct advantages over telephone consultations. When integrated with current systems VCs can provide a time-saving alternative to face-to-face consultations when formal physical examination is not required, especially for people who work. Demand for VC services in primary care is likely to rise, but improved technical infrastructure is required to allow VC to become routine. However, for complex or sensitive problems face-to-face consultations remain preferable.

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TL;DR: Performing GWAS for self-reported habitual sleep duration in adults, supported by accelerometer-derived measures, and identifying genetic correlation with psychiatric and metabolic traits provides insights into the genetic basis for inter-individual variation in sleep duration implicating multiple biological pathways.
Abstract: Sleep is an essential state of decreased activity and alertness but molecular factors regulating sleep duration remain unknown. Through genome-wide association analysis in 446,118 adults of European ancestry from the UK Biobank, we identify 78 loci for self-reported habitual sleep duration (p < 5 × 10−8; 43 loci at p < 6 × 10−9). Replication is observed for PAX8, VRK2, and FBXL12/UBL5/PIN1 loci in the CHARGE study (n = 47,180; p < 6.3 × 10−4), and 55 signals show sign-concordant effects. The 78 loci further associate with accelerometer-derived sleep duration, daytime inactivity, sleep efficiency and number of sleep bouts in secondary analysis (n = 85,499). Loci are enriched for pathways including striatum and subpallium development, mechanosensory response, dopamine binding, synaptic neurotransmission and plasticity, among others. Genetic correlation indicates shared links with anthropometric, cognitive, metabolic, and psychiatric traits and two-sample Mendelian randomization highlights a bidirectional causal link with schizophrenia. This work provides insights into the genetic basis for inter-individual variation in sleep duration implicating multiple biological pathways.

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06 Nov 2019-Nature
TL;DR: A roadmap for sex and gender analysis across scientific disciplines is provided and it is called on researchers, funding agencies, peer-reviewed journals and universities to coordinate efforts to implement robust methods of sex andGender analysis.
Abstract: The goal of sex and gender analysis is to promote rigorous, reproducible and responsible science. Incorporating sex and gender analysis into experimental design has enabled advancements across many disciplines, such as improved treatment of heart disease and insights into the societal impact of algorithmic bias. Here we discuss the potential for sex and gender analysis to foster scientific discovery, improve experimental efficiency and enable social equality. We provide a roadmap for sex and gender analysis across scientific disciplines and call on researchers, funding agencies, peer-reviewed journals and universities to coordinate efforts to implement robust methods of sex and gender analysis. The authors discuss the potential for sex and gender analysis to foster scientific discovery, improve experimental efficiency and enable social equality.