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Showing papers by "University of East Anglia published in 2018"


Journal ArticleDOI
Corinne Le Quéré1, Robbie M. Andrew, Pierre Friedlingstein2, Stephen Sitch2, Judith Hauck3, Julia Pongratz4, Julia Pongratz5, Penelope A. Pickers1, Jan Ivar Korsbakken, Glen P. Peters, Josep G. Canadell6, Almut Arneth7, Vivek K. Arora, Leticia Barbero8, Leticia Barbero9, Ana Bastos5, Laurent Bopp10, Frédéric Chevallier11, Louise Chini12, Philippe Ciais11, Scott C. Doney13, Thanos Gkritzalis14, Daniel S. Goll11, Ian Harris1, Vanessa Haverd6, Forrest M. Hoffman15, Mario Hoppema3, Richard A. Houghton16, George C. Hurtt12, Tatiana Ilyina4, Atul K. Jain17, Truls Johannessen18, Chris D. Jones19, Etsushi Kato, Ralph F. Keeling20, Kees Klein Goldewijk21, Kees Klein Goldewijk22, Peter Landschützer4, Nathalie Lefèvre23, Sebastian Lienert24, Zhu Liu25, Zhu Liu1, Danica Lombardozzi26, Nicolas Metzl23, David R. Munro27, Julia E. M. S. Nabel4, Shin-Ichiro Nakaoka28, Craig Neill29, Craig Neill30, Are Olsen18, T. Ono, Prabir K. Patra31, Anna Peregon11, Wouter Peters32, Wouter Peters33, Philippe Peylin11, Benjamin Pfeil34, Benjamin Pfeil18, Denis Pierrot9, Denis Pierrot8, Benjamin Poulter35, Gregor Rehder36, Laure Resplandy37, Eddy Robertson19, Matthias Rocher11, Christian Rödenbeck4, Ute Schuster2, Jörg Schwinger34, Roland Séférian11, Ingunn Skjelvan34, Tobias Steinhoff38, Adrienne J. Sutton39, Pieter P. Tans39, Hanqin Tian40, Bronte Tilbrook29, Bronte Tilbrook30, Francesco N. Tubiello41, Ingrid T. van der Laan-Luijkx32, Guido R. van der Werf42, Nicolas Viovy11, Anthony P. Walker15, Andy Wiltshire19, Rebecca Wright1, Sönke Zaehle4, Bo Zheng11 
University of East Anglia1, University of Exeter2, Alfred Wegener Institute for Polar and Marine Research3, Max Planck Society4, Ludwig Maximilian University of Munich5, Commonwealth Scientific and Industrial Research Organisation6, Karlsruhe Institute of Technology7, Cooperative Institute for Marine and Atmospheric Studies8, Atlantic Oceanographic and Meteorological Laboratory9, École Normale Supérieure10, Centre national de la recherche scientifique11, University of Maryland, College Park12, University of Virginia13, Flanders Marine Institute14, Oak Ridge National Laboratory15, Woods Hole Research Center16, University of Illinois at Urbana–Champaign17, Geophysical Institute, University of Bergen18, Met Office19, University of California, San Diego20, Netherlands Environmental Assessment Agency21, Utrecht University22, University of Paris23, Oeschger Centre for Climate Change Research24, Tsinghua University25, National Center for Atmospheric Research26, Institute of Arctic and Alpine Research27, National Institute for Environmental Studies28, Hobart Corporation29, Cooperative Research Centre30, Japan Agency for Marine-Earth Science and Technology31, Wageningen University and Research Centre32, University of Groningen33, Bjerknes Centre for Climate Research34, Goddard Space Flight Center35, Leibniz Institute for Baltic Sea Research36, Princeton University37, Leibniz Institute of Marine Sciences38, National Oceanic and Atmospheric Administration39, Auburn University40, Food and Agriculture Organization41, VU University Amsterdam42
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 data and bookkeeping models.
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 and 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 (2008–2017), EFF was 9.4±0.5 GtC yr −1 , ELUC 1.5±0.7 GtC yr −1 , GATM 4.7±0.02 GtC yr −1 , SOCEAN 2.4±0.5 GtC yr −1 , and SLAND 3.2±0.8 GtC yr −1 , with a budget imbalance BIM of 0.5 GtC yr −1 indicating overestimated emissions and/or underestimated sinks. For the year 2017 alone, the growth in EFF was about 1.6 % and emissions increased to 9.9±0.5 GtC yr −1 . Also for 2017, ELUC was 1.4±0.7 GtC yr −1 , GATM was 4.6±0.2 GtC yr −1 , SOCEAN was 2.5±0.5 GtC yr −1 , and SLAND was 3.8±0.8 GtC yr −1 , with a BIM of 0.3 GtC. The global atmospheric CO2 concentration reached 405.0±0.1 ppm averaged over 2017. For 2018, preliminary data for the first 6–9 months indicate a renewed growth in EFF of + 2.7 % (range of 1.8 % to 3.7 %) based on national emission projections for China, the US, 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. The analysis presented here shows that the mean and trend in the five components of the global carbon budget are consistently estimated over the period of 1959–2017, 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 show (1) no consensus in the mean and trend in land-use change emissions, (2) a persistent low agreement among 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, originating 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 the global carbon cycle compared with previous publications of this data set (Le Quere et al., 2018, 2016, 2015a, b, 2014, 2013). All results presented here can be downloaded from https://doi.org/10.18160/GCP-2018 .

1,458 citations


Journal ArticleDOI
TL;DR: Ultra-long reads enabled assembly and phasing of the 4-Mb major histocompatibility complex (MHC) locus in its entirety, measurement of telomere repeat length, and closure of gaps in the reference human genome assembly GRCh38.
Abstract: We report the sequencing and assembly of a reference genome for the human GM12878 Utah/Ceph cell line using the MinION (Oxford Nanopore Technologies) nanopore sequencer. 91.2 Gb of sequence data, representing ∼30× theoretical coverage, were produced. Reference-based alignment enabled detection of large structural variants and epigenetic modifications. De novo assembly of nanopore reads alone yielded a contiguous assembly (NG50 ∼3 Mb). We developed a protocol to generate ultra-long reads (N50 > 100 kb, read lengths up to 882 kb). Incorporating an additional 5× coverage of these ultra-long reads more than doubled the assembly contiguity (NG50 ∼6.4 Mb). The final assembled genome was 2,867 million bases in size, covering 85.8% of the reference. Assembly accuracy, after incorporating complementary short-read sequencing data, exceeded 99.8%. Ultra-long reads enabled assembly and phasing of the 4-Mb major histocompatibility complex (MHC) locus in its entirety, measurement of telomere repeat length, and closure of gaps in the reference human genome assembly GRCh38.

1,425 citations


Journal ArticleDOI
TL;DR: Greenspace exposure is associated with wide ranging health benefits across 143 included studies, and meta‐analysis showed statistically significant reductions in diastolic blood pressure, salivary cortisol and heart rate.

776 citations


Journal ArticleDOI
TL;DR: In this article, a new version of the Europe-wide OBS temperature (daily minimum, mean and maximum values) and precipitation dataset is presented, which provides an improved estimation of interpolation uncertainty through the calculation of a 100-member ensemble of realizations of each daily field.
Abstract: We describe the construction of a new version of the Europe‐wide E‐OBS temperature (daily minimum, mean and maximum values) and precipitation dataset. This version provides an improved estimation of interpolation uncertainty through the calculation of a 100‐member ensemble of realizations of each daily field. The dataset covers the period back to 1950, and provides gridded fields at a spacing of 0.25° x 0.25° in regular latitude/longitude coordinates. As with the original E‐OBS dataset, the ensemble version is based on the station series collated as part of the ECA&D initiative. Station density varies significantly over the domain, and over time, and a reliable estimation of interpolation uncertainty in the gridded fields is therefore important for users of the dataset. The uncertainty quantified by the ensemble dataset is more realistic than the uncertainty estimates in the original version, although uncertainty is still underestimated in data‐sparse regions. The new dataset is compared against the earlier version of E‐OBS and against regional gridded datasets produced by a selection of National Meteorological Services (NMSs). In terms of both climatological averages and extreme values, the new version of E‐OBS is broadly comparable to the earlier version. Nonetheless, users will notice differences between the two E‐OBS versions, especially for precipitation, which arises from the different gridding method used.

766 citations


Journal ArticleDOI
TL;DR: This study constructed the time-series of CO2 emission inventories for China and its 30 provinces following the Intergovernmental Panel on Climate Change (IPCC) emissions accounting method with a territorial administrative scope from 1997 to 2015.
Abstract: China is the world's top energy consumer and CO2 emitter, accounting for 30% of global emissions. Compiling an accurate accounting of China's CO2 emissions is the first step in implementing reduction policies. However, no annual, officially published emissions data exist for China. The current emissions estimated by academic institutes and scholars exhibit great discrepancies. The gap between the different emissions estimates is approximately equal to the total emissions of the Russian Federation (the 4th highest emitter globally) in 2011. In this study, we constructed the time-series of CO2 emission inventories for China and its 30 provinces. We followed the Intergovernmental Panel on Climate Change (IPCC) emissions accounting method with a territorial administrative scope. The inventories include energy-related emissions (17 fossil fuels in 47 sectors) and process-related emissions (cement production). The first version of our dataset presents emission inventories from 1997 to 2015. We will update the dataset annually. The uniformly formatted emission inventories provide data support for further emission-related research as well as emissions reduction policy-making in China.

704 citations


Journal ArticleDOI
TL;DR: In this paper, the authors developed a narrative of future change based on observable trends that results in low energy demand and showed how changes in the quantity and type of energy services drive structural change in intermediate and upstream supply sectors (energy and land use).
Abstract: Scenarios that limit global warming to 1.5 °C describe major transformations in energy supply and ever-rising energy demand. Here, we provide a contrasting perspective by developing a narrative of future change based on observable trends that results in low energy demand. We describe and quantify changes in activity levels and energy intensity in the global North and global South for all major energy services. We project that global final energy demand by 2050 reduces to 245 EJ, around 40% lower than today, despite rises in population, income and activity. Using an integrated assessment modelling framework, we show how changes in the quantity and type of energy services drive structural change in intermediate and upstream supply sectors (energy and land use). Down-sizing the global energy system dramatically improves the feasibility of a low-carbon supply-side transformation. Our scenario meets the 1.5 °C climate target as well as many sustainable development goals, without relying on negative emission technologies. Achieving sustainable development goals while meeting the 1.5 °C climate target requires radical changes to how we use energy. A scenario of low energy demand shows how this can be done by down-sizing the global energy system to enable feasible deployment rates of renewable energy resources.

680 citations


Journal ArticleDOI
TL;DR: The pace of progress achieved between 1990 and 2016 varied, with markedly faster improvements occurring between 2000 and 2016 for many countries in sub-Saharan Africa and southeast Asia, whereas several countries in Latin America and elsewhere saw progress stagnate after experiencing considerable advances in the HAQ Index between1990 and 2000.

623 citations


Ove Hoegh-Guldberg, Daniela Jacob, Marco Bindi, Sally Brown, I. A. Camilloni, Arona Diedhiou, Riyanti Djalante, Kristie L. Ebi1, Francois Engelbrecht1, Joel Guiot, Yasuaki Hijioka, S. Mehrotra, Antony J. Payne2, Sonia I. Seneviratne3, Adelle Thomas3, Rachel Warren4, G. Zhou4, Sharina Abdul Halim, Michelle Achlatis, Lisa V. Alexander, Myles R. Allen, Peter Berry, Christopher Boyer, Edward Byers, Lorenzo Brilli, Marcos Silveira Buckeridge, William W. L. Cheung, Marlies Craig, Neville Ellis, Jason P. Evans, Hubertus Fischer, Klaus Fraedrich, Sabine Fuss, Anjani Ganase, Jean-Pierre Gattuso, Peter Greve, Tania Guillén Bolaños, Naota Hanasaki, Tomoko Hasegawa, Katie Hayes, Annette L. Hirsch, Chris D. Jones, Thomas Jung, Markku Kanninen, Gerhard Krinner, David M. Lawrence, Timothy M. Lenton, Debora Ley, Diana Liverman, Natalie M. Mahowald, Kathleen L. McInnes, Katrin J. Meissner, Richard J. Millar, Katja Mintenbeck, Daniel M. Mitchell, Alan C. Mix, Dirk Notz, Leonard Nurse, Andrew Emmanuel Okem, Lennart Olsson, Michael Oppenheimer, Shlomit Paz, Juliane Petersen, Jan Petzold, Swantje Preuschmann, Mohammad Feisal Rahman, Joeri Rogelj, Hanna Scheuffele, Carl-Friedrich Schleussner, Daniel Scott, Roland Séférian, Jana Sillmann, Chandni Singh, Raphael Slade, Kimberly Stephenson, Tannecia S. Stephenson, Mouhamadou Bamba Sylla, Mark Tebboth, Petra Tschakert, Robert Vautard, Richard Wartenburger, Michael Wehner, Nora Marie Weyer, Felicia S. Whyte, Gary W. Yohe, Xuebin Zhang, Robert B. Zougmoré 
01 Jan 2018
TL;DR: In this article, the authors present a survey of women's sportswriters in South Africa and Ivory Coast, including: Marco Bindi (Italy), Sally Brown (UK), Ines Camilloni (Argentina), Arona Diedhiou (Ivory Coast/Senegal), Riyanti Djalante (Japan/Indonesia), Kristie L. Ebi (USA), Francois Engelbrecht (South Africa), Joel Guiot (France), Yasuaki Hijioka (Japan), Shagun Mehrotra (USA/India), Ant
Abstract: Lead Authors: Marco Bindi (Italy), Sally Brown (UK), Ines Camilloni (Argentina), Arona Diedhiou (Ivory Coast/Senegal), Riyanti Djalante (Japan/Indonesia), Kristie L. Ebi (USA), Francois Engelbrecht (South Africa), Joel Guiot (France), Yasuaki Hijioka (Japan), Shagun Mehrotra (USA/India), Antony Payne (UK), Sonia I. Seneviratne (Switzerland), Adelle Thomas (Bahamas), Rachel Warren (UK), Guangsheng Zhou (China)

614 citations


Journal ArticleDOI
TL;DR: The Atlas confirmed that high-income and middle-income ESC member countries, where the facilities for the contemporary treatment of coronary disease were best developed, were often those in which declines in coronary mortality have been most pronounced.
Abstract: Background: The European Society of Cardiology (ESC) Atlas has been compiled by the European Heart Agency to document cardiovascular disease (CVD) statistics of the 56 ESC member countries. A major aim of this 2017 data presentation has been to compare high income and middle income ESC member countries, in order to identify inequalities in disease burden, outcomes and service provision. Methods: The Atlas utilizes a variety of data sources, including the World Health Organization, the Institute for Health Metrics and Evaluation, and the World Bank to document risk factors, prevalence and mortality of cardiovascular disease and national economic indicators. It also includes novel ESC sponsored survey data of health infrastructure and cardiovascular service provision provided by the national societies of the ESC member countries. Data presentation is descriptive with no attempt to attach statistical significance to differences observed in stratified analyses. Results: Important differences were identified between the high income and middle income member countries of the ESC with regard to CVD risk factors, disease incidence and mortality. For both women and men, the age-standardised prevalence of hypertension was lower in high income countries (18.3% and 27.3%) compared with middle income countries (23.5% and 30.3%). Smoking prevalence in men (not women) was also lower (26% vs 41.3%), and together these inequalities are likely to have contributed to the higher CVD mortality in middle income countries. Declines in CVD mortality have seen cancer becoming a more common cause of death in a number of high income member countries, but in middle income countries declines in CVD mortality have been less consistent where CVD remains the leading cause of death. Inequalities in CVD mortality are emphasised by the smaller contribution they make to potential years of life lost in high income compared with middle income countries both for women (13% vs. 23%) and men (20% vs. 27%). The downward mortality trends for CVD may, however, be threatened by the emerging obesity epidemic that is seeing rates of diabetes increasing across all ESC member countries. Survey data from the National Cardiac Societies (n=41) showed that rates of cardiac catheterization and coronary artery bypass surgery, as well as the number of specialist centres required to deliver them, were greatest in the high income member countries of the ESC. The Atlas confirmed that these ESC member countries, where the facilities for the contemporary treatment of coronary disease were best developed, were often those in which declines in coronary mortality have been most pronounced. Economic resources were not the only driver for delivery of equitable cardiovascular healthcare, as some middle income ESC member countries reported rates for interventional procedures and device implantations that matched or exceeded the rates in wealthier member countries. Conclusion: In documenting national CVD statistics, the Atlas provides valuable insights into the inequalities in risk factors, healthcare delivery and outcomes of CVD across ESC member countries. The availability of these data will underpin the ESC’s ambitious mission “to reduce the burden of cardiovascular disease” not only in its member countries, but also in nation states around the world.

600 citations


Journal ArticleDOI
Sagi Abelson1, Grace Collord2, Grace Collord3, Stanley W.K. Ng4, Omer Weissbrod5, Netta Mendelson Cohen5, Elisabeth Niemeyer5, Noam Barda, Philip C. Zuzarte6, Lawrence E. Heisler6, Yogi Sundaravadanam6, Robert Luben2, Shabina Hayat2, Ting Ting Wang4, Ting Ting Wang1, Zhen Zhao1, Iulia Cirlan1, Trevor J. Pugh6, Trevor J. Pugh4, Trevor J. Pugh1, David Soave6, Karen Ng6, Calli Latimer3, Claire Hardy3, Keiran Raine3, David T. Jones3, Diana Hoult2, Abigail Britten2, John Douglas Mcpherson6, Mattias Johansson7, Faridah Mbabaali6, Jenna Eagles6, Jessica Miller6, Danielle Pasternack6, Lee Timms6, Paul M. Krzyzanowski6, Philip Awadalla6, Rui Costa8, Eran Segal5, Scott V. Bratman4, Scott V. Bratman6, Scott V. Bratman1, Philip A. Beer3, Sam Behjati2, Sam Behjati3, Inigo Martincorena3, Jean C.Y. Wang1, Jean C.Y. Wang9, Jean C.Y. Wang4, Kristian M. Bowles10, Kristian M. Bowles11, J. Ramón Quirós, Anna Karakatsani12, Carlo La Vecchia13, Antonia Trichopoulou, Elena Salamanca-Fernández14, José María Huerta, Aurelio Barricarte, Ruth C. Travis15, Rosario Tumino, Giovanna Masala16, Heiner Boeing, Salvatore Panico17, Rudolf Kaaks18, Alwin Krämer18, Sabina Sieri, Elio Riboli19, Paolo Vineis19, Matthieu Foll7, James McKay7, Silvia Polidoro, Núria Sala, Kay-Tee Khaw2, Roel Vermeulen20, Peter J. Campbell3, Peter J. Campbell2, Elli Papaemmanuil21, Elli Papaemmanuil3, Mark D. Minden, Amos Tanay5, Ran D. Balicer, Nicholas J. Wareham2, Moritz Gerstung8, Moritz Gerstung3, John E. Dick1, John E. Dick4, Paul Brennan7, George S. Vassiliou2, George S. Vassiliou3, Liran I. Shlush1, Liran I. Shlush5 
09 Jul 2018-Nature
TL;DR: Deep sequencing is used to analyse genes that are recurrently mutated in AML to distinguish between individuals who have a high risk of developing AML and those with benign ARCH, providing proof-of-concept that it is possible to discriminate ARCH from pre-AML many years before malignant transformation.
Abstract: The incidence of acute myeloid leukaemia (AML) increases with age and mortality exceeds 90% when diagnosed after age 65. Most cases arise without any detectable early symptoms and patients usually present with the acute complications of bone marrow failure1. The onset of such de novo AML cases is typically preceded by the accumulation of somatic mutations in preleukaemic haematopoietic stem and progenitor cells (HSPCs) that undergo clonal expansion2,3. However, recurrent AML mutations also accumulate in HSPCs during ageing of healthy individuals who do not develop AML, a phenomenon referred to as age-related clonal haematopoiesis (ARCH)4–8. Here we use deep sequencing to analyse genes that are recurrently mutated in AML to distinguish between individuals who have a high risk of developing AML and those with benign ARCH. We analysed peripheral blood cells from 95 individuals that were obtained on average 6.3 years before AML diagnosis (pre-AML group), together with 414 unselected age- and gender-matched individuals (control group). Pre-AML cases were distinct from controls and had more mutations per sample, higher variant allele frequencies, indicating greater clonal expansion, and showed enrichment of mutations in specific genes. Genetic parameters were used to derive a model that accurately predicted AML-free survival; this model was validated in an independent cohort of 29 pre-AML cases and 262 controls. Because AML is rare, we also developed an AML predictive model using a large electronic health record database that identified individuals at greater risk. Collectively our findings provide proof-of-concept that it is possible to discriminate ARCH from pre-AML many years before malignant transformation. This could in future enable earlier detection and monitoring, and may help to inform intervention.

567 citations


Journal ArticleDOI
TL;DR: Wang et al. as discussed by the authors proposed a deep video saliency network consisting of two modules, for capturing the spatial and temporal saliency information, respectively, which can directly produce spatio-temporal saliency inference without time-consuming optical flow computation.
Abstract: This paper proposes a deep learning model to efficiently detect salient regions in videos. It addresses two important issues: 1) deep video saliency model training with the absence of sufficiently large and pixel-wise annotated video data and 2) fast video saliency training and detection. The proposed deep video saliency network consists of two modules, for capturing the spatial and temporal saliency information, respectively. The dynamic saliency model, explicitly incorporating saliency estimates from the static saliency model, directly produces spatiotemporal saliency inference without time-consuming optical flow computation. We further propose a novel data augmentation technique that simulates video training data from existing annotated image data sets, which enables our network to learn diverse saliency information and prevents overfitting with the limited number of training videos. Leveraging our synthetic video data (150K video sequences) and real videos, our deep video saliency model successfully learns both spatial and temporal saliency cues, thus producing accurate spatiotemporal saliency estimate. We advance the state-of-the-art on the densely annotated video segmentation data set (MAE of .06) and the Freiburg-Berkeley Motion Segmentation data set (MAE of .07), and do so with much improved speed (2 fps with all steps).

Journal ArticleDOI
TL;DR: This work evaluates the performance of four primer sets targeting COI and 16S regions characterizing arthropod diversity in bat faecal samples, and investigates how metabarcoding results are affected by parameters including number of PCR replicates per sample, sequencing depth, and similarity thresholds for Operational Taxonomic Unit (OTU) clustering.
Abstract: 1.Metabarcoding of environmental samples has many challenges and limitations that require carefully considered laboratory and analysis pipelines to ensure reliable results. We explore how decisions regarding study design, laboratory work and bioinformatic processing affect the final results, and provide guidelines for reliable study of environmental samples. 2.We evaluate the performance of four primer sets targeting COI and 16S regions characterising arthropod diversity in bat faecal samples, and investigate how metabarcoding results are affected by parameters including: i) number of PCR replicates per sample, ii) sequencing depth, iii) PCR replicate processing strategy (i.e. either additively, by combining the sequences obtained from the PCR replicates, or restrictively, by only retaining sequences that occur in multiple PCR replicates for each sample), iv) minimum copy number for sequences to be retained, v) chimera removal, and vi) similarity thresholds for OTU clustering. Lastly, we measure within- and between-taxa dissimilarities when using sequences from public databases to determine the most appropriate thresholds for OTU clustering and taxonomy assignment. 3.Our results show that the use of multiple primer sets reduces taxonomic biases and increases taxonomic coverage. Taxonomic profiles resulting from each primer set are principally affected by how many PCR replicates are carried out per sample and how sequences are filtered across them, the sequence copy number threshold and the OTU clustering threshold. We also report considerable diversity differences between PCR replicates from each sample. Sequencing depth increases the dissimilarity between PCR replicates unless the bioinformatic strategies to remove allegedly artefactual sequences are adjusted according to the number of analysed sequences. Finally, we show that the appropriate identity thresholds for OTU clustering and taxonomy assignment differ between target markers. 4.Metabarcoding of complex environmental samples ideally requires i) investigation of whether more than one primer sets targeting the same taxonomic group is needed to offset the effect of primer biases, ii) more than one PCR replicate per sample, iii) bioinformatic processing approaches of sequences that balance diversity detection with removal of artificial sequences, and iv) empirical selection of OTU clustering and taxonomy assignment thresholds tailored to each genetic marker and the obtained taxa. This article is protected by copyright. All rights reserved.

Journal ArticleDOI
TL;DR: Meta-analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all-cause mortality, coronary heart disease (CHD) mortality, cardiovascular mortality and stroke, and it may makelittle or no difference to CHD events.
Abstract: Background: Researchers have suggested that omega-3 polyunsaturated fatty acids from oily fish (long-chain omega-3 (LCn3), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), as well as from plants (alpha-linolenic acid (ALA)) benefit cardiovascular health. Guidelines recommend increasing omega-3-rich foods, and sometimes supplementation, but recent trials have not confirmed this. Objectives: To assess effects of increased intake of fish- and plant-based omega-3 for all-cause mortality, cardiovascular (CVD) events, adiposity and lipids. Search methods: We searched CENTRAL, MEDLINE and Embase to April 2017, plus ClinicalTrials.gov and World Health Organization International Clinical Trials Registry to September 2016, with no language restrictions. We handsearched systematic review references and bibliographies and contacted authors. Selection criteria: We included randomised controlled trials (RCTs) that lasted at least 12 months and compared supplementation and/or advice to increase LCn3 or ALA intake versus usual or lower intake. Data collection and analysis: Two review authors independently assessed studies for inclusion, extracted data and assessed validity. We performed separate random-effects meta-analysis for ALA and LCn3 interventions, and assessed dose-response relationships through meta-regression. Main results: We included 79 RCTs (112,059 participants) in this review update and found that 25 were at low summary risk of bias. Trials were of 12 to 72 months' duration and included adults at varying cardiovascular risk, mainly in high-income countries. Most studies assessed LCn3 supplementation with capsules, but some used LCn3- or ALA-rich or enriched foods or dietary advice compared to placebo or usual diet. Meta-analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all-cause mortality (RR 0.98, 95% CI 0.90 to 1.03, 92,653 participants; 8189 deaths in 39 trials, high-quality evidence), cardiovascular mortality (RR 0.95, 95% CI 0.87 to 1.03, 67,772 participants; 4544 CVD deaths in 25 RCTs), cardiovascular events (RR 0.99, 95% CI 0.94 to 1.04, 90,378 participants; 14,737 people experienced events in 38 trials, high-quality evidence), coronary heart disease (CHD) mortality (RR 0.93, 95% CI 0.79 to 1.09, 73,491 participants; 1596 CHD deaths in 21 RCTs), stroke (RR 1.06, 95% CI 0.96 to 1.16, 89,358 participants; 1822 strokes in 28 trials) or arrhythmia (RR 0.97, 95% CI 0.90 to 1.05, 53,796 participants; 3788 people experienced arrhythmia in 28 RCTs). There was a suggestion that LCn3 reduced CHD events (RR 0.93, 95% CI 0.88 to 0.97, 84,301 participants; 5469 people experienced CHD events in 28 RCTs); however, this was not maintained in sensitivity analyses - LCn3 probably makes little or no difference to CHD event risk. All evidence was of moderate GRADE quality, except as noted. Increasing ALA intake probably makes little or no difference to all-cause mortality (RR 1.01, 95% CI 0.84 to 1.20, 19,327 participants; 459 deaths, 5 RCTs),cardiovascular mortality (RR 0.96, 95% CI 0.74 to 1.25, 18,619 participants; 219 cardiovascular deaths, 4 RCTs), and it may make little or no difference to CHD events (RR 1.00, 95% CI 0.80 to 1.22, 19,061 participants, 397 CHD events, 4 RCTs, low-quality evidence). However, increased ALA may slightly reduce risk of cardiovascular events (from 4.8% to 4.7%, RR 0.95, 95% CI 0.83 to 1.07, 19,327 participants; 884 CVD events, 5 RCTs, low-quality evidence), and probably reduces risk of CHD mortality (1.1% to 1.0%, RR 0.95, 95% CI 0.72 to 1.26, 18,353 participants; 193 CHD deaths, 3 RCTs), and arrhythmia (3.3% to 2.6%, RR 0.79, 95% CI 0.57 to 1.10, 4,837 participants; 141 events, 1 RCT). Effects on stroke are unclear. Sensitivity analysis retaining only trials at low summary risk of bias moved effect sizes towards the null (RR 1.0) for all LCn3 primary outcomes except arrhythmias, but for most ALA outcomes, effect sizes moved to suggest protection. LCn3 funnel plots suggested that adding in missing studies/results would move effect sizes towards null for most primary outcomes. There were no dose or duration effects in subgrouping or meta-regression. There was no evidence that increasing LCn3 or ALA altered serious adverse events, adiposity or lipids, although LCn3 slightly reduced triglycerides and increased HDL. ALA probably reduces HDL (high- or moderate-quality evidence). Authors' conclusions: This is the most extensive systematic assessment of effects of omega-3 fats on cardiovascular health to date. Moderate- and high-quality evidence suggests that increasing EPA and DHA has little or no effect on mortality or cardiovascular health (evidence mainly from supplement trials). Previous suggestions of benefits from EPA and DHA supplements appear to spring from trials with higher risk of bias. Low-quality evidence suggests ALA may slightly reduce CVD event risk, CHD mortality and arrhythmia.

Journal ArticleDOI
TL;DR: Beta-blockers improve LVEf and prognosis for patients with heart failure in sinus rhythm with a reduced LVEF and similar benefit was observed in the subgroup of patients with LVEFs 40-49%, but did not improve prognosis.
Abstract: Aims Recent guidelines recommend that patients with heart failure and left ventricular ejection fraction (LVEF) 40-49% should be managed similar to LVEF ≥ 50%. We investigated the effect of beta-blockers according to LVEF in double-blind, randomized, placebo-controlled trials. Methods and results Individual patient data meta-analysis of 11 trials, stratified by baseline LVEF and heart rhythm (Clinicaltrials.gov: NCT0083244; PROSPERO: CRD42014010012). Primary outcomes were all-cause mortality and cardiovascular death over 1.3 years median follow-up, with an intention-to-treat analysis. For 14 262 patients in sinus rhythm, median LVEF was 27% (interquartile range 21-33%), including 575 patients with LVEF 40-49% and 244 ≥ 50%. Beta-blockers reduced all-cause and cardiovascular mortality compared to placebo in sinus rhythm, an effect that was consistent across LVEF strata, except for those in the small subgroup with LVEF ≥ 50%. For LVEF 40-49%, death occurred in 21/292 [7.2%] randomized to beta-blockers compared to 35/283 [12.4%] with placebo; adjusted hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.34-1.03]. Cardiovascular death occurred in 13/292 [4.5%] with beta-blockers and 26/283 [9.2%] with placebo; adjusted HR 0.48 (95% CI 0.24-0.97). Over a median of 1.0 years following randomization (n = 4601), LVEF increased with beta-blockers in all groups in sinus rhythm except LVEF ≥50%. For patients in atrial fibrillation at baseline (n = 3050), beta-blockers increased LVEF when < 50% at baseline, but did not improve prognosis. Conclusion Beta-blockers improve LVEF and prognosis for patients with heart failure in sinus rhythm with a reduced LVEF. The data are most robust for LVEF < 40%, but similar benefit was observed in the subgroup of patients with LVEF 40-49%.

Journal ArticleDOI
14 Aug 2018
TL;DR: In this article, sustainable intensification of agricultural systems offers synergistic opportunities for the co-production of agricultural and natural capital outcomes, but system redesign is essential to deliver optimum outcomes as ecological and economic conditions change.
Abstract: The sustainable intensification of agricultural systems offers synergistic opportunities for the co-production of agricultural and natural capital outcomes. Efficiency and substitution are steps towards sustainable intensification, but system redesign is essential to deliver optimum outcomes as ecological and economic conditions change. We show global progress towards sustainable intensification by farms and hectares, using seven sustainable intensification sub-types: integrated pest management, conservation agriculture, integrated crop and biodiversity, pasture and forage, trees, irrigation management and small or patch systems. From 47 sustainable intensification initiatives at scale (each >104 farms or hectares), we estimate 163 million farms (29% of all worldwide) have crossed a redesign threshold, practising forms of sustainable intensification on 453 Mha of agricultural land (9% of worldwide total). Key challenges include investment to integrate more forms of sustainable intensification in farming systems, creating agricultural knowledge economies and establishing policy measures to scale sustainable intensification further. We conclude that sustainable intensification may be approaching a tipping point where it could be transformative.

Journal ArticleDOI
11 Sep 2018
TL;DR: In this article, the authors summarized the ATTD consensus recommendations and represented the current understanding of how CGM results can affect outcomes, as well as the current criteria for matching people with diabetes to the most appropriate glucose monitoring methodologies.
Abstract: Measurement of glycated hemoglobin (HbA1c) has been the traditional method for assessing glycemic control. However, it does not reflect intra- and interday glycemic excursions that may lead to acute events (such as hypoglycemia) or postprandial hyperglycemia, which have been linked to both microvascular and macrovascular complications. Continuous glucose monitoring (CGM), either from real-time use (rtCGM) or intermittently viewed (iCGM), addresses many of the limitations inherent in HbA1c testing and self-monitoring of blood glucose. Although both provide the means to move beyond the HbA1c measurement as the sole marker of glycemic control, standardized metrics for analyzing CGM data are lacking. Moreover, clear criteria for matching people with diabetes to the most appropriate glucose monitoring methodologies, as well as standardized advice about how best to use the new information they provide, have yet to be established. In February 2017, the Advanced Technologies & Treatments for Diabetes (ATTD) Congress convened an international panel of physicians, researchers, and individuals with diabetes who are expert in CGM technologies to address these issues. This article summarizes the ATTD consensus recommendations and represents the current understanding of how CGM results can affect outcomes.

Journal ArticleDOI
TL;DR: This work proposes a simple yet effective unsupervised hashing framework, named Similarity-Adaptive Deep Hashing (SADH), which alternatingly proceeds over three training modules: deep hash model training, similarity graph updating and binary code optimization.
Abstract: Recent vision and learning studies show that learning compact hash codes can facilitate massive data processing with significantly reduced storage and computation. Particularly, learning deep hash functions has greatly improved the retrieval performance, typically under the semantic supervision. In contrast, current unsupervised deep hashing algorithms can hardly achieve satisfactory performance due to either the relaxed optimization or absence of similarity-sensitive objective. In this work, we propose a simple yet effective unsupervised hashing framework, named Similarity-Adaptive Deep Hashing (SADH), which alternatingly proceeds over three training modules: deep hash model training, similarity graph updating and binary code optimization. The key difference from the widely-used two-step hashing method is that the output representations of the learned deep model help update the similarity graph matrix, which is then used to improve the subsequent code optimization. In addition, for producing high-quality binary codes, we devise an effective discrete optimization algorithm which can directly handle the binary constraints with a general hashing loss. Extensive experiments validate the efficacy of SADH, which consistently outperforms the state-of-the-arts by large gaps.

Journal ArticleDOI
TL;DR: In this article, the authors quantitatively evaluate the drivers of the peak and decline of China's CO2 emissions between 2007 and 2016 using the latest available energy, economic and industry data, and conclude that the decline of Chinese emissions is structural and is likely to be sustained if the nascent industrial and energy system transitions continue.
Abstract: As part of the Paris Agreement, China pledged to peak its CO2 emissions by 2030. In retrospect, the commitment may have been fulfilled as it was being made—China’s emissions peaked in 2013 at a level of 9.53 gigatons of CO2, and have declined in each year from 2014 to 2016. However, the prospect of maintaining the continuance of these reductions depends on the relative contributions of different changes in China. Here, we quantitatively evaluate the drivers of the peak and decline of China’s CO2 emissions between 2007 and 2016 using the latest available energy, economic and industry data. We find that slowing economic growth in China has made it easier to reduce emissions. Nevertheless, the decline is largely associated with changes in industrial structure and a decline in the share of coal used for energy. Decreasing energy intensity (energy per unit gross domestic product) and emissions intensity (emissions per unit energy) also contributed to the decline. Based on an econometric (cumulative sum) test, we confirm that there is a clear structural break in China’s emission pattern around 2015. We conclude that the decline of Chinese emissions is structural and is likely to be sustained if the nascent industrial and energy system transitions continue.

Journal ArticleDOI
TL;DR: Trade among developing nations (i.e., South–South trade) has more than doubled between 2004 and 2011, which reflects a new phase of globalization, and some energy-intensive production activities are relocating from China and India to other developing countries.
Abstract: Economic globalization and concomitant growth in international trade since the late 1990s have profoundly reorganized global production activities and related CO2 emissions. Here we show trade among developing nations (i.e., South-South trade) has more than doubled between 2004 and 2011, which reflects a new phase of globalization. Some production activities are relocating from China and India to other developing countries, particularly raw materials and intermediate goods production in energy-intensive sectors. In turn, the growth of CO2 emissions embodied in Chinese exports has slowed or reversed, while the emissions embodied in exports from less-developed regions such as Vietnam and Bangladesh have surged. Although China's emissions may be peaking, ever more complex supply chains are distributing energy-intensive industries and their CO2 emissions throughout the global South. This trend may seriously undermine international efforts to reduce global emissions that increasingly rely on rallying voluntary contributions of more, smaller, and less-developed nations.

Posted Content
TL;DR: A novel and yet actionable claim is made: of the hundreds of papers that show an improvement over the standard baseline ( 1-nearest neighbor classification ), a fraction might be mis-attributing the reasons for their improvement.
Abstract: The UCR Time Series Archive - introduced in 2002, has become an important resource in the time series data mining community, with at least one thousand published papers making use of at least one data set from the archive. The original incarnation of the archive had sixteen data sets but since that time, it has gone through periodic expansions. The last expansion took place in the summer of 2015 when the archive grew from 45 to 85 data sets. This paper introduces and will focus on the new data expansion from 85 to 128 data sets. Beyond expanding this valuable resource, this paper offers pragmatic advice to anyone who may wish to evaluate a new algorithm on the archive. Finally, this paper makes a novel and yet actionable claim: of the hundreds of papers that show an improvement over the standard baseline (1-nearest neighbor classification), a large fraction may be mis-attributing the reasons for their improvement. Moreover, they may have been able to achieve the same improvement with a much simpler modification, requiring just a single line of code.

Journal ArticleDOI
25 Apr 2018-BMJ
TL;DR: A robust association between some classes of anticholinergic drugs and future dementia incidence was observed, and this could be caused by a class specific effect, or by drugs being used for very early symptoms of dementia.
Abstract: Objectives To estimate the association between the duration and level of exposure to different classes of anticholinergic drugs and subsequent incident dementia. Design Case-control study. Setting General practices in the UK contributing to the Clinical Practice Research Datalink. Participants 40 770 patients aged 65-99 with a diagnosis of dementia between April 2006 and July 2015, and 283 933 controls without dementia. Interventions Daily defined doses of anticholinergic drugs coded using the Anticholinergic Cognitive Burden (ACB) scale, in total and grouped by subclass, prescribed 4-20 years before a diagnosis of dementia. Main outcome measures Odds ratios for incident dementia, adjusted for a range of demographic and health related covariates. Results 14 453 (35%) cases and 86 403 (30%) controls were prescribed at least one anticholinergic drug with an ACB score of 3 (definite anticholinergic activity) during the exposure period. The adjusted odds ratio for any anticholinergic drug with an ACB score of 3 was 1.11 (95% confidence interval 1.08 to 1.14). Dementia was associated with an increasing average ACB score. When considered by drug class, gastrointestinal drugs with an ACB score of 3 were not distinctively linked to dementia. The risk of dementia increased with greater exposure for antidepressant, urological, and antiparkinson drugs with an ACB score of 3. This result was also observed for exposure 15-20 years before a diagnosis. Conclusions A robust association between some classes of anticholinergic drugs and future dementia incidence was observed. This could be caused by a class specific effect, or by drugs being used for very early symptoms of dementia. Future research should examine anticholinergic drug classes as opposed to anticholinergic effects intrinsically or summing scales for anticholinergic exposure. Trial registration Registered to the European Union electronic Register of Post-Authorisation Studies EUPAS8705.

Journal ArticleDOI
21 Dec 2018
TL;DR: In this paper, the authors argue that the concept of responsible innovation has not been widely considered in agriculture, although two recent papers have made useful suggestions, namely, anticipation, inclusion, reflexivity, and responsiveness.
Abstract: Agriculture is undergoing a technology revolution supported by policy-makers around the world. While smart technologies will play an important role in achieving enhanced productivity and greater eco-efficiency, critics have suggested that a consideration of social impacts is being side-lined. Research illustrates that some agricultural practitioners are concerned about using certain technologies. Indeed, some studies argue that agricultural societies may be changed, or ‘re-scripted’, in undesirable ways, and there is precedent to suggest that wider society may be concerned about radical new technologies. We therefore encourage policy-makers, funders, technology companies, and researchers to consider the views of both farming communities and wider society. In agriculture, the concept of responsible innovation has not been widely considered, although two recent papers have made useful suggestions. We build on these interventions by arguing that key dimensions of responsible innovation - anticipation, inclusion, reflexivity, and responsiveness - should be applied to this fourth agricultural revolution. We argue, however, that ideas in responsible innovation should be further developed in order to make them relevant and robust for emergent agri-tech, and further that frameworks should be tested in practice to see if they can actively shape innovation trajectories. In making suggestions on how to construct a more comprehensive framework for responsible innovation in agriculture, we call for: (i) a more systemic approach that maps and attends to the wider ecology of innovations associated with this fourth agricultural revolution; (ii) a broadening of notions of ‘inclusion’ in responsible innovation to account better for diverse and already existing spaces...

Journal ArticleDOI
TL;DR: Among infants with bronchiolitis who were treated outside an ICU, those who received high‐flow oxygen therapy had significantly lower rates of escalation of care due to treatment failure than those in the group that received standard oxygen therapy.
Abstract: Background High-flow oxygen therapy through a nasal cannula has been increasingly used in infants with bronchiolitis, despite limited high-quality evidence of its efficacy. The efficacy of high-flow oxygen therapy through a nasal cannula in settings other than intensive care units (ICUs) is unclear. Methods In this multicenter, randomized, controlled trial, we assigned infants younger than 12 months of age who had bronchiolitis and a need for supplemental oxygen therapy to receive either high-flow oxygen therapy (high-flow group) or standard oxygen therapy (standard-therapy group). Infants in the standard-therapy group could receive rescue high-flow oxygen therapy if their condition met criteria for treatment failure. The primary outcome was escalation of care due to treatment failure (defined as meeting ≥3 of 4 clinical criteria: persistent tachycardia, tachypnea, hypoxemia, and medical review triggered by a hospital early-warning tool). Secondary outcomes included duration of hospital stay, dur...

Journal ArticleDOI
TL;DR: Interactions between circulating gut-derived microbial metabolites, and the blood–brain barrier (BBB) also contribute to the gut-brain axis, representing a fourth facet of the gut–brain axis that warrants further attention.
Abstract: Gut microbiota composition and function are symbiotically linked with host health and altered in metabolic, inflammatory and neurodegenerative disorders. Three recognised mechanisms exist by which the microbiome influences the gut–brain axis: modification of autonomic/sensorimotor connections, immune activation, and neuroendocrine pathway regulation. We hypothesised interactions between circulating gut-derived microbial metabolites, and the blood–brain barrier (BBB) also contribute to the gut–brain axis. Propionate, produced from dietary substrates by colonic bacteria, stimulates intestinal gluconeogenesis and is associated with reduced stress behaviours, but its potential endocrine role has not been addressed. After demonstrating expression of the propionate receptor FFAR3 on human brain endothelium, we examined the impact of a physiologically relevant propionate concentration (1 μM) on BBB properties in vitro. Propionate inhibited pathways associated with non-specific microbial infections via a CD14-dependent mechanism, suppressed expression of LRP-1 and protected the BBB from oxidative stress via NRF2 (NFE2L2) signalling. Together, these results suggest gut-derived microbial metabolites interact with the BBB, representing a fourth facet of the gut–brain axis that warrants further attention.

Journal ArticleDOI
TL;DR: The main objective was an updated assessment of the impact of unsafe water, sanitation and hygiene (WaSH) on childhood diarrhoeal disease.
Abstract: OBJECTIVES: Safe drinking water, sanitation and hygiene are protective against diarrhoeal disease; a leading cause of child mortality. The main objective was an updated assessment of the impact of unsafe water, sanitation and hygiene (WaSH) on childhood diarrhoeal disease. METHODS: We undertook a systematic review of articles published between 1970 and February 2016. Study results were combined and analysed using meta-analysis and meta-regression. RESULTS: A total of 135 studies met the inclusion criteria. Several water, sanitation and hygiene interventions were associated with lower risk of diarrhoeal morbidity. Point-of-use filter interventions with safe storage reduced diarrhoea risk by 61% (RR = 0.39; 95% CI: 0.32, 0.48); piped water to premises of higher quality and continuous availability by 75% and 36% (RR = 0.25 (0.09, 0.67) and 0.64 (0.42, 0.98)), respectively compared to a baseline of unimproved drinking water; sanitation interventions by 25% (RR = 0.75 (0.63, 0.88)) with evidence for greater reductions when high sanitation coverage is reached; and interventions promoting handwashing with soap by 30% (RR = 0.70 (0.64, 0.77)) vs. no intervention. Results of the analysis of sanitation and hygiene interventions are sensitive to certain differences in study methods and conditions. Correcting for non-blinding would reduce the associations with diarrhoea to some extent. CONCLUSIONS: Although evidence is limited, results suggest that household connections of water supply and higher levels of community coverage for sanitation appear particularly impactful which is in line with targets of the Sustainable Development Goals.

Proceedings ArticleDOI
18 Jun 2018
TL;DR: A Viewpoint-aware Attentive Multi-view Inference (VAMI) model that only requires visual information to solve the multi-view vehicle reID problem and achieves consistent improvements over state-of-the-art vehicle re-ID methods on two public datasets: VeRi and VehicleID.
Abstract: Vehicle re-identification (re-ID) has the huge potential to contribute to the intelligent video surveillance. However, it suffers from challenges that different vehicle identities with a similar appearance have little inter-instance discrepancy while one vehicle usually has large intra-instance differences under viewpoint and illumination variations. Previous methods address vehicle re-ID by simply using visual features from originally captured views and usually exploit the spatial-temporal information of the vehicles to refine the results. In this paper, we propose a Viewpoint-aware Attentive Multi-view Inference (VAMI) model that only requires visual information to solve the multi-view vehicle reID problem. Given vehicle images of arbitrary viewpoints, the VAMI extracts the single-view feature for each input image and aims to transform the features into a global multiview feature representation so that pairwise distance metric learning can be better optimized in such a viewpointinvariant feature space. The VAMI adopts a viewpoint-aware attention model to select core regions at different viewpoints and implement effective multi-view feature inference by an adversarial training architecture. Extensive experiments validate the effectiveness of each proposed component and illustrate that our approach achieves consistent improvements over state-of-the-art vehicle re-ID methods on two public datasets: VeRi and VehicleID.

Journal ArticleDOI
TL;DR: Spatial navigation is emerging as a potential cost-effective cognitive biomarker to detect AD in the preclinical stages, which has important implications for future diagnostics and treatment approaches.
Abstract: Detection of incipient Alzheimer disease (AD) pathophysiology is critical to identify preclinical individuals and target potentially disease-modifying therapies towards them. Current neuroimaging and biomarker research is strongly focused in this direction, with the aim of establishing AD fingerprints to identify individuals at high risk of developing this disease. By contrast, cognitive fingerprints for incipient AD are virtually non-existent as diagnostics and outcomes measures are still focused on episodic memory deficits as the gold standard for AD, despite their low sensitivity and specificity for identifying at-risk individuals. This Review highlights a novel feature of cognitive evaluation for incipient AD by focusing on spatial navigation and orientation deficits, which are increasingly shown to be present in at-risk individuals. Importantly, the navigation system in the brain overlaps substantially with the regions affected by AD in both animal models and humans. Notably, spatial navigation has fewer verbal, cultural and educational biases than current cognitive tests and could enable a more uniform, global approach towards cognitive fingerprints of AD and better cognitive treatment outcome measures in future multicentre trials. The current Review appraises the available evidence for spatial navigation and/or orientation deficits in preclinical, prodromal and confirmed AD and identifies research gaps and future research priorities.

Journal ArticleDOI
TL;DR: The GEOTRACES Intermediate Data Product 2017 (IDP2017) as discussed by the authors is the second publicly available data product of the international GEOTrACES programme, and contains data measured and quality controlled before the end of 2016.

Journal ArticleDOI
TL;DR: Antimicrobial stewardship programmes should be instituted in all care settings, based on resistance rates and audit of compliance with guidelines, but should be augmented by improved surveillance of outcome in Gram-negative bacteraemia, and feedback to prescribers.
Abstract: The Working Party makes more than 100 tabulated recommendations in antimicrobial prescribing for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB) and suggest further research, and algorithms for hospital and community antimicrobial usage in urinary infection. The international definition of MDR is complex, unsatisfactory and hinders the setting and monitoring of improvement programmes. We give a new definition of multiresistance. The background information on the mechanisms, global spread and UK prevalence of antibiotic prescribing and resistance has been systematically reviewed. The treatment options available in hospitals using intravenous antibiotics and in primary care using oral agents have been reviewed, ending with a consideration of antibiotic stewardship and recommendations. The guidance has been derived from current peer-reviewed publications and expert opinion with open consultation. Methods for systematic review were NICE compliant and in accordance with the SIGN 50 Handbook; critical appraisal was applied using AGREE II. Published guidelines were used as part of the evidence base and to support expert consensus. The guidance includes recommendations for stakeholders (including prescribers) and antibiotic-specific recommendations. The clinical efficacy of different agents is critically reviewed. We found there are very few good-quality comparative randomized clinical trials to support treatment regimens, particularly for licensed older agents. Susceptibility testing of MDR GNB causing infection to guide treatment needs critical enhancements. Meropenem- or imipenem-resistant Enterobacteriaceae should have their carbapenem MICs tested urgently, and any carbapenemase class should be identified: mandatory reporting of these isolates from all anatomical sites and specimens would improve risk assessments. Broth microdilution methods should be adopted for colistin susceptibility testing. Antimicrobial stewardship programmes should be instituted in all care settings, based on resistance rates and audit of compliance with guidelines, but should be augmented by improved surveillance of outcome in Gram-negative bacteraemia, and feedback to prescribers. Local and national surveillance of antibiotic use, resistance and outcomes should be supported and antibiotic prescribing guidelines should be informed by these data. The diagnosis and treatment of both presumptive and confirmed cases of infection by GNB should be improved. This guidance, with infection control to arrest increases in MDR, should be used to improve the outcome of infections with such strains. Anticipated users include medical, scientific, nursing, antimicrobial pharmacy and paramedical staff where they can be adapted for local use.

Journal ArticleDOI
TL;DR: New, city-level estimates of CO2 emissions for 182 Chinese cities are presented and sector-based analysis of each city suggests that technological improvements could be a practical and effective means of reducing emissions while maintaining growth and the current economic structure and energy system.
Abstract: As national efforts to reduce CO2 emissions intensify, policy-makers need increasingly specific, subnational information about the sources of CO2 and the potential reductions and economic implications of different possible policies. This is particularly true in China, a large and economically diverse country that has rapidly industrialized and urbanized and that has pledged under the Paris Agreement that its emissions will peak by 2030. We present new, city-level estimates of CO2 emissions for 182 Chinese cities, decomposed into 17 different fossil fuels, 46 socioeconomic sectors, and 7 industrial processes. We find that more affluent cities have systematically lower emissions per unit of gross domestic product (GDP), supported by imports from less affluent, industrial cities located nearby. In turn, clusters of industrial cities are supported by nearby centers of coal or oil extraction. Whereas policies directly targeting manufacturing and electric power infrastructure would drastically undermine the GDP of industrial cities, consumption-based policies might allow emission reductions to be subsidized by those with greater ability to pay. In particular, sector-based analysis of each city suggests that technological improvements could be a practical and effective means of reducing emissions while maintaining growth and the current economic structure and energy system. We explore city-level emission reductions under three scenarios of technological progress to show that substantial reductions (up to 31%) are possible by updating a disproportionately small fraction of existing infrastructure.