Showing papers by "University of Exeter published in 2017"

Diagnosis and management of dementia with Lewy bodies Fourth consensus report of the DLB Consortium

Abstract: The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade. The revised DLB consensus criteria now distinguish clearly between clinical features and diagnostic biomarkers, and give guidance about optimal methods to establish and interpret these. Substantial new information has been incorporated about previously reported aspects of DLB, with increased diagnostic weighting given to REM sleep behavior disorder and 123iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. The diagnostic role of other neuroimaging, electrophysiologic, and laboratory investigations is also described. Minor modifications to pathologic methods and criteria are recommended to take account of Alzheimer disease neuropathologic change, to add previously omitted Lewy-related pathology categories, and to include assessments for substantia nigra neuronal loss. Recommendations about clinical management are largely based upon expert opinion since randomized controlled trials in DLB are few. Substantial progress has been made since the previous report in the detection and recognition of DLB as a common and important clinical disorder. During that period it has been incorporated into DSM-5, as major neurocognitive disorder with Lewy bodies. There remains a pressing need to understand the underlying neurobiology and pathophysiology of DLB, to develop and deliver clinical trials with both symptomatic and disease-modifying agents, and to help patients and carers worldwide to inform themselves about the disease, its prognosis, best available treatments, ongoing research, and how to get adequate support.

Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research

Abstract: Additional co-authors: Endre Czeiter, Marek Czosnyka, Ramon Diaz-Arrastia, Jens P Dreier, Ann-Christine Duhaime, Ari Ercole, Thomas A van Essen, Valery L Feigin, Guoyi Gao, Joseph Giacino, Laura E Gonzalez-Lara, Russell L Gruen, Deepak Gupta, Jed A Hartings, Sean Hill, Ji-yao Jiang, Naomi Ketharanathan, Erwin J O Kompanje, Linda Lanyon, Steven Laureys, Fiona Lecky, Harvey Levin, Hester F Lingsma, Marc Maegele, Marek Majdan, Geoffrey Manley, Jill Marsteller, Luciana Mascia, Charles McFadyen, Stefania Mondello, Virginia Newcombe, Aarno Palotie, Paul M Parizel, Wilco Peul, James Piercy, Suzanne Polinder, Louis Puybasset, Todd E Rasmussen, Rolf Rossaint, Peter Smielewski, Jeannette Soderberg, Simon J Stanworth, Murray B Stein, Nicole von Steinbuchel, William Stewart, Ewout W Steyerberg, Nino Stocchetti, Anneliese Synnot, Braden Te Ao, Olli Tenovuo, Alice Theadom, Dick Tibboel, Walter Videtta, Kevin K W Wang, W Huw Williams, Kristine Yaffe for the InTBIR Participants and Investigators

Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia

Abstract: BackgroundPreterm preeclampsia is an important cause of maternal and perinatal death and complications. It is uncertain whether the intake of low-dose aspirin during pregnancy reduces the risk of preterm preeclampsia. MethodsIn this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1776 women with singleton pregnancies who were at high risk for preterm preeclampsia to receive aspirin, at a dose of 150 mg per day, or placebo from 11 to 14 weeks of gestation until 36 weeks of gestation. The primary outcome was delivery with preeclampsia before 37 weeks of gestation. The analysis was performed according to the intention-to-treat principle. ResultsA total of 152 women withdrew consent during the trial, and 4 were lost to follow up, which left 798 participants in the aspirin group and 822 in the placebo group. Preterm preeclampsia occurred in 13 participants (1.6%) in the aspirin group, as compared with 35 (4.3%) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidenc...

Interactions of microplastic debris throughout the marine ecosystem

Abstract: Marine microscopic plastic (microplastic) debris is a modern societal issue, illustrating the challenge of balancing the convenience of plastic in daily life with the prospect of causing ecological harm by careless disposal. Here we develop the concept of microplastic as a complex, dynamic mixture of polymers and additives, to which organic material and contaminants can successively bind to form an 'ecocorona', increasing the density and surface charge of particles and changing their bioavailability and toxicity. Chronic exposure to microplastic is rarely lethal, but can adversely affect individual animals, reducing feeding and depleting energy stores, with knock-on effects for fecundity and growth. We explore the extent to which ecological processes could be impacted, including altered behaviours, bioturbation and impacts on carbon flux to the deep ocean. We discuss how microplastic compares with other anthropogenic pollutants in terms of ecological risk, and consider the role of science and society in tackling this global issue in the future.

Global Carbon Budget 2017

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. CO2 emissions from fossil fuels and industry (EFF) are based on energy statistics and cement production data, respectively, while emissions from land-use change (ELUC), mainly deforestation, are based on land-cover change data and bookkeeping models. The global atmospheric CO2 concentration is measured directly and its rate of growth (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 (2007–2016), EFF was 9.4 ± 0.5 GtC yr−1, ELUC 1.3 ± 0.7 GtC yr−1, GATM 4.7 ± 0.1 GtC yr−1, SOCEAN 2.4 ± 0.5 GtC yr−1, and SLAND 3.0 ± 0.8 GtC yr−1, with a budget imbalance BIM of 0.6 GtC yr−1 indicating overestimated emissions and/or underestimated sinks. For year 2016 alone, the growth in EFF was approximately zero and emissions remained at 9.9 ± 0.5 GtC yr−1. Also for 2016, ELUC was 1.3 ± 0.7 GtC yr−1, GATM was 6.1 ± 0.2 GtC yr−1, SOCEAN was 2.6 ± 0.5 GtC yr−1, and SLAND was 2.7 ± 1.0 GtC yr−1, with a small BIM of −0.3 GtC. GATM continued to be higher in 2016 compared to the past decade (2007–2016), reflecting in part the high fossil emissions and the small SLAND consistent with El Nino conditions. The global atmospheric CO2 concentration reached 402.8 ± 0.1 ppm averaged over 2016. For 2017, preliminary data for the first 6–9 months indicate a renewed growth in EFF of +2.0 % (range of 0.8 to 3.0 %) based on national emissions projections for China, USA, and India, and projections of gross domestic product (GDP) corrected for recent changes in the carbon intensity of the economy for the rest of the world. This living data update documents changes in the methods and data sets used in this new global carbon budget compared with previous publications of this data set (Le Quere et al., 2016, 2015b, a, 2014, 2013). All results presented here can be downloaded from https://doi.org/10.18160/GCP-2017 (GCP, 2017).

Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease

Abstract: Genetic association studies have identified 215 risk loci for inflammatory bowel disease, thereby uncovering fundamental aspects of its molecular biology. We performed a genome-wide association study of 25,305 individuals and conducted a meta-analysis with published summary statistics, yielding a total sample size of 59,957 subjects. We identified 25 new susceptibility loci, 3 of which contain integrin genes that encode proteins in pathways that have been identified as important therapeutic targets in inflammatory bowel disease. The associated variants are correlated with expression changes in response to immune stimulus at two of these genes (ITGA4 and ITGB8) and at previously implicated loci (ITGAL and ICAM1). In all four cases, the expression-increasing allele also increases disease risk. We also identified likely causal missense variants in a gene implicated in primary immune deficiency, PLCG2, and a negative regulator of inflammation, SLAMF8. Our results demonstrate that new associations at common variants continue to identify genes relevant to therapeutic target identification and prioritization.

The Met Office Unified Model Global Atmosphere 7.0/7.1 and JULES Global Land 7.0 configurations

Abstract: . We describe Global Atmosphere 3.0 (GA3.0): a configuration of the Met Office Unified Model (MetUM) developed for use across climate research and weather prediction activities. GA3.0 has been formulated by converging the development paths of the Met Office's weather and climate global atmospheric model components such that wherever possible, atmospheric processes are modelled or parametrized seamlessly across spatial resolutions and timescales. This unified development process will provide the Met Office and its collaborators with regular releases of a configuration that has been evaluated, and can hence be applied, over a variety of modelling regimes. We also describe Global Land 3.0 (GL3.0): a configuration of the JULES community land surface model developed for use with GA3.0. This paper provides a comprehensive technical and scientific description of the GA3.0 and GL3.0 (and related GA3.1 and GL3.1) configurations and presents the results of some initial evaluations of their performance in various applications. It is to be the first in a series of papers describing each subsequent Global Atmosphere release; this will provide a single source of reference for established users and developers as well as researchers requiring access to a current, but trusted, global MetUM setup.

GRIPP2 reporting checklists: tools to improve reporting of patient and public involvement in research

Abstract: While the patient and public involvement (PPI) evidence base has expanded over the past decade, the quality of reporting within papers is often inconsistent, limiting our understanding of how it works, in what context, for whom, and why. To develop international consensus on the key items to report to enhance the quality, transparency, and consistency of the PPI evidence base. To collaboratively involve patients as research partners at all stages in the development of GRIPP2. The EQUATOR method for developing reporting guidelines was used. The original GRIPP (Guidance for Reporting Involvement of Patients and the Public) checklist was revised, based on updated systematic review evidence. A three round Delphi survey was used to develop consensus on items to be included in the guideline. A subsequent face-to-face meeting produced agreement on items not reaching consensus during the Delphi process. One hundred forty-three participants agreed to participate in round one, with an 86% (123/143) response for round two and a 78% (112/143) response for round three. The Delphi survey identified the need for long form (LF) and short form (SF) versions. GRIPP2-LF includes 34 items on aims, definitions, concepts and theory, methods, stages and nature of involvement, context, capture or measurement of impact, outcomes, economic assessment, and reflections and is suitable for studies where the main focus is PPI. GRIPP2-SF includes five items on aims, methods, results, outcomes, and critical perspective and is suitable for studies where PPI is a secondary focus. GRIPP2-LF and GRIPP2-SF represent the first international evidence based, consensus informed guidance for reporting patient and public involvement in research. Both versions of GRIPP2 aim to improve the quality, transparency, and consistency of the international PPI evidence base, to ensure PPI practice is based on the best evidence. In order to encourage its wide dissemination this article is freely accessible on The BMJ and Research Involvement and Engagement journal websites.

The worldwide costs of dementia 2015 and comparisons with 2010

Abstract: Introduction In 2010, Alzheimer's Disease International presented estimates of the global cost of illness (COI) of dementia. Since then, new studies have been conducted, and the number of people with dementia has increased. Here, we present an update of the global cost estimates. Methods This is a societal, prevalence-based global COI study. Results The worldwide costs of dementia were estimated at United States (US) $818 billion in 2015, an increase of 35% since 2010; 86% of the costs occur in high-income countries. Costs of informal care and the direct costs of social care still contribute similar proportions of total costs, whereas the costs in the medical sector are much lower. The threshold of US $1 trillion will be crossed by 2018. Discussion Worldwide costs of dementia are enormous and still inequitably distributed. The increase in costs arises from increases in numbers of people with dementia and in increases in per person costs.

The flipped classroom

Abstract: Compared with a traditional teaching framework where students attend a lecture, tutorial or seminar, and the learning comes during and after the teaching, the fl ipped classroom turns this round so that most learning comes fi rst, allowing the teaching session to refl ect on the material and build on prior learning. The articles reviewed below highlight how the fl ippedclassroom approach , although potentially a very powerful method of learning, requires further evidence to confi rm its effectiveness.

Use of the Instantaneous Wave-free Ratio or Fractional Flow Reserve in PCI

Abstract: BackgroundCoronary revascularization guided by fractional flow reserve (FFR) is associated with better patient outcomes after the procedure than revascularization guided by angiography alone. It is unknown whether the instantaneous wave-free ratio (iFR), an alternative measure that does not require the administration of adenosine, will offer benefits similar to those of FFR. MethodsWe randomly assigned 2492 patients with coronary artery disease, in a 1:1 ratio, to undergo either iFR-guided or FFR-guided coronary revascularization. The primary end point was the 1-year risk of major adverse cardiac events, which were a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization. The trial was designed to show the noninferiority of iFR to FFR, with a margin of 3.4 percentage points for the difference in risk. ResultsAt 1 year, the primary end point had occurred in 78 of 1148 patients (6.8%) in the iFR group and in 83 of 1182 patients (7.0%) in the FFR group (difference i...

Sampling, isolating and identifying microplastics ingested by fish and invertebrates

Abstract: Microplastic debris (<5 mm) is a prolific environmental pollutant, found worldwide in marine, freshwater and terrestrial ecosystems. Interactions between biota and microplastics are prevalent, and there is growing evidence that microplastics can incite significant health effects in exposed organisms. To date, the methods used to quantify such interactions have varied greatly between studies. Here, we critically review methods for sampling, isolating and identifying microplastics ingested by environmentally and laboratory exposed fish and invertebrates. We aim to draw attention to the strengths and weaknesses of the suite of published microplastic extraction and enumeration techniques. Firstly, we highlight the risk of microplastic losses and accumulation during biotic sampling and storage, and suggest protocols for mitigating contamination in the field and laboratory. We evaluate a suite of methods for extracting microplastics ingested by biota, including dissection, depuration, digestion and density separation. Lastly, we consider the applicability of visual identification and chemical analyses in categorising microplastics. We discuss the urgent need for the standardisation of protocols to promote consistency in data collection and analysis. Harmonized methods will allow for more accurate assessment of the impacts and risks microplastics pose to biota and increase comparability between studies.

Cognitive decline in Parkinson disease

Abstract: Dementia is a frequent problem encountered in advanced stages of Parkinson disease (PD). In recent years, research has focused on the pre-dementia stages of cognitive impairment in PD, including mild cognitive impairment (MCI). Several longitudinal studies have shown that MCI is a harbinger of dementia in PD, although the course is variable, and stabilization of cognition - or even reversal to normal cognition - is not uncommon. In addition to limbic and cortical spread of Lewy pathology, several other mechanisms are likely to contribute to cognitive decline in PD, and a variety of biomarker studies, some using novel structural and functional imaging techniques, have documented in vivo brain changes associated with cognitive impairment. The evidence consistently suggests that low cerebrospinal fluid levels of amyloid-β42, a marker of comorbid Alzheimer disease (AD), predict future cognitive decline and dementia in PD. Emerging genetic evidence indicates that in addition to the APOE*e4 allele (an established risk factor for AD), GBA mutations and SCNA mutations and triplications are associated with cognitive decline in PD, whereas the findings are mixed for MAPT polymorphisms. Cognitive enhancing medications have some effect in PD dementia, but no convincing evidence that progression from MCI to dementia can be delayed or prevented is available, although cognitive training has shown promising results.

An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans

Abstract: To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects) We identified 13 novel T2D-associated loci (P < 5 × 10-8), including variants near the GLP2R, GIP, and HLA-DQA1 genes Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common single nucleotide variants Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion and in adipocytes, monocytes, and hepatocytes for insulin action-associated loci These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology

Corporate Social Responsibility and Firm Risk: Theory and Empirical Evidence

Abstract: This paper presents an industry equilibrium model where firms have a choice to engage in corporate social responsibility (CSR) activities. We model CSR activities as a product differentiation strategy allowing firms to benefit from higher profit margins. The model predicts that CSR decreases systematic risk and increases firm value and that these effects are stronger for firms operating in differentiated goods industries and when consumers' expenditure share on CSR goods is small. We find supporting evidence for our predictions. We address a potential endogeneity problem by instrumenting CSR using data on the political affiliation of the firm's home state.

The Nature and Origins of Misperceptions: Understanding False and Unsupported Beliefs About Politics

Abstract: Political misperceptions can distort public debate and undermine people's ability to form meaningful opinions. Why do people often hold these false or unsupported beliefs, and why is it sometimes so difficult to convince them otherwise? We argue that political misperceptions are typically rooted in directionally motivated reasoning, which limits the effectiveness of corrective information about controversial issues and political figures. We discuss factors known to affect the prevalence of directionally motivated reasoning and assess strategies for accurately measuring misperceptions in surveys. Finally, we address the normative implications of misperceptions for democracy and suggest important topics for future research.

Hippocampal GABAergic Inhibitory Interneurons.

Abstract: In the hippocampus GABAergic local circuit inhibitory interneurons represent only ~10–15% of the total neuronal population; however, their remarkable anatomical and physiological diversity allows them to regulate virtually all aspects of cellular and circuit function. Here we provide an overview of the current state of the field of interneuron research, focusing largely on the hippocampus. We discuss recent advances related to the various cell types, including their development and maturation, expression of subtype-specific voltage- and ligand-gated channels, and their roles in network oscillations. We also discuss recent technological advances and approaches that have permitted high-resolution, subtype-specific examination of their roles in numerous neural circuit disorders and the emerging therapeutic strategies to ameliorate such pathophysiological conditions. The ultimate goal of this review is not only to provide a touchstone for the current state of the field, but to help pave the way for future research by highlighting where gaps in our knowledge exist and how a complete appreciation of their roles will aid in future therapeutic strategies.

BedMachine v3: Complete Bed Topography and Ocean Bathymetry Mapping of Greenland From Multibeam Echo Sounding Combined With Mass Conservation.

Abstract: Greenland's bed topography is a primary control on ice flow, grounding line migration, calving dynamics, and subglacial drainage. Moreover, fjord bathymetry regulates the penetration of warm Atlantic water (AW) that rapidly melts and undercuts Greenland's marine-terminating glaciers. Here we present a new compilation of Greenland bed topography that assimilates seafloor bathymetry and ice thickness data through a mass conservation approach. A new 150 m horizontal resolution bed topography/bathymetric map of Greenland is constructed with seamless transitions at the ice/ocean interface, yielding major improvements over previous data sets, particularly in the marine-terminating sectors of northwest and southeast Greenland. Our map reveals that the total sea level potential of the Greenland ice sheet is 7.42 ± 0.05 m, which is 7 cm greater than previous estimates. Furthermore, it explains recent calving front response of numerous outlet glaciers and reveals new pathways by which AW can access glaciers with marine-based basins, thereby highlighting sectors of Greenland that are most vulnerable to future oceanic forcing.

Artificially lit surface of Earth at night increasing in radiance and extent

Abstract: A central aim of the "lighting revolution" (the transition to solid-state lighting technology) is decreased energy consumption. This could be undermined by a rebound effect of increased use in response to lowered cost of light. We use the first-ever calibrated satellite radiometer designed for night lights to show that from 2012 to 2016, Earth's artificially lit outdoor area grew by 2.2% per year, with a total radiance growth of 1.8% per year. Continuously lit areas brightened at a rate of 2.2% per year. Large differences in national growth rates were observed, with lighting remaining stable or decreasing in only a few countries. These data are not consistent with global scale energy reductions but rather indicate increased light pollution, with corresponding negative consequences for flora, fauna, and human well-being.

Home‐based versus centre‐based cardiac rehabilitation

Abstract: Background Cardiovascular disease is the most common cause of death globally. Traditionally, centre-based cardiac rehabilitation programmes are offered to individuals after cardiac events to aid recovery and prevent further cardiac illness. Home-based cardiac rehabilitation programmes have been introduced in an attempt to widen access and participation. This is an update of a review originally published in 2009. Objectives To compare the effect of home-based and supervised centre-based cardiac rehabilitation on mortality and morbidity, health-related quality of life, and modifiable cardiac risk factors in patients with heart disease. Search methods To update searches from the previous Cochrane review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 9, 2014), MEDLINE (Ovid, 1946 to October week 1 2014), EMBASE (Ovid, 1980 to 2014 week 41), PsycINFO (Ovid, 1806 to October week 2 2014), and CINAHL (EBSCO, to October 2014). We checked reference lists of included trials and recent systematic reviews. No language restrictions were applied. Selection criteria Randomised controlled trials (RCTs) that compared centre-based cardiac rehabilitation (e.g. hospital, gymnasium, sports centre) with home-based programmes in adults with myocardial infarction (MI), angina, heart failure or who had undergone revascularisation. Data collection and analysis Two authors independently assessed the eligibility of the identified trials and data were extracted by a single author and checked by a second. Authors were contacted where possible to obtain missing information. Main results Seventeen trials included a total of 2172 participants undergoing cardiac rehabilitation following an acute MI or revascularisation, or with heart failure. This update included an additional five trials on 345 patients with heart failure. Authors of a number of included trials failed to give sufficient detail to assess their potential risk of bias, and details of generation and concealment of random allocation sequence were particularly poorly reported. In the main, no difference was seen between home- and centre-based cardiac rehabilitation in outcomes up to 12 months of follow up: mortality (relative risk (RR) = 0.79, 95% confidence interval (CI) 0.43 to 1.47, P = 0.46, fixed-effect), cardiac events (data not poolable), exercise capacity (standardised mean difference (SMD) = -0.10, 95% CI -0.29 to 0.08, P = 0.29, random-effects), modifiable risk factors (total cholesterol: mean difference (MD) = 0.07 mmol/L, 95% CI -0.24 to 0.11, P = 0.47, random-effects; low density lipoprotein cholesterol: MD = -0.06 mmol/L, 95% CI -0.27 to 0.15, P = 0.55, random-effects; systolic blood pressure: mean difference (MD) = 0.19 mmHg, 95% CI -3.37 to 3.75, P = 0.92, random-effects; proportion of smokers at follow up (RR = 0.98, 95% CI 0.79 to 1.21, P = 0.83, fixed-effect), or health-related quality of life (not poolable). Small outcome differences in favour of centre-based participants were seen in high density lipoprotein cholesterol (MD = -0.07 mmol/L, 95% CI -0.11 to -0.03, P = 0.001, fixed-effect), and triglycerides (MD = -0.18 mmol/L, 95% CI -0.34 to -0.02, P = 0.03, fixed-effect, diastolic blood pressure (MD = -1.86 mmHg; 95% CI -0.76 to -2.95, P = 0.0009, fixed-effect). In contrast, in home-based participants, there was evidence of a marginally higher levels of programme completion (RR = 1.04, 95% CI 1.01 to 1.07, P = 0.009, fixed-effect) and adherence to the programme (not poolable). No consistent difference was seen in healthcare costs between the two forms of cardiac rehabilitation. Authors' conclusions This updated review supports the conclusions of the previous version of this review that home- and centre-based forms of cardiac rehabilitation seem to be equally effective for improving the clinical and health-related quality of life outcomes in low risk patients after MI or revascularisation, or with heart failure. This finding, together with the absence of evidence of important differences in healthcare costs between the two approaches, supports the continued expansion of evidence-based, home-based cardiac rehabilitation programmes. The choice of participating in a more traditional and supervised centre-based programme or a home-based programme should reflect the preference of the individual patient. Further data are needed to determine whether the effects of home- and centre-based cardiac rehabilitation reported in these short-term trials can be confirmed in the longer term. A number of studies failed to give sufficient detail to assess their risk of bias.

Compensatory water effects link yearly global land CO2 sink changes to temperature

Abstract: Large interannual variations in the measured growth rate of atmospheric carbon dioxide (CO2) originate primarily from fluctuations in carbon uptake by land ecosystems. It remains uncertain, however, to what extent temperature and water availability control the carbon balance of land ecosystems across spatial and temporal scales. Here we use empirical models based on eddy covariance data and process-based models to investigate the effect of changes in temperature and water availability on gross primary productivity (GPP), terrestrial ecosystem respiration (TER) and net ecosystem exchange (NEE) at local and global scales. We find that water availability is the dominant driver of the local interannual variability in GPP and TER. To a lesser extent this is true also for NEE at the local scale, but when integrated globally, temporal NEE variability is mostly driven by temperature fluctuations. We suggest that this apparent paradox can be explained by two compensatory water effects. Temporal water-driven GPP and TER variations compensate locally, dampening water-driven NEE variability. Spatial water availability anomalies also compensate, leaving a dominant temperature signal in the year-to-year fluctuations of the land carbon sink. These findings help to reconcile seemingly contradictory reports regarding the importance of temperature and water in controlling the interannual variability of the terrestrial carbon balance. Our study indicates that spatial climate covariation drives the global carbon cycle response.

Exome-wide association study of plasma lipids in > 300,000 individuals

Abstract: We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.

The biology of color

Abstract: Coloration mediates the relationship between an organism and its environment in important ways, including social signaling, antipredator defenses, parasitic exploitation, thermoregulation, and protection from ultraviolet light, microbes, and abrasion. Methodological breakthroughs are accelerating knowledge of the processes underlying both the production of animal coloration and its perception, experiments are advancing understanding of mechanism and function, and measurements of color collected noninvasively and at a global scale are opening windows to evolutionary dynamics more generally. Here we provide a roadmap of these advances and identify hitherto unrecognized challenges for this multi- and interdisciplinary field.

The changing prevalence and incidence of dementia over time — current evidence

Abstract: Dementia is an increasing focus for policymakers, civil organizations and multidisciplinary researchers. The most recent descriptive epidemiological research into dementia is enabling investigation into how the prevalence and incidence are changing over time. To establish clear trends, such comparisons need to be founded on population-based studies that use similar diagnostic and research methods consistently over time. This narrative Review synthesizes the findings from 14 studies that investigated trends in dementia prevalence (nine studies) and incidence (five studies) from Sweden, Spain, the UK, the Netherlands, France, the USA, Japan and Nigeria. Besides the Japanese study, these studies indicate stable or declining prevalence and incidence of dementia, and some provide evidence of sex-specific changes. No single risk or protective factor has been identified that fully explains the observed trends, but major societal changes and improvements in living conditions, education and healthcare might have favourably influenced physical, mental and cognitive health throughout an individual's life course, and could be responsible for a reduced risk of dementia in later life. Analytical epidemiological approaches combined with translational neuroscientific research could provide a unique opportunity to explore the neuropathology that underlies changing occurrence of dementia in the general population.

Psychological interventions for coronary heart disease

Abstract: BACKGROUND: Psychological interventions can form part of comprehensive cardiac rehabilitation programmes (CCR). These interventions may include stress management interventions, which aim to reduce stress, either as an end in itself or to reduce risk for further cardiac events in patients with heart disease. OBJECTIVES: To determine the effectiveness of psychological interventions, in particular stress management interventions, on mortality and morbidity, psychological measures, quality of life, and modifiable cardiac risk factors, in patients with coronary heart disease (CHD). SEARCH STRATEGY: We searched CCTR to December 2001 (Issue 4, 2001), MEDLINE 1999 to December 2001 and EMBASE 1998 to the end of 2001, PsychINFO and CINAHL to December 2001. In addition, searches of reference lists of papers were made and expert advice was sought. SELECTION CRITERIA: RCTs of non-pharmacological psychological interventions, administered by trained staff, either single modality interventions or a part of CCR with minimum follow up of 6 months. Adults of all ages with CHD (prior myocardial infarction, coronary artery bypass graft or percutaneous transluminal coronary angioplasty, angina pectoris or coronary artery disease defined by angiography). Stress management (SM) trials were identified and reported in combination with other psychological interventions and separately. DATA COLLECTION AND ANALYSIS: Studies were selected, and data were abstracted, independently by two reviewers. Authors were contacted where possible to obtain missing information. MAIN RESULTS: Thirty six trials with 12,841 patients were included. Of these, 18 (5242 patients) were SM trials. Quality of many trials was poor with the majority not reporting adequate concealment of allocation, and only 6 blinded outcome assessors. Combining the results of all trials showed no strong evidence of effect on total or cardiac mortality, or revascularisation. There was a reduction in the number of non-fatal reinfarctions in the intervention group (OR 0.78 (0.67, 0.90), but the two largest trials (with 4809 patients randomized) were null for this outcome, and there was statistical evidence of publication bias. Similar results were seen for the SM subgroup of trials. Provision of any psychological intervention or SM intervention caused small reductions in anxiety and depression. Few trials reported modifiable cardiac risk factors or quality of life. REVIEWERS' CONCLUSIONS: Overall psychological interventions showed no evidence of effect on total or cardiac mortality, but did show small reductions in anxiety and depression in patients with CHD. Similar results were seen for SM interventions when considered separately. However, the poor quality of trials, considerable heterogeneity observed between trials and evidence of significant publication bias make the pooled finding of a reduction in non-fatal myocardial infarction insecure.

Emission budgets and pathways consistent with limiting warming to 1.5 °C

Abstract: The Paris Agreement has opened debate on whether limiting warming to 1.5 °C is compatible with current emission pledges and warming of about 0.9 °C from the mid-nineteenth century to the present decade. We show that limiting cumulative post-2015 CO2 emissions to about 200 GtC would limit post-2015 warming to less than 0.6 °C in 66% of Earth system model members of the CMIP5 ensemble with no mitigation of other climate drivers, increasing to 240 GtC with ambitious non-CO2 mitigation. We combine a simple climate–carbon-cycle model with estimated ranges for key climate system properties from the IPCC Fifth Assessment Report. Assuming emissions peak and decline to below current levels by 2030, and continue thereafter on a much steeper decline, which would be historically unprecedented but consistent with a standard ambitious mitigation scenario (RCP2.6), results in a likely range of peak warming of 1.2–2.0 °C above the mid-nineteenth century. If CO2 emissions are continuously adjusted over time to limit 2100 warming to 1.5 °C, with ambitious non-CO2 mitigation, net future cumulative CO2 emissions are unlikely to prove less than 250 GtC and unlikely greater than 540 GtC. Hence, limiting warming to 1.5 °C is not yet a geophysical impossibility, but is likely to require delivery on strengthened pledges for 2030 followed by challengingly deep and rapid mitigation. Strengthening near-term emissions reductions would hedge against a high climate response or subsequent reduction rates proving economically, technically or politically unfeasible.