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Showing papers by "University of Leeds published in 2014"


Journal ArticleDOI
07 Mar 2014-BMJ
TL;DR: The TIDieR checklist and guide should improve the reporting of interventions and make it easier for authors to structure accounts of their interventions, reviewers and editors to assess the descriptions, and readers to use the information.
Abstract: Without a complete published description of interventions, clinicians and patients cannot reliably implement interventions that are shown to be useful, and other researchers cannot replicate or build on research findings. The quality of description of interventions in publications, however, is remarkably poor. To improve the completeness of reporting, and ultimately the replicability, of interventions, an international group of experts and stakeholders developed the Template for Intervention Description and Replication (TIDieR) checklist and guide. The process involved a literature review for relevant checklists and research, a Delphi survey of an international panel of experts to guide item selection, and a face to face panel meeting. The resultant 12 item TIDieR checklist (brief name, why, what (materials), what (procedure), who provided, how, where, when and how much, tailoring, modifications, how well (planned), how well (actual)) is an extension of the CONSORT 2010 statement (item 5) and the SPIRIT 2013 statement (item 11). While the emphasis of the checklist is on trials, the guidance is intended to apply across all evaluative study designs. This paper presents the TIDieR checklist and guide, with an explanation and elaboration for each item, and examples of good reporting. The TIDieR checklist and guide should improve the reporting of interventions and make it easier for authors to structure accounts of their interventions, reviewers and editors to assess the descriptions, and readers to use the information.

5,237 citations


Book
19 Sep 2014

2,968 citations


Journal ArticleDOI
TL;DR: The second iteration of the European Society of Cardiology (ESC) and European Association for the Study of Diabetes (EASD) joining forces to write guidelines on the management of diabetes mellitus (DM), pre-diabetes, and cardiovascular disease (CVD), designed to assist clinicians and other healthcare workers to make evidence-based management decisions.
Abstract: This is the second iteration of the European Society of Cardiology (ESC) and European Association for the Study of Diabetes (EASD) joining forces to write guidelines on the management of diabetes mellitus (DM), pre-diabetes, and cardiovascular disease (CVD), designed to assist clinicians and other healthcare workers to make evidence-based management decisions. The growing awareness of the strong biological relationship between DM and CVD rightly prompted these two large organizations to collaborate to generate guidelines relevant to their joint interests, the first of which were published in 2007. Some assert that too many guidelines are being produced but, in this burgeoning field, five years in the development of both basic and clinical science is a long time and major trials have reported in this period, making it necessary to update the previous Guidelines.

2,809 citations


Journal ArticleDOI
Andrew R. Wood1, Tõnu Esko2, Jian Yang3, Sailaja Vedantam4  +441 moreInstitutions (132)
TL;DR: This article identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height, and all common variants together captured 60% of heritability.
Abstract: Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

1,872 citations


Journal ArticleDOI
TL;DR: In this article, the authors review the leading CO2 capture technologies, available in the short and long term, and their technological maturity, before discussing CO2 transport and storage, as well as the economic and legal aspects of CCS.
Abstract: In recent years, Carbon Capture and Storage (Sequestration) (CCS) has been proposed as a potential method to allow the continued use of fossil-fuelled power stations whilst preventing emissions of CO2 from reaching the atmosphere. Gas, coal (and biomass)-fired power stations can respond to changes in demand more readily than many other sources of electricity production, hence the importance of retaining them as an option in the energy mix. Here, we review the leading CO2 capture technologies, available in the short and long term, and their technological maturity, before discussing CO2 transport and storage. Current pilot plants and demonstrations are highlighted, as is the importance of optimising the CCS system as a whole. Other topics briefly discussed include the viability of both the capture of CO2 from the air and CO2 reutilisation as climate change mitigation strategies. Finally, we discuss the economic and legal aspects of CCS.

1,752 citations


Journal ArticleDOI
TL;DR: This work analyzed a global database of directly harvested trees at 58 sites, spanning a wide range of climatic conditions and vegetation types, and found a pantropical model incorporating wood density, trunk diameter, and the variable E outperformed previously published models without height.
Abstract: Terrestrial carbon stock mapping is important for the successful implementation of climate change mitigation policies. Its accuracy depends on the availability of reliable allometric models to infer oven-dry aboveground biomass of trees from census data. The degree of uncertainty associated with previously published pantropical aboveground biomass allometries is large. We analyzed a global database of directly harvested trees at 58 sites, spanning a wide range of climatic conditions and vegetation types (4004 trees ≥ 5 cm trunk diameter). When trunk diameter, total tree height, and wood specific gravity were included in the aboveground biomass model as covariates, a single model was found to hold across tropical vegetation types, with no detectable effect of region or environmental factors. The mean percent bias and variance of this model was only slightly higher than that of locally fitted models. Wood specific gravity was an important predictor of aboveground biomass, especially when including a much broader range of vegetation types than previous studies. The generic tree diameter-height relationship depended linearly on a bioclimatic stress variable E, which compounds indices of temperature variability, precipitation variability, and drought intensity. For cases in which total tree height is unavailable for aboveground biomass estimation, a pantropical model incorporating wood density, trunk diameter, and the variable E outperformed previously published models without height. However, to minimize bias, the development of locally derived diameter-height relationships is advised whenever possible. Both new allometric models should contribute to improve the accuracy of biomass assessment protocols in tropical vegetation types, and to advancing our understanding of architectural and evolutionary constraints on woody plant development.

1,750 citations


Journal ArticleDOI
TL;DR: In this paper, a comprehensive summary of studies that simulate climate change impacts on agriculture are reported in a meta-analysis, which suggests that aggregate yield losses should be expected for wheat, rice and maize in temperate and tropical growing regions even under relatively moderate levels of local warming.
Abstract: A comprehensive summary of studies that simulate climate change impacts on agriculture are now reported in a meta-analysis. Findings suggest that, without measures to adapt to changing conditions, aggregate yield losses should be expected for wheat, rice and maize in temperate and tropical growing regions even under relatively moderate levels of local warming.

1,458 citations


Journal ArticleDOI
TL;DR: It is found that the majority of urban bird and plant species are native in the world's cities, with the most common being Columba livia and Poa annua and few plants and birds are cosmopolitan.
Abstract: Urbanization contributes to the loss of the world's biodiversity and the homogenization of its biota. However, comparative studies of urban biodiversity leading to robust generalities of the status and drivers of biodiversity in cities at the global scale are lacking. Here, we compiled the largest global dataset to date of two diverse taxa in cities: birds (54 cities) and plants (110 cities). We found that the majority of urban bird and plant species are native in the world's cities. Few plants and birds are cosmopolitan, the most common being Columba livia and Poa annua. The density of bird and plant species (the number of species per km2) has declined substantially: only 8% of native bird and 25% of native plant species are currently present compared with estimates of non-urban density of species. The current density of species in cities and the loss in density of species was best explained by anthropogenic features (landcover, city age) rather than by non-anthropogenic factors (geography, climate, topography). As urbanization continues to expand, efforts directed towards the conservation of intact vegetation within urban landscapes could support higher concentrations of both bird and plant species. Despite declines in the density of species, cities still retain endemic native species, thus providing opportunities for regional and global biodiversity conservation, restoration and education.

1,100 citations


Journal ArticleDOI
TL;DR: In this paper, the authors examine the factors that give rise to food waste throughout the food supply chain, and propose a framework to identify and prioritize the most appropriate options for prevention and management of food waste.

1,016 citations


Reference EntryDOI
TL;DR: The average risk of high blood pressure was reduced with calcium supplementation compared with placebo and the composite outcome maternal death or serious morbidity was reduced, but there was an anomalous increase in the risk of HELLP.
Abstract: Background Pre-eclampsia and eclampsia are common causes of serious morbidity and death. Calcium supplementation may reduce the risk of pre-eclampsia, and may help to prevent preterm birth. Objectives To assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child outcomes. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 March 2013) and contacted study authors for more data where possible. We updated the search in May 2014 and added the results to the 'Awaiting Classification' section of the review. Selection criteria Randomised controlled trials (RCTs) comparing high-dose (at least 1 g daily of calcium) or low-dose calcium supplementation during pregnancy with placebo or no calcium. Data collection and analysis We assessed eligibility and trial quality, extracted and double-entered data. Main results High-dose calcium supplementation (≥1 g/day) We included 14 studies in the review, however one study contributed no data. We included 13 high-quality studies in our meta-analyses (15,730 women). The average risk of high blood pressure (BP) was reduced with calcium supplementation compared with placebo (12 trials, 15,470 women: risk ratio (RR) 0.65, 95% confidence interval (CI) 0.53 to 0.81; I² = 74%). There was also a significant reduction in the risk of pre-eclampsia associated with calcium supplementation (13 trials, 15,730 women: RR 0.45, 95% CI 0.31 to 0.65; I² = 70%). The effect was greatest for women with low calcium diets (eight trials, 10,678 women: average RR 0.36, 95% CI 0.20 to 0.65; I² = 76%) and women at high risk of pre-eclampsia (five trials, 587 women: average RR 0.22, 95% CI 0.12 to 0.42; I² = 0%). These data should be interpreted with caution because of the possibility of small-study effect or publication bias. The composite outcome maternal death or serious morbidity was reduced (four trials, 9732 women; RR 0.80, 95% CI 0.65 to 0.97; I² = 0%). Maternal deaths were not significantly different (one trial of 8312 women: calcium group one death versus placebo group six deaths). There was an anomalous increase in the risk of HELLP (haemolysis, elevated liver enzymes and low platelets) syndrome (two trials, 12,901 women: RR 2.67, 95% CI 1.05 to 6.82; I² = 0%) in the calcium group, however, the absolute number of events was low (16 versus six). The average risk of preterm birth was reduced in the calcium group (11 trials, 15,275 women: RR 0.76, 95% CI 0.60 to 0.97; I² = 60%) and amongst women at high risk of developing pre-eclampsia (four trials, 568 women: average RR 0.45, 95% CI 0.24 to 0.83; I² = 60%), but no significant reduction in neonatal high care admission. There was no overall effect on the risk of stillbirth or infant death before discharge from hospital (11 trials 15,665 babies: RR 0.90, 95% CI 0.74 to 1.09; I² = 0%). One study showed a reduction in childhood systolic BP greater than 95th percentile among children exposed to calcium supplementation in utero (514 children: RR 0.59, 95% CI 0.39 to 0.91). In a subset of these children, dental caries at 12 years old was also reduced (195 children, RR 0.73, 95% CI 0.62 to 0.87). Low-dose calcium supplementation (< 1 g/day) We included 10 trials (2234 women) that evaluated low-dose supplementation with calcium alone (4) or in association with vitamin D (3), linoleic acid (2), or antioxidants (1). Most studies recruited women at high risk for pre-eclampsia, and were at high risk of bias, thus the results should be interpreted with caution. Supplementation with low doses of calcium significantly reduced the risk of pre-eclampsia (RR 0.38, 95% CI 0.28 to 0.52; I² = 0%). There was also a reduction in hypertension, low birthweight and neonatal intensive care unit admission. Authors' conclusions Calcium supplementation (≥ 1 g/day) is associated with a significant reduction in the risk of pre-eclampsia, particularly for women with low calcium diets. The treatment effect may be overestimated due to small-study effects or publication bias. It also reduces preterm birth and the occurrence of the composite outcome 'maternal death or serious morbidity'. We considered these benefits to outweigh the increased risk of HELLP syndrome, which was small in absolute numbers. The World Health Organization recommends calcium 1.5 g to 2 g daily for pregnant women with low dietary calcium intake. The limited evidence on low-dose calcium supplementation suggests a reduction in pre-eclampsia, but needs to be confirmed by larger, high-quality trials. Pending such results, in settings of low dietary calcium where high-dose supplementation is not feasible, the option of lower-dose supplements (500 to 600 mg/day) might be considered in preference to no supplementation.

997 citations


Journal ArticleDOI
Jacy R Crosby1, Gina M. Peloso2, Gina M. Peloso3, Paul L. Auer4, David R. Crosslin5, Nathan O. Stitziel6, Leslie A. Lange7, Yingchang Lu8, Zheng-Zheng Tang7, He Zhang9, George Hindy10, Nicholas G. D. Masca11, Kathleen Stirrups12, Stavroula Kanoni12, Ron Do2, Ron Do3, Goo Jun9, Youna Hu9, Hyun Min Kang9, Chenyi Xue9, Anuj Goel13, Martin Farrall13, Stefano Duga14, Pier Angelica Merlini, Rosanna Asselta14, Domenico Girelli15, Oliviero Olivieri15, Nicola Martinelli15, Wu Yin16, Dermot F. Reilly16, Elizabeth K. Speliotes9, Caroline S. Fox17, Kristian Hveem18, Oddgeir L. Holmen19, Majid Nikpay20, Deborah N. Farlow2, Themistocles L. Assimes21, Nora Franceschini7, Jennifer G. Robinson22, Kari E. North7, Lisa W. Martin23, Mark A. DePristo2, Namrata Gupta2, Stefan A. Escher10, Jan-Håkan Jansson24, Natalie R. van Zuydam25, Colin N. A. Palmer25, Nicholas J. Wareham26, Werner Koch27, Thomas Meitinger27, Annette Peters, Wolfgang Lieb28, Raimund Erbel, Inke R. König29, Jochen Kruppa29, Franziska Degenhardt30, Omri Gottesman8, Erwin P. Bottinger8, Christopher J. O'Donnell17, Bruce M. Psaty31, Bruce M. Psaty5, Christie M. Ballantyne32, Christie M. Ballantyne33, Gonçalo R. Abecasis9, Jose M. Ordovas34, Jose M. Ordovas35, Olle Melander10, Hugh Watkins13, Marju Orho-Melander10, Diego Ardissino, Ruth J. F. Loos8, Ruth McPherson20, Cristen J. Willer9, Jeanette Erdmann29, Alistair S. Hall36, Nilesh J. Samani11, Panos Deloukas37, Panos Deloukas38, Panos Deloukas12, Heribert Schunkert27, James G. Wilson39, Charles Kooperberg40, Stephen S. Rich41, Russell P. Tracy42, Danyu Lin7, David Altshuler3, David Altshuler2, Stacey Gabriel2, Deborah A. Nickerson5, Gail P. Jarvik5, L. Adrienne Cupples43, L. Adrienne Cupples26, Alexander P. Reiner5, Alexander P. Reiner40, Eric Boerwinkle33, Sekar Kathiresan3, Sekar Kathiresan2 
TL;DR: Rare mutations that disrupt AP OC3 function were associated with lower levels of plasma triglycerides and APOC3, and carriers of these mutations were found to have a reduced risk of coronary heart disease.
Abstract: Background Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. Methods We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. Results An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G→A and IVS3+1G→T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1×10 − 20 ), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P = 8×10 − 10 ). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P = 4×10 − 6 ). Conclusions Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.)

Journal ArticleDOI
TL;DR: The current systematic literature review and meta-analysis extends and confirms the associations of obesity with an unfavourable overall and breast cancer survival in pre and postmenopausal breast cancer, regardless of when BMI is ascertained.

Journal ArticleDOI
TL;DR: The history and development of coupling reactions between aryl halides and various classes of nucleophiles is discussed, focusing mostly on the different mechanisms proposed through the years.
Abstract: Cu-catalysed arylation reactions devoted to the formation of C–C and C–heteroatom bonds (Ullmann-type couplings) have acquired great importance in the last decade. This review discusses the history and development of coupling reactions between aryl halides and various classes of nucleophiles, focusing mostly on the different mechanisms proposed through the years. Selected mechanistic investigations are treated more in depth than others. For example, evidence in favour or against radical mechanisms is discussed. Cu(I) and Cu(III) complexes involved in the Ullmann reaction and N/O selectivity in aminoalcohol arylation are discussed. A separate section has been dedicated to the synthesis of heterocyclic rings through intramolecular couplings. Finally, recent developments in green chemistry for these reactions, such as reactions in aqueous media and heterogeneous catalysis, have also been reviewed.

Journal ArticleDOI
TL;DR: Significance This study provides evidence of change in the relative importance of different crop plants in national food supplies worldwide over the past 50 years, which heightens interdependence among countries in their food supplies, plant genetic resources, and nutritional priorities, and gives further urgency to nutrition development priorities aimed at bolstering food security.
Abstract: The narrowing of diversity in crop species contributing to the world’s food supplies has been considered a potential threat to food security. However, changes in this diversity have not been quantified globally. We assess trends over the past 50 y in the richness, abundance, and composition of crop species in national food supplies worldwide. Over this period, national per capita food supplies expanded in total quantities of food calories, protein, fat, and weight, with increased proportions of those quantities sourcing from energy-dense foods. At the same time the number of measured crop commodities contributing to national food supplies increased, the relative contribution of these commodities within these supplies became more even, and the dominance of the most significant commodities decreased. As a consequence, national food supplies worldwide became more similar in composition, correlated particularly with an increased supply of a number of globally important cereal and oil crops, and a decline of other cereal, oil, and starchy root species. The increase in homogeneity worldwide portends the establishment of a global standard food supply, which is relatively species-rich in regard to measured crops at the national level, but species-poor globally. These changes in food supplies heighten interdependence among countries in regard to availability and access to these food sources and the genetic resources supporting their production, and give further urgency to nutrition development priorities aimed at bolstering food security.

Journal ArticleDOI
13 Nov 2014-Nature
TL;DR: Piezo1 channels are shown as sensors of frictional force (shear stress) and determinants of vascular structure in both development and adult physiology and the data suggest that Piezo 1 channels function as pivotal integrators in vascular biology.
Abstract: The mechanisms by which physical forces regulate endothelial cells to determine the complexities of vascular structure and function are enigmatic. Studies of sensory neurons have suggested Piezo proteins as subunits of Ca(2+)-permeable non-selective cationic channels for detection of noxious mechanical impact. Here we show Piezo1 (Fam38a) channels as sensors of frictional force (shear stress) and determinants of vascular structure in both development and adult physiology. Global or endothelial-specific disruption of mouse Piezo1 profoundly disturbed the developing vasculature and was embryonic lethal within days of the heart beating. Haploinsufficiency was not lethal but endothelial abnormality was detected in mature vessels. The importance of Piezo1 channels as sensors of blood flow was shown by Piezo1 dependence of shear-stress-evoked ionic current and calcium influx in endothelial cells and the ability of exogenous Piezo1 to confer sensitivity to shear stress on otherwise resistant cells. Downstream of this calcium influx there was protease activation and spatial reorganization of endothelial cells to the polarity of the applied force. The data suggest that Piezo1 channels function as pivotal integrators in vascular biology.

Journal ArticleDOI
TL;DR: New analysis is presented that tentatively links increases in climate variability with increasing food insecurity in the future and highlights the need to reframe research questions in such a way that they can provide decision makers throughout the food system with actionable answers.
Abstract: The focus of the great majority of climate change impact studies is on changes in mean climate. In terms of climate model output, these changes are more robust than changes in climate variability. By concentrating on changes in climate means, the full impacts of climate change on biological and human systems are probably being seriously underestimated. Here, we briefly review the possible impacts of changes in climate variability and the frequency of extreme events on biological and food systems, with a focus on the developing world. We present new analysis that tentatively links increases in climate variability with increasing food insecurity in the future. We consider the ways in which people deal with climate variability and extremes and how they may adapt in the future. Key knowledge and data gaps are highlighted. These include the timing and interactions of different climatic stresses on plant growth and development, particularly at higher temperatures, and the impacts on crops, livestock and farming systems of changes in climate variability and extreme events on pest-weed-disease complexes. We highlight the need to reframe research questions in such a way that they can provide decision makers throughout the food system with actionable answers, and the need for investment in climate and environmental monitoring. Improved understanding of the full range of impacts of climate change on biological and food systems is a critical step in being able to address effectively the effects of climate variability and extreme events on human vulnerability and food security, particularly in agriculturally based developing countries facing the challenge of having to feed rapidly growing populations in the coming decades.

Journal ArticleDOI
TL;DR: Autonomous Underwater Vehicles (AUVs) have a wide range of applications in marine geoscience, and are increasingly being used in the scientific, military, commercial, and policy sectors as mentioned in this paper.


Journal ArticleDOI
TL;DR: Analyses revealed psychological therapies to be beneficial for children with chronic pain on seven outcomes, and the impact of psychological therapies on depression and anxiety, which were previously combined as 'mood'.
Abstract: Background This is an update of the original Cochrane review first published in Issue 1, 2003, and previously updated in 2009 and 2012. Chronic pain affects many children, who report severe pain, disability, and distressed mood. Psychological therapies are emerging as effective interventions to treat children with chronic or recurrent pain. This update focuses specifically on psychological therapies delivered face-to-face, adds new randomised controlled trials (RCTs), and additional data from previously included trials. Objectives There were three objectives to this review. First, to determine the effectiveness on clinical outcomes of pain severity, disability, depression, and anxiety of psychological therapy delivered face-to-face for chronic and recurrent pain in children and adolescents compared with active treatment, waiting-list, or standard medical care. Second, to evaluate the impact of psychological therapies on depression and anxiety, which were previously combined as 'mood'. Third, we assessed the risk of bias of the included studies and the quality of outcomes using the GRADE criteria. Search methods Searches were undertaken of CENTRAL, MEDLINE, EMBASE, and PsycINFO. We searched for further RCTs in the references of all identified studies, meta-analyses, and reviews. Trial registry databases were also searched. The date of most recent search was January 2014. Selection criteria RCTs with at least 10 participants in each arm post-treatment comparing psychological therapies with active treatment, standard medical care, or waiting-list control for children or adolescents with episodic, recurrent or persistent pain were eligible for inclusion. Only trials conducted in person (face-to-face) were considered. Studies that delivered treatment remotely were excluded from this update. Data collection and analysis All included studies were analysed and the quality of outcomes were assessed. All treatments were combined into one class, psychological treatments. Pain conditions were split into headache and non-headache. Both conditions were assessed on four outcomes: pain, disability, depression, and anxiety. Data were extracted at two time points; post-treatment (immediately or the earliest data available following end of treatment) and at follow-up (between three and 12 months post-treatment). Main results Seven papers were identified in the updated search. Of these papers, five presented new trials and two presented follow-up data for previously included trials. Five studies that were previously included in this review were excluded as therapy was delivered remotely. The review thus included a total of 37 studies. The total number of participants completing treatments was 2111. Twenty studies addressed treatments for headache (including migraine); nine for abdominal pain; two for mixed pain conditions including headache pain, two for fibromyalgia, two for recurrent abdominal pain or irritable bowel syndrome, and two for pain associated with sickle cell disease. Analyses revealed psychological therapies to be beneficial for children with chronic pain on seven outcomes. For headache pain, psychological therapies reduced pain post-treatment and at follow-up respectively (risk ratio (RR) 2.47, 95% confidence interval (CI) 1.97 to 3.09, z = 7.87, p 0.05). At follow-up, only one study was eligible, therefore no analysis was possible and no conclusions can be drawn. Analyses revealed a small beneficial effect for anxiety post-treatment (SMD -0.33, 95% CI -0.61 to -0.04, z = 2.25, p 0.05). Analyses revealed two beneficial effects of psychological treatment for children with non-headache pain. Pain was found to improve post-treatment (SMD -0.57, 95% CI -0.86 to -0.27, z = 3.74, p 0.05). Psychological therapies also had a beneficial effect for disability post-treatment (SMD -0.45, 95% CI -0.71 to -0.19, z = 3.40, p 0.05). No effect was found for depression or anxiety post-treatment (SMD -0.07, 95% CI -0.30 to 0.17, z = 0.54, p > 0.05; SMD -0.15, 95% CI -0.36 to 0.07, z = 1.33, p > 0.05) or at follow-up (SMD 0.06, 95% CI -0.16 to 0.28, z = 0.53, p > 0.05; SMD 0.05, 95% CI -0.24 to 0.33, z = 0.32, p > 0.05). Authors' conclusions Psychological treatments delivered face-to-face are effective in reducing pain intensity and disability for children and adolescents (<18 years) with headache, and therapeutic gains appear to be maintained, although this should be treated with caution for the disability outcome as only two studies could be included in the follow-up analysis. Psychological therapies are also beneficial at reducing anxiety post-treatment for headache. For non-headache conditions, psychological treatments were found to be beneficial for pain and disability post-treatment but these effects were not maintained at follow-up. There is limited evidence available to estimate the effects of psychological therapies on depression and anxiety for children and adolescents with headache and non-headache pain. The conclusions of this update replicate and add to those of the previous review which found that psychological therapies were effective in reducing pain intensity for children with headache and non-headache pain conditions, and these effects were maintained at follow-up for children with headache conditions.

Journal ArticleDOI
TL;DR: The presence of CD8+ T cells in breast cancer is associated with a significant reduction in the relative risk of death from disease in both the ER-negative and ER-positive HER2-positive subtypes and may improve risk stratification in Breast cancer patients classified into these subtypes.

Journal ArticleDOI
Natasha Merat1, A. Hamish Jamson1, Frank Lai1, M. C. Daly1, Oliver Carsten1 
TL;DR: In this article, a driving simulator study was designed to investigate drivers' ability to resume control from a highly automated vehicle in two conditions: (i) when automation was switched off and manual control was required at a system-based, regular interval and (ii) when transition to manual was based on the length of time drivers were looking away from the road ahead.
Abstract: A driving simulator study was designed to investigate drivers’ ability to resume control from a highly automated vehicle in two conditions: (i) when automation was switched off and manual control was required at a system-based, regular interval and (ii) when transition to manual was based on the length of time drivers were looking away from the road ahead. In addition to studying the time it took drivers to successfully resume control from the automated system, eye tracking data were used to observe visual attention to the surrounding environment and the pattern of drivers’ eye fixations as manual control was resumed in the two conditions. Results showed that drivers’ pattern of eye movement fixations remained variable for some time after automation was switched off, if disengagement was actually based on drivers’ distractions away from the road ahead. When disengagement was more predictable and system-based, drivers’ attention towards the road centre was higher and more stable. Following a lag of around 10 s, drivers’ lateral control of driving and steering corrections (as measured by SDLP and high frequency component of steering, respectively) were more stable when transition to manual control was predictable and based on a fixed time. Whether automation transition to manual was based on a fixed or variable interval, it took drivers around 35–40 s to stabilise their lateral control of the vehicle. The results of this study indicate that if drivers are out of the loop due to control of the vehicle in a limited self-driving situation (Level 3 automation), their ability to regain control of the vehicle is better if they are expecting automation to be switched off. As regular disengagement of automation is not a particularly practical method for keeping drivers in the loop, future research should consider how to best inform drivers of their obligation to resume control of driving from an automated system.

Journal ArticleDOI
TL;DR: Moderate hypothermia after perinatal asphyxia resulted in improved neurocognitive outcomes in middle childhood.
Abstract: Background In the Total Body Hypothermia for Neonatal Encephalopathy Trial (TOBY), newborns with asphyxial encephalopathy who received hypothermic therapy had improved neurologic outcomes at 18 months of age, but it is uncertain whether such therapy results in longer-term neurocognitive benefits. Methods We randomly assigned 325 newborns with asphyxial encephalopathy who were born at a gestational age of 36 weeks or more to receive standard care alone (control) or standard care with hypothermia to a rectal temperature of 33 to 34°C for 72 hours within 6 hours after birth. We evaluated the neurocognitive function of these children at 6 to 7 years of age. The primary outcome of this analysis was the frequency of survival with an IQ score of 85 or higher. Results A total of 75 of 145 children (52%) in the hypothermia group versus 52 of 132 (39%) in the control group survived with an IQ score of 85 or more (relative risk, 1.31; P = 0.04). The proportions of children who died were similar in the hypothermia group and the control group (29% and 30%, respectively). More children in the hypothermia group than in the control group survived without neurologic abnormalities (65 of 145 [45%] vs. 37 of 132 [28%]; relative risk, 1.60; 95% confidence interval, 1.15 to 2.22). Among survivors, children in the hypothermia group, as compared with those in the control group, had significant reductions in the risk of cerebral palsy (21% vs. 36%, P = 0.03) and the risk of moderate or severe disability (22% vs. 37%, P = 0.03); they also had significantly better motor-function scores. There was no significant between-group difference in parental assessments of children’s health status and in results on 10 of 11 psychometric tests. Conclusions Moderate hypothermia after perinatal asphyxia resulted in improved neurocognitive outcomes in middle childhood. (Funded by the United Kingdom Medical Research Council and others; TOBY ClinicalTrials.gov number, NCT01092637.)

Journal ArticleDOI
31 Jan 2014-Science
TL;DR: Using data from 2154 sites in savannas across Africa, Australia, and South America, it is found that increasing moisture availability drives increases in fire and tree basal area, whereas fire reduces tree basal Area.
Abstract: Ecologists have long sought to understand the factors controlling the structure of savanna vegetation. Using data from 2154 sites in savannas across Africa, Australia, and South America, we found that increasing moisture availability drives increases in fire and tree basal area, whereas fire reduces tree basal area. However, among continents, the magnitude of these effects varied substantially, so that a single model cannot adequately represent savanna woody biomass across these regions. Historical and environmental differences drive the regional variation in the functional relationships between woody vegetation, fire, and climate. These same differences will determine the regional responses of vegetation to future climates, with implications for global carbon stocks.

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TL;DR: Recent progress in the use of biosensors for the detection of whole bacterial cells for sensitive and earlier identification of bacteria without the need for sample processing is discussed, with a particular focus on electrochemical biosensing systems.
Abstract: Bacterial pathogens are important targets for detection and identification in medicine, food safety, public health, and security. Bacterial infection is a common cause of morbidity and mortality worldwide. In spite of the availability of antibiotics, these infections are often misdiagnosed or there is an unacceptable delay in diagnosis. Current methods of bacterial detection rely upon laboratory-based techniques such as cell culture, microscopic analysis, and biochemical assays. These procedures are time-consuming and costly and require specialist equipment and trained users. Portable stand-alone biosensors can facilitate rapid detection and diagnosis at the point of care. Biosensors will be particularly useful where a clear diagnosis informs treatment, in critical illness (e.g., meningitis) or to prevent further disease spread (e.g., in case of food-borne pathogens or sexually transmitted diseases). Detection of bacteria is also becoming increasingly important in antibioterrorism measures (e.g., anthrax detection). In this review, we discuss recent progress in the use of biosensors for the detection of whole bacterial cells for sensitive and earlier identification of bacteria without the need for sample processing. There is a particular focus on electrochemical biosensors, especially impedance-based systems, as these present key advantages in terms of ease of miniaturization, lack of reagents, sensitivity, and low cost.

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20 May 2014-BMJ
TL;DR: Limited, moderate quality evidence is provided that searching for and eradicating H pylori reduces the incidence of gastric cancer in healthy asymptomatic infected Asian individuals, but these data cannot necessarily be extrapolated to other populations.
Abstract: Objectives To determine whether searching for Helicobacter pylori and treating with eradication therapy leads to a reduction in incidence of gastric cancer among healthy asymptomatic infected individuals. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, Embase, and the Cochrane central register of controlled trials were searched through to December 2013. Conference proceedings between 2001 and 2013 were hand searched. A recursive search was performed with bibliographies of relevant studies. There were no language restrictions. Eligibility criteria for selecting studies Randomised controlled trials examining the effect of at least seven days of eradication therapy on subsequent occurrence of gastric cancer in adults who tested positive for Helicobacter pylori but otherwise healthy and asymptomatic were eligible. The control arm had to receive placebo or no treatment. Subjects had to be followed for ≥2 years. Main outcome measures Primary outcome, defined a priori, was the effect of eradication therapy on the subsequent occurrence of gastric cancer expressed as a relative risk of gastric cancer with 95% confidence intervals. Results The search strategy identified 1560 citations, of which six individual randomised controlled trials were eligible. Fifty one (1.6%) gastric cancers occurred among 3294 individuals who received eradication therapy versus 76 (2.4%) in 3203 control subjects (relative risk 0.66, 95% confidence interval 0.46 to 0.95), with no heterogeneity between studies (I2=0%, P=0.60). If the benefit of eradication therapy was assumed to persist lifelong the number needed to treat was as low as 15 for Chinese men and as high as 245 for US women. Conclusions These data provide limited, moderate quality evidence that searching for and eradicating H pylori reduces the incidence of gastric cancer in healthy asymptomatic infected Asian individuals, but these data cannot necessarily be extrapolated to other populations.

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TL;DR: The authors provide an extensive review of the key research traditions on framing across management and organizational literature, noting the salient contributions to date and highlighting potenti... and their general aim is to consolidate and advance the current body of research on framing in management and organisational literature.
Abstract: There are few constructs that are as ubiquitous across traditions of management and organizational research, and indeed the social sciences more generally, as that of frame or framing. The widespread popularity and use of the concept has led to rich streams of research, ranging from work in managerial cognition and decision-making to strategic and organizational change, and social movements and institutions. At the same time, the popularity of framing across these literatures has perhaps also come at a price. Indeed, it has meant that these streams of research have essentially developed along separate paths, despite the prospect and promise of a greater connection between them. In this paper, our general aim is to consolidate and advance the current body of research on framing in the management and organizational literature. We do this by providing an extensive review of the key research traditions on framing across this literature, noting the salient contributions to date and highlighting potenti...

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TL;DR: To what extent redox changes are involved in plant drought responses and the roles that different ROS-generating processes may play are asked and the likely importance of thiol systems in drought-induced redox signaling is discussed.
Abstract: Drought is considered to cause oxidative stress, but the roles of oxidant-induced modifications in plant responses to water deficit remain obscure. Key unknowns are the roles of reactive oxygen species (ROS) produced at specific intracellular or apoplastic sites and the interactions between the complex, networking antioxidative systems in restricting ROS accumulation or in redox signal transmission. This Update discusses the physiological aspects of ROS production during drought, and analyzes the relationship between oxidative stress and drought from different but complementary perspectives. We ask to what extent redox changes are involved in plant drought responses and discuss the roles that different ROS-generating processes may play. Our discussion emphasizes the complexity and the specificity of antioxidant systems, and the likely importance of thiol systems in drought-induced redox signaling. We identify candidate drought-responsive redox-associated genes and analyze the potential importance of different metabolic pathways in drought-associated oxidative stress signaling.

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TL;DR: The experimental results suggest that the paradigm of color normalization, as a preprocessing step, can significantly help histological image analysis algorithms to demonstrate stable performance which is insensitive to imaging conditions in general and scanner variations in particular.
Abstract: Histopathology diagnosis is based on visual examination of the morphology of histological sections under a microscope. With the increasing popularity of digital slide scanners, decision support systems based on the analysis of digital pathology images are in high demand. However, computerized decision support systems are fraught with problems that stem from color variations in tissue appearance due to variation in tissue preparation, variation in stain reactivity from different manufacturers/batches, user or protocol variation, and the use of scanners from different manufacturers. In this paper, we present a novel approach to stain normalization in histopathology images. The method is based on nonlinear mapping of a source image to a target image using a representation derived from color deconvolution. Color deconvolution is a method to obtain stain concentration values when the stain matrix, describing how the color is affected by the stain concentration, is given. Rather than relying on standard stain matrices, which may be inappropriate for a given image, we propose the use of a color-based classifier that incorporates a novel stain color descriptor to calculate image-specific stain matrix. In order to demonstrate the efficacy of the proposed stain matrix estimation and stain normalization methods, they are applied to the problem of tumor segmentation in breast histopathology images. The experimental results suggest that the paradigm of color normalization, as a preprocessing step, can significantly help histological image analysis algorithms to demonstrate stable performance which is insensitive to imaging conditions in general and scanner variations in particular.

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TL;DR: The findings suggest that attempts to apply the two theories commonly used in this review more extensively are unlikely to increase intervention effectiveness.
Abstract: Objective: To systematically investigate the extent and type of theory use in physical activity and dietary interventions, as well as associations between extent and type of theory use with intervention effectiveness. Methods: An in-depth analysis of studies included in two systematic reviews of physical activity and healthy eating interventions (k = 190). Extent and type of theory use was assessed using the Theory Coding Scheme (TCS) and intervention effectiveness was calculated using Hedges’s g. Metaregressions assessed the relationships between these measures. Results: Fifty-six percent of interventions reported a theory base. Of these, 90% did not report links between all of their behavior change techniques (BCTs) with specific theoretical constructs and 91% did not report links between all the specified constructs with BCTs. The associations between a composite score or specific items on the TCS and intervention effectiveness were inconsistent. Interventions based on Social Cognitive Theory or the Transtheoretical Model were similarly effective and no more effective than interventions not reporting a theory base. Conclusions: The coding of theory in these studies suggested that theory was not often used extensively in the development of interventions. Moreover, the relationships between type of theory used and the extent of theory use with effectiveness were generally weak. The findings suggest that attempts to apply the two theories commonly used in this review more extensively are unlikely to increase intervention effectiveness.

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TL;DR: The British Geriatrics Society Fit for Frailty guideline is consensus best practice guidance for the management of frailty in community and outpatient settings and an holistic medical review is recommended for all older people identified with frailty.
Abstract: UNLABELLED Older people are majority users of health and social care services in the UK and internationally. Many older people who access these services have frailty, which is a state of vulnerability to adverse outcomes. The existing health care response to frailty is mainly secondary care-based and reactive to the acute health crises of falls, delirium and immobility. A more proactive, integrated, person-centred and community-based response to frailty is required. The British Geriatrics Society Fit for Frailty guideline is consensus best practice guidance for the management of frailty in community and outpatient settings. RECOGNITION OF FRAILTY The BGS recommends that all encounters between health and social care staff and older people in community and outpatient settings should include an assessment for frailty. A gait speed 10s; and a score of ≥3 on the PRISMA 7 questionnaire can indicate frailty. The common clinical presentations of frailty (falls, delirium, sudden immobility) can also be used to indicate the possible presence of frailty. MANAGEMENT OF FRAILTY The BGS recommends an holistic medical review based on the principles of comprehensive geriatric assessment (CGA) for all older people identified with frailty. This will: diagnose medical illnesses to optimise treatment; apply evidence-based medication review checklists (e.g. STOPP/START criteria); include discussion with older people and carers to define the impact of illness; work with the older person to create an individualised care and support plan. SCREENING FOR FRAILTY The BGS does not recommend population screening for frailty using currently available instruments.