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Showing papers by "University of Leeds published in 2013"


Journal ArticleDOI
TL;DR: Developing more efficient methods to detect frailty and measure its severity in routine clinical practice would greatly inform the appropriate selection of elderly people for invasive procedures or drug treatments and would be the basis for a shift in the care of frail elderly people towards more appropriate goal-directed care.

5,456 citations


Journal ArticleDOI
TL;DR: In this paper, the authors provided an assessment of black-carbon climate forcing that is comprehensive in its inclusion of all known and relevant processes and that is quantitative in providing best estimates and uncertainties of the main forcing terms: direct solar absorption; influence on liquid, mixed phase, and ice clouds; and deposition on snow and ice.
Abstract: Black carbon aerosol plays a unique and important role in Earth's climate system. Black carbon is a type of carbonaceous material with a unique combination of physical properties. This assessment provides an evaluation of black-carbon climate forcing that is comprehensive in its inclusion of all known and relevant processes and that is quantitative in providing best estimates and uncertainties of the main forcing terms: direct solar absorption; influence on liquid, mixed phase, and ice clouds; and deposition on snow and ice. These effects are calculated with climate models, but when possible, they are evaluated with both microphysical measurements and field observations. Predominant sources are combustion related, namely, fossil fuels for transportation, solid fuels for industrial and residential uses, and open burning of biomass. Total global emissions of black carbon using bottom-up inventory methods are 7500 Gg yr−1 in the year 2000 with an uncertainty range of 2000 to 29000. However, global atmospheric absorption attributable to black carbon is too low in many models and should be increased by a factor of almost 3. After this scaling, the best estimate for the industrial-era (1750 to 2005) direct radiative forcing of atmospheric black carbon is +0.71 W m−2 with 90% uncertainty bounds of (+0.08, +1.27) W m−2. Total direct forcing by all black carbon sources, without subtracting the preindustrial background, is estimated as +0.88 (+0.17, +1.48) W m−2. Direct radiative forcing alone does not capture important rapid adjustment mechanisms. A framework is described and used for quantifying climate forcings, including rapid adjustments. The best estimate of industrial-era climate forcing of black carbon through all forcing mechanisms, including clouds and cryosphere forcing, is +1.1 W m−2 with 90% uncertainty bounds of +0.17 to +2.1 W m−2. Thus, there is a very high probability that black carbon emissions, independent of co-emitted species, have a positive forcing and warm the climate. We estimate that black carbon, with a total climate forcing of +1.1 W m−2, is the second most important human emission in terms of its climate forcing in the present-day atmosphere; only carbon dioxide is estimated to have a greater forcing. Sources that emit black carbon also emit other short-lived species that may either cool or warm climate. Climate forcings from co-emitted species are estimated and used in the framework described herein. When the principal effects of short-lived co-emissions, including cooling agents such as sulfur dioxide, are included in net forcing, energy-related sources (fossil fuel and biofuel) have an industrial-era climate forcing of +0.22 (−0.50 to +1.08) W m−2 during the first year after emission. For a few of these sources, such as diesel engines and possibly residential biofuels, warming is strong enough that eliminating all short-lived emissions from these sources would reduce net climate forcing (i.e., produce cooling). When open burning emissions, which emit high levels of organic matter, are included in the total, the best estimate of net industrial-era climate forcing by all short-lived species from black-carbon-rich sources becomes slightly negative (−0.06 W m−2 with 90% uncertainty bounds of −1.45 to +1.29 W m−2). The uncertainties in net climate forcing from black-carbon-rich sources are substantial, largely due to lack of knowledge about cloud interactions with both black carbon and co-emitted organic carbon. In prioritizing potential black-carbon mitigation actions, non-science factors, such as technical feasibility, costs, policy design, and implementation feasibility play important roles. The major sources of black carbon are presently in different stages with regard to the feasibility for near-term mitigation. This assessment, by evaluating the large number and complexity of the associated physical and radiative processes in black-carbon climate forcing, sets a baseline from which to improve future climate forcing estimates.

4,591 citations


Journal ArticleDOI
29 Mar 2013-Science
TL;DR: Overall, wild insects pollinated crops more effectively; an increase in wild insect visitation enhanced fruit set by twice as much as an equivalent increase in honey bee visitation.
Abstract: The diversity and abundance of wild insect pollinators have declined in many agricultural landscapes. Whether such declines reduce crop yields, or are mitigated by managed pollinators such as honey bees, is unclear. We found universally positive associations of fruit set with flower visitation by wild insects in 41 crop systems worldwide. In contrast, fruit set increased significantly with flower visitation by honey bees in only 14% of the systems surveyed. Overall, wild insects pollinated crops more effectively; an increase in wild insect visitation enhanced fruit set by twice as much as an equivalent increase in honey bee visitation. Visitation by wild insects and honey bees promoted fruit set independently, so pollination by managed honey bees supplemented, rather than substituted for, pollination by wild insects. Our results suggest that new practices for integrated management of both honey bees and diverse wild insect assemblages will enhance global crop yields.

1,881 citations


Journal ArticleDOI
TL;DR: An association analysis in CAD cases and controls identifies 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants strongly associated with CAD at a 5% false discovery rate (FDR).
Abstract: Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.

1,518 citations


Journal ArticleDOI
05 Jul 2013-Science
TL;DR: Clearer understanding is needed of the premises underlying SI and how it relates to food-system priorities and climate change poses challenges to agriculture.
Abstract: Food security is high on the global policy agenda. Demand for food is increasing as populations grow and gain wealth to purchase more varied and resource-intensive diets. There is increased competition for land, water, energy, and other inputs into food production. Climate change poses challenges to agriculture, particularly in developing countries ( 1 ), and many current farming practices damage the environment and are a major source of greenhouse gases (GHG). In an increasingly globalized world, food insecurity in one region can have widespread political and economic ramifications ( 2 ).

1,309 citations


Journal ArticleDOI
TL;DR: This document addresses the need for agreement on specific standards for the interpretation and post-processing of CMR studies by providing consensus recommendations developed by the Task Force for Post Processing of the Society for Cardiovascular MR.
Abstract: With mounting data on its accuracy and prognostic value, cardiovascular magnetic resonance (CMR) is becoming an increasingly important diagnostic tool with growing utility in clinical routine. Given its versatility and wide range of quantitative parameters, however, agreement on specific standards for the interpretation and post-processing of CMR studies is required to ensure consistent quality and reproducibility of CMR reports. This document addresses this need by providing consensus recommendations developed by the Task Force for Post Processing of the Society for Cardiovascular MR (SCMR). The aim of the task force is to recommend requirements and standards for image interpretation and post processing enabling qualitative and quantitative evaluation of CMR images. Furthermore, pitfalls of CMR image analysis are discussed where appropriate.

1,163 citations


Journal ArticleDOI
TL;DR: In this article, the authors present the largest standardized model intercomparison for climate change impacts so far, finding that individual crop models are able to simulate measured wheat grain yields accurately under a range of environments, particularly if the input information is sufficient.
Abstract: Projections of climate change impacts on crop yields are inherently uncertain(1). Uncertainty is often quantified when projecting future greenhouse gas emissions and their influence on climate(2). However, multi-model uncertainty analysis of crop responses to climate change is rare because systematic and objective comparisons among process-based crop simulation models(1,3) are difficult(4). Here we present the largest standardized model intercomparison for climate change impacts so far. We found that individual crop models are able to simulate measured wheat grain yields accurately under a range of environments, particularly if the input information is sufficient. However, simulated climate change impacts vary across models owing to differences in model structures and parameter values. A greater proportion of the uncertainty in climate change impact projections was due to variations among crop models than to variations among downscaled general circulation models. Uncertainties in simulated impacts increased with CO2 concentrations and associated warming. These impact uncertainties can be reduced by improving temperature and CO2 relationships in models and better quantified through use of multi-model ensembles. Less uncertainty in describing how climate change may affect agricultural productivity will aid adaptation strategy development and policymaking.

1,049 citations


Journal ArticleDOI
TL;DR: Eleven evidence-based recommendations for the non-pharmacological core management of hip and knee OA were developed, concerning the following nine topics: assessment, general approach, patient information and education, lifestyle changes, exercise, weight loss, assistive technology and adaptations, footwear and work.
Abstract: The objective was to develop evidence -based recommendations and a research and educational agenda for the non-pharmacological management of hip and knee osteoarthritis (OA). The multidisciplinary task force comprised 21 experts: nurses, occupational therapists, physiotherapists, rheumatologists, orthopaedic surgeons, general practitioner, psychologist, dietician, clinical epidemiologist and patient representatives. After a preliminary literature review, a first task force meeting and five Delphi rounds, provisional recommendations were formulated in order to perform a systematic review. A literature search of Medline and eight other databases was performed up to February 2012. Evidence was graded in categories I-IV and agreement with the recommendations was determined through scores from 0 (total disagreement) to 10 (total agreement). Eleven evidence-based recommendations for the non-pharmacological core management of hip and knee OA were developed, concerning the following nine topics: assessment, general approach, patient information and education, lifestyle changes, exercise, weight loss, assistive technology and adaptations, footwear and work. The average level of agreement ranged between 8.0 and 9.1. The proposed research agenda included an overall need for more research into non-pharmacological interventions for hip OA, moderators to optimise individualised treatment, healthy lifestyle with economic evaluation and long-term follow-up, and the prevention and reduction of work disability. Proposed educational activities included the required skills to teach, initiate and establish lifestyle changes. The 11 recommendations provide guidance on the delivery of non-pharmacological interventions to people with hip or knee OA. More research and educational activities are needed, particularly in the area of lifestyle changes.

1,029 citations


Journal ArticleDOI
Hans ter Steege1, Hans ter Steege2, Nigel C. A. Pitman3, Daniel Sabatier4, Christopher Baraloto5, Rafael de Paiva Salomão6, Juan Ernesto Guevara7, Oliver L. Phillips8, Carolina V. Castilho9, William E. Magnusson10, Jean-François Molino4, Abel Monteagudo, Percy Núñez Vargas11, Juan Carlos Montero10, Ted R. Feldpausch8, Ted R. Feldpausch12, Eurídice N. Honorio Coronado8, Timothy J. Killeen13, Bonifacio Mostacedo14, Rodolfo Vasquez, Rafael L. Assis15, Rafael L. Assis10, John Terborgh3, Florian Wittmann16, Ana Andrade10, William F. Laurance17, Susan G. Laurance17, Beatriz Schwantes Marimon18, Ben Hur Marimon18, Ima Célia Guimarães Vieira6, Iêda Leão do Amaral10, Roel J. W. Brienen8, Hernán Castellanos, Dairon Cárdenas López, Joost F. Duivenvoorden19, Hugo Mogollón20, Francisca Dionízia de Almeida Matos10, Nállarett Dávila21, Roosevelt García-Villacorta22, Pablo Roberto Stevenson Diaz23, Flávia R. C. Costa10, Thaise Emilio10, Carolina Levis10, Juliana Schietti10, Priscila Souza10, Alfonso Alonso24, Francisco Dallmeier24, Álvaro Javier Duque Montoya25, Maria Teresa Fernandez Piedade10, Alejandro Araujo-Murakami, Luzmila Arroyo, Rogério Gribel, Paul V. A. Fine7, Carlos A. Peres26, Marisol Toledo14, A C Gerardo Aymard, Timothy R. Baker8, Carlos Cerón27, Julien Engel28, Terry W. Henkel29, Paul J. M. Maas2, Pascal Petronelli, Juliana Stropp, Charles E. Zartman10, Doug Daly30, David A. Neill, Marcos Silveira31, Marcos Ríos Paredes, Jérôme Chave32, Diogenes de Andrade Lima Filho10, Peter M. Jørgensen33, Alfredo F. Fuentes33, Jochen Schöngart16, Fernando Cornejo Valverde34, Anthony Di Fiore35, E. M. Jimenez25, Maria Cristina Peñuela Mora25, Juan Fernando Phillips, Gonzalo Rivas36, Tinde van Andel2, Patricio von Hildebrand, Bruce Hoffman2, Egleé L. Zent37, Yadvinder Malhi38, Adriana Prieto25, Agustín Rudas25, Ademir R. Ruschell9, Natalino Silva39, Vincent A. Vos, Stanford Zent37, Alexandre Adalardo de Oliveira40, Angela Cano Schutz23, Therany Gonzales34, Marcelo Trindade Nascimento41, Hirma Ramírez-Angulo23, Rodrigo Sierra, Milton Tirado, Maria Natalia Umaña Medina23, Geertje M. F. van der Heijden42, Geertje M. F. van der Heijden43, César I.A. Vela11, Emilio Vilanova Torre23, Corine Vriesendorp, Ophelia Wang44, Kenneth R. Young35, Cláudia Baider40, Henrik Balslev45, Cid Ferreira10, Italo Mesones7, Armando Torres-Lezama23, Ligia Estela Urrego Giraldo25, Roderick Zagt46, Miguel Alexiades47, Lionel Hernández, Isau Huamantupa-Chuquimaco, William Milliken48, Walter Palacios Cuenca, Daniela Pauletto, Elvis H. Valderrama Sandoval49, Elvis H. Valderrama Sandoval50, Luis Valenzuela Gamarra, Kyle G. Dexter22, Kenneth J. Feeley51, Kenneth J. Feeley52, Gabriela Lopez-Gonzalez8, Miles R. Silman53 
Utrecht University1, Naturalis2, Duke University3, Institut de recherche pour le développement4, Institut national de la recherche agronomique5, Museu Paraense Emílio Goeldi6, University of California, Berkeley7, University of Leeds8, Empresa Brasileira de Pesquisa Agropecuária9, National Institute of Amazonian Research10, National University of Saint Anthony the Abbot in Cuzco11, University of Exeter12, World Wide Fund for Nature13, Universidad Autónoma Gabriel René Moreno14, Norwegian University of Life Sciences15, Max Planck Society16, James Cook University17, Universidade do Estado de Mato Grosso18, University of Amsterdam19, Silver Spring Networks20, State University of Campinas21, University of Edinburgh22, University of Los Andes23, Smithsonian Conservation Biology Institute24, National University of Colombia25, University of East Anglia26, Central University of Ecuador27, Centre national de la recherche scientifique28, Humboldt State University29, New York Botanical Garden30, Universidade Federal do Acre31, Paul Sabatier University32, Missouri Botanical Garden33, Amazon.com34, University of Texas at Austin35, University of Florida36, Venezuelan Institute for Scientific Research37, Environmental Change Institute38, Federal Rural University of Amazonia39, University of São Paulo40, State University of Norte Fluminense41, Smithsonian Tropical Research Institute42, University of Wisconsin–Milwaukee43, Northern Arizona University44, Aarhus University45, Tropenbos International46, University of Kent47, Royal Botanic Gardens48, University of Missouri–St. Louis49, Universidad Nacional de la Amazonía Peruana50, Florida International University51, Fairchild Tropical Botanic Garden52, Wake Forest University53
18 Oct 2013-Science
TL;DR: The finding that Amazonia is dominated by just 227 tree species implies that most biogeochemical cycling in the world’s largest tropical forest is performed by a tiny sliver of its diversity.
Abstract: The vast extent of the Amazon Basin has historically restricted the study of its tree communities to the local and regional scales. Here, we provide empirical data on the commonness, rarity, and richness of lowland tree species across the entire Amazon Basin and Guiana Shield (Amazonia), collected in 1170 tree plots in all major forest types. Extrapolations suggest that Amazonia harbors roughly 16,000 tree species, of which just 227 (1.4%) account for half of all trees. Most of these are habitat specialists and only dominant in one or two regions of the basin. We discuss some implications of the finding that a small group of species—less diverse than the North American tree flora—accounts for half of the world’s most diverse tree community.

963 citations


Journal ArticleDOI
07 Nov 2013-Nature
TL;DR: A sensitivity analysis on a global model is performed to quantify the uncertainty in cloud radiative forcing over the industrial period caused by uncertainties in aerosol emissions and processes and suggests that improved measurements and evaluation of simulated aerosols in polluted present-day conditions will not necessarily result in commensurate reductions in the uncertainty of forcing estimates.
Abstract: The effect of anthropogenic aerosols on cloud droplet concentrations and radiative properties is the source of one of the largest uncertainties in the radiative forcing of climate over the industrial period. This uncertainty affects our ability to estimate how sensitive the climate is to greenhouse gas emissions. Here we perform a sensitivity analysis on a global model to quantify the uncertainty in cloud radiative forcing over the industrial period caused by uncertainties in aerosol emissions and processes. Our results show that 45 per cent of the variance of aerosol forcing since about 1750 arises from uncertainties in natural emissions of volcanic sulphur dioxide, marine dimethylsulphide, biogenic volatile organic carbon, biomass burning and sea spray. Only 34 per cent of the variance is associated with anthropogenic emissions. The results point to the importance of understanding pristine pre-industrial-like environments, with natural aerosols only, and suggest that improved measurements and evaluation of simulated aerosols in polluted present-day conditions will not necessarily result in commensurate reductions in the uncertainty of forcing estimates. The impact of aerosol changes on cloud albedo (called the aerosol first indirect forcing) 1 is estimated 2 to exert a global mean radiative forcing of climate over the industrial period between 20.4 W m 22 and 21.8 W m 22 . Other aerosol–cloud interaction effects, involving rapid adjustments, may be of comparable magnitude 3 but their radiative effects are even less well understood on a global scale 3,4 . The uncertainty in the aerosol forcing is much larger than the uncertainty in the well-constrained positive forcing of 1.7 6 0.2 W m 22 that is due to

818 citations


Journal ArticleDOI
TL;DR: This project used multiple sources to develop and draw together evidence and expertise in realist synthesis, and synthesized expert input, evidence syntheses and real-time problem analysis into a definitive set of standards.
Abstract: There is growing interest in realist synthesis as an alternative systematic review method. This approach offers the potential to expand the knowledge base in policy-relevant areas -for example, by explaining the success, failure or mixed fortunes of complex interventions. No previous publication standards exist for reporting realist syntheses. This standard was developed as part of the RAMESES (Realist And MEta-narrative Evidence Syntheses: Evolving Standards) project. The project's aim is to produce preliminary publication standards for realist systematic reviews. We (a) collated and summarized existing literature on the principles of good practice in realist syntheses; (b) considered the extent to which these principles had been followed by published syntheses, thereby identifying how rigor may be lost and how existing methods could be improved; (c) used a three-round online Delphi method with an interdisciplinary panel of national and international experts in evidence synthesis, realist research, policy and/or publishing to produce and iteratively refine a draft set of methodological steps and publication standards; (d) provided real-time support to ongoing realist syntheses and the open-access RAMESES online discussion list so as to capture problems and questions as they arose; and (e) synthesized expert input, evidence syntheses and real-time problem analysis into a definitive set of standards. We identified 35 published realist syntheses, provided real-time support to 9 on-going syntheses and captured questions raised in the RAMESES discussion list. Through analysis and discussion within the project team, we summarized the published literature and common questions and challenges into briefing materials for the Delphi panel, comprising 37 members. Within three rounds this panel had reached consensus on 19 key publication standards, with an overall response rate of 91%. This project used multiple sources to develop and draw together evidence and expertise in realist synthesis. For each item we have included an explanation for why it is important and guidance on how it might be reported. Realist synthesis is a relatively new method for evidence synthesis and as experience and methodological developments occur, we anticipate that these standards will evolve to reflect further methodological developments. We hope that these standards will act as a resource that will contribute to improving the reporting of realist syntheses. To encourage dissemination of the RAMESES publication standards, this article is co-published in the Journal of Advanced Nursing and is freely accessible on Wiley Online Library ( http://www.wileyonlinelibrary.com/journal/jan ). Please see related article http://www.biomedcentral.com/1741-7015/11/20 and http://www.biomedcentral.com/1741-7015/11/22

Journal ArticleDOI
TL;DR: In this paper, the authors analyzed the texts of eleven declarations, charters, and partnerships developed for higher education institutions to represent university leaders' intentions to help improve the effectiveness of education for sustainable development (ESD).

Journal ArticleDOI
Joao Almeida1, Joao Almeida2, Siegfried Schobesberger3, Andreas Kürten2, Ismael K. Ortega3, Oona Kupiainen-Määttä3, Arnaud P. Praplan4, Alexey Adamov3, António Amorim5, F. Bianchi4, Martin Breitenlechner6, A. David1, Josef Dommen4, Neil M. Donahue7, Andrew J. Downard8, Eimear M. Dunne9, Jonathan Duplissy3, Sebastian Ehrhart2, Richard C. Flagan8, Alessandro Franchin3, Roberto Guida1, Jani Hakala3, Armin Hansel6, Martin Heinritzi6, Henning Henschel3, Tuija Jokinen3, Heikki Junninen3, Maija Kajos3, Juha Kangasluoma3, Helmi Keskinen10, Agnieszka Kupc11, Theo Kurtén3, Alexander N. Kvashin12, Ari Laaksonen13, Ari Laaksonen10, Katrianne Lehtipalo3, Markus Leiminger2, Johannes Leppä13, Ville Loukonen3, Vladimir Makhmutov12, Serge Mathot1, Matthew J. McGrath14, Tuomo Nieminen3, Tuomo Nieminen15, Tinja Olenius3, Antti Onnela1, Tuukka Petäjä3, Francesco Riccobono4, Ilona Riipinen16, Matti P. Rissanen3, Linda Rondo2, Taina Ruuskanen3, Filipe Duarte Santos5, Nina Sarnela3, Simon Schallhart3, R. Schnitzhofer6, John H. Seinfeld8, Mario Simon2, Mikko Sipilä15, Mikko Sipilä3, Yuri Stozhkov12, Frank Stratmann17, António Tomé5, Jasmin Tröstl4, Georgios Tsagkogeorgas17, Petri Vaattovaara10, Yrjö Viisanen13, Annele Virtanen10, Aron Vrtala11, Paul E. Wagner11, Ernest Weingartner4, Heike Wex17, Christina Williamson2, Daniela Wimmer3, Daniela Wimmer2, Penglin Ye7, Taina Yli-Juuti3, Kenneth S. Carslaw9, Markku Kulmala3, Markku Kulmala15, Joachim Curtius2, Urs Baltensperger4, Douglas R. Worsnop, Hanna Vehkamäki3, Jasper Kirkby2, Jasper Kirkby1 
17 Oct 2013-Nature
TL;DR: The results show that, in regions of the atmosphere near amine sources, both amines and sulphur dioxide should be considered when assessing the impact of anthropogenic activities on particle formation.
Abstract: Nucleation of aerosol particles from trace atmospheric vapours is thought to provide up to half of global cloud condensation nuclei(1). Aerosols can cause a net cooling of climate by scattering sun ...

Journal ArticleDOI
05 Jul 2013-Science
TL;DR: In this paper, the authors use spatially explicit models in conjunction with valuation methods to estimate comparable economic values for ecosystem services, taking account of climate change impacts, and show that highly significant value increases can be obtained from targeted planning by incorporating all potential ecosystem services and their values.
Abstract: Landscapes generate a wide range of valuable ecosystem services, yet land-use decisions often ignore the value of these services. Using the example of the United Kingdom, we show the significance of land-use change not only for agricultural production but also for emissions and sequestration of greenhouse gases, open-access recreational visits, urban green space, and wild-species diversity. We use spatially explicit models in conjunction with valuation methods to estimate comparable economic values for these services, taking account of climate change impacts. We show that, although decisions that focus solely on agriculture reduce overall ecosystem service values, highly significant value increases can be obtained from targeted planning by incorporating all potential services and their values and that this approach also conserves wild-species diversity.

Journal ArticleDOI
TL;DR: Interventions in countries of low and middle income to increase birthweight and linear growth during the first 2 years of life are likely to result in substantial gains in height and schooling and give some protection from adult chronic disease risk factors, with few adverse trade-offs.

Journal ArticleDOI
Veryan Codd1, Christopher P. Nelson1, Eva Albrecht, Massimo Mangino2, Joris Deelen3, Jessica L. Buxton4, Jouke-Jan Hottenga5, Krista Fischer6, Tõnu Esko6, Ida Surakka7, Linda Broer, Dale R. Nyholt8, Irene Mateo Leach9, Perttu Salo, Sara Hägg10, Mary K. Matthews1, Jutta Palmen11, Giuseppe Danilo Norata, Paul F. O'Reilly4, Danish Saleheen12, Najaf Amin13, Anthony J. Balmforth14, Marian Beekman3, Rudolf A. de Boer9, Stefan Böhringer3, Peter S. Braund1, Paul Burton1, Anton J. M. de Craen3, Matthew Denniff1, Yanbin Dong15, Konstantinos Douroudis6, Elena Dubinina1, Johan G. Eriksson, Katia Garlaschelli, Dehuang Guo15, Anna-Liisa Hartikainen16, Anjali K. Henders8, Jeanine J. Houwing-Duistermaat3, Laura Kananen7, Lennart C. Karssen13, Johannes Kettunen7, Norman Klopp, Vasiliki Lagou17, Elisabeth M. van Leeuwen13, Pamela A. F. Madden18, Reedik Mägi6, Patrik K. E. Magnusson10, Satu Männistö19, Satu Männistö20, Mark I. McCarthy21, Mark I. McCarthy22, Mark I. McCarthy17, Sarah E. Medland8, Evelin Mihailov6, Grant W. Montgomery8, Ben A. Oostra13, Aarno Palotie, Annette Peters, Helen Pollard1, Anneli Pouta20, Anneli Pouta16, Inga Prokopenko17, Samuli Ripatti, Veikko Salomaa20, Veikko Salomaa19, H. Eka D. Suchiman3, Ana M. Valdes2, Niek Verweij9, Ana Viñuela2, Xiaoling Wang23, Xiaoling Wang24, H-Erich Wichmann25, Elisabeth Widen7, Gonneke Willemsen5, Margaret J. Wright8, Kai Xia26, Xiangjun Xiao27, Dirk J. van Veldhuisen9, Alberico L. Catapano28, Martin D. Tobin1, Alistair S. Hall14, Alexandra I. F. Blakemore4, Wiek H. van Gilst9, Haidong Zhu23, Haidong Zhu24, Jeanette Erdmann, Muredach P. Reilly29, Sekar Kathiresan30, Sekar Kathiresan31, Heribert Schunkert, Philippa J. Talmud11, Nancy L. Pedersen10, Markus Perola6, Markus Perola20, Markus Perola7, Willem H. Ouwehand, Jaakko Kaprio, Nicholas G. Martin8, Cornelia M. van Duijn, Iiris Hovatta20, Iiris Hovatta7, Christian Gieger11, Andres Metspalu6, Dorret I. Boomsma5, Marjo-Riitta Järvelin, P. Eline Slagboom3, John R Thompson1, Tim D. Spector2, Pim van der Harst1, Nilesh J. Samani32, Nilesh J. Samani1 
TL;DR: In this paper, a genome-wide meta-analysis of 37,684 individuals with replication of selected variants in an additional 10,739 individuals was carried out to identify seven loci, including five new loci associated with mean leukocyte telomere length (LTL) (P < 5 × 10−8).
Abstract: Interindividual variation in mean leukocyte telomere length (LTL) is associated with cancer and several age-associated diseases. We report here a genome-wide meta-analysis of 37,684 individuals with replication of selected variants in an additional 10,739 individuals. We identified seven loci, including five new loci, associated with mean LTL (P < 5 × 10(-8)). Five of the loci contain candidate genes (TERC, TERT, NAF1, OBFC1 and RTEL1) that are known to be involved in telomere biology. Lead SNPs at two loci (TERC and TERT) associate with several cancers and other diseases, including idiopathic pulmonary fibrosis. Moreover, a genetic risk score analysis combining lead variants at all 7 loci in 22,233 coronary artery disease cases and 64,762 controls showed an association of the alleles associated with shorter LTL with increased risk of coronary artery disease (21% (95% confidence interval, 5-35%) per standard deviation in LTL, P = 0.014). Our findings support a causal role of telomere-length variation in some age-related diseases.


Journal ArticleDOI
TL;DR: The 100th anniversary of the British Ecological Society in 2013 is an opportune moment to reflect on the current status of ecology as a science and look forward to high-light priorities for future work.
Abstract: Summary 1. Fundamental ecological research is both intrinsically interesting and provides the basic knowledge required to answer applied questions of importance to the management of the natural world. The 100th anniversary of the British Ecological Society in 2013 is an opportune moment to reflect on the current status of ecology as a science and look forward to high-light priorities for future work.

Journal ArticleDOI
TL;DR: In this multinational sample of rheumatoid arthritis patients, variability among countries was wide, not only in prevalence but also in compliance with recommendations for preventing and managing these comorbidities.
Abstract: Background Patients with rheumatoid arthritis (RA) are at increased risk of developing comorbid conditions. Objectives To evaluate the prevalence of comorbidities and compare their management in RA patients from different countries worldwide. Methods Study design: international, cross-sectional. Patients: consecutive RA patients. Data collected: demographics, disease characteristics (activity, severity, treatment), comorbidities (cardiovascular, infections, cancer, gastrointestinal, pulmonary, osteoporosis and

Journal ArticleDOI
TL;DR: In this paper, the authors focus on research practices but also offer guidelines for reviewers, editors, journal management, teachers, granting institutions, and university promotion committees, highlighting some of the emerging and existing practical solutions that can facilitate implementation of these recommendations.
Abstract: Replicability of findings is at the heart of any empirical science. The aim of this article is to move the current replicability debate in psychology towards concrete recommendations for improvement. We focus on research practices but also offer guidelines for reviewers, editors, journal management, teachers, granting institutions, and university promotion committees, highlighting some of the emerging and existing practical solutions that can facilitate implementation of these recommendations. The challenges for improving replicability in psychological science are systemic. Improvement can occur only if changes are made at many levels of practice, evaluation, and reward. Copyright © 2013 John Wiley & Sons, Ltd.

Journal ArticleDOI
TL;DR: This analysis identifies key genetic changes linked to the rapid transcontinental dissemination of epidemic C. difficile 027/BI/NAP1 and highlights the routes by which it spreads through the global healthcare system.
Abstract: Epidemic C. difficile (027/BI/NAP1) has rapidly emerged in the past decade as the leading cause of antibiotic-associated diarrhea worldwide. However, the key events in evolutionary history leading to its emergence and the subsequent patterns of global spread remain unknown. Here, we define the global population structure of C. difficile 027/BI/NAP1 using whole-genome sequencing and phylogenetic analysis. We show that two distinct epidemic lineages, FQR1 and FQR2, not one as previously thought, emerged in North America within a relatively short period after acquiring the same fluoroquinolone resistance-conferring mutation and a highly related conjugative transposon. The two epidemic lineages showed distinct patterns of global spread, and the FQR2 lineage spread more widely, leading to healthcare-associated outbreaks in the UK, continental Europe and Australia. Our analysis identifies key genetic changes linked to the rapid transcontinental dissemination of epidemic C. difficile 027/BI/NAP1 and highlights the routes by which it spreads through the global healthcare system.

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TL;DR: In this paper, the authors review the environmental factors controlling the structure and distribution of forests and evaluate their current and future trajectory, concluding that forest biomass is a complex property affected by forest distribution, structure, and ecological processes.
Abstract: Forests are the dominant terrestrial ecosystem on Earth. We review the environmental factors controlling their structure and global distribution and evaluate their current and future trajectory. Adaptations of trees to climate and resource gradients, coupled with disturbances and forest dynamics, create complex geographical patterns in forest assemblages and structures. These patterns are increasingly discernible through new satellite and airborne observation systems, improved forest inventories, and global ecosystem models. Forest biomass is a complex property affected by forest distribution, structure, and ecological processes. Since at least 1990, biomass density has consistently increased in global established forests, despite increasing mortality in some regions, suggesting that a global driver such as elevated CO2 may be enhancing biomass gains. Global forests have also apparently become more dynamic. Advanced information about the structure, distribution, and biomass of the world's forests provides...

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TL;DR: A global-scale analysis of the presence of 203 pharmaceuticals across 41 countries is presented and it is shown that contamination is extensive due to widespread consumption and subsequent disposal to rivers.
Abstract: Pharmaceuticals have emerged as a major group of environmental contaminants over the past decade but relatively little is known about their occurrence in freshwaters compared to other pollutants. We present a global-scale analysis of the presence of 203 pharmaceuticals across 41 countries and show that contamination is extensive due to widespread consumption and subsequent disposal to rivers. There are clear regional biases in current understanding with little work outside North America, Europe, and China, and no work within Africa. Within individual countries, research is biased around a small number of populated provinces/states and the majority of research effort has focused upon just 14 compounds. Most research has adopted sampling techniques that are unlikely to provide reliable and representative data. This analysis highlights locations where concentrations of antibiotics, cardiovascular drugs, painkillers, contrast media, and antiepileptic drugs have been recorded well above thresholds known to cause toxic effects in aquatic biota. Studies of pharmaceutical occurrence and effects need to be seen as a global research priority due to increasing consumption, particularly among societies with aging populations. Researchers in all fields of environmental management need to work together more effectively to identify high risk compounds, improve the reliability and coverage of future monitoring studies, and develop new mitigation measures.

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TL;DR: The development of these minimum measurement standards is intended to promote the appropriate use of PRO measures to inform PCOR and CER, which in turn can improve the effectiveness and efficiency of healthcare delivery.
Abstract: Purpose An essential aspect of patient-centered outcomes research (PCOR) and comparative effectiveness research (CER) is the integration of patient perspectives and experiences with clinical data to evaluate interventions. Thus, PCOR and CER require capturing patient-reported outcome (PRO) data appropriately to inform research, healthcare delivery, and policy. This initiative’s goal was to identify minimum standards for the design and selection of a PRO measure for use in PCOR and CER.

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TL;DR: This Review discusses the relevance of PPIs and, in particular, the importance of α-helix-mediated PPIs to chemical biology and drug discovery with a focus on designing inhibitors, including constrained peptides, foldamers and proteomimetic-derived ligands.
Abstract: Inhibition of protein-protein interactions (PPIs) represents a significant challenge because it is unclear how they can be effectively and selectively targeted using small molecules. Achieving this goal is critical given the defining role of these interactions in biological processes. A rational approach to inhibitor design based on the secondary structure at the interface is the focus of much research, and different classes of designed ligands have emerged, some of which effectively and selectively disrupt targeted PPIs. This Review discusses the relevance of PPIs and, in particular, the importance of α-helix-mediated PPIs to chemical biology and drug discovery with a focus on designing inhibitors, including constrained peptides, foldamers and proteomimetic-derived ligands. In doing so, key challenges and major advances in developing generic approaches for the elaboration of PPI inhibitors are highlighted. The challenges faced in developing such ligands as drug leads--and how criteria applied to these may differ from conventional small-molecule drugs--are summarized.

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20 Jun 2013-Nature
TL;DR: The results from a global aerosol model study suggest that feldspar ice nuclei are globally distributed and that fellspar particles may account for a large proportion of the iceuclei in Earth’s atmosphere that contribute to freezing at temperatures below about −15 °C.
Abstract: The amount of ice present in mixed-phase clouds, which contain both supercooled liquid water droplets and ice particles, affects cloud extent, lifetime, particle size and radiative properties. The freezing of cloud droplets can be catalysed by the presence of aerosol particles known as ice nuclei. One of the most important ice nuclei is thought to be mineral dust aerosol from arid regions. It is generally assumed that clay minerals, which contribute approximately two-thirds of the dust mass, dominate ice nucleation by mineral dust, and many experimental studies have therefore focused on these materials. Here we use an established droplet-freezing technique to show that feldspar minerals dominate ice nucleation by mineral dusts under mixed-phase cloud conditions, despite feldspar being a minor component of dust emitted from arid regions. We also find that clay minerals are relatively unimportant ice nuclei. Our results from a global aerosol model study suggest that feldspar ice nuclei are globally distributed and that feldspar particles may account for a large proportion of the ice nuclei in Earth's atmosphere that contribute to freezing at temperatures below about -15 °C.

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TL;DR: The MMM app, a self-monitoring weight management intervention delivered by a smartphone app, is an acceptable and feasible weight loss intervention and a full RCT of this approach is warranted.
Abstract: Background: There is growing interest in the use of information communication technologies to treat obesity. An intervention delivered by smartphone could be a convenient, potentially cost-effective, and wide-reaching weight management strategy. Although there have been studies of texting-based interventions and smartphone applications (apps) used as adjuncts to other treatments, there are currently no randomized controlled trials (RCT) of a stand-alone smartphone application for weight loss that focuses primarily on self-monitoring of diet and physical activity. Objective: The aim of this pilot study was to collect acceptability and feasibility outcomes of a self-monitoring weight management intervention delivered by a smartphone app, compared to a website and paper diary. Methods: A sample of 128 overweight volunteers were randomized to receive a weight management intervention delivered by smartphone app, website, or paper diary. The smartphone app intervention, My Meal Mate (MMM), was developed by the research team using an evidence-based behavioral approach. The app incorporates goal setting, self-monitoring of diet and activity, and feedback via weekly text message. The website group used an existing commercially available slimming website from a company called Weight Loss Resources who also provided the paper diaries. The comparator groups delivered a similar self-monitoring intervention to the app, but by different modes of delivery. Participants were recruited by email, intranet, newsletters, and posters from large local employers. Trial duration was 6 months. The intervention and comparator groups were self-directed with no ongoing human input from the research team. The only face-to-face components were at baseline enrollment and brief follow-up sessions at 6 weeks and 6 months to take anthropometric measures and administer questionnaires. Results: Trial retention was 40/43 (93%) in the smartphone group, 19/42 (55%) in the website group, and 20/43 (53%) in the diary group at 6 months. Adherence was statistically significantly higher in the smartphone group with a mean of 92 days (SD 67) of dietary recording compared with 35 days (SD 44) in the website group and 29 days (SD 39) in the diary group ( P <.001). Self-monitoring declined over time in all groups. In an intention-to-treat analysis using baseline observation carried forward for missing data, mean weight change at 6 months was -4.6 kg (95% CI –6.2 to –3.0) in the smartphone app group, –2.9 kg (95% CI –4.7 to –1.1) in the diary group, and –1.3 kg (95% CI –2.7 to 0.1) in the website group. BMI change at 6 months was –1.6 kg/m 2 (95% CI –2.2 to –1.1) in the smartphone group, –1.0 kg/m 2 (95% CI –1.6 to –0.4) in the diary group, and –0.5 kg/m 2 (95% CI –0.9 to 0.0) in the website group. Change in body fat was –1.3% (95% CI –1.7 to –0.8) in the smartphone group, –0.9% (95% CI –1.5 to –0.4) in the diary group, and –0.5% (95% CI –0.9 to 0.0) in the website group. Conclusions: The MMM app is an acceptable and feasible weight loss intervention and a full RCT of this approach is warranted. Trial Registration: ClinicalTrials.gov NCT01744535; http://clinicaltrials.gov/ct2/show/NCT01744535 (Archived by WebCite at http://www.webcitation.org/6FEtc3PVB) [J Med Internet Res 2013;15(4):e32]

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Sonja I. Berndt1, Stefan Gustafsson2, Stefan Gustafsson3, Reedik Mägi4  +382 moreInstitutions (117)
TL;DR: A genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry finds a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
Abstract: Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

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TL;DR: Tocilizumab monotherapy was superior to adalimumabmonotherapy for reduction of signs and symptoms of rheumatoid arthritis in patients for whom methotrexate was deemed inappropriate.

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TL;DR: The authors proposed and tested a model that explains consumer skepticism toward the corporate social responsibility of grocery retailers and its influence on important consumer-related outcomes, finding that attributions of egoistic and stakeholder-driven motives elicit consumer skepticism towards CSR, while values-driven attributions inhibit skepticism.