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Showing papers by "University of Copenhagen published in 2013"


Journal ArticleDOI
TL;DR: The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol, is presented in this paper.
Abstract: The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol.The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

3,672 citations


Journal ArticleDOI
29 Aug 2013-Nature
TL;DR: The authors' classifications based on variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at increased risk of progressing to adiposity-associated co-morbidities.
Abstract: We are facing a global metabolic health crisis provoked by an obesity epidemic. Here we report the human gut microbial composition in a population sample of 123 non-obese and 169 obese Danish individuals. We find two groups of individuals that differ by the number of gut microbial genes and thus gut bacterial richness. They contain known and previously unknown bacterial species at different proportions; individuals with a low bacterial richness (23% of the population) are characterized by more marked overall adiposity, insulin resistance and dyslipidaemia and a more pronounced inflammatory phenotype when compared with high bacterial richness individuals. The obese individuals among the lower bacterial richness group also gain more weight over time. Only a few bacterial species are sufficient to distinguish between individuals with high and low bacterial richness, and even between lean and obese participants. Our classifications based on variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at increased risk of progressing to adiposity-associated co-morbidities.

3,448 citations


Journal ArticleDOI
06 Sep 2013-Science
TL;DR: The results reveal that transmissible and modifiable interactions between diet and microbiota influence host biology and that adiposity is transmissible from human to mouse and that it was associated with changes in serum levels of branched-chain amino acids.
Abstract: How much does the microbiota influence the host's phenotype? Ridaura et al. ([1241214][1] ; see the Perspective by [ Walker and Parkhill ][2]) obtained uncultured fecal microbiota from twin pairs discordant for body mass and transplanted them into adult germ-free mice. It was discovered that adiposity is transmissible from human to mouse and that it was associated with changes in serum levels of branched-chain amino acids. Moreover, obese-phenotype mice were invaded by members of the Bacteroidales from the lean mice, but, happily, the lean animals resisted invasion by the obese microbiota. [1]: http://www.sciencemag.org/content/341/6150/1241214.full [2]: /lookup/doi/10.1126/science.1243787

2,929 citations


Journal ArticleDOI
TL;DR: The 13th St Gallen International Breast Cancer Conference (2013) Expert Panel reviewed and endorsed substantial new evidence on aspects of the local and regional therapies for early breast cancer, supporting less extensive surgery to the axilla and shorter durations of radiation therapy.

2,831 citations


Journal ArticleDOI
TL;DR: The gut microbiota has a beneficial role during normal homeostasis, modulating the host's immune system as well as influencing host development and physiology, including organ development and morphogenesis, and host metabolism.
Abstract: Establishing and maintaining beneficial interactions between the host and its associated microbiota are key requirements for host health. Although the gut microbiota has previously been studied in the context of inflammatory diseases, it has recently become clear that this microbial community has a beneficial role during normal homeostasis, modulating the host's immune system as well as influencing host development and physiology, including organ development and morphogenesis, and host metabolism. The underlying molecular mechanisms of host-microorganism interactions remain largely unknown, but recent studies have begun to identify the key signalling pathways of the cross-species homeostatic regulation between the gut microbiota and its host.

2,585 citations


Journal ArticleDOI
06 Jun 2013-Nature
TL;DR: This work uses shotgun sequencing to characterize the faecal metagenome of 145 European women with normal, impaired or diabetic glucose control, and develops a mathematical model based on metagenomic profiles that identified T2D with high accuracy.
Abstract: Recent evidence has suggested that altered gut microbiota are associated with various metabolic diseases including obesity, diabetes and cardiovascular disease. Fredrik Bckhed and colleagues characterized the faecal metagenome of a cohort of European women with normal, impaired or diabetic glucose control and compared these findings to a recently described Chinese cohort. Their analysis reveals differences in the discriminant metagenomic markers for type 2 diabetes between the two cohorts, suggesting that metagenomic predictive tools may have to be specific for age and geographical populations under investigation.

2,248 citations


Journal ArticleDOI
S. Hong Lee1, Stephan Ripke2, Stephan Ripke3, Benjamin M. Neale3  +402 moreInstitutions (124)
TL;DR: Empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
Abstract: Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

2,058 citations


Journal ArticleDOI
TL;DR: There is an urgent worldwide need for diagnostic screening together with early and aggressive treatment of this extremely high-risk condition, familial hypercholesterolaemia.
Abstract: Aims The first aim was to critically evaluate the extent to which familial hypercholesterolaemia (FH) is underdiagnosed and undertreated. The second aim was to provide guidance for screening and treatment of FH, in order to prevent coronary heart disease (CHD). Methods and results Of the theoretical estimated prevalence of 1/500 for heterozygous FH, <1% are diagnosed in most countries. Recently, direct screening in a Northern European general population diagnosed approximately 1/200 with heterozygous FH. All reported studies document failure to achieve recommended LDL cholesterol targets in a large proportion of individuals with FH, and up to 13-fold increased risk of CHD. Based on prevalences between 1/500 and 1/200, between 14 and 34 million individuals worldwide have FH. We recommend that children, adults, and families should be screened for FH if a person or family member presents with FH, a plasma cholesterol level in an adult ≥8 mmol/L(≥310 mg/dL) or a child ≥6 mmol/L(≥230 mg/dL), premature CHD, tendon xanthomas, or sudden premature cardiac death. In FH, low-density lipoprotein cholesterol targets are <3.5 mmol/L(<135 mg/dL) for children, <2.5 mmol/L(<100 mg/dL) for adults, and <1.8 mmol/L(<70 mg/dL) for adults with known CHD or diabetes. In addition to lifestyle and dietary counselling, treatment priorities are (i) in children, statins, ezetimibe, and bile acid binding resins, and (ii) in adults, maximal potent statin dose, ezetimibe, and bile acid binding resins. Lipoprotein apheresis can be offered in homozygotes and in treatment-resistant heterozygotes with CHD. Conclusion Owing to severe underdiagnosis and undertreatment of FH, there is an urgent worldwide need for diagnostic screening together with early and aggressive treatment of this extremely high-risk condition.

2,039 citations


Journal ArticleDOI
TL;DR: It is suggested that the gut microbiota not only regulates secondary bile acids metabolism but also inhibits bile acid synthesis in the liver by alleviating FXR inhibition in the ileum.

1,576 citations


Journal ArticleDOI
TL;DR: The metabolic responses and molecular mechanisms that underpin the adaptatation of skeletal muscle to acute exercise and exercise training are reviewed.

1,505 citations


Posted Content
TL;DR: In this paper, an analysis of prior research on how firms leverage external sources of innovation is presented, which suggests a four-phase model in which a linear process of obtaining, integrating, integrating and commercializing external innovations is combined with interaction between the firm and its collaborators.
Abstract: This article reviews research on open innovation that considers how and why firms commercialize external sources of innovations. It examines both the “outside-in” and “coupled” modes of Enkel et al. (2009). From an analysis of prior research on how firms leverage external sources of innovation, it suggests a four-phase model in which a linear process — (1) obtaining, (2) integrating and (3) commercializing external innovations — is combined with (4) interaction between the firm and its collaborators. This model is used to classify papers taken from the top 25 innovation journals identified by Linton and Thongpapan (2004), complemented by highly cited work beyond those journals. A review of 291 open innovation-related publications from these sources shows that the majority of these articles indeed address elements of this inbound open innovation process model. Specifically, it finds that researchers have front-loaded their examination of the leveraging process, with an emphasis on obtaining innovations from external sources. However, there is a relative dearth of research related to integrating and commercializing these innovations.Research on obtaining innovations includes searching, enabling, filtering, and acquiring — each category with its own specific set of mechanisms and conditions. Integrating innovations has been mostly studied from an absorptive capacity perspective, with less attention given to the impact of competencies and culture (including not-invented-here). Commercializing innovations puts the most emphasis on how external innovations create value rather than how firms capture value from those innovations. Finally, the interaction phase considers both feedback for the linear process and reciprocal innovation processes such as co-creation, network collaboration and community innovation.This review and synthesis suggests several gaps in prior research. One is a tendency to ignore the importance of business models, despite their central role in distinguishing open innovation from earlier research on inter-organizational collaboration in innovation. Another gap is a tendency in open innovation to use “innovation” in a way inconsistent with earlier definitions in innovation management. The article concludes with recommendations for future research that include examining the end-to-end innovation commercialization process, and studying the moderators and limits of leveraging external sources of innovation.

Journal ArticleDOI
Natalie M. Batalha1, Natalie M. Batalha2, Jason F. Rowe2, Stephen T. Bryson2, Thomas Barclay2, Christopher J. Burke2, Douglas A. Caldwell2, Jessie L. Christiansen2, Fergal Mullally2, Susan E. Thompson2, Timothy M. Brown3, Andrea K. Dupree4, Daniel C. Fabrycky5, Eric B. Ford6, Jonathan J. Fortney5, Ronald L. Gilliland7, Howard Isaacson8, David W. Latham4, Geoffrey W. Marcy8, Samuel N. Quinn9, Samuel N. Quinn4, Darin Ragozzine4, Avi Shporer3, William J. Borucki2, David R. Ciardi10, Thomas N. Gautier10, Michael R. Haas2, Jon M. Jenkins2, David G. Koch2, Jack J. Lissauer2, William Rapin2, Gibor Basri8, Alan P. Boss11, Lars A. Buchhave12, Joshua A. Carter4, David Charbonneau4, Joergen Christensen-Dalsgaard13, Bruce D. Clarke10, William D. Cochran14, Brice-Olivier Demory15, Jean-Michel Desert4, Edna DeVore16, Laurance R. Doyle16, Gilbert A. Esquerdo4, Mark E. Everett, Francois Fressin4, John C. Geary4, Forrest R. Girouard2, Alan Gould17, Jennifer R. Hall2, Matthew J. Holman4, Andrew W. Howard8, Steve B. Howell2, Khadeejah A. Ibrahim2, Karen Kinemuchi2, Hans Kjeldsen13, Todd C. Klaus2, Jie Li2, Philip W. Lucas18, Søren Meibom4, Robert L. Morris2, Andrej Prsa19, Elisa V. Quintana2, Dwight T. Sanderfer2, Dimitar Sasselov4, Shawn Seader2, Jeffrey C. Smith2, Jason H. Steffen20, Martin Still2, Martin C. Stumpe2, Jill Tarter16, Peter Tenenbaum2, Guillermo Torres4, Joseph D. Twicken2, Kamal Uddin2, Jeffrey Van Cleve2, Lucianne M. Walkowicz21, William F. Welsh22 
TL;DR: In this paper, the authors verified nearly 5000 periodic transit-like signals against astrophysical and instrumental false positives yielding 1108 viable new transiting planet candidates, bringing the total count up to over 2300.
Abstract: New transiting planet candidates are identified in 16 months (2009 May-2010 September) of data from the Kepler spacecraft. Nearly 5000 periodic transit-like signals are vetted against astrophysical and instrumental false positives yielding 1108 viable new planet candidates, bringing the total count up to over 2300. Improved vetting metrics are employed, contributing to higher catalog reliability. Most notable is the noise-weighted robust averaging of multi-quarter photo-center offsets derived from difference image analysis that identifies likely background eclipsing binaries. Twenty-two months of photometry are used for the purpose of characterizing each of the candidates. Ephemerides (transit epoch, T_0, and orbital period, P) are tabulated as well as the products of light curve modeling: reduced radius (R_P/R_★), reduced semimajor axis (d/R_★), and impact parameter (b). The largest fractional increases are seen for the smallest planet candidates (201% for candidates smaller than 2 R_⊕ compared to 53% for candidates larger than 2 R_⊕) and those at longer orbital periods (124% for candidates outside of 50 day orbits versus 86% for candidates inside of 50 day orbits). The gains are larger than expected from increasing the observing window from 13 months (Quarters 1-5) to 16 months (Quarters 1-6) even in regions of parameter space where one would have expected the previous catalogs to be complete. Analyses of planet frequencies based on previous catalogs will be affected by such incompleteness. The fraction of all planet candidate host stars with multiple candidates has grown from 17% to 20%, and the paucity of short-period giant planets in multiple systems is still evident. The progression toward smaller planets at longer orbital periods with each new catalog release suggests that Earth-size planets in the habitable zone are forthcoming if, indeed, such planets are abundant.

Journal ArticleDOI
TL;DR: The meta-analyses showed a statistically significant association between risk for lung cancer and PM10 and PM2·5, and no association between lungcancer and nitrogen oxides concentration or traffic intensity on the nearest street.
Abstract: Summary Background Ambient air pollution is suspected to cause lung cancer. We aimed to assess the association between long-term exposure to ambient air pollution and lung cancer incidence in European populations. Methods This prospective analysis of data obtained by the European Study of Cohorts for Air Pollution Eff ects used data from 17 cohort studies based in nine European countries. Baseline addresses were geocoded and we assessed air pollution by land-use regression models for particulate matter (PM) with diameter of less than 10 μm (PM10), less than 2·5 μm (PM2·5), and between 2·5 and 10 μm (PMcoarse), soot (PM2·5absorbance), nitrogen oxides, and two traffi c indicators. We used Cox regression models with adjustment for potential confounders for cohort-specifi c analyses and random eff ects models for meta-analyses. Findings The 312 944 cohort members contributed 4 013 131 person-years at risk. During follow-up (mean 12·8 years), 2095 incident lung cancer cases were diagnosed. The meta-analyses showed a statistically signifi cant association between risk for lung cancer and PM10 (hazard ratio [HR] 1·22 [95% CI 1·03–1·45] per 10 μg/m³). For PM2·5 the HR was 1·18 (0·96–1·46) per 5 μg/m³. The same increments of PM10 and PM2·5 were associated with HRs for adenocarcinomas of the lung of 1·51 (1·10–2·08) and 1·55 (1·05–2·29), respectively. An increase in road traffi c of 4000 vehicle-km per day within 100 m of the residence was associated with an HR for lung cancer of 1·09 (0·99–1·21). The results showed no association between lung cancer and nitrogen oxides concentration (HR 1·01 [0·95–1·07] per 20 μg/m³) or traffi c intensity on the nearest street (HR 1·00 [0·97–1·04] per 5000 vehicles per day).

Journal ArticleDOI
TL;DR: In this paper, a toolbox for MATLAB is presented to support improved visualisation and sensitivity analyses of PARAFAC models in fluorescence spectroscopy, demonstrated using a dissolved organic matter (DOM) fluorescence dataset.
Abstract: PARAllel FACtor analysis (PARAFAC) is increasingly used to decompose fluorescence excitation emission matrices (EEMs) into their underlying chemical components. In the ideal case where fluorescence conforms to Beers Law, this process can lead to the mathematical identification and quantification of independently varying fluorophores. However, many practical and analytical hurdles stand between EEM datasets and their chemical interpretation. This article provides a tutorial in the practical application of PARAFAC to fluorescence datasets, demonstrated using a dissolved organic matter (DOM) fluorescence dataset. A new toolbox for MATLAB is presented to support improved visualisation and sensitivity analyses of PARAFAC models in fluorescence spectroscopy.

Journal ArticleDOI
TL;DR: This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
Abstract: Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 10 × 10(-4)) In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 50 × 10(-8)), 3 of which we found after conditioning on previously identified variants Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals

Journal ArticleDOI
TL;DR: The carbohydrate-digestive capacity of a simplified but representative mini-microbiome is examined in order to highlight the abundance and variety of bacterial CAZymes that are represented in the human gut microbiota.
Abstract: The human genome encodes very few enzymes involved in the digestion of complex polysaccharides, and this deficit is compensated for by the myriad of carbohydrate-active enzymes (CAZymes) encoded by members of the gut microbiome. In this Analysis article, Henrissat and colleagues characterize the CAZymes present in a representative human mini-microbiome.

Journal ArticleDOI
TL;DR: A genetic engineering approach using human cell lines to simplify O‐glycosylation (SimpleCells) that enables proteome‐wide discovery of O-glycan sites using ‘bottom‐up’ ETD‐based mass spectrometric analysis and an improved NetOGlyc4.0 model for prediction of O‐ Glycoproteins.
Abstract: Glycosylation is the most abundant and diverse posttranslational modification of proteins. While several types of glycosylation can be predicted by the protein sequence context, and substantial knowledge of these glycoproteomes is available, our knowledge of the GalNAc‐type O ‐glycosylation is highly limited. This type of glycosylation is unique in being regulated by 20 polypeptide GalNAc‐transferases attaching the initiating GalNAc monosaccharides to Ser and Thr (and likely some Tyr) residues. We have developed a genetic engineering approach using human cell lines to simplify O ‐glycosylation (SimpleCells) that enables proteome‐wide discovery of O ‐glycan sites using ‘bottom‐up’ ETD‐based mass spectrometric analysis. We implemented this on 12 human cell lines from different organs, and present a first map of the human O ‐glycoproteome with almost 3000 glycosites in over 600 O ‐glycoproteins as well as an improved NetOGlyc4.0 model for prediction of O ‐glycosylation. The finding of unique subsets of O ‐glycoproteins in each cell line provides evidence that the O ‐glycoproteome is differentially regulated and dynamic. The greatly expanded view of the O ‐glycoproteome should facilitate the exploration of how site‐specific O ‐glycosylation regulates protein function.

Journal ArticleDOI
TL;DR: The 2013 version of the European Association of Urology guidelines on the treatment and follow-up of male lower urinary tract symptoms (LUTS) provides practical guidance for the management of men experiencing LUTS.

Journal ArticleDOI
TL;DR: This work describes mapDamage 2.0, a user-friendly package that extends the original features of mapDamage by incorporating a statistical model of DNA damage, and provides estimates of four key features of aDNA molecules: the average length of overhangs, nick frequency, cytosine deamination rates in both double-stranded regions and overhangers, and base quality scores according to their probability of being damaged.
Abstract: Motivation: Ancient DNA (aDNA) molecules in fossilized bones and teeth, coprolites, sediments, mummified specimens and museum collections represent fantastic sources of information for evolutionary biologists, revealing the agents of past epidemics and the dynamics of past populations. However, the analysis of aDNA generally faces two major issues. Firstly, sequences consist of a mixture of endogenous and various exogenous backgrounds, mostly microbial. Secondly, high nucleotide misincorporation rates can be observed as a result of severe post-mortem DNA damage. Such misincorporation patterns are instrumental to authenticate ancient sequences versus modern contaminants. We recently developed the user-friendly mapDamage package that identifies such patterns from next-generation sequencing (NGS) sequence datasets. The absence of formal statistical modeling of the DNA damage process however precluded rigorous quantitative comparisons across samples. Results: Here, we describe mapDamage 2.0 that extends the original features of mapDamage by incorporating a statistical model of DNA damage. Assuming that damage events depend only on sequencing position and post-mortem deamination, our Bayesian statistical framework provides estimates of four key features of aDNA molecules: the average length of overhangs (�), nick frequency (�), and cytosine deamination rates in both double stranded regions (�d) and overhangs (�s). Our model enables rescaling base quality scores according to their probability of being damaged. mapDamage 2.0 handles NGS datasets with ease and is compatible with a wide range of DNA library protocols. Availability: mapDamage 2.0 is available at XXXXX as a Python package and documentation is maintained at the Centre for GeoGenetics website (geogenetics.ku.dk/publications/mapdamage/).

Journal ArticleDOI
TL;DR: A meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, and identified 29,807 SNPs for further genotyping suggests that more than 1,000 additional loci are involved in breast cancer susceptibility.
Abstract: Breast cancer is the most common cancer among women Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC) The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10(-8)) Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility

Journal ArticleDOI
TL;DR: These liver CEUS guidelines and recommendations are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis and improve the management of patients worldwide.
Abstract: Initially, a set of guidelines for the use of ultrasound contrast agents was published in 2004 dealing only with liver applications. A second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some non-liver applications. Time has moved on, and the need for international guidelines on the use of CEUS in the liver has become apparent. The present document describes the third iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS) using contrast specific imaging techniques. This joint WFUMB-EFSUMB initiative has implicated experts from major leading ultrasound societies worldwide. These liver CEUS guidelines are simultaneously published in the official journals of both organizing federations (i.e., Ultrasound in Medicine and Biology for WFUMB and Ultraschall in der Medizin/European Journal of Ultrasound for EFSUMB). These guidelines and recommendations provide general advice on the use of all currently clinically available ultrasound contrast agents (UCA). They are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis and improve the management of patients worldwide.

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.


Journal ArticleDOI
04 Jan 2013-Science
TL;DR: A global map of zoogeographic regions is generated by combining data on the distributions and phylogenetic relationships of 21,037 species of amphibians, birds, and mammals, and it is shown that spatial turnover in the phylogenetic composition of vertebrate assemblages is higher in the Southern than in the Northern Hemisphere.
Abstract: Modern attempts to produce biogeographic maps focus on the distribution of species, and the maps are typically drawn without phylogenetic considerations. Here, we generate a global map of zoogeographic regions by combining data on the distributions and phylogenetic relationships of 21,037 species of amphibians, birds, and mammals. We identify 20 distinct zoogeographic regions, which are grouped into 11 larger realms. We document the lack of support for several regions previously defined based on distributional data and show that spatial turnover in the phylogenetic composition of vertebrate assemblages is higher in the Southern than in the Northern Hemisphere. We further show that the integration of phylogenetic information provides valuable insight on historical relationships among regions, permitting the identification of evolutionarily unique regions of the world.

Journal ArticleDOI
TL;DR: This work reports the ∼738-Mb draft whole genome shotgun sequence of CDC Frontier, a kabuli chickpea variety, which contains an estimated 28,269 genes, and identifies targets of both breeding-associated genetic sweeps and breeding- associated balancing selection.
Abstract: Chickpea (Cicer arietinum) is the second most widely grown legume crop after soybean, accounting for a substantial proportion of human dietary nitrogen intake and playing a crucial role in food security in developing countries. We report the ~738-Mb draft whole genome shotgun sequence of CDC Frontier, a kabuli chickpea variety, which contains an estimated 28,269 genes. Resequencing and analysis of 90 cultivated and wild genotypes from ten countries identifies targets of both breeding-associated genetic sweeps and breeding-associated balancing selection. Candidate genes for disease resistance and agronomic traits are highlighted, including traits that distinguish the two main market classes of cultivated chickpea—desi and kabuli. These data comprise a resource for chickpea improvement through molecular breeding and provide insights into both genome diversity and domestication.

Journal ArticleDOI
TL;DR: In this article, the authors estimate the galaxy stellar mass function and stellar mass density for star-forming and quiescent galaxies with 0.2 − 1.5 consistent with the expected uncertainties.
Abstract: We estimate the galaxy stellar mass function and stellar mass density for star-forming and quiescent galaxies with 0.2 1.5 consistent with the expected uncertainties. We also develop a new method to infer the specific star formation rate from the mass function of star-forming galaxies. We find that the specific star formation rate of 1010 − 10.5ℳ⊙ galaxies increases continuously in the redshift range 1 < z < 4. Finally, we compare our results with a semi-analytical model and find that these models overestimate the density of low mass quiescent galaxies by an order of magnitude, while the density of low-mass star-forming galaxies is successfully reproduced.

Journal ArticleDOI
TL;DR: Exercise training is the most potent stimulus to increase skeletal muscle GLUT4 expression, an effect that may partly contribute to improved insulin action and glucose disposal and enhanced muscle glycogen storage following exercise training in health and disease.
Abstract: Glucose is an important fuel for contracting muscle, and normal glucose metabolism is vital for health. Glucose enters the muscle cell via facilitated diffusion through the GLUT4 glucose transporte...

Journal ArticleDOI
TL;DR: These revised Porto criteria for the diagnosis of P IBD have been developed to meet present challenges and developments in PIBD and provide up-to-date guidelines for the definition and diagnosis of the IBD spectrum.
Abstract: Background: The diagnosis of pediatric-onset inflammatory bowel disease (PIBD) can be challenging in choosing the most informative diagnostic tests and correctly classifying PIBD into its different subtypes. Recent advances in our understanding of the natural history and phenotype of PIBD, increasing availability of serological and fecal biomarkers, and the emergence of novel endoscopic and imaging technologies taken together have made the previous Porto criteria for the diagnosis of PIBD obsolete. Methods: We aimed to revise the original Porto criteria using an evidencebased approach and consensus process to yield specific practice recommendations for the diagnosis of PIBD. These revised criteria are based on the Paris classification of PIBD and the original Porto criteria while incorporating novel data, such as for serum and fecal biomarkers. A consensus of at least 80% of participants was achieved for all recommendations and the summary algorithm. Results: The revised criteria depart from existing criteria by defining 2 categories of ulcerative colitis (UC, typical and atypical); atypical phenotypes of UC should be treated as UC. A novel approach based on multiple criteria for diagnosing IBD-unclassified (IBD-U) is proposed. Specifically, these revised criteria recommend upper gastrointestinal endoscopy and ileocolonscopy for all suspected patients with PIBD, with small bowel imaging (unless typical UC after endoscopy and histology) by magnetic resonance enterography or wireless capsule endoscopy.

Journal ArticleDOI
TL;DR: Improved tick surveillance with harmonized approaches for comparison of data enabling the follow-up of trends at EU level will improve the messages on risk related to tick-borne diseases to policy makers, other stake holders and to the general public.
Abstract: Many factors are involved in determining the latitudinal and altitudinal spread of the important tick vector Ixodes ricinus (Acari: Ixodidae) in Europe, as well as in changes in the distribution within its prior endemic zones. This paper builds on published literature and unpublished expert opinion from the VBORNET network with the aim of reviewing the evidence for these changes in Europe and discusses the many climatic, ecological, landscape and anthropogenic drivers. These can be divided into those directly related to climatic change, contributing to an expansion in the tick’s geographic range at extremes of altitude in central Europe, and at extremes of latitude in Scandinavia; those related to changes in the distribution of tick hosts, particularly roe deer and other cervids; other ecological changes such as habitat connectivity and changes in land management; and finally, anthropogenically induced changes. These factors are strongly interlinked and often not well quantified. Although a change in climate plays an important role in certain geographic regions, for much of Europe it is non-climatic factors that are becoming increasingly important. How we manage habitats on a landscape scale, and the changes in the distribution and abundance of tick hosts are important considerations during our assessment and management of the public health risks associated with ticks and tick-borne disease issues in 21st century Europe. Better understanding and mapping of the spread of I. ricinus (and changes in its abundance) is, however, essential to assess the risk of the spread of infections transmitted by this vector species. Enhanced tick surveillance with harmonized approaches for comparison of data enabling the follow-up of trends at EU level will improve the messages on risk related to tick-borne diseases to policy makers, other stake holders and to the general public.

Journal ArticleDOI
Moinuddin Ahmed1, Kevin J. Anchukaitis2, Kevin J. Anchukaitis3, Asfawossen Asrat4, H. P. Borgaonkar5, Martina Braida6, Brendan M. Buckley3, Ulf Büntgen7, Brian M. Chase8, Brian M. Chase9, Duncan A. Christie10, Duncan A. Christie11, Edward R. Cook3, Mark A. J. Curran12, Mark A. J. Curran13, Henry F. Diaz14, Jan Esper15, Ze-Xin Fan16, Narayan Prasad Gaire17, Quansheng Ge18, Joelle Gergis19, J. Fidel González-Rouco20, Hugues Goosse21, Stefan W. Grab22, Nicholas E. Graham23, Rochelle Graham23, Martin Grosjean24, Sami Hanhijärvi25, Darrell S. Kaufman26, Thorsten Kiefer, Katsuhiko Kimura27, Atte Korhola25, Paul J. Krusic28, Antonio Lara11, Antonio Lara10, Anne-Marie Lézine29, Fredrik Charpentier Ljungqvist28, Andrew Lorrey30, Jürg Luterbacher31, Valérie Masson-Delmotte29, Danny McCarroll32, Joseph R. McConnell33, Nicholas P. McKay26, Mariano S. Morales34, Andrew D. Moy12, Andrew D. Moy13, Robert Mulvaney35, Ignacio A. Mundo34, Takeshi Nakatsuka36, David J. Nash37, David J. Nash22, Raphael Neukom7, Sharon E. Nicholson38, Hans Oerter39, Jonathan G. Palmer40, Jonathan G. Palmer41, Steven J. Phipps41, María Prieto32, Andrés Rivera42, Masaki Sano36, Mirko Severi43, Timothy M. Shanahan44, Xuemei Shao18, Feng Shi, Michael Sigl33, Jason E. Smerdon3, Olga Solomina45, Eric J. Steig46, Barbara Stenni6, Meloth Thamban47, Valerie Trouet48, Chris S. M. Turney41, Mohammed Umer4, Tas van Ommen13, Tas van Ommen12, Dirk Verschuren49, A. E. Viau50, Ricardo Villalba34, Bo Møllesøe Vinther51, Lucien von Gunten, Sebastian Wagner, Eugene R. Wahl14, Heinz Wanner24, Johannes P. Werner31, James W. C. White52, Koh Yasue53, Eduardo Zorita 
Federal Urdu University1, Woods Hole Oceanographic Institution2, Columbia University3, Addis Ababa University4, Indian Institute of Tropical Meteorology5, University of Trieste6, Swiss Federal Institute for Forest, Snow and Landscape Research7, University of Bergen8, University of Montpellier9, Austral University of Chile10, University of Chile11, Australian Antarctic Division12, University of Tasmania13, National Oceanic and Atmospheric Administration14, University of Mainz15, Xishuangbanna Tropical Botanical Garden16, Nepal Academy of Science and Technology17, Chinese Academy of Sciences18, University of Melbourne19, Complutense University of Madrid20, Université catholique de Louvain21, University of the Witwatersrand22, Hydrologic Research Center23, University of Bern24, University of Helsinki25, Northern Arizona University26, Fukushima University27, Stockholm University28, Université Paris-Saclay29, National Institute of Water and Atmospheric Research30, University of Giessen31, Swansea University32, Desert Research Institute33, National Scientific and Technical Research Council34, British Antarctic Survey35, Nagoya University36, University of Brighton37, Florida State University38, Alfred Wegener Institute for Polar and Marine Research39, University of Exeter40, University of New South Wales41, Centro de Estudios Científicos42, University of Florence43, University of Texas at Austin44, Russian Academy of Sciences45, University of Washington46, National Centre for Antarctic and Ocean Research47, University of Arizona48, Ghent University49, University of Ottawa50, University of Copenhagen51, University of Colorado Boulder52, Shinshu University53
TL;DR: The authors reconstructed past temperatures for seven continental-scale regions during the past one to two millennia and found that the most coherent feature in nearly all of the regional temperature reconstructions is a long-term cooling trend, which ended late in the nineteenth century.
Abstract: Past global climate changes had strong regional expression To elucidate their spatio-temporal pattern, we reconstructed past temperatures for seven continental-scale regions during the past one to two millennia The most coherent feature in nearly all of the regional temperature reconstructions is a long-term cooling trend, which ended late in the nineteenth century At multi-decadal to centennial scales, temperature variability shows distinctly different regional patterns, with more similarity within each hemisphere than between them There were no globally synchronous multi-decadal warm or cold intervals that define a worldwide Medieval Warm Period or Little Ice Age, but all reconstructions show generally cold conditions between ad 1580 and 1880, punctuated in some regions by warm decades during the eighteenth century The transition to these colder conditions occurred earlier in the Arctic, Europe and Asia than in North America or the Southern Hemisphere regions Recent warming reversed the long-term cooling; during the period ad 1971–2000, the area-weighted average reconstructed temperature was higher than any other time in nearly 1,400 years