Showing papers by "University of Southern Denmark published in 2015"
TL;DR: In the Global Burden of Disease Study 2013 (GBD 2013) as discussed by the authors, the authors used the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data.
5,792 citations
Mohammad H. Forouzanfar1, Lily Alexander, H. Ross Anderson, Victoria F Bachman1 +733 more•Institutions (289)
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as discussed by the authors provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.
5,668 citations
TL;DR: In the Global Burden of Disease Study 2013 (GBD 2013) as mentioned in this paper, the authors estimated the quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013.
4,510 citations
University Hospital Bonn1, University of California, Riverside2, Harvard University3, Case Western Reserve University4, University of Illinois at Chicago5, European Institute6, VA Palo Alto Healthcare System7, Stanford University8, Spanish National Research Council9, Cleveland Clinic Lerner Research Institute10, Hong Kong University of Science and Technology11, University of California, Los Angeles12, University of Southern Denmark13, University of Cambridge14, University of the Basque Country15, Ikerbasque16, University of Manchester17, RIKEN Brain Science Institute18, University of Eastern Finland19, University of Bonn20, University of Massachusetts Medical School21, Center of Advanced European Studies and Research22, University of Southern California23, University of South Florida24, Duke University25, Southampton General Hospital26, Moorgreen Hospital27, University of Southampton28, Louisiana State University29, Imperial College London30, Centre national de la recherche scientifique31, Karolinska Institutet32, Max Planck Society33, University of Tübingen34, University of Groningen35, University of Colorado Denver36, Douglas Mental Health University Institute37
TL;DR: Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction.
Abstract: Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.
3,947 citations
University of Helsinki1, Semmelweis University2, Hungarian Academy of Sciences3, University of Szeged4, University of Palermo5, Institute of Molecular Pathology and Immunology of the University of Porto6, University of Porto7, Autonomous University of Barcelona8, Instituto de Biologia Molecular e Celular9, Ikerbasque10, Harvard University11, University of Duisburg-Essen12, Paracelsus Private Medical University of Salzburg13, Salk Institute for Biological Studies14, University of Colorado Denver15, Bilkent University16, Middle East Technical University17, Statens Serum Institut18, University of Southern Denmark19, Ghent University Hospital20, Oslo University Hospital21, University of Belgrade22, University of Ljubljana23, University of Mainz24, Finnish Red Cross25, University of Gothenburg26, Latvian Biomedical Research and Study centre27, University of Applied Sciences and Arts Northwestern Switzerland FHNW28, University of Valencia29, Centro Nacional de Investigaciones Cardiovasculares30, University of Freiburg31, Utrecht University32, Trinity College, Dublin33, Catalan Institution for Research and Advanced Studies34, University of Barcelona35, International University Of Catalonia36, Aarhus University Hospital37
TL;DR: A comprehensive overview of the current understanding of the physiological roles of EVs is provided, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia.
Abstract: In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.
3,690 citations
Mohammad H. Forouzanfar1, Lily Alexander1, H. Ross Anderson2, Victoria F Bachman1 +718 more•Institutions (295)
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as mentioned in this paper provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.
1,656 citations
Christopher J L Murray1, Ryan M Barber, Kyle J Foreman2, Ayse Abbasoglu Ozgoren +608 more•Institutions (251)
TL;DR: Patterns of the epidemiological transition with a composite indicator of sociodemographic status, which was constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population, were quantified.
1,609 citations
National University of Cordoba1, Addis Ababa University2, National Autonomous University of Mexico3, State University of Campinas4, United Nations Environment Programme5, UNESCO6, United States Department of Agriculture7, Indiana University8, University of British Columbia9, Commonwealth Scientific and Industrial Research Organisation10, University of Paris-Sud11, Landcare Research12, University College London13, Autonomous University of Madrid14, University of Cambridge15, Council for Scientific and Industrial Research16, University of Southern Denmark17, United Nations University18, Virginia Tech College of Natural Resources and Environment19, The Nature Conservancy20, University of the South Pacific21, University of East Anglia22, Kyushu University23, King Abdulaziz City for Science and Technology24, University of Washington25, Budapest University of Technology and Economics26, Environmental Law Institute27, Ankara University28, University of Portsmouth29, Chinese Academy of Sciences30, Indian Institute of Technology Bombay31, Kyoto University32, Joseph Fourier University33, National Scientific and Technical Research Council34, University of Yaoundé35, Polish Academy of Sciences36, University of São Paulo37, École Normale Supérieure38, University of Otago39, Stanford University40, University of Queensland41, Azim Premji University42, Helmholtz Centre for Environmental Research - UFZ43, University of Ghana44, Corvinus University of Budapest45, Stockholm University46, Lakehead University47, Indian Institute of Forest Management48, Seoul National University49, Sofia University50
TL;DR: The first public product of the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES) is its Conceptual Framework as discussed by the authors, which will underpin all IPBES functions and provide structure and comparability to the syntheses that will produce at different spatial scales, on different themes, and in different regions.
1,585 citations
Katholieke Universiteit Leuven1, Vrije Universiteit Brussel2, University of Copenhagen3, Rega Institute for Medical Research4, Institut national de la recherche agronomique5, Technical University of Denmark6, Molecular Medicine Partnership Unit7, University Hospital Heidelberg8, Aalborg University9, University of Southern Denmark10, King's College London11
TL;DR: A unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa is reported, highlighting the need to disentangle gut microbiota signatures of specific human diseases from those of medication.
Abstract: In recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported. In most of these reports, treatment regimens were not controlled for and conclusions could thus be confounded by the effects of various drugs on the microbiota, which may obscure microbial causes, protective factors or diagnostically relevant signals. Our study addresses disease and drug signatures in the human gut microbiome of type 2 diabetes mellitus (T2D). Two previous quantitative gut metagenomics studies of T2D patients that were unstratified for treatment yielded divergent conclusions regarding its associated gut microbial dysbiosis. Here we show, using 784 available human gut metagenomes, how antidiabetic medication confounds these results, and analyse in detail the effects of the most widely used antidiabetic drug metformin. We provide support for microbial mediation of the therapeutic effects of metformin through short-chain fatty acid production, as well as for potential microbiota-mediated mechanisms behind known intestinal adverse effects in the form of a relative increase in abundance of Escherichia species. Controlling for metformin treatment, we report a unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa. These in turn cause functional microbiome shifts, in part alleviated by metformin-induced changes. Overall, the present study emphasizes the need to disentangle gut microbiota signatures of specific human diseases from those of medication.
1,473 citations
TL;DR: A keyword analysis identifies the most popular subjects covered by bibliometric analysis, and multidisciplinary articles are shown to have the highest impact.
Abstract: Bibliometric methods or "analysis" are now firmly established as scientific specialties and are an integral part of research evaluation methodology especially within the scientific and applied fields. The methods are used increasingly when studying various aspects of science and also in the way institutions and universities are ranked worldwide. A sufficient number of studies have been completed, and with the resulting literature, it is now possible to analyse the bibliometric method by using its own methodology. The bibliometric literature in this study, which was extracted from Web of Science, is divided into two parts using a method comparable to the method of Jonkers et al. (Characteristics of bibliometrics articles in library and information sciences (LIS) and other journals, pp. 449---551, 2012: The publications either lie within the Information and Library Science (ILS) category or within the non-ILS category which includes more applied, "subject" based studies. The impact in the different groupings is judged by means of citation analysis using normalized data and an almost linear increase can be observed from 1994 onwards in the non-ILS category. The implication for the dissemination and use of the bibliometric methods in the different contexts is discussed. A keyword analysis identifies the most popular subjects covered by bibliometric analysis, and multidisciplinary articles are shown to have the highest impact. A noticeable shift is observed in those countries which contribute to the pool of bibliometric analysis, as well as a self-perpetuating effect in giving and taking references.
1,098 citations
University of Copenhagen1, Finnish Institute of Occupational Health2, University of Southern Denmark3, University of Basel4, Lund University5, Autonomous University of Barcelona6, University of Coimbra7, Katholieke Universiteit Leuven8, University of Osnabrück9, Karolinska Institutet10, VU University Amsterdam11, Jagiellonian University Medical College12, St Thomas' Hospital13, University of Erlangen-Nuremberg14
TL;DR: The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact dermatitis or other delayed‐type hypersensitivity skin and mucosal conditions.
Abstract: The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact dermatitis or other delayed-type hypersensitivity skin and mucosal conditions. Sections with brief descriptions and discussions of different pertinent topics are followed by a highlighted short practical recommendation. Topics comprise, after an introduction with important definitions, materials, technique, modifications of epicutaneous testing, individual factors influencing the patch test outcome or necessitating special considerations, children, patients with occupational contact dermatitis and drug eruptions as special groups, patch testing of materials brought in by the patient, adverse effects of patch testing, and the final evaluation and patient counselling based on this judgement. Finally, short reference is made to aspects of (continuing) medical education and to electronic collection of data for epidemiological surveillance.
TL;DR: A large and growing body of literature on green supplier evaluation that considers environmental factors is relatively limited as discussed by the authors, and the most common criterion considered for green supplier selection was "environmental management systems".
TL;DR: Daratumumab monotherapy had a favorable safety profile and encouraging efficacy in patients with heavily pretreated and refractory myeloma, and no maximum tolerated dose was identified in part 1.
Abstract: BACKGROUND Multiple myeloma cells uniformly overexpress CD38. We studied daratumumab, a CD38-targeting, human IgG1κ monoclonal antibody, in a phase 1–2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy. METHODS In part 1, the dose-escalation phase, we administered daratumumab at doses of 0.005 to 24 mg per kilogram of body weight. In part 2, the dose-expansion phase, 30 patients received 8 mg per kilogram of daratumumab and 42 received 16 mg per kilogram, administered once weekly (8 doses), twice monthly (8 doses), and monthly for up to 24 months. End points included safety, efficacy, and pharmacokinetics. RESULTS No maximum tolerated dose was identified in part 1. In part 2, the median time since diagnosis was 5.7 years. Patients had received a median of four prior treatments; 79% of the patients had disease that was refractory to the last therapy received (64% had disease refractory to proteasome inhibitors and immunomodulatory drugs and 64% had disease refractory to bortezomib and lenalidomide), and 76% had received autologous stem-cell transplants. Infusion-related reactions in part 2 were mild (71% of patients had an event of any grade, and 1% had an event of grade 3), with no dose-dependent adverse events. The most common adverse events of grade 3 or 4 (in ≥5% of patients) were pneumonia and thrombocytope nia. The overall response rate was 36% in the cohort that received 16 mg per kilogram (15 patients had a partial response or better, including 2 with a complete response and 2 with a very good partial response) and 10% in the cohort that received 8 mg per kilogram (3 had a partial response). In the cohort that received 16 mg per kilogram, the median progression-free survival was 5.6 months (95% confidence interval [CI], 4.2 to 8.1), and 65% (95% CI, 28 to 86) of the patients who had a response did not have progression at 12 months. CONCLUSIONS Daratumumab monotherapy had a favorable safety profile and encouraging efficacy in patients with heavily pretreated and refractory myeloma. (Funded by Janssen Research and Development and Genmab; ClinicalTrials.gov number, NCT00574288.)
TL;DR: In this article, the authors present the development and design of coherent smart energy systems as an integrated part of achieving future 100% renewable energy and transport solutions, which can potentially pave the way to a bioenergy-free, renewable energy- and transport system.
University of Southern Denmark1, Brigham and Women's Hospital2, University of Barcelona3, Autonomous University of Madrid4, University of Arizona5, University of Colorado Denver6, Manchester Academic Health Science Centre7, Autonomous University of Chile8, Harvard University9, Lovelace Respiratory Research Institute10, University of New Mexico11
TL;DR: It is suggested that low FEV1 in early adulthood is important in the genesis of COPD and that accelerated decline inFEV1 is not an obligate feature of COPd.
Abstract: BackgroundChronic obstructive pulmonary disease (COPD) is thought to result from an accelerated decline in forced expiratory volume in 1 second (FEV1) over time. Yet it is possible that a normal decline in FEV1 could also lead to COPD in persons whose maximally attained FEV1 is less than population norms. MethodsWe stratified participants in three independent cohorts (the Framingham Offspring Cohort, the Copenhagen City Heart Study, and the Lovelace Smokers Cohort) according to lung function (FEV1 ≥80% or <80% of the predicted value) at cohort inception (mean age of patients, approximately 40 years) and the presence or absence of COPD at the last study visit. We then determined the rate of decline in FEV1 over time among the participants according to their FEV1 at cohort inception and COPD status at study end. ResultsAmong 657 persons who had an FEV1 of less than 80% of the predicted value before 40 years of age, 174 (26%) had COPD after 22 years of observation, whereas among 2207 persons who had a baseli...
Woolcock Institute of Medical Research1, University of Cape Town2, University of Manitoba3, Laval University4, Federal University of Bahia5, Harvard University6, Helsinki University Central Hospital7, Kagoshima University8, Erasmus University Rotterdam9, University of Wisconsin-Madison10, McMaster University11, University of Pisa12, University of Southern Denmark13, Universidade Federal de Santa Catarina14, University of Costa Rica15, Boston Children's Hospital16, The Chinese University of Hong Kong17, University of British Columbia18
TL;DR: The changes include a revised asthma definition, tools for assessing symptom control and risk factors for adverse outcomes, and updated strategies for adaptation and implementation of GINA recommendations.
Abstract: Over the past 20 years, the Global Initiative for Asthma (GINA) has regularly published and annually updated a global strategy for asthma management and prevention that has formed the basis for many national guidelines. However, uptake of existing guidelines is poor. A major revision of the GINA report was published in 2014, and updated in 2015, reflecting an evolving understanding of heterogeneous airways disease, a broader evidence base, increasing interest in targeted treatment, and evidence about effective implementation approaches. During development of the report, the clinical utility of recommendations and strategies for their practical implementation were considered in parallel with the scientific evidence.This article provides a summary of key changes in the GINA report, and their rationale. The changes include a revised asthma definition; tools for assessing symptom control and risk factors for adverse outcomes; expanded indications for inhaled corticosteroid therapy; a framework for targeted treatment based on phenotype, modifiable risk factors, patient preference, and practical issues; optimisation of medication effectiveness by addressing inhaler technique and adherence; revised recommendations about written asthma action plans; diagnosis and initial treatment of the asthma-chronic obstructive pulmonary disease overlap syndrome; diagnosis in wheezing pre-school children; and updated strategies for adaptation and implementation of GINA recommendations.
Thomas W. Winkler1, Anne E. Justice2, Mariaelisa Graff2, Llilda Barata3 +435 more•Institutions (106)
TL;DR: In this paper, the authors performed meta-analyses of 114 studies with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium.
Abstract: Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.
National Institute for Health Research1, University of Bristol2, University of London3, Loughborough University4, University of Cambridge5, University of Southern Denmark6, Norwegian School of Sport Sciences7, Ghent University8, University of Canberra9, Universidade Federal de Pelotas10, University of Iowa11, University of Zurich12, University of South Carolina13, University Hospital of Lausanne14, University of Strathclyde15, Deakin University16, University of Lisbon17
TL;DR: Boys were less sedentary and more active than girls at all ages, and overweight/obese participants were less active than their normal weight counterparts from age seven onwards.
Abstract: Physical activity and sedentary behaviour in youth have been reported to vary by sex, age, weight status and country. However, supporting data are often self-reported and/or do not encompass a wide range of ages or geographical locations. This study aimed to describe objectively-measured physical activity and sedentary time patterns in youth. The International Children’s Accelerometry Database (ICAD) consists of ActiGraph accelerometer data from 20 studies in ten countries, processed using common data reduction procedures. Analyses were conducted on 27,637 participants (2.8–18.4 years) who provided at least three days of valid accelerometer data. Linear regression was used to examine associations between age, sex, weight status, country and physical activity outcomes. Boys were less sedentary and more active than girls at all ages. After 5 years of age there was an average cross-sectional decrease of 4.2 % in total physical activity with each additional year of age, due mainly to lower levels of light-intensity physical activity and greater time spent sedentary. Physical activity did not differ by weight status in the youngest children, but from age seven onwards, overweight/obese participants were less active than their normal weight counterparts. Physical activity varied between samples from different countries, with a 15–20 % difference between the highest and lowest countries at age 9–10 and a 26–28 % difference at age 12–13. Physical activity differed between samples from different countries, but the associations between demographic characteristics and physical activity were consistently observed. Further research is needed to explore environmental and sociocultural explanations for these differences.
TL;DR: MRI findings of neuromyelitis optica and its spectrum disorder (NMOSD) are reviewed, finding brain, optic nerve, and spinal cord MRI findings of NMOSD to be of increased interest.
Abstract: Since its initial reports in the 19th century, neuromyelitis optica (NMO) had been thought to involve only the optic nerves and spinal cord. However, the discovery of highly specific anti-aquaporin-4 antibody diagnostic biomarker for NMO enabled recognition of more diverse clinical spectrum of manifestations. Brain MRI abnormalities in patients seropositive for anti-aquaporin-4 antibody are common and some may be relatively unique by virtue of localization and configuration. Some seropositive patients present with brain involvement during their first attack and/or continue to relapse in the same location without optic nerve and spinal cord involvement. Thus, characteristics of brain abnormalities in such patients have become of increased interest. In this regard, MRI has an increasingly important role in the differential diagnosis of NMO and its spectrum disorder (NMOSD), particularly from multiple sclerosis. Differentiating these conditions is of prime importance because early initiation of effective immunosuppressive therapy is the key to preventing attack-related disability in NMOSD, whereas some disease-modifying drugs for multiple sclerosis may exacerbate the disease. Therefore, identifying the MRI features suggestive of NMOSD has diagnostic and prognostic implications. We herein review the brain, optic nerve, and spinal cord MRI findings of NMOSD.
TL;DR: In patients with knee osteoarthritis who were eligible for unilateral total knee replacements, treatment with total knee replacement followed by nonsurgical treatment resulted in greater pain relief and functional improvement after 12 months than did nons surgical treatment alone.
Abstract: BackgroundMore than 670,000 total knee replacements are performed annually in the United States; however, high-quality evidence to support the effectiveness of the procedure, as compared with nonsurgical interventions, is lacking. MethodsIn this randomized, controlled trial, we enrolled 100 patients with moderate-to-severe knee osteoarthritis who were eligible for unilateral total knee replacement. Patients were randomly assigned to undergo total knee replacement followed by 12 weeks of nonsurgical treatment (total-knee-replacement group) or to receive only the 12 weeks of nonsurgical treatment (nonsurgical-treatment group), which was delivered by physiotherapists and dietitians and consisted of exercise, education, dietary advice, use of insoles, and pain medication. The primary outcome was the change from baseline to 12 months in the mean score on four Knee Injury and Osteoarthritis Outcome Score subscales, covering pain, symptoms, activities of daily living, and quality of life (KOOS4); scores range fr...
Mahidol University1, University of California, San Francisco2, University of Cape Town3, University of Tübingen4, Wellcome Trust5, University of Oxford6, University of Western Australia7, University of Paris8, World Health Organization9, University of Bamako10, Swiss Tropical and Public Health Institute11, University of Lausanne12, Pasteur Institute13, Novartis14, Liverpool School of Tropical Medicine15, Karolinska Institutet16, Walter and Eliza Hall Institute of Medical Research17, Drugs for Neglected Diseases Initiative18, University of Southern Denmark19, National University of Laos20, Mahosot Hospital21, International Military Sports Council22, Muhimbili University of Health and Allied Sciences23, Yale University24, Uppsala University25, University of Washington26, University of Amsterdam27
TL;DR: Higher, more frequent, or prolonged dosage regimens should now be evaluated in very young children, particularly if malnourished, and in patients with hyperparasitemia, as well as patients in very low transmission intensity areas with emerging parasite resistance.
Abstract: Background: Achieving adequate antimalarial drug exposure is essential for curing malaria. Day 7 blood or plasma lumefantrine concentrations provide a simple measure of drug exposure that correlates well with artemether-lumefantrine efficacy. However, the 'therapeutic' day 7 lumefantrine concentration threshold needs to be defined better, particularly for important patient and parasite sub-populations. Methods: The WorldWide Antimalarial Resistance Network (WWARN) conducted a large pooled analysis of individual pharmacokinetic-pharmacodynamic data from patients treated with artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria, to define therapeutic day 7 lumefantrine concentrations and identify patient factors that substantially alter these concentrations. A systematic review of PubMed, Embase, Google Scholar, ClinicalTrials.gov and conference proceedings identified all relevant studies. Risk of bias in individual studies was evaluated based on study design, methodology and missing data. Results: Of 31 studies identified through a systematic review, 26 studies were shared with WWARN and 21 studies with 2,787 patients were included. Recrudescence was associated with low day 7 lumefantrine concentrations (HR 1.59 (95 % CI 1.36 to 1.85) per halving of day 7 concentrations) and high baseline parasitemia (HR 1.87 (95 % CI 1.22 to 2.87) per 10-fold increase). Adjusted for mg/kg dose, day 7 concentrations were lowest in very young children (98 % cure rates (if parasitemia <135,000/μL). Conclusions: Current artemether-lumefantrine dosing recommendations achieve day 7 lumefantrine concentrations ≥200 ng/ml and high cure rates in most uncomplicated malaria patients. Three groups are at increased risk of treatment failure: very young children (particularly those underweight-for-age); patients with high parasitemias; and patients in very low transmission intensity areas with emerging parasite resistance. In these groups, adherence and treatment response should be monitored closely. Higher, more frequent, or prolonged dosage regimens should now be evaluated in very young children, particularly if malnourished, and in patients with hyperparasitemia.
Heidelberg University1, University Hospital Heidelberg2, Saarland University3, Princeton University4, Siemens5, French Institute of Health and Medical Research6, University College London7, Aarhus University Hospital8, Umeå University9, University of Milan10, University of Pavia11, University of Southern Denmark12
TL;DR: This is to the authors' knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes and underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics.
Abstract: Aim: We were able to show that targeted Next-Generation Sequencing is well suited to be applied in clinical routine diagnostics, substantiating the ongoing paradigm shift from low- to high-throughp ...
College of Charleston1, West Chester University of Pennsylvania2, Columbia University3, Colorado State University4, Australian National University5, University of North Carolina at Chapel Hill6, University of Arizona7, Rensselaer Polytechnic Institute8, University of Colorado Boulder9, University of Minnesota10, University of Southern Denmark11, University of Connecticut12
TL;DR: It is advocated for the view that relaxed selection and variable selection intensities are likely more important constraints to the evolution of plasticity than the costs of Plasticity, and opportunities to offset costs of phenotypes through ontogeny, amelioration of phenotypic costs across environments, and the condition-dependent hypothesis are examined.
Abstract: Phenotypic plasticity is ubiquitous and generally regarded as a key mechanism for enabling organisms to survive in the face of environmental change Because no organism is infinitely or ideally plastic, theory suggests that there must be limits (for example, the lack of ability to produce an optimal trait) to the evolution of phenotypic plasticity, or that plasticity may have inherent significant costs Yet numerous experimental studies have not detected widespread costs Explicitly differentiating plasticity costs from phenotype costs, we re-evaluate fundamental questions of the limits to the evolution of plasticity and of generalists vs specialists We advocate for the view that relaxed selection and variable selection intensities are likely more important constraints to the evolution of plasticity than the costs of plasticity Some forms of plasticity, such as learning, may be inherently costly In addition, we examine opportunities to offset costs of phenotypes through ontogeny, amelioration of phenotypic costs across environments, and the condition-dependent hypothesis We propose avenues of further inquiry in the limits of plasticity using new and classic methods of ecological parameterization, phylogenetics and omics in the context of answering questions on the constraints of plasticity Given plasticity's key role in coping with environmental change, approaches spanning the spectrum from applied to basic will greatly enrich our understanding of the evolution of plasticity and resolve our understanding of limits
TL;DR: The goals of this review are to stimulate use of standardized nomenclature for OA that could serve as building blocks for describing OA and defining OA phenotypes to provide unifying disease concepts for a heterogeneous disorder.
TL;DR: A systematic literature review and a synthesis of high-quality contributions in this field with a focus on a general overview of research on co-copetition, coopetition as a strategy, and the management of co-opetition is presented in this article.
Abstract: Coopetition describes an interorganizational relationship that combines “cooperation” and “competition”. During recent years, coopetition has become an important domain for industrial practice which has led to an increasing rate of publications in academic journals. Despite the growing interest, coopetition research is still fragmented, reflected by divergent uses of the coopetition concept, a lack of generalizability, and a limited contextual focus. This article presents a systematic literature review and a synthesis of high-quality contributions in this field with a focus on a general overview of research on coopetition, coopetition as a strategy, and the management of coopetition. By critically evaluating the current body of literature and definitions, and connecting it to other promising domains, we develop a new definition of coopetition and highlight several promising areas for future research, such as the elaboration of theoretical and empirical approaches, the consideration of contextual contingencies, and implications for innovation that involves interorganizational knowledge flow.
TL;DR: A scan of Inuit genomes for signatures of adaptation revealed signals at several loci, with the strongest signal located in a cluster of fatty acid desaturases that determine PUFA levels, which indicates that the Inuit have genetic and physiological adaptations to a diet rich in PUFAs.
Abstract: The indigenous people of Greenland, the Inuit, have lived for a long time in the extreme conditions of the Arctic, including low annual temperatures, and with a specialized diet rich in protein and fatty acids, particularly omega-3 polyunsaturated fatty acids (PUFAs). A scan of Inuit genomes for signatures of adaptation revealed signals at several loci, with the strongest signal located in a cluster of fatty acid desaturases that determine PUFA levels. The selected alleles are associated with multiple metabolic and anthropometric phenotypes and have large effect sizes for weight and height, with the effect on height replicated in Europeans. By analyzing membrane lipids, we found that the selected alleles modulate fatty acid composition, which may affect the regulation of growth hormones. Thus, the Inuit have genetic and physiological adaptations to a diet rich in PUFAs.
Charité1, Medical University of Graz2, University of Southern Denmark3, University of Silesia in Katowice4, University of Genoa5, Federal University of São Paulo6, Autonomous University of Barcelona7, University of Coimbra8, St. John's University9, Hiroshima University10, Medical University of South Carolina11, Hannover Medical School12, Hospital Kuala Lumpur13, University of Zurich14, University of Manitoba15, University of Mainz16, University of Toronto17, University of Bari18, Peking University19
TL;DR: This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomecha.
Abstract: This guideline is the result of a systematic literature review using the ‘Grading of Recommendations Assessment, Development and Evaluation’ (GRADE) methodology and a structured consensus conference held on 28 and 29 November 2012, in Berlin. It is a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA 2 LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international societies. Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The life-time prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomecha
TL;DR: It is demonstrated that circRNAs are highly abundant and dynamically expressed in a spatio-temporal manner in porcine fetal brain, suggesting important functions during mammalian brain development.
Abstract: Recently, thousands of circular RNAs (circRNAs) have been discovered in various tissues and cell types from human, mouse, fruit fly and nematodes. However, expression of circRNAs across mammalian brain development has never been examined. Here we profile the expression of circRNA in five brain tissues at up to six time-points during fetal porcine development, constituting the first report of circRNA in the brain development of a large animal. An unbiased analysis reveals a highly complex regulation pattern of thousands of circular RNAs, with a distinct spatio-temporal expression profile. The amount and complexity of circRNA expression was most pronounced in cortex at day 60 of gestation. At this time-point we find 4634 unique circRNAs expressed from 2195 genes out of a total of 13,854 expressed genes. Approximately 20 % of the porcine splice sites involved in circRNA production are functionally conserved between mouse and human. Furthermore, we observe that “hot-spot” genes produce multiple circRNA isoforms, which are often differentially expressed across porcine brain development. A global comparison of porcine circRNAs reveals that introns flanking circularized exons are longer than average and more frequently contain proximal complementary SINEs, which potentially can facilitate base pairing between the flanking introns. Finally, we report the first use of RNase R treatment in combination with in situ hybridization to show dynamic subcellular localization of circRNA during development. These data demonstrate that circRNAs are highly abundant and dynamically expressed in a spatio-temporal manner in porcine fetal brain, suggesting important functions during mammalian brain development.
TL;DR: Experimental evidence suggests form-to-meaning correspondences serve different functions in language processing, development, and communication: systematicity facilitates category learning by means of phonological cues, iconicity facilitates word learning and communication by Means of perceptuomotor analogies, and arbitrariness facilitates meaning individuation through distinctive forms.
TL;DR: This study pioneers using the decision-making trial and evaluation laboratory (DEMATEL) method with intuitionistic fuzzy sets to handle the important and causal relationships between GSCM practices and performances to find the main practices to improve both environmental and economic performances.
Abstract: Proposed a intuitionistic fuzzy based DEMATEL method for developing green practices.A case study from automotive industry is used for validation.Sensitivity analysis is performed to check the robustness of the method. Environmental topics have gained much consideration in corporate green operations. Globalization, stakeholder pressures, and stricter environmental regulations have made organizations develop environmental practices. Thus, green supply chain management (GSCM) is now a proactive approach for organizations to enhance their environmental performance and achieve competitive advantages. This study pioneers using the decision-making trial and evaluation laboratory (DEMATEL) method with intuitionistic fuzzy sets to handle the important and causal relationships between GSCM practices and performances. DEMATEL evaluates GSCM practices to find the main practices to improve both environmental and economic performances. This study uses intuitionistic fuzzy set theory to handle the linguistic imprecision and the ambiguity of human being's judgment. A case study from the automotive industry is presented to evaluate the efficiency of the proposed method. The results reveal "internal management support", "green purchasing" and "ISO 14001 certification" are the most significant GSCM practices. The practical results of this study offer useful insights for managers to become more environmentally responsible, while improving their economic and environmental performance goals. Further, a sensitivity analysis of results, managerial implications, conclusions, limitations and future research opportunities are provided.