Showing papers by "University of Southern Denmark published in 2014"
Tufts Medical Center1, University of Oxford2, Pierre-and-Marie-Curie University3, Erasmus University Rotterdam4, Women's College Hospital5, University of Liège6, American Physical Therapy Association7, Royal North Shore Hospital8, University of Tokyo9, University of Arizona10, Lund University11, Paris Descartes University12, University of Southern Denmark13, Coventry Health Care14
TL;DR: These evidence-based consensus recommendations provide guidance to patients and practitioners on treatments applicable to all individuals with knee OA, as well as therapies that can be considered according to individualized patient needs and preferences.
2,467 citations
Nicholas J Kassebaum1, Amelia Bertozzi-Villa1, Megan Coggeshall1, Katya Anne Shackelford1 +349 more•Institutions (179)
TL;DR: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015, with evidence of continued acceleration in the MMR, and MMR was highest in the oldest age groups in both 1990 and 2013.
1,383 citations
TL;DR: To control the pandemic of developmental neurotoxicity, a global prevention strategy is proposed and chemicals in existing use and all new chemicals must therefore be tested for developmental neurotoxicants is proposed.
Abstract: Neurodevelopmental disabilities, including autism, attention-defi cit hyperactivity disorder, dyslexia, and other cognitive impairments, aff ect millions of children worldwide, and some diagnoses seem to be increasing in frequency. Industrial chemicals that injure the developing brain are among the known causes for this rise in prevalence. In 2006, we did a systematic review and identifi ed fi ve industrial chemicals as developmental neurotoxicants: lead, methylmercury, polychlorinated biphenyls, arsenic, and toluene. Since 2006, epidemiological studies have documented six additional developmental neurotoxicants—manganese, fl uoride, chlorpyrifos, dichlorodiphenyltrichloroethane, tetrachloroethylene, and the polybrominated diphenyl ethers. We postulate that even more neurotoxicants remain undiscovered. To control the pandemic of developmental neurotoxicity, we propose a global prevention strategy. Untested chemicals should not be presumed to be safe to brain development, and chemicals in existing use and all new chemicals must therefore be tested for developmental neurotoxicity. To coordinate these eff orts and to accelerate translation of science into prevention, we propose the urgent formation of a new international clearinghouse.
1,303 citations
Mayo Clinic1, Johns Hopkins University2, Memorial Sloan Kettering Cancer Center3, University of Paris-Sud4, Institut Gustave Roussy5, VU University Amsterdam6, Medical University of Vienna7, Nottingham University Hospitals NHS Trust8, University of Utah9, Netherlands Cancer Institute10, Iuliu Hațieganu University of Medicine and Pharmacy11, University of Copenhagen12, University of Southern Denmark13, University of Texas MD Anderson Cancer Center14, Oregon Health & Science University15, Bristol-Myers Squibb16, Radboud University Nijmegen17
TL;DR: There was no significant difference between the ipilimumab group and the placebo group in terms of overall survival in the primary analysis, but there were signs of activity with the drug that warrant further investigation.
Abstract: BACKGROUND: Ipilimumab is a fully human monoclonal antibody that binds cytotoxic T-lymphocyte antigen 4 to enhance antitumour immunity. Our aim was to assess the use of ipilimumab after radiotherapy in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel chemotherapy. METHODS: We did a multicentre, randomised, double-blind, phase 3 trial in which men with at least one bone metastasis from castration-resistant prostate cancer that had progressed after docetaxel treatment were randomly assigned in a 1:1 ratio to receive bone-directed radiotherapy (8 Gy in one fraction) followed by either ipilimumab 10 mg/kg or placebo every 3 weeks for up to four doses. Non-progressing patients could continue to receive ipilimumab at 10 mg/kg or placebo as maintenance therapy every 3 months until disease progression, unacceptable toxic effect, or death. Patients were randomly assigned to either treatment group via a minimisation algorithm, and stratified by Eastern Cooperative Oncology Group performance status, alkaline phosphatase concentration, haemoglobin concentration, and investigator site. Patients and investigators were masked to treatment allocation. The primary endpoint was overall survival, assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00861614. FINDINGS: From May 26, 2009, to Feb 15, 2012, 799 patients were randomly assigned (399 to ipilimumab and 400 to placebo), all of whom were included in the intention-to-treat analysis. Median overall survival was 11.2 months (95% CI 9.5-12.7) with ipilimumab and 10.0 months (8.3-11.0) with placebo (hazard ratio [HR] 0.85, 0.72-1.00; p=0.053). However, the assessment of the proportional hazards assumption showed that it was violated (p=0.0031). A piecewise hazard model showed that the HR changed over time: the HR for 0-5 months was 1.46 (95% CI 1.10-1.95), for 5-12 months was 0.65 (0.50-0.85), and beyond 12 months was 0.60 (0.43-0.86). The most common grade 3-4 adverse events were immune-related, occurring in 101 (26%) patients in the ipilimumab group and 11 (3%) of patients in the placebo group. The most frequent grade 3-4 adverse events included diarrhoea (64 [16%] of 393 patients in the ipilimumab group vs seven [2%] of 396 in the placebo group), fatigue (40 [11%] vs 35 [9%]), anaemia (40 [10%] vs 43 [11%]), and colitis (18 [5%] vs 0). Four (1%) deaths occurred because of toxic effects of the study drug, all in the ipilimumab group. INTERPRETATION: Although there was no significant difference between the ipilimumab group and the placebo group in terms of overall survival in the primary analysis, there were signs of activity with the drug that warrant further investigation. FUNDING: Bristol-Myers Squibb.
1,236 citations
Vilnius University1, University of Ferrara2, Aarhus University3, University of Oslo4, Royal Institute of Technology5, Electromagnetic Geoservices6, University of Trieste7, Norwegian Computing Center8, University of Southern Denmark9, University of Santiago de Compostela10, Danske Bank11, Ruhr University Bochum12, Norwegian Meteorological Institute13, Norwegian Defence Research Establishment14, University of Auckland15, Norwegian University of Science and Technology16, Information Technology University17, Technical University of Ostrava18, Linköping University19, Karlsruhe Institute of Technology20, ETH Zurich21, Australian National University22, University of Modena and Reggio Emilia23, Cisco Systems, Inc.24, University of Buenos Aires25, University of Copenhagen26, University of Erlangen-Nuremberg27, Kazimierz Wielki University in Bydgoszcz28, National Scientific and Technical Research Council29, University of Valencia30, Paul Sabatier University31, University of Melbourne32, University of Nottingham33, University of Bristol34, CLC bio35, Princeton University36, La Trobe University37, Clemson University38
TL;DR: Dalton is a powerful general‐purpose program system for the study of molecular electronic structure at the Hartree–Fock, Kohn–Sham, multiconfigurational self‐consistent‐field, Møller–Plesset, configuration‐interaction, and coupled‐cluster levels of theory.
Abstract: Dalton is a powerful general-purpose program system for the study of molecular electronic structure at the Hartree-Fock, Kohn-Sham, multiconfigurational self-consistent-field, MOller-Plesset, confi ...
1,212 citations
Charité1, Medical University of Graz2, University of Southern Denmark3, Medical University of Silesia4, 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, Johns Hopkins University14, University of Zurich15, University of Manitoba16, University of Mainz17, University of Toronto18, Technion – Israel Institute of Technology19, University of Bari20, Peking University21
TL;DR: This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms, and outlines evidence-based diagnostic and therapeutic approaches for the different subtypes ofUrticaria.
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 pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).
1,150 citations
Christopher J L Murray1, Katrina F Ortblad1, Caterina Guinovart1, Stephen S Lim1 +367 more•Institutions (179)
TL;DR: The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration.
875 citations
Technical University of Denmark1, Institut national de la recherche agronomique2, South China University of Technology3, Commissariat à l'énergie atomique et aux énergies alternatives4, University of Copenhagen5, University of Southern Denmark6, VU University Amsterdam7, Katholieke Universiteit Leuven8, Wageningen University and Research Centre9, Tokyo Institute of Technology10, King Abdulaziz University11
TL;DR: This work presents a method, based on binning co-abundant genes across a series of metagenomic samples, that enables comprehensive discovery of new microbial organisms, viruses and co-inherited genetic entities and aids assembly of microbial genomes without the need for reference sequences.
Abstract: Most current approaches for analyzing metagenomic data rely on comparisons to reference genomes, but the microbial diversity of many environments extends far beyond what is covered by reference databases. De novo segregation of complex metagenomic data into specific biological entities, such as particular bacterial strains or viruses, remains a largely unsolved problem. Here we present a method, based on binning co-abundant genes across a series of metagenomic samples, that enables comprehensive discovery of new microbial organisms, viruses and co-inherited genetic entities and aids assembly of microbial genomes without the need for reference sequences. We demonstrate the method on data from 396 human gut microbiome samples and identify 7,381 co-abundance gene groups (CAGs), including 741 metagenomic species (MGS). We use these to assemble 238 high-quality microbial genomes and identify affiliations between MGS and hundreds of viruses or genetic entities. Our method provides the means for comprehensive profiling of the diversity within complex metagenomic samples.
866 citations
University of Southern Denmark1, Max Planck Society2, University of Queensland3, Institut national d'études démographiques4, University of Pennsylvania5, Stockholm University6, Spanish National Research Council7, Archbold Biological Station8, University of Central Florida9, Woods Hole Oceanographic Institution10, Population Research Institute11
TL;DR: Great variation among these species, including increasing, constant, decreasing, humped and bowed trajectories for both long- and short-lived species, challenges theoreticians to develop broader perspectives on the evolution of ageing and empiricists to study the demography of more species.
Abstract: Evolution drives, and is driven by, demography. A genotype moulds its phenotype’s age patterns of mortality and fertility in an environment; these two patterns in turn determine the genotype’s fitness in that environment. Hence, to understand the evolution of ageing, age patterns of mortality and reproduction need to be compared for species across the tree of life. However, few studies have done so and only for a limited range of taxa. Here we contrast standardized patterns over age for 11 mammals, 12 other vertebrates, 10 invertebrates, 12 vascular plants and a green alga. Although it has been predicted that evolution should inevitably lead to increasing mortality and declining fertility with age after maturity, there is great variation among these species, including increasing, constant, decreasing, humped and bowed trajectories for both long- and short-lived species. This diversity challenges theoreticians to develop broader perspectives on the evolution of ageing and empiricists to study the demography of more species.
786 citations
Haidong Wang1, Chelsea A. Liddell1, Matthew M Coates1, Meghan D. Mooney1 +228 more•Institutions (123)
TL;DR: Decreases since 2000 in under-5 mortality rates are accelerating in many developing countries, especially in sub-Saharan Africa, and rising income per person and maternal education and changes in secular trends led to 4·2 million fewer deaths.
684 citations
TL;DR: Differences in the composition and stability of the microbial community between pregnant and non-pregnant women were observed and can serve as the basis to study the relationship between the vaginal microbiome and adverse pregnancy outcomes.
Abstract: Background: This study was undertaken to characterize the vaginal microbiota throughout normal human pregnancy using sequence-based techniques. We compared the vaginal microbial composition of non-pregnant patients with a group of pregnant women who delivered at term. Results: A retrospective case–control longitudinal study was designed and included non-pregnant women (n = 32) and pregnant women who delivered at term (38 to 42 weeks) without complications (n = 22). Serial samples of vaginal fluid were collected from both non-pregnant and pregnant patients. A 16S rRNA gene sequence-based survey was conducted using pyrosequencing to characterize the structure and stability of the vaginal microbiota. Linear mixed effects models and generalized estimating equations were used to identify the phylotypes whose relative abundance was different between the two study groups. The vaginal microbiota of normal pregnant women was different from that of non-pregnant women (higher abundance of Lactobacillus vaginalis, L. crispatus, L. gasseri and L. jensenii and lower abundance of 22 other phylotypes in pregnant women). Bacterial community state type (CST) IV-B or CST IV-A characterized by high relative abundance of species of genus Atopobium as well as the presence of Prevotella, Sneathia, Gardnerella, Ruminococcaceae, Parvimonas, Mobiluncus and other taxa previously shown to be associated with bacterial vaginosis were less frequent in normal pregnancy. The stability of the vaginal microbiota of pregnant women was higher than that of non-pregnant women; however, during normal pregnancy, bacterial communities shift almost exclusively from one CST dominated by Lactobacillus spp. to another CST dominated by Lactobacillus spp. Conclusion: We report the first longitudinal study of the vaginal microbiota in normal pregnancy. Differences in the composition and stability of the microbial community between pregnant and non-pregnant women were observed. Lactobacillus spp. were the predominant members of the microbial community in normal pregnancy. These results can serve as the basis to study the relationship between the vaginal microbiome and adverse pregnancy outcomes.
TL;DR: In this article, the authors focus on identifying barriers to the implementation of a green supply chain management (Green SCM) based on procurement effectiveness and a total of 47 barriers are identified, both through detailed literature and discussion with industrial experts and through a questionnaire-based survey from various industrial sectors.
TL;DR: In this article, the causal role of alcohol consumption in cardiovascular disease was investigated using a Mendelian randomisation meta-analysis of 56 epidemiological studies, including 20 259 coronary heart disease cases and 10 164 stroke events.
Abstract: OBJECTIVE: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. DESIGN: Mendelian randomisation meta-analysis of 56 epidemiological studies. PARTICIPANTS: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. MAIN OUTCOME MEASURES: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. RESULTS: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)). CONCLUSIONS: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.
TL;DR: In this article, the authors used genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies and found robust evidence for 123 signals at 106 genomic loci associated with age at menarche.
Abstract: Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.
Copenhagen University Hospital1, Children's Hospital of Philadelphia2, Technical University of Denmark3, Barcelona Supercomputing Center4, University of Manchester5, Erasmus University Rotterdam6, University Medical Center Groningen7, University of Bristol8, University of Southampton9, University of Copenhagen10, University of Southern Denmark11, Southampton General Hospital12, Catalan Institution for Research and Advanced Studies13, Statens Serum Institut14
TL;DR: The results demonstrate the strength of applying specific phenotyping in the search for asthma susceptibility genes, and obtain strong evidence for a new susceptibility gene, CDHR3 (encoding cadherin-related family member 3), which is highly expressed in airway epithelium.
Abstract: Asthma exacerbations are among the most frequent causes of hospitalization during childhood, but the underlying mechanisms are poorly understood. We performed a genome-wide association study of a specific asthma phenotype characterized by recurrent, severe exacerbations occurring between 2 and 6 years of age in a total of 1,173 cases and 2,522 controls. Cases were identified from national health registries of hospitalization, and DNA was obtained from the Danish Neonatal Screening Biobank. We identified five loci with genome-wide significant association. Four of these, GSDMB, IL33, RAD50 and IL1RL1, were previously reported as asthma susceptibility loci, but the effect sizes for these loci in our cohort were considerably larger than in the previous genome-wide association studies of asthma. We also obtained strong evidence for a new susceptibility gene, CDHR3 (encoding cadherin-related family member 3), which is highly expressed in airway epithelium. These results demonstrate the strength of applying specific phenotyping in the search for asthma susceptibility genes.
TL;DR: Results indicate that the hybrid approach achieves better solutions compared to others, and that crowding distance method for LSP outperforms the former Grids method.
TL;DR: This theory explains surprisingly well both the frequency shifts and size-dependent damping in individual metallic nanoparticles as well as the observed broadening of the crossover regime from bonding-dipole plasmons to charge-transfer plasmon in metal nanoparticle dimers, thus unravelling a classical broadening mechanism that even dominates the widely anticipated short circuiting by quantum tunnelling.
Abstract: As plasmonic structures shrink towards sub-nanometre scales, it becomes more important to develop theoretical tools to explain their optical properties. Towards this aim, the authors present a semiclassical approach to describe experimental results for the non-local optical response of nanostructures.
TL;DR: It is now clear that multiple TFs team up to induce PPARγ during adipogenesis, and that other TFs cooperate withPPARγ to ensure adipocyte-specific genomic binding and function.
Abstract: Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor (NR) superfamily of ligand-dependent transcription factors (TFs) and function as a master regulator of adipocyte differentiation and metabolism. We review recent breakthroughs in the understanding of PPARγ gene regulation and function in the chromatin context. It is now clear that multiple TFs team up to induce PPARγ during adipogenesis, and that other TFs cooperate with PPARγ to ensure adipocyte-specific genomic binding and function. We discuss how this differs in other PPARγ-expressing cells such as macrophages and how these genome-wide mechanisms are preserved across species despite modest conservation of specific binding sites. These emerging considerations inform our understanding of PPARγ function as well as of adipocyte development and physiology.
TL;DR: In this paper, a systematic review and meta-analysis of randomized controlled trials were performed to identify the optimal exercise program, characterized by type and intensity of exercise, length of program, duration of individual supervised sessions, and number of sessions per week, for reducing pain and patient-reported disability in knee OA.
Abstract: Objective
To identify the optimal exercise program, characterized by type and intensity of exercise, length of program, duration of individual supervised sessions, and number of sessions per week, for reducing pain and patient-reported disability in knee osteoarthritis (OA).
Methods
A systematic review and meta-analysis of randomized controlled trials were performed. Standardized mean differences (SMDs) were combined using a random-effects model. Study-level covariates were applied in meta-regression analyses in order to reduce between-study heterogeneity.
Results
Forty-eight trials were included. Similar effects in reducing pain were found for aerobic, resistance, and performance exercise (SMD 0.67, 0.62, and 0.48, respectively; P = 0.733). These single-type exercise programs were more efficacious than programs that included different exercise types (SMD 0.61 versus 0.16; P < 0.001). The effect of aerobic exercise on pain relief increased with an increased number of supervised sessions (slope 0.022 [95% confidence interval 0.002, 0.043]). More pain reduction occurred with quadriceps-specific exercise than with lower limb exercise (SMD 0.85 versus 0.39; P = 0.005) and when supervised exercise was performed at least 3 times a week (SMD 0.68 versus 0.41; P = 0.017). No impact of intensity, duration of individual sessions, or patient characteristics was found. Similar results were found for the effect on patient-reported disability.
Conclusion
Optimal exercise programs for knee OA should have one aim and focus on improving aerobic capacity, quadriceps muscle strength, or lower extremity performance. For best results, the program should be supervised and carried out 3 times a week. Such programs have a similar effect regardless of patient characteristics, including radiographic severity and baseline pain.
TL;DR: It is shown that nutrient starvation causes rapid depletion of AcCoA, and multiple distinct manipulations designed to increase or reduce cytosolic Ac CoA led to the suppression or induction of autophagy, respectively, both in cultured human cells and in mice, delineating Ac coenzyme A-centered pharmacological strategies that allow for the therapeutic manipulation ofautophagy.
Harvard University1, Broad Institute2, deCODE genetics3, University of Oxford4, University of Copenhagen5, University of Michigan6, Yeshiva University7, Texas Biomedical Research Institute8, Wake Forest University9, University of Southern Denmark10, Pfizer11, Imperial College London12, National Health Service13, Ealing Hospital14, Hallym University15, Lund University16, University of Helsinki17, University of Texas Health Science Center at Houston18, Norwegian University of Science and Technology19, Uppsala University20, University of Bergen21, Aalborg University22, Novo Nordisk23, University of Eastern Finland24, Technische Universität München25, University of North Carolina at Chapel Hill26, University of Liverpool27, National Institute for Health and Welfare28, National University of Singapore29, Agency for Science, Technology and Research30, University of Iceland31, Danube University Krems32, King Abdulaziz University33, University of Pennsylvania34, University of Mississippi35, Churchill Hospital36, Massachusetts Institute of Technology37
TL;DR: In this article, the authors identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels.
Abstract: Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ~150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 × 10(-6)), and non-diabetic Icelandic carriers of a frameshift variant (p.Lys34Serfs*50) demonstrated reduced glucose levels (-0.17 s.d., P = 4.6 × 10(-4)). The two most common protein-truncating variants (p.Arg138* and p.Lys34Serfs*50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk, and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts. In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention.
TL;DR: The results from most observational studies suggested an inverse relationship between the peripheral BDNF level and habitual physical activity or cardiorespiratory fitness and more research is needed to confirm the findings from the observational studies.
Abstract: The purpose of this study was to summarize the effects of physical activity and exercise on peripheral brain-derived neurotrophic factor (BDNF) in healthy humans Experimental and observational studies were identified from PubMed, Web of Knowledge, Scopus, and SPORT Discus A total of 32 articles met the inclusion criteria Evidence from experimental studies suggested that peripheral BDNF concentrations were elevated by acute and chronic aerobic exercise The majority of the studies suggested that strength training had no influence on peripheral BDNF The results from most observational studies suggested an inverse relationship between the peripheral BDNF level and habitual physical activity or cardiorespiratory fitness More research is needed to confirm the findings from the observational studies
University of Bristol1, Medical Research Council2, Newcastle University3, University of London4, University of Glasgow5, University of Southampton6, Seconda Università degli Studi di Napoli7, Ghent University8, University of Southern Denmark9, University of British Columbia10, Tulane University11, University of Edinburgh12, University of Michigan13, University of Washington14, University of Utah15, Kyungpook National University16, Yeshiva University17, Rutgers University18, Kyushu University19, King's College London20, Katholieke Universiteit Leuven21, Lund University22, Umeå University23, University of Calgary24, The Chinese University of Hong Kong25, University of Groningen26, University of Texas Southwestern Medical Center27, National Institutes of Health28
TL;DR: Telomere length is longer in females than males, although this difference was not universally found in studies that did not use Southern blot methods, and further research on explanations for the methodological differences is required.
TL;DR: Despite a few outlying studies, consistently favourable estimates were obtained for all injury prevention measures except for stretching, and intention-to-treat sensitivity analyses consistently revealed even more robust effect estimates.
Abstract: Background Physical activity is important in both prevention and treatment of many common diseases, but sports injuries can pose serious problems.
Objective To determine whether physical activity exercises can reduce sports injuries and perform stratified analyses of strength training, stretching, proprioception and combinations of these, and provide separate acute and overuse injury estimates.
Material and methods PubMed, EMBASE, Web of Science and SPORTDiscus were searched and yielded 3462 results. Two independent authors selected relevant randomised, controlled trials and quality assessments were conducted by all authors of this paper using the Cochrane collaboration domain-based quality assessment tool. Twelve studies that neglected to account for clustering effects were adjusted. Quantitative analyses were performed in STATA V.12 and sensitivity analysed by intention-to-treat. Heterogeneity (I2) and publication bias (Harbord's small-study effects) were formally tested.
Results 25 trials, including 26 610 participants with 3464 injuries, were analysed. The overall effect estimate on injury prevention was heterogeneous. Stratified exposure analyses proved no beneficial effect for stretching (RR 0.963 (0.846–1.095)), whereas studies with multiple exposures (RR 0.655 (0.520–0.826)), proprioception training (RR 0.550 (0.347–0.869)), and strength training (RR 0.315 (0.207–0.480)) showed a tendency towards increasing effect. Both acute injuries (RR 0.647 (0.502–0.836)) and overuse injuries (RR 0.527 (0.373–0.746)) could be reduced by physical activity programmes. Intention-to-treat sensitivity analyses consistently revealed even more robust effect estimates.
Conclusions Despite a few outlying studies, consistently favourable estimates were obtained for all injury prevention measures except for stretching. Strength training reduced sports injuries to less than 1/3 and overuse injuries could be almost halved.
TL;DR: In this paper, the underlying physical principles of radiation nanofocusing in metallic nanostructures, and the recent progress, future directions and potential applications of this subfield of nano-optics are reviewed.
Abstract: This article reviews the underlying physical principles of radiation nanofocusing in metallic nanostructures, and the recent progress, future directions and potential applications of this subfield of nano-optics.
University Hospital Centre Zagreb1, Charles University in Prague2, Amager Hospital3, University of Southern Denmark4, Aarhus University Hospital5, Tartu University Hospital6, Semmelweis University7, Ben-Gurion University of the Negev8, University of Padua9, Lithuanian University of Health Sciences10, Hospital de São João11, University of Porto12, Linköping University13, Örebro University14, Imperial College London15, Hull Royal Infirmary16, Gentofte Hospital17
TL;DR: Whether an East–West gradient in the incidence of inflammatory bowel disease in Europe exists is investigated to find out whether international guidelines for diagnosis and initial treatment are not being followed uniformly by physicians.
Abstract: Objective: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe. The reasons for these changes remain unknown. The aim of this study was to investigate whether an East– ...
TL;DR: In this paper, the authors performed association mapping of T2D-related quantitative traits in up to 2,575 Greenlandic individuals without known diabetes and discovered a nonsense p.Arg684Ter variant (in which arginine is replaced by a termination codon) in the gene TBC1D4 with an allele frequency of 17%.
Abstract: An association mapping study of type-2-diabetes-related quantitative traits in the Greenlandic population identified a common variant in TBC1D4 that increases plasma glucose levels and serum insulin levels after an oral glucose load and type 2 diabetes risk, with effect sizes several times larger than any previous findings of large-scale genome-wide association studies for these traits. This systematic genetic association study of quantitative traits related to type 2 diabetes (T2D) has identified a nonsense variant in the gene TBC1D4 which is present in 17% of the Greenlandic population, known to be a small founder population with a high incidence of T2D. The gene variant increases the levels of plasma glucose, serum insulin, and dramatically increases T2D risk. It also modestly reduces the concentrations of fasting plasma and fasting serum insulin. This work illustrates the value of founder populations — or of small and historically isolated populations — in maximizing the effectiveness of genetic association studies of this type. The Greenlandic population, a small and historically isolated founder population comprising about 57,000 inhabitants, has experienced a dramatic increase in type 2 diabetes (T2D) prevalence during the past 25 years1. Motivated by this, we performed association mapping of T2D-related quantitative traits in up to 2,575 Greenlandic individuals without known diabetes. Using array-based genotyping and exome sequencing, we discovered a nonsense p.Arg684Ter variant (in which arginine is replaced by a termination codon) in the gene TBC1D4 with an allele frequency of 17%. Here we show that homozygous carriers of this variant have markedly higher concentrations of plasma glucose (β = 3.8 mmol l−1, P = 2.5 × 10−35) and serum insulin (β = 165 pmol l−1, P = 1.5 × 10−20) 2 hours after an oral glucose load compared with individuals with other genotypes (both non-carriers and heterozygous carriers). Furthermore, homozygous carriers have marginally lower concentrations of fasting plasma glucose (β = −0.18 mmol l−1, P = 1.1 × 10−6) and fasting serum insulin (β = −8.3 pmol l−1, P = 0.0014), and their T2D risk is markedly increased (odds ratio (OR) = 10.3, P = 1.6 × 10−24). Heterozygous carriers have a moderately higher plasma glucose concentration 2 hours after an oral glucose load than non-carriers (β = 0.43 mmol l−1, P = 5.3 × 10−5). Analyses of skeletal muscle biopsies showed lower messenger RNA and protein levels of the long isoform of TBC1D4, and lower muscle protein levels of the glucose transporter GLUT4, with increasing number of p.Arg684Ter alleles. These findings are concomitant with a severely decreased insulin-stimulated glucose uptake in muscle, leading to postprandial hyperglycaemia, impaired glucose tolerance and T2D. The observed effect sizes are several times larger than any previous findings in large-scale genome-wide association studies of these traits2,3,4 and constitute further proof of the value of conducting genetic association studies outside the traditional setting of large homogeneous populations.
TL;DR: It is concluded that epidemiological studies with inclusion of all persons in a population followed for decades available relatively fast are important data sources for modern epidemiology, but it is important to acknowledge the data limitations.
Abstract: Studies based on databases, medical records and registers are used extensively today in epidemiological research. Despite the increasing use, no developed methodological literature on use and evaluation of population-based registers is available, even though data collection in register-based studies differs from researcher-collected data, all persons in a population are available and traditional statistical analyses focusing on sampling error as the main source of uncertainty may not be relevant. We present the main strengths and limitations of register-based studies, biases especially important in register-based studies and methods for evaluating completeness and validity of registers. The main strengths are that data already exist and valuable time has passed, complete study populations minimizing selection bias and independently collected data. Main limitations are that necessary information may be unavailable, data collection is not done by the researcher, confounder information is lacking, missing information on data quality, truncation at start of follow-up making it difficult to differentiate between prevalent and incident cases and the risk of data dredging. We conclude that epidemiological studies with inclusion of all persons in a population followed for decades available relatively fast are important data sources for modern epidemiology, but it is important to acknowledge the data limitations.
TL;DR: In 2032, at least an additional 26,000 individuals per 1 million population aged ≥45 years are estimated to have consulted a physician for OA in a peripheral joint compared to 2012, underscore the need to address modifiable risk factors and develop new effective OA treatments.
TL;DR: The ability of carbon cloth to accelerate DIET should be considered in anaerobic digester designs that incorporate carbon cloth, although the syntrophic partners were too far apart for cell-to-cell biological electrical connections to be feasible.