Showing papers by "University of Southern Denmark published in 2018"
TL;DR: Intensified research efforts and global initiatives are clearly needed to address the burden of low back pain as a public health problem, where health and other systems are often fragile and not equipped to cope with this growing burden.
2,114 citations
TL;DR: It is found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero.
1,831 citations
TL;DR: This work presents a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and shows that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods.
Abstract: Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.
1,620 citations
Verneri Anttila1, Verneri Anttila2, Brendan Bulik-Sullivan1, Brendan Bulik-Sullivan2 +717 more•Institutions (270)
TL;DR: It is demonstrated that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine, and it is shown that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures.
Abstract: Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.
1,357 citations
TL;DR: In insights into the role of alcohol consumption in the genetic architecture of hypertension, a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions is conducted.
Abstract: Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
1,218 citations
Christopher Troeger1, Brigette F. Blacker1, Ibrahim A Khalil1, Puja C Rao1 +148 more•Institutions (28)
TL;DR: The findings show substantial progress in the reduction of lower respiratory infection burden, but this progress has not been equal across locations, has been driven by decreases in several primary risk factors, and might require more effort among elderly adults.
Abstract: Summary Background Lower respiratory infections are a leading cause of morbidity and mortality around the world The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, provides an up-to-date analysis of the burden of lower respiratory infections in 195 countries This study assesses cases, deaths, and aetiologies spanning the past 26 years and shows how the burden of lower respiratory infection has changed in people of all ages Methods We used three separate modelling strategies for lower respiratory infections in GBD 2016: a Bayesian hierarchical ensemble modelling platform (Cause of Death Ensemble model), which uses vital registration, verbal autopsy data, and surveillance system data to predict mortality due to lower respiratory infections; a compartmental meta-regression tool (DisMod-MR), which uses scientific literature, population representative surveys, and health-care data to predict incidence, prevalence, and mortality; and modelling of counterfactual estimates of the population attributable fraction of lower respiratory infection episodes due to Streptococcus pneumoniae, Haemophilus influenzae type b, influenza, and respiratory syncytial virus We calculated each modelled estimate for each age, sex, year, and location We modelled the exposure level in a population for a given risk factor using DisMod-MR and a spatio-temporal Gaussian process regression, and assessed the effectiveness of targeted interventions for each risk factor in children younger than 5 years We also did a decomposition analysis of the change in LRI deaths from 2000–16 using the risk factors associated with LRI in GBD 2016 Findings In 2016, lower respiratory infections caused 652 572 deaths (95% uncertainty interval [UI] 586 475–720 612) in children younger than 5 years (under-5s), 1 080 958 deaths (943 749–1 170 638) in adults older than 70 years, and 2 377 697 deaths (2 145 584–2 512 809) in people of all ages, worldwide Streptococcus pneumoniae was the leading cause of lower respiratory infection morbidity and mortality globally, contributing to more deaths than all other aetiologies combined in 2016 (1 189 937 deaths, 95% UI 690 445–1 770 660) Childhood wasting remains the leading risk factor for lower respiratory infection mortality among children younger than 5 years, responsible for 61·4% of lower respiratory infection deaths in 2016 (95% UI 45·7–69·6) Interventions to improve wasting, household air pollution, ambient particulate matter pollution, and expanded antibiotic use could avert one under-5 death due to lower respiratory infection for every 4000 children treated in the countries with the highest lower respiratory infection burden Interpretation Our findings show substantial progress in the reduction of lower respiratory infection burden, but this progress has not been equal across locations, has been driven by decreases in several primary risk factors, and might require more effort among elderly adults By highlighting regions and populations with the highest burden, and the risk factors that could have the greatest effect, funders, policy makers, and programme implementers can more effectively reduce lower respiratory infections among the world's most susceptible populations Funding Bill & Melinda Gates Foundation
1,147 citations
University of Oxford1, University of Michigan2, Wellcome Trust Sanger Institute3, Amgen4, University of Cambridge5, University of Copenhagen6, University of Liverpool7, University of Freiburg8, Boston University9, University of Tartu10, Erasmus University Medical Center11, Leiden University Medical Center12, Pasteur Institute13, Icahn School of Medicine at Mount Sinai14, UCLA Medical Center15, Vanderbilt University Medical Center16, Wake Forest University17, National University of Singapore18, Imperial College London19, London North West Healthcare NHS Trust20, Charité21, Innsbruck Medical University22, Washington University in St. Louis23, Queen Mary University of London24, University of Southern Denmark25, National and Kapodistrian University of Athens26, Robertson Centre for Biostatistics27, University of Exeter28, Uppsala University29, University of Düsseldorf30, Steno Diabetes Center31, Aalborg University32, University of Eastern Finland33, Broad Institute34, Frederiksberg Hospital35, Lund University36, University of Bergen37, Technische Universität München38, University of North Carolina at Chapel Hill39, Ninewells Hospital40, University of Edinburgh41, University of Minnesota42, University of Glasgow43, Ludwig Maximilian University of Munich44, University of Iceland45, Aarhus University46, Stanford University47, Science for Life Laboratory48, University of Helsinki49, National Institutes of Health50, University of Dundee51, Harvard University52
TL;DR: Combining 32 genome-wide association studies with high-density imputation provides a comprehensive view of the genetic contribution to type 2 diabetes in individuals of European ancestry with respect to locus discovery, causal-variant resolution, and mechanistic insight.
Abstract: We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci, 135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency 2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).
1,136 citations
Humboldt University of Berlin1, Medical University of Graz2, Hospital Kuala Lumpur3, University of Zurich4, University of Cincinnati5, University of Southern Denmark6, Medical University of Silesia7, Humanitas University8, Charité9, Penn State Milton S. Hershey Medical Center10, Federal University of São Paulo11, Autonomous University of Barcelona12, St Thomas' Hospital13, Laval University14, Hiroshima University15, Medical University of South Carolina16, Hannover Medical School17, Campbelltown Hospital18, Mahidol University19, Royal Free Hospital20, University of Bari21, University Medical Center Groningen22, Johns Hopkins University23, University of Toronto24, Technion – Israel Institute of Technology25, Aarhus University Hospital26, Peking University27
TL;DR: In this paper, an evidence-and consensus-based guideline was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group.
Abstract: This evidence- and consensus-based guideline was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. The conference was held on 1 December 2016. It is a joint initiative of the Dermatology Sectionof the European Academy of Allergology and Clinical Immunology (EAACI), the EU-founded 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 48 delegates of 42 national and international societies. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria are disabling, impair quality of life and affect performance at work and school. 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.
819 citations
TL;DR: A critical review that summarizes state-of-the-art technologies for biogas upgrading and enhancement with particular attention to the emerging biological methanation processes.
815 citations
VU University Amsterdam1, Erasmus University Rotterdam2, Karolinska Institutet3, Charité4, Virginia Commonwealth University5, South London and Maudsley NHS Foundation Trust6, QIMR Berghofer Medical Research Institute7, King's College London8, University of Southern Denmark9, University of California, Riverside10, University of Southern California11, University of Minnesota12, University of Queensland13, University College London14, Johns Hopkins University15, University of California, Los Angeles16, University of Crete17, Veterans Health Administration18, Icahn School of Medicine at Mount Sinai19, Harvard University20, Yale University21, Haukeland University Hospital22, Trinity College, Dublin23, University of Edinburgh24, Hofstra University25, North Shore-LIJ Health System26, National Institutes of Health27, Oslo University Hospital28, University of Bergen29, National University of Ireland, Galway30, University of Helsinki31, University of Oslo32, Martin Luther University of Halle-Wittenberg33, Duke University34, National and Kapodistrian University of Athens35, Mental Health Research Institute36, University of Colorado Boulder37, Imperial College London38, University of Manchester39, Wellcome Trust40, Manchester Academic Health Science Centre41, Stanford University42, University of Oregon43, University of Toronto44, University of Michigan45, Erasmus University Medical Center46, Broad Institute47, University of North Carolina at Chapel Hill48
TL;DR: A large-scale genetic association study of intelligence identifies 190 new loci and implicates 939 new genes related to neurogenesis, neuron differentiation and synaptic structure, a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
Abstract: Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
800 citations
TL;DR: BCG vaccination induced genome-wide epigenetic reprograming of monocytes and protected against experimental infection with an attenuated yellow fever virus vaccine strain, with a key role for IL-1β as a mediator of trained immunity responses.
TL;DR: Some differences are identified compared to the previous overview regarding the recommendations for assessment of psychosocial factors, the use of some medications as well as an increasing amount of information regarding the types of exercise, mode of delivery, acupuncture, herbal medicines, and invasive treatments.
Abstract: The aim of this study was to provide an overview of the recommendations regarding the diagnosis and treatment contained in current clinical practice guidelines for patients with non-specific low back pain in primary care. We also aimed to examine how recommendations have changed since our last overview in 2010. The searches for clinical practice guidelines were performed for the period from 2008 to 2017 in electronic databases. Guidelines including information regarding either the diagnosis or treatment of non-specific low back pain, and targeted at a multidisciplinary audience in the primary care setting, were considered eligible. We extracted data regarding recommendations for diagnosis and treatment, and methods for development of guidelines. We identified 15 clinical practice guidelines for the management of low back pain in primary care. For diagnosis of patients with non-specific low back pain, the clinical practice guidelines recommend history taking and physical examination to identify red flags, neurological testing to identify radicular syndrome, use of imaging if serious pathology is suspected (but discourage routine use), and assessment of psychosocial factors. For treatment of patients with acute low back pain, the guidelines recommend reassurance on the favourable prognosis and advice on returning to normal activities, avoiding bed rest, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and weak opioids for short periods. For treatment of patients with chronic low back pain, the guidelines recommend the use of NSAIDs and antidepressants, exercise therapy, and psychosocial interventions. In addition, referral to a specialist is recommended in case of suspicion of specific pathologies or radiculopathy or if there is no improvement after 4 weeks. While there were a few discrepancies across the current clinical practice guidelines, a substantial proportion of recommendations was consistently endorsed. In the current review, we identified some differences compared to the previous overview regarding the recommendations for assessment of psychosocial factors, the use of some medications (e.g., paracetamol) as well as an increasing amount of information regarding the types of exercise, mode of delivery, acupuncture, herbal medicines, and invasive treatments. These slides can be retrieved under Electronic Supplementary Material.
ETH Zurich1, Northeastern University2, University of Georgia3, Macquarie University4, Stanford University5, National Institutes of Health6, Boston University7, Scripps Research Institute8, University of Maryland, College Park9, University of Pennsylvania10, University of Wisconsin-Madison11, Harvard University12, Memorial Sloan Kettering Cancer Center13, University of Illinois at Urbana–Champaign14, University of Salzburg15, University of Southern Denmark16, Northwestern University17, Massachusetts Institute of Technology18, University of California, San Francisco19, University of California, Los Angeles20, Royal Institute of Technology21, University of Washington22, Princeton University23, Saint Mary's College of California24, Salk Institute for Biological Studies25, Genentech26, University of Hamburg27, Yale University28, Cedars-Sinai Medical Center29, University of California, Berkeley30, Ohio State University31, University of Pittsburgh32, Baylor College of Medicine33
TL;DR: This work frames central issues regarding determination of protein-level variation and PTMs, including some paradoxes present in the field today, and uses this framework to assess existing data and ask the question, "How many distinct primary structures of proteins (proteoforms) are created from the 20,300 human genes?"
Abstract: Despite decades of accumulated knowledge about proteins and their post-translational modifications (PTMs), numerous questions remain regarding their molecular composition and biological function O
Haramaya University1, Université de Montréal2, Université de Moncton3, National Heart Foundation of Australia4, University of Ibadan5, University of La Frontera6, University of Cuenca7, University of Waterloo8, University of the Republic9, Ghent University10, National Taiwan University11, Karolinska Institutet12, University of Ottawa13, Technische Universität München14, University of Cape Town15, University of the Witwatersrand16, Swansea University17, Lithuanian Sports University18, Emory University19, University of Los Andes20, Central University of Venezuela21, Hong Kong Baptist University22, Qatar Airways23, University of Tartu24, University of Regina25, The Chinese University of Hong Kong26, Mahidol University27, Pennington Biomedical Research Center28, University of Queensland29, Seoul National University30, Queen's University31, Linköping University32, University of Medicine and Health Sciences33, University of Guadalajara34, Shanghai University of Sport35, National University of Science and Technology36, University of Primorska37, University of Porto38, University of Ghana39, University of Strathclyde40, University of Girona41, Carlos III Health Institute42, Universidade Federal de Santa Catarina43, Katholieke Universiteit Leuven44, University of South Australia45, University of Southern Denmark46, University of Auckland47, Bath Spa University48, University of Ljubljana49, Tribhuvan University50, Utrecht University51, J. F. Oberlin University52, University of Botswana53, Stamford University Bangladesh54, National Chung Hsing University55, University of Warsaw56
TL;DR: The present study provides rich new evidence showing that the situation regarding the physical activity of children and youth is a concern worldwide and strategic public investments to implement effective interventions to increase physical activity opportunities are needed.
Abstract: Background: Accumulating sufficient moderate to vigorous physical activity is recognized as a key determinant of physical, physiological, developmental, mental, cognitive, and social health among children and youth (aged 5–17 y). The Global Matrix 3.0ofReportCardgradesonphysicalactivitywasdevelopedtoachieveabetterunderstandingoftheglobalvariationinchildand youth physical activity and associated supports. Methods: Work groups from 49 countries followed harmonized procedures to develop their Report Cards by grading 10 common indicators using the best available data. The participating countries were divided into 3 categories using the United Nations’ human development index (HDI) classification (low or medium, high, and very high HDI). Results: A total of 490 grades, including 369 letter grades and 121 incomplete grades, were assigned by the 49 work groups. Overall, an average grade of “C−,”“D+,” and “C−” was obtained for the low and medium HDI countries, high HDI countries, and very high HDI countries, respectively. Conclusions: The present study provides rich new evidence showing that the situation regarding the physical activity of children and youth is a concern worldwide. Strategic public investments to implement effective interventions to increase physical activity opportunities are needed.
University Hospital Heidelberg1, Humboldt University of Berlin2, Charité3, University of Düsseldorf4, University of Southern Denmark5, Children's Hospital at Westmead6, Tohoku University7, Walton Centre8, Ruhr University Bochum9, Ludwig Maximilian University of Munich10, Johns Hopkins University11, John Radcliffe Hospital12, University of Barcelona13, Hannover Medical School14, Mayo Clinic15
TL;DR: In this article, the authors proposed indications for MOG-IgG testing based on expert consensus, and gave a list of conditions atypical for MG-EM (red flags) that should prompt physicians to challenge a positive MOG IgG test result, and provided recommendations regarding assay methodology, specimen sampling and data interpretation.
Abstract: Over the past few years, new-generation cell-based assays have demonstrated a robust association of autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis and brainstem encephalitis, as well as with acute disseminated encephalomyelitis (ADEM)-like presentations. Most experts now consider MOG-IgG-associated encephalomyelitis (MOG-EM) a disease entity in its own right, immunopathogenetically distinct from both classic multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorders (NMOSD). Owing to a substantial overlap in clinicoradiological presentation, MOG-EM was often unwittingly misdiagnosed as MS in the past. Accordingly, increasing numbers of patients with suspected or established MS are currently being tested for MOG-IgG. However, screening of large unselected cohorts for rare biomarkers can significantly reduce the positive predictive value of a test. To lessen the hazard of overdiagnosing MOG-EM, which may lead to inappropriate treatment, more selective criteria for MOG-IgG testing are urgently needed. In this paper, we propose indications for MOG-IgG testing based on expert consensus. In addition, we give a list of conditions atypical for MOG-EM (“red flags”) that should prompt physicians to challenge a positive MOG-IgG test result. Finally, we provide recommendations regarding assay methodology, specimen sampling and data interpretation.
TL;DR: It is inferred that dissolved oxygen led to the transformation of hopane precursors into rearranged hopanes during the early stages of diagenesis, and the hydrocarbon signatures point towards oxic bottom waters during the deposition of Unit 3 of the Xiamaling Formation, which is consistent with the earlier oxygen-minimum zone environmental interpretation of this Unit.
Abstract: The Xiamaling Formation in the North China Block contains a well-preserved 1400 Ma sedimentary sequence with a low degree of thermal maturity. Previous studies have confirmed the dynamic and complex nature of this evolving marine setting, including the existence of an oxygen-minimum zone, using multi-proxy approaches, including iron speciation, trace metal dynamics, and organic geochemistry. Here, we investigate the prevailing redox conditions during diagenesis via the biomarkers of rearranged hopanes from the finely laminated sediments of the organic-rich black shales in Units 2 and 3 of the Xiamaling Formation. We find that rearranged hopanes are prominent in the biomarker composition of the oxygen-minimum zone sediment, which is completely different from that of the sediment in the overlying anoxic strata. Since the transition process from hopanes to rearranged hopanes requires oxygen via oxidation at the C-l6 alkyl position of 17α(H)-hopanes, we infer that dissolved oxygen led to the transformation of hopane precursors into rearranged hopanes during the early stages of diagenesis. The use of hopanoid hydrocarbons as biomarkers of marine redox conditions has rarely been previously reported, and the hydrocarbon signatures point towards oxic bottom waters during the deposition of Unit 3 of the Xiamaling Formation, which is consistent with the earlier oxygen-minimum zone environmental interpretation of this Unit.
TL;DR: The fundamental building blocks essential for the realization of metasurfaces are discussed in order to elucidate the underlying physics of various physical realizations of both plasmonic and purely dielectric metAsurfaces.
Abstract: In the wake of intense research on metamaterials the two-dimensional analogue, known as metasurfaces, has attracted progressively increasing attention in recent years due to the ease of fabrication and smaller insertion losses, while enabling an unprecedented control over spatial distributions of transmitted and reflected optical fields. Metasurfaces represent optically thin planar arrays of resonant subwavelength elements that can be arranged in a strictly or quasi periodic fashion, or even in an aperiodic manner, depending on targeted optical wavefronts to be molded with their help. This paper reviews a broad subclass of metasurfaces, viz. gradient metasurfaces, which are devised to exhibit spatially varying optical responses resulting in spatially varying amplitudes, phases and polarizations of scattered fields. Starting with introducing the concept of gradient metasurfaces, we present classification of different metasurfaces from the viewpoint of their responses, differentiating electrical-dipole, geometric, reflective and Huygens' metasurfaces. The fundamental building blocks essential for the realization of metasurfaces are then discussed in order to elucidate the underlying physics of various physical realizations of both plasmonic and purely dielectric metasurfaces. We then overview the main applications of gradient metasurfaces, including waveplates, flat lenses, spiral phase plates, broadband absorbers, color printing, holograms, polarimeters and surface wave couplers. The review is terminated with a short section on recently developed nonlinear metasurfaces, followed by the outlook presenting our view on possible future developments and perspectives for future applications.
TL;DR: It is shown that the human gut microbiome can recover after a clinically relevant, broad-spectrum antibiotic treatment and characterization of the resistome indicates that antibiotic resistance genes can impact the recovery process.
Abstract: To minimize the impact of antibiotics, gut microorganisms harbour and exchange antibiotics resistance genes, collectively called their resistome. Using shotgun sequencing-based metagenomics, we analysed the partial eradication and subsequent regrowth of the gut microbiota in 12 healthy men over a 6-month period following a 4-day intervention with a cocktail of 3 last-resort antibiotics: meropenem, gentamicin and vancomycin. Initial changes included blooms of enterobacteria and other pathobionts, such as Enterococcus faecalis and Fusobacterium nucleatum, and the depletion of Bifidobacterium species and butyrate producers. The gut microbiota of the subjects recovered to near-baseline composition within 1.5 months, although 9 common species, which were present in all subjects before the treatment, remained undetectable in most of the subjects after 180 days. Species that harbour β-lactam resistance genes were positively selected for during and after the intervention. Harbouring glycopeptide or aminoglycoside resistance genes increased the odds of de novo colonization, however, the former also decreased the odds of survival. Compositional changes under antibiotic intervention in vivo matched results from in vitro susceptibility tests. Despite a mild yet long-lasting imprint following antibiotics exposure, the gut microbiota of healthy young adults are resilient to a short-term broad-spectrum antibiotics intervention and their antibiotics resistance gene carriage modulates their recovery processes.
TL;DR: A comprehensive literature search was conducted to determine if the use of the patient, intervention, comparison, outcome (PICO) model as a search strategy tool affects the quality of a literature search.
Abstract: Objective: This review aimed to determine if the use of the patient, intervention, comparison, outcome (PICO) model as a search strategy tool affects the quality of a literature search. Methods: A comprehensive literature search was conducted in PubMed, Embase, CINAHL, PsycINFO, Cochrane Library, Web of Science, Library and Information Science Abstracts (LISA), Scopus, and the National Library of Medicine (NLM) catalog up until January 9, 2017. Reference lists were scrutinized, and citation searches were performed on the included studies. The primary outcome was the quality of literature searches and the secondary outcome was time spent on the literature search when the PICO model was used as a search strategy tool, compared to the use of another conceptualizing tool or unguided searching. Results: A total of 2,163 records were identified, and after removal of duplicates and initial screening, 22 full-text articles were assessed. Of these, 19 studies were excluded and 3 studies were included, data were extracted, risk of bias was assessed, and a qualitative analysis was conducted. The included studies compared PICO to the PIC truncation or links to related articles in PubMed, PICOS, and sample, phenomenon of interest, design, evaluation, research type (SPIDER). One study compared PICO to unguided searching. Due to differences in intervention, no quantitative analysis was performed. Conclusions: Only few studies exist that assess the effect of the PICO model vis-a-vis other available models or even vis-a-vis the use of no model. Before implications for current practice can be drawn, well-designed studies are needed to evaluate the role of the tool used to devise a search strategy. This article has been approved for the Medical Library Association’s Independent Reading Program .
TL;DR: The aim was to provide an updated description of the register focusing on structure, content, and coverage since 1997.
Abstract: The Danish Medical Birth Register was established in 1973. It is a key component of the Danish health information system. The register enables monitoring of the health of pregnant women and their offspring, it provides data for quality assessment of the perinatal care in Denmark, and it is used extensively for research. The register underwent major changes in construction and content in 1997, and new variables have been added during the last 20 years. The aim was to provide an updated description of the register focusing on structure, content, and coverage since 1997. The register includes data on all births in Denmark and comprises primarily of data from the Danish National Patient Registry supplemented with forms on home deliveries and stillbirths. It contains information on maternal age provided by the Civil Registration System. Information on pre-pregnancy body mass index and smoking in first trimester is collected in early pregnancy (first antenatal visit). The individual-level data can be linked to other Danish health registers such as the National Patient Registry and the Danish National Prescription Registry. The register informs several other registers/databases such as the Danish Twin Registry and the Danish Fetal Medicine Database. Aggregated data can be publicly accessed on the Danish Health Data Authority web page (
www.esundhed.dk/sundhedsregistre/MFR
). Researchers can obtain access to individual-level pseudo-anonymised data via servers at Statistics Denmark and the Danish Health Data Authority.
TL;DR: The current state of knowledge of the complex interactions of commensal microorganisms with the intestinal mucosal barrier is discussed, and strategies used by pathogenic microorganisms to establish infection by either exploiting different epithelial cell lineages or disrupting the mucous layer are discussed.
Abstract: The intestinal mucosal barrier is composed of epithelial cells that are protected by an overlying host-secreted mucous layer and functions as the first line of defence against pathogenic and non-pathogenic microorganisms. Some microorganisms have evolved strategies to either survive in the mucosal barrier or circumvent it to establish infection. In this Review, we discuss the current state of knowledge of the complex interactions of commensal microorganisms with the intestinal mucosal barrier, and we discuss strategies used by pathogenic microorganisms to establish infection by either exploiting different epithelial cell lineages or disrupting the mucous layer, as well as the role of defects in mucus production in chronic disease.
TL;DR: An integrated fuzzy AHP-VIKOR approach-based framework for sustainable global supplier selection that takes sustainability risks from sub-suppliers (i.e., (1 + n) th-tier suppliers) into account is presented in this article.
TL;DR: Recommendations about 20 non-surgical interventions for recent onset non-specific low back pain (LBP) and lumbar radiculopathy based on two guidelines from the Danish Health Authority are summarized.
Abstract: To summarise recommendations about 20 non-surgical interventions for recent onset (<12 weeks) non-specific low back pain (LBP) and lumbar radiculopathy (LR) based on two guidelines from the Danish Health Authority. Two multidisciplinary working groups formulated recommendations based on the GRADE approach. Sixteen recommendations were based on evidence, and four on consensus. Management of LBP and LR should include information about prognosis, warning signs, and advise to remain active. If treatment is needed, the guidelines suggest using patient education, different types of supervised exercise, and manual therapy. The guidelines recommend against acupuncture, routine use of imaging, targeted treatment, extraforaminal glucocorticoid injection, paracetamol, NSAIDs, and opioids. Recommendations are based on low to moderate quality evidence or on consensus, but are well aligned with recommendations from international guidelines. The guideline working groups recommend that research efforts in relation to all aspects of management of LBP and LR be intensified.
Federal University of Paraná1, Oswaldo Cruz Foundation2, University of Nottingham3, Aston University4, University of Southampton5, University of São Paulo6, University of Gothenburg7, University of Oxford8, University of St Andrews9, Federal University of São Paulo10, London Metropolitan University11, University of Southern Denmark12, Technische Universität München13, University of Glasgow14, Oxford Brookes University15
TL;DR: Small sizes and the limited quantities that can usually be obtained from patient-derived samples pose a number of challenges to their isolation, study and characterization, which are discussed in this review.
Abstract: Extracellular Vesicles (EVs) are gaining interest as central players in liquid biopsies, with potential applications in diagnosis, prognosis and therapeutic guidance in most pathological conditions. These nanosized particles transmit signals determined by their protein, lipid, nucleic acid and sugar content, and the unique molecular pattern of EVs dictates the type of signal to be transmitted to recipient cells. However, their small sizes and the limited quantities that can usually be obtained from patient-derived samples pose a number of challenges to their isolation, study and characterization. These challenges and some possible options to overcome them are discussed in this review.
TL;DR: Trans-ethnic analyses of exome array data identify new risk loci for type 2 diabetes and fine-mapping analyses using genome-wide association data show that the index coding variants represent the likely causal variants at only a subset of these loci.
Abstract: We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
TL;DR: A global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends and a estimates of health-related SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous.
TL;DR: Using UbiSite, an antibody-based approach that specifically detects protein lysine and N-terminal ubiquitination, Blagoev and colleagues uncover lack of correlation between changes in protein Ubiquitination and abundance upon proteasome inhibition.
Abstract: Ubiquitination is a post-translational modification (PTM) that is essential for balancing numerous physiological processes. To enable delineation of protein ubiquitination at a site-specific level, we generated an antibody, denoted UbiSite, recognizing the C-terminal 13 amino acids of ubiquitin, which remain attached to modified peptides after proteolytic digestion with the endoproteinase LysC. Notably, UbiSite is specific to ubiquitin. Furthermore, besides ubiquitination on lysine residues, protein N-terminal ubiquitination is readily detected as well. By combining UbiSite enrichment with sequential LysC and trypsin digestion and high-accuracy MS, we identified over 63,000 unique ubiquitination sites on 9,200 proteins in two human cell lines. In addition to uncovering widespread involvement of this PTM in all cellular aspects, the analyses reveal an inverse association between protein N-terminal ubiquitination and acetylation, as well as a complete lack of correlation between changes in protein abundance and alterations in ubiquitination sites upon proteasome inhibition.
Medical University of Graz1, University of Southampton2, University Hospital Southampton NHS Foundation Trust3, Copenhagen University Hospital4, Swiss Institute of Allergy and Asthma Research5, University of Alcalá6, Jagiellonian University Medical College7, Medical University of Silesia8, University of Giessen9, University of Freiburg10, University of Ljubljana11, Medical University of Warsaw12, University of Tirana13, National and Kapodistrian University of Athens14, University of Southern Denmark15, University of Groningen16, Heidelberg University17, University of Cyprus18, Ludwig Maximilian University of Munich19, Ankara University20, Transylvania University21, Northern General Hospital22, Charité23, University of Messina24, National Institutes of Health25, Hospital Clínico San Carlos26, Odense University Hospital27, Wrocław Medical University28, University of Amsterdam29, University of Edinburgh30, Erasmus University Rotterdam31, University of Bradford32
TL;DR: This guideline aims to provide evidence‐based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta‐analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach.
Abstract: Hymenoptera venom allergy is a potentially life-threatening allergic reaction following a honeybee, vespid, or ant sting. Systemic-allergic sting reactions have been reported in up to 7.5% of adults and up to 3.4% of children. They can be mild and restricted to the skin or moderate to severe with a risk of life-threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H1 -antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence-based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta-analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included representation from a range of stakeholders. Venom immunotherapy is indicated in venom-allergic children and adults to prevent further moderate-to-severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline autoinjector. This guideline aims to give practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence-based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence.
TL;DR: The so-called PA health paradox, where workers in many occupations, such as construction, cleaning, refuse collection, elderly care, farming and manufacturing, are physically active for large parts of their working days, for most of the year, but have relatively poor health.
Abstract: Physical activity (PA) is well documented to improve health. However, this documentation is restricted to leisure time physical activity (LTPA; eg, sports, recreation and transportation). Increasing evidence shows that occupational physical activity (OPA) does not improve health.1 Actually, OPA can be detrimental. These contrasting health effects of LTPA and OPA constitute the so-called PA health paradox.2
For a considerable fraction of the adult population, work constitutes the main setting for PA. Workers in many occupations, such as construction, cleaning, refuse collection, elderly care, farming and manufacturing, are physically active for large parts of their working days, for most of the year. Despite this PA at work, these and other manual workers have relatively poor health.
Many epidemiological studies document that high OPA increases the risk for cardiovascular disease (CVD) and mortality outcomes, even after extensive adjustments for other risk factors including socioeconomic status, LTPA and other health behaviours.1 This increased risk from high OPA has been shown to be particularly pronounced among workers with low job resources, low cardiorespiratory fitness3 or pre-existing …
Christopher J L Murray1, Charlton S K H Callender1, Xie Rachel Kulikoff1, Vinay Srinivasan1 +1092 more•Institutions (424)
TL;DR: This work estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods and used the cohort-component method of population projection, with inputs of fertility, mortality, population, and migration data.