Showing papers by "University of Bergen 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
TL;DR: It is shown that the visual interpretability of ROC plots in the context of imbalanced datasets can be deceptive with respect to conclusions about the reliability of classification performance, owing to an intuitive but wrong interpretation of specificity.
Abstract: Binary classifiers are routinely evaluated with performance measures such as sensitivity and specificity, and performance is frequently illustrated with Receiver Operating Characteristics (ROC) plots. Alternative measures such as positive predictive value (PPV) and the associated Precision/Recall (PRC) plots are used less frequently. Many bioinformatics studies develop and evaluate classifiers that are to be applied to strongly imbalanced datasets in which the number of negatives outweighs the number of positives significantly. While ROC plots are visually appealing and provide an overview of a classifier's performance across a wide range of specificities, one can ask whether ROC plots could be misleading when applied in imbalanced classification scenarios. We show here that the visual interpretability of ROC plots in the context of imbalanced datasets can be deceptive with respect to conclusions about the reliability of classification performance, owing to an intuitive but wrong interpretation of specificity. PRC plots, on the other hand, can provide the viewer with an accurate prediction of future classification performance due to the fact that they evaluate the fraction of true positives among positive predictions. Our findings have potential implications for the interpretation of a large number of studies that use ROC plots on imbalanced datasets.
2,451 citations
University of Washington1, Institute for Health Metrics and Evaluation2, Iran University of Medical Sciences3, King's College London4, Arabian Gulf University5, University of North Texas6, Auckland University of Technology7, Alaska Native Tribal Health Consortium8, Columbia University9, Wuhan University10, Imperial College London11, University of Alabama at Birmingham12, University at Albany, SUNY13, City University of New York14, University of California, San Francisco15, Griffith University16, Environment Agency17, New York University18, Southern University College19, Emory University20, University of Ottawa21, Kosin University22, University of Toronto23, University of British Columbia24, United Arab Emirates University25, Albert Einstein College of Medicine26, University of São Paulo27, Nova Southeastern University28, University of Sydney29, Heidelberg University30, Case Western Reserve University31, Cancer Treatment Centers of America32, University of Oxford33, George Mason University34, James Cook University35, University of Trieste36, University of Calgary37, Wageningen University and Research Centre38, University of Gothenburg39, University of the Witwatersrand40, Harvard University41, Jackson State University42, University of Arizona43, University of Hong Kong44, Tehran University of Medical Sciences45, University of Western Australia46, Aintree University Hospitals NHS Foundation Trust47, Veterans Health Administration48, University of Colorado Denver49, University of Melbourne50, Royal Children's Hospital51, Australian National University52, University of Marburg53, Charité54, Health Canada55, College of Health Sciences, Bahrain56, Karolinska Institutet57, Northumbria University58, University of Edinburgh59, National Research University – Higher School of Economics60, Queen Mary University of London61, Addis Ababa University62, Northwestern University63, Northeastern University64, Mario Negri Institute for Pharmacological Research65, Arak University of Medical Sciences66, University of Nottingham67, University of Tokyo68, Public Health Foundation of India69, University of Groningen70, University of the Philippines Manila71, University of Bologna72, Kyung Hee University73, Brighton and Sussex Medical School74, Stavanger University Hospital75, University of Bergen76, University of Queensland77, National Centre for Disease Control78, University of Sheffield79, Universidad Autónoma Metropolitana80, University College London81, Genentech82, Universiti Tunku Abdul Rahman83, Norwegian Institute of Public Health84
TL;DR: To estimate mortality, incidence, years lived with disability, years of life lost, and disability-adjusted life-years for 28 cancers in 188 countries by sex from 1990 to 2013, the general methodology of the Global Burden of Disease 2013 study was used.
Abstract: Importance Cancer is among the leading causes of death worldwide. Current estimates of cancer burden in individual countries and regions are necessary to inform local cancer control strategies. Objective To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 28 cancers in 188 countries by sex from 1990 to 2013. Evidence Review The general methodology of the Global Burden of Disease (GBD) 2013 study was used. Cancer registries were the source for cancer incidence data as well as mortality incidence (MI) ratios. Sources for cause of death data include vital registration system data, verbal autopsy studies, and other sources. The MI ratios were used to transform incidence data to mortality estimates and cause of death estimates to incidence estimates. Cancer prevalence was estimated using MI ratios as surrogates for survival data; YLDs were calculated by multiplying prevalence estimates with disability weights, which were derived from population-based surveys; YLLs were computed by multiplying the number of estimated cancer deaths at each age with a reference life expectancy; and DALYs were calculated as the sum of YLDs and YLLs. Findings In 2013 there were 14.9 million incident cancer cases, 8.2 million deaths, and 196.3 million DALYs. Prostate cancer was the leading cause for cancer incidence (1.4 million) for men and breast cancer for women (1.8 million). Tracheal, bronchus, and lung (TBL) cancer was the leading cause for cancer death in men and women, with 1.6 million deaths. For men, TBL cancer was the leading cause of DALYs (24.9 million). For women, breast cancer was the leading cause of DALYs (13.1 million). Age-standardized incidence rates (ASIRs) per 100 000 and age-standardized death rates (ASDRs) per 100 000 for both sexes in 2013 were higher in developing vs developed countries for stomach cancer (ASIR, 17 vs 14; ASDR, 15 vs 11), liver cancer (ASIR, 15 vs 7; ASDR, 16 vs 7), esophageal cancer (ASIR, 9 vs 4; ASDR, 9 vs 4), cervical cancer (ASIR, 8 vs 5; ASDR, 4 vs 2), lip and oral cavity cancer (ASIR, 7 vs 6; ASDR, 2 vs 2), and nasopharyngeal cancer (ASIR, 1.5 vs 0.4; ASDR, 1.2 vs 0.3). Between 1990 and 2013, ASIRs for all cancers combined (except nonmelanoma skin cancer and Kaposi sarcoma) increased by more than 10% in 113 countries and decreased by more than 10% in 12 of 188 countries. Conclusions and Relevance Cancer poses a major threat to public health worldwide, and incidence rates have increased in most countries since 1990. The trend is a particular threat to developing nations with health systems that are ill-equipped to deal with complex and expensive cancer treatments. The annual update on the Global Burden of Cancer will provide all stakeholders with timely estimates to guide policy efforts in cancer prevention, screening, treatment, and palliation.
2,375 citations
QIMR Berghofer Medical Research Institute1, Garvan Institute of Medical Research2, University of Queensland3, Royal North Shore Hospital4, University of Western Sydney5, Fremantle Hospital6, Royal Adelaide Hospital7, Princess Alexandra Hospital8, University of Western Australia9, Glasgow Royal Infirmary10, Beatson West of Scotland Cancer Centre11, University of Bergen12, Dresden University of Technology13, Johns Hopkins University School of Medicine14, University of Texas MD Anderson Cancer Center15, Memorial Sloan Kettering Cancer Center16, University of Verona17, University of California, San Francisco18, University of Glasgow19
TL;DR: Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency, and 4 of 5 individuals with these measures of defective DNA maintenance responded to platinum therapy.
Abstract: Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded.
2,035 citations
TL;DR: In patients with type 2 diabetes and a recent acute coronary syndrome, the addition of lixisenatide to usual care did not significantly alter the rate of major cardiovascular events or other serious adverse events.
Abstract: BackgroundCardiovascular morbidity and mortality are higher among patients with type 2 diabetes, particularly those with concomitant cardiovascular diseases, than in most other populations. We assessed the effects of lixisenatide, a glucagon-like peptide 1–receptor agonist, on cardiovascular outcomes in patients with type 2 diabetes who had had a recent acute coronary event. MethodsWe randomly assigned patients with type 2 diabetes who had had a myocardial infarction or who had been hospitalized for unstable angina within the previous 180 days to receive lixisenatide or placebo in addition to locally determined standards of care. The trial was designed with adequate statistical power to assess whether lixisenatide was noninferior as well as superior to placebo, as defined by an upper boundary of the 95% confidence interval for the hazard ratio of less than 1.3 and 1.0, respectively, for the primary composite end point of cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable ...
1,745 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
TL;DR: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4ℓ decay channels.
Abstract: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4l decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is mH=125.09±0.21 (stat)±0.11 (syst) GeV.
1,567 citations
TL;DR: The presence of a lymphatic vessel network in the dura mater of the mouse brain is discovered and it is shown that these dural lymphatic vessels are important for the clearance of macromolecules from the brain.
Abstract: The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel network in the dura mater of the mouse brain. We show that dural lymphatic vessels absorb CSF from the adjacent subarachnoid space and brain interstitial fluid (ISF) via the glymphatic system. Dural lymphatic vessels transport fluid into deep cervical LNs (dcLNs) via foramina at the base of the skull. In a transgenic mouse model expressing a VEGF-C/D trap and displaying complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was attenuated and transport from the subarachnoid space into dcLNs was abrogated. Surprisingly, brain ISF pressure and water content were unaffected. Overall, these findings indicate that the mechanism of CSF flow into the dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. Importantly, these results call for a reexamination of the role of the lymphatic system in CNS physiology and disease.
Utrecht University1, Université catholique de Louvain2, Institut national de la recherche agronomique3, Centre national de la recherche scientifique4, Université du Québec à Montréal5, Royal Society for the Protection of Birds6, University of Cambridge7, University of Padua8, University of Sussex9, Natural Resources Canada10, Purdue University11, Helmholtz Centre for Environmental Research - UFZ12, Smithsonian Institution13, University of Neuchâtel14, University of Saskatchewan15, Washington State University16, University of Bergen17, University of Stirling18
TL;DR: In this paper, a review of the global literature explores these risks and show a growing body of evidence that persistent, low concentrations of these insecticides pose serious risks of undesirable environmental impacts.
Abstract: Since their discovery in the late 1980s, neonicotinoid pesticides have become the most widely used class of insecticides worldwide, with large-scale applications ranging from plant protection (crops, vegetables, fruits), veterinary products, and biocides to invertebrate pest control in fish farming. In this review, we address the phenyl-pyrazole fipronil together with neonicotinoids because of similarities in their toxicity, physicochemical profiles, and presence in the environment. Neonicotinoids and fipronil currently account for approximately one third of the world insecticide market; the annual world production of the archetype neonicotinoid, imidacloprid, was estimated to be ca. 20,000 tonnes active substance in 2010. There were several reasons for the initial success of neonicotinoids and fipronil: (1) there was no known pesticide resistance in target pests, mainly because of their recent development, (2) their physicochemical properties included many advantages over previous generations of insecticides (i.e., organophosphates, carbamates, pyrethroids, etc.), and (3) they shared an assumed reduced operator and consumer risk. Due to their systemic nature, they are taken up by the roots or leaves and translocated to all parts of the plant, which, in turn, makes them effectively toxic to herbivorous insects. The toxicity persists for a variable period of time—depending on the plant, its growth stage, and the amount of pesticide applied. A wide variety of applications are available, including the most common prophylactic non-Good Agricultural Practices (GAP) application by seed coating. As a result of their extensive use and physicochemical properties, these substances can be found in all environmental compartments including soil, water, and air. Neonicotinoids and fipronil operate by disrupting neural transmission in the central nervous system of invertebrates. Neonicotinoids mimic the action of neurotransmitters, while fipronil inhibits neuronal receptors. In doing so, they continuously stimulate neurons leading ultimately to death of target invertebrates. Like virtually all insecticides, they can also have lethal and sublethal impacts on non-target organisms, including insect predators and vertebrates. Furthermore, a range of synergistic effects with other stressors have been documented. Here, we review extensively their metabolic pathways, showing how they form both compound-specific and common metabolites which can themselves be toxic. These may result in prolonged toxicity. Considering their wide commercial expansion, mode of action, the systemic properties in plants, persistence and environmental fate, coupled with limited information about the toxicity profiles of these compounds and their metabolites, neonicotinoids and fipronil may entail significant risks to the environment. A global evaluation of the potential collateral effects of their use is therefore timely. The present paper and subsequent chapters in this review of the global literature explore these risks and show a growing body of evidence that persistent, low concentrations of these insecticides pose serious risks of undesirable environmental impacts.
Medical University of Vienna1, University of South Florida2, University of Bergen3, Laval University4, University of Washington5, University of Copenhagen6, Oswaldo Cruz Foundation7, University of Hong Kong8, Aarhus University9, Mahidol University10, University of British Columbia11, University of Hamburg12, Mackay Memorial Hospital13, Queen Mary University of London14, University of Melbourne15, University of Alabama16, Merck & Co.17
TL;DR: The 9vHPV vaccine prevented infection and disease related to HPV-31, 33, 45, 52, and 58 in a susceptible population and generated an antibody response to HPV -6, 11, 16, and 18 that was noninferior to that generated by the qHPV Vaccine.
Abstract: BackgroundThe investigational 9-valent viruslike particle vaccine against human papillomavirus (HPV) includes the HPV types in the quadrivalent HPV (qHPV) vaccine (6, 11, 16, and 18) and five additional oncogenic types (31, 33, 45, 52, and 58). Here we present the results of a study of the efficacy and immunogenicity of the 9vHPV vaccine in women 16 to 26 years of age. MethodsWe performed a randomized, international, double-blind, phase 2b–3 study of the 9vHPV vaccine in 14,215 women. Participants received the 9vHPV vaccine or the qHPV vaccine in a series of three intramuscular injections on day 1 and at months 2 and 6. Serum was collected for analysis of antibody responses. Swabs of labial, vulvar, perineal, perianal, endocervical, and ectocervical tissue were obtained and used for HPV DNA testing, and liquid-based cytologic testing (Papanicolaou testing) was performed regularly. Tissue obtained by means of biopsy or as part of definitive therapy (including a loop electrosurgical excision procedure and c...
TL;DR: The data indicate that the FTO allele associated with obesity represses mitochondrial thermogenesis in adipocyte precursor cells in a tissue-autonomous manner, and points to a pathway for adipocyte thermogenesis regulation involving ARID5B, rs1421085, IRX3, and IRX5, which, when manipulated, had pronounced pro-obesity and anti-ob obesity effects.
Abstract: BackgroundGenomewide association studies can be used to identify disease-relevant genomic regions, but interpretation of the data is challenging The FTO region harbors the strongest genetic association with obesity, yet the mechanistic basis of this association remains elusive MethodsWe examined epigenomic data, allelic activity, motif conservation, regulator expression, and gene coexpression patterns, with the aim of dissecting the regulatory circuitry and mechanistic basis of the association between the FTO region and obesity We validated our predictions with the use of directed perturbations in samples from patients and from mice and with endogenous CRISPR–Cas9 genome editing in samples from patients ResultsOur data indicate that the FTO allele associated with obesity represses mitochondrial thermogenesis in adipocyte precursor cells in a tissue-autonomous manner The rs1421085 T-to-C single-nucleotide variant disrupts a conserved motif for the ARID5B repressor, which leads to derepression of a pot
TL;DR: The discovery of ‘Lokiarchaeota’ is described, a novel candidate archaeal phylum which forms a monophyletic group with eukaryotes in phylogenomic analyses, and whose genomes encode an expanded repertoire of eUKaryotic signature proteins that are suggestive of sophisticated membrane remodelling capabilities.
Abstract: The origin of the eukaryotic cell remains one of the most contentious puzzles in modern biology. Recent studies have provided support for the emergence of the eukaryotic host cell from within the archaeal domain of life, but the identity and nature of the putative archaeal ancestor remain a subject of debate. Here we describe the discovery of 'Lokiarchaeota', a novel candidate archaeal phylum, which forms a monophyletic group with eukaryotes in phylogenomic analyses, and whose genomes encode an expanded repertoire of eukaryotic signature proteins that are suggestive of sophisticated membrane remodelling capabilities. Our results provide strong support for hypotheses in which the eukaryotic host evolved from a bona fide archaeon, and demonstrate that many components that underpin eukaryote-specific features were already present in that ancestor. This provided the host with a rich genomic 'starter-kit' to support the increase in the cellular and genomic complexity that is characteristic of eukaryotes.
TL;DR: In this paper, the authors conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts.
Abstract: The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.
TL;DR: In this paper, a clinical classification is used to stratify management based on simple (non-perforated) and complex (gangrenous or perforated), although many patients remain with an equivocal diagnosis, which is one of the most challenging dilemmas.
University Hospital Heidelberg1, German Cancer Research Center2, Heidelberg University3, Ludwig Maximilian University of Munich4, University of Würzburg5, University of Bonn6, University of Bergen7, Medical University of Vienna8, Max Planck Society9, University of Tübingen10, University of Calgary11
TL;DR: It is shown that many tumour cells in astrocytomas extend ultra-long membrane protrusions, and use these distinct tumour microtubes as routes for brain invasion, proliferation, and to interconnect over long distances, which develops functional multicellular network structures.
Abstract: Astrocytic brain tumours, including glioblastomas, are incurable neoplasms characterized by diffusely infiltrative growth. Here we show that many tumour cells in astrocytomas extend ultra-long membrane protrusions, and use these distinct tumour microtubes as routes for brain invasion, proliferation, and to interconnect over long distances. The resulting network allows multicellular communication through microtube-associated gap junctions. When damage to the network occurred, tumour microtubes were used for repair. Moreover, the microtube-connected astrocytoma cells, but not those remaining unconnected throughout tumour progression, were protected from cell death inflicted by radiotherapy. The neuronal growth-associated protein 43 was important for microtube formation and function, and drove microtube-dependent tumour cell invasion, proliferation, interconnection, and radioresistance. Oligodendroglial brain tumours were deficient in this mechanism. In summary, astrocytomas can develop functional multicellular network structures. Disconnection of astrocytoma cells by targeting their tumour microtubes emerges as a new principle to reduce the treatment resistance of this disease.
TL;DR: Patients with myasthenia gravis should be classified into subgroups to help with therapeutic decisions and prognosis, and additional immunomodulatory drugs are emerging, but therapeutic decisions are hampered by the scarcity of controlled studies.
Abstract: Myasthenia gravis is an autoimmune disease that is characterised by muscle weakness and fatigue, is B-cell mediated, and is associated with antibodies directed against the acetylcholine receptor, muscle-specific kinase (MUSK), lipoprotein-related protein 4 (LRP4), or agrin in the postsynaptic membrane at the neuromuscular junction. Patients with myasthenia gravis should be classified into subgroups to help with therapeutic decisions and prognosis. Subgroups based on serum antibodies and clinical features include early-onset, late-onset, thymoma, MUSK, LRP4, antibody-negative, and ocular forms of myasthenia gravis. Agrin-associated myasthenia gravis might emerge as a new entity. The prognosis is good with optimum symptomatic, immunosuppressive, and supportive treatment. Pyridostigmine is the preferred symptomatic treatment, and for patients who do not adequately respond to symptomatic therapy, corticosteroids, azathioprine, and thymectomy are first-line immunosuppressive treatments. Additional immunomodulatory drugs are emerging, but therapeutic decisions are hampered by the scarcity of controlled studies. Long-term drug treatment is essential for most patients and must be tailored to the particular form of myasthenia gravis.
Utrecht University1, Institut national de la recherche agronomique2, French Institute of Health and Medical Research3, University of Sussex4, Natural Resources Canada5, Purdue University6, Helmholtz Centre for Environmental Research - UFZ7, Smithsonian Institution8, University of Saskatchewan9, Université catholique de Louvain10, Washington State University11, University of Bergen12
TL;DR: Enough knowledge exists to conclude that existing levels of pollution with neonicotinoids and fipronil resulting from presently authorized uses frequently exceed the lowest observed adverse effect concentrations and are thus likely to have large-scale and wide ranging negative biological and ecological impacts on a wide range of non-target invertebrates in terrestrial, aquatic, marine and benthic habitats.
Abstract: We assessed the state of knowledge regarding the effects of large-scale pollution with neonicotinoid insecticides and fipronil on non-target invertebrate species of terrestrial, freshwater and marine environments. A large section of the assessment is dedicated to the state of knowledge on sublethal effects on honeybees (Apis mellifera) because this important pollinator is the most studied non-target invertebrate species. Lepidoptera (butterflies and moths), Lumbricidae (earthworms), Apoidae sensu lato (bumblebees, solitary bees) and the section “other invertebrates” review available studies on the other terrestrial species. The sections on freshwater and marine species are rather short as little is known so far about the impact of neonicotinoid insecticides and fipronil on the diverse invertebrate fauna of these widely exposed habitats. For terrestrial and aquatic invertebrate species, the known effects of neonicotinoid pesticides and fipronil are described ranging from organismal toxicology and behavioural effects to population-level effects. For earthworms, freshwater and marine species, the relation of findings to regulatory risk assessment is described. Neonicotinoid insecticides exhibit very high toxicity to a wide range of invertebrates, particularly insects, and field-realistic exposure is likely to result in both lethal and a broad range of important sublethal impacts. There is a major knowledge gap regarding impacts on the grand majority of invertebrates, many of which perform essential roles enabling healthy ecosystem functioning. The data on the few non-target species on which field tests have been performed are limited by major flaws in the outdated test protocols. Despite large knowledge gaps and uncertainties, enough knowledge exists to conclude that existing levels of pollution with neonicotinoids and fipronil resulting from presently authorized uses frequently exceed the lowest observed adverse effect concentrations and are thus likely to have large-scale and wide ranging negative biological and ecological impacts on a wide range of non-target invertebrates in terrestrial, aquatic, marine and benthic habitats.
University of East Anglia1, University of Oslo2, Commonwealth Scientific and Industrial Research Organisation3, University of Exeter4, Oak Ridge National Laboratory5, Woods Hole Research Center6, University of Bristol7, Scripps Institution of Oceanography8, National Oceanic and Atmospheric Administration9, Karlsruhe Institute of Technology10, University of Miami11, Centre national de la recherche scientifique12, University of Maryland, College Park13, Aix-Marseille University14, Flanders Marine Institute15, Alfred Wegener Institute for Polar and Marine Research16, Max Planck Society17, University of Illinois at Urbana–Champaign18, Plymouth Marine Laboratory19, Netherlands Environmental Assessment Agency20, Lawrence Berkeley National Laboratory21, ETH Zurich22, Bjerknes Centre for Climate Research23, University of Paris24, Woods Hole Oceanographic Institution25, Institute of Arctic and Alpine Research26, Japan Agency for Marine-Earth Science and Technology27, National Institute for Environmental Studies28, University of Washington29, University of Bergen30, Spanish National Research Council31, Montana State University32, Leibniz Institute for Baltic Sea Research33, Japan Meteorological Agency34, Leibniz Institute of Marine Sciences35, University of Bern36, Imperial College London37, Joint Institute for the Study of the Atmosphere and Ocean38, Lamont–Doherty Earth Observatory39, Hobart Corporation40, Wageningen University and Research Centre41, VU University Amsterdam42, University of New Hampshire43, Met Office44
TL;DR: In this article, the authors presented a methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics, and model estimates and their interpretation by a broad scientific community.
Abstract: Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and a methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics, and model estimates and their interpretation by a broad scientific community. We discuss changes compared to previous estimates as well as consistency within and among components, alongside methodology and data limitations. CO2 emissions from fossil fuels and industry (EFF) are based on energy statistics and cement production data, while emissions from land-use change (ELUC), mainly deforestation, are based on combined evidence from land-cover-change data, fire activity associated with deforestation, and models. The global atmospheric CO2 concentration is measured directly and its rate of growth (GATM) is computed from the annual changes in concentration. The mean ocean CO2 sink (SOCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in SOCEAN is evaluated with data products based on surveys of ocean CO2 measurements. The global residual terrestrial CO2 sink (SLAND) is estimated by the difference of the other terms of the global carbon budget and compared to results of independent dynamic global vegetation models forced by observed climate, CO2, and land-cover change (some including nitrogen–carbon interactions). We compare the mean land and ocean fluxes and their variability to estimates from three atmospheric inverse methods for three broad latitude bands. All uncertainties are reported as ±1σ, reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. For the last decade available (2005–2014), EFF was 9.0 ± 0.5 GtC yr−1, ELUC was 0.9 ± 0.5 GtC yr−1, GATM was 4.4 ± 0.1 GtC yr−1, SOCEAN was 2.6 ± 0.5 GtC yr−1, and SLAND was 3.0 ± 0.8 GtC yr−1. For the year 2014 alone, EFF grew to 9.8 ± 0.5 GtC yr−1, 0.6 % above 2013, continuing the growth trend in these emissions, albeit at a slower rate compared to the average growth of 2.2 % yr−1 that took place during 2005–2014. Also, for 2014, ELUC was 1.1 ± 0.5 GtC yr−1, GATM was 3.9 ± 0.2 GtC yr−1, SOCEAN was 2.9 ± 0.5 GtC yr−1, and SLAND was 4.1 ± 0.9 GtC yr−1. GATM was lower in 2014 compared to the past decade (2005–2014), reflecting a larger SLAND for that year. The global atmospheric CO2 concentration reached 397.15 ± 0.10 ppm averaged over 2014. For 2015, preliminary data indicate that the growth in EFF will be near or slightly below zero, with a projection of −0.6 [range of −1.6 to +0.5] %, based on national emissions projections for China and the USA, and projections of gross domestic product corrected for recent changes in the carbon intensity of the global economy for the rest of the world. From this projection of EFF and assumed constant ELUC for 2015, cumulative emissions of CO2 will reach about 555 ± 55 GtC (2035 ± 205 GtCO2) for 1870–2015, about 75 % from EFF and 25 % from ELUC. This living data update documents changes in the methods and data sets used in this new carbon budget compared with previous publications of this data set (Le Quere et al., 2015, 2014, 2013). All observations presented here can be downloaded from the Carbon Dioxide Information Analysis Center (doi:10.3334/CDIAC/GCP_2015).
TL;DR: It is concluded that haploinsufficiency of TBK1 causes ALS and fronto-temporal dementia.
Abstract: Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative syndrome hallmarked by adult-onset loss of motor neurons. We performed exome sequencing of 252 familial ALS (fALS) and 827 control individuals. Gene-based rare variant analysis identified an exome-wide significant enrichment of eight loss-of-function (LoF) mutations in TBK1 (encoding TANK-binding kinase 1) in 13 fALS pedigrees. No enrichment of LoF mutations was observed in a targeted mutation screen of 1,010 sporadic ALS and 650 additional control individuals. Linkage analysis in four families gave an aggregate LOD score of 4.6. In vitro experiments confirmed the loss of expression of TBK1 LoF mutant alleles, or loss of interaction of the C-terminal TBK1 coiled-coil domain (CCD2) mutants with the TBK1 adaptor protein optineurin, which has been shown to be involved in ALS pathogenesis. We conclude that haploinsufficiency of TBK1 causes ALS and fronto-temporal dementia.
TL;DR: A systematic literature search was conducted in PubMed Cochrane Library and CABI databases to evaluate the effect of breastfeeding on longterm (breast carcinoma ovarian carcinoma osteoporosis and type 2 diabetes mellitus) and short-term (lactational amenorrhoea post-partum depression postpartum weight change) maternal health outcomes.
Abstract: Aim: To evaluate the effect of breastfeeding on long-term (breast carcinoma ovarian carcinoma osteoporosis and type 2 diabetes mellitus) and short-term (lactational amenorrhoea postpartum depression postpartum weight change) maternal health outcomes. Methods: A systematic literature search was conducted in PubMed Cochrane Library and CABI databases. Outcome estimates of odds ratios or relative risks or standardised mean differences were pooled. In cases of heterogeneity subgroup analysis and meta-regression were explored. Results: Breastfeeding >12 months was associated with reduced risk of breast and ovarian carcinoma by 26% and 37% respectively. No conclusive evidence of an association between breastfeeding and bone mineral density was found. Breastfeeding was associated with 32% lower risk of type 2 diabetes. Exclusive breastfeeding and predominant breastfeeding were associated with longer duration of amenorrhoea. Shorter duration of breastfeeding was associated with higher risk of postpartum depression. Evidence suggesting an association of breastfeeding with postpartum weight change was lacking. Conclusion: This review supports the hypothesis that breastfeeding is protective against breast and ovarian carcinoma and exclusive breastfeeding and predominant breastfeeding increase the duration of lactational amenorrhoea. There is evidence that breastfeeding reduces the risk of type 2 diabetes. However an association between breastfeeding and bone mineral density or maternal depression or postpartum weight change was not evident. ©2015 The Authors. Open Access.
University of Edinburgh1, University of Bergen2, Harvard University3, University of Michigan4, Erasmus University Rotterdam5, Utrecht University6, University of Düsseldorf7, Katholieke Universiteit Leuven8, Swiss Tropical and Public Health Institute9, University of Basel10, National Institute for Health and Welfare11, University of Helsinki12, University of Maryland, Baltimore13, University of Sheffield14
TL;DR: An enduring positive association between long-term exposure to air pollution and total and cardiovascular mortality is established, mainly due to coronary artery disease.
Abstract: Air pollution has wide-ranging and deleterious effects on human health and is a major issue for the global community. The Global Burden of Disease study has described the worldwide impact of air pollution with as many as 3.1 million of 52.8 million all-cause and all-age deaths being attributable to ambient air pollution in the year 2010.1 Moreover, ambient air pollution ranked ninth among the modifiable disease risk factors, being listed above other commonly recognized factors, such as low physical activity, a high-sodium diet, high cholesterol, and drug use. Finally, air pollution accounts for 3.1% of global disability-adjusted life years, an index that measures the time spent in states of reduced health.1
Although it is intuitive that air pollution is an important stimulus for the development and exacerbation of respiratory diseases, such as asthma, chronic obstructive pulmonary disease, and lung cancer, there is generally less public awareness of its substantial impact on cardiovascular disease. Historically, the 1952 Great Smog of London led to an increase in cardiovascular death as well as deaths due to respiratory disease. Subsequent studies in the 1990s, such as the Harvard Six Cities2 and American Cancer Society cohort studies,2,3 established an enduring positive association between long-term exposure to air pollution and total and cardiovascular mortality, mainly due to coronary artery disease.4 In Europe, the first study that supported this association between long-term exposure and mortality was the Netherlands Cohort Study on Diet and Cancer.5 Associations with cardiovascular morbidity and mortality are also seen with short-term (e.g. day-to-day fluctuations) pollutant exposures of residents in large urban areas worldwide, including the United States of America6 …
TL;DR: A review of online social network site addiction can be found in this paper, which suggests that SNS addiction shares many similarities with those of other addictions, including tolerance, withdrawal, conflict, salience, relapse, and mood modification.
Abstract: Research into online social network site (SNS) addiction (i.e., excessive and compulsive online social networking) has expanded over the last years. This paper aims to give a review of this research. Although not formally recognized as a diagnosis, SNS addiction shares many similarities with those of other addictions, including tolerance, withdrawal, conflict, salience, relapse, and mood modification. Several screening instruments to identify SNS addicts have been developed—approaching the phenomenon in various ways, disclosing a conceptual and empirical obscurity in this field. Theoretical and empirical models suggest that SNS addiction is molded by several factors; including dispositional, sociocultural, and behavioral reinforcement. Also, empirical findings generally unveil that SNS addiction is related to impaired health and well-being. There has been little, if any, empirical testing of prevention or treatment for this behavioral addiction, although certain self-help strategies, therapies, and interventions have been proposed.
TL;DR: The emergence of diverse subsets of human NK cells selectively lacking expression of signaling proteins after human cytomegalovirus (HCMV) infection is described, uncovering a spectrum of epigenetically unique adaptive NK cell subsets that diversify in response to viral infection and have distinct functional capabilities compared to canonical NK cells.
TL;DR: The evidence for effects of optimal breastfeeding on all‐cause and infection‐related mortality in infants and children aged 0–23 months is synthesised.
Abstract: Social inequality in BMI change and gestational weight gain in the first and second pregnancy among women in Sweden
TL;DR: TMB as discussed by the authors is an open source R package that enables quick implementation of complex nonlinear random effect (latent variable) models in a manner similar to the established AD Model Builder package (ADMB, this http URL).
Abstract: TMB is an open source R package that enables quick implementation of complex nonlinear random effect (latent variable) models in a manner similar to the established AD Model Builder package (ADMB, this http URL). In addition, it offers easy access to parallel computations. The user defines the joint likelihood for the data and the random effects as a C++ template function, while all the other operations are done in R; e.g., reading in the data. The package evaluates and maximizes the Laplace approximation of the marginal likelihood where the random effects are automatically integrated out. This approximation, and its derivatives, are obtained using automatic differentiation (up to order three) of the joint likelihood. The computations are designed to be fast for problems with many random effects (~10^6) and parameters (~10^3). Computation times using ADMB and TMB are compared on a suite of examples ranging from simple models to large spatial models where the random effects are a Gaussian random field. Speedups ranging from 1.5 to about 100 are obtained with increasing gains for large problems. The package and examples are available at this http URL.
TL;DR: PeptideShaker is described, a proteomics informatics software that can be used at any stage in the proteomics data cycle for the analysis and interpretation of primary data, enabling data sharing and dissemination and re-analysis of publicly available proteomicsData.
Abstract: VOLUME 33 NUMBER 1 JANUARY 2015 NATURE BIOTECHNOLOGY methods (Supplementary Note 1). The reliability of all statistical metrics has been validated in detail using the complex Pyrococcus furiosus standard with an entrapment database for FDR accuracy verification14 (Supplementary Note 1). PeptideShaker’s user-oriented interface is divided into nine linked tabs, such that selections in any one tab are automatically propagated to the other tabs. The initial display is the ‘Overview’ tab (Fig. 2), which shows a single interactive view that includes identified proteins, peptides and spectra. Additional tabs feature specific aspects of a typical proteomics analysis pipeline, including spectrum identification details (with an emphasis on multiple search engine comparison), protein fractionation analysis, modification site localization analysis, protein three-dimensional structures (with mapped modifications), link to functional annotation resources, gene ontology analysis, identification validation and quality control (Supplementary Note 1). Numerous visualizations are provided in PeptideShaker to help the user understand the significance of the underlying data. For example, the software takes advantage of the identification multiplicity typical of proteomics experiments by visualizing multiple recorded PSMs15 for a given peptide or by displaying posttranslational modification localization both within and across spectra (Supplementary Note 1). Moreover, PeptideShaker provides chromosome and gene mapping, modification analysis and intuitive coverage annotation on the sequence of every identified protein, meeting the goals of the Human Proteome Project16. Results from PeptideShaker can be readily submitted to PRIDE and ProteomeXchange using the built-in PRIDE and mzIdentML17 exports; at the time of writing, this has already resulted in 52 publicly available PeptideShaker-derived ProteomeXchange assays. Other export options include spreadsheet-compatible text files, a descriptive certificate of analysis, highresolution image formats for all displayed graphics, exports to common graph database formats including Cytoscape (http:// cytoscape.org), and export to the widely used Nonlinear (http://www.nonlinear.com) Progenesis liquid chromatography (LC)-MS package for label-free quantification. To the Editor: Mass spectrometry (MS)-based proteomics is commonly used to identify and quantify the hundreds to thousands of proteins that are present in complex biological samples. Widespread data sharing via publicly accessible repositories, such as PRIDE1, has now become standard practice, aided by robust user-oriented tools for data submission2,3 and inspection4 and bolstered by the advent of the ProteomeXchange initiative5. Importantly, repository data sharing has enabled the first high-profile studies in which the repurposing of publicly available proteomics data has revealed new biological insights6,7. However, proteomics data processing and (re-)analysis currently remain far from routine practice. There is a pressing need for a user-friendly, open source tool that empowers users to carry out state-of-the-art proteomics data analysis at any stage in the data life cycle8,9. To maximize the value of public proteomics data, reuse and repurposing must become straightforward, allowing the completion of the proteomics data cycle. Here we describe PeptideShaker (http://peptideshaker.googlecode.com), a proteomics informatics software that can be used at any stage in the proteomics data cycle for the analysis and interpretation of primary data, enabling data sharing and dissemination and re-analysis of publicly available proteomics data. Importantly, PeptideShaker can work with the combined output of multiple identification algorithms (Fig. 1). To identify peptides and proteins PeptideShaker uses the target-decoy search strategy10 to estimate posterior error probabilities and uses these to unify the peptide-to-spectrum match (PSM) lists of different search engines, thus increasing the confidence and sensitivity of hits compared with single-search-engine processing11,12. PeptideShaker provides statistical confidence estimates for each peptide and protein, taking into account protein inference issues13. Furthermore, as well as providing false discovery rates (FDRs) at the PSM, peptide and protein levels, PeptideShaker calculates reliable false negative rates (FNRs), providing the user with a novel and highly useful interface to filter results according to an FDR-versus-FNR cost-benefit rationale that has so far been absent from proteomics. This filter for specificity and sensitivity includes interactive graphs providing immediate feedback on the values of FDR and FNR for PSMs, peptides and proteins at any chosen threshold. In addition to these identification reliability measures, PeptideShaker also provides confident modification site inference using the latest localization PeptideShaker enables reanalysis of MS-derived proteomics data sets
TL;DR: In this article, a conceptual framework for food system resilience is developed, and how this could be implemented through stakeholder participation to ensure food security for everyone. But, the framework is limited to a single region and does not consider other regions of the world.