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1.	Kehoe, Laura, et al. (författare) Make EU trade with Brazil sustainable 2019 Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341- Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
2.	Allan, Eric, et al. (författare) Interannual variation in land-use intensity enhances grassland multidiversity 2014 Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 111:1, s. 308-313 Tidskriftsartikel (refereegranskat)abstract Although temporal heterogeneity is a well-accepted driver of biodiversity, effects of interannual variation in land-use intensity (LUI) have not been addressed yet. Additionally, responses to land use can differ greatly among different organisms; therefore, overall effects of land-use on total local biodiversity are hardly known. To test for effects of LUI (quantified as the combined intensity of fertilization, grazing, and mowing) and interannual variation in LUI (SD in LUI across time), we introduce a unique measure of whole-ecosystem biodiversity, multidiversity. This synthesizes individual diversity measures across up to 49 taxonomic groups of plants, animals, fungi, and bacteria from 150 grasslands. Multidiversity declined with increasing LUI among grasslands, particularly for rarer species and aboveground organisms, whereas common species and belowground groups were less sensitive. However, a high level of interannual variation in LUI increased overall multidiversity at low LUI and was even more beneficial for rarer species because it slowed the rate at which the multidiversity of rare species declined with increasing LUI. In more intensively managed grasslands, the diversity of rarer species was, on average, 18% of the maximum diversity across all grasslands when LUI was static over time but increased to 31% of the maximum when LUI changed maximally over time. In addition to decreasing overall LUI, we suggest varying LUI across years as a complementary strategy to promote biodiversity conservation.
3.	Karlina, Ruth, et al. (författare) Identification and characterization of distinct brown adipocyte subtypes in C57BL/6J mice 2021 Ingår i: Life Science Alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 4:1 Tidskriftsartikel (refereegranskat)abstract Brown adipose tissue (BAT) plays an important role in the regulation of body weight and glucose homeostasis. Although increasing evidence supports white adipose tissue heterogeneity, little is known about heterogeneity within murine BAT. Recently, UCP1 high and low expressing brown adipocytes were identified, but a developmental origin of these subtypes has not been studied. To obtain more insights into brown preadipocyte heterogeneity, we use single-cell RNA sequencing of the BAT stromal vascular fraction of C57/BL6 mice and characterize brown preadipocyte and adipocyte clonal cell lines. Statistical analysis of gene expression profiles from brown preadipocyte and adipocyte clones identify markers distinguishing brown adipocyte subtypes. We confirm the presence of distinct brown adipocyte populations in vivo using the markers EIF5, TCF25, and BIN1. We also demonstrate that loss of Bin1 enhances UCP1 expression and mitochondrial respiration, suggesting that BIN1 marks dormant brown adipocytes. The existence of multiple brown adipocyte subtypes suggests distinct functional properties of BAT depending on its cellular composition, with potentially distinct functions in thermogenesis and the regulation of whole body energy homeostasis.
4.	Lieske, Julia, et al. (författare) On-chip crystallization for serial crystallography experiments and on-chip ligand-binding studies 2019 Ingår i: IUCrJ. - 2052-2525. ; 6:4, s. 714-728 Tidskriftsartikel (refereegranskat)abstract Efficient and reliable sample delivery has remained one of the bottlenecks for serial crystallography experiments. Compared with other methods, fixed-target sample delivery offers the advantage of significantly reduced sample consumption and shorter data collection times owing to higher hit rates. Here, a new method of on-chip crystallization is reported which allows the efficient and reproducible growth of large numbers of protein crystals directly on micro-patterned silicon chips for in-situ serial crystallography experiments. Crystals are grown by sitting-drop vapor diffusion and previously established crystallization conditions can be directly applied. By reducing the number of crystal-handling steps, the method is particularly well suited for sensitive crystal systems. Excessive mother liquor can be efficiently removed from the crystals by blotting, and no sealing of the fixed-target sample holders is required to prevent the crystals from dehydrating. As a consequence, 'naked' crystals are obtained on the chip, resulting in very low background scattering levels and making the crystals highly accessible for external manipulation such as the application of ligand solutions. Serial diffraction experiments carried out at cryogenic temperatures at a synchrotron and at room temperature at an X-ray free-electron laser yielded high-quality X-ray structures of the human membrane protein aquaporin 2 and two new ligand-bound structures of thermolysin and the human kinase DRAK2. The results highlight the applicability of the method for future high-throughput on-chip screening of pharmaceutical compounds.
5.	Wang, Haidong, et al. (författare) Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015 : the Global Burden of Disease Study 2015. 2016 Ingår i: The lancet. HIV. - : Elsevier. - 2352-3018. ; 3:8, s. e361-e387 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.METHODS: For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification.FINDINGS: Global HIV incidence reached its peak in 1997, at 3·3 million new infections (95% uncertainty interval [UI] 3·1-3·4 million). Annual incidence has stayed relatively constant at about 2·6 million per year (range 2·5-2·8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38·8 million (95% UI 37·6-40·4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1·8 million deaths (95% UI 1·7-1·9 million) in 2005, to 1·2 million deaths (1·1-1·3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections.INTERPRETATION: Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030.
6.	Abercrombie, Daniel, et al. (författare) Dark Matter benchmark models for early LHC Run-2 Searches : Report of the ATLAS/CMS Dark Matter Forum 2020 Ingår i: Physics of the Dark Universe. - : Elsevier BV. - 2212-6864. ; 27 Tidskriftsartikel (refereegranskat)abstract This document is the final report of the ATLAS-CMS Dark Matter Forum, a forum organized by the ATLAS and CMS collaborations with the participation of experts on theories of Dark Matter, to select a minimal basis set of dark matter simplified models that should support the design of the early LHC Run-2 searches. A prioritized, compact set of benchmark models is proposed, accompanied by studies of the parameter space of these models and a repository of generator implementations. This report also addresses how to apply the Effective Field Theory formalism for collider searches and present the results of such interpretations.
7.	Arrhenius, Karine, et al. (författare) Analytical methods for the determination of oil carryover from CNG/biomethane refueling stations recovered in a solvent 2020 Ingår i: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 10:20, s. 11907-11917 Tidskriftsartikel (refereegranskat)abstract Vehicle gas is often compressed to about 200 bar at the refueling station prior to charging to the vehicle's tank. If a high amount of oil is carried over to the gas, it may cause damage to the vehicles; it is therefore necessary to accurately measure oil carryover. In this paper, three analytical methods for accurate quantification of the oil content are presented whereby two methods are based on gas chromatography and one on FTIR. To better evaluate the level of complexity of the matrix, 10 different compressor oils in use at different refueling stations were initially collected and analysed with GC and FTIR to identify their analytical traces. The GC traces could be divided into three different profiles: oils exhibiting some well resolved peaks, oils exhibiting globally unresolved peaks with some dominant peaks on top of the hump and oils exhibiting globally unresolved peaks. After selection of three oils; one oil from each type, the three methods were evaluated with regards to the detection and quantification limits, the working range, precision, trueness and robustness. The evaluation of the three measurement methods demonstrated that any of these three methods presented were suitable for the quantification of compressor oil for samples. The FTIR method and the GC/MS method both resulted in measurement uncertainties close to 20% rel. while the GC/FID method resulted in a higher measurement uncertainty (U = 30% rel.).
8.	Bach, Lennart T, et al. (författare) Influence of Ocean Acidification on a Natural Winter-to-Summer Plankton Succession: First Insights from a Long-Term Mesocosm Study Draw Attention to Periods of Low Nutrient Concentrations 2016 Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:8 Tidskriftsartikel (refereegranskat)abstract Every year, the oceans absorb about 30% of anthropogenic carbon dioxide (CO2) leading to a re-equilibration of the marine carbonate system and decreasing seawater pH. Today, there is increasing awareness that these changes-summarized by the term ocean acidification (OA)-could differentially affect the competitive ability of marine organisms, thereby provoking a restructuring of marine ecosystems and biogeochemical element cycles. In winter 2013, we deployed ten pelagic mesocosms in the Gullmar Fjord at the Swedish west coast in order to study the effect of OA on plankton ecology and biogeochemistry under close to natural conditions. Five of the ten mesocosms were left unperturbed and served as controls (similar to 380 mu atm pCO(2)), whereas the others were enriched with CO2-saturated water to simulate realistic end-of-the-century carbonate chemistry conditions (mu 760 mu atm pCO(2)). We ran the experiment for 113 days which allowed us to study the influence of high CO2 on an entire winter-to-summer plankton succession and to investigate the potential of some plankton organisms for evolutionary adaptation to OA in their natural environment. This paper is the first in a PLOS collection and provides a detailed overview on the experimental design, important events, and the key complexities of such a "long-term mesocosm" approach. Furthermore, we analyzed whether simulated end-of-the-century carbonate chemistry conditions could lead to a significant restructuring of the plankton community in the course of the succession. At the level of detail analyzed in this overview paper we found that CO2-induced differences in plankton community composition were non-detectable during most of the succession except for a period where a phytoplankton bloom was fueled by remineralized nutrients. These results indicate: (1) Long-term studies with pelagic ecosystems are necessary to uncover OA-sensitive stages of succession. (2) Plankton communities fueled by regenerated nutrients may be more responsive to changing carbonate chemistry than those having access to high inorganic nutrient concentrations and may deserve particular attention in future studies.
9.	Beal, Jacob, et al. (författare) Robust estimation of bacterial cell count from optical density 2020 Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1 Tidskriftsartikel (refereegranskat)abstract Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
10.	Berndtsson, Tim, 1989- (författare) The Order and the Archive : Masonic Archiving as Idea and Practice in 18th Century Europe 2018 Licentiatavhandling (övrigt vetenskapligt/konstnärligt)
11.	Berndtsson, Tim, 1989- (författare) The Order and the Archive : Freemasonic Archival Culture in Eighteenth-Century Europe 2020 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract This study explores how eighteenth-century European Masons created archives, and how these archives in turn created Masons. It is an exploration of how a masonic archival culture was formed, and how different ideas, hopes, and anxieties were co-produced along with the records and manuscripts kept by masonic associations. At stake in these archival practices was the goal of establishing “order”. I draw theoretical inspiration from works by e.g. Markus Friedrich, Randolph C. Head, and Cornelia Vismann, all of whom have articulated a process-oriented view of archival history. By using materials found in historical collections from masonic associations in present-day archives, especially registers and archival regulations, I provide an overview of the documents accumulated in masonic archives and collections. Through studying not only the Masons’ practices of archiving and collecting, but also their discourses about “collections” and “archives”, I can show how archiving filled administrative functions but also had implications for the kind of knowledge that Masons found their order to be a container for. A historical exposé of archival history in a period stretching from early modernity to the modern period situates the archives of the masonic associations in a wider cultural-historical context. A general investigation of different repositories and means for archival accumulation within masonic associations shows how their record-keeping was frequently combined with collecting, and how both practices served to establish order at different levels. Two case studies, about the German based Order of the Strict Observance, and the Swedish Order of Freemasons, respectively, illustrate the effects of the notion of archived “secrets”, and explore the relation between masonic archiving and state administration. The final chapter discusses how masonic archives had an impact in the sphere of published literature: on the one hand, as a source of materials for sensationalist “exposures” and internal masonic-historiography and, on the other, as a theme for fantasies in literary fiction.My claim is that archival practices stood at the centre, both of organisational efforts of building wide organisational networks with the capacity for strategic action, and of personal quests to acquire the “higher knowledge” believed to be on the orders’ inside.
12.	Birkhofer, Klaus, et al. (författare) General Relationships between Abiotic Soil Properties and Soil Biota across Spatial Scales and Different Land-Use Types. 2012 Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:8 Tidskriftsartikel (refereegranskat)abstract Very few principles have been unraveled that explain the relationship between soil properties and soil biota across large spatial scales and different land-use types. Here, we seek these general relationships using data from 52 differently managed grassland and forest soils in three study regions spanning a latitudinal gradient in Germany. We hypothesize that, after extraction of variation that is explained by location and land-use type, soil properties still explain significant proportions of variation in the abundance and diversity of soil biota. If the relationships between predictors and soil organisms were analyzed individually for each predictor group, soil properties explained the highest amount of variation in soil biota abundance and diversity, followed by land-use type and sampling location. After extraction of variation that originated from location or land-use, abiotic soil properties explained significant amounts of variation in fungal, meso- and macrofauna, but not in yeast or bacterial biomass or diversity. Nitrate or nitrogen concentration and fungal biomass were positively related, but nitrate concentration was negatively related to the abundances of Collembola and mites and to the myriapod species richness across a range of forest and grassland soils. The species richness of earthworms was positively correlated with clay content of soils independent of sample location and land-use type. Our study indicates that after accounting for heterogeneity resulting from large scale differences among sampling locations and land-use types, soil properties still explain significant proportions of variation in fungal and soil fauna abundance or diversity. However, soil biota was also related to processes that act at larger spatial scales and bacteria or soil yeasts only showed weak relationships to soil properties. We therefore argue that more general relationships between soil properties and soil biota can only be derived from future studies that consider larger spatial scales and different land-use types.
13.	Birkhofer, Klaus, et al. (författare) Soil fauna feeding activity in temperate grassland soils increases with legume and grass species richness 2011 Ingår i: Soil Biology & Biochemistry. - : Elsevier BV. - 0038-0717. ; 43:10, s. 2200-2207 Tidskriftsartikel (refereegranskat)abstract Edaphic fauna contributes to important ecosystem functions in grassland soils such as decomposition and nutrient mineralization. Since this functional role is likely to be altered by global change and associated shifts in plant communities, a thorough understanding of large scale drivers on below-ground processes independent of regional differences in soil type or climate is essential. We investigated the relationship between abiotic (soil properties, management practices) and biotic (plant functional group composition, vegetation characteristics, soil fauna abundance) predictors and feeding activity of soil fauna after accounting for sample year and study region. Our study was carried out over a period of two consecutive years in 92 agricultural grasslands in three regions of Germany, spanning a latitudinal gradient of more than 500 km. A structural equation model suggests that feeding activity of soil fauna as measured by the bait-lamina test was positively related to legume and grass species richness in both years. Most probably, a diverse vegetation promotes feeding activity of soil fauna via alterations of both microclimate and resource availability. Feeding activity of soil fauna also increased with earthworm biomass via a pathway over Collembola abundance. The effect of earthworms on the feeding activity in soil may be attributed to their important role as ecosystem engineers. As no additional effects of agricultural management such as fertilization, livestock density or number of cuts on bait consumption were observed, our results suggest that the positive effect of legume and grass species richness on the feeding activity in soil fauna is a general one that will not be overruled by regional differences in management or environmental conditions. We thus suggest that agri-environment schemes aiming at the protection of belowground activity and associated ecosystem functions in temperate grasslands may generally focus on maintaining plant diversity, especially with regard to the potential effects of climate change on future vegetation structure.
14.	Decaesteker, Bieke, et al. (författare) SOX11 regulates SWI/SNF complex components as member of the adrenergic neuroblastoma core regulatory circuitry 2023 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1 Tidskriftsartikel (refereegranskat)abstract The pediatric extra-cranial tumor neuroblastoma displays a low mutational burden while recurrent copy number alterations are present in most high-risk cases. Here, we identify SOX11 as a dependency transcription factor in adrenergic neuroblastoma based on recurrent chromosome 2p focal gains and amplifications, specific expression in the normal sympatho-adrenal lineage and adrenergic neuroblastoma, regulation by multiple adrenergic specific (super-)enhancers and strong dependency on high SOX11 expression in adrenergic neuroblastomas. SOX11 regulated direct targets include genes implicated in epigenetic control, cytoskeleton and neurodevelopment. Most notably, SOX11 controls chromatin regulatory complexes, including 10 SWI/SNF core components among which SMARCC1, SMARCA4/BRG1 and ARID1A. Additionally, the histone deacetylase HDAC2, PRC1 complex component CBX2, chromatin-modifying enzyme KDM1A/LSD1 and pioneer factor c-MYB are regulated by SOX11. Finally, SOX11 is identified as a core transcription factor of the core regulatory circuitry (CRC) in adrenergic high-risk neuroblastoma with a potential role as epigenetic master regulator upstream of the CRC.
15.	Do, Ron, et al. (författare) Common variants associated with plasma triglycerides and risk for coronary artery disease 2013 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345- Tidskriftsartikel (refereegranskat)abstract Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
16.	Fall, Tove, et al. (författare) Age- and sex-specific causal effects of adiposity on cardiovascular risk factors 2015 Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 64:5, s. 1841-1852 Tidskriftsartikel (refereegranskat)abstract Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 × 10(-107)) and stratified analyses (all P < 3.3 × 10(-30)). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the <55-year stratum. Further, we found evidence of a smaller causal effect on total cholesterol (P for difference = 0.015) in the ≥55-year stratum than in the <55-year stratum, a finding that could be explained by biology, survival bias, or differential medication. In conclusion, this study extends previous knowledge of the effects of adiposity by providing sex- and age-specific causal estimates on cardiovascular risk factors.
17.	Fall, Tove, et al. (författare) The Role of Adiposity in Cardiometabolic Traits : A Mendelian Randomization Analysis 2013 Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 10:6, s. e1001474- Tidskriftsartikel (refereegranskat)abstract Background: The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. Methods and Findings: We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age-and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p = 0.001). Conclusions: We provide novel evidence for a causal relationship between adiposity and heart failure as well as between adiposity and increased liver enzymes.
18.	Fischer, Joern, et al. (författare) Advancing sustainability through mainstreaming a social–ecological systems perspective 2015 Ingår i: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435 .- 1877-3443. ; 14, s. 144-149 Tidskriftsartikel (refereegranskat)abstract The concept of social-ecological systems is useful for understanding the interlinked dynamics of environmental and societal change. The concept has helped facilitate: (1) increased recognition of the dependence of humanity on ecosystems; (2) improved collaboration across disciplines, and between science and society; (3) increased methodological pluralism leading to improved systems understanding; and (4) major policy frameworks considering social-ecological interactions. Despite these advances, the potential of a social-ecological systems perspective to improve sustainability outcomes has not been fully realized. Key priorities are to: (1) better understand and govern social-ecological interactions between regions; (2) pay greater attention to long-term drivers; (3) better understand the interactions among power relations, justice, and ecosystem stewardship; and (4) develop a stronger science-society interface.
19.	Fischer, Tim, et al. (författare) Creep-fatigue properties of austenitic cast iron D5S with tension and compression dwell : A dislocation density-based crystal plasticity study 2022 Ingår i: Materials Science & Engineering. - : Elsevier BV. - 0921-5093 .- 1873-4936. ; 860, s. 144212- Tidskriftsartikel (refereegranskat)abstract To predict and better understand the creep-fatigue behaviour of austenitic cast iron D5S under tension and compression dwell at 800 degrees C, a physics-based crystal plasticity model that describes the complex rate-and temperature-dependent deformation of the material as a function of the dislocation density is implemented. In addition to the tension and compression dwell direction, the effect of three different dwell times (30, 180 and 600 s) on the creep-fatigue properties is investigated. The dislocation density-based crystal plasticity simulations are compared to experimental tests from a prior work. While relaxation tests and low-cycle fatigue (LCF) tests without dwell assist in systematically identifying the material parameters, creep-fatigue (CF) data is used to validate the predictions. The virtual testing is performed on a large-scale representation of the actual test specimen with a polycrystalline structure. To analyse the fatigue damage mechanism, small-scale predictions are also conducted using a micromechanical unit cell approach. Here, a single graphite nodule frequently found in the material is embedded into the austenitic matrix. In the present work, a close agreement is achieved between the predicted CF behaviour and the experimental results. Consistent with the experimental findings, the simulation results show that the addition of compression dwell leads to an uplift of the overall tensile stress level, which significantly reduces the fatigue life of the material. The unit cell studies demonstrate that during this uplift, a strong localisation of stresses and strains arises at the graphite/matrix interface, triggering the nucleation and growth of cavities and/or debonding.
20.	Fischer, Tim, et al. (författare) Micromechanical prediction of the elastic and plastic properties of sintered steels 2024 Ingår i: Materials Science & Engineering. - : Elsevier BV. - 0921-5093 .- 1873-4936. ; 897 Tidskriftsartikel (refereegranskat)abstract One of the characteristic features of sintered steels is the porosity in their microstructure resulting from the compaction and sintering process. This porosity strongly influences the mechanical properties. To enhance the understanding for the structure–property relationship of sintered Astaloy®85Mo with 0.4 wt.%C, a micromechanical modelling approach based on face-centred cubic (fcc) representative volume elements (RVE) is proposed. The fcc-like periodic arrangement of the sintered particles in the RVE enables the consideration of a realistic non-spherical pore morphology. To compare the predictions with experimental results, accompanying uniaxial tensile tests are considered at different pore volume fractions after initial microstructure characterisation. In addition to the effect of pore volume fraction, the influence of sinter necks on the predicted overall strength is also systematically investigated. Despite the fairly simple nature of the underlying fcc structure, the RVE simulations are perfectly capable of reproducing the experimental trend, showing that the elasto-plastic properties decrease with increasing porosity. This is in contrast to analytical predictions, which underestimate the decrease in properties due to spherical pore assumptions. Moreover, the finite element-based simulations reveal a less pronounced influence of the sinter neck shape on the macroscopic behaviour, even though substantial differences in plastic strain localisation are discernible at the microscopic scale.
21.	Fischer, Tim, et al. (författare) Morphological and Crystallographic Effects in the Laser Powder-Bed Fused Stainless Steel Microstructure 2021 Ingår i: Crystals. - : MDPI AG. - 2073-4352. ; 11:6, s. 672- Tidskriftsartikel (refereegranskat)abstract One of the key aspects in additive manufacturing of stainless steels is the relationship between process parameters and the resulting microstructure. The selected process parameters typically cause a rapid solidification of the material, which leads to a microstructure that is highly textured both morphologically and crystallographically. While the morphological texture is characterised by a mainly columnar shape of the grains, the crystallographic texture is marked by a preferred grain orientation in the direction (fibre texture). Due to the texture effects, pronounced anisotropic mechanical properties are present in the material. In this report, a series of virtual microstructures with different morphological and crystallographic features are generated to develop a fundamental understanding of the individual texture effects on the mechanical properties. The grain morphology is based on Voronoi tessellations, and the crystallographic texture is captured with crystal plasticity. Furthermore, the numerical predictions are compared with experimental studies. The mechanical properties predicted on the basis of the virtual microstructures show that the crystallographic effect is much more dominant than the morphology of the individual grains. Consistent with the experiments, the highest load-bearing capacity of the material occurs when the macroscopic loading acts under an angle of 45 degrees to the preferred orientation of the crystals.
22.	Fischer, Tim, et al. (författare) Relating stress/strain heterogeneity to lath martensite strength by experiments and dislocation density-based crystal plasticity 2024 Ingår i: International journal of plasticity. - : Elsevier BV. - 0749-6419 .- 1879-2154. ; 174 Tidskriftsartikel (refereegranskat)abstract To enhance the fundamental understanding for micromechanical lath martensite deformation, the microstructure as well as macro- and microscopic tensile properties of as -quenched 15-5 PH stainless steel are systematically analysed depending on the austenitisation temperature. Based on electron backscatter diffraction (EBSD) and backscattered electron (BSE) analysis, it is noted that the martensite morphology alters from a less defined to a more clearly defined parallel arrangement of the block and lath structure with increasing temperature. For an indepth quantification of the hierarchical boundary strengthening contributions in relation to local stress/strain heterogeneity, separate high-fidelity virtual microstructures are realised for the different scales (prior austenite grains, packets and blocks). This is consistent with the materials transformation process. The virtual microstructures are simulated employing the crystal plasticity finite element method (CPFEM) adapted for handling high dislocation density and encompassing all relevant strengthening mechanisms by boundaries, dislocations and solute atoms. While accurately capturing the measured size -dependent stress-strain behaviour, the simulations reveal in line with the experiments (Hall-Petch) that blocks are the most effective dislocation motion barrier, causing increased strain hardening and stress/strain heterogeneity. Furthermore, since strain localisation is predicted strongest in the distinct block structure, the experimentally observed early plastic material yielding is thought to be favoured here.
23.	Fischer, Tim, et al. (författare) Sensitivity of local cyclic deformation in lath martensite to flow rule and slip system in crystal plasticity 2023 Ingår i: Computational materials science. - : Elsevier BV. - 0927-0256 .- 1879-0801. ; 222, s. 112106- Tidskriftsartikel (refereegranskat)abstract The prediction of the cyclic deformation behaviour in lath martensite-based high-strength steels requires constitutive models that reflect the local stress and strain fields as accurately as possible. At the same time, the constitutive models should act as efficiently as possible in order to achieve the required high number of cycles in a finite time. Only few research works have studied the sensitivity of the local cyclic deformation in lath martensite to the power law-based flow rule (Hutchinson or Chaboche-Cailletaud) and the active body-centred cubic (bcc) slip systems ({110}(111) and {112}(111)) in the crystal plasticity finite element method (CPFEM). This paper, therefore, aims to provide some guidance in the selection of suitable flow rule and slip systems. Based on full-field micromechanical modelling of a medium-carbon steel under symmetric strain-controlled cyclic loading, it can be shown that the two most commonly used flow rules according to Hutchinson and Chaboche-Cailletaud are equally capable of predicting the local stress and strain distributions within the hierarchical martensitic microstructure. However, using the Hutchinson flow rule increases the computational performance for the quasi-rate-independent problem considered here. The local distributions found differ strongly from those in the parent austenitic microstructure. If plastic deformation is assumed not only on the slip systems {110}(111), as often done, but also on the {112}(111) type, a redistribution of the bimodal distributed local stresses occurs at a significantly lower stress level. The unimodal distributed local strains are less affected by this. In addition, it is found that slightly different critical resolved shear stress (CRSS) values for both slip system types influence the local stress and strain distributions less severely than the additional plastic slip activation in the material.
24.	Frkatović-Hodžić, Azra, et al. (författare) Mapping of the gene network that regulates glycan clock of ageing 2023 Ingår i: Aging. - 1945-4589. ; 15:24, s. 14509-14552 Tidskriftsartikel (refereegranskat)abstract Glycans are an essential structural component of immunoglobulin G (IgG) that modulate its structure and function. However, regulatory mechanisms behind this complex posttranslational modification are not well known. Previous genome-wide association studies (GWAS) identified 29 genomic regions involved in regulation of IgG glycosylation, but only a few were functionally validated. One of the key functional features of IgG glycosylation is the addition of galactose (galactosylation), a trait which was shown to be associated with ageing. We performed GWAS of IgG galactosylation (N=13,705) and identified 16 significantly associated loci, indicating that IgG galactosylation is regulated by a complex network of genes that extends beyond the galactosyltransferase enzyme that adds galactose to IgG glycans. Gene prioritization identified 37 candidate genes. Using a recently developed CRISPR/dCas9 system we manipulated gene expression of candidate genes in the in vitro IgG expression system. Upregulation of three genes, EEF1A1, MANBA and TNFRSF13B, changed the IgG glycome composition, which confirmed that these three genes are involved in IgG galactosylation in this in vitro expression system.
25.	From Dust to Dawn : Archival Studies After the Archival Turna 2021 Samlingsverk (redaktörskap) (refereegranskat)
26.	Fullman, Nancy, et al. (författare) Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: A systematic analysis from the Global Burden of Disease Study 2016 2018 Ingår i: The Lancet. - : Lancet Publishing Group. - 1474-547X .- 0140-6736. ; 391:10136, s. 2236-2271 Tidskriftsartikel (refereegranskat)
27.	Haycock, Philip C., et al. (författare) Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study 2017 Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651 Tidskriftsartikel (refereegranskat)abstract IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
28.	Hägg, Sara, et al. (författare) Adiposity as a cause of cardiovascular disease : a Mendelian randomization study 2015 Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 44:2, s. 578-586 Tidskriftsartikel (refereegranskat)abstract Background: Adiposity, as indicated by body mass index (BMI), has been associated with risk of cardiovascular diseases in epidemiological studies. We aimed to investigate if these associations are causal, using Mendelian randomization (MR) methods. Methods: The associations of BMI with cardiovascular outcomes [coronary heart disease (CHD), heart failure and ischaemic stroke], and associations of a genetic score (32 BMI single nucleotide polymorphisms) with BMI and cardiovascular outcomes were examined in up to 22 193 individuals with 3062 incident cardiovascular events from nine prospective follow-up studies within the ENGAGE consortium. We used random-effects meta-analysis in an MR framework to provide causal estimates of the effect of adiposity on cardiovascular outcomes. Results: There was a strong association between BMI and incident CHD (HR = 1.20 per SD-increase of BMI, 95% CI, 1.12-1.28, P = 1.9.10(-7)), heart failure (HR = 1.47, 95% CI, 1.35-1.60, P = 9.10(-19)) and ischaemic stroke (HR = 1.15, 95% CI, 1.06-1.24, P = 0.0008) in observational analyses. The genetic score was robustly associated with BMI (beta = 0.030 SD-increase of BMI per additional allele, 95% CI, 0.028-0.033, P = 3.10(-107)). Analyses indicated a causal effect of adiposity on development of heart failure (HR = 1.93 per SD-increase of BMI, 95% CI, 1.12-3.30, P = 0.017) and ischaemic stroke (HR = 1.83, 95% CI, 1.05-3.20, P = 0.034). Additional cross-sectional analyses using both ENGAGE and CARDIoGRAMplusC4D data showed a causal effect of adiposity on CHD. Conclusions: Using MR methods, we provide support for the hypothesis that adiposity causes CHD, heart failure and, previously not demonstrated, ischaemic stroke.
29.	Kassebaum, Nicholas J., et al. (författare) Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015 2016 Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1603-1658 Tidskriftsartikel (refereegranskat)abstract Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
30.	Loaiza, Tania, 1994-, et al. (författare) Micromechanical response of dual-hardening martensitic bearing steel before and after rolling contact fatigue Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Material decay in bearing steels under rolling contact fatigue (RCF) leads to fatigue initiation and failure. This study examines the local structure-property relationshipin decayed material through in-situ compression testing of micropillars prepared froma dual-hardening martensitic bearing steel (Hybrid 60) before and after RCF testing. Specific crystal orientations are tested, revealing differing plastic behavior in the virgin and decayed material. RCF-induced ferritic microbands create highly localized deformation, that alters the micromechanical response. Crystal plasticity simulations confirm these findings, highlighting increased critical resolved shear stress and reduced strain hardening in decayed micropillars.
31.	Loaiza, Tania, 1994-, et al. (författare) Micromechanical response of dual-hardening martensitic bearing steel before and after rolling contact fatigue 2024 Ingår i: Journal of Materials Research and Technology. - : Elsevier BV. - 2238-7854. ; 29, s. 4728-4734 Tidskriftsartikel (refereegranskat)abstract Material decay in bearing steels under rolling contact fatigue (RCF) leads to fatigue initiation and failure. This study examines the local structure-property relationship in decayed material through in-situ compression testing of micropillars prepared from a dual-hardening martensitic bearing steel (Hybrid 60) before and after RCF testing. The results demonstrate a pronounced enhancement in local yield strength for decayed regions (2200–2340 MPa) as compared to non-decayed regions (1755–1780 MPa). The higher initial stress for dislocations glide in the decayed regions and their discontinuous yield behavior are attributed to the presence of ferrite microbands. Crystal plasticity simulations corroborated these findings, showingincreased critical resolved shear stress (CRSS) and reduced strain hardening in decayed samples.
32.	Locke, Adam E, et al. (författare) Genetic studies of body mass index yield new insights for obesity biology. 2015 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401 Tidskriftsartikel (refereegranskat)abstract Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
33.	Lozano, Rafael, et al. (författare) Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017 2018 Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138 Tidskriftsartikel (refereegranskat)abstract Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). 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. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
34.	Mattsson, Annie, 1981-, et al. (författare) Reflections on Reading Archives after the Archival Turn 2022. - 1 Ingår i: From Dust to Dawn. - Uppsala : Litteraturvetenskapliga institutionen. ; , s. 18-55 Bokkapitel (övrigt vetenskapligt/konstnärligt)
35.	Mohammed Taha, Hiba, et al. (författare) The NORMAN Suspect List Exchange (NORMAN-SLE) : facilitating European and worldwide collaboration on suspect screening in high resolution mass spectrometry 2022 Ingår i: Environmental Sciences Europe. - : Springer. - 2190-4707 .- 2190-4715. ; 34:1 Tidskriftsartikel (refereegranskat)abstract Background: The NORMAN Association (https://www.norman-network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for “suspect screening” lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide.Results: The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https://zenodo.org/communities/norman-sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN-SLE content is progressively integrated into large open chemical databases such as PubChem (https://pubchem.ncbi.nlm.nih.gov/) and the US EPA’s CompTox Chemicals Dashboard (https://comptox.epa.gov/dashboard/), enabling further access to these lists, along with the additional functionality and calculated properties these resources offer. PubChem has also integrated significant annotation content from the NORMAN-SLE, including a classification browser (https://pubchem.ncbi.nlm.nih.gov/classification/#hid=101).Conclusions: The NORMAN-SLE offers a specialized service for hosting suspect screening lists of relevance for the environmental community in an open, FAIR manner that allows integration with other major chemical resources. These efforts foster the exchange of information between scientists and regulators, supporting the paradigm shift to the “one substance, one assessment” approach. New submissions are welcome via the contacts provided on the NORMAN-SLE website (https://www.norman-network.com/nds/SLE/).
36.	Murray, Christopher J. L., et al. (författare) Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017 2018 Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051 Tidskriftsartikel (refereegranskat)abstract Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
37.	Muscheler, Raimund, et al. (författare) Solar and volcanic forcing of decadal- to millennial-scale climatic variations 2012 Ingår i: The SAGE Handbook of Environmental Change. - 1 Oliver's Yard, 55 City Road, London EC1Y 1SP United Kingdom : SAGE Publications Ltd. - 9781446253045 - 9780857023605 ; 1, s. 444-470 Bokkapitel (refereegranskat)
38.	Patterson, Nick, et al. (författare) Large-scale migration into Britain during the Middle to Late Bronze Age 2022 Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594 Tidskriftsartikel (refereegranskat)abstract Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
39.	Pega, Frank, et al. (författare) Global, regional, and national burdens of ischemic heart disease and stroke attributable to exposure to long working hours for 194 countries, 2000-2016 : A systematic analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury 2021 Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 154 Tidskriftsartikel (refereegranskat)abstract Background: World Health Organization (WHO) and International Labour Organization (ILO) systematic reviews reported sufficient evidence for higher risks of ischemic heart disease and stroke amongst people working long hours (>= 55 hours/week), compared with people working standard hours (35-40 hours/week). This article presents WHO/ILO Joint Estimates of global, regional, and national exposure to long working hours, for 194 countries, and the attributable burdens of ischemic heart disease and stroke, for 183 countries, by sex and age, for 2000, 2010, and 2016.Methods and Findings: We calculated population-attributable fractions from estimates of the population exposed to long working hours and relative risks of exposure on the diseases from the systematic reviews. The exposed population was modelled using data from 2324 cross-sectional surveys and 1742 quarterly survey datasets. Attributable disease burdens were estimated by applying the population-attributable fractions to WHO's Global Health Estimates of total disease burdens.Results: In 2016, 488 million people (95% uncertainty range: 472-503 million), or 8.9% (8.6-9.1) of the global population, were exposed to working long hours (>= 55 hours/week). An estimated 745,194 deaths (705,786-784,601) and 23.3 million disability-adjusted life years (22.2-24.4) from ischemic heart disease and stroke combined were attributable to this exposure. The population-attributable fractions for deaths were 3.7% (3.4-4.0) for ischemic heart disease and 6.9% for stroke (6.4-7.5); for disability-adjusted life years they were 5.3% (4.9-5.6) for ischemic heart disease and 9.3% (8.7-9.9) for stroke.Conclusions: WHO and ILO estimate exposure to long working hours (>= 55 hours/week) is common and causes large attributable burdens of ischemic heart disease and stroke. Protecting and promoting occupational and workers' safety and health requires interventions to reduce hazardous long working hours.
40.	Putora, Paul Martin, et al. (författare) Diagnostic imaging strategies of acute intracerebral hemorrhage in European academic hospitals—a decision-making analysis 2023 Ingår i: Neuroradiology. - : Springer Science and Business Media LLC. - 0028-3940 .- 1432-1920. ; 65:4, s. 729-736 Tidskriftsartikel (refereegranskat)abstract Purpose: To evaluate and compare which factors are relevant to the diagnostic decision-making and imaging workup of intracerebral hemorrhages in large, specialized European centers. Methods: Expert neuroradiologists from ten large, specialized centers (where endovascular stroke treatment is routinely performed) in nine European countries were selected in cooperation with the European Society of Neuroradiology (ESNR). The experts were asked to describe how and when they would investigate specific causes in a patient who presented with an acute, atraumatic, intracerebral hemorrhage for two given locations: (1) basal ganglia, thalamus, pons or cerebellum; (2) lobar hemorrhage. Answers were collected, and decision trees were compared. Results: Criteria that were considered relevant for decision-making reflect recommendations from current guidelines and were similar in all participating centers. CT Angiography or MR angiography was considered essential by the majority of centers regardless of other factors. Imaging in clinical practice tended to surpass guideline recommendations and was heterogeneous among different centers, e.g., in a scenario suggestive of typical hypertensive hemorrhage, recommendations ranged from no further follow-up imaging to CT angiography and MR angiography. In no case was a consensus above 60% achieved. Conclusion: In European clinical practices, existing guidelines for diagnostic imaging strategies in ICH evaluation are followed as a basis but in most cases, additional imaging investigation is undertaken. Significant differences in imaging workup were observed among the centers. Results suggest a high level of awareness and caution regarding potentially underlying pathology other than hypertensive disease.
41.	Ripatti, Samuli, et al. (författare) GENESTAT : an information portal for design and analysis of genetic association studies 2009 Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 17:4, s. 533-536 Tidskriftsartikel (refereegranskat)abstract We present the rationale, the background and the structure for version 2.0 of the GENESTAT information portal (www.genestat.org) for statistical genetics. The fast methodological advances, coupled with a range of standalone software, makes it difficult for expert as well as non-expert users to orientate when designing and analysing their genetic studies. The ultimate ambition of GENESTAT is to guide on statistical methodology related to the broad spectrum of research in genetic epidemiology. GENESTAT 2.0 focuses on genetic association studies. Each entry provides a summary of a topic and gives links to key papers, websites and software. The flexibility of the internet is utilised for cross-referencing and for open editing. This paper gives an overview of GENESTAT and gives short introductions to the current main topics in GENESTAT, with additional entries on the website. Methods and software developers are invited to contribute to the portal, which is powered by a Wikipedia-type engine and allows easy additions and editing.
42.	Ripatti, Samuli, et al. (författare) GENESTAT: An Information Portal for Design and Analysis of Genetic Association Studies. 2009 Ingår i: European Journal of Human Genetics. ; 17:4, s. 533-6 Tidskriftsartikel (refereegranskat)
43.	Ripatti, Samuli, et al. (författare) Genestat: An information portal for design and analysis of genetic association studies 2008 Ingår i: European Journal of Human Genetics. Tidskriftsartikel (refereegranskat)
44.	Sanchez, Erlan, et al. (författare) Association of plasma biomarkers with cognition, cognitive decline, and daily function across and within neurodegenerative diseases: Results from the Ontario Neurodegenerative Disease Research Initiative 2024 Ingår i: Alzheimer's and Dementia. - 1552-5260 .- 1552-5279. ; 20:3, s. 1753-1770 Tidskriftsartikel (refereegranskat)abstract INTRODUCTION: We investigated whether novel plasma biomarkers are associated with cognition, cognitive decline, and functional independence in activities of daily living across and within neurodegenerative diseases. METHODS: Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau (p-tau)181 and amyloid beta (Aβ)42/40 were measured using ultra-sensitive Simoa immunoassays in 44 healthy controls and 480 participants diagnosed with Alzheimer's disease/mild cognitive impairment (AD/MCI), Parkinson's disease (PD), frontotemporal dementia (FTD) spectrum disorders, or cerebrovascular disease (CVD). RESULTS: GFAP, NfL, and/or p-tau181 were elevated among all diseases compared to controls, and were broadly associated with worse baseline cognitive performance, greater cognitive decline, and/or lower functional independence. While GFAP, NfL, and p-tau181 were highly predictive across diseases, p-tau181 was more specific to the AD/MCI cohort. Sparse associations were found in the FTD and CVD cohorts and for Aβ42/40. DISCUSSION: GFAP, NfL, and p-tau181 are valuable predictors of cognition and function across common neurodegenerative diseases, and may be useful in specialized clinics and clinical trials.
45.	Schumann, Gunter, et al. (författare) KLB is associated with alcohol drinking, and its gene product beta-Klotho is necessary for FGF21 regulation of alcohol preference 2016 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:50, s. 14372-14377 Tidskriftsartikel (refereegranskat)abstract Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified beta-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 x 10(-12)). beta-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific beta-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.
46.	Shungin, Dmitry, et al. (författare) New genetic loci link adipose and insulin biology to body fat distribution. 2015 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378 Tidskriftsartikel (refereegranskat)abstract Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
47.	Skirgård, Hedvig, et al. (författare) Grambank reveals the importance of genealogical constraints on linguistic diversity and highlights the impact of language loss. Science Advances 2023 Ingår i: Science Advances. ; 9:16:eadg6175, s. 1-15 Tidskriftsartikel (refereegranskat)
48.	Soliveres, Santiago, et al. (författare) Biodiversity at multiple trophic levels is needed for ecosystem multifunctionality 2016 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7617, s. 456-459 Tidskriftsartikel (refereegranskat)abstract Many experiments have shown that loss of biodiversity reduces the capacity of ecosystems to provide the multiple services on which humans depend. However, experiments necessarily simplify the complexity of natural ecosystems and will normally control for other important drivers of ecosystem functioning, such as the environment or land use. In addition, existing studies typically focus on the diversity of single trophic groups, neglecting the fact that biodiversity loss occurs across many taxa and that the functional effects of any trophic group may depend on the abundance and diversity of others. Here we report analysis of the relationships between the species richness and abundance of nine trophic groups, including 4,600 above- and below-ground taxa, and 14 ecosystem services and functions and with their simultaneous provision (or multifunctionality) in 150 grasslands. We show that high species richness in multiple trophic groups (multitrophic richness) had stronger positive effects on ecosystem services than richness in any individual trophic group; this includes plant species richness, the most widely used measure of biodiversity. On average, three trophic groups influenced each ecosystem service, with each trophic group influencing at least one service. Multitrophic richness was particularly beneficial for 'regulating' and 'cultural' services, and for multifunctionality, whereas a change in the total abundance of species or biomass in multiple trophic groups (the multitrophic abundance) positively affected supporting services. Multitrophic richness and abundance drove ecosystem functioning as strongly as abiotic conditions and land-use intensity, extending previous experimental results to real-world ecosystems. Primary producers, herbivorous insects and microbial decomposers seem to be particularly important drivers of ecosystem functioning, as shown by the strong and frequent positive associations of their richness or abundance with multiple ecosystem services. Our results show that multitrophic richness and abundance support ecosystem functioning, and demonstrate that a focus on single groups has led to researchers to greatly underestimate the functional importance of biodiversity.
49.	Soliveres, Santiago, et al. (författare) Locally rare species influence grassland ecosystem multifunctionality 2016 Ingår i: Philosophical Transactions of the Royal Society B: Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 371:1694 Tidskriftsartikel (refereegranskat)abstract Species diversity promotes the delivery of multiple ecosystem functions (multifunctionality). However, the relative functional importance of rare and common species in driving the biodiversity-multifunctionality relationship remains unknown. We studied the relationship between the diversity of rare and common species (according to their local abundances and across nine different trophic groups), and multifunctionality indices derived from 14 ecosystem functions on 150 grasslands across a land-use intensity (LUI) gradient. The diversity of above-and below-ground rare species had opposite effects, with rare above-ground species being associated with high levels of multifunctionality, probably because their effects on different functions did not trade off against each other. Conversely, common species were only related to average, not high, levels of multifunctionality, and their functional effects declined with LUI. Apart from the community-level effects of diversity, we found significant positive associations between the abundance of individual species and multifunctionality in 6% of the species tested. Species-specific functional effects were best predicted by their response to LUI: species that declined in abundance with land use intensification were those associated with higher levels of multifunctionality. Our results highlight the importance of rare species for ecosystem multifunctionality and help guiding future conservation priorities.
50.	Stanaway, Jeffrey D., et al. (författare) Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017 2018 Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994 Tidskriftsartikel (refereegranskat)abstract Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.

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