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2. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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3. |
- Aad, G, et al.
(author)
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- 2015
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swepub:Mat__t
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4. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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5. |
- Vos, T., et al.
(author)
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Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016
- 2017
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In: Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1211-1259
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Journal article (peer-reviewed)abstract
- Background As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016. Methods We estimated prevalence and incidence for 328 diseases and injuries and 2982 sequelae, their non-fatal consequences. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between incidence, prevalence, remission, and cause of death rates for each condition. For some causes, we used alternative modelling strategies if incidence or prevalence needed to be derived from other data. YLDs were estimated as the product of prevalence and a disability weight for all mutually exclusive sequelae, corrected for comorbidity and aggregated to cause level. We updated the Socio-demographic Index (SDI), a summary indicator of income per capita, years of schooling, and total fertility rate. GBD 2016 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, low back pain, migraine, age-related and other hearing loss, iron-deficiency anaemia, and major depressive disorder were the five leading causes of YLDs in 2016, contributing 57.6 million (95% uncertainty interval [UI] 40.8-75.9 million [7.2%, 6.0-8.3]), 45.1 million (29.0-62.8 million [5.6%, 4.0-7.2]), 36.3 million (25.3-50.9 million [4.5%, 3.8-5.3]), 34.7 million (23.0-49.6 million [4.3%, 3.5-5.2]), and 34.1 million (23.5-46.0 million [4.2%, 3.2-5.3]) of total YLDs, respectively. Age-standardised rates of YLDs for all causes combined decreased between 1990 and 2016 by 2.7% (95% UI 2.3-3.1). Despite mostly stagnant age-standardised rates, the absolute number of YLDs from non-communicable diseases has been growing rapidly across all SDI quintiles, partly because of population growth, but also the ageing of populations. The largest absolute increases in total numbers of YLDs globally were between the ages of 40 and 69 years. Age-standardised YLD rates for all conditions combined were 10.4% (95% UI 9.0-11.8) higher in women than in men. Iron-deficiency anaemia, migraine, Alzheimer's disease and other dementias, major depressive disorder, anxiety, and all musculoskeletal disorders apart from gout were the main conditions contributing to higher YLD rates in women. Men had higher age-standardised rates of substance use disorders, diabetes, cardiovascular diseases, cancers, and all injuries apart from sexual violence. Globally, we noted much less geographical variation in disability than has been documented for premature mortality. In 2016, there was a less than two times difference in age-standardised YLD rates for all causes between the location with the lowest rate (China, 9201 YLDs per 100 000, 95% UI 6862-11943) and highest rate (Yemen, 14 774 YLDs per 100 000, 11 018-19 228). Interpretation The decrease in death rates since 1990 for most causes has not been matched by a similar decline in age-standardised YLD rates. For many large causes, YLD rates have either been stagnant or have increased for some causes, such as diabetes. As populations are ageing, and the prevalence of disabling disease generally increases steeply with age, health systems will face increasing demand for services that are generally costlier than the interventions that have led to declines in mortality in childhood or for the major causes of mortality in adults. Up-todate information about the trends of disease and how this varies between countries is essential to plan for an adequate health-system response. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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6. |
- Thomas, HS, et al.
(author)
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- 2019
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swepub:Mat__t
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9. |
- Delios, A., et al.
(author)
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Examining the generalizability of research findings from archival data
- 2022
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:30
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Journal article (peer-reviewed)abstract
- This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability-for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples.
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10. |
- Menden, MP, et al.
(author)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Journal article (peer-reviewed)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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11. |
- Pulit, S. L., et al.
(author)
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Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
- 2018
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In: Neurology-Genetics. - : Ovid Technologies (Wolters Kluwer Health). - 2376-7839. ; 4:6
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Journal article (peer-reviewed)abstract
- Objective We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 x 10(-4) in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 x 10(-48)), explaining similar to 20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07,p = 0.004), but no other primary stroke subtypes (all p > 0.1). Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.
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12. |
- Wang, HD, et al.
(author)
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Global, regional, national, and selected subnational levels of stillbirths, neonatal, infant, and under-5 mortality, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015
- 2016
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In: Lancet (London, England). - : Elsevier. - 1474-547X .- 0140-6736. ; 388:10053, s. 1725-1774
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Journal article (peer-reviewed)
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14. |
- Borsato, M., et al.
(author)
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Unleashing the full power of LHCb to probe stealth new physics
- 2022
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In: Reports on Progress in Physics. - : IOP Publishing. - 0034-4885 .- 1361-6633. ; 85:2
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Journal article (peer-reviewed)abstract
- In this paper, we describe the potential of the LHCb experiment to detect stealth physics. This refers to dynamics beyond the standard model that would elude searches that focus on energetic objects or precision measurements of known processes. Stealth signatures include long-lived particles and light resonances that are produced very rarely or together with overwhelming backgrounds. We will discuss why LHCb is equipped to discover this kind of physics at the Large Hadron Collider and provide examples of well-motivated theoretical models that can be probed with great detail at the experiment.
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15. |
- Conde, Lucia, et al.
(author)
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Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:8, s. 661-664
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Journal article (peer-reviewed)abstract
- To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 x 10(-29) and rs7755224, combined P = 2.00 x 10(-19); r(2) = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 x 10(-9)).
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16. |
- Dalerum, Fredrik, et al.
(author)
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Spatial and temporal dimensions to the taxonomic diversity of arthropods in an arid grassland savannah
- 2017
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In: Journal of Arid Environments. - : Elsevier BV. - 0140-1963 .- 1095-922X. ; 144, s. 21-30
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Journal article (peer-reviewed)abstract
- Quantifying the drivers of biodiversity variation is a key topic in contemporary ecology. While the geographic distribution of biodiversity is broadly determined by water and energy, local environmental conditions may be important. We evaluated the relative effects of spatial and temporal variation on taxonomic diversity of ground living arthropod communities in central South Africa. Seasonal climate variation was a major driver of arthropod abundance, but seasonal effects differed between habitats. We did not find any evidence for modular community structures, even across different habitats, or any evidence for a nested pattern across seasons. Instead, we observed a spatial nestedness which was only partly related to specific habitats. Our results suggest that neutral processes had influenced arthropod community structure, but also that very local processes may have been pivotal in determining local and regional arthropod diversity. Such processes may not necessarily have been neutral, but could have been caused by niche deterministic processes acting at scales smaller the distinct habitat classes we used for our study. We further suggest that alterations in climate likely will have substantial effects on the spatial and temporal distribution of arthropod diversity in this arid region.
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17. |
- Johansson, Maria E, 1977, et al.
(author)
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Innate immune receptor NOD2 promotes vascular inflammation and formation of lipid-rich necrotic cores in hypercholesterolemic mice
- 2014
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In: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 44:10, s. 3081-3092
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Journal article (peer-reviewed)abstract
- Atherosclerosis is an inflammatory disease associated with the activation of innate immune TLRs and nucleotide-binding oligomerization domain-containing protein (NOD)like receptor pathways. However, the function of most innate immune receptors in atherosclerosis remains unclear. Here, we show that NOD2 is a crucial innate immune receptor influencing vascular inflammation and atherosclerosis severity. 10-week stimulation with muramyl dipeptide (MDP), the NOD2 cognate ligand, aggravated atherosclerosis, as indicated by the augmented lesion burden, increased vascular inflammation and enlarged lipid-rich necrotic cores in Ldlr(-/-) mice. Myeloid-specific ablation of NOD2, but not its downstream kinase, receptor-interacting serine/threonine-protein kinase 2, restrained the expansion of the lipid-rich necrotic core in Ldlr(-/-) chimeric mice. In vitro stimulation of macrophages with MDP enhanced the uptake of oxidized low-density lipoprotein and impaired cholesterol efflux in concordance with upregulation of scavenger receptor A1/2 and downregulation of ATP-binding cassette transporter A1. Ex vivo stimulation of human carotid plaques with MDP led to increased activation of inflammatory signaling pathways p38 MAPK and NF-kappa B-mediated release of proinflammatory cytokines. Altogether, this study suggests that NOD2 contributes to the expansion of the lipid-rich necrotic core and promotes vascular inflammation in atherosclerosis.
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- Moles, A. T., et al.
(author)
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Putting plant resistance traits on the map : A test of the idea that plants are better defended at lower latitudes
- 2011
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In: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 191:3, s. 777-788
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Journal article (peer-reviewed)abstract
- It has long been believed that plant species from the tropics have higher levels of traits associated with resistance to herbivores than do species from higher latitudes. A meta-analysis recently showed that the published literature does not support this theory. However, the idea has never been tested using data gathered with consistent methods from a wide range of latitudes. ⢠We quantified the relationship between latitude and a broad range of chemical and physical traits across 301 species from 75 sites world-wide. ⢠Six putative resistance traits, including tannins, the concentration of lipids (an indicator of oils, waxes and resins), and leaf toughness were greater in high-latitude species. Six traits, including cyanide production and the presence of spines, were unrelated to latitude. Only ash content (an indicator of inorganic substances such as calcium oxalates and phytoliths) and the properties of species with delayed greening were higher in the tropics. ⢠Our results do not support the hypothesis that tropical plants have higher levels of resistance traits than do plants from higher latitudes. If anything, plants have higher resistance toward the poles. The greater resistance traits of high-latitude species might be explained by the greater cost of losing a given amount of leaf tissue in low-productivity environments. © 2011 New Phytologist Trust.
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20. |
- Roselli, Carolina, et al.
(author)
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Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
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Journal article (peer-reviewed)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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21. |
- Shell, Y. H., et al.
(author)
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A generic symbiotic simulation framework
- 2006
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In: Proceedings - Workshop on Principles of Advanced and Distributed Simulation, PADS. - 0769525873 - 9780769525877
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Conference paper (peer-reviewed)abstract
- A symbiotic or online simulation is defined as one that interacts with the physical system in a mutually beneficial way. The simulation is driven by real time data collected from a physical system under control and needs to meet the real-time requirements of the physical system. In turn, the results from the "what-if experiments performed by the simulator can be used to control the dynamic behaviour of the physical system. Such a simulation tool is for real-time planning and is to foresee and advise on real time problems. It aims to improve performance, to adapt to sudden and unexpected events and to improve aspects of safety and security of the physical system. There are some research efforts, for example, the Dynamic Data-Driven Application Systems (DDDAS) which are currently advocated by the National Science Foundation (NSF) of the United States. However, work in this area is far from complete and many of the research issues are not fully addressed. We see the need for a general framework for symbiotic simulation. In this project, simulators based on the same general framework will be developed using symbiotic simulation techniques and will be used to provide adaptive decision support to manage the resources in several application environments. The objectives of this project are: To develop a generic, agent-based, symbiotic simulation system architecture. To develop mechanisms to support dynamic coupling between the symbiotic simulation system and the physical system. To conduct pilot case studies of the simulation framework. To explore and evaluate the service oriented architecture approach for parallel simulation in the multi-agent symbiotic simulation framework.
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