| 1. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 2. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 3. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 4. |
- Grüning, Björn, et al.
(författare)
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Bioconda: A sustainable and comprehensive software distribution for the life sciences
- 2017
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We present Bioconda (https://bioconda.github.io), a distribution of bioinformatics software for the lightweight, multi-platform and language-agnostic package manager Conda. Currently, Bioconda offers a collection of over 3000 software packages, which is continuously maintained, updated, and extended by a growing global community of more than 200 contributors. Bioconda improves analysis reproducibility by allowing users to define isolated environments with defined software versions, all of which are easily installed and managed without administrative privileges.
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| 5. |
- Jones, Lesley, et al.
(författare)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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| 6. |
- Justice, Anne E., et al.
(författare)
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
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Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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| 7. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 8. |
- Naghavi, Mohsen, et al.
(författare)
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Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
- 2015
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
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Tidskriftsartikel (refereegranskat)abstract
- Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
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| 9. |
- Schinnerer, Eva, et al.
(författare)
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PHANGS-JWST First Results : Rapid Evolution of Star Formation in the Central Molecular Gas Ring of NGC 1365
- 2023
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 944:2
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale bars can fuel galaxy centers with molecular gas, often leading to the development of dense ringlike structures where intense star formation occurs, forming a very different environment compared to galactic disks. We pair ∼0.″3 (30 pc) resolution new JWST/MIRI imaging with archival ALMA CO(2-1) mapping of the central ∼5 kpc of the nearby barred spiral galaxy NGC 1365 to investigate the physical mechanisms responsible for this extreme star formation. The molecular gas morphology is resolved into two well-known bright bar lanes that surround a smooth dynamically cold gas disk (R gal ∼ 475 pc) reminiscent of non-star-forming disks in early-type galaxies and likely fed by gas inflow triggered by stellar feedback in the lanes. The lanes host a large number of JWST-identified massive young star clusters. We find some evidence for temporal star formation evolution along the ring. The complex kinematics in the gas lanes reveal strong streaming motions and may be consistent with convergence of gas streamlines expected there. Indeed, the extreme line widths are found to be the result of inter-“cloud” motion between gas peaks; ScousePy decomposition reveals multiple components with line widths of 〈σ CO,scouse〉 ≈ 19 km s−1 and surface densities of 〈 Σ H 2 , scouse 〉 ≈ 800 M ⊙ pc − 2 , similar to the properties observed throughout the rest of the central molecular gas structure. Tailored hydrodynamical simulations exhibit many of the observed properties and imply that the observed structures are transient and highly time-variable. From our study of NGC 1365, we conclude that it is predominantly the high gas inflow triggered by the bar that is setting the star formation in its CMZ.
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| 10. |
- Surendran, Praveen, et al.
(författare)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
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Tidskriftsartikel (refereegranskat)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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| 11. |
- Thilker, David A., et al.
(författare)
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PHANGS–JWST First Results : The Dust Filament Network of NGC 628 and Its Relation to Star Formation Activity
- 2023
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 944:2
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Tidskriftsartikel (refereegranskat)abstract
- PHANGS–JWST mid-infrared (MIR) imaging of nearby spiral galaxies has revealed ubiquitous filaments of dust emission in intricate detail. We present a pilot study to systematically map the dust filament network (DFN) at multiple scales between 25 and 400 pc in NGC 628. MIRI images at 7.7, 10, 11.3, and 21 μm of NGC 628 are used to generate maps of the filaments in emission, while PHANGS–HST B-band imaging yields maps of dust attenuation features. We quantify the correspondence between filaments traced by MIR thermal continuum/polycyclic aromatic hydrocarbon (PAH) emission and filaments detected via extinction/scattering of visible light; the fraction of MIR flux contained in the DFN; and the fraction of H ii regions, young star clusters, and associations within the DFN. We examine the dependence of these quantities on the physical scale at which the DFN is extracted. With our highest-resolution DFN maps (25 pc filament width), we find that filaments in emission and attenuation are cospatial in 40% of sight lines, often exhibiting detailed morphological agreement; that ∼30% of the MIR flux is associated with the DFN; and that 75%–80% of the star formation in H ii regions and 60% of the mass in star clusters younger than 5 Myr are contained within the DFN. However, the DFN at this scale is anticorrelated with looser associations of stars younger than 5 Myr identified using PHANGS–HST near-UV imaging. We discuss the impact of these findings on studies of star formation and the interstellar medium, and the broad range of new investigations enabled by multiscale maps of the DFN.
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| 12. |
- van Dalen, Jan Willem, et al.
(författare)
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Association of Systolic Blood Pressure With Dementia Risk and the Role of Age, U-Shaped Associations, and Mortality.
- 2022
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Ingår i: JAMA internal medicine. - : American Medical Association (AMA). - 2168-6114 .- 2168-6106. ; 182:2, s. 142-152
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Tidskriftsartikel (refereegranskat)abstract
- The optimal systolic blood pressure (SBP) to minimize the risk of dementia in older age is unknown.To investigate whether the association between SBP and dementia risk is U-shaped and whether age and comorbidity play a role in this association.This cohort study used an individual participant data approach to analyze 7 prospective, observational, population-based cohort studies that were designed to evaluate incident dementia in older adults. These studies started between 1987 and 2006 in Europe and the US. Participants had no dementia diagnosis and had SBP and/or diastolic blood pressure (BP) data at baseline and incident dementia status during follow-up. Data analysis was conducted from November 7, 2019, to October 3, 2021.Baseline systolic BP.All-cause dementia (defined using Diagnostic and Statistical Manual of Mental Disorders [Third Edition Revised] or Diagnostic and Statistical Manual of Mental Disorders [Fourth Edition] and established at follow-up measurements or in clinical practice), mortality, and combined dementia and mortality were the outcomes. Covariates included baseline antihypertensive medication use, sex, educational level, body mass index, smoking status, diabetes, stroke history, myocardial infarction history, and polypharmacy. Cox proportional hazards regression models were used, and nonlinear associations were explored using natural splines.The study analyzed 7 cohort studies with a total of 17286 participants, among whom 10393 were women (60.1%) and the mean (SD) baseline age was 74.5 (7.3) years. Overall, dementia risk was lower for individuals with higher SBP, with the lowest risk associated with an SBP of approximately 185 mm Hg (95% CI, 161-230 mm Hg; P=.001). Stratified by overlapping 10-year baseline age groups, the lowest dementia risk was observed at somewhat lower systolic BP levels in those older than 75 years (158 [95% CI, 152-178] mm Hg to 170 [95% CI, 160-260] mm Hg). For mortality, there was a clear U-shaped association, with the lowest risk at 160 mm Hg (95% CI, 154-181 mm Hg; P<.001). This U-shape occurred across all age groups, with the lowest dementia risk associated with an SBP of 134 mm Hg (95% CI, 102-149 mm Hg; P=.03) in those aged 60 to 70 years and increasing to between 155 mm Hg (95% CI, 150-166 mm Hg; P<.001) and 166 mm Hg (95% CI, 154-260 mm Hg; P=.02) for age groups between 70 and 95 years. Combined dementia and mortality risk curves closely resembled those for mortality. Associations of diastolic BP with dementia risk were generally similar but were less distinct.This cohort study found that dementia risk was lower for older individuals with higher SBP levels and that more distinctly U-shaped associations appeared for those older than 75 years, but these associations cannot be explained by SBP-associated changes in mortality risk. The findings may warrant future trials on tailored BP management in older age groups that take life expectancy and health context into consideration.
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| 13. |
- Vos, Theo, et al.
(författare)
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Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
- 2015
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 386:9995, s. 743-800
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Tidskriftsartikel (refereegranskat)abstract
- Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. Findings Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2.4 billion and 1.6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537.6 million in 1990 to 764.8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114.87 per 1000 people to 110.31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21.1% in 1990 to 31.2% in 2013. Interpretation Ageing of the world's population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.
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| 14. |
- Wang, Li-San, et al.
(författare)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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| 15. |
- Andersson, Jim
(författare)
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Systems Analysis of Chemicals Production via Integrated Entrained Flow Biomass Gasification : Quantification and improvement of techno-economic performance
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lignocellulosic biomass gasification is a promising production pathway for green chemicals, which can support the development towards a more sustainable society where fossil fuels are replaced. To be able to compete with fossil fuels, a highly efficient production of biomassbased products is required in order to maximize overall process economics and to minimizenegative environmental impact. Large production plants will likely be required to obtain favourable economy-of-scale effects and reasonable production cost. Entrained flow gasification (EFG) is a favourable technology due to its suitability for large-scale implementation and ability to produce a high quality syngas from various biomass feedstocks. In order to estimate overall energy efficiency and production costs for gasification-based biorefineries, it is important to be able to characterise the gasifiers’ performance. This in turnrequires reliable estimations of the gasification process. Integration of EFG-based biorefineries with existing pulp mills or other large-scale forestindustries can be achieved by integration of material and/or energy flows, as well as by coutilisation of process equipment. This could potentially induce both technical and economic added-values. At chemical pulp mills, an important feedstock for green chemical production may be the black liquor from the pulp production, since it provides an attractive combinationof advantages. The black liquor availability is, however, directly correlated to the pulp production (i.e. the mill size) and the potential green chemical production volume via pure black liquor gasification (BLG) is therefore limited.In this thesis, two systems are considered that expand on the BLG concept with the intent to increase the chemical production volume, since this could generate positive economy-of-scale effects and is a rather unexamined area. In addition to this, an EFG configuration entailing a lower availability related risk for the considered host pulp mill is also considered. The threeconsidered integrated systems are: (i) co-gasification of biomass-based pyrolysis oil blended with black liquor for methanol production, (ii) parallel operation of BLG and solid biomass EFG for methanol or ammonia production, and (iii) replacing the bark boiler with solid biomass EFG for methanol or ammonia production. These system solutions establish a combination of material, energy and equipment integration. The main aim of this thesis is to increase the knowledge of the characteristics of entrained flow biomass gasification systems and their opportunities for integration in existing industries for production of green chemicals (methanol and ammonia). An appropriate modelling framework that combines chemical modelling on a high level of detail with holistic industrial site modelling is designed and used to identify and quantify energetic and economic addedvalues for the integrated biorefineries. Mathematical process integration models based on Mixed Integer Linear Programming (MILP) of pulp mills are used to study integration of the biomass gasification systems with the mills. An iterative modelling approach is applied between the process integration model and the detailed biomass gasification models based on Aspen Plus or a Matlab-based thermodynamic equilibrium model. As a complement to themodelling framework, a multi-scale equivalent reactor network (ERN) solid biomass-based EFG model is developed to be able to identify and study influential parameters on the gasifiers’ performance in the Aspen Plus platform. This is approached by considering the effect of mass and heat transfer as well as chemical kinetics. The results show that replacing a recovery or a bark boiler with EFG for green chemicals production improves the overall energy system efficiency and the economic performance,compared to the original operation mode of the mill as well as compared to a stand-alone gasification plant. Significant economy-of-scale effects can be obtained from co-gasification of black liquor and pyrolysis oil. Co-gasification will add extra revenue per produced unit of methanol and reduces the production cost significantly compared to gasification of pure pyrolysis oil. In general, integrated EFG systems producing methanol sold to replace fossilgasoline are shown to constitute attractive investments if the product is exempted from taxes. Ammonia produced via EFG is per unit of produced chemical significantly more capital intense than the corresponding system producing methanol. The economic viability in the considered ammonia configurations is therefore found to be lower compared to methanol.The ERN model is shown to be able to estimate key performance indicators such as carbon conversion, cold gas efficiency, syngas composition, etc. for a real gasification process, showing good agreement with experimental results obtained from a pilot scale gasifier. This simulation tool can in future work be implemented in more global models to study and use to improve the techno-economic performance of EFG-based biorefineries, by quantifying theinfluence of important operational parameters. The main conclusion from this work is that production of green chemicals from biomass EFG integrated with a pulp mill is techno-economically advantageous compared to stand-alonealternatives. It is also concluded that the pulp mill size will be decisive for what integration route is the most favourable. Integration of an individual BLG plant with a pulp mill of maximum size would be the most economically beneficial alternative. However, the possibility to increase the green chemical production from a given black liquor volume improves the viability for integration in smaller mills. Increasing the production volume would therefore result in the highest efficiency and economic benefits given mill sizes up to300 kADt/y. From a resource perspective, this would however lead to an increased demand for biomass import to the mill, and this expansion could be limited by the overall availability of biomass resources.Keywords: Pulp mills, integration, biomass, gasification, green chemicals, methanol, ammonia.
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| 16. |
- Armus, Lee, et al.
(författare)
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GOALS-JWST: Mid-infrared Spectroscopy of the Nucleus of NGC 7469
- 2023
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 942:2
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Tidskriftsartikel (refereegranskat)abstract
- We present mid-infrared spectroscopic observations of the nucleus of the nearby Seyfert galaxy NGC 7469 taken with the MIRI instrument on the James Webb Space Telescope (JWST) as part of Directors Discretionary Time Early Release Science program 1328. The high-resolution nuclear spectrum contains 19 emission lines covering a wide range of ionization. The high-ionization lines show broad, blueshifted emission reaching velocities up to 1700 km s−1 and FWHM ranging from ∼500 to 1100 km s−1. The width of the broad emission and the broad-to-narrow line flux ratios correlate with ionization potential. The results suggest a decelerating, stratified, AGN-driven outflow emerging from the nucleus. The estimated mass outflow rate is 1-2 orders of magnitude larger than the current black hole accretion rate needed to power the AGN. Eight pure rotational H2 emission lines are detected with intrinsic widths ranging from FWHM ∼125 to 330 km s−1. We estimate a total mass of warm H2 gas of ∼1.2 × 107 M ⊙ in the central 100 pc. The PAH features are extremely weak in the nuclear spectrum, but a 6.2 μm PAH feature with an equivalent width of ∼0.07 μm and a flux of 2.7 × 10−17 W m−2 is detected. The spectrum is steeply rising in the mid-infrared, with a silicate strength of ∼0.02, significantly smaller than seen in most PG QSOs but comparable to other Seyfert 1s. These early MIRI mid-infrared IFU data highlight the power of JWST to probe the multiphase interstellar media surrounding actively accreting supermassive black holes.
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| 17. |
- Azar, Christian, et al.
(författare)
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Carbon capture and storage from fossil fuels and biomass - : Costs and potential role in stabilizing the atmosphere
- 2006
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Ingår i: Climatic Change. - : Springer Nature. - 0165-0009 .- 1573-1480. ; 74:1-3, s. 47-79
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Tidskriftsartikel (refereegranskat)abstract
- The capture and storage of CO2 from combustion of fossil fuels is gaining attraction as a means to deal with climate change. CO2 emissions from biomass conversion processes can also be captured. If that is done, biomass energy with CO2 capture and storage (BECS) would become a technology that removes CO2 from the atmosphere and at the same time deliver CO2-neutral energy carriers (heat, electricity or hydrogen) to society. Here we present estimates of the costs and conversion efficiency of electricity, hydrogen and heat generation from fossil fuels and biomass with CO2 capture and storage. We then insert these technology characteristics into a global energy and transportation model (GET 5.0), and calculate costs of stabilizing atmospheric CO2 concentration at 350 and 450 ppm. We find that carbon capture and storage technologies applied to fossil fuels have the potential to reduce the cost of meeting the 350 ppm stabilisation targets by 50% compared to a case where these technologies are not available and by 80% when BECS is allowed. For the 450 ppm scenario, the reduction in costs is 40 and 42%, respectively. Thus, the difference in costs between cases where BECS technologies are allowed and where they are not is marginal for the 450 ppm stabilization target. It is for very low stabilization targets that negative emissions become warranted, and this makes BECS more valuable than in cases with higher stabilization targets. Systematic and stochastic sensitivity analysis is performed. Finally, BECS opens up the possibility to remove CO2 from the atmosphere. But this option should not be seen as an argument in favour of doing nothing about the climate problem now and then switching on this technology if climate change turns out to be a significant problem. It is not likely that BECS can be initiated sufficiently rapidly at a sufficient scale to follow this path to avoiding abrupt and serious climate changes if that would happen.
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| 18. |
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| 19. |
- Bianchin, Marina, et al.
(författare)
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GOALS-JWST: Gas Dynamics and Excitation in NGC 7469 Revealed by NIRSpec
- 2024
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Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 965:2
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Tidskriftsartikel (refereegranskat)abstract
- We present new JWST NIRSpec integral field spectroscopy (IFS) data for the luminous infrared galaxy NGC 7469, a nearby (70.6 Mpc) active galaxy with a Seyfert 1.5 nucleus that drives a highly ionized gas outflow and a prominent nuclear star-forming ring. Using the superb sensitivity and high spatial resolution of the JWST instrument NIRSpec IFS, we investigate the role of the Seyfert nucleus in the excitation and dynamics of the circumnuclear gas. Our analysis focuses on the [Fe ii], H2, and hydrogen recombination lines that trace the radiation/shocked-excited molecular and ionized interstellar medium around the active galactic nucleus (AGN). We investigate gas excitation through H2/Brγ and [Fe ii]/Paβ emission line ratios and find that photoionization by the AGN dominates within the central 300 pc of the galaxy except in a small region that shows signatures of shock-heated gas; these shock-heated regions are likely associated with a compact radio jet. In addition, the velocity field and velocity dispersion maps reveal complex gas kinematics. Rotation is the dominant feature, but we also identify noncircular motions consistent with gas inflows as traced by the velocity residuals and the spiral pattern in the Paα velocity dispersion map. The inflow is 2 orders of magnitude higher than the AGN accretion rate. The compact nuclear radio jet has enough power to drive the highly ionized outflow. This scenario suggests that the inflow and outflow are in a self-regulating feeding-feedback process, with a contribution from the radio jet helping to drive the outflow.
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| 20. |
- Bohn, Thomas, et al.
(författare)
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GOALS-JWST: NIRCam and MIRI Imaging of the Circumnuclear Starburst Ring in NGC 7469
- 2023
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 942:2
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Tidskriftsartikel (refereegranskat)abstract
- We present James Webb Space Telescope (JWST) imaging of NGC 7469 with the Near-Infrared Camera and the Mid-InfraRed Instrument. NGC 7469 is a nearby, z = 0.01627, luminous infrared galaxy that hosts both a Seyfert Type-1.5 nucleus and a circumnuclear starburst ring with a radius of ∼0.5 kpc. The new near-infrared (NIR) JWST imaging reveals 66 star-forming regions, 37 of which were not detected by Hubble Space Telescope (HST) observations. Twenty-eight of the 37 sources have very red NIR colors that indicate obscurations up to A v ∼ 7 and a contribution of at least 25% from hot dust emission to the 4.4 μm band. Their NIR colors are also consistent with young (<5 Myr) stellar populations and more than half of them are coincident with the mid-infrared (MIR) emission peaks. These younger, dusty star-forming regions account for ∼6% and ∼17% of the total 1.5 and 4.4 μm luminosity of the starburst ring, respectively. Thanks to JWST, we find a significant number of young dusty sources that were previously unseen due to dust extinction. The newly identified 28 young sources are a significant increase compared to the number of HST-detected young sources (4-5). This makes the total percentage of the young population rise from ∼15% to 48%. These results illustrate the effectiveness of JWST in identifying and characterizing previously hidden star formation in the densest star-forming environments around active galactic nuclei (AGN).
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| 21. |
- Bosveld, Fred C., et al.
(författare)
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The Third GABLS Intercomparison Case for Evaluation Studies of Boundary-Layer Models. Part B : Results and Process Understanding
- 2014
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Ingår i: Boundary-layer Meteorology. - : Springer Science and Business Media LLC. - 0006-8314 .- 1573-1472. ; 152:2, s. 157-187
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Tidskriftsartikel (refereegranskat)abstract
- We describe and analyze the results of the third global energy and water cycle experiment atmospheric boundary layer Study intercomparison and evaluation study for single-column models. Each of the nineteen participating models was operated with its own physics package, including land-surface, radiation and turbulent mixing schemes, for a full diurnal cycle selected from the Cabauw observatory archive. By carefully prescribing the temporal evolution of the forcings on the vertical column, the models could be evaluated against observations. We focus on the gross features of the stable boundary layer (SBL), such as the onset of evening momentum decoupling, the 2-m minimum temperature, the evolution of the inertial oscillation and the morning transition. New process diagrams are introduced to interpret the variety of model results and the relative importance of processes in the SBL; the diagrams include the results of a number of sensitivity runs performed with one of the models. The models are characterized in terms of thermal coupling to the soil, longwave radiation and turbulent mixing. It is shown that differences in longwave radiation schemes among the models have only a small effect on the simulations; however, there are significant variations in downward radiation due to different boundary-layer profiles of temperature and humidity. The differences in modelled thermal coupling to the land surface are large and explain most of the variations in 2-m air temperature and longwave incoming radiation among models. Models with strong turbulent mixing overestimate the boundary-layer height, underestimate the wind speed at 200 m, and give a relatively large downward sensible heat flux. The result is that 2-m air temperature is relatively insensitive to turbulent mixing intensity. Evening transition times spread 1.5 h around the observed time of transition, with later transitions for models with coarse resolution. Time of onset in the morning transition spreads 2 h around the observed transition time. With this case, the morning transition appeared to be difficult to study, no relation could be found between the studied processes, and the variation in the time of the morning transition among the models.
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| 22. |
- Brinkmalm, Gunnar, et al.
(författare)
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An online nano-LC-ESI-FTICR-MS method for comprehensive characterization of endogenous fragments from amyloid β and amyloid precursor protein in human and cat cerebrospinal fluid.
- 2012
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Ingår i: Journal of mass spectrometry : JMS. - : Wiley. - 1096-9888 .- 1076-5174. ; 47:5, s. 591-603
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid precursor protein (APP) is the precursor protein to amyloid β (Aβ), the main constituent of senile plaques in Alzheimer's disease (AD). Endogenous Aβ peptides reflect the APP processing, and greater knowledge of different APP degradation pathways is important to understand the mechanism underlying AD pathology. When one analyzes longer Aβ peptides by low-energy collision-induced dissociation tandem mass spectrometry (MS/MS), mainly long b-fragments are observed, limiting the possibility to determine variations such as amino acid variants or post-translational modifications (PTMs) within the N-terminal half of the peptide. However, by using electron capture dissociation (ECD), we obtained a more comprehensive sequence coverage for several APP/Aβ peptide species, thus enabling a deeper characterization of possible variants and PTMs. Abnormal APP/Aβ processing has also been described in the lysosomal storage disease Niemann-Pick type C and the major large animal used for studying this disease is cat. By ECD MS/MS, a substitution of Asp7 → Glu in cat Aβ was identified. Further, sialylated core 1 like O-glycans at Tyr10, recently discovered in human Aβ (a previously unknown glycosylation type), were identified also in cat cerebrospinal fluid (CSF). It is therefore likely that this unusual type of glycosylation is common for (at least) species belonging to the magnorder Boreoeutheria. We here describe a detailed characterization of endogenous APP/Aβ peptide species in CSF by using an online top-down MS-based method.
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| 23. |
- Chatterjee, Saion, et al.
(författare)
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Type 2 Diabetes as a Risk Factor for Dementia in Women Compared With Men: A Pooled Analysis of 2.3 Million People Comprising More Than 100,000 Cases of Dementia
- 2016
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 39:2, s. 300-307
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Type 2 diabetes confers a greater excess risk of cardiovascular disease in women than in men. Diabetes is also a risk factor for dementia, but whether the association is similar in women and men remains unknown. We performed a meta-analysis of unpublished data to estimate the sex-specific relationship between women and men with diabetes with incident dementia. RESEARCH DESIGN AND METHODS A systematic search identified studies published prior to November 2014 that had reported on the prospective association between diabetes and dementia. Study authors contributed unpublished sex-specific relative risks (RRs) and 95% CIs on the association between diabetes and all dementia and its subtypes. Sex-specific RRs and the women-to-men ratio of RRs (RRRs) were pooled using random-effects meta-analyses. RESULTS Study-level data from 14 studies, 2,310,330 individuals, and 102,174 dementia case patients were included. In multiple-adjusted analyses, diabetes was associated with a 60% increased risk of any dementia in both sexes (women: pooled RR 1.62 [95% CI 1.45–1.80]; men: pooled RR 1.58 [95% CI 1.38–1.81]). The diabetes-associated RRs for vascular dementia were 2.34 (95% CI 1.86–2.94) in women and 1.73 (95% CI 1.61–1.85) in men, and for nonvascular dementia the RRs were 1.53 (95% CI 1.35–1.73) in women and 1.49 (95% CI 1.31–1.69) in men. Overall, women with diabetes had a 19% greater risk for the development of vascular dementia than men (multiple-adjusted RRR 1.19 [95% CI 1.08–1.30]; P < 0.001). CONCLUSIONS Individuals with type 2 diabetes are at ∼60% greater risk for the development of dementia compared with those without diabetes. For vascular dementia, but not for nonvascular dementia, the additional risk is greater in women.
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| 24. |
- Cooper-DeHoff, Rhonda M., et al.
(författare)
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The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms
- 2022
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Ingår i: Clinical Pharmacology and Therapeutics. - : John Wiley & Sons. - 0009-9236 .- 1532-6535. ; 111:5, s. 1007-1021
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Tidskriftsartikel (refereegranskat)abstract
- Statins reduce cholesterol, prevent cardiovascular disease, and are among the most commonly prescribed medications in the world. Statin-associated musculoskeletal symptoms (SAMS) impact statin adherence and ultimately can impede the long-term effectiveness of statin therapy. There are several identified pharmacogenetic variants that impact statin disposition and adverse events during statin therapy. SLCO1B1 encodes a transporter (SLCO1B1; alternative names include OATP1B1 or OATP-C) that facilitates the hepatic uptake of all statins. ABCG2 encodes an efflux transporter (BCRP) that modulates the absorption and disposition of rosuvastatin. CYP2C9 encodes a phase I drug metabolizing enzyme responsible for the oxidation of some statins. Genetic variation in each of these genes alters systemic exposure to statins (i.e., simvastatin, rosuvastatin, pravastatin, pitavastatin, atorvastatin, fluvastatin, lovastatin), which can increase the risk for SAMS. We summarize the literature supporting these associations and provide therapeutic recommendations for statins based on SLCO1B1, ABCG2, and CYP2C9 genotype with the goal of improving the overall safety, adherence, and effectiveness of statin therapy. This document replaces the 2012 and 2014 Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for SLCO1B1 and simvastatin-induced myopathy.
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| 25. |
- Cox, Michael, et al.
(författare)
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How academic podcasting can change academia and its relationship with society : A conversation and guide
- 2023
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Ingår i: Frontiers in Communication. - 2297-900X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we explore the potential of academic podcasting to e ect positive change within academia and between academia and society. Building on the concept of epistemic living spaces, we consider how podcasting can change how we evaluate what is legitimate knowledge and methods for knowledge production, who has access to what privileges and power, the nature of our connections within academia and with other partners, and how we experience the constraints and opportunities of space and time. We conclude by o ering a guide for others who are looking to develop their own academic podcasting projects and discuss the potential for podcasting to be formalized as amainstream academic output. To listen to an abridged and annotated version of this paper, visit: https://soundcloud.com/conservechange/podcastinginacademia.
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