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| 2. |
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| 3. |
- Tran, K. B., et al.
(author)
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The global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019
- 2022
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In: Lancet. - 0140-6736. ; 400:10352, s. 563-591
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Journal article (peer-reviewed)abstract
- Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 4. |
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| 5. |
- Ikuta, K. S., et al.
(author)
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Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019
- 2022
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In: Lancet. - : Elsevier BV. - 0140-6736. ; 400:10369, s. 2221-2248
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Journal article (peer-reviewed)abstract
- Background Reducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes. Methods We estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2.5th and 97.5th percentiles across 1000 posterior draws for each quantity of interest. Findings From an estimated 13.7 million (95% UI 10.9-17.1) infection-related deaths in 2019, there were 7.7 million deaths (5.7-10.2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13.6% (10.2-18.1) of all global deaths and 56.2% (52.1-60.1) of all sepsis-related deaths in 2019. Five leading pathogens-Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa-were responsible for 54.9% (52.9-56.9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185-285) per 100 000 population, and lowest in the high-income super-region, with 52.2 deaths (37.4-71.5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths. Interpretation The 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vaccines. These estimates can be used to help set priorities for vaccine need, demand, and development. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 7. |
- Frostad, J. J., et al.
(author)
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Mapping development and health effects of cooking with solid fuels in low-income and middle-income countries, 2000-18: a geospatial modelling study
- 2022
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In: Lancet Global Health. - 2214-109X. ; 10:10
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Journal article (peer-reviewed)abstract
- Background More than 3 billion people do not have access to clean energy and primarily use solid fuels to cook. Use of solid fuels generates household air pollution, which was associated with more than 2 million deaths in 2019. Although local patterns in cooking vary systematically, subnational trends in use of solid fuels have yet to be comprehensively analysed. We estimated the prevalence of solid-fuel use with high spatial resolution to explore subnational inequalities, assess local progress, and assess the effects on health in low-income and middle-income countries (LMICs) without universal access to clean fuels. Methods We did a geospatial modelling study to map the prevalence of solid-fuel use for cooking at a 5 km x 5 km resolution in 98 LMICs based on 2.1 million household observations of the primary cooking fuel used from 663 population-based household surveys over the years 2000 to 2018. We use observed temporal patterns to forecast household air pollution in 2030 and to assess the probability of attaining the Sustainable Development Goal (SDG) target indicator for clean cooking. We aligned our estimates of household air pollution to geospatial estimates of ambient air pollution to establish the risk transition occurring in LMICs. Finally, we quantified the effect of residual primary solid-fuel use for cooking on child health by doing a counterfactual risk assessment to estimate the proportion of deaths from lower respiratory tract infections in children younger than 5 years that could be associated with household air pollution. Findings Although primary reliance on solid-fuel use for cooking has declined globally, it remains widespread. 593 million people live in districts where the prevalence of solid-fuel use for cooking exceeds 95%. 66% of people in LMICs live in districts that are not on track to meet the SDG target for universal access to clean energy by 2030. Household air pollution continues to be a major contributor to particulate exposure in LMICs, and rising ambient air pollution is undermining potential gains from reductions in the prevalence of solid-fuel use for cooking in many countries. We estimated that, in 2018, 205000 (95% uncertainty interval 147000-257000) children younger than 5 years died from lower respiratory tract infections that could be attributed to household air pollution. Interpretation Efforts to accelerate the adoption of clean cooking fuels need to be substantially increased and recalibrated to account for subnational inequalities, because there are substantial opportunities to improve air quality and avert child mortality associated with household air pollution. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.
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| 8. |
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| 9. |
- Kinyoki, DK, et al.
(author)
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Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017
- 2020
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In: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 26:5, s. 750-759
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Journal article (peer-reviewed)abstract
- A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic.
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| 12. |
- Sbarra, AN, et al.
(author)
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Mapping routine measles vaccination in low- and middle-income countries
- 2021
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 589:7842, s. 415-
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Journal article (peer-reviewed)abstract
- The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs)1–4. Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)5–8. Here we generated annual estimates of routine childhood MCV1 coverage at 5 × 5-km2pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children.
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| 17. |
- Ederle, Joerg, et al.
(author)
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Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
- 2010
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In: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Journal article (peer-reviewed)abstract
- Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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| 18. |
- Abbafati, Cristiana, et al.
(author)
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- 2020
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Journal article (peer-reviewed)
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| 19. |
- Sumaila, U. Rashid, et al.
(author)
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WTO must ban harmful fisheries subsidies
- 2021
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
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Journal article (other academic/artistic)
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| 20. |
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| 21. |
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| 22. |
- Dareng, EO, et al.
(author)
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Polygenic risk modeling for prediction of epithelial ovarian cancer risk
- 2022
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In: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 30:3, s. 349-362
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Journal article (peer-reviewed)abstract
- Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, “select and shrink for summary statistics” (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28–1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08–1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21–1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29–1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35–1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
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| 23. |
- Elks, Cathy E, et al.
(author)
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Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
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Journal article (peer-reviewed)abstract
- To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
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| 24. |
- Estrada, Karol, et al.
(author)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Journal article (peer-reviewed)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 25. |
- Fripiat, F., et al.
(author)
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Macro-nutrient concentrations in Antarctic pack ice: Overall patterns and overlooked processes
- 2017
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In: Elementa. - : University of California Press. - 2325-1026. ; 5
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Journal article (peer-reviewed)abstract
- Antarctic pack ice is inhabited by a diverse and active microbial community reliant on nutrients for growth. Seeking patterns and overlooked processes, we performed a large-scale compilation of macro-nutrient data (hereafter termed nutrients) in Antarctic pack ice (306 ice-cores collected from 19 research cruises). Dissolved inorganic nitrogen and silicic acid concentrations change with time, as expected from a seasonally productive ecosystem. In winter, salinity-normalized nitrate and silicic acid concentrations (C∗) in sea ice are close to seawater concentrations (Cw), indicating little or no biological activity. In spring, nitrate and silicic acid concentrations become partially depleted with respect to seawater (C∗ < Cw), commensurate with the seasonal build-up of ice microalgae promoted by increased insolation. Stronger and earlier nitrate than silicic acid consumption suggests that a significant fraction of the primary productivity in sea ice is sustained by flagellates. By both consuming and producing ammonium and nitrite, the microbial community maintains these nutrients at relatively low concentrations in spring. With the decrease in insolation beginning in late summer, dissolved inorganic nitrogen and silicic acid concentrations increase, indicating imbalance between their production (increasing or unchanged) and consumption (decreasing) in sea ice. Unlike the depleted concentrations of both nitrate and silicic acid from spring to summer, phosphate accumulates in sea ice (C∗ > Cw). The phosphate excess could be explained by a greater allocation to phosphorus-rich biomolecules during ice algal blooms coupled with convective loss of excess dissolved nitrogen, preferential remineralization of phosphorus, and/or phosphate adsorption onto metal-organic complexes. Ammonium also appears to be efficiently adsorbed onto organic matter, with likely consequences to nitrogen mobility and availability. This dataset supports the view that the sea ice microbial community is highly efficient at processing nutrients but with a dynamic quite different from that in oceanic surface waters calling for focused future investigations. Copyright © 2017 The Author(s).
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| 26. |
- Hathazi, D., et al.
(author)
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Metabolic shift underlies recovery in reversible infantile respiratory chain deficiency
- 2020
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In: Embo Journal. - : EMBO. - 0261-4189 .- 1460-2075. ; 39:23
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Journal article (peer-reviewed)abstract
- Reversible infantile respiratory chain deficiency (RIRCD) is a rare mitochondrial myopathy leading to severe metabolic disturbances in infants, which recover spontaneously after 6-months of age. RIRCD is associated with the homoplasmic m.14674T>C mitochondrial DNA mutation; however, only similar to 1/100 carriers develop the disease. We studied 27 affected and 15 unaffected individuals from 19 families and found additional heterozygous mutations in nuclear genes interacting with mt-tRNAGlu including EARS2 and TRMU in the majority of affected individuals, but not in healthy carriers of m.14674T>C, supporting a digenic inheritance. Our transcriptomic and proteomic analysis of patient muscle suggests a stepwise mechanism where first, the integrated stress response associated with increased FGF21 and GDF15 expression enhances the metabolism modulated by serine biosynthesis, one carbon metabolism, TCA lipid oxidation and amino acid availability, while in the second step mTOR activation leads to increased mitochondrial biogenesis. Our data suggest that the spontaneous recovery in infants with digenic mutations may be modulated by the above described changes. Similar mechanisms may explain the variable penetrance and tissue specificity of other mtDNA mutations and highlight the potential role of amino acids in improving mitochondrial disease.
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| 27. |
- Wang, Thomas J, et al.
(author)
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Common genetic determinants of vitamin D insufficiency: a genome-wide association study.
- 2010
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In: Lancet. - 1474-547X. ; 376:9736, s. 180-8
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Journal article (peer-reviewed)abstract
- BACKGROUND: Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25-hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency. METHODS: We undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L. We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis. Genotype scores were constructed for confirmed variants. FINDINGS: Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts: 4p12 (overall p=1.9x10(-109) for rs2282679, in GC); 11q12 (p=2.1x10(-27) for rs12785878, near DHCR7); and 11p15 (p=3.3x10(-20) for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6.0x10(-10) for rs6013897). Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L (OR 2.47, 95% CI 2.20-2.78, p=2.3x10(-48)) or lower than 50 nmol/L (1.92, 1.70-2.16, p=1.0x10(-26)) compared with those in the lowest quartile. INTERPRETATION: Variants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency. FUNDING: Full funding sources listed at end of paper (see Acknowledgments).
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| 28. |
- Hassler, B., et al.
(author)
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Past changes in the vertical distribution of ozone - Part 1: Measurement techniques, uncertainties and availability
- 2014
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In: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 7:5, s. 1395-1427
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Journal article (peer-reviewed)abstract
- Peak stratospheric chlorofluorocarbon (CFC) and other ozone depleting substance (ODS) concentrations were reached in the mid- to late 1990s. Detection and attribution of the expected recovery of the stratospheric ozone layer in an atmosphere with reduced ODSs as well as efforts to understand the evolution of stratospheric ozone in the presence of increasing greenhouse gases are key current research topics. These require a critical examination of the ozone changes with an accurate knowledge of the spatial (geographical and vertical) and temporal ozone response. For such an examination, it is vital that the quality of the measurements used be as high as possible and measurement uncertainties well quantified. In preparation for the 2014 United Nations Environment Programme (UNEP)/World Meteorological Organization (WMO) Scientific Assessment of Ozone Depletion, the SPARC/IO3C/IGACO-O3/NDACC (SI2N) Initiative was designed to study and document changes in the global ozone profile distribution. This requires assessing long-term ozone profile data sets in regards to measurement stability and uncertainty characteristics. The ultimate goal is to establish suitability for estimating long-term ozone trends to contribute to ozone recovery studies. Some of the data sets have been improved as part of this initiative with updated versions now available. This summary presents an overview of stratospheric ozone profile measurement data sets (ground and satellite based) available for ozone recovery studies. Here we document measurement techniques, spatial and temporal coverage, vertical resolution, native units and measurement uncertainties. In addition, the latest data versions are briefly described (including data version updates as well as detailing multiple retrievals when available for a given satellite instrument). Archive location information for each data set is also given.
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| 29. |
- Van Haute, L., et al.
(author)
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TEFM variants impair mitochondrial transcription causing childhood-onset neurological disease
- 2023
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- Mutations in the mitochondrial or nuclear genomes are associated with a diverse group of human disorders characterized by impaired mitochondrial respiration. Within this group, an increasing number of mutations have been identified in nuclear genes involved in mitochondrial RNA biology. The TEFM gene encodes the mitochondrial transcription elongation factor responsible for enhancing the processivity of mitochondrial RNA polymerase, POLRMT. We report for the first time that TEFM variants are associated with mitochondrial respiratory chain deficiency and a wide range of clinical presentations including mitochondrial myopathy with a treatable neuromuscular transmission defect. Mechanistically, we show muscle and primary fibroblasts from the affected individuals have reduced levels of promoter distal mitochondrial RNA transcripts. Finally, tefm knockdown in zebrafish embryos resulted in neuromuscular junction abnormalities and abnormal mitochondrial function, strengthening the genotype-phenotype correlation. Our study highlights that TEFM regulates mitochondrial transcription elongation and its defect results in variable, tissue-specific neurological and neuromuscular symptoms.
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| 30. |
- Butler, Geraldine, et al.
(author)
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Evolution of pathogenicity and sexual reproduction in eight Candida genomes.
- 2009
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 459:7247, s. 657-62
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Journal article (peer-reviewed)abstract
- Candida species are the most common cause of opportunistic fungal infection worldwide. Here we report the genome sequences of six Candida species and compare these and related pathogens and non-pathogens. There are significant expansions of cell wall, secreted and transporter gene families in pathogenic species, suggesting adaptations associated with virulence. Large genomic tracts are homozygous in three diploid species, possibly resulting from recent recombination events. Surprisingly, key components of the mating and meiosis pathways are missing from several species. These include major differences at the mating-type loci (MTL); Lodderomyces elongisporus lacks MTL, and components of the a1/2 cell identity determinant were lost in other species, raising questions about how mating and cell types are controlled. Analysis of the CUG leucine-to-serine genetic-code change reveals that 99% of ancestral CUG codons were erased and new ones arose elsewhere. Lastly, we revise the Candida albicans gene catalogue, identifying many new genes.
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| 31. |
- Wei, Tzu-Chieh, et al.
(author)
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Quantifying multipartite entanglement
- 2004
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In: Quantum communication, meaurement and computing. - : AIP. - 0735402167 ; , s. 241-244
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Conference paper (peer-reviewed)abstract
- A natural way of quantifying the degree of entanglement for a pure quantum state is to compare how far this state is from the set of all unentangled pure states. This geometric measure of entanglement is explored for bipartite and multipartite pure and mixed states. It is determined analytically for arbitrary two-qubit mixed states and for generalized Werner and isotropic states. It is also applied to certain multipartite mixed states. including two multipartite bound entangeled states discovered by Smolin and Dur. Moreover, the geometric measure of entanglement is applied to the ground state of the Ising model in a transverse magnetic field. From this model the entanglement is shown to exhibit singular behavior at the quantum critical point.
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| 32. |
- Dunsby, C., et al.
(author)
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An electronically tunable ultrafast laser source applied to fluorescence imaging and fluorescence lifetime imaging microscopy
- 2004
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In: Journal of Physics D. - : IOP Publishing. - 0022-3727 .- 1361-6463. ; 37:23, s. 3296-3303
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Journal article (peer-reviewed)abstract
- Fluorescence imaging is used widely in microscopy and macroscopic imaging applications for fields ranging from biomedicine to materials science. A critical component for any fluorescence imaging system is the excitation source. Traditionally, wide-field systems use filtered thermal or arc-generated white light sources, while point scanning confocal microscope systems require spatially coherent (point-like) laser sources. Unfortunately, the limited range of visible wavelengths available from conventional laser sources constrains the design and usefulness of fluorescent probes in confocal microscopy. A 'hands-off' laser-like source, electronically tunable across the visible spectrum, would be invaluable for fluorescence imaging and provide new opportunities, e.g. automated excitation fingerprinting and in situ measurement of excitation cross-sections. Yet more information can be obtained using fluorescence lifetime imaging (FLIM), which requires that the light source be pulsed or rapidly modulated. We show how a white light continuum, generated by injecting femtosecond optical radiation into a micro-structured optical fibre, coupled with a simple prism-based tunable filter arrangement, can fulfil all these roles as a continuously electronically tunable (435-1150 nm) visible ultrafast light source in confocal, wide-field and FLIM systems.
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| 33. |
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| 34. |
- Goodall, G., et al.
(author)
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Biphasic insulin aspart 70/30 vs. insulin glargine in insulin naïve type 2 diabetes patients : modelling the long-term health economic implications in a Swedish setting
- 2008
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In: International journal of clinical practice (Esher). - : Wiley-Blackwell Publishing Inc.. - 1368-5031 .- 1742-1241. ; 62:6, s. 869-876
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To evaluate the long-term clinical and economic outcomes of biphasic insulin aspart 70/30 (BIAsp 70/30) treatment vs. insulin glargine in insulin naïve, type 2 diabetes patients failing oral antidiabetic drugs in a Swedish setting.METHODS: A published and validated computer simulation model (the CORE Diabetes Model) was used to project life expectancy, quality-adjusted life expectancy (QALE) and costs over patient lifetimes. Cohort characteristics [54.5% male, mean age 52.4 years, 9 years mean diabetes duration, mean glycosylated haemoglobin (HbA1c) 9.77%] and treatment effects were based on results from the Initiate Insulin by Aggressive Titration and Education (INITIATE) clinical trial. Direct medical costs were accounted in 2006 Swedish Kronor (SEK) and economic and clinical benefits were discounted at 3% per annum.RESULTS: Biphasic insulin aspart 70/30 treatment when compared with insulin glargine treatment was associated with improvements in discounted life expectancy of 0.21 years (13.10 vs. 12.89 years) and QALE of 0.21 quality-adjusted life years (QALYs) (9.16 vs. 8.96 QALYs). Reductions in the incidence of diabetes-related complications in the BIAsp 70/30 treatment arm led to reduced total costs of SEK 10,367 when compared with insulin glargine (SEK 396,475 vs. SEK 406,842) over patient lifetimes. BIAsp 70/30 treatment was projected to be dominant (cost and lifesaving) when compared with insulin glargine in the base case analysis.CONCLUSIONS: Biphasic insulin aspart 70/30 treatment was associated with improved clinical outcomes and reduced costs compared with insulin glargine treatment over patient lifetimes. These results were driven by improved HbA1c levels associated with BIAsp 70/30 compared with insulin glargine and the accompanying reduction in diabetes-related complications despite increases in body mass index.
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| 35. |
- Haas, Brian J., et al.
(author)
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Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans
- 2009
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461:7262, s. 393-398
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Journal article (peer-reviewed)abstract
- Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement(1). To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population(1). Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion(2). Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars(3,4). Here we report the sequence of the P. infestans genome, which at similar to 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for similar to 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.
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