| 1. |
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| 2. |
- Lind, Lars, et al.
(författare)
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Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
- 2021
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Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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| 12. |
- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 17. |
- Saevarsdottir, S., et al.
(författare)
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Multiomics analysis of rheumatoid arthritis yields sequence variants that have large effects on risk of the seropositive subset
- 2022
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 81:8
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To find causal genes for rheumatoid arthritis (RA) and its seropositive (RF and/or ACPA positive) and seronegative subsets. Methods We performed a genome-wide association study (GWAS) of 31 313 RA cases (68% seropositive) and similar to 1 million controls from Northwestern Europe. We searched for causal genes outside the HLA-locus through effect on coding, mRNA expression in several tissues and/or levels of plasma proteins (SomaScan) and did network analysis (Qiagen). Results We found 25 sequence variants for RA overall, 33 for seropositive and 2 for seronegative RA, altogether 37 sequence variants at 34 non-HLA loci, of which 15 are novel. Genomic, transcriptomic and proteomic analysis of these yielded 25 causal genes in seropositive RA and additional two overall. Most encode proteins in the network of interferon-alpha/beta and IL-12/23 that signal through the JAK/STAT-pathway. Highlighting those with largest effect on seropositive RA, a rare missense variant in STAT4 (rs140675301-A) that is independent of reported non-coding STAT4-variants, increases the risk of seropositive RA 2.27-fold (p=2.1x10(-9)), more than the rs2476601-A missense variant in PTPN22 (OR=1.59, p=1.3x10(-160)). STAT4 rs140675301-A replaces hydrophilic glutamic acid with hydrophobic valine (Glu128Val) in a conserved, surface-exposed loop. A stop-mutation (rs76428106-C) in FLT3 increases seropositive RA risk (OR=1.35, p=6.6x10(-11)). Independent missense variants in TYK2 (rs34536443-C, rs12720356-C, rs35018800-A, latter two novel) associate with decreased risk of seropositive RA (ORs=0.63-0.87, p=10(-9)-10(-27)) and decreased plasma levels of interferon-alpha/beta receptor 1 that signals through TYK2/JAK1/STAT4. Conclusion Sequence variants pointing to causal genes in the JAK/STAT pathway have largest effect on seropositive RA, while associations with seronegative RA remain scarce.
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| 18. |
- Taddei, C, et al.
(författare)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Tidskriftsartikel (refereegranskat)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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| 19. |
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| 22. |
- Ferreira, MA, et al.
(författare)
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Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1741-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
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| 23. |
- Jiang, X., et al.
(författare)
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Shared heritability and functional enrichment across six solid cancers
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
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| 24. |
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| 25. |
- Appeltans, W., et al.
(författare)
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The Magnitude of Global Marine Species Diversity
- 2012
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 22:23, s. 2189-2202
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Tidskriftsartikel (refereegranskat)abstract
- Background: The question of how many marine species exist is important because it provides a metric for how much we do and do not know about life in the oceans. We have compiled the first register of the marine species of the world and used this baseline to estimate how many more species, partitioned among all major eukaryotic groups, may be discovered. Results: There are similar to 226,000 eukaryotic marine species described. More species were described in the past decade (similar to 20,000) than in any previous one. The number of authors describing new species has been increasing at a faster rate than the number of new species described in the past six decades. We report that there are similar to 170,000 synonyms, that 58,000-72,000 species are collected but not yet described, and that 482,000-741,000 more species have yet to be sampled. Molecular methods may add tens of thousands of cryptic species. Thus, there may be 0.7-1.0 million marine species. Past rates of description of new species indicate there may be 0.5 +/- 0.2 million marine species. On average 37% (median 31%) of species in over 100 recent field studies around the world might be new to science. Conclusions: Currently, between one-third and two-thirds of marine species may be undescribed, and previous estimates of there being well over one million marine species appear highly unlikely. More species than ever before are being described annually by an increasing number of authors. If the current trend continues, most species will be discovered this century.
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| 26. |
- Bergin, E. A., et al.
(författare)
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Sensitive limits on the abundance of cold water vapor in the DM Tauri protoplanetary disk
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L33-
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Tidskriftsartikel (refereegranskat)abstract
- We performed a sensitive search for the ground-state emission lines of ortho-and para-water vapor in the DM Tau protoplanetary disk using the Herschel/HIFI instrument. No strong lines are detected down to 3 sigma levels in 0.5 km s(-1) channels of 4.2 mK for the 1(10)-1(01) line and 12.6 mK for the 1(11)-0(00) line. We report a very tentative detection, however, of the 1(10)-1(01) line in the wide band spectrometer, with a strength of T-mb = 2.7 mK, a width of 5.6 km s(-1) and an integrated intensity of 16.0 mK km s(-1). The latter constitutes a 6 sigma detection. Regardless of the reality of this tentative detection, model calculations indicate that our sensitive limits on the line strengths preclude efficient desorption of water in the UV illuminated regions of the disk. We hypothesize that more than 95-99% of the water ice is locked up in coagulated grains that have settled to the midplane.
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| 27. |
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| 28. |
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| 29. |
- Dork, T, et al.
(författare)
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Two truncating variants in FANCC and breast cancer risk
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 12524-
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Tidskriftsartikel (refereegranskat)abstract
- Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
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| 30. |
- Gezelius, E., et al.
(författare)
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Coagulation biomarkers and prediction of venous thromboembolism and survival in small cell lung cancer : A sub-study of RASTEN - A randomized trial with low molecular weight heparin
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- Coagulation activation and venous thromboembolism (VTE) are hallmarks of cancer; however, there is an unmet need of improved biomarkers for individualized anticoagulant treatment. The present sub-study of the RASTEN trial was designed to explore the role of coagulation biomarkers in predicting VTE risk and outcome in a homogenous cancer patient population. RASTEN is a multicenter, randomized phase-3 trial investigating the survival effect of low molecular weight heparin enoxaparin when added to standard treatment in newly diagnosed small cell lung cancer (SCLC) patients. Plasma collected at baseline, during treatment, and at follow-up was used in this ad hoc sub-study (N = 242). Systemic coagulation was assessed using four assays reflecting various facets of the coagulation system: Total tissue factor (TF); extracellular vesicle associated TF (EV-TF); procoagulant phospholipids (PPL); and thrombin generation (TG). We found small variations of biomarker levels between baseline, during treatment and at follow-up, and appeared independent on low molecular weight heparin treatment. Overall, none of the measured biomarkers at any time-point did significantly associate with VTE incidence, although increased total TF at baseline showed significant association in control patients not receiving low molecular weight heparin (P = 0.03). Increased TG-Peak was significantly associated with decreased overall survival (OS; P = 0.03), especially in patients with extensive disease. Low baseline EV-TF predicted a worse survival in the low molecular weight heparin as compared with the control group (HR 1.42; 95% CI 1.04–1.95; P = 0.03; P for interaction = 0.12). We conclude that the value of the analyzed coagulation biomarkers for the prediction of VTE risk was very limited in SCLC patients. The associations between TG-Peak and EV-TF with patient survival and response to low molecular weight heparin therapy, respectively, warrant further studies on the role of coagulation activation in SCLC aggressiveness.
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| 31. |
- Heggebo, L. C., et al.
(författare)
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Investigating survival, quality of life and cognition in PROton versus photon therapy for IDH-mutated diffuse grade 2 and 3 GLIOmas (PRO-GLIO): a randomised controlled trial in Norway and Sweden
- 2023
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThe use of proton therapy increases globally despite a lack of randomised controlled trials demonstrating its efficacy and safety. Proton therapy enables sparing of non-neoplastic tissue from radiation. This is principally beneficial and holds promise of reduced long-term side effects. However, the sparing of seemingly non-cancerous tissue is not necessarily positive for isocitrate dehydrogenase (IDH)-mutated diffuse gliomas grade 2-3, which have a diffuse growth pattern. With their relatively good prognosis, yet incurable nature, therapy needs to be delicately balanced to achieve a maximal survival benefit combined with an optimised quality of life.Methods and analysisPRO-GLIO (PROton versus photon therapy in IDH-mutated diffuse grade 2 and 3 GLIOmas) is an open-label, multicentre, randomised phase III non-inferiority study. 224 patients aged 18-65 years with IDH-mutated diffuse gliomas grade 2-3 from Norway and Sweden will be randomised 1:1 to radiotherapy delivered with protons (experimental arm) or photons (standard arm). First intervention-free survival at 2 years is the primary endpoint. Key secondary endpoints are fatigue and cognitive impairment, both at 2 years. Additional secondary outcomes include several survival measures, health-related quality of life parameters and health economy endpoints.Ethics and disseminationTo implement proton therapy as part of standard of care for patients with IDH-mutated diffuse gliomas grade 2-3, it should be deemed safe. With its randomised controlled design testing proton versus photon therapy, PRO-GLIO will provide important information for this patient population concerning safety, cognition, fatigue and other quality of life parameters. As proton therapy is considerably more costly than its photon counterpart, cost-effectiveness will also be evaluated. PRO-GLIO is approved by ethical committees in Norway (Regional Committee for Medical & Health Research Ethics) and Sweden (The Swedish Ethical Review Authority) and patient inclusion has commenced. Trial results will be published in international peer-reviewed journals, relevant conferences, national and international meetings and expert forums.Trial registration numberClinicalTrials.gov Registry (NCT05190172).
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| 35. |
- van der Tak, F. F. S., et al.
(författare)
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Water abundance variations around high-mass protostars: HIFI observations of the DR21 region
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518:Article Number: L107
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Tidskriftsartikel (refereegranskat)abstract
- Context. Water is a key molecule in the star formation process, but its spatial distribution in star-forming regions is not well known. Aims. We study the distribution of dust continuum and H2O and (CO)-C-13 line emission in DR21, a luminous star-forming region with a powerful outflow and a compact H II region. Methods. Herschel-HIFI spectra near 1100 GHz show narrow (CO)-C-13 10-9 emission and H2O 1(11)-0(00) absorption from the dense core and broad emission from the outflow in both lines. The H2O line also shows absorption by a foreground cloud known from ground-based observations of low-J CO lines. Results. The dust continuum emission is extended over 36 '' FWHM, while the (CO)-C-13 and H2O lines are confined to approximate to 24 '' or less. The foreground absorption appears to peak further North than the other components. Radiative transfer models indicate very low abundances of similar to 2 x 10(-10) for H2O and similar to 8 x 10(-7) for (CO)-C-13 in the dense core, and higher H2O abundances of similar to 4 x 10(-9) in the foreground cloud and similar to 7 x 10(-7) in the outflow. Conclusions. The high H2O abundance in the warm outflow is probably due to the evaporation of water-rich icy grain mantles, while the H2O abundance is kept down by freeze-out in the dense core and by photodissociation in the foreground cloud.
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| 36. |
- van Dishoeck, E. F., et al.
(författare)
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Water in Star-forming Regions with the Herschel Space Observatory (WISH). I. Overview of Key Program and First Results
- 2011
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Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 123:900, s. 138-170
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Tidskriftsartikel (refereegranskat)abstract
- Water In Star-forming regions with Herschel (WISH) is a key program on the Herschel Space Observatory designed to probe the physical and chemical structures of young stellar objects using water and related molecules and to follow the water abundance from collapsing clouds to planet-forming disks. About 80 sources are targeted, covering a wide ranee of luminosities-from low ( 10(5) L-circle dot)-and a wide range of evolutionary stages-from cold prestellar cores to warm protostellar envelopes and outflows to disks around young stars. Both the HIFI and PACS instruments are used to observe a variety of lines of H2O, (H2O)-O-18 and chemically related species at the source position and in small maps around the protostars and selected outflow positions. In addition, high-frequency lines of CO, (CO)-C-13, and (CO)-O-18 are obtained with Herschel and are complemented by ground-based observations of dust continuum, HDO, CO and its isotopologs, and other molecules to ensure a self-consistent data set for analysis. An overview of the scientific motivation and observational strategy of the program is given, together with the modeling approach and analysis tools that have been developed. Initial science results are presented. These include a lack of water in cold gas at abundances that are lower than most predictions, strong water emission from shocks in protostellar environments, the importance of UV radiation in heating the gas along outflow walls across the full range of luminosities, and surprisingly widespread detection of the chemically related hydrides OH+ and H2O+ in outflows and foreground gas. Quantitative estimates of the energy budget indicate that H2O is generally not the dominant coolant in the warm dense gas associated with protostars. Very deep limits on the cold gaseous water reservoir in the outer regions of protoplanetary disks are obtained that have profound implications for our understanding of grain growth and mixing in disks.
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| 37. |
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| 38. |
- Aidas, Kestutis, et al.
(författare)
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The Dalton quantum chemistry program system
- 2014
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Ingår i: WIREs Computational Molecular Science. - : Wiley. - 1759-0876 .- 1759-0884. ; 4:3, s. 269-284
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Tidskriftsartikel (refereegranskat)abstract
- Dalton is a powerful general-purpose program system for the study of molecular electronic structure at the Hartree-Fock, Kohn-Sham, multiconfigurational self-consistent-field, MOller-Plesset, configuration-interaction, and coupled-cluster levels of theory. Apart from the total energy, a wide variety of molecular properties may be calculated using these electronic-structure models. Molecular gradients and Hessians are available for geometry optimizations, molecular dynamics, and vibrational studies, whereas magnetic resonance and optical activity can be studied in a gauge-origin-invariant manner. Frequency-dependent molecular properties can be calculated using linear, quadratic, and cubic response theory. A large number of singlet and triplet perturbation operators are available for the study of one-, two-, and three-photon processes. Environmental effects may be included using various dielectric-medium and quantum-mechanics/molecular-mechanics models. Large molecules may be studied using linear-scaling and massively parallel algorithms. Dalton is distributed at no cost from for a number of UNIX platforms.
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| 39. |
- Al-Karadaghi, Salam, et al.
(författare)
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A decade of progress in understanding the structural basis of protein synthesis
- 2000
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Ingår i: Progress in Biophysics and Molecular Biology. - 1873-1732. ; 73:2, s. 167-193
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Forskningsöversikt (refereegranskat)abstract
- The key reaction of protein synthesis, peptidyl transfer, is catalysed in all living organisms by the ribosome - an advanced and highly efficient molecular machine. During the last decade extensive X-ray crystallographic and NMR studies of the three-dimensional structure of ribosomal proteins, ribosomal RNA components and their complexes with ribosomal proteins, and of several translation factors in different functional states have taken us to a new level of understanding of the mechanism of function of the protein synthesis machinery. Among the new remarkable features revealed by structural studies, is the mimicry of the tRNA molecule by elongation factor G, ribosomal recycling factor and the eukaryotic release factor 1. Several other translation factors, for which three-dimensional structures are not yet known, are also expected to show some form of tRNA mimicry. The efforts of several crystallographic and biochemical groups have resulted in the determination by X-ray crystallography of the structures of the 30S and 50S subunits at moderate resolution, and of the structure of the 70S subunit both by X-ray crystallography and cryo-electron microscopy (EM). In addition, low resolution cryo-EM models of the ribosome with different translation factors and tRNA have been obtained. The new ribosomal models allowed for the first time a clear identification of the functional centres of the ribosome and of the binding sites for tRNA and ribosomal proteins with known three-dimensional structure. The new structural data have opened a way for the design of new experiments aimed at deeper understanding at an atomic level of the dynamics of the system.
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| 40. |
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| 41. |
- Arora, Tulika, et al.
(författare)
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Microbial fermentation of flaxseed fibers modulates the transcriptome of GPR41-expressing enteroendocrine cells and protects mice against diet-induced obesity
- 2019
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Ingår i: American Journal of Physiology - Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 316:3
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Tidskriftsartikel (refereegranskat)abstract
- Dietary fibers, an integral part of the human diet, require the enzymatic activity of the gut microbiota for complete metabolism into short-chain fatty acids (SCFAs). SCFAs are important modulators of host metabolism and physiology and act in part as signaling molecules by activating G protein-coupled receptors (GPCRs), such as GPR41. Flaxseed fibers improve metabolism in rodents and mice, but their fermentation profiles, effects on enteroendocrine cells, and associated metabolic benefits are unknown. We fed GPR41-red fluorescent protein mice, an enteroendocrine reporter mouse strain, chow, high-fat diet (HFD), or HFD supplemented either with 10% nonfermentable fiber cellulose or fermentable flaxseed fibers for 12 wk to assess changes in cecal gut microbiota, enteroendocrine cell transcriptome in the ileum and colon, and physiological parameters. We observed that flaxseed fibers restructured the gut microbiota and promoted proliferation of the genera Bifidobacterium and Akkermansia compared with HFD. The shifts in cecal bacterial composition restored levels of the SCFAs butyrate similar to the chow diet, resulting in colonic but not ileal enteroendocrine cell transcriptional changes in genes related to cell cycle, mRNA, and protein transport compared with HFD. Consistent with the effects on enteroendocrine functions, flaxseed fibers also protected mice from diet-induced obesity, potentially by preventing a reduction in energy expenditure induced by an HFD. Our study shows that flaxseed fibers alter cecal microbial ecology, are fermented to SCFAs in the cecum, and modulate enteroendocrine cell transcriptome in the colon, which may contribute to their metabolically favorable phenotype. © 2019 the American Physiological Society.
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| 42. |
- Basnet, A., et al.
(författare)
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Donepezil provides positive effects to patients treated with gabapentin for neuropathic pain : an exploratory study
- 2014
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 58:1, s. 61-73
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe first-line medication gabapentin and the acetylcholinesterase inhibitor donepezil represent a new promising combination to improve treatment outcomes for patients with severe neuropathic pain. The drugs have previously shown synergism following co-administration in nerve-injured rats. MethodsThe clinical relevance of adding donepezil to existing gabapentin treatment in patients with post-traumatic neuropathic pain was explored in this open-label study. The study comprised two consecutive periods of minimum 6 weeks: (1) titration of gabapentin to the highest tolerable dose or maximum 2400mg daily, and (2) addition of donepezil 5mg once daily to the fixed gabapentin dose. Efficacy and tolerability were assessed by ratings of pain intensity, questionnaires for pain and health-related quality of life, and reporting of adverse events. Pain scores were also analysed using mixed-effects analysis with the software NONMEM to account for intersubject variability. ResultsEight patients commenced treatment with donepezil, of which two withdrew because of adverse events. Addition of donepezil resulted in clinically relevant reductions of pain (>11 units on a 0-100 scale) and improved mental wellness in three of six patients. The remaining three patients had no obvious supplemental effect. Mixed-effects analysis revealed that pain scores were significantly lower during co-administration (P<0.0001 combination vs. monotherapy). ConclusionDonepezil may provide additional analgesia to neuropathic pain patients with insufficient pain relief from gabapentin as monotherapy. The promising results support controlled clinical trials of the drug combination. The usefulness of mixed-effects analysis in small-scale trials and/or for data with high intersubject variability was also demonstrated.
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| 43. |
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| 44. |
- Benz, A. O., et al.
(författare)
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Hydrides in young stellar objects : Radiation tracers in a protostar-disk-outflow system
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L35-
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Tidskriftsartikel (refereegranskat)abstract
- Context. Hydrides of the most abundant heavier elements are fundamental molecules in cosmic chemistry. Some of them trace gas irradiated by UV or X-rays. Aims: We explore the abundances of major hydrides in W3 IRS5, a prototypical region of high-mass star formation. Methods: W3 IRS5 was observed by HIFI on the Herschel Space Observatory with deep integration (≃2500 s) in 8 spectral regions. Results: The target lines including CH, NH, H3O+, and the new molecules SH+, H2O+, and OH+ are detected. The H2O+ and OH+ J = 1-0 lines are found mostly in absorption, but also appear to exhibit weak emission (P-Cyg-like). Emission requires high density, thus originates most likely near the protostar. This is corroborated by the absence of line shifts relative to the young stellar object (YSO). In addition, H2O+ and OH+ also contain strong absorption components at a velocity shifted relative to W3 IRS5, which are attributed to foreground clouds. Conclusions: The molecular column densities derived from observations correlate well with the predictions of a model that assumes the main emission region is in outflow walls, heated and irradiated by protostellar UV radiation. Herschel is an ESA space observatory with science instruments provided by a European-led Principal Investigator consortia and with important participation from NASA.Appendix (page 5) is only available in electronic form at http://www.aanda.org
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| 45. |
- Benz, A. O., et al.
(författare)
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Water in star-forming regions with Herschel (WISH): VI. Constraints on UV and X-ray irradiation from a survey of hydrides in low- to high-mass young stellar objects
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 590, s. Art. no. A105-
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Tidskriftsartikel (refereegranskat)abstract
- Context. Hydrides are simple compounds containing one or a few hydrogen atoms bonded to a heavier atom. They are fundamental precursor molecules in cosmic chemistry and many hydride ions have become observable in high quality for the first time thanks to the Herschel Space Observatory. Ionized hydrides such as CH+ and OH+ (and also HCO+), which affect the chemistry of molecules such as water, provide complementary information on irradiation by far-UV (FUV) or X-rays and gas temperature. Aims. We explore hydrides of the most abundant heavier elements in an observational survey covering young stellar objects (YSOs) with different mass and evolutionary state. The focus is on hydrides associated with the dense protostellar envelope and outflows, contrary to previous work that focused on hydrides in diffuse foreground clouds. Methods. Twelve YSOs were observed with HIFI on Herschel in six spectral settings providing fully velocity-resolved line profiles as part of the Water in star-forming regions with Herschel (WISH) program. The YSOs include objects of low (Class 0 and I), intermediate, and high mass, with luminosities ranging from 4 L? to 2 × 105 L?. Results. The targeted lines of CH+, OH+, H2O+, C+, and CH are detected mostly in blue-shifted absorption. H3O+ and SH+ are detected in emission and only toward some high-mass objects. The observed line parameters and correlations suggest two different origins related to gas entrained by the outflows and to the circumstellar envelope. The derived column densities correlate with bolometric luminosity and envelope mass for all molecules, best for CH, CH+, and HCO+. The column density ratios of CH+/OH+ are estimated from chemical slab models, assuming that the H2 density is given by the specific density model of each object at the beam radius. For the low-mass YSOs the observed ratio can be reproduced for an FUV flux of 2-400 times the interstellar radiation field (ISRF) at the location of the molecules. In two high-mass objects, the UV flux is 20-200 times the ISRF derived from absorption lines, and 300-600 ISRF using emission lines. Upper limits for the X-ray luminosity can be derived from H3O+ observations for some low-mass objects. Conclusions. If the FUV flux required for low-mass objects originates at the central protostar, a substantial FUV luminosity, up to 1.5 L?, is required. There is no molecular evidence for X-ray induced chemistry in the low-mass objects on the observed scales of a few 1000 AU. For high-mass regions, the FUV flux required to produce the observed molecular ratios is smaller than the unattenuated flux expected from the central object(s) at the Herschel beam radius. This is consistent with an FUV flux reduced by circumstellar extinction or by bloating of the protostar.
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| 46. |
- Bilenberg, B., et al.
(författare)
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High resolution 100kV electron beam lithography in SU-8
- 2006
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Ingår i: Microelectronic Engineering. - : Elsevier BV. - 0167-9317. ; 83:4-9, s. 1609-1612
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Tidskriftsartikel (refereegranskat)abstract
- High resolution 100 kV electron beam lithography in thin layers of the negative resist SU-8 is demonstrated. Sub-30 nm lines with a pitch down to 300 nm are written in 100 nm thick SU-8. Two reactive ion etch processes are developed in order to transfer the SU-8 structures into a silicon substrate, a Soft O-2-Plasma process to remove SU-8 residues on the silicon surface after development and a highly anisotropic SF6/O-2/CHF3 based process to transfer the pattern into a silicon substrate, with selectivity between silicon and SU-8 of approximately 2. 30 nm lines patterned in SU-8 are successfully transferred into a silicon substrate, which is used as a stamp in a nanoimprint lithography process to fabricate a nanochannel device for DNA stretching experiments. (c) 2006 Elsevier B.V. All rights reserved.
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| 47. |
- Bilenberg, B, et al.
(författare)
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Topas-based lab-on-a-chip microsystems fabricated by thermal nanoimprint lithography
- 2005
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Ingår i: Journal of Vacuum Science and Technology B. - : American Vacuum Society. - 1520-8567. ; 23:6, s. 2944-2949
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Tidskriftsartikel (refereegranskat)abstract
- We, present a one-step technology for fabrication of Topas-based lab-on-a-chip (LOC) microsysterris by the use of thermal nanoimprint lithography (NIL). The technology is demonstrated by the fabrication of two working devices: a particle separator and a LOC with integrated optics for absorbance measurements. These applications demonstrate the fabrication of millimeter to micrometer-sized structures in one lithographic step. The use of NIL makes the technology easily scalable into the nanometer regime by the use of a suitable lithographic technique in the fabrication of the stamp. Processing issues such as environmental stress cracking of the Topas and the requirements to anti-sticking layers on the stamp when imprinting into Topas are discussed.
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| 48. |
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| 49. |
- Bruderer, S., et al.
(författare)
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Herschel/HIFI detections of hydrides towards AFGL 2591. Envelope emission versus tenuous cloud absorption
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L44-
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Tidskriftsartikel (refereegranskat)abstract
- The Heterodyne Instrument for the Far Infrared (HIFI) onboard the Herschel Space Observatory allows the first observations of light diatomic molecules at high spectral resolution and in multiple transitions. Here, we report deep integrations using HIFI in different lines of hydrides towards the high-mass star forming region AFGL 2591. Detected are CH, CH+, NH, OH+, H2O+, while NH+ and SH+ have not been detected. All molecules except for CH and CH+ are seen in absorption with low excitation temperatures and at velocities different from the systemic velocity of the protostellar envelope. Surprisingly, the CH(JF,P = 3/22,- - 1/21,+ ) and CH+(J = 1-0, J = 2-1) lines are detected in emission at the systemic velocity. We can assign the absorption features to a foreground cloud and an outflow lobe, while the CH and CH+ emission stems from the envelope. The observed abundance and excitation of CH and CH+ can be explained in the scenario of FUV irradiated outflow walls, where a cavity etched out by the outflow allows protostellar FUV photons to irradiate and heat the envelope at larger distances driving the chemical reactions that produce these molecules. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.Apppendices and Table 1 (pages 6 to 7) are only available in electronic form at http://www.aanda.org
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| 50. |
- Bruun Kristensen, Kasper, et al.
(författare)
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Nonaspirin Nonsteroidal Antiinflammatory Drug Use in the Nordic Countries from a Cardiovascular Risk Perspective, 2000-2016 : A Drug Utilization Study
- 2019
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Ingår i: Pharmacotherapy. - : Wiley. - 0277-0008 .- 1875-9114. ; 39:2, s. 150-160
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Tidskriftsartikel (refereegranskat)abstract
- Study ObjectiveEvidence on the cardiotoxicity of nonaspirin nonsteroidal antiinflammatory drugs (NSAIDs), particularly diclofenac and the newer selective cyclooxygenase (COX)-2 inhibitors, has accumulated over the last decade. Our objective was to examine whether the use of NSAIDs in the Nordic countries changed with the emerging evidence, regulatory statements, and clinical guidelines advocating caution for the use of specific NSAIDs.DesignDrug utilization study.Data SourcesNationwide wholesale statistics and prescription registries in Denmark, Finland, Iceland, Norway, and Sweden (2000-2016).Measurements and Main ResultsOur main outcome measures were yearly total sales, expressed as number of sold defined daily doses (DDDs)/1000 inhabitants/day, and yearly prevalence of prescription use, expressed as number of prescription users per 1000 inhabitants. The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults. Total sales of NSAIDs increased in all countries and were highest in Iceland, with 74.3 DDDs/1000 inhabitants/day sold in 2016, followed by Finland (73.9), Sweden (54.4), Norway (43.8), and Denmark (31.8). Diclofenac use declined after 2008 in all countries but remained the most widely prescribed NSAID in Norway, with 63 prescription users/1000 inhabitants in 2016. Diclofenac sales also remained high in Iceland (12.7 DDD/1000 inhabitants/day), Norway (8.1), and Sweden (7.8). Since its introduction in 2003, the use of etoricoxib, a newer selective COX-2 inhibitor, increased in all countries except Denmark, with highest sales in Finland (6.7 DDD/1000 inhabitants/day in 2016).ConclusionSales and prescription patterns of NSAIDs in the Nordic countries has changed along with the accumulating evidence for the cardiovascular risks of specific NSAIDs. However, given existing evidence on the cardiovascular risks associated with the use of diclofenac and etoricoxib, the persistent high use of diclofenac in Iceland, Norway, and Sweden, the persistent over-the-counter availability of diclofenac in Norway and Sweden, and the increasing use of etoricoxib in most of the Nordic countries pose a cardiovascular health concern.
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