| 1. |
- 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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| 2. |
- Gudbjartsson, Daniel F., et al.
(författare)
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Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:3, s. 342-347
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).
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| 3. |
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| 4. |
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| 5. |
- Uusitupa, M., et al.
(författare)
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Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome : a randomized study (SYSDIET)
- 2013
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 274:1, s. 52-66
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Tidskriftsartikel (refereegranskat)abstract
- Background Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome. Methods We conducted a randomized dietary study lasting for 18-24weeks in individuals with features of metabolic syndrome (mean age 55years, BMI 31.6kgm-2, 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids. Results Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (-0.18, mmolL-1 95% CI -0.35; -0.01, P=0.04), LDL to HDL cholesterol (-0.15, -0.28; -0.00, P=0.046) and apolipoprotein B to apolipoprotein A1 ratios (-0.04, -0.07; -0.00, P=0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference -84, -133; -37ngL-1, P= 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P=0.049) and magnesium (mg, -0.23, -0.41; -0.05, P=0.012) were associated with IL-1 Ra. Conclusions Healthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation.
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| 6. |
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| 7. |
- Collins, C. G., et al.
(författare)
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Experimental warming differentially affects vegetative and reproductive phenology of tundra plants
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Rapid climate warming is altering Arctic and alpine tundra ecosystem structure and function, including shifts in plant phenology. While the advancement of green up and flowering are well-documented, it remains unclear whether all phenophases, particularly those later in the season, will shift in unison or respond divergently to warming. Here, we present the largest synthesis to our knowledge of experimental warming effects on tundra plant phenology from the International Tundra Experiment. We examine the effect of warming on a suite of season-wide plant phenophases. Results challenge the expectation that all phenophases will advance in unison to warming. Instead, we find that experimental warming caused: (1) larger phenological shifts in reproductive versus vegetative phenophases and (2) advanced reproductive phenophases and green up but delayed leaf senescence which translated to a lengthening of the growing season by approximately 3%. Patterns were consistent across sites, plant species and over time. The advancement of reproductive seasons and lengthening of growing seasons may have significant consequences for trophic interactions and ecosystem function across the tundra. It is unclear whether climate driven phenological shifts of tundra plants are consistent across the plant growing season. Here the authors analyse data from a network of field warming experiments in Arctic and alpine tundra, finding that warming differentially affects the timing and duration of reproductive and vegetative phenology.
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| 8. |
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| 9. |
- Maes, S.L., et al.
(författare)
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Environmental drivers of increased ecosystem respiration in a warming tundra
- 2024
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 629:8010, s. 105-113
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Tidskriftsartikel (refereegranskat)abstract
- Arctic and alpine tundra ecosystems are large reservoirs of organic carbon. Climate warming may stimulate ecosystem respiration and release carbon into the atmosphere. The magnitude and persistency of this stimulation and the environmental mechanisms that drive its variation remain uncertain. This hampers the accuracy of global land carbon–climate feedback projections. Here we synthesize 136 datasets from 56 open-top chamber in situ warming experiments located at 28 arctic and alpine tundra sites which have been running for less than 1 year up to 25 years. We show that a mean rise of 1.4 °C [confidence interval (CI) 0.9–2.0 °C] in air and 0.4 °C [CI 0.2–0.7 °C] in soil temperature results in an increase in growing season ecosystem respiration by 30% [CI 22–38%] (n = 136). Our findings indicate that the stimulation of ecosystem respiration was due to increases in both plant-related and microbial respiration (n = 9) and continued for at least 25 years (n = 136). The magnitude of the warming effects on respiration was driven by variation in warming-induced changes in local soil conditions, that is, changes in total nitrogen concentration and pH and by context-dependent spatial variation in these conditions, in particular total nitrogen concentration and the carbon:nitrogen ratio. Tundra sites with stronger nitrogen limitations and sites in which warming had stimulated plant and microbial nutrient turnover seemed particularly sensitive in their respiration response to warming. The results highlight the importance of local soil conditions and warming-induced changes therein for future climatic impacts on respiration.
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| 10. |
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| 11. |
- Prevey, J. S., et al.
(författare)
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Warming shortens flowering seasons of tundra plant communities
- 2019
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Ingår i: Nature Ecology & Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 3:1, s. 45-52
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Tidskriftsartikel (refereegranskat)abstract
- Advancing phenology is one of the most visible effects of climate change on plant communities, and has been especially pronounced in temperature-limited tundra ecosystems. However, phenological responses have been shown to differ greatly between species, with some species shifting phenology more than others. We analysed a database of 42,689 tundra plant phenological observations to show that warmer temperatures are leading to a contraction of community-level flowering seasons in tundra ecosystems due to a greater advancement in the flowering times of late-flowering species than early-flowering species. Shorter flowering seasons with a changing climate have the potential to alter trophic interactions in tundra ecosystems. Interestingly, these findings differ from those of warmer ecosystems, where early-flowering species have been found to be more sensitive to temperature change, suggesting that community-level phenological responses to warming can vary greatly between biomes.
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| 12. |
- Rixen, C., et al.
(författare)
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Winters are changing: snow effects on Arctic and alpine tundra ecosystems
- 2022
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Ingår i: Arctic Science. - : Canadian Science Publishing. - 2368-7460. ; 8:3, s. 572-608
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Tidskriftsartikel (refereegranskat)abstract
- Snow is an important driver of ecosystem processes in cold biomes. Snow accumulation determines ground temperature, light conditions, and moisture availability during winter. It also affects the growing season's start and end, and plant access to moisture and nutrients. Here, we review the current knowledge of the snow cover's role for vegetation, plant-animal interactions, permafrost conditions, microbial processes, and biogeochemical cycling. We also compare studies of natural snow gradients with snow experimental manipulation studies to assess time scale difference of these approaches. The number of tundra snow studies has increased considerably in recent years, yet we still lack a comprehensive overview of how altered snow conditions will affect these ecosystems. Specifically, we found a mismatch in the timing of snowmelt when comparing studies of natural snow gradients with snow manipulations. We found that snowmelt timing achieved by snow addition and snow removal manipulations (average 7.9 days advance and 5.5 days delay, respectively) were substantially lower than the temporal variation over natural spatial gradients within a given year (mean range 56 days) or among years (mean range 32 days). Differences between snow study approaches need to be accounted for when projecting snow dynamics and their impact on ecosystems in future climates.
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| 13. |
- Thorgeirsson, T. E., et al.
(författare)
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A rare missense mutation in CHRNA4 associates with smoking behavior and its consequences
- 2016
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:5, s. 594-600
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Tidskriftsartikel (refereegranskat)abstract
- Using Icelandic whole-genome sequence data and an imputation approach we searched for rare sequence variants in CHRNA4 and tested them for association with nicotine dependence. We show that carriers of a rare missense variant (allele frequency = 0.24%) within CHRNA4, encoding an R336C substitution, have greater risk of nicotine addiction than non-carriers as assessed by the Fagerstrom Test for Nicotine Dependence (P = 1.2 x 10(-4)). The variant also confers risk of several serious smoking-related diseases previously shown to be associated with the D398N substitution in CHRNA5. We observed odds ratios (ORs) of 1.7-2.3 for lung cancer (LC; P = 4.0 x 10(-4)), chronic obstructive pulmonary disease (COPD; P = 9.3 x 10(-4)), peripheral artery disease (PAD; P = 0.090) and abdominal aortic aneurysms (AAAs; P = 0.12), and the variant associates strongly with the early-onset forms of LC (OR = 4.49, P = 2.2 x 10(-4)), COPD (OR = 3.22, P = 2.9 x 10(-4)), PAD (OR = 3.47, P = 9.2 x 10(-3)) and AAA (OR = 6.44, P = 6.3 x 10(-3)). Joint analysis of the four smoking-related diseases reveals significant association (P = 6.8 x 10(-5)), particularly for early-onset cases (P = 2.1 x 10(-7)). Our results are in agreement with functional studies showing that the human alpha 4 beta 2 isoform of the channel containing R336C has less sensitivity for its agonists than the wild-type form following nicotine incubation.
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| 14. |
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| 15. |
- Barrio, I. C., et al.
(författare)
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Biotic interactions mediate patterns of herbivore diversity in the Arctic
- 2016
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Ingår i: Global Ecology and Biogeography. - : Wiley-Blackwell. - 1466-822X .- 1466-8238. ; 25:9, s. 1108-1118
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Understanding the forces shaping biodiversity patterns, particularly for groups of organisms with key functional roles, will help predict the responses of ecosystems to environmental changes. Our aim was to evaluate the relative role of different drivers in shaping the diversity patterns of vertebrate herbivores, a group of organisms exerting a strong trophic influence in terrestrial Arctic ecosystems. This biome, traditionally perceived as homogeneous and low in biodiversity, includes wide variation in biotic and physical conditions and is currently undergoing major environmental change. Location: The Arctic (including the High Arctic, Low Arctic and Subarctic) MethodsWe compiled available data on vertebrate (birds and mammals) herbivore distribution at a pan-Arctic scale, and used eight variables that represent the most relevant hypotheses for explaining patterns of species richness. We used range maps rasterized on a 100kmx100km equal-area grid to analyse richness patterns of all vertebrate herbivore species combined, and birds and mammalian herbivores separately. Results: Overall, patterns of herbivore species richness in the Arctic were positively related to plant productivity (measured using the normalized difference vegetation index) and to the species richness of predators. Greater species richness of herbivores was also linked to areas with a higher mean annual temperature. Species richness of avian and mammalian herbivores were related to the distance from the coast, with the highest avian richness in coastal areas and mammalian richness peaking further inland. Main conclusions: Herbivore richness in the Arctic is most strongly linked to primary productivity and the species richness of predators. Our results suggest that biotic interactions, with either higher or lower trophic levels or both, can drive patterns of species richness at a biome-wide scale. Rapid ongoing environmental changes in the Arctic are likely to affect herbivore diversity through impacts on both primary productivity and changes in predator communities via range expansion of predators from lower latitudes.
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| 16. |
- Barrio, I. C., et al.
(författare)
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Developing common protocols to measure tundra herbivory across spatial scales
- 2022
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Ingår i: Arctic Science. - : Canadian Science Publishing. - 2368-7460. ; 8:3, s. 638-679
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Tidskriftsartikel (refereegranskat)abstract
- Understanding and predicting large-scale ecological responses to global environmental change requires comparative studies across geographic scales with coordinated efforts and standardized methodologies. We designed, applied, and assessed standardized protocols to measure tundra herbivory at three spatial scales: plot, site (habitat), and study area (landscape). The plot-and site-level protocols were tested in the field during summers 2014–2015 at 11 sites, nine of them consisting of warming experimental plots included in the International Tundra Experiment (ITEX). The study area protocols were assessed during 2014–2018 at 24 study areas across the Arctic. Our protocols provide comparable and easy to implement methods for assessing the intensity of invertebrate herbivory within ITEX plots and for characterizing vertebrate herbivore communities at larger spatial scales. We discuss methodological constraints and make recommendations for how these protocols can be used and how sampling effort can be optimized to obtain comparable estimates of herbivory, both at ITEX sites and at large landscape scales. The application of these protocols across the tundra biome will allow characterizing and comparing herbivore communities across tundra sites and at ecologically relevant spatial scales, providing an important step towards a better understanding of tundra ecosystem responses to large-scale environmental change.
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| 17. |
- Blain, H., et al.
(författare)
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A comprehensive fracture prevention strategy in older adults : the European union geriatric medicine society (EUGMS) statement
- 2016
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Ingår i: European Geriatric Medicine. - : Elsevier. - 1878-7649 .- 1878-7657. ; 7:6, s. 519-525
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Tidskriftsartikel (refereegranskat)abstract
- Prevention of fragility fractures in older people has become a public health priority, although the most appropriate and cost-effective strategy remains unclear. In the present statement, the Interest group on falls and fracture prevention of the European union geriatric medicine society (EUGMS), in collaboration with the International association of gerontology and geriatrics for the European region (IAGG-ER), the European union of medical specialists (EUMS), the Fragility fracture network (FFN), the International osteoporosis foundation (IOF) - European society for clinical and economic aspects of osteoporosis and osteoarthritis (ECCEO), outlines its views on the main points in the current debate in relation to the primary and secondary prevention of falls, the diagnosis and treatment of bone fragility, and the place of combined falls and fracture liaison services for fracture prevention in older people.
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| 18. |
- Elmendorf, S. C., et al.
(författare)
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Experiment, monitoring, and gradient methods used to infer climate change effects on plant communities yield consistent patterns
- 2015
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 112:2, s. 448-452
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Tidskriftsartikel (refereegranskat)abstract
- Inference about future climate change impacts typically relies on one of three approaches: manipulative experiments, historical comparisons (broadly defined to include monitoring the response to ambient climate fluctuations using repeat sampling of plots, dendroecology, and paleoecology techniques), and space-for-time substitutions derived from sampling along environmental gradients. Potential limitations of all three approaches are recognized. Here we address the congruence among these three main approaches by comparing the degree to which tundra plant community composition changes (i) in response to in situ experimental warming, (ii) with interannual variability in summer temperature within sites, and (iii) over spatial gradients in summer temperature. We analyzed changes in plant community composition from repeat sampling (85 plant communities in 28 regions) and experimental warming studies (28 experiments in 14 regions) throughout arctic and alpine North America and Europe. Increases in the relative abundance of species with a warmer thermal niche were observed in response to warmer summer temperatures using all three methods; however, effect sizes were greater over broad-scale spatial gradients relative to either temporal variability in summer temperature within a site or summer temperature increases induced by experimental warming. The effect sizes for change over time within a site and with experimental warming were nearly identical. These results support the view that inferences based on space-for-time substitution overestimate the magnitude of responses to contemporary climate warming, because spatial gradients reflect long-term processes. In contrast, in situ experimental warming and monitoring approaches yield consistent estimates of the magnitude of response of plant communities to climate warming.
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| 19. |
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| 20. |
- Gislason, S.R., et al.
(författare)
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Environmental pressure from the 2014–15 eruption of Bárðarbunga volcano, Iceland
- 2015
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Ingår i: Geochemical Perspectives Letters. - : European Association of Geochemistry. - 2410-3403 .- 2410-339X. ; 1:2015, s. 84 - 93
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Tidskriftsartikel (refereegranskat)abstract
- The effusive six months long 2014-2015 Bárðarbunga eruption (31 August-27 February) was the largest in Iceland for more than 200 years, producing 1.6 ± 0.3 km3 of lava. The total SO2 emission was 11 ± 5 Mt, more than the amount emitted from Europe in 2011. The ground level concentration of SO2 exceeded the 350 μg m−3 hourly average health limit over much of Iceland for days to weeks. Anomalously high SO2 concentrations were also measured at several locations in Europe in September. The lowest pH of fresh snowmelt at the eruption site was 3.3, and 3.2 in precipitation 105 km away from the source. Elevated dissolved H2SO4, HCl, HF, and metal concentrations were measured in snow and precipitation. Environmental pressures from the eruption and impacts on populated areas were reduced by its remoteness, timing, and the weather. The anticipated primary environmental pressure is on the surfacewaters, soils, and vegetation of Iceland.
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| 21. |
- Hollister, R. D., et al.
(författare)
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A review of open top chamber (OTC) performance across the ITEX Network
- 2023
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Ingår i: Arctic Science. - : Canadian Science Publishing. - 2368-7460. ; 9:2, s. 331-344
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Tidskriftsartikel (refereegranskat)abstract
- Open top chambers (OTCs) were adopted as the recommended warming mechanism by the International Tundra Experiment network in the early 1990s. Since then, OTCs have been deployed across the globe. Hundreds of papers have reported the im-pacts of OTCs on the abiotic environment and the biota. Here, we review the impacts of the OTC on the physical environment, with comments on the appropriateness of using OTCs to characterize the response of biota to warming. The purpose of this review is to guide readers to previously published work and to provide recommendations for continued use of OTCs to under -stand the implications of warming on low stature ecosystems. In short, the OTC is a useful tool to experimentally manipulate temperature; however, the characteristics and magnitude of warming varies greatly in different environments; therefore, it is important to document chamber performance to maximize the interpretation of biotic response. When coupled with long-term monitoring, warming experiments are a valuable means to understand the impacts of climate change on natural ecosystems.
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| 22. |
- Jónsdóttir, I. S., et al.
(författare)
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Intraspecific trait variability is a key feature underlying high Arctic plant community resistance to climate warming
- 2022
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Ingår i: Ecological Monographs. - : Wiley. - 0012-9615 .- 1557-7015.
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Tidskriftsartikel (refereegranskat)abstract
- In the high Arctic, plant community species composition generally responds slowly to climate warming, whereas less is known about the community functional trait responses and consequences for ecosystem functioning. Slow species turnover and large distribution ranges of many Arctic plant species suggest a significant role of intraspecific trait variability in functional responses to climate change. Here, we compare taxonomic and functional community compositional responses to a long-term (17years) warming experiment in Svalbard, replicated across three major high Arctic habitats shaped by topography and contrasting snow regimes. We observed taxonomic compositional changes in all plant communities over time. Still, responses to experimental warming were minor and most pronounced in the drier habitats with relatively early snowmelt timing and long growing seasons (Cassiope and Dryas heaths). The habitats were clearly separated in functional trait space, defined by twelve size- and leaf economics-related traits, primarily due to interspecific trait variation. Functional traits also responded to experimental warming, most prominently in the Dryas heath and mostly due to intraspecific trait variation. Leaf area and leaf mass increased, and leaf δ15N decreased in response to the warming treatment. Intraspecific trait variability ranged between 30% and 71% of the total trait variation, reflecting functional resilience of those communities, dominated by long-lived plants, due to either phenotypic plasticity or genotypic variation that most likely underlies the observed resistance of high Arctic vegetation to climate warming. We further explored the consequences of trait variability for ecosystem functioning by measuring peak season CO2 fluxes. Together, environmental, taxonomic, and functional trait variables explained a large proportion of the variation in net ecosystem exchange (NEE), which increased when intraspecific trait variation was accounted for. In contrast, even though ecosystem respiration and gross ecosystem production both increased in response to warming across habitats, they were mainly driven by the direct kinetic impacts of temperature on plant physiology and biochemical processes. Our study shows that long-term experimental warming has a modest but significant effect on plant community functional trait composition and suggests that intraspecific trait variability is a key feature underlying high Arctic ecosystem resistance to climate warming.
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| 23. |
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| 24. |
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| 25. |
- Kerkhof, H. J. M., et al.
(författare)
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Recommendations for standardization and phenotype definitions in genetic studies of osteoarthritis: the TREAT-OA consortium
- 2011
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 19:3, s. 254-264
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To address the need for standardization of osteoarthritis (OA) phenotypes by examining the effect of heterogeneity among symptomatic (SOA) and radiographic osteoarthritis (ROA) phenotypes. Methods: Descriptions of OA phenotypes of the 28 studies involved in the TREAT-OA consortium were collected. We investigated whether different OA definitions result in different association results by creating various hip OA definitions in one large population based cohort (the Rotterdam Study I (RSI)) and testing those for association with gender, age and body mass index using one-way ANOVA. For ROA, we standardized the hip-, knee- and hand ROA definitions and calculated prevalence's of ROA before and after standardization in nine cohort studies. This procedure could only be performed in cohort studies and standardization of SOA definitions was not feasible at this moment. Results: In this consortium, all studies with SOA phenotypes (knee, hip and hand) used a different definition and/or assessment of OA status. For knee-, hip- and hand ROA five, four and seven different definitions were used, respectively. Different hip ROA definitions do lead to different association results. For example, we showed in the RSI that hip OA defined as "at least definite joint space narrowing (JSN) and one definite osteophyte" was not associated with gender (P=0.22), but defined as "at least one definite osteophyte" was significantly associated with gender (P=3 x 10(-9)). Therefore, a standardization process was undertaken for ROA definitions. Before standardization a wide range of ROA prevalence's was observed in the nine cohorts studied. After standardization the range in prevalence of knee- and hip ROA was small. Conclusion: Phenotype definitions influence the prevalence of OA and association with clinical variables. ROA phenotypes within the TREAT-OA consortium were standardized to reduce heterogeneity and improve power in future genetics studies. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 26. |
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| 27. |
- Kular, L, et al.
(författare)
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DNA methylation as a mediator of HLA-DRB1*15:01 and a protective variant in multiple sclerosis
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2397-
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Tidskriftsartikel (refereegranskat)abstract
- The human leukocyte antigen (HLA) haplotype DRB1*15:01 is the major risk factor for multiple sclerosis (MS). Here, we find that DRB1*15:01 is hypomethylated and predominantly expressed in monocytes among carriers of DRB1*15:01. A differentially methylated region (DMR) encompassing HLA-DRB1 exon 2 is particularly affected and displays methylation-sensitive regulatory properties in vitro. Causal inference and Mendelian randomization provide evidence that HLA variants mediate risk for MS via changes in the HLA-DRB1 DMR that modify HLA-DRB1 expression. Meta-analysis of 14,259 cases and 171,347 controls confirms that these variants confer risk from DRB1*15:01 and also identifies a protective variant (rs9267649, p < 3.32 × 10−8, odds ratio = 0.86) after conditioning for all MS-associated variants in the region. rs9267649 is associated with increased DNA methylation at the HLA-DRB1 DMR and reduced expression of HLA-DRB1, suggesting a modulation of the DRB1*15:01 effect. Our integrative approach provides insights into the molecular mechanisms of MS susceptibility and suggests putative therapeutic strategies targeting a methylation-mediated regulation of the major risk gene.
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| 28. |
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| 29. |
- Mikaelsdottir, E, et al.
(författare)
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Genetic variants associated with platelet count are predictive of human disease and physiological markers
- 2021
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 4:1, s. 1132-
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Tidskriftsartikel (refereegranskat)abstract
- Platelets play an important role in hemostasis and other aspects of vascular biology. We conducted a meta-analysis of platelet count GWAS using data on 536,974 Europeans and identified 577 independent associations. To search for mechanisms through which these variants affect platelets, we applied cis-expression quantitative trait locus, DEPICT and IPA analyses and assessed genetic sharing between platelet count and various traits using polygenic risk scoring. We found genetic sharing between platelet count and counts of other blood cells (except red blood cells), in addition to several other quantitative traits, including markers of cardiovascular, liver and kidney functions, height, and weight. Platelet count polygenic risk score was predictive of myeloproliferative neoplasms, rheumatoid arthritis, ankylosing spondylitis, hypertension, and benign prostate hyperplasia. Taken together, these results advance understanding of diverse aspects of platelet biology and how they affect biological processes in health and disease.
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| 30. |
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| 31. |
- Prevey, J., et al.
(författare)
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Greater temperature sensitivity of plant phenology at colder sites: implications for convergence across northern latitudes
- 2017
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 23:7, s. 2660-2671
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Tidskriftsartikel (refereegranskat)abstract
- Warmer temperatures are accelerating the phenology of organisms around the world. Temperature sensitivity of phenology might be greater in colder, higher latitude sites than in warmer regions, in part because small changes in temperature constitute greater relative changes in thermal balance at colder sites. To test this hypothesis, we examined up to 20 years of phenology data for 47 tundra plant species at 18 high-latitude sites along a climatic gradient. Across all species, the timing of leaf emergence and flowering was more sensitive to a given increase in summer temperature at colder than warmer high-latitude locations. A similar pattern was seen over time for the flowering phenology of a widespread species, Cassiope tetragona. These are among the first results highlighting differential phenological responses of plants across a climatic gradient and suggest the possibility of convergence in flowering times and therefore an increase in gene flow across latitudes as the climate warms.
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| 32. |
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| 33. |
- Sonderby, Ida E., et al.
(författare)
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Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602
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Tidskriftsartikel (refereegranskat)abstract
- Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
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| 34. |
- Steinthorsdottir, V, et al.
(författare)
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Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 5976-
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Tidskriftsartikel (refereegranskat)abstract
- Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia.
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| 35. |
- Sörbo, Ann, 1955, et al.
(författare)
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Pre-traumatic conditions can influence cortisol levels before and after a brain injury
- 2020
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 141:4, s. 342-350
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Tidskriftsartikel (refereegranskat)abstract
- Objective Satisfactory anabolic reactions, including the activation of the hypothalamic-pituitary-adrenal (HPA) axis, are essential following severe traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH). Many factors may influence this activation. This study aimed to investigate whether individuals who reported chronic diseases, psychosocial afflictions, or stressful events before a severe brain injury display a different pattern regarding cortisol levels retrospectively and up to three months compared with those who did not report stressful experiences. Materials and Methods Fifty-five patients aged 16-68 years who were admitted to the neurointensive care unit (NICU) were included. Hair cortisol measurements offer a unique opportunity to monitor cortisol levels retrospectively and after the trauma. Hair strands were collected as soon as possible after admission to the NICU and every month until three months after the injury/insult. The participants/relatives were asked about stressful events, psychosocial afflictions and recent and chronic diseases. Results The group who reported chronic diseases and/or stressful events before the brain injury had more than twice as high median hair cortisol levels before the brain injury compared with those who did not report stress, but the difference was not statistically significant (P = .12). Those who reported stress before the brain injury had statistically significantly lower hair cortisol values after the brain injury and they remained until three months after the injury. Conclusions Stressful events and/or chronic disease before brain injury might affect mobilization of adequate stress reactions following the trauma. However, the large variability in cortisol levels in these patients does not allow firm conclusions and more studies are needed.
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| 36. |
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| 37. |
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| 38. |
- Abrahamson, Magnus, et al.
(författare)
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Hereditary cystatin C amyloid angiopathy: Identification of the disease causing mutation and specific diagnosis by polymerase chain reaction based analysis
- 1992
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Ingår i: Human Genetics. - 1432-1203. ; 89:4, s. 377-380
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary cystatin C amyloid angiopathy (HCCAA) is a dominantly inherited disease characterized by amyloidosis, dementia and fatal cerebral hemorrhage of young adults. A method for rapid and simple diagnosis of HCCAA is described. It is based upon oligonucleotide-directed enzymatic amplification of a 275-bp genomic DNA segment containing exon 2 of the cystatin C gene from a blood sample, followed by digestion of the amplification product with AluI. Loss of an AluI recognition site in the amplified DNA segment from HCCAA patients results in a deviating band-pattern at agarose gel electrophoresis, compared with that obtained from normal subjects or unaffected HCCAA family members. In a population of 9 patients with manifest HCCAA, 14 patients with other causes of brain hemorrhage and 16 healthy individuals, the diagnostic procedure displayed a sensitivity and specificity for HCCAA of 100%. Amplified DNA segments from 4 HCCAA patients of four different families were analyzed by nucleotide sequencing; the HCCAA-causing mutation in all families was found to be a single TrarrA substitution in the codon for amino acid residue 68 of cystatin C.
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| 39. |
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| 40. |
- Alriksson-Schmidt, Ann I, et al.
(författare)
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CP-North: living life in the Nordic countries? : A retrospective register research protocol on individuals with cerebral palsy and their parents living in Sweden, Norway, Denmark, Finland and Iceland
- 2019
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Cerebral palsy (CP) is one of the most common neurodevelopmental disabilities. Yet, most individuals with CP are adults. How individuals with CP fare in terms of health, quality of life (QoL), education, employment and income is largely unknown. Further, little is known about the effects of having a child with CP on the parents. The Nordic countries are known for their strong welfare systems, yet it is unknown to what extent the added burden related to disability is actually compensated for. We will explore how living with CP affects health, QoL, healthcare utilisation, education, labour market outcomes, socioeconomic status and mortality throughout the lifespan of individuals with CP and their parents. We will also investigate if these effects differ between subgroups, within and across the Nordic countries. METHODS AND ANALYSES: CP-North is a multidisciplinary 4-year (1 August 2017 to 31 July 2021) register research project. The research consortium comprises researchers and users from Sweden, Norway, Denmark, Iceland and Finland. Data from CP registries and follow-up programmes, or cohorts of individuals with CP, will be merged with general national registries. All individual studies are structured under three themes: medical outcomes, social and public health outcomes, and health economics. Both case-control and cohort designs will be included depending on the particular research question. Data will be analysed in the individual countries and later merged across nations.ETHICS AND DISSEMINATION: The ethics approval processes in each individual country are followed. Findings will be published (open access) in international peer-reviewed journals in related fields. Updates on CP-North will be published online at http://rdi.arcada.fi/cpnorth/en/.
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| 41. |
- Alriksson-Schmidt, Ann I, et al.
(författare)
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Living life with cerebral palsy? A description of the social safety nets for individuals with cerebral palsy in the Nordic countries
- 2021
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 49:6, s. 653-665
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Forskningsöversikt (refereegranskat)abstract
- AIMS: This report reviews major laws, acts and regulations of social benefits and services for individuals with disabilities, focusing on cerebral palsy in the five Nordic countries. It summarizes the available benefits and services and the re-application process and provides comparative analyses among the countries.METHODS: Published reports, articles and relevant government and municipal websites were reviewed for each respective country and used to compile an overview and comparison between the countries.RESULTS: In the Nordic countries, there are a number of laws and regulations in place to support individuals with cerebral palsy and their families. In addition, there are numerous social benefits available for which individuals with disabilities can apply. Although there are national differences, the similarities across the five countries regarding laws, social benefits offered for individuals with cerebral palsy and the application processes are clear. However, the application processes seem cumbersome and, at times, redundant. Physicians and other healthcare specialists repeatedly need to write 'medical certificates' describing the diagnosis and its consequences for a disability that is chronic and lifelong.CONCLUSIONS: Participation in society for individuals with cerebral palsy disabilities can be enabled by social benefits. By extension, social benefits may indirectly have implications for public health in individuals with disabilities. Although the lives of individuals with cerebral palsy - as with others - can improve in certain areas, the need for social benefits will generally increase, not decrease, over time. Although it is clearly important to have checks and balances that prevent system misuse, it might be worthwhile from a cost-benefit perspective to investigate whether the current systems could be improved to better manage time and resources and avoid emotional distress by streamlining the application process.
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| 42. |
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| 43. |
- Boy, M., et al.
(författare)
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Interactions between the atmosphere, cryosphere, and ecosystems at northern high latitudes
- 2019
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 19:3, s. 2015-2061
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Tidskriftsartikel (refereegranskat)abstract
- The Nordic Centre of Excellence CRAICC (Cryosphere-Atmosphere Interactions in a Changing Arctic Climate), funded by NordForsk in the years 2011-2016, is the largest joint Nordic research and innovation initiative to date, aiming to strengthen research and innovation regarding climate change issues in the Nordic region. CRAICC gathered more than 100 scientists from all Nordic countries in a virtual centre with the objectives of identifying and quantifying the major processes controlling Arctic warming and related feedback mechanisms, outlining strategies to mitigate Arctic warming, and developing Nordic Earth system modelling with a focus on short-lived climate forcers (SLCFs), including natural and anthropogenic aerosols. The outcome of CRAICC is reflected in more than 150 peer-reviewed scientific publications, most of which are in the CRAICC special issue of the journal Atmospheric Chemistry and Physics. This paper presents an overview of the main scientific topics investigated in the centre and provides the reader with a state-of-the-art comprehensive summary of what has been achieved in CRAICC with links to the particular publications for further detail. Faced with a vast amount of scientific discovery, we do not claim to completely summarize the results from CRAICC within this paper, but rather concentrate here on the main results which are related to feedback loops in climate change-cryosphere interactions that affect Arctic amplification.
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- Brandt, Åse, et al.
(författare)
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Reliability test-retest of the Nordic Assisted Mobility Evaluation (NAME 1.0)
- 2007
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Ingår i: Challenges for Assistive Technology. - 9781586037918 ; , s. 85-87
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This paper describes preliminary results from the test-retest of the NAME 1.0. Four scales were tested: Mobility-related participation frequency; Mobility ease/difficulty; Mobility dependence; Extent of assistance in mobility. The test was conducted in the five Nordic countries. In all 147 mobility device users took part in the study, mean age 60 years (range 19 - 93). Each participant was interviewed twice by means of the NAME 1.0 with seven days' interval (SD 4) by interviewers trained in using the instrument. The reliability of two scales was good, and the reliability of one scale became good after it had been regrouped into fewer grades. The reliablity of the Mobility ease/difficulty scale was only moderate. Possible reasons for this are discussed. There is a need for further research.
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| 48. |
- Börjesson, Mats, 1965, et al.
(författare)
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Fysisk aktivitet och stress
- 2010
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Ingår i: Svensk Idrottsforskning. ; 19, s. 10-12
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 49. |
- Dagsson-Waldhauserova, P., et al.
(författare)
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Physical properties of suspended dust during moist and low wind conditions in Iceland
- 2014
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Ingår i: Icelandic Agricultural Sciences. - 1670-567X. ; 27, s. 25-39
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Tidskriftsartikel (refereegranskat)abstract
- We measured a dust event which occurred during wet and low wind/windless conditions as the result of surface heating in August 2013. Maximum particle number concentration (PM similar to 0.3-10 mu m) reached 149,954 particles cm(-3) min(-1) while mass concentration (PM<10 m) was 1757 g m-3 min-1. The suspended dust was very fine with the highest number of particles in the size range 0.3-0.337 mu m, followed by particles 1.5-5 mu m in diameter. Close-to-ultrafine particle size distributions showed a significant increase in number with the severity of the measured dust event (during dust peaks). Number concentrations were well correlated with mass concentrations. The mineralogy and geochemical compositions showed that glaciogenic dust contains sharp-tipped shards with bubbles and 80 % of the particulate matter is volcanic glass rich in heavy metals. Wet dust particles were mobilized within < 4 hours. This is the first scientific study of particle size distributions in an Icelandic dust event including findings on initiation of dust suspension.
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| 50. |
- Dans, Madeline G., et al.
(författare)
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Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- With resistance to most antimalarials increasing, it is imperative that new drugs are developed. We previously identified an aryl acetamide compound, MMV006833 (M-833), that inhibited the ring-stage development of newly invaded merozoites. Here, we select parasites resistant to M-833 and identify mutations in the START lipid transfer protein (PF3D7_0104200, PfSTART1). Introducing PfSTART1 mutations into wildtype parasites reproduces resistance to M-833 as well as to more potent analogues. PfSTART1 binding to the analogues is validated using organic solvent-based Proteome Integral Solubility Alteration (Solvent PISA) assays. Imaging of invading merozoites shows the inhibitors prevent the development of ring-stage parasites potentially by inhibiting the expansion of the encasing parasitophorous vacuole membrane. The PfSTART1-targeting compounds also block transmission to mosquitoes and with multiple stages of the parasite’s lifecycle being affected, PfSTART1 represents a drug target with a new mechanism of action.
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