| 1. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 2. |
- Pilotto, Francesca, et al.
(författare)
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Meta-analysis of multidecadal biodiversity trends in Europe
- 2020
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Local biodiversity trends over time are likely to be decoupled from global trends, as local processes may compensate or counteract global change. We analyze 161 long-term biological time series (15-91 years) collected across Europe, using a comprehensive dataset comprising ~6,200 marine, freshwater and terrestrial taxa. We test whether (i) local long-term biodiversity trends are consistent among biogeoregions, realms and taxonomic groups, and (ii) changes in biodiversity correlate with regional climate and local conditions. Our results reveal that local trends of abundance, richness and diversity differ among biogeoregions, realms and taxonomic groups, demonstrating that biodiversity changes at local scale are often complex and cannot be easily generalized. However, we find increases in richness and abundance with increasing temperature and naturalness as well as a clear spatial pattern in changes in community composition (i.e. temporal taxonomic turnover) in most biogeoregions of Northern and Eastern Europe. The global biodiversity decline might conceal complex local and group-specific trends. Here the authors report a quantitative synthesis of longterm biodiversity trends across Europe, showing how, despite overall increase in biodiversity metric and stability in abundance, trends differ between regions, ecosystem types, and taxa.
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| 3. |
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| 4. |
- Alhadad, Alaa, et al.
(författare)
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Renal angioplasty causes a rapid transient increase in inflammatory biomarkers, but reduced levels of interleukin-6 and endothelin-1 1 month after intervention.
- 2007
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Ingår i: Journal of hypertension. - 0263-6352 .- 1473-5598. ; 25:9, s. 1907-14
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine prospectively whether inflammatory biomarkers and endothelin (ET)-1 are increased in patients with renal artery stenosis (RAS), and to investigate how treatment with percutaneous transluminal renal angioplasty (PTRA) affects these variables during the first month after intervention. METHODS: One hundred patients with suspected RAS undergoing renal angiography were included. PTRA was performed if the trans-stenotic mean arterial pressure gradient was>or=10 mmHg. High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFalpha), neopterin, CD40 ligand (CD40L) and endothelin-1 (ET-1) were measured before, and 1 day and 1 month after PTRA (n=61) or diagnostic angiography only (n=39). RESULTS: At baseline there were no significant differences in inflammatory biomarkers or ET-1 levels between patients subsequently undergoing PTRA or angiography only. After angiography, IL-6 and hs-CRP had increased in both groups compared to baseline (P<0.001). At this time point hs-CRP (10.90+/-1.48 versus 6.37+/-1.61 mg/l; P<0.05) and IL-6 (13.70+/-0.94 versus 13.00+/-0.17 pg/ml; P<0.01) were higher in the PTRA group than in patients subjected to angiography only. One month after PTRA, systolic blood pressure and levels of IL-6 and ET-1 were lower than before intervention (P<0.05), whereas CD40L had increased compared to baseline (P<0.01). CONCLUSION: In patients with RAS, PTRA triggers rapid transient increases in hs-CRP and IL-6; however, 1 month after PTRA, both IL-6 and ET-1 had decreased compared to before intervention, indicating beneficial effects of PTRA on inflammation and the endothelin system.
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| 5. |
- Bache, Iben, et al.
(författare)
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An excess of chromosome 1 breakpoints in male infertility.
- 2004
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 12:12, s. 993-1000
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Tidskriftsartikel (refereegranskat)abstract
- In a search for potential infertility loci, which might be revealed by clustering of chromosomal breakpoints, we compiled 464 infertile males with a balanced rearrangement from Mendelian Cytogenetics Network database (MCNdb) and compared their karyotypes with those of a Danish nation-wide cohort. We excluded Robertsonian translocations, rearrangements involving sex chromosomes and common variants. We identified 10 autosomal bands, five of which were on chromosome 1, with a large excess of breakpoints in the infertility group. Some of these could potentially harbour a male-specific infertility locus. However, a general excess of breakpoints almost everywhere on chromosome 1 was observed among the infertile males: 26.5 versus 14.5% in the cohort. This excess was observed both for translocation and inversion carriers, especially pericentric inversions, both for published and unpublished cases, and was significantly associated with azoospermia. The largest number of breakpoints was reported in 1q21; FISH mapping of four of these breakpoints revealed that they did not involve the same region at the molecular level. We suggest that chromosome 1 harbours a critical domain whose integrity is essential for male fertility.
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| 6. |
- Bedard, Annabelle, et al.
(författare)
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Mobile technology offers novel insights into the control and treatment of allergic rhinitis : The MASK study
- 2019
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Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 144:1, s. 135-143
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mobile health can be used to generate innovative insights into optimizing treatment to improve allergic rhinitis (AR) control. Objectives: A cross-sectional real-world observational study was undertaken in 22 countries to complement a pilot study and provide novel information on medication use, disease control, and work productivity in the everyday life of patients with AR. Methods: A mobile phone app (Allergy Diary, which is freely available on Google Play and Apple stores) was used to collect the data of daily visual analogue scale (VAS) scores for (1) overall allergic symptoms; (2) nasal, ocular, and asthma symptoms; (3) work; and (4) medication use by using a treatment scroll list including all allergy medications (prescribed and over-the-counter) customized for 22 countries. The 4 most common intranasal medications containing intranasal corticosteroids and 8 oral H-1-antihistamines were studied. Results: Nine thousand one hundred twenty-two users filled in 112,054 days of VASs in 2016 and 2017. Assessment of days was informative. Control of days with rhinitis differed between no (best control), single (good control for intranasal corticosteroid-treated days), or multiple (worst control) treatments. Users with the worst control increased the range of treatments being used. The same trend was found for asthma, eye symptoms, and work productivity. Differences between oral H-1-antihistamines were found. Conclusions: This study confirms the usefulness of the Allergy Diary in accessing and assessing behavior in patients with AR. This observational study using a very simple assessment tool (VAS) on a mobile phone had the potential to answer questions previously thought infeasible.
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| 7. |
- Bousquet, J. Jean, et al.
(författare)
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Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases
- 2019
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Ingår i: Clinical and Translational Allergy. - : BMC. - 2045-7022. ; 9
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Forskningsöversikt (refereegranskat)abstract
- Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Sante as a Good Practice in the field of digitally-enabled, integrated, person-centred care.Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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| 8. |
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| 9. |
- Elberling, Bo, et al.
(författare)
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Arctic vegetation damage by winter-generated coal mining pollution released upon thawing
- 2007
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 41:7, s. 2407-2413
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Tidskriftsartikel (refereegranskat)abstract
- Acid mine drainage (known as AMD) is a well-known environmental problem resulting from the oxidation of sulfidic mine waste. In cold regions, AMD is often considered limited by low temperatures most of the year and observed environmental impact is related to pollution generated during the warm summer period. Here we show that heat generation within an oxidizing, sulfidic, coal-mining waste-rock pile in Svalbard (78 degrees N) is high enough to keep the pile warm (roughly 5 degrees C throughout the year) despite mean annual air temperatures below -5 degrees C. Consequently, weathering processes continue year-round within the waste-rock pile. During the winter, weathering products accumulate within the pile because of a frozen outer layer on the pile and are released as a flush within 2 weeks of soil thawing in the spring. Consequently, spring runoff water contains elevated concentrations of metals. Several of these metals are taken up and accumulated in plants where they reach phytotoxic levels, including aluminum and manganese. Laboratory experiments document that uptake of Al and Mn in native plant species is highly correlated with dissolved concentrations. Therefore, future remedial actions to control the adverse environmental impacts of cold region coal-mining need to pay more attention to winter processes including AMD generation and accumulation of weathering products.
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| 10. |
- Elinder, Carl-Gustaf, et al.
(författare)
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Variations in graft and patient survival after kidney transplantation in Sweden: caveats in interpretation of center effects when benchmarking.
- 2009
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Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - : Frontiers Media SA. - 1432-2277 .- 0934-0874. ; 22:11, s. 1051-7
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Tidskriftsartikel (refereegranskat)abstract
- Benchmarking and comparisons between transplantation centers are becoming more common. A crude comparison indicated a 50% difference in patient survival between centers in Sweden. A 'task group' was formed to refute or confirm and learn from this observation. Patient survival and graft survival of 5 933 patients transplanted at three different transplantation centers in Sweden (Stockholm, Göteborg, and Malmö) were followed up until February 2007. Patient survival and graft survival were compared between the centers with and without consideration being given to important covariates such as time period, type of donation (living or deceased donor), gender, and age. A refined cohort of 2,956 adult patients that had been transplanted for the first time between 1991 and 2007 was assessed in more detail using Cox regression analysis. The difference in patient and transplant outcome observed in the crude comparison diminished considerably after adjustment for differences in case mix and time period of transplantation, and was neither evident nor significant after 1999. Patient survival and graft survival have improved considerably during the time period since 1991. The adjusted hazards ratio for mortality was 0.39 (95% CI 0.29-0.53) for patients who were transplanted after 1999 when compared with those transplanted between 1991 and 1994. Crude comparisons between results from transplantation centers may be severely confounded not only by case mix but also by differences in the proportion of patients transplanted during different time periods. Patient outcome and graft outcome have improved considerably since 1991, and after 1999 center effects were no longer apparent in Sweden.
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