| 1. |
- Schmidt, Amand F., et al.
(författare)
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PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study
- 2017
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Ingår i: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 5:2, s. 97-105
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Tidskriftsartikel (refereegranskat)abstract
- Background Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way off sets their substantial benefi ts. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely eff ects of PCSK9 inhibitors on diabetes risk. Methods In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA 1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. Findings Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0.09 mmol/L, 95% CI 0.02 to 0.15), bodyweight (1.03 kg, 0.24 to 1.82), waist-to-hip ratio (0.006, 0.003 to 0.010), and an odds ratio for type diabetes of 1.29 (1.11 to 1.50). Based on the collected data, we did not identify associations with HbA 1c (0.03%, -0.01 to 0.08), fasting insulin (0.00%, -0.06 to 0.07), and BMI (0.11 kg/m(2), -0.09 to 0.30). Interpretation PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefi ts of PCSK9 inhibitor treatment, as was previously done for statins.
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| 2. |
- Schmidt, Amand F., et al.
(författare)
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Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9
- 2019
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Ingår i: BMC Cardiovascular Disorders. - : BMC. - 1471-2261 .- 1471-2261. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
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| 3. |
- Wain, Louise V, et al.
(författare)
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Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:3, s. 416-425
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20-1.27), P = 5.05 × 10(-49)), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes for development, elastic fibers and epigenetic regulation pathways. We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.
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| 4. |
- Blösch, Günter, et al.
(författare)
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Twenty-three unsolved problems in hydrology (UPH) - a community perspective
- 2019
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Ingår i: Hydrological Sciences Journal. - : Informa UK Limited. - 0262-6667 .- 2150-3435. ; 64:10, s. 1141-1158
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Tidskriftsartikel (refereegranskat)abstract
- This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through online media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focused on the process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come.
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| 5. |
- Aumayr, Friedrich, et al.
(författare)
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Roadmap on photonic, electronic and atomic collision physics : III. Heavy particles
- 2019
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Ingår i: Journal of Physics B. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 52:17
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Tidskriftsartikel (refereegranskat)abstract
- We publish three Roadmaps on photonic, electronic and atomic collision physics in order to celebrate the 60th anniversary of the ICPEAC conference. Roadmap III focusses on heavy particles: with zero to relativistic speeds. Modern theoretical and experimental approaches provide detailed insight into the wide range of many-body interactions involving projectiles and targets of varying complexity ranging from simple atoms, through molecules and clusters, complex biomolecules and nanoparticles to surfaces and crystals. These developments have been driven by technological progress and future developments will expand the horizon of the systems that can be studied. This Roadmap aims at looking back along the road, explaining the evolution of the field, and looking forward, collecting nineteen contributions from leading scientists in the field.
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| 6. |
- Fett, Michel, et al.
(författare)
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A survey on the industry’s perception of digital twins – a follow-up to the digital twin workshop at the DESIGN Conference 2022
- 2024
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Ingår i: Proceedings of the Design Society. - 2732-527X. ; 4, s. 2039-2048
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Konferensbidrag (refereegranskat)abstract
- Digital Twins are perceived differently between and within industry and academia regarding applications and potentials. For this reason, a round table was formed based on the Digital Twin Workshop of the Design Conference 2022. One of the results of this round table is this contribution, which deals with a survey within the industry. The survey captured the understanding of the different roles in the creation and use of Digital Twins, the requirements and hurdles as well as the perception of methodological support. In addition, factors that influence the perception were identified.
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| 7. |
- Gottselig, N., et al.
(författare)
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Elemental Composition of Natural Nanoparticles and Fine Colloids in European Forest Stream Waters and Their Role as Phosphorus Carriers
- 2017
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Ingår i: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 31:10, s. 1592-1607
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Tidskriftsartikel (refereegranskat)abstract
- Biogeochemical cycling of elements largely occurs in dissolved state, but many elements may also be bound to natural nanoparticles (NNP, 1-100 nm) and fine colloids (100-450 nm). We examined the hypothesis that the size and composition of stream water NNP and colloids vary systematically across Europe. To test this hypothesis, 96 stream water samples were simultaneously collected in 26 forested headwater catchments along two transects across Europe. Three size fractions (~1-20 nm, >20-60 nm, and >60 nm) of NNP and fine colloids were identified with Field Flow Fractionation coupled to inductively coupled plasma mass spectrometry and an organic carbon detector. The results showed that NNP and fine colloids constituted between 2 ± 5% (Si) and 53 ± 21% (Fe; mean ± SD) of total element concentrations, indicating a substantial contribution of particles to element transport in these European streams, especially for P and Fe. The particulate contents of Fe, Al, and organic C were correlated to their total element concentrations, but those of particulate Si, Mn, P, and Ca were not. The fine colloidal fractions >60 nm were dominated by clay minerals across all sites. The resulting element patterns of NNP <60 nm changed from North to South Europe from Fe- to Ca-dominated particles, along with associated changes in acidity, forest type, and dominant lithology.
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| 8. |
- Heinimäki, Leena, et al.
(författare)
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Actualizing Sámi Rights: International Comparative Research : [Saamelaisten oikeuksientoteutuminen: kansainvälinenoikeusvertaileva tutkimus]: [Förverkligandet av samiska rättigheter: Internationell jämförande forskning]
- 2017. - 1
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I Finland har erkännandet och implementeringen av samiska rättigheter varit komplicerat. Syftet med detta forskningsprojekt är att ge kunskap om förhållanden som finska regeringen efterfrågat, särskilt i förhållande till samers markrättigheter, deltagande/konsultationer och frågan om vem som är same. Forskningen är en internationell och komparativ studie som avser att ge ny kunskap om den senaste tidens rättsutveckling vad gäller urfolks rättigheter inom internationell rätt samt på nationell nivå med en jämförande ansats av några relevanta länder. Forskningsrapporten består av fyra delar. Den första delen fokuserar på folkrättens krav och internationell standard vad gäller urfolks rättigheter och tar främst sikte på samernas rättsliga status. Den andra delen diskuterar problematiken med att definiera vem som är same, i ljuset av internationell rätt och Högsta förvaltningsdomstolens domar i Finland. Denna del innehåller även en beskrivning av bakgrund och skälen till tvisterna gällande definitionen. Den tredje delen behandlar urfolks rättsliga status och rättigheter enligt internationell rätt, med särskilt fokus på principen om urfolks fria och informerade samtycke, liksom tolkningen av artiklarna rörande landrättigheter i ILOs konvention 169. Den fjärde delen innehåller information om och jämförelse av urfolks rättsliga status i ett antal utvalda rättsystem: Norge, Sverige, Aotearoa Nya Zeeland och Kanada samt ett gemensamt kapitel om Latinamerika. Denna del innehåller sammanfattningar av centrala element och rättsliga lösningar i respektive rättssystem, liksom en sammanfattande konklusion gällande lösningar som kan vara till nytta för erkännandet av samiska rättigheter i Finland.
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| 9. |
- Heinämäki, Leena, 1974-, et al.
(författare)
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Saamelaisten oikeuksien toteutuminen : kansainvälinen oikeusvertaileva tutkimus
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Saamelaisten oikeuksien eteenpäin vieminen Suomessa on kohdannut haasteita. Tämä tutkimus pyrkii vastaamaan valtioneuvoston määrittelemään tietotarpeeseen, joka liittyy erityisesti saamelaisten maa- ja osallistumisoikeuksiin sekä saamelaismääritelmään. Kyseessä on kansainvälinen oikeusvertaileva tutkimus, joka pyrkii tarjoamaan uutta tietoa sekä kansainvälisen alkuperäiskansaoikeuden kehityksestä että siitä, miten muissa aiheen kannalta keskeisissä valtioissa on ratkaistu alkuperäiskansojen oikeuksiin liittyviä kysymyksiä. Tutkimusraportti koostuu neljästä pääosiosta. Ensimmäinen osio tarkastelee saamelaisten oikeusasemaa Suomessa sekä siihen liittyviä ehdotuksia, joita tarkastellaan kansainvälisen oikeuden luomien velvoitteiden näkökulmasta. Toinen kokonaisuus pitää sisällään saamelaismääritelmän problematiikan tarkastelua kansainvälisen oikeuden sekä korkeimman hallinto-oikeuden tapauskäytännön valossa, sisältäen myös kuvauksen saamelaisuuden määrittelyyn liittyvien kiistojen taustoista ja syistä. Kolmas pääosio keskittyy alkuperäiskansojen kansainvälisoikeudellisen aseman ja oikeuksien kehitykseen pääfokuksena ns. ennakkosuostumuksen periaate (FPIC). Tämä osio pitää sisällään myös ILO sopimus 169:n sisältämien maaoikeuksien analyysiin. Neljäs pääkokonaisuus on oikeusvertaileva osio, jossa on mukana Norjaa, Ruotsia, Uutta-Seelantia, Kanadaa ja Latinalaisen Amerikan maita koskevat maaraportit. Tämä kappalekokonaisuus sisältää myös yhteenvedon vertailun piirissä olleiden valtioiden oikeuskäytänteiden keskeisistä elementeistä, joista voidaan löytää parhaita käytänteitä Suomen saamelaisten oikeuksien toteuttamiseksi.
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| 10. |
- Kyllönen, Katri-Maaria, et al.
(författare)
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Indigenous rights, social media and protest movements in Sápmi
- 2024
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Ingår i: Mineral Economics. - : Springer Nature. - 2191-2203 .- 2191-2211.
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Tidskriftsartikel (refereegranskat)abstract
- Following the rush to minerals that would enable the shift towards green economies, the Sámi homeland is quickly becoming a crucible for the rising tensions surrounding the potential for new mining projects and large-scale infrastructure projects. The roots of these conflicts date back to the colonization of the north and continue in the present with the ongoing fight to maintain the Sámi heritage, language and culture, and increasingly to gain ownership of their lands. What initially began as activism within the legal system has, on occasions, transformed into outright protests. Social media increasingly plays a key role in disseminating the message of Indigenous protest among the protesters themselves and feeding into the national and international mainstream media. This shift occurs simultaneously with the construction of a dual narrative, constituted of both land-use protest and intensified demands for Indigenous rights, including, first and foremost, the right to self-determination. Drawing from Social media theory literature and the concepts of political opportunity structures (POS) and legal opportunity structures (LOS), this study argues that social media is one of the most essential tools used by Sámi activists to raise awareness about issue-based protests as well as to communicate demands for the right to self-determination when legal and political opportunity structures are not enough to support the cause. The power of social media lies in its accessibility, immediacy and visuality, which is illustrated in the article via specific examples of mining and railway construction protests in Finland and Sweden. Social media does not replace older tools, such as international human rights litigation, but their use can complement existing strategies for defending and advancing Indigenous rights.
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