| 1. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 2. |
- Chambers, Josephine M., et al.
(författare)
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Co-productive agility and four collaborative pathways to sustainability transformations
- 2022
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Ingår i: Global Environmental Change. - : Elsevier BV. - 0959-3780 .- 1872-9495. ; 72
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Tidskriftsartikel (refereegranskat)abstract
- Co-production, the collaborative weaving of research and practice by diverse societal actors, is argued to play an important role in sustainability transformations. Yet, there is still poor understanding of how to navigate the tensions that emerge in these processes. Through analyzing 32 initiatives worldwide that co-produced knowledge and action to foster sustainable social-ecological relations, we conceptualize 'co-productive agility' as an emergent feature vital for turning tensions into transformations. Co-productive agility refers to the willingness and ability of diverse actors to iteratively engage in reflexive dialogues to grow shared ideas and actions that would not have been possible from the outset. It relies on embedding knowledge production within processes of change to constantly recognize, reposition, and navigate tensions and opportunities. Co-productive agility opens up multiple pathways to transformation through: (1) elevating marginalized agendas in ways that maintain their integrity and broaden struggles for justice; (2) questioning dominant agendas by engaging with power in ways that challenge assumptions, (3) navigating conflicting agendas to actively transform interlinked paradigms, practices, and structures; (4) exploring diverse agendas to foster learning and mutual respect for a plurality of perspectives. We explore six process considerations that vary by these four pathways and provide a framework to enable agility in sustainability transformations. We argue that research and practice spend too much time closing down debate over different agendas for change - thereby avoiding, suppressing, or polarizing tensions, and call for more efforts to facilitate better interactions among different agendas.
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| 3. |
- Chambers, Josephine M., et al.
(författare)
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Six modes of co-production for sustainability
- 2021
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Ingår i: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 4, s. 983-996
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Tidskriftsartikel (refereegranskat)abstract
- Co-production includes diverse aims, terminologies and practices. This study explores such diversity by mapping differences in how 32 initiatives from 6 continents co-produce diverse outcomes for the sustainable development of ecosystems at local to global scales. The promise of co-production to address complex sustainability challenges is compelling. Yet, co-production, the collaborative weaving of research and practice, encompasses diverse aims, terminologies and practices, with poor clarity over their implications. To explore this diversity, we systematically mapped differences in how 32 initiatives from 6 continents co-produce diverse outcomes for the sustainable development of ecosystems at local to global scales. We found variation in their purpose for utilizing co-production, understanding of power, approach to politics and pathways to impact. A cluster analysis identified six modes of co-production: (1) researching solutions; (2) empowering voices; (3) brokering power; (4) reframing power; (5) navigating differences and (6) reframing agency. No mode is ideal; each holds unique potential to achieve particular outcomes, but also poses unique challenges and risks. Our analysis provides a heuristic tool for researchers and societal actors to critically explore this diversity and effectively navigate trade-offs when co-producing sustainability.
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| 4. |
- Chambers, Joshua R., et al.
(författare)
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Correcting for Systematic Underestimation of Topographic Glacier Aerodynamic Roughness Values From Hintereisferner, Austria
- 2021
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Ingår i: Frontiers in Earth Science. - : Frontiers Media SA. - 2296-6463. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Spatially-distributed values of glacier aerodynamic roughness (z0) are vital for robust estimates of turbulent energy fluxes and ice and snow melt. Microtopographic data allow rapid estimates of z0 over discrete plot-scale areas, but are sensitive to data scale and resolution. Here, we use an extensive multi-scale dataset from Hintereisferner, Austria, to develop a correction factor to derive z0 values from coarse resolution (up to 30 m) topographic data that are more commonly available over larger areas. Resulting z0 estimates are within an order of magnitude of previously validated, plot-scale estimates and aerodynamic values. The method is developed and tested using plot-scale microtopography data generated by structure from motion photogrammetry combined with glacier-scale data acquired by a permanent in-situ terrestrial laser scanner. Finally, we demonstrate the application of the method to a regional-scale digital elevation model acquired by airborne laser scanning. Our workflow opens up the possibility of including spatio-temporal variations of z0 within glacier surface energy balance models without the need for extensive additional field data collection.
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| 5. |
- Erzurumluoglu, A. Mesut, et al.
(författare)
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Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:10, s. 2392-2409
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Tidskriftsartikel (refereegranskat)abstract
- Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
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| 6. |
- Lim, Wanggi, et al.
(författare)
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Star cluster formation in Orion A
- 2021
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Ingår i: Publication of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 2053-051X .- 0004-6264. ; 73, s. S239-S255
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Tidskriftsartikel (refereegranskat)abstract
- We introduce new analysis methods for studying the star cluster formation processes in Orion A, especially examining the scenario of a cloud-cloud collision. We utilize the CARMA-NRO Orion survey (CO)-C-13 (1-0) data to compare molecular gas to the properties of young stellar objects from the SDSS III IN-SYNC survey. We show that the increase of v(13CO) - v(YSO) and Sigma scatter of older YSOs can be signals of cloud-cloud collision. SOFIA-upGREAT 158 mu m [C II] archival data toward the northern part of Orion A are also compared to the (CO)-C-13 data to test whether the position and velocity offsets between the emission from these two transitions resemble those predicted by a cloud-cloud collision model. We find that the northern part of Orion A, including regions ONC-OMC-1, OMC-2, OMC-3, and OMC-4, shows qualitative agreements with the cloud-cloud collision scenario, while in one of the southern regions, NGC 1999, there is no indication of such a process in causing the birth of new stars. On the other hand, another southern cluster, L 1641 N, shows slight tendencies of cloud-cloud collision. Overall, our results support the cloud-cloud collision process as being an important mechanism for star cluster formation in Orion A.
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| 10. |
- Smith, Thomas, et al.
(författare)
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A scale-dependent model to represent changing aerodynamic roughness of ablating glacier ice based on repeat topographic surveys
- 2020
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Ingår i: Journal of Glaciology. - : Cambridge University Press (CUP). - 0022-1430 .- 1727-5652. ; 66:260, s. 950-964
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Forskningsöversikt (refereegranskat)abstract
- Turbulent fluxes make a substantial and growing contribution to the energy balance of ice surfaces globally, but are poorly constrained owing to challenges in estimating the aerodynamic roughness length (z0). Here, we used structure from motion (SfM) photogrammetry and terrestrial laser scanning (TLS) surveys to make plot-scale 2-D and 3-D microtopographic estimations of z0 and upscale these to map z0 across an ablating mountain glacier. At plot scales, we found spatial variability in z0 estimates of over two orders of magnitude with unpredictable z0 trajectories, even when classified into ice surface types. TLS-derived surface roughness exhibited strong relationships with plot-scale SfM z0 estimates. At the glacier scale, a consistent increase in z0 of ∼0.1 mm d-1 was observed. Space-for-time substitution based on time since surface ice was exposed by snow melt confirmed this gradual increase in z0 over 60 d. These measurements permit us to propose a scale-dependent temporal z0 evolution model where unpredictable variability at the plot scale gives way to more predictable changes of z0 at the glacier scale. This model provides a critical step towards deriving spatially and temporally distributed representations of z0 that are currently lacking in the parameterisation of distributed glacier surface energy balance models.
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