| 1. |
- Fazey, Ioan, et al.
(författare)
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Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
- 2020
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Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
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Tidskriftsartikel (refereegranskat)abstract
- Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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| 2. |
- Ji, Xuemei, et al.
(författare)
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Protein-altering germline mutations implicate novel genes related to lung cancer development
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio=8.82, P=1.18x10(-15)) and replication (adjusted OR=2.93, P=2.22x10(-3)) that is more pronounced in females (adjusted OR=6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR=2.61, P=7.98x10(-22)) and replication datasets (adjusted OR=1.55, P=0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk. In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.
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| 3. |
- Botvinik-Nezer, Rotem, et al.
(författare)
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Variability in the analysis of a single neuroimaging dataset by many teams
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
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Tidskriftsartikel (refereegranskat)abstract
- Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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| 4. |
- Dekkers, Ilona A., et al.
(författare)
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Consensus-based technical recommendations for clinical translation of renal T1 and T2 mapping MRI
- 2020
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Ingår i: Magnetic Resonance Materials in Physics, Biology, and Medicine. - : Springer Science and Business Media LLC. - 1352-8661 .- 0968-5243. ; 33:1, s. 163-176
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Forskningsöversikt (refereegranskat)abstract
- To develop technical recommendations on the acquisition and post-processing of renal longitudinal (T1) and transverse (T2) relaxation time mapping. A multidisciplinary panel consisting of 18 experts in the field of renal T1 and T2 mapping participated in a consensus project, which was initiated by the European Cooperation in Science and Technology Action PARENCHIMA CA16103. Consensus recommendations were formulated using a two-step modified Delphi method. The first survey consisted of 56 items on T1 mapping, of which 4 reached the pre-defined consensus threshold of 75% or higher. The second survey was expanded to include both T1 and T2 mapping, and consisted of 54 items of which 32 reached consensus. Recommendations based were formulated on hardware, patient preparation, acquisition, analysis and reporting. Consensus-based technical recommendations for renal T1 and T2 mapping were formulated. However, there was considerable lack of consensus for renal T1 and particularly renal T2 mapping, to some extent surprising considering the long history of relaxometry in MRI, highlighting key knowledge gaps that require further work. This paper should be regarded as a first step in a long-term evidence-based iterative process towards ever increasing harmonization of scan protocols across sites, to ultimately facilitate clinical implementation.
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| 5. |
- Escala-Garcia, Maria, et al.
(författare)
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A network analysis to identify mediators of germline-driven differences in breast cancer prognosis
- 2020
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies similar to 7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.
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| 6. |
- Feng, Shaohong, et al.
(författare)
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Dense sampling of bird diversity increases power of comparative genomics
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7833
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Tidskriftsartikel (refereegranskat)abstract
- Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
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| 7. |
- Lim, Soon Tjin, et al.
(författare)
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Platelet function/reactivity testing and prediction of risk of recurrent vascular events and outcomes after TIA or ischaemic stroke : systematic review and meta-analysis
- 2020
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 267:10, s. 3021-3037
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prevalence of ex vivo ‘high on-treatment platelet reactivity (HTPR)’ and its relationship with recurrent vascular events/outcomes in patients with ischaemic cerebrovascular disease (CVD) is unclear. Methods: A systematic review and meta-analysis was performed in accordance with the PRISMA statement. MEDLINE, EMBASE and Cochrane Library were searched for completed manuscripts until May 2019 on TIA/ischaemic stroke patients, ≥ 18 years, treated with commonly-prescribed antiplatelet therapy, who had platelet function/reactivity testing and prospective follow-up data on recurrent stroke/TIA, myocardial infarction, vascular death or other cerebrovascular outcomes. Data were pooled using random-effects meta-analysis. Primary outcome was the composite risk of recurrent stroke/TIA, myocardial infarction or vascular death. Secondary outcomes were recurrent stroke/TIA, severe stroke (NIHSS > 16) or disability/impairment (modified Rankin scale ≥ 3) during follow-up. Results: Antiplatelet–HTPR prevalence was 3–65% with aspirin, 8–56% with clopidogrel and 1.8–35% with aspirin–clopidogrel therapy. Twenty studies (4989 patients) were included in our meta-analysis. There was a higher risk of the composite primary outcome (OR 2.93, 95% CI 1.90–4.51) and recurrent ischaemic stroke/TIA (OR 2.43, 95% CI 1.51–3.91) in patients with vs. those without ‘antiplatelet–HTPR’ on any antiplatelet regimen. These risks were also more than twofold higher in patients with vs. those without ‘aspirin–HTPR’ and ‘dual antiplatelet–HTPR’, respectively. Clopidogrel–HTPR status did not significantly predict outcomes, but the number of eligible studies was small. The risk of severe stroke was higher in those with vs. without antiplatelet–HTPR (OR 2.65, 95% CI 1.00–7.01). Discussion: Antiplatelet–HTPR may predict risks of recurrent vascular events/outcomes in CVD patients. Given the heterogeneity between studies, further prospective, multi-centre studies are warranted.
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| 8. |
- Moore, Amy, et al.
(författare)
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Genetically Determined Height and Risk of Non-hodgkin Lymphoma
- 2020
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Ingår i: Frontiers in Oncology. - : FRONTIERS MEDIA SA. - 2234-943X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00-1.17, p = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01-1.31, p = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes.
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