| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Beven, Keith, et al.
(författare)
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Epistemic uncertainties and natural hazard risk assessment - Part 2 : What should constitute good practice?
- 2018
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Ingår i: Natural hazards and earth system sciences. - : COPERNICUS GESELLSCHAFT MBH. - 1561-8633 .- 1684-9981. ; 18:10, s. 2769-2783
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Tidskriftsartikel (refereegranskat)abstract
- Part 1 of this paper has discussed the uncertainties arising from gaps in knowledge or limited understanding of the processes involved in different natural hazard areas. Such deficits may include uncertainties about frequencies, process representations, parameters, present and future boundary conditions, consequences and impacts, and the meaning of observations in evaluating simulation models. These are the epistemic uncertainties that can be difficult to constrain, especially in terms of event or scenario probabilities, even as elicited probabilities rationalized on the basis of expert judgements. This paper reviews the issues raised by trying to quantify the effects of epistemic uncertainties. Such scientific uncertainties might have significant influence on decisions made, say, for risk management, so it is important to examine the sensitivity of such decisions to different feasible sets of assumptions, to communicate the meaning of associated uncertainty estimates, and to provide an audit trail for the analysis. A conceptual framework for good practice in dealing with epistemic uncertainties is outlined and the implications of applying the principles to natural hazard assessments are discussed. Six stages are recognized, with recommendations at each stage as follows: (1) framing the analysis, preferably with input from potential users; (2) evaluating the available data for epistemic uncertainties, especially when they might lead to inconsistencies; (3) eliciting information on sources of uncertainty from experts; (4) defining a workflow that will give reliable and accurate results; (5) assessing robustness to uncertainty, including the impact on any decisions that are dependent on the analysis; and (6) communicating the findings and meaning of the analysis to potential users, stakeholders, and decision makers. Visualizations are helpful in conveying the nature of the uncertainty outputs, while recognizing that the deeper epistemic uncertainties might not be readily amenable to visualizations.
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| 3. |
- Gallego-Sala, Angela V., et al.
(författare)
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Latitudinal limits to the predicted increase of the peatland carbon sink with warming
- 2018
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Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 8:10, s. 907-
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Tidskriftsartikel (refereegranskat)abstract
- The carbon sink potential of peatlands depends on the balance of carbon uptake by plants and microbial decomposition. The rates of both these processes will increase with warming but it remains unclear which will dominate the global peatland response. Here we examine the global relationship between peatland carbon accumulation rates during the last millennium and planetary-scale climate space. A positive relationship is found between carbon accumulation and cumulative photosynthetically active radiation during the growing season for mid- to high-latitude peatlands in both hemispheres. However, this relationship reverses at lower latitudes, suggesting that carbon accumulation is lower under the warmest climate regimes. Projections under Representative Concentration Pathway (RCP)2.6 and RCP8.5 scenarios indicate that the present-day global sink will increase slightly until around AD 2100 but decline thereafter. Peatlands will remain a carbon sink in the future, but their response to warming switches from a negative to a positive climate feedback (decreased carbon sink with warming) at the end of the twenty-first century.
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| 4. |
- Graff, M., et al.
(författare)
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Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults
- 2017
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Ingår i: PLoS Genet. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
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| 5. |
- Sawcer, Stephen, et al.
(författare)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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| 6. |
- Dittrich, Sabine, et al.
(författare)
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Target Product Profile for a Diagnostic Assay to Differentiate between Bacterial and Non-Bacterial Infections and Reduce Antimicrobial Overuse in Resource-Limited Settings : An Expert Consensus
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- Acute fever is one of the most common presenting symptoms globally. In order to reduce the empiric use of antimicrobial drugs and improve outcomes, it is essential to improve diagnostic capabilities. In the absence of microbiology facilities in low-income settings, an assay to distinguish bacterial from non-bacterial causes would be a critical first step. To ensure that patient and market needs are met, the requirements of such a test should be specified in a target product profile (TPP). To identify minimal/optimal characteristics for a bacterial vs. non-bacterial fever test, experts from academia and international organizations with expertise in infectious diseases, diagnostic test development, laboratory medicine, global health, and health economics were convened. Proposed TPPs were reviewed by this working group, and consensus characteristics were defined. The working group defined non-severely ill, non-malaria infected children as the target population for the desired assay. To provide access to the most patients, the test should be deployable to community health centers and informal health settings, and staff should require <2 days of training to perform the assay. Further, given that the aim is to reduce inappropriate antimicrobial use as well as to deliver appropriate treatment for patients with bacterial infections, the group agreed on minimal diagnostic performance requirements of >90% and >80% for sensitivity and specificity, respectively. Other key characteristics, to account for the challenging environment at which the test is targeted, included: i) time-to-result <10 min (but maximally <2 hrs); ii) storage conditions at 0-40 degrees C, <= 90% non-condensing humidity with a minimal shelf life of 12 months; iii) operational conditions of 5-40 degrees C, <= 90% non-condensing humidity; and iv) minimal sample collection needs (50-100 mu L, capillary blood). This expert approach to define assay requirements for a bacterial vs. non-bacterial assay should guide product development, and enable targeted and timely efforts by industry partners and academic institutions.
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| 7. |
- 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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| 8. |
- Folkersen, Lasse, et al.
(författare)
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Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
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Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
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Tidskriftsartikel (refereegranskat)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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| 9. |
- Page, Paul, et al.
(författare)
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Do Flower Color and Floral Scent of Silene Species affect Host Preference of Hadena bicruris, a Seed-Eating Pollinator, under Field Conditions?
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e98755-
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Tidskriftsartikel (refereegranskat)abstract
- Specialization in plant-insect interactions is an important driver of evolutionary divergence; yet, plant traits mediating such interactions are poorly understood. In this study, we investigated how flower color and floral scent are related to seed predation by a seed-eating pollinator. We used field-transplanted recombinant F-2 hybrids between Silene latifolia and S. dioica that are the preferred and alternative hosts of the moth Hadena bicruris and crosses within these species for comparison. We scored seed predation and flower color and analyzed floral scent. Pinker S. dioica-like flowers and emission of a-pinene decreased the odds of seed predation while emission of benzyl acetate and 6-methyl-5-hepten-2-one increased the odds of seed predation. Emission of these compounds did not differ significantly between the two Silene species. Our results suggest that flower color plays an important role in the specific interaction of H. bicruris with its preferred host S. latifolia. The compounds alpha-pinene, benzyl acetate and 6-methyl-5-hepten-2-one could represent non-specific deterrents and attractants to ovipositing moths. Alternatively, emission of these compounds could be related to herbivory or pathogen attack and act as a signal for host quality. This would weaken the predictability of the plant's costs and benefits of the interaction and act to maintain an imperfect degree of specialization.
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| 10. |
- Saunders, Gary, et al.
(författare)
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Leveraging European infrastructures to access 1 million human genomes by 2022
- 2019
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Ingår i: Nature reviews genetics. - : Springer Nature. - 1471-0056 .- 1471-0064. ; 20:11, s. 693-701
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Tidskriftsartikel (refereegranskat)abstract
- Human genomics is undergoing a step change from being a predominantly research-driven activity to one driven through health care as many countries in Europe now have nascent precision medicine programmes. To maximize the value of the genomic data generated, these data will need to be shared between institutions and across countries. In recognition of this challenge, 21 European countries recently signed a declaration to transnationally share data on at least 1 million human genomes by 2022. In this Roadmap, we identify the challenges of data sharing across borders and demonstrate that European research infrastructures are well-positioned to support the rapid implementation of widespread genomic data access.
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