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Sökning: WFRF:(George Julia)

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51.
  • Ruggeri, Kai, et al. (författare)
  • The globalizability of temporal discounting
  • 2022
  • Ingår i: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 6:10, s. 1386-1397
  • Tidskriftsartikel (refereegranskat)abstract
    • Economic inequality is associated with preferences for smaller, immediate gains over larger, delayed ones. Such temporal discounting may feed into rising global inequality, yet it is unclear whether it is a function of choice preferences or norms, or rather the absence of sufficient resources for immediate needs. It is also not clear whether these reflect true differences in choice patterns between income groups. We tested temporal discounting and five intertemporal choice anomalies using local currencies and value standards in 61 countries (N = 13,629). Across a diverse sample, we found consistent, robust rates of choice anomalies. Lower-income groups were not significantly different, but economic inequality and broader financial circumstances were clearly correlated with population choice patterns. Ruggeri et al. find in a study of 61 countries that temporal discounting patterns are globally generalizable. Worse financial environments, greater inequality and high inflation are associated with extreme or inconsistent long-term decisions.
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52.
  • Schoville, Sean D., et al. (författare)
  • A model species for agricultural pest genomics : The genome of the Colorado potato beetle, Leptinotarsa decemlineata (Coleoptera: Chrysomelidae)
  • 2018
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • The Colorado potato beetle is one of the most challenging agricultural pests to manage. It has shown a spectacular ability to adapt to a variety of solanaceaeous plants and variable climates during its global invasion, and, notably, to rapidly evolve insecticide resistance. To examine evidence of rapid evolutionary change, and to understand the genetic basis of herbivory and insecticide resistance, we tested for structural and functional genomic changes relative to other arthropod species using genome sequencing, transcriptomics, and community annotation. Two factors that might facilitate rapid evolutionary change include transposable elements, which comprise at least 17% of the genome and are rapidly evolving compared to other Coleoptera, and high levels of nucleotide diversity in rapidly growing pest populations. Adaptations to plant feeding are evident in gene expansions and differential expression of digestive enzymes in gut tissues, as well as expansions of gustatory receptors for bitter tasting. Surprisingly, the suite of genes involved in insecticide resistance is similar to other beetles. Finally, duplications in the RNAi pathway might explain why Leptinotarsa decemlineata has high sensitivity to dsRNA. The L. decemlineata genome provides opportunities to investigate a broad range of phenotypes and to develop sustainable methods to control this widely successful pest.
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53.
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54.
  • Speetjens, Niek Jesse, et al. (författare)
  • Dissolved organic matter characterization in soils and streams in a small coastal low-Arctic catchment
  • 2022
  • Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 19:12, s. 3073-3097
  • Tidskriftsartikel (refereegranskat)abstract
    • Ongoing climate warming in the western Canadian Arctic is leading to thawing of permafrost soils and subsequent mobilization of its organic matter pool. Part of this mobilized terrestrial organic matter enters the aquatic system as dissolved organic matter (DOM) and is laterally transported from land to sea. Mobilized organic matter is an important source of nutrients for ecosystems, as it is available for microbial breakdown, and thus a source of greenhouse gases. We are beginning to understand spatial controls on the release of DOM as well as the quantities and fate of this material in large Arctic rivers. Yet, these processes remain systematically understudied in small, high-Arctic watersheds, despite the fact that these watersheds experience the strongest warming rates in comparison. Here, we sampled soil (active layer and permafrost) and water (porewater and stream water) from a small ice wedge polygon (IWP) catchment along the Yukon coast, Canada, during the summer of 2018. We assessed the organic carbon (OC) quantity (using dissolved (DOC) and particulate OC (POC) concentrations and soil OC content), quality (δ13C DOC, optical properties and source apportionment) and bioavailability (incubations; optical indices such as slope ratio, Sr; and humification index, HIX) along with stream water properties (temperature, T; pH; electrical conductivity, EC; and water isotopes). We classify and compare different landscape units and their soil horizons that differ in microtopography and hydrological connectivity, giving rise to differences in drainage capacity. Our results show that porewater DOC concentrations and yield reflect drainage patterns and waterlogged conditions in the watershed. DOC yield (in mg DOC g−1 soil OC) generally increases with depth but shows a large variability near the transition zone (around the permafrost table). Active-layer porewater DOC generally is more labile than permafrost DOC, due to various reasons (heterogeneity, presence of a paleo-active-layer and sampling strategies). Despite these differences, the very long transport times of porewater DOC indicate that substantial processing occurs in soils prior to release into streams. Within the stream, DOC strongly dominates over POC, illustrated by DOC/POC ratios around 50, yet storm events decrease that ratio to around 5. Source apportionment of stream DOC suggests a contribution of around 50 % from permafrost/deep-active-layer OC, which contrasts with patterns observed in large Arctic rivers (12 ± 8 %; Wild et al., 2019). Our 10 d monitoring period demonstrated temporal DOC patterns on multiple scales (i.e., diurnal patterns, storm events and longer-term trends), underlining the need for high-resolution long-term monitoring. First estimates of Black Creek annual DOC (8.2 ± 6.4 t DOC yr−1) and POC (0.21 ± 0.20 t yr−1) export allowed us to make a rough upscaling towards the entire Yukon Coastal Plain (34.51 ± 2.7 kt DOC yr−1 and 8.93 ± 8.5 kt POC yr−1). Rising Arctic temperatures, increases in runoff, soil organic matter (OM) leaching, permafrost thawing and primary production are likely to increase the net lateral OC flux. Consequently, altered lateral fluxes may have strong impacts on Arctic aquatic ecosystems and Arctic carbon cycling.
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55.
  • Stahl, Bernd Carsten, et al. (författare)
  • From Responsible Research and Innovation to responsibility by design
  • 2021
  • Ingår i: Journal of Responsible Innovation. - : Taylor & Francis. - 2329-9460 .- 2329-9037. ; 8:2, s. 175-198
  • Tidskriftsartikel (refereegranskat)abstract
    • Drawing on more than eight years working to implement Responsible Research and Innovation (RRI) in the Human Brain Project, a large EU-funded research project that brings together neuroscience, computing, social sciences, and the humanities, and one of the largest investments in RRI in one project, this article offers insights on RRI and explores its possible future. We focus on the question of how RRI can have long-lasting impact and persist beyond the time horizon of funded projects. For this purpose, we suggest the concept of ‘responsibility by design’ which is intended to encapsulate the idea of embedding RRI in research and innovation in a way that makes it part of the fabric of the resulting outcomes, in our case, a distributed European Research Infrastructure.
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56.
  • Stevens, Kristen N, et al. (författare)
  • 19p13.1 is a triple negative-specific breast cancer susceptibility locus
  • 2012
  • Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 72, s. 1795-
  • Tidskriftsartikel (refereegranskat)abstract
    • The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with risk of ovarian cancer. Here we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 Odds Ratio (OR)=1.10, 95% Confidence Interval (CI) 1.05 - 1.15, p=3.49 x 10-5] and triple negative (TN) (ER, PR and HER2 negative) breast cancer [rs8170 OR=1.22, 95% CI 1.13 - 1.31, p=2.22 x 10-7]. However, rs8170 was no longer associated with ER-negative breast cancer risk when TN cases were excluded [OR=0.98, 95% CI 0.89 - 1.07, p=0.62]. In addition, a combined analysis of TN cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC) (n=3,566) identified a genome-wide significant association between rs8170 and TN breast cancer risk [OR=1.25, 95% CI 1.18 - 1.33, p=3.31 x 10-13]. Thus, 19p13.1 is the first triple negative-specific breast cancer risk locus and the first locus specific to a histological subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple negative tumors and other subtypes likely arise through distinct etiologic pathways.
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57.
  • Swen, JesseJ, et al. (författare)
  • A 12-gene pharmacogenetic panel to prevent adverse drug reactions : an open-label, multicentre, controlled, cluster-randomised crossover implementation study
  • 2023
  • Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 401:10374, s. 347-356
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The benefit of pharmacogenetic testing before starting drug therapy has been well documented for several single gene-drug combinations. However, the clinical utility of a pre-emptive genotyping strategy using a pharmacogenetic panel has not been rigorously assessed.Methods: We conducted an open-label, multicentre, controlled, cluster-randomised, crossover implementation study of a 12-gene pharmacogenetic panel in 18 hospitals, nine community health centres, and 28 community pharmacies in seven European countries (Austria, Greece, Italy, the Netherlands, Slovenia, Spain, and the UK). Patients aged 18 years or older receiving a first prescription for a drug clinically recommended in the guidelines of the Dutch Pharmacogenetics Working Group (ie, the index drug) as part of routine care were eligible for inclusion. Exclusion criteria included previous genetic testing for a gene relevant to the index drug, a planned duration of treatment of less than 7 consecutive days, and severe renal or liver insufficiency. All patients gave written informed consent before taking part in the study. Participants were genotyped for 50 germline variants in 12 genes, and those with an actionable variant (ie, a drug-gene interaction test result for which the Dutch Pharmacogenetics Working Group [DPWG] recommended a change to standard-of-care drug treatment) were treated according to DPWG recommendations. Patients in the control group received standard treatment. To prepare clinicians for pre-emptive pharmacogenetic testing, local teams were educated during a site-initiation visit and online educational material was made available. The primary outcome was the occurrence of clinically relevant adverse drug reactions within the 12-week follow-up period. Analyses were irrespective of patient adherence to the DPWG guidelines. The primary analysis was done using a gatekeeping analysis, in which outcomes in people with an actionable drug-gene interaction in the study group versus the control group were compared, and only if the difference was statistically significant was an analysis done that included all of the patients in the study. Outcomes were compared between the study and control groups, both for patients with an actionable drug-gene interaction test result (ie, a result for which the DPWG recommended a change to standard-of-care drug treatment) and for all patients who received at least one dose of index drug. The safety analysis included all participants who received at least one dose of a study drug. This study is registered with ClinicalTrials.gov, NCT03093818 and is closed to new participants.Findings: Between March 7, 2017, and June 30, 2020, 41 696 patients were assessed for eligibility and 6944 (51.4 % female, 48.6% male; 97.7% self-reported European, Mediterranean, or Middle Eastern ethnicity) were enrolled and assigned to receive genotype-guided drug treatment (n=3342) or standard care (n=3602). 99 patients (52 [1.6%] of the study group and 47 [1.3%] of the control group) withdrew consent after group assignment. 652 participants (367 [11.0%] in the study group and 285 [7.9%] in the control group) were lost to follow-up. In patients with an actionable test result for the index drug (n=1558), a clinically relevant adverse drug reaction occurred in 152 (21 center dot 0%) of 725 patients in the study group and 231 (27.7%) of 833 patients in the control group (odds ratio [OR] 0 center dot 70 [95% CI 0 center dot 54-0 center dot 91]; p=0.0075), whereas for all patients, the incidence was 628 (21.5%) of 2923 patients in the study group and 934 (28. 6%) of 3270 patients in the control group (OR 0.70 [95% CI 0.61-0.79]; p <0.0001).Interpretation: Genotype-guided treatment using a 12-gene pharmacogenetic panel significantly reduced the incidence of clinically relevant adverse drug reactions and was feasible across diverse European health-care system organisations and settings. Large-scale implementation could help to make drug therapy increasingly safe.
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58.
  • Tanski, George, et al. (författare)
  • The Permafrost Young Researchers Network (PYRN) is getting older : The past, present, and future of our evolving community
  • 2019
  • Ingår i: Polar Record. - 0032-2474 .- 1475-3057. ; 55:4, s. 216-219
  • Tidskriftsartikel (refereegranskat)abstract
    • A lasting legacy of the International Polar Year (IPY) 2007-2008 was the promotion of the Permafrost Young Researchers Network (PYRN), initially an IPY outreach and education activity by the International Permafrost Association (IPA). With the momentum of IPY, PYRN developed into a thriving network that still connects young permafrost scientists, engineers, and researchers from other disciplines. This research note summarises (1) PYRN's development since 2005 and the IPY's role, (2) the first 2015 PYRN census and survey results, and (3) PYRN's future plans to improve international and interdisciplinary exchange between young researchers. The review concludes that PYRN is an established network within the polar research community that has continually developed since 2005. PYRN's successful activities were largely fostered by IPY. With >200 of the 1200 registered members active and engaged, PYRN is capitalising on the availability of social media tools and rising to meet environmental challenges while maintaining its role as a successful network honouring the legacy of IPY.
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59.
  • ter Steege, Hans, et al. (författare)
  • Mapping density, diversity and species-richness of the Amazon tree flora
  • 2023
  • Ingår i: COMMUNICATIONS BIOLOGY. - 2399-3642. ; 6:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Using 2.046 botanically-inventoried tree plots across the largest tropical forest on Earth, we mapped tree species-diversity and tree species-richness at 0.1-degree resolution, and investigated drivers for diversity and richness. Using only location, stratified by forest type, as predictor, our spatial model, to the best of our knowledge, provides the most accurate map of tree diversity in Amazonia to date, explaining approximately 70% of the tree diversity and species-richness. Large soil-forest combinations determine a significant percentage of the variation in tree species-richness and tree alpha-diversity in Amazonian forest-plots. We suggest that the size and fragmentation of these systems drive their large-scale diversity patterns and hence local diversity. A model not using location but cumulative water deficit, tree density, and temperature seasonality explains 47% of the tree species-richness in the terra-firme forest in Amazonia. Over large areas across Amazonia, residuals of this relationship are small and poorly spatially structured, suggesting that much of the residual variation may be local. The Guyana Shield area has consistently negative residuals, showing that this area has lower tree species-richness than expected by our models. We provide extensive plot meta-data, including tree density, tree alpha-diversity and tree species-richness results and gridded maps at 0.1-degree resolution. A study mapping the tree species richness in Amazonian forests shows that soil type exerts a strong effect on species richness, probably caused by the areas of these forest types. Cumulative water deficit, tree density and temperature seasonality affect species richness at a regional scale.
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60.
  • van der Wouden, Cathelijne H., et al. (författare)
  • Generating evidence for precision medicine : considerations made by the Ubiquitous Pharmacogenomics Consortium when designing and operationalizing the PREPARE study
  • 2020
  • Ingår i: Pharmacogenetics & Genomics. - 1744-6872 .- 1744-6880. ; 30:6, s. 131-144
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Pharmacogenetic panel-based testing represents a new model for precision medicine. A sufficiently powered prospective study assessing the (cost-)effectiveness of a panel-based pharmacogenomics approach to guide pharmacotherapy is lacking. Therefore, the Ubiquitous Pharmacogenomics Consortium initiated the PREemptive Pharmacogenomic testing for prevention of Adverse drug Reactions (PREPARE) study. Here, we provide an overview of considerations made to mitigate multiple methodological challenges that emerged during the design.Methods An evaluation of considerations made when designing the PREPARE study across six domains: study aims and design, primary endpoint definition and collection of adverse drug events, inclusion and exclusion criteria, target population, pharmacogenomics intervention strategy, and statistical analyses.Results Challenges and respective solutions included: (1) defining and operationalizing a composite primary endpoint enabling measurement of the anticipated effect, by including only severe, causal, and drug genotype-associated adverse drug reactions; (2) avoiding overrepresentation of frequently prescribed drugs within the patient sample while maintaining external validity, by capping drugs of enrolment; (3) designing the pharmacogenomics intervention strategy to be applicable across ethnicities and healthcare settings; and (4) designing a statistical analysis plan to avoid dilution of effect by initially excluding patients without a gene–drug interaction in a gatekeeping analysis.Conclusion Our design considerations will enable quantification of the collective clinical utility of a panel of pharmacogenomics-markers within one trial as a proof-of-concept for pharmacogenomics-guided pharmacotherapy across multiple actionable gene–drug interactions. These considerations may prove useful to other investigators aiming to generate evidence for precision medicine.
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