| 1. |
- Kindmark, Andreas, et al.
(author)
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Genome-wide pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests an underlying immune pathogenesis
- 2008
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In: The Pharmacogenomics Journal. - : Springer Science and Business Media LLC. - 1470-269X .- 1473-1150. ; 8:3, s. 186-195
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Journal article (peer-reviewed)abstract
- One of the major goals of pharmacogenetics is to elucidate mechanisms and identify patients at increased risk of adverse events (AEs). To date, however, there have been only a few successful examples of this type of approach. In this paper, we describe a retrospective case–control pharmacogenetic study of an AE of unknown mechanism, characterized by elevated levels of serum alanine aminotransferase (ALAT) during long-term treatment with the oral direct thrombin inhibitor ximelagatran. The study was based on 74 cases and 130 treated controls and included both a genome-wide tag single nucleotide polymorphism and large-scale candidate gene analysis. A strong genetic association between elevated ALAT and the MHC alleles DRB1*07 and DQA1*02 was discovered and replicated, suggesting a possible immune pathogenesis. Consistent with this hypothesis, immunological studies suggest that ximelagatran may have the ability to act as a contact sensitizer, and hence be able to stimulate an adaptive immune response.
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| 2. |
- Andresen, Louise C., 1974, et al.
(author)
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Shifting Impacts of Climate Change: Long-Term Patterns of Plant Response to Elevated CO2, Drought, and Warming Across Ecosystems
- 2016
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In: Large-Scale Ecology: Model Systems to Global Perspectives. - : Elsevier. - 9780081009352 ; , s. 437-473
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Book chapter (peer-reviewed)abstract
- Field experiments that expose terrestrial ecosystems to climate change factors by manipulations are expensive to maintain, and typically only last a few years. Plant biomass is commonly used to assess responses to climate treatments and to predict climate change impacts. However, response to the treatments might be considerably different between the early years and a decade later. The aim of this data analysis was to develop and apply a method for evaluating changes in plant biomass responses through time, in order to provide a firm basis for discussing how the ‘short-term’ response might differ from the ‘long-term’ response. Across 22 sites situated in the northern hemisphere, which covered three continents, and multiple ecosystems (grasslands, shrublands, moorlands, forests, and deserts), we evaluated biomass datasets from long-term experiments with exposure to elevated CO2 (eCO2), warming, or drought. We developed methods for assessing biomass response patterns to the manipulations using polynomial and linear (piecewise) model analysis and linked the responses to sitespecific variables such as temperature and rainfall. Polynomial patterns across sites indicated changes in response direction over time under eCO2, warming, and drought. In addition, five distinct pattern types were confirmed within sites: ‘no response’, ‘delayed response’, ‘directional response’, ‘dampening response’, and ‘altered response’ patterns. We found that biomass response direction was as likely to change over time as it was to be consistent, and therefore suggest that climate manipulation experiments should be carried out over timescales covering both short- and long-term responses, in order to realistically assess future impacts of climate change.
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| 3. |
- Hovenden, Mark J., et al.
(author)
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Globally consistent influences of seasonal precipitation limit grassland biomass response to elevated CO2
- 2019
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In: Nature Plants. - : Springer Science and Business Media LLC. - 2055-0278. ; 5, s. 167-173
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Journal article (peer-reviewed)abstract
- © 2019, The Author(s), under exclusive licence to Springer Nature Limited. Rising atmospheric carbon dioxide concentration should stimulate biomass production directly via biochemical stimulation of carbon assimilation, and indirectly via water savings caused by increased plant water-use efficiency. Because of these water savings, the CO 2 fertilization effect (CFE) should be stronger at drier sites, yet large differences among experiments in grassland biomass response to elevated CO 2 appear to be unrelated to annual precipitation, preventing useful generalizations. Here, we show that, as predicted, the impact of elevated CO 2 on biomass production in 19 globally distributed temperate grassland experiments reduces as mean precipitation in seasons other than spring increases, but that it rises unexpectedly as mean spring precipitation increases. Moreover, because sites with high spring precipitation also tend to have high precipitation at other times, these effects of spring and non-spring precipitation on the CO 2 response offset each other, constraining the response of ecosystem productivity to rising CO 2 . This explains why previous analyses were unable to discern a reliable trend between site dryness and the CFE. Thus, the CFE in temperate grasslands worldwide will be constrained by their natural rainfall seasonality such that the stimulation of biomass by rising CO 2 could be substantially less than anticipated.
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| 4. |
- Maschler, Julia, et al.
(author)
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Links across ecological scales: Plant biomass responses to elevated CO2
- 2022
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In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 28:21, s. 6115-6134
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Journal article (peer-reviewed)abstract
- The degree to which elevated CO2 concentrations (e[CO2]) increase the amount of carbon (C) assimilated by vegetation plays a key role in climate change. However, due to the short-term nature of CO2 enrichment experiments and the lack of reconciliation between different ecological scales, the effect of e[CO2] on plant biomass stocks remains a major uncertainty in future climate projections. Here, we review the effect of e[CO2] on plant biomass across multiple levels of ecological organization, scaling from physiological responses to changes in population-, community-, ecosystem-, and global-scale dynamics. We find that evidence for a sustained biomass response to e[CO2] varies across ecological scales, leading to diverging conclusions about the responses of individuals, populations, communities, and ecosystems. While the distinct focus of every scale reveals new mechanisms driving biomass accumulation under e[CO2], none of them provides a full picture of all relevant processes. For example, while physiological evidence suggests a possible long-term basis for increased biomass accumulation under e[CO2] through sustained photosynthetic stimulation, population-scale evidence indicates that a possible e[CO2]-induced increase n mortality rates might potentially outweigh the effect of increases in plant growth rates on biomass levels. Evidence at the global scale may indicate that e[CO2] has contributed to increased biomass cover over recent decades, but due to the difficulty to disentangle the effect of e[CO2] from a variety of climatic and land-use-related drivers of plant biomass stocks, it remains unclear whether nutrient limitations or other ecological mechanisms operating at finer scales will dampen the e[CO2] effect over time. By exploring these discrepancies, we identify key research gaps in our understanding of the effect of e[CO2] on plant biomass and highlight the need to integrate knowledge across scales of ecological organization so that large-scale modeling can represent the finer-scale mechanisms needed to constrain our understanding of future terrestrial C storage.
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| 8. |
- Pfaltz, Monique C., et al.
(author)
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Social Functioning in Individuals Affected by Childhood Maltreatment : Establishing a Research Agenda to Inform Interventions
- 2022
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In: Psychotherapy and Psychosomatics. - : S. Karger AG. - 0033-3190 .- 1423-0348. ; 91:4, s. 238-251
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Research review (peer-reviewed)abstract
- Childhood maltreatment (CM) is linked to impairments in various domains of social functioning. Here, we argue that it is critical to identify factors that underlie impaired social functioning as well as processes that mediate the beneficial health effects of positive relationships in individuals exposed to CM. Key research recommendations are presented, focusing on: (1) identifying attachment-related alterations in specific inter- and intrapersonal processes (e.g., regulation of closeness and distance) that underlie problems in broader domains of social functioning (e.g., lack of perceived social support) in individuals affected by CM; (2) identifying internal (e.g., current emotional state) and external situational factors (e.g., cultural factors, presence of close others) that modulate alterations in specific social processes; and (3) identifying mechanisms that explain the positive health effects of intact social functioning. Methodological recommendations include: (1) assessing social processes through interactive and (close to) real-life assessments inside and outside the laboratory; (2) adopting an interdisciplinary, lifespan perspective to assess social processes, using multi-method assessments; (3) establishing global research collaborations to account for cultural influences on social processes and enable replications across laboratories and countries. The proposed line of research will contribute to globally develop and refine interventions that prevent CM and further positive relationships, which - likely through buffering the effects of chronic stress and corresponding allostatic load - foster resilience and improve mental and physical health, thereby reducing personal suffering and the societal and economic costs of CM and its consequences. Interventions targeting euthymia and psychological well-being are promising therapeutic concepts in this context.
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| 10. |
- van Gestel, Natasja, et al.
(author)
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Predicting soil carbon loss with warming
- 2018
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 554:E4-5
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Journal article (peer-reviewed)
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