| 31. |
- Erhardt, Tobias, et al.
(author)
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Decadal-scale progression of the onset of Dansgaard-Oeschger warming events
- 2019
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In: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 15:2, s. 811-825
-
Journal article (peer-reviewed)abstract
- During the last glacial period, proxy records throughout the Northern Hemisphere document a succession of rapid millennial-scale warming events, called Dansgaard-Oeschger (DO) events. A range of different mechanisms has been proposed that can produce similar warming in model experiments; however, the progression and ultimate trigger of the events are still unknown. Because of their fast nature, the progression is challenging to reconstruct from paleoclimate data due to the limited temporal resolution achievable in many archives and cross-dating uncertainties between records. Here, we use new high-resolution multi-proxy records of sea-salt (derived from sea spray and sea ice over the North Atlantic) and terrestrial (derived from the central Asian deserts) aerosol concentrations over the period 10-60 ka from the North Greenland Ice Core Project (NGRIP) and North Greenland Eemian Ice Drilling (NEEM) ice cores in conjunction with local precipitation and temperature proxies from the NGRIP ice core to investigate the progression of environmental changes at the onset of the warming events at annual to multi-annual resolution. Our results show on average a small lead of the changes in both local precipitation and terrestrial dust aerosol concentrations over the change in sea-salt aerosol concentrations and local temperature of approximately one decade. This suggests that, connected to the reinvigoration of the Atlantic meridional overturning circulation and the warming in the North Atlantic, both synoptic and hemispheric atmospheric circulation changes at the onset of the DO warming, affecting both the moisture transport to Greenland and the Asian monsoon systems. Taken at face value, this suggests that a collapse of the sea-ice cover may not have been the initial trigger for the DO warming.
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| 32. |
- Forsberg, A., et al.
(author)
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The Immune Response of the Human Brain to Abdominal Surgery
- 2017
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In: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 81:4, s. 572-582
-
Journal article (peer-reviewed)abstract
- Objective: Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans. This study examines the short-and long-term impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function. Methods: Eight males undergoing prostatectomy under general anesthesia were included. Prior to surgery (baseline), at postoperative days 3 to 4, and after 3 months, patients were examined using [C-11]PBR28 brain PET imaging to assess brain immune cell activation. Concurrently, systemic inflammatory biomarkers, ex vivo blood tests on immunoreactivity to lipopolysaccharide (LPS) stimulation, and cognitive function were assessed. Results: Patients showed a global downregulation of gray matter [C-11]PBR28 binding of 26 +/- 26% (mean +/- standard deviation) at 3 to 4 days postoperatively compared to baseline (p=0.023), recovering or even increasing after 3 months. LPS-induced release of the proinflammatory marker tumor necrosis factor-a in blood displayed a reduction (41 +/- 39%) on the 3rd to 4th postoperative day, corresponding to changes in [C-11]PBR28 distribution volume. Change in Stroop Color-Word Test performance between postoperative days 3 to 4 and 3 months correlated to change in [C-11]PBR28 binding (p=0.027). Interpretation: This study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may be related to postsurgical impairments of cognitive function.
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| 33. |
- Freitag, Daniel F., et al.
(author)
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Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis
- 2015
-
In: The Lancet Diabetes & Endocrinology. - 2213-8595. ; 3:4, s. 243-253
-
Journal article (peer-reviewed)abstract
- Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1.03 (1.02-1.04; p=3.9 x 10(-10)). Perallele odds ratios were 0.97 (0.95-0.99; p=9.9 x 10(-4)) for rheumatoid arthritis, 0.99 (0.97-1.01; p=0.47) for type 2 diabetes, 1.00 (0.98-1.02; p=0.92) for ischaemic stroke, and 1.08 (1.04-1.12; p=1.8 x 10(-5)) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1 alpha/beta inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Copyright (C) The Interleukin 1 Genetics Consortium. Open Access article distributed under the terms of CC-BY-NC-ND.
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| 34. |
- Furendal, Markus, 1989-
(author)
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Do Your Bit, Claim Your Share : Justice, Ethos, and the Individual Duty to Contribute
- 2020
-
Doctoral thesis (other academic/artistic)abstract
- Contemporary political philosophy primarily conceives of justice as a virtue of major social institutions. Yet, much advocacy of justice is increasingly focused on how well particular individuals live up to its demands, and proceeds by calling out and criticising their unjust behaviour. The institutional focus renders political philosophy unable to inform and evaluate such attempts to change, not legal frameworks, but rather the principles that people find acceptable and act on in their daily lives. To address this shortcoming, this dissertation provides a political philosophical analysis of what justice requires of individuals, and why. It does so by developing and defending an account of contributive justice, which answers the inquiry’s guiding questions of who should contribute to justice and why, as well as what a contribution is, and how individual duties of justice should be enforced. The arguments provided support the conclusion that achieving a just society is not simply a question of designing and complying with the right kind of institutions, but that we all have a pro tanto duty to contribute in our day-to-day lives towards the furthering of a just society, and that relying on informal and decentralised social sanctions is the best way to promote adherence to this duty.The duty to contribute defended in this dissertation differs from existing policies that make access to welfare state services conditional on individuals’ willingness to work or study. It also differs from prominent existing philosophical defences of similar positions, centred around the ideas of equality, reciprocity, and fairly sharing burdens. Critically analysing these accounts, the dissertation shows that, although each account can justify a duty to contribute, their specific answers to the guiding questions are ultimately unsatisfactory. For instance, they are unable to explain both why it is unjust to opt out from doing your bit of the labour necessary to meet the demands of justice, and why individuals who cannot contribute should nevertheless be able to claim the share that they are due.These shortcomings can be avoided, however, by combining concerns about equality, reciprocity, and fairly sharing burdens into a hybrid account. This generates a two-part pro tanto duty to contribute whereby, firstly, everyone has a duty to contribute towards making sure that everyone receives what they are due as a matter of justice. If and when this level is reached, everyone then has an obligation to benefit others, conditional upon them benefitting from the work of others. While it is unjust to refuse to contribute in the first way, the hybrid account leaves room for people to reject additional benefits and thereby absolve themselves from having to contribute further. Furthermore, the pro tanto nature of this duty means that it could be outweighed by other morally important considerations. Although demanding, it will hence not crowd out all personal pursuits.The dissertation also suggests that adherence to this duty should be enforced not through state action, but rather by individuals responding to and upholding a system of social sanctions. Contrasting this so-called ethos of justice with similar systems of social control, such as peer-to-peer online monitoring and sanctioning, and the Social Credit System currently being implemented in China, arguably shows that the informal and decentralised nature of the ethos allows it to avoid the potentially freedom-curtailing effects of the similar systems.
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| 35. |
- Gopalakrishnan, Shyam, et al.
(author)
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The population genomic legacy of the second plague pandemic
- 2022
-
In: Current Biology. - : Elsevier. - 0960-9822 .- 1879-0445. ; 32:21, s. 4743-4751.e6
-
Journal article (peer-reviewed)abstract
- Human populations have been shaped by catastrophes that may have left long-lasting signatures in their genomes. One notable example is the second plague pandemic that entered Europe in ca. 1,347 CE and repeatedly returned for over 300 years, with typical village and town mortality estimated at 10%–40%.1 It is assumed that this high mortality affected the gene pools of these populations. First, local population crashes reduced genetic diversity. Second, a change in frequency is expected for sequence variants that may have affected survival or susceptibility to the etiologic agent (Yersinia pestis).2 Third, mass mortality might alter the local gene pools through its impact on subsequent migration patterns. We explored these factors using the Norwegian city of Trondheim as a model, by sequencing 54 genomes spanning three time periods: (1) prior to the plague striking Trondheim in 1,349 CE, (2) the 17th–19th century, and (3) the present. We find that the pandemic period shaped the gene pool by reducing long distance immigration, in particular from the British Isles, and inducing a bottleneck that reduced genetic diversity. Although we also observe an excess of large FST values at multiple loci in the genome, these are shaped by reference biases introduced by mapping our relatively low genome coverage degraded DNA to the reference genome. This implies that attempts to detect selection using ancient DNA (aDNA) datasets that vary by read length and depth of sequencing coverage may be particularly challenging until methods have been developed to account for the impact of differential reference bias on test statistics.
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| 36. |
- Göransson, Hanna, et al.
(author)
-
Quantification of normal cell fraction and copy number neutral LOH in clinical lung cancer samples using SNP array data
- 2009
-
In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:6, s. e6057-
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Technologies based on DNA microarrays have the potential to provide detailed information on genomic aberrations in tumor cells. In practice a major obstacle for quantitative detection of aberrations is the heterogeneity of clinical tumor tissue. Since tumor tissue invariably contains genetically normal stromal cells, this may lead to a failure to detect aberrations in the tumor cells. PRINCIPAL FINDING: Using SNP array data from 44 non-small cell lung cancer samples we have developed a bioinformatic algorithm that accurately models the fractions of normal and tumor cells in clinical tumor samples. The proportion of normal cells in combination with SNP array data can be used to detect and quantify copy number neutral loss-of-heterozygosity (CNNLOH) in the tumor cells both in crude tumor tissue and in samples enriched for tumor cells by laser capture microdissection. CONCLUSION: Genome-wide quantitative analysis of CNNLOH using the CNNLOH Quantifier method can help to identify recurrent aberrations contributing to tumor development in clinical tumor samples. In addition, SNP-array based analysis of CNNLOH may become important for detection of aberrations that can be used for diagnostic and prognostic purposes.
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| 37. |
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| 38. |
- Haugsgjerd Allern, Elin, et al.
(author)
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All about the money? A cross-national study of parties' relations with trade unions in 12 western democracies
- 2021
-
In: Party Politics. - : SAGE Publications. - 1460-3683 .- 1354-0688. ; 27:3, s. 407-417
-
Journal article (peer-reviewed)abstract
- This article examines political parties’ approach to trade unions and the role of private and public party finance in contemporary democracies. We suggest that both unions’ direct donations and states’ party finance regimes may account for variation in the strength of parties’ organizational links to unions. We investigate this argument with a new data set covering parties historically aligned with trade unions and union confederations in 12 mature democracies. Our empirical analysis provides support for the hypothesis that financial contributions are positively associated with stronger organizational links but also suggests that this relationship is constrained by the level of public subsidies and state regulation of donations. The findings point to the need for more research on how private and public money affects parties’ interactions with civil society actors.
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| 39. |
- Haugsgjerd Allern, Elin, et al.
(author)
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Introducing the party-interest group relationships in contemporary democracies datasets
- 2023
-
In: Party Politics. - : SAGE Publications. - 1460-3683 .- 1354-0688. ; 29:2
-
Journal article (peer-reviewed)abstract
- Few existing datasets on parties and interest groups include data from both sides and a wide variety of interest groups and parties. We contribute to filling this gap by making several interconnected new datasets publicly available. The Party-Interest Group Relationships in Contemporary Democracies (PAIRDEM) datasets include cross-national data from three different surveys of (1) central party organizations, (2) legislative party groups, and (3) interest groups. A fourth dataset based on coding of party statutes and party finance data was established together with the Political Party Database. The datasets contain novel indicators on party-group relationships in up to 21 mature democracies. In this research note, we first present the main content of the datasets and the research design. Second, we present descriptive statistics documenting the extent of organizational ties between parties and groups in contemporary democracies. Third, we illustrate more advanced usage through a simple application.
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| 40. |
- Hendriksen, Rene S., et al.
(author)
-
Global monitoring of antimicrobial resistance based on metagenomics analyses of urban sewage
- 2019
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
-
Journal article (peer-reviewed)abstract
- © 2019, The Author(s). Antimicrobial resistance (AMR) is a serious threat to global public health, but obtaining representative data on AMR for healthy human populations is difficult. Here, we use metagenomic analysis of untreated sewage to characterize the bacterial resistome from 79 sites in 60 countries. We find systematic differences in abundance and diversity of AMR genes between Europe/North-America/Oceania and Africa/Asia/South-America. Antimicrobial use data and bacterial taxonomy only explains a minor part of the AMR variation that we observe. We find no evidence for cross-selection between antimicrobial classes, or for effect of air travel between sites. However, AMR gene abundance strongly correlates with socio-economic, health and environmental factors, which we use to predict AMR gene abundances in all countries in the world. Our findings suggest that global AMR gene diversity and abundance vary by region, and that improving sanitation and health could potentially limit the global burden of AMR. We propose metagenomic analysis of sewage as an ethically acceptable and economically feasible approach for continuous global surveillance and prediction of AMR.
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