| 1. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 2. |
- Burrascano, S., et al.
(author)
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Where are we now with European forest multi-taxon biodiversity and where can we head to?
- 2023
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In: Biological Conservation. - 0006-3207. ; 284
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Journal article (peer-reviewed)abstract
- The European biodiversity and forest strategies rely on forest sustainable management (SFM) to conserve forest biodiversity. However, current sustainability assessments hardly account for direct biodiversity indicators. We focused on forest multi-taxon biodiversity to: i) gather and map the existing information; ii) identify knowledge and research gaps; iii) discuss its research potential. We established a research network to fit data on species, standing trees, lying deadwood and sampling unit description from 34 local datasets across 3591 sampling units. A total of 8724 species were represented, with the share of common and rare species varying across taxonomic classes: some included many species with several rare ones (e.g., Insecta); others (e.g., Bryopsida) were repre-sented by few common species. Tree-related structural attributes were sampled in a subset of sampling units (2889; 2356; 2309 and 1388 respectively for diameter, height, deadwood and microhabitats). Overall, multi-taxon studies are biased towards mature forests and may underrepresent the species related to other develop-mental phases. European forest compositional categories were all represented, but beech forests were over-represented as compared to thermophilous and boreal forests. Most sampling units (94%) were referred to a habitat type of conservation concern. Existing information may support European conservation and SFM stra-tegies in: (i) methodological harmonization and coordinated monitoring; (ii) definition and testing of SFM in-dicators and thresholds; (iii) data-driven assessment of the effects of environmental and management drivers on multi-taxon forest biological and functional diversity, (iv) multi-scale forest monitoring integrating in-situ and remotely sensed information.
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| 3. |
- Dahl-Jensen, D., et al.
(author)
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Eemian interglacial reconstructed from a Greenland folded ice core
- 2013
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 493:7433, s. 489-494
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Journal article (peer-reviewed)abstract
- Efforts to extract a Greenland ice core with a complete record of the Eemian interglacial (130,000 to 115,000 years ago) have until now been unsuccessful. The response of the Greenland ice sheet to the warmer-than-present climate of the Eemian has thus remained unclear. Here we present the new North Greenland Eemian Ice Drilling ('NEEM') ice core and show only a modest ice-sheet response to the strong warming in the early Eemian. We reconstructed the Eemian record from folded ice using globally homogeneous parameters known from dated Greenland and Antarctic ice-core records. On the basis of water stable isotopes, NEEM surface temperatures after the onset of the Eemian (126,000 years ago) peaked at 8 +/- 4 degrees Celsius above the mean of the past millennium, followed by a gradual cooling that was probably driven by the decreasing summer insolation. Between 128,000 and 122,000 years ago, the thickness of the northwest Greenland ice sheet decreased by 400 +/- 250 metres, reaching surface elevations 122,000 years ago of 130 +/- 300 metres lower than the present. Extensive surface melt occurred at the NEEM site during the Eemian, a phenomenon witnessed when melt layers formed again at NEEM during the exceptional heat of July 2012. With additional warming, surface melt might become more common in the future.
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| 4. |
- Bruggmann, P., et al.
(author)
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Historical epidemiology of hepatitis C virus (HCV) in selected countries
- 2014
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In: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21, s. 5-33
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Journal article (peer-reviewed)abstract
- Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6358000 cases in 2008 and Brazil with 2106000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.
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| 5. |
- Razavi, H., et al.
(author)
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The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm
- 2014
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In: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21:Suppl. 1, s. 34-59
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Journal article (peer-reviewed)abstract
- The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.
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| 6. |
- Wedemeyer, H., et al.
(author)
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Strategies to manage hepatitis C virus (HCV) disease burden
- 2014
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In: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21, s. 60-89
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Journal article (peer-reviewed)abstract
- The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.
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| 7. |
- Williamson, Alice, et al.
(author)
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Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
- 2023
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:6, s. 973-983
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Journal article (peer-reviewed)abstract
- Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
- Hwang, K. -J, et al.
(author)
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Sequential Observations of Flux Transfer Events, Poleward-Moving Auroral Forms, and Polar Cap Patches
- 2020
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In: Journal of Geophysical Research - Space Physics. - : AMER GEOPHYSICAL UNION. - 2169-9380 .- 2169-9402. ; 125:6
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Journal article (peer-reviewed)abstract
- We report the observation of solar wind-magnetosphere-ionosphere interactions using a series of flux transfer events (FTEs) observed by Magnetospheric MultiScale (MMS) mission located near the dayside magnetopause on 18 December 2017. The FTEs were observed to propagate duskward and either southward or slightly northward, as predicted under duskward and southward interplanetary magnetic field (IMF). The Cooling model also predicted a significant dawnward propagation of northward-moving FTEs. Near the MMS footprint, a series of poleward-moving auroral forms (PMAFs) occurred almost simultaneously with those FTEs. They propagated poleward and westward, consistent with the modeled FTE propagation. The intervals between FTEs, relatively consistent with those between PMAFs, strongly suggest a one-to-one correspondence between the dayside transients and ionospheric responses. The FTEs embedded in continuous reconnection observed by MMS and corresponding PMAFs individually occurred during persistent auroral activity recorded by an all-sky imager strongly indicate that those FTEs/PMAFs resulted from the temporal modulation of the reconnection rate during continuous reconnection. With the decay of the PMAFs associated with the FTEs, patch-like plasma density enhancements were detected to form and propagate poleward and then dawnward. Propagation to the dawn was also suggested by the Super Dual Auroral Radar Network (SuperDARN) convection and Global Positioning System (GPS) total electron content data. We relate the temporal variation of the driving solar-wind and magnetospheric mechanism to that of the high-latitude and polar ionospheric responses and estimate the response time.
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| 12. |
- Kostrzewski, T., et al.
(author)
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Modelling human liver fibrosis in the context of non-alcoholic steatohepatitis using a microphysiological system
- 2021
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 4:1
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Journal article (peer-reviewed)abstract
- Kostrzewski et al. introduce an in vitro microphysiological model of non-alcoholic steatohepatitis (NASH), consisting of co-cultured primary human liver cells. The authors characterised the transcriptomic, inflammatory and fibrotic phenotype of the model and show that major features of NASH can be recapitulated and therapeutic interventions mimicked. Non-alcoholic steatohepatitis (NASH) is a common form of chronic liver disease characterised by lipid accumulation, infiltration of immune cells, hepatocellular ballooning, collagen deposition and liver fibrosis. There is a high unmet need to develop treatments for NASH. We have investigated how liver fibrosis and features of advanced clinical disease can be modelled using an in vitro microphysiological system (MPS). The NASH MPS model comprises a co-culture of primary human liver cells, which were cultured in a variety of conditions including+/- excess sugar, fat, exogenous TGF beta or LPS. The transcriptomic, inflammatory and fibrotic phenotype of the model was characterised and compared using a system biology approach to identify conditions that mimic more advanced clinical disease. The transcriptomic profile of the model was shown to closely correlate with the profile of patient samples and the model displayed a quantifiable fibrotic phenotype. The effects of Obeticholic acid and Elafibranor, were evaluated in the model, as wells as the effects of dietary intervention, with all able to significantly reduce inflammatory and fibrosis markers. Overall, we demonstrate how the MPS NASH model can be used to model different aspects of clinical NASH but importantly demonstrate its ability to model advanced disease with a quantifiable fibrosis phenotype.
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| 13. |
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| 14. |
- Ruzzante, D. E., et al.
(author)
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Biocomplexity in a highly migratory pelagic marine fish, Atlantic herring
- 2006
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In: Proceedings of the Royal Society B-Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 273:1593, s. 1459-1464
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Journal article (peer-reviewed)abstract
- The existence of biologically differentiated populations has been credited with a major role in conferring sustainability and in buffering overall productivity of anadromous fish population complexes where evidence for spatial structure is uncontroversial. Here, we describe evidence of correlated genetic and life history (spawning season linked to spawning location) differentiation in an abundant and highly migratory pelagic fish, Atlantic herring, Clupea harengus, in the North Sea (NS) and adjacent areas. The existence of genetically and phenotypically diverse stocks in this region despite intense seasonal mixing strongly implicates natal homing in this species. Based on information from genetic markers and otolith morphology, we estimate the proportional contribution by NS, Skagerrak (SKG) and Kattegat and western Baltic (WBS) fish to mixed aggregations targeted by the NS fishery. We use these estimates to identify spatial and temporal differences in life history (migratory behaviour) and habitat use among genetically differentiated migratory populations that mix seasonally. Our study suggests the existence of more complex patterns of intraspecific diversity than was previously recognized. Sustainability may be compromised if such complex patterns are reduced through generalized management (e.g. area closures) that overlooks population differences in spatial use throughout the life cycle.
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| 15. |
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| 16. |
- Tedersoo, L., et al.
(author)
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The Global Soil Mycobiome consortium dataset for boosting fungal diversity research
- 2021
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In: Fungal Diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 111, s. 573-588
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Journal article (peer-reviewed)abstract
- Fungi are highly important biotic components of terrestrial ecosystems, but we still have a very limited understanding about their diversity and distribution. This data article releases a global soil fungal dataset of the Global Soil Mycobiome consortium (GSMc) to boost further research in fungal diversity, biogeography and macroecology. The dataset comprises 722,682 fungal operational taxonomic units (OTUs) derived from PacBio sequencing of full-length ITS and 18S-V9 variable regions from 3200 plots in 108 countries on all continents. The plots are supplied with geographical and edaphic metadata. The OTUs are taxonomically and functionally assigned to guilds and other functional groups. The entire dataset has been corrected by excluding chimeras, index-switch artefacts and potential contamination. The dataset is more inclusive in terms of geographical breadth and phylogenetic diversity of fungi than previously published data. The GSMc dataset is available over the PlutoF repository.
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| 17. |
- Aust, Birgit, et al.
(author)
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The Danish national return-to-work program - aims, content, and design of the process and effect evaluation
- 2012
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In: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 38:2, s. 120-133
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Journal article (peer-reviewed)abstract
- The Danish national return-to-work (RTW) program aims to improve the management of municipal sickness benefit in Denmark. A study is currently ongoing to evaluate the RTW program. The purpose of this article is to describe the study protocol. The program includes 21 municipalities encompassing approximately 19 500 working-age adults on long-term sickness absence, regardless of reason for sickness absence or employment status. It consists of three core elements: (i) establishment of multidisciplinary RTW teams, (ii) introduction of standardized workability assessments and sickness absence management procedures, and (iii) a comprehensive training course for the RTW teams. The effect evaluation is based on a parallel group randomized trial and a stratified cluster-controlled trial and focuses on register-based primary outcomes-duration of sickness absence and RTW and questionnaire-based secondary outcomes such as health and workability. The process evaluation utilizes questionnaires, interviews, and municipal data. The effect evaluation tests whether participants in the intervention have a (i) shorter duration of full-time sickness absence, (ii) longer time until recurrent long-term sickness absence, (iii) faster full RTW, (iv) more positive development in health, workability, pain, and sleep; it also tests whether the program is (v) cost-effective. The process evaluation investigates: (i) whether the expected target population is reached; (ii) if the program is implemented as intended; (iii) how the beneficiaries, the RTW teams, and the external stakeholders experience the program; and (iv) whether contextual factors influenced the implementation. The program has the potential to contribute markedly to lowering human and economic costs and increasing labor force supply. First results will be available in 2013. The trial registrations are ISRCTN43004323, and ISRCTN51445682.
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| 18. |
- Bach, Anders, et al.
(author)
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A high-affinity, dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage
- 2012
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In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:9, s. 3317-3322
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Journal article (peer-reviewed)abstract
- Inhibition of the ternary protein complex of the synaptic scaffolding protein postsynaptic density protein-95 (PSD-95), neuronal nitric oxide synthase (nNOS), and the N-methyl-D-aspartate (NMDA) receptor is a potential strategy for treating ischemic brain damage, but high-affinity inhibitors are lacking. Here we report the design and synthesis of a novel dimeric inhibitor, Tat-NPEG4(IETDV)(2) (Tat-N-dimer), which binds the tandem PDZ1-2 domain of PSD-95 with an unprecedented high affinity of 4.6 nM, and displays extensive protease-resistance as evaluated in vitro by stability-measurements in human blood plasma. X-ray crystallography, NMR, and small-angle X-ray scattering (SAXS) deduced a true bivalent interaction between dimeric inhibitor and PDZ1-2, and also provided a dynamic model of the conformational changes of PDZ1-2 induced by the dimeric inhibitor. A single intravenous injection of Tat-N-dimer (3 nmol/g) to mice subjected to focal cerebral ischemia reduces infarct volume with 40% and restores motor functions. Thus, Tat-N-dimer is a highly efficacious neuroprotective agent with therapeutic potential in stroke.
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| 19. |
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| 20. |
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| 21. |
- Carnohan, Shane, et al.
(author)
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Next generation application of DPSIR for sustainable policy implementation
- 2023
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In: Current Research in Environmental Sustainability. - : Elsevier B.V.. - 2666-0490. ; 5
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Journal article (peer-reviewed)abstract
- As our societies and natural systems are becoming ever more interconnected, it is critical that sustainable management can adapt to new knowledge from both the ecological and the social domains, and act on it in a timely and effective manner. This need is amplifying in the Anthropocene as we are approaching the limit for humanity's safe operating space, leading to irreversible change to ecosystem function. This urgently requires increased attention and concern regarding the information feedbacks between the silos of science, policy and society. A web of policies is in place to protect the health of people and the planet, but to ensure that they are effective we need frameworks to make sense of real-world complexities and interlinkages between multiple factors. The Drivers-Pressures-State-Impacts-Response (DPSIR) framework was created for this purpose, however, its' implicit focus on 1) analytical and 2) procedural aspects must be made explicit, to enable coordination across silos and studies. Continued creation of new DPSIR derivatives may limit its impact, while more explicit coordination between these two aspects can improve the effectiveness of DPSIR while retaining its flexibility. We thus propose five elements to support sustainable policy development and implementation using DPSIR: 1) iteration; 2) risk, uncertainty and analytical bias; 3) flexible integration; 4) use of quantitative methods, and; 5) clear and standard definitions for DPSIR. We illustrate these elements in four cases: Three highlight missing feedbacks when DPSIR elements are not made explicit and a fourth case – on per-and-polyfluorinated alkyl substances (PFAS) – showing a potential roadmap to successful policy implementation using DPSIR. © 2022 The Authors
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| 22. |
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Fan, Y., et al.
(author)
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The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice
- 2023
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In: Nature Microbiology. - : Nature Publishing Group. - 2058-5276. ; 8, s. 787-802
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Journal article (peer-reviewed)abstract
- Anorexia nervosa (AN) is an eating disorder with a high mortality. About 95% of cases are women and it has a population prevalence of about 1%, but evidence-based treatment is lacking. The pathogenesis of AN probably involves genetics and various environmental factors, and an altered gut microbiota has been observed in individuals with AN using amplicon sequencing and relatively small cohorts. Here we investigated whether a disrupted gut microbiota contributes to AN pathogenesis. Shotgun metagenomics and metabolomics were performed on faecal and serum samples, respectively, from a cohort of 77 females with AN and 70 healthy females. Multiple bacterial taxa (for example, Clostridium species) were altered in AN and correlated with estimates of eating behaviour and mental health. The gut virome was also altered in AN including a reduction in viral-bacterial interactions. Bacterial functional modules associated with the degradation of neurotransmitters were enriched in AN and various structural variants in bacteria were linked to metabolic features of AN. Serum metabolomics revealed an increase in metabolites associated with reduced food intake (for example, indole-3-propionic acid). Causal inference analyses implied that serum bacterial metabolites are potentially mediating the impact of an altered gut microbiota on AN behaviour. Further, we performed faecal microbiota transplantation from AN cases to germ-free mice under energy-restricted feeding to mirror AN eating behaviour. We found that the reduced weight gain and induced hypothalamic and adipose tissue gene expression were related to aberrant energy metabolism and eating behaviour. Our 'omics' and mechanistic studies imply that a disruptive gut microbiome may contribute to AN pathogenesis. Faecal metagenomics and serum metabolomics reveal compositional and functional alterations in the gut microbiota of women with anorexia nervosa, and faecal transplants could transfer an anorexia-associated phenotype to germ-free mice.
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| 27. |
- Goodwin, L. V., et al.
(author)
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Swarm in situ observations of F region polar cap patches created by cusp precipitation
- 2015
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In: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 42:4, s. 996-1003
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Journal article (peer-reviewed)abstract
- High-resolution in situ measurements from the three Swarm spacecraft, in a string-of-pearls configuration, provide new insights about the combined role of flow channel events and particle impact ionization in creating F region electron density structures in the northern Scandinavian dayside cusp. We present a case of polar cap patch formation where a reconnection-driven low-density relative westward flow channel is eroding the dayside solar-ionized plasma but where particle impact ionization in the cusp dominates the initial plasma structuring. In the cusp, density features are observed which are twice as dense as the solar-ionized background. These features then follow the polar cap convection and become less structured and lower in amplitude. These are the first in situ observations tracking polar cap patch evolution from creation by plasma transport and enhancement by cusp precipitation, through entrainment in the polar cap flow and relaxation into smooth patches as they approach the nightside auroral oval.
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| 28. |
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| 29. |
- Graco-Roza, Caio, et al.
(author)
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Distance decay 2.0 – A global synthesis of taxonomic and functional turnover in ecological communities
- 2022
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In: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 31:7, s. 1399-1421
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Journal article (peer-reviewed)abstract
- Aim: Understanding the variation in community composition and species abundances (i.e., beta-diversity) is at the heart of community ecology. A common approach to examine beta-diversity is to evaluate directional variation in community composition by measuring the decay in the similarity among pairs of communities along spatial or environmental distance. We provide the first global synthesis of taxonomic and functional distance decay along spatial and environmental distance by analysing 148 datasets comprising different types of organisms and environments.Location: Global.Time period: 1990 to present.Major taxa studied: From diatoms to mammals.Method: We measured the strength of the decay using ranked Mantel tests (Mantel r) and the rate of distance decay as the slope of an exponential fit using generalized linear models. We used null models to test whether functional similarity decays faster or slower than expected given the taxonomic decay along the spatial and environmental distance. We also unveiled the factors driving the rate of decay across the datasets, including latitude, spatial extent, realm and organismal features.Results: Taxonomic distance decay was stronger than functional distance decay along both spatial and environmental distance. Functional distance decay was random given the taxonomic distance decay. The rate of taxonomic and functional spatial distance decay was fastest in the datasets from mid-latitudes. Overall, datasets covering larger spatial extents showed a lower rate of decay along spatial distance but a higher rate of decay along environmental distance. Marine ecosystems had the slowest rate of decay along environmental distances.Main conclusions: In general, taxonomic distance decay is a useful tool for biogeographical research because it reflects dispersal-related factors in addition to species responses to climatic and environmental variables. Moreover, functional distance decay might be a cost-effective option for investigating community changes in heterogeneous environments.
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| 30. |
- Hustad, J.E., et al.
(author)
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Reactivity measurements of coke particles in five different flow reactors
- 1990
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In: Rivista dei Combustibili. - 0370-5463. ; 44:10, s. 257-267
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Journal article (other academic/artistic)abstract
- Experiments on reactivity of 128 μm coke particles in the gas temperature range from 1150 K to 1370 K have been performed in five different flow reactors in the Nordic countries and all the results were calculated by the shrinking particle model. The activation energy is found to be 25 kcal/mol indicating combustion control by the combined effects of chemical kinetic and pore diffusion (zone II combustion). The overall apparent reaction order was found to be 1.0
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| 31. |
- Kotthoff, U., et al.
(author)
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Reconstructing Holocene temperature and salinity variations in the western Baltic Sea region: a multi-proxy comparison from the Little Belt (IODP Expedition 347, Site M0059)
- 2017
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In: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 14, s. 5607-5632
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Journal article (peer-reviewed)abstract
- Sediment records recovered from the Baltic Sea during Integrated Ocean Drilling Program Expedition 347 provide a unique opportunity to study paleoenvironmental and climate change in central and northern Europe. Such studies contribute to a better understanding of how environmental parameters change in continental shelf seas and enclosed basins. Here we present a multi-proxy-based reconstruction of paleotemperature (both marine and terrestrial), paleosalinity, and paleoecosystem changes from the Little Belt (Site M0059) over the past ∼ 8000 years and evaluate the applicability of inorganic- and organic-based proxies in this particular setting. All salinity proxies (diatoms, aquatic palynomorphs, ostracods, diol index) show that lacustrine conditions occurred in the Little Belt until ∼ 7400 cal yr BP. A connection to the Kattegat at this time can thus be excluded, but a direct connection to the Baltic Proper may have existed. The transition to the brackish–marine conditions of the Littorina Sea stage (more saline and warmer) occurred within ∼ 200 years when the connection to the Kattegat became established after ∼ 7400 cal yr BP. The different salinity proxies used here generally show similar trends in relative changes in salinity, but often do not allow quantitative estimates of salinity. The reconstruction of water temperatures is associated with particularly large uncertainties and variations in absolute values by up to 8 °C for bottom waters and up to 16 °C for surface waters. Concerning the reconstruction of temperature using foraminiferal Mg / Ca ratios, contamination by authigenic coatings in the deeper intervals may have led to an overestimation of temperatures. Differences in results based on the lipid paleothermometers (long chain diol index and TEXL86) can partly be explained by the application of modern-day proxy calibrations to intervals that experienced significant changes in depositional settings: in the case of our study, the change from freshwater to marine conditions. Our study shows that particular caution has to be taken when applying and interpreting proxies in coastal environments and marginal seas, where water mass conditions can experience more rapid and larger changes than in open ocean settings. Approaches using a multitude of independent proxies may thus allow a more robust paleoenvironmental assessment.
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| 32. |
- Misic, J., et al.
(author)
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Mammalian RNase H1 directs RNA primer formation for mtDNA replication initiation and is also necessary for mtDNA replication completion
- 2022
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In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 50:15, s. 8749-8766
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Journal article (peer-reviewed)abstract
- The in vivo role for RNase H1 in mammalian mitochondria has been much debated. Loss of RNase H1 is embryonic lethal and to further study its role in mtDNA expression we characterized a conditional knockout of Rnaseh1 in mouse heart. We report that RNase H1 is essential for processing of RNA primers to allow site-specific initiation of mtDNA replication. Without RNase H1, the RNA:DNA hybrids at the replication origins are not processed and mtDNA replication is initiated at non-canonical sites and becomes impaired. Importantly, RNase H1 is also needed for replication completion and in its absence linear deleted mtDNA molecules extending between the two origins of mtDNA replication are formed accompanied by mtDNA depletion. The steady-state levels of mitochondrial transcripts follow the levels of mtDNA, and RNA processing is not altered in the absence of RNase H1. Finally, we report the first patient with a homozygous pathogenic mutation in the hybrid-binding domain of RNase H1 causing impaired mtDNA replication. In contrast to catalytically inactive variants of RNase H1, this mutant version has enhanced enzyme activity but shows impaired primer formation. This finding shows that the RNase H1 activity must be strictly controlled to allow proper regulation of mtDNA replication.
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| 33. |
- Munch, Marie W., et al.
(author)
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Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia The COVID STEROID 2 Randomized Trial
- 2021
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In: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 326:18, s. 1807-1817
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Journal article (peer-reviewed)abstract
- Question What is the effect of 12 mg vs 6 mg of dexamethasone on the number of days alive without life support at 28 days in patients with COVID-19 and severe hypoxemia? Findings In this randomized trial that included 1000 patients with COVID-19 and severe hypoxemia, treatment with 12 mg/d of dexamethasone resulted in 22.0 days alive without life support at 28 days compared with 20.5 days in those receiving 6 mg/d of dexamethasone. This difference was not statistically significant. Meaning Compared with 6 mg of dexamethasone, 12 mg of dexamethasone did not statistically significantly reduce the number of days alive without life support at 28 days. This multicenter randomized clinical trial compares the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. IMPORTANCE A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. OBJECTIVE To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. INTERVENTIONS Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and >= 1 serious adverse reactions at 28 days). RESULTS Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). CONCLUSIONS AND RELEVANCE Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference.
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- Andersen, Lars L, et al.
(author)
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Effect of physical exercise on workplace social capital: cluster randomized controlled trial
- 2015
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In: Scandinavian Journal of Public Health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 43:8, s. 810-818
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Journal article (peer-reviewed)abstract
- While workplace health promotion with group-based physical exercise can improve workers' physical health, less is known about potential carry-over effects to psychosocial factors. This study investigates the effect of physical exercise on social capital at work.
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| 41. |
- Bekkevold, D., et al.
(author)
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Environmental correlates of population differentiation in Atlantic herring
- 2005
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In: Evolution. - 0014-3820. ; 59:12, s. 2656-2668
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Journal article (peer-reviewed)abstract
- The marine environment is characterized by few physical barriers, and pelagic fishes commonly show high migratory potential and low, albeit in some cases statistically significant, levels of genetic divergence in neutral genetic marker analyses. However, it is not clear whether low levels of differentiation reflect spatially separated populations experiencing gene flow or shallow population histories coupled with limited random genetic drift in large, demographically isolated populations undergoing independent evolutionary processes. Using information for nine microsatellite loci in a total of 1951 fish, we analyzed genetic differentiation among Atlantic herring from eleven spawning locations distributed along a longitudinal gradient from the North Sea to the Western Baltic. Overall genetic differentiation was low (theta = 0.008) but statistically significant. The area is characterized by a dramatic shift in hydrography from the highly saline and temperature stable North Sea to the brackish Baltic Sea, where temperatures show high annual variation. We used two different methods, a novel computational geometric approach and partial Mantel correlation analysis coupled with detailed environmental information from spawning locations to show that patterns of reproductive isolation covaried with salinity differences among spawning locations, independent of their geographical distance. We show that reproductive isolation can be maintained in marine fish populations exhibiting substantial mixing during larval and adult life stages. Analyses incorporating genetic, spatial, and environmental parameters indicated that isolating mechanisms are associated with the specific salinity conditions on spawning locations.
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| 42. |
- Bekkevold, D., et al.
(author)
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Genetic mixed-stock analysis of Atlantic herring populations in a mixed feeding area
- 2011
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In: Marine Ecology Progress Series. - : Inter-Research Science Center. - 0171-8630 .- 1616-1599. ; 442, s. 187-199
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Journal article (peer-reviewed)abstract
- Determining spatio-temporal distributions of fish populations is of interest to marine ecology, in general, and to fisheries science in particular. Genetic mixed-stock analysis is routinely applied in several anadromous fishes for determining migratory routes and timing but has rarely been used for marine fishes, for which population differentiation is commonly weak and the method presumably less powerful. We used microsatellite information for Northeast Atlantic herring Clupea harengus L. populations and mixed stocks to address 2 questions. We used simulated mixture samples and 3 different statistical approaches to determine whether mixed stock composition could be determined with accuracy. Simulations showed that the applied approaches and mixture samples of 100 individuals enabled detailed composition analyses on a regional level, with resolution for tracing the ecologically dominant Rügen (Greifswalder Bodden) herring population. We then estimated spatio-temporal variation in herring migratory behaviour in the Skagerrak from 17 mixed samples collected over 2 seasons and 2 yr, and identified hitherto undescribed differences in distributions among populations that feed and winter in the area.
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| 43. |
- Brekke, Eva, et al.
(author)
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Service User Experiences of How Flexible Assertive Community Treatment May Support or Inhibit Citizenship : A Qualitative Study
- 2021
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In: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 12
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Journal article (peer-reviewed)abstract
- The aim of this study was to explore and describe service user experiences of how receiving services from a Flexible Assertive Community Treatment (FACT) team may support or inhibit citizenship. Within a participatory design, individual interviews with 32 service users from five Norwegian FACT teams were analyzed using thematic, cross-sectional analysis. The findings showed that FACT may support citizenship by relating to service users as whole people, facilitating empowerment and involvement, and providing practical and accessible help. Experiences of coercion, limited involvement and authoritarian aspects of the system surrounding FACT had inhibited citizenship for participants in this study.
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| 44. |
- Clausen, Anders Ranegaard, et al.
(author)
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Pasteurella multocida thymidine kinase 1 efficiently activates pyrimidine nucleoside analogs.
- 2010
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In: Nucleosides, Nucleotides & Nucleic Acids. - : Informa UK Limited. - 1525-7770 .- 1532-2335. ; 29:4-6, s. 359-362
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Journal article (peer-reviewed)abstract
- In the Pasteurella multocida genome only one putative deoxyribonucleoside kinase encoding gene, for thymidine kinase 1 (PmTK1), was identified. The PmTK1 gene was sub-cloned into Escherichia coli KY895 and it sensitized the host towards 2',2'-difluoro-deoxycytidine (gemcitabine, dFdC), 3'-azido-thymidine (AZT) and 5-fluoro-deoxyuridine (5F-dU). PmTK1 was over-expressed and purified with two different tags. Apparently, deoxyuridine (dU), and not thymidine (dT), is the preferred substrate. We suggest that PmTK1s could be employed as a species-specific activator of uracil-based nucleoside antibiotics.
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| 45. |
- Clausen, Bettina Hjelm, et al.
(author)
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Systemically administered anti-TNF therapy ameliorates functional outcomes after focal cerebral ischemia
- 2014
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In: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 11
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Journal article (peer-reviewed)abstract
- Background: The innate immune system contributes to the outcome after stroke, where neuroinflammation and post-stroke systemic immune depression are central features. Tumor necrosis factor (TNF), which exists in both a transmembrane (tm) and soluble (sol) form, is known to sustain complex inflammatory responses associated with stroke. We tested the effect of systemically blocking only solTNF versus blocking both tmTNF and solTNF on infarct volume, functional outcome and inflammation in focal cerebral ischemia. Methods: We used XPro1595 (a dominant-negative inhibitor of solTNF) and etanercept (which blocks both solTNF and tmTNF) to test the effect of systemic administration on infarct volume, functional recovery and inflammation after focal cerebral ischemia in mice. Functional recovery was evaluated after one, three and five days, and infarct volumes at six hours, 24 hours and five days after ischemia. Brain inflammation, liver acute phase response (APR), spleen and blood leukocyte profiles, along with plasma microvesicle analysis, were evaluated. Results: We found that both XPro1595 and etanercept significantly improved functional outcomes, altered microglial responses, and modified APR, spleen T cell and microvesicle numbers, but without affecting infarct volumes. Conclusions: Our data suggest that XPro1595 and etanercept improve functional outcome after focal cerebral ischemia by altering the peripheral immune response, changing blood and spleen cell populations and decreasing granulocyte infiltration into the brain. Blocking solTNF, using XPro1595, was just as efficient as blocking both solTNF and tmTNF using etanercept. Our findings may have implications for future treatments with anti-TNF drugs in TNF-dependent diseases.
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| 46. |
- Clausen, Frederik Banch, et al.
(author)
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Recommendation for validation and quality assurance of non-invasive prenatal testing for foetal blood groups and implications for IVD risk classification according to EU regulations
- 2022
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In: Vox Sanguinis. - : Wiley. - 0042-9007 .- 1423-0410. ; 117:2, s. 157-165
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Research review (peer-reviewed)abstract
- Background and Objectives: Non-invasive assays for predicting foetal blood group status in pregnancy serve as valuable clinical tools in the management of pregnancies at risk of detrimental consequences due to blood group antigen incompatibility. To secure clinical applicability, assays for non-invasive prenatal testing of foetal blood groups need to follow strict rules for validation and quality assurance. Here, we present a multi-national position paper with specific recommendations for validation and quality assurance for such assays and discuss their risk classification according to EU regulations. Materials and Methods: We reviewed the literature covering validation for in-vitro diagnostic (IVD) assays in general and for non-invasive foetal RHD genotyping in particular. Recommendations were based on the result of discussions between co-authors. Results: In relation to Annex VIII of the In-Vitro-Diagnostic Medical Device Regulation 2017/746 of the European Parliament and the Council, assays for non-invasive prenatal testing of foetal blood groups are risk class D devices. In our opinion, screening for targeted anti-D prophylaxis for non-immunized RhD negative women should be placed under risk class C. To ensure high quality of non-invasive foetal blood group assays within and beyond the European Union, we present specific recommendations for validation and quality assurance in terms of analytical detection limit, range and linearity, precision, robustness, pre-analytics and use of controls in routine testing. With respect to immunized women, different requirements for validation and IVD risk classification are discussed. Conclusion: These recommendations should be followed to ensure appropriate assay performance and applicability for clinical use of both commercial and in-house assays.
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| 47. |
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| 48. |
- Clausen, Henrik, et al.
(author)
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Towards universally acceptable blood
- 2019
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In: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 4:9, s. 1426-1427
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Journal article (peer-reviewed)
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| 49. |
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| 50. |
- Clausen, Per Axel, et al.
(author)
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Simultaneous extraction of di(2-ethylhexyl) phthalate and nonionic surfactants from house dust. Concentrations in floor dust from 15 Danish schools.
- 2003
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In: Journal of Chromatography A. - 0021-9673. ; 986:2, s. 179-190
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Journal article (peer-reviewed)abstract
- Static extraction, supercritical fluid extraction (SFE), pressurized liquid extraction (PLE) and Soxhlet extraction were compared for simultaneous extraction of di(2-ethylhexyl) phthalate (DEHP) and nonionic surfactants from house dust. Homogenized office floor dust from a vacuum cleaner dust bag ("standard dust") was used for the evaluation. One portion of the extracts was used for analysis of nonionic surfactants with LC–MS and another portion was used for DEHP analysis with GC–MS. The extraction yield of DEHP was comparable for all the methods whereas SFE and PLE were the most efficient extraction techniques for the nonionic surfactants. The PLE extraction was found most suitable as a routine method for simultaneous extraction of both types of compounds and was used in a field study of floor dust from 15 Danish schools. The mean concentration of DEHP in the school dust samples was ~4 times higher than observed in other studies of dust from homes in different countries. The concentrations of nonionic surfactants were one order of magnitude lower than soap and linear alkylbenzene sulfonates measured in other studies of floor dust from offices and other public buildings. However, for the first time nonionic surfactants have been identified in house dust.
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