| 1. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 2. |
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| 3. |
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| 4. |
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| 5. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 6. |
- Pihl, E., et al.
(författare)
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Ten new insights in climate science 2020- A horizon scan
- 2020
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Ingår i: Global Sustainability. - : Cambridge University Press. - 2059-4798.
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Tidskriftsartikel (refereegranskat)abstract
- Non-technical summary We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding of Earth's sensitivity to carbon dioxide, finds that permafrost thaw could release more carbon emissions than expected and that the uptake of carbon in tropical ecosystems is weakening. Adverse impacts on human society include increasing water shortages and impacts on mental health. Options for solutions emerge from rethinking economic models, rights-based litigation, strengthened governance systems and a new social contract. The disruption caused by COVID-19 could be seized as an opportunity for positive change, directing economic stimulus towards sustainable investments. Technical summary A synthesis is made of ten fields within climate science where there have been significant advances since mid-2019, through an expert elicitation process with broad disciplinary scope. Findings include: (1) a better understanding of equilibrium climate sensitivity; (2) abrupt thaw as an accelerator of carbon release from permafrost; (3) changes to global and regional land carbon sinks; (4) impacts of climate change on water crises, including equity perspectives; (5) adverse effects on mental health from climate change; (6) immediate effects on climate of the COVID-19 pandemic and requirements for recovery packages to deliver on the Paris Agreement; (7) suggested long-term changes to governance and a social contract to address climate change, learning from the current pandemic, (8) updated positive cost-benefit ratio and new perspectives on the potential for green growth in the short- A nd long-term perspective; (9) urban electrification as a strategy to move towards low-carbon energy systems and (10) rights-based litigation as an increasingly important method to address climate change, with recent clarifications on the legal standing and representation of future generations. Social media summary Stronger permafrost thaw, COVID-19 effects and growing mental health impacts among highlights of latest climate science.
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| 7. |
- Ahnberg, H., et al.
(författare)
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Stabilising effects of different binders in some Swedish soils
- 2003
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Ingår i: Ground Improvement. - : Thomas Telford Ltd.. - 1365-781X .- 1751-7621. ; 7:1, s. 9-23
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Tidskriftsartikel (refereegranskat)abstract
- In Sweden, lime and lime-cement have been used for several decades as stabilising agents in deep stabilisation of soft soils. More recently, other types of binder have come into use, but so far only to a limited extent. In order to gather experience about the effect of various binders, laboratory tests have been performed on different types of soil stabilised with a range of binders. Lime, cement, fly ash and blast furnace slag in different combinations together with different admixtures, such as gypsum, silica fume and calcium chloride, have been used in the investigations. The variation in strength with type of binder has been studied, and comparisons have also been made with results from some previous investigations using different binders. The tests showed that there is no optimal, universal binder for stabilisation of the soils. Whereas some binders are robust, yielding good results in most types of soil, there are also binders that produce very good results in certain soils but poor results in others. Both similarities and differences in effects were found for different binders.
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| 8. |
- Boström, C., et al.
(författare)
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Distribution, structure and function of Nordic eelgrass (Zostera marina) ecosystems: Implications for coastal management and conservation
- 2014
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Ingår i: Aquatic conservation. - : Wiley. - 1052-7613. ; 24:3, s. 410-434
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Forskningsöversikt (refereegranskat)abstract
- This paper focuses on the marine foundation eelgrass species, Zostera marina, along a gradient from the northern Baltic Sea to the north-east Atlantic. This vast region supports a minimum of 1480km2 eelgrass (maximum >2100km2), which corresponds to more than four times the previously quantified area of eelgrass in Western Europe. Eelgrass meadows in the low salinity Baltic Sea support the highest diversity (4-6 spp.) of angiosperms overall, but eelgrass productivity is low (<2g dw m-2 d-1) and meadows are isolated and genetically impoverished. Higher salinity areas support monospecific meadows, with higher productivity (3-10g dw m-2 d-1) and greater genetic connectivity. The salinity gradient further imposes functional differences in biodiversity and food webs, in particular a decline in number, but increase in biomass of mesograzers in the Baltic. Significant declines in eelgrass depth limits and areal cover are documented, particularly in regions experiencing high human pressure. The failure of eelgrass to re-establish itself in affected areas, despite nutrient reductions and improved water quality, signals complex recovery trajectories and calls for much greater conservation effort to protect existing meadows. The knowledge base for Nordic eelgrass meadows is broad and sufficient to establish monitoring objectives across nine national borders. Nevertheless, ensuring awareness of their vulnerability remains challenging. Given the areal extent of Nordic eelgrass systems and the ecosystem services they provide, it is crucial to further develop incentives for protecting them. © 2014 The Authors.
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| 9. |
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| 10. |
- Chandrasekaran, Abinaya, et al.
(författare)
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Astrocytic reactivity triggered by defective autophagy and metabolic failure causes neurotoxicity in frontotemporal dementia type 3
- 2021
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Ingår i: Stem Cell Reports. - : Elsevier BV. - 2213-6711. ; , s. 2736-2751
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia type 3 (FTD3), caused by a point mutation in the charged multivesicular body protein 2B (CHMP2B), affects mitochondrial ultrastructure and the endolysosomal pathway in neurons. To dissect the astrocyte-specific impact of mutant CHMP2B expression, we generated astrocytes from human induced pluripotent stem cells (hiPSCs) and confirmed our findings in CHMP2B mutant mice. Our data provide mechanistic insights into how defective autophagy causes perturbed mitochondrial dynamics with impaired glycolysis, increased reactive oxygen species, and elongated mitochondrial morphology, indicating increased mitochondrial fusion in FTD3 astrocytes. This shift in astrocyte homeostasis triggers a reactive astrocyte phenotype and increased release of toxic cytokines, which accumulate in nuclear factor kappa b (NF-κB) pathway activation with increased production of CHF, LCN2, and C3 causing neurodegeneration.
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| 11. |
- Gunnarsson, K, et al.
(författare)
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Programmable motion and separation of single magnetic particles on patterned magnetic surfaces
- 2005
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Ingår i: Advanced Materials. - : Wiley. - 0935-9648 .- 1521-4095. ; 17:14, s. 1730-1734
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Tidskriftsartikel (refereegranskat)abstract
- Motion of single micrometer-sized magnetic particles on patterned magnetic surfaces is controlled by a rotating magnetic field (see Figure and cover). Patterns of thin-film magnetic elements are tailored to form transport lines. Individual particles are separated by adding junctions to the transport lines. The method can improve existing applications in biotechnology and generate new ones in life sciences.
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| 12. |
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| 13. |
- Hjaeresen, S., et al.
(författare)
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MIF in the cerebrospinal fluid is decreased during relapsing-remitting while increased in secondary progressive multiple sclerosis
- 2022
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Ingår i: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X. ; 439
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Tidskriftsartikel (refereegranskat)abstract
- Background: Macrophage migration inhibitory factor (MIF) is involved in the function of both the innate and adaptive immune systems and in neuroprotection and has recently been implicated in multiple sclerosis (MS). Objectives: Determination of MIF levels in the cerebrospinal fluid (CSF) of patients with distinct subtypes of MS and the cellular localization of MIF in human brain tissue. Methods: The levels of MIF were investigated in CSF from patients with clinically isolated syndrome (CIS) (n = 26), relapsing-remitting MS (RRMS) (n = 22), secondary progressive MS (SPMS) (n = 19), and healthy controls (HCs) (n = 24), using ELISA. The effect of disease-modifying therapies in the RRMS and SPMS cohorts were examined. Cellular distribution of MIF in the human brain was studied using immunochemistry and the newly available OligoInternode database. Results: MIF was significantly decreased in treatmentnaive CIS and RRMS patients compared to HCs but was elevated in SPMS. Interestingly, MIF levels were sex-dependent and significantly higher in women with CIS and RRMS. MIF expression in the human brain was localized to neurons, astrocytes, pericytes, and oligo5 oligodendrocytes but not in microglia. Conclusion: The finding that MIF was decreased in newly diagnosed CIS and RRMS patients but was high in patients with SPMS may suggest that MIF levels in CSF are regulated by local MIF receptor expression that affects the overall MIF signaling in the brain and may represent a protective mechanism that eventually fails.
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| 14. |
- Hjaeresen, S., et al.
(författare)
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The levels of the serine protease HTRA1 in cerebrospinal fluid correlate with progression and disability in multiple sclerosis
- 2021
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 268, s. 3316-3324
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Tidskriftsartikel (refereegranskat)abstract
- Background High Temperature Requirement Serine Protease A1 (HTRA1) degrades extracellular matrix molecules (ECMs) and growth factors. It interacts with several proteins implicated in multiple sclerosis (MS), but has not previously been linked to the disease. Objective Investigate the levels of HTRA1 in cerebrospinal fluid (CSF) in different subtypes of MS and brain tissue. Methods Using ELISA, HTRA1 levels were compared in CSF from untreated patients with relapsing-remitting MS (RRMS, n = 23), secondary progressive MS (SPMS, n = 26) and healthy controls (HCs, n = 26). The effect of disease modifying therapies (DMTs) were examined in both patient groups. Cellular distribution in human brain was studied using immunochemistry and the oligointernode database, based on a single-nuclei RNA expression map. Results HTRA1 increased in RRMS and SPMS compared to HCs. DMT decreased HTRA1 levels in both types of MS. Using ROC analysis, HTRA1 cut-offs could discriminate HCs from RRMS patients with 100% specificity and 82.6% sensitivity. In the brain, HTRA1 was expressed in glia and neurons. Conclusion HTRA1 is a promising CSF biomarker for MS correlating with disease- and disability progression. Most cell species of the normal and diseased CNS express HTRA1 and the expression pattern could reflect pathological processes involved in MS pathogenesis.
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| 15. |
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| 16. |
- Kalogirou, S., et al.
(författare)
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Shrimp trap selectivity in a Mediterranean small-scale-fishery
- 2019
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Ingår i: Fisheries Research. - : Elsevier BV. - 0165-7836. ; 211, s. 131-140
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Tidskriftsartikel (refereegranskat)abstract
- Small-scale shrimp trap fisheries, which have received very little attention in areas with limited potential for economic diversification, could offer a sustainable and socially beneficial option for profitable businesses in these regions. This study explores the effect of mesh size on selectivity of the commercially important narwal shrimp, Plesionika narval, in the Mediterranean Sea. Three different mesh sizes (8 × 8, 12 × 12 and 12 × 25 mm) were tested in fishing trials, with a theoretical Minimum Landing Size (MLS) using a defined maturity size of 12 mm to support interpretation of the results. Using the retention rates and the estimations on population fractions above and below MLS, we show that the use of the smallest- and largest-sized meshes would not support sustainable or efficient fishery. The results demonstrate a significant decrease in capture probability of undersized narwal shrimps with increased mesh size. The medium-sized mesh traps prove to be the best compromise for the fishery with high catch efficiency of commercial size shrimp and a low capture probability of undersized individuals. The results outlined in this article could be used to develop management plans for small-scale trap fisheries as a basis for developing viable enterprises in remote coastal communities. © 2018 Elsevier B.V.
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| 17. |
- Karlsson, P.E., et al.
(författare)
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Twenty years of nitrogen deposition to Norway spruce forests in Sweden
- 2022
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 809, s. 152192-152192
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Tidskriftsartikel (refereegranskat)abstract
- The yearly, total (dry+wet) deposition of inorganic nitrogen (inorg-N) to Norway spruce forests was estimated with afull spatial coverage over Sweden for a twenty-year period, 2001–2020, based on combined measurements with Teflonstring samplers, throughfall deposition and bulk deposition to the open field.The results were based on a novel methodto apply estimates of the dry deposition based on measurements at a limited number of sites, to a larger number of siteswith only bulk deposition measurements, in turn based on the existence of a strong geographical gradient in the dry depositionof inorg-N from southwest to northeast Sweden. The method should be applicable for other geographical regionswhere gaseous NH3, NO2 and HNO3 are not main drivers of N dry deposition and where geographical gradientsin dry deposition could be defined.It was shown that Norway spruce forests in south Sweden receive more N from depositionthan has been previously estimated, based onmodelling. Clear time trends were demonstrated for decreased depositionof inorg-N to Norway spruce forests in all parts of Sweden. The decreaseswere somewhat larger thanwhat couldbe expected from the decrease in the reported emissions of inorg-N from Europe. The results emphasize that estimates of the total deposition are necessary in order to map levels and follow the development of N deposition in forests.
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| 18. |
- Khilji, M. S., et al.
(författare)
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The inducible β5i proteasome subunit contributes to proinsulin degradation in GRP94-deficient β-cells and is overexpressed in type 2 diabetes pancreatic islets
- 2020
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Ingår i: American Journal of Physiology - Endocrinology and Metabolism. - 0193-1849. ; 318:6
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Tidskriftsartikel (refereegranskat)abstract
- Proinsulin is a misfolding-prone protein, and its efficient breakdown is critical when β-cells are confronted with high-insulin biosynthetic demands, to prevent endoplasmic reticulum stress, a key trigger of secretory dysfunction and, if uncompensated, apoptosis. Proinsulin degradation is thought to be performed by the constitutively expressed standard proteasome, while the roles of other proteasomes are unknown. We recently demonstrated that deficiency of the proinsulin chaperone glucoseregulated protein 94 (GRP94) causes impaired proinsulin handling and defective insulin secretion associated with a compensated endoplasmic reticulum stress response. Taking advantage of this model of restricted folding capacity, we investigated the role of different proteasomes in proinsulin degradation, reasoning that insulin secretory dynamics require an inducible protein degradation system. We show that the expression of only one enzymatically active proteasome subunit, namely, the inducible β5i-subunit, was increased in GRP94 CRISPR/Cas9 knockout (KO) cells. Additionally, the level of β5i-containing intermediate proteasomes was significantly increased in these cells, as was β5i-related chymotrypsin-like activity. Moreover, proinsulin levels were restored in GRP94 KO upon β5i small interfering RNA-mediated knockdown. Finally, the fraction of β-cells expressing the β5i subunit is increased in human islets from type 2 diabetes patients. We conclude that β5i is an inducible proteasome subunit dedicated to the degradation of mishandled proinsulin. Copyright © 2020 the American Physiological Society.
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| 19. |
- Khilji, M. S., et al.
(författare)
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The intermediate proteasome is constitutively expressed in pancreatic beta cells and upregulated by stimulatory, low concentrations of interleukin 1 beta
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:2
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Tidskriftsartikel (refereegranskat)abstract
- A central and still open question regarding the pathogenesis of autoimmune diseases, such as type 1 diabetes, concerns the processes that underlie the generation of MHC-presented autoantigenic epitopes that become targets of autoimmune attack. Proteasomal degradation is a key step in processing of proteins for MHC class I presentation. Different types of proteasomes can be expressed in cells dictating the repertoire of peptides presented by the MHC class I complex. Of particular interest for type 1 diabetes is the proteasomal configuration of pancreatic beta cells, as this might facilitate autoantigen presentation by beta cells and thereby their T-cell mediated destruction. Here we investigated whether so-called inducible subunits of the proteasome are constitutively expressed in beta cells, regulated by inflammatory signals and participate in the formation of active intermediate or immuno-proteasomes. We show that inducible proteasomal subunits are constitutively expressed in human and rodent islets and an insulin-secreting cell-line. Moreover, the beta 5i subunit is incorporated into active intermediate proteasomes that are bound to 19S or 11S regulatory particles. Finally, inducible subunit expression along with increase in total proteasome activities are further upregulated by low concentrations of IL-1 beta stimulating proinsulin biosynthesis. These findings suggest that the beta cell proteasomal repertoire is more diverse than assumed previously and may be highly responsive to a local inflammatory islet environment.
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| 20. |
- Klingberg, Jenny, 1978, et al.
(författare)
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Observed annual surface ozone maxima and minima in northern and central Europe from 1990–2015 — latitude dependence and temporal trends
- 2019
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Ingår i: Boreal environment research. - 1239-6095. ; 24, s. 201-214
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Tidskriftsartikel (refereegranskat)abstract
- Ground-level ozone is an air pollutant that, despite reductions in precursor emission in Europe, still represents a risk to vegetation and human health. This study is based on observations of ozone concentrations ([O3]) from 25 European monitoring stations, north of the Alps within the EMEP network, during the 26-year period from 1990–2015. We analyzed the maximum and minimum hourly [O3] as well as the seasonal cycle in relation to latitude. In addition, temporal trends were studied. The maximum [O3] increased towards the south of the study area, while the yearly minimum of daytime mean increased towards the north. There was a strong correlation between the day of year when the maximum [O3] occurred and latitude: the maximum [O3] occurred earlier in the north. The maximum daytime [O3] decreased at all stations while the minimum daytime [O3] increased at most stations during the studied time period.
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| 21. |
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| 22. |
- Kvile, KØ, et al.
(författare)
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Kelp Forest Distribution in the Nordic Region.
- 2022
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Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Kelp forests are productive coastal ecosystems that provide a range of ecosystem services. Mapping the distribution and area occupied by kelp forests is a critical step to identify their ecosystem functions and services, including their role in the carbon cycle, and to detect changes in their distribution. We compiled quantitative data of the dominant genera Laminaria and Saccharina across the Nordic region, allowing us to separate kelp forests (areas with dense or moderately dense kelp coverage) from occurrences of single or few individuals. By fitting boosted regression trees to the compiled data, we modelled and predicted the distribution of kelp forests across the Nordic region. Despite the large scale of the analyses, the models captured well the kelps’ environmental affinities and predicted the presence of kelp forests with high accuracy. Dense kelp forests are found along the rocky shores of all the Nordic countries, except in the brackish Baltic Sea, with largest areas in Norway, Greenland and Iceland. The results of this study set the scene for future studies on the importance of kelp forests in the Nordic region, including their contribution to the marine carbon budget.
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| 23. |
- Liptzin, Daniel, et al.
(författare)
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Spatial and Temporal Patterns in Atmospheric Deposition of Dissolved Organic Carbon
- 2022
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Ingår i: Global Biogeochemical Cycles. - : American Geophysical Union (AGU). - 0886-6236 .- 1944-9224. ; 36:10
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Tidskriftsartikel (refereegranskat)abstract
- Atmospheric deposition of dissolved organic carbon (DOC) to terrestrial ecosystems is a small, but rarely studied component of the global carbon (C) cycle.Emissions of volatile organic compounds (VOC) and organic particulates are the sources of atmospheric C and deposition represents a major pathway for the removal of organic C from the atmosphere.Here, we evaluate the spatial and temporal patterns of DOC deposition using 70 data sets at least one year in length ranging from 40° south to 66° north latitude. Globally, the median DOC concentration in bulk deposition was 1.7 mg L −1. The DOC concentrations were significantly higher in tropical (<25°) latitudes compared to temperate (>25°) latitudes.DOC deposition was significantly higher in the tropics because of both higher DOC concentrations and precipitation. Using the global median or latitudinal specific DOC concentrations leads to a calculated global deposition of 202 or 295 Tg C yr −1 respectively.Many sites exhibited seasonal variability in DOC concentration. At temperate sites, DOC concentrations were higher during the growing season; at tropical sites, DOC concentrations were higher during the dry season. Thirteen of the thirty-four long-term (>10 years) data sets showed significant declines in DOC concentration over time with the others showing no significant change.Based on the magnitude and timing of the various sources of organic C to the atmosphere, biogenic VOCs likely explain the latitudinal pattern and the seasonal pattern at temperate latitudes while decreases in anthropogenic emissions are the most likely explanation for the declines in DOC concentration.
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| 24. |
- Ludvigsson, Johnny, et al.
(författare)
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Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial
- 2011
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Ingår i: DIABETOLOGIA. - : Springer Science Business Media. - 0012-186X .- 1432-0428. ; 54:3, s. 634-640
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the safety and efficacy of alum formulated glutamic acid decarboxylase GAD(65) (GAD-alum) treatment of children and adolescents with type 1 diabetes after 4 years of follow-up. Seventy children and adolescents aged 10-18 years with recent onset type 1 diabetes participated in a phase II, double-blind, randomised placebo-controlled clinical trial. Patients identified as possible participants attended one of eight clinics in Sweden to receive information about the study and for an eligibility check, including a medical history. Participants were randomised to one of the two treatment groups and received either a subcutaneous injection of 20 mu g of GAD-alum or placebo at baseline and 1 month later. The study was blinded to participants and investigators until month 30. The study was unblinded at 15 months to the sponsor and statistician in order to evaluate the data. At follow-up after 30 months there was a significant preservation of residual insulin secretion, as measured by C-peptide, in the group receiving GAD-alum compared with placebo. This was particularly evident in patients with andlt; 6 months disease duration at baseline. There were no treatment-related serious adverse events. We have now followed these patients for 4 years. Overall, 59 patients, 29 who had been treated with GAD-alum and 30 who had received placebo, gave their informed consent. One patient in each treatment group experienced an episode of keto-acidosis between months 30 and 48. There were no treatment-related adverse events. The primary efficacy endpoint was the change in fasting C-peptide concentration from baseline to 15 months after the prime injection for all participants per protocol set. In the GAD-alum group fasting C-peptide was 0.332 +/- 0.032 nmol/l at day 1 and 0.215 +/- 0.031 nmol/l at month 15. The corresponding figures for the placebo group were 0.354 +/- 0.039 and 0.184 +/- 0.033 nmol/l, respectively. The decline in fasting C-peptide levels between day 1 and month 1, was smaller in the GAD-alum group than the placebo group. The difference between the treatment groups was not statistically significant. In those patients who were treated within 6 months of diabetes diagnosis, fasting C-peptide had decreased significantly less in the GAD-alum group than in the placebo-treated group after 4 years. Four years after treatment with GAD-alum, children and adolescents with recent-onset type 1 diabetes continue to show no adverse events and possibly to show clinically relevant preservation of C-peptide. ClinicalTrials.gov NCT00435981 The study was funded by The Swedish Research Council K2008-55X-20652-01-3, Barndiabetesfonden (The Swedish Child Diabetes Foundation), the Research Council of Southeast Sweden, and an unrestricted grant from Diamyd Medical AB.
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| 25. |
- Macri, E. M., et al.
(författare)
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Importance of patellofemoral and tibiofemoral cartilage lesions on trajectory of self-reported outcomes in patients at high risk of knee OA : 4–6 years follow-up of patients undergoing meniscal surgery
- 2021
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 29:9, s. 1291-1295
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We evaluated whether patient-reported outcome trajectories (i.e., changes over time) differed by intraoperative compartmental cartilage lesion pattern over 4–6 years following arthroscopic meniscal surgery. Methods: In this ancillary study of the Knee Arthroscopy Cohort Southern Denmark cohort, we intraoperatively categorized cartilage lesions as isolated patellofemoral, isolated tibiofemoral, or combined patellofemoral/tibiofemoral. Participants completed the Knee injury and Osteoarthritis Outcome Score (KOOS) pre-operatively, at 3 and 12 months, and at 4–6 years post-operatively and reported overall satisfaction at final follow-up. Our main outcome was KOOS4 (grand mean of four subscale means). We evaluated whether KOOS4 scores changed over time according to cartilage lesion patterns using adjusted mixed linear regression. We also estimated probability of treatment satisfaction using logistic regression. Results: Of 630 participants with complete cartilage scores, 280 (44%) were women, mean (standard deviation) age was 49 (13) years, and BMI was 27.3 (4.4) kg/m2. KOOS4 scores at baseline were slightly lower in all lesion groups compared to the no lesion group, yet only the combined group was statistically significantly lower. KOOS4 trajectories were similar across cartilage lesion patterns, but by final follow-up, adjusted mean KOOS4 scores were 6.8 (95% CI 2.2, 11.4) to 9.8 (1.1, 18.5) points lower in groups with cartilage lesions compared to the no lesion group. Probability of patient-reported satisfaction did not differ statistically by group. Conclusions: Though KOOS4 scores were slightly lower in groups with arthroscopically assessed cartilage lesions compared to the no lesion group, trajectories were similar across all groups.
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