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1.
  • Alalam, Hanna, et al. (författare)
  • A High-Throughput Method for Screening for Genes Controlling Bacterial Conjugation of Antibiotic Resistance.
  • 2020
  • Ingår i: mSystems. - 2379-5077. ; 5:6
  • Tidskriftsartikel (refereegranskat)abstract
    • The rapid horizontal transmission of antibiotic resistance genes on conjugative plasmids between bacterial host cells is a major cause of the accelerating antibiotic resistance crisis. There are currently no experimental platforms for fast and cost-efficient screening of genetic effects on antibiotic resistance transmission by conjugation, which prevents understanding and targeting conjugation. We introduce a novel experimental framework to screen for conjugation-based horizontal transmission of antibiotic resistance between >60,000 pairs of cell populations in parallel. Plasmid-carrying donor strains are constructed in high-throughput. We then mix the resistance plasmid-carrying donors with recipients in a design where only transconjugants can reproduce, measure growth in dense intervals, and extract transmission times as the growth lag. As proof-of-principle, we exhaustively explore chromosomal genes controlling F-plasmid donation within Escherichia coli populations, by screening the Keio deletion collection in high replication. We recover all seven known chromosomal gene mutants affecting conjugation as donors and identify many novel mutants, all of which diminish antibiotic resistance transmission. We validate nine of the novel genes' effects in liquid mating assays and complement one of the novel genes' effect on conjugation (rseA). The new framework holds great potential for exhaustive disclosing of candidate targets for helper drugs that delay resistance development in patients and societies and improve the longevity of current and future antibiotics. Further, the platform can easily be adapted to explore interspecies conjugation, plasmid-borne factors, and experimental evolution and be used for rapid construction of strains.IMPORTANCE The rapid transmission of antibiotic resistance genes on conjugative plasmids between bacterial host cells is a major cause of the accelerating antibiotic resistance crisis. There are currently no experimental platforms for fast and cost-efficient screening of genetic effects on antibiotic resistance transmission by conjugation, which prevents understanding and targeting conjugation. We introduce a novel experimental framework to screen for conjugation-based horizontal transmission of antibiotic resistance between >60,000 pairs of cell populations in parallel. As proof-of-principle, we exhaustively explore chromosomal genes controlling F-plasmid donation within E. coli populations. We recover all previously known and many novel chromosomal gene mutants that affect conjugation efficiency. The new framework holds great potential for rapid screening of compounds that decrease transmission. Further, the platform can easily be adapted to explore interspecies conjugation, plasmid-borne factors, and experimental evolution and be used for rapid construction of strains.
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2.
  • Asplund, Maria. E., 1970, et al. (författare)
  • Methane Emissions From Nordic Seagrass Meadow Sediments
  • 2022
  • Ingår i: Frontiers in Marine Science. - : Frontiers Media S.A.. - 2296-7745. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Shallow coastal soft bottoms are important carbon sinks. Submerged vegetation has been shown to sequester carbon, increase sedimentary organic carbon (C-org) and thus suppress greenhouse gas (GHG) emissions. The ongoing regression of seagrass cover in many areas of the world can therefore lead to accelerated emission of GHGs. In Nordic waters, seagrass meadows have a high capacity for carbon storage, with some areas being recognized as blue carbon hotspots. To what extent these carbon stocks lead to emission of methane (CH4) is not yet known. We investigated benthic CH4 emission (i.e., net release from the sediment) in relation to seagrass (i.e. Zostera marina) cover and sedimentary C-org content (%) during the warm summer period (when emissions are likely to be highest). Methane exchange was measured in situ with benthic chambers at nine sites distributed in three regions along a salinity gradient from similar to 6 in the Baltic Sea (Finland) to similar to 20 in Kattegat (Denmark) and similar to 26 in Skagerrak (Sweden). The net release of CH4 from seagrass sediments and adjacent unvegetated areas was generally low compared to other coastal habitats in the region (such as mussel banks and wetlands) and to other seagrass areas worldwide. The lowest net release was found in Finland. We found a positive relationship between CH4 net release and sedimentary C-org content in both seagrass meadows and unvegetated areas, whereas no clear relationship between seagrass cover and CH4 net release was observed. Overall, the data suggest that Nordic Zostera marina meadows release average levels of CH4 ranging from 0.3 to 3.0 mu g CH4 m(-2) h(-1), which is at least 12-78 times lower (CO2 equivalents) than their carbon accumulation rates previously estimated from seagrass meadows in the region, thereby not hampering their role as carbon sinks. Thus, the relatively weak CH4 emissions from Nordic Z. marina meadows will not outweigh their importance as carbon sinks under present environmental conditions.
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3.
  • Frigyesi, Attila, et al. (författare)
  • Plasma proenkephalin A 119-159 on intensive care unit admission is a predictor of organ failure and 30-day mortality
  • 2021
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Proenkephalin A 119-159 (penKid) has been suggested as a marker of renal failure and poor outcome. We aimed to investigate the association of penKid on ICU admission with organ dysfunction and mortality in a mixed ICU population. In this retrospective, observational study, admission penKid levels from prospectively collected blood samples of consecutive patients admitted to four Swedish ICUs were analysed. The association of penKid with day-two sequential organ failure assessment (SOFA) scores and 30-day mortality was investigated using (ordinal) logistic regression. The predictive power of penKid for 30-day mortality and dialysis was assessed using the area under the receiver operating characteristic curve (AUC).RESULTS: Of 1978 included patients, 632 fulfilled the sepsis 3-criteria, 190 had a cardiac arrest, and 157 had experienced trauma. Admission penKid was positively associated with 30-day mortality with an odds ratio of 1.95 (95% confidence interval 1.75-2.18, p < 0.001), and predicted 30-day mortality in the entire ICU population with an AUC of 0.71 (95% confidence interval 0.68-0.73) as well as in the sepsis, cardiac arrest and trauma subgroups (AUCs of 0.61-0.84). Correction for admission plasma creatinine revealed that penKid correlated with neurological dysfunction.CONCLUSION: Plasma penKid on ICU admission is associated with day-two organ dysfunction and predictive of 30-day mortality in a mixed ICU-population, as well as in sepsis, cardiac arrest and trauma subgroups. In addition to being a marker of renal dysfunction, plasma penKid is associated with neurologic dysfunction in the entire ICU population, and cardiovascular dysfunction in sepsis.
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4.
  • Krause-Jensen, D, et al. (författare)
  • Nordic Blue Carbon Ecosystems: Status and Outlook
  • 2022
  • Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 9
  • Forskningsöversikt (refereegranskat)abstract
    • Vegetated coastal and marine habitats in the Nordic region include salt marshes, eelgrass meadows and, in particular, brown macroalgae (kelp forests and rockweed beds). Such habitats contribute to storage of organic carbon (Blue Carbon – BC) and support coastal protection, biodiversity and water quality. Protection and restoration of these habitats therefore have the potential to deliver climate change mitigation and co-benefits. Here we present the existing knowledge on Nordic BC habitats in terms of habitat area, C-stocks and sequestration rates, co-benefits, policies and management status to inspire a coherent Nordic BC roadmap. The area extent of BC habitats in the region is incompletely assessed, but available information sums up to 1,440 km2 salt marshes, 1,861 (potentially 2,735) km2 seagrass meadows, and 16,532 km2 (potentially 130,735 km2, including coarse Greenland estimates) brown macroalgae, yielding a total of 19,833 (potentially 134,910) km2. Saltmarshes and seagrass meadows have experienced major declines over the past century, while macroalgal trends are more diverse. Based on limited salt marsh data, sediment C-stocks average 3,311 g Corg m-2 (top 40-100 cm) and sequestration rates average 142 g Corg m-2 yr-1. Eelgrass C-stocks average 2,414 g Corg m-2 (top 25 cm) and initial data for sequestration rates range 5-33 g Corg m-2, quantified for one Greenland site and one short term restoration. For Nordic brown macroalgae, peer-reviewed estimates of sediment C-stock and sequestration are lacking. Overall, the review reveals substantial Nordic BC-stocks, but highlights that evidence is still insufficient to provide a robust estimate of all Nordic BC-stocks and sequestration rates. Needed are better quantification of habitat area, C-stocks and fluxes, particularly for macroalgae, as well as identification of target areas for BC management. The review also points to directives and regulations protecting Nordic marine vegetation, and local restoration initiatives with potential to increase C-sequestration but underlines that increased coordination at national and Nordic scales and across sectors is needed. We propose a Nordic BC roadmap for science and management to maximize the potential of BC habitats to mitigate climate change and support coastal protection, biodiversity and additional ecosystem functions.
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5.
  • Kreisel, Katrin, 1991, et al. (författare)
  • DNA polymerase η contributes to genome-wide lagging strand synthesis.
  • 2019
  • Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 47:5, s. 2425-2435
  • Tidskriftsartikel (refereegranskat)abstract
    • DNA polymerase η (pol η) is best known for its ability to bypass UV-induced thymine-thymine (T-T) dimers and other bulky DNA lesions, but pol ηalso has other cellular roles. Here, we present evidence that pol η competes with DNA polymerases α and δfor the synthesis of the lagging strand genome-wide, where it also shows a preference for T-T in the DNA template. Moreover, we found that the C-terminus of pol η,which contains a PCNA-Interacting Protein motif is required for pol ηto function in lagging strand synthesis. Finally, we provide evidence that a pol η dependent signature is also found to be lagging strand specific in patients with skin cancer. Taken together, these findings provide insight into the physiological role of DNA synthesis by pol η and have implications for our understanding of how our genome is replicated to avoid mutagenesis, genome instability and cancer.
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7.
  • Röhr, Maria Emilia, et al. (författare)
  • Blue Carbon Storage Capacity of Temperate Eelgrass (Zostera marina) Meadows
  • 2018
  • Ingår i: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 32:10, s. 1457-1475
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite the importance of coastal ecosystems for the global carbon budgets, knowledge of their carbon storage capacity and the factors driving variability in storage capacity is still limited. Here we provide an estimate on the magnitude and variability of carbon stocks within a widely distributed marine foundation species throughout its distribution area in temperate Northern Hemisphere. We sampled 54 eelgrass (Zostera marina) meadows, spread across eight ocean margins and 36° of latitude, to determine abiotic and biotic factors influencing organic carbon (Corg) stocks in Zostera marina sediments. The Corg stocks (integrated over 25-cm depth) showed a large variability and ranged from 318 to 26,523gC/m2 with an average of 2,721gC/m2. The projected Corg stocks obtained by extrapolating over the top 1m of sediment ranged between 23.1 and 351.7MgC/ha, which is in line with estimates for other seagrasses and other blue carbon ecosystems. Most of the variation in Corg stocks was explained by five environmental variables (sediment mud content, dry density and degree of sorting, and salinity and water depth), while plant attributes such as biomass and shoot density were less important to Corg stocks. Carbon isotopic signatures indicated that at most sites <50% of the sediment carbon is derived from seagrass, which is lower than reported previously for seagrass meadows. The high spatial carbon storage variability urges caution in extrapolating carbon storage capacity between geographical areas as well as within and between seagrass species.
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8.
  • Alopaeus, Tea, et al. (författare)
  • Med de nya svenska klimatmålen i sikte : Gapanalys samt strategier och förutsättningar för att nå etappmålen 2030 med utblick mot 2045
  • 2017
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Under våren 2017 presenterade Naturvårdsverket scenarier för hur växthusgasutsläppen i Sverige skulle kunna utvecklas till 2035. Sedan Naturvårdsverket presenterade scenarierna har ett nytt klimatpolitiskt ramverk för Sverige beslutats av riksdagen med nya klimatmål till 2030, 2040 och 2045. Regeringen har även presenterat ett antal nya styrmedel i budgetpropositionen.Naturvårdsverket ska inom miljömålssystemet löpande och strategiskt analysera och utvärdera styrmedel och åtgärder. Naturvårdsverket har mellan maj och november 2017 gjort en första uppföljning mot de nya klimatmålen. I denna rapport presenteras hur beslutade och planerade styrmedel kan komma att falla ut givet olika antagande. En översiktlig analys av styrmedel görs också.Arbetsgruppens sammansättning har varierat över tid. Sammantaget har följande personer på Naturvårdsverket deltagit i arbetsgruppen: Tea Alopaeus (projektledare), Björn Boström, Mats Björsell, Martin Boije, Joanna Dickinson, Dag Henning, Daniel Engström Stenson, Eva Jernbäcker (projektledare till september), Julien Morel, Miriam Münnich Vass, Karl-Anders Stigzelius, Ulrika Svensson, Per Wollin.Stockholm 29 november 2017Björn RisingerGeneraldirektör
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9.
  • Andersson, Magnus, et al. (författare)
  • Fiskbestånd och miljö i hav och sötvatten : Resurs- och miljööversikt 2012
  • 2012
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Detta är den nionde utgåvan av den samlade översikten över fisk- och kräftdjursbeståndens status i våra vatten. Kunskap om fiskbestånden och miljön är en förutsättning för att utnyttjandet av fiskresurserna skall bli bärkraftigt. För svenska vattenområden beskrivs miljöutvecklingen i ett ekosystemsperspektiv, dels för att tydliggöra fiskens ekologiska roll och beskriva yttre miljöfaktorer som påverkar fiskbestånden, dels för att belysa fiskets effekter på miljön.Fiskbestånd och miljö i hav och sötvatten är utarbetad av Sveriges lantbruksuniversitet (SLU), Institutionen för akvatiska resurser (SLU Aqua), på uppdrag av Havs- och vattenmyndigheten. Rapporten sammanfattar utveckling och beståndsstatus för de kommersiellt viktigaste fisk- och kräftdjursarterna i våra vatten. Bedömningar och förvaltningsråd är baserade på Internationella Havsforskningsrådets (ICES) rådgivning, SLU Aquas nationella och regionala provfiskedata, samt yrkesfiskets rapportering.
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10.
  • Bergqvist, David, et al. (författare)
  • Akupunktur kan ge kärlskador
  • 1998
  • Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 95:3, s. 180-181
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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11.
  • Bergström, Ulf, et al. (författare)
  • Evaluating eutrophication management scenarios in the Baltic Sea using species distribution modelling
  • 2013
  • Ingår i: Journal of Applied Ecology. - : Wiley. - 1365-2664 .- 0021-8901. ; 50:3, s. 680-690
  • Tidskriftsartikel (refereegranskat)abstract
    • Eutrophication is severely affecting species distributions and ecosystem functioning in coastal areas. Targets for eutrophication reduction have been set in the Baltic Sea Action Plan (BSAP) using Secchi depth, a measure of water transparency, as the main status indicator. Despite the high economic costs involved, the potential effects of this political decision on key species and habitats have not been assessed. In a case study including species central to coastal ecosystem functioning, we modelled the effects of changing Secchi depth on the distribution of bladderwrack Fucus vesiculosus and eelgrass Zostera marina vegetation as well as recruitment areas of the main predatory fish species, perch Perca fluviatilis and pikeperch Sander lucioperca. Specifically, we explored the effects of changing Secchi depth on species distributions under a set of scenarios based on the BSAP, using three fundamentally different modelling techniques: maximum entropy, generalized additive and random forest modelling. Improved Secchi depth (reduced eutrophication) was predicted to cause a substantial increase in the distribution of bladderwrack, while the distribution of eelgrass remained largely unaffected. For the fish, a large increase in perch recruitment areas was predicted and a concurrent decrease in recruitment areas of pikeperch. These changes are likely to have effects on biodiversity and ecosystem services. The three modelling methods exposed differences in the quantitative predictions for species with a weaker coupling to Secchi depth. Qualitatively, however, the results were consistent for all species. Synthesis and applications. We show how ecological effects of environmental policies can be evaluated in an explicit spatial context using species distribution modelling. The model-specific responses to changes in eutrophication status emphasize the importance of using ensemble modelling for exploring how species distributions may respond to alternative management regimes. A pronounced difference in response between species suggests that eutrophication mitigation will have consequences for ecosystem functioning, and thus ecosystem goods and services, by inducing changes in the simple food webs of the Baltic Sea. These model predictions form a basis for spatially explicit cost-benefit estimates under different scenarios, providing valuable information for both decision-makers and the wider society.
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13.
  • Boström, Anna-Karin, et al. (författare)
  • Effects of TGF-β signaling in Clear Cell Renal Cell Carcinoma cells.
  • 2013
  • Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 435:1, s. 126-133
  • Tidskriftsartikel (refereegranskat)abstract
    • Clear cell renal cell carcinoma (ccRCC) is by far the most common type of kidney cancer and is characterized by loss of the tumor suppressor gene von Hippel-Lindau (VHL). ccRCC patients with metastatic disease has poor prognosis and today's therapy is insufficient. The cytokine Transforming Growth Factor-β (TGF-β) has been extensively studied in tumor biology and is believed to serve a variety of functions in tumor progression. We have previously shown that inhibition of NOTCH signaling causes a reduced migratory and invasive capacity of ccRCC cells, at least partly by a cross-talk with the TGF-β pathway. In the present study we aimed to further clarify the role of TGF-β signaling in ccRCC. We investigated the effects of TGF-β pathway modulation and showed that TGF-β inhibition attenuates the invasive capacity of ccRCC cells. By performing expression profiling we obtained a gene signature of the TGF-β induced response in ccRCC cells. The expression analyses revealed an extensive overlap between the TGF-β response and genes regulated by the hypoxia inducible factor (HIF). The link between the hypoxic and the TGF-β pathways was further corroborated by functional experiments, which demonstrated that TGF-β pathway activity was attenuated upon reintroduction of functional VHL in ccRCC.
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14.
  • Boström, Anna-Karin, et al. (författare)
  • Sarcomatoid conversion of clear cell renal cell carcinoma in relation to epithelial-to-mesenchymal transition.
  • 2012
  • Ingår i: Human Pathology. - : Elsevier BV. - 1532-8392 .- 0046-8177. ; 43, s. 708-719
  • Tidskriftsartikel (refereegranskat)abstract
    • Approximately 8% of clear cell renal cell carcinoma cases contain regions of radically different morphology, demonstrating a mesenchymal appearance histologically resembling sarcomas. These biphasic neoplasms are called sarcomatoid clear cell renal cell carcinoma. Patients diagnosed with sarcomatoid clear cell renal cell carcinoma face a considerably worse prognosis due to an increased propensity for metastasis. In the present study we investigate whether the sarcomatoid conversion of clear cell renal cell carcinoma could be interpreted as linked to the process of epithelial-mesenchymal transition. Using 6 biphasic clear cell renal cell carcinoma cases we show that sarcomatoid clear cell renal cell carcinoma shares characteristic markers associated with loss of von Hippel-Lindau tumor suppressor with conventional clear cell renal cell carcinoma and also exhibits a markedly higher proliferative index. Furthermore the sarcomatoid elements demonstrate an enhanced expression of epithelial-mesenchymal transition related mesenchymal markers as compared with the clear cell renal cell carcinoma counterparts. We further selected a representative case, clinically demonstrating direct overgrowth of the sarcomatoid component into the liver and colon, for extended immunohistochemical characterization, resulting in a further set of positive and negative epithelial-mesenchymal transition markers as well as pronounced transforming growth factor β positivity, indicating that sarcomatoid clear cell renal cell carcinoma may be associated to epithelial-mesenchymal transition. Transforming growth factor β1 exposure of in vitro cultured primary clear cell renal cell carcinoma cells resulted in cells adopting a mesenchymal morphology similar to sarcomatoid clear cell renal cell carcinoma. Corresponding changes in RNA levels for key epithelial-mesenchymal transition markers were also seen. We therefore suggest that sarcomatoid clear cell renal cell carcinoma morphologically and immunohistochemically may represent a completed epithelial-mesenchymal transition and that transforming growth factor β1 could be an important driving force during the sarcomatoid transdifferentiation of clear cell renal cell carcinoma.
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15.
  • Boström, Curt-Åke, et al. (författare)
  • PRENOX-försök på sodapanna 70 vid Norrsundets bruk. En emissionsstudie av NOx vid tillsats av natriumnitrat
  • 1988
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Den nyligen utvecklade metoden (PRENOX) att förbehandla massa med kvävedioxid före blekning innebär bland annat att mängden kväve i procesströmmar blir högre. En av dessa är den lut som brännes i sodapannan. Försök har gjorts med att simulera vad som händer med kväveoxidemissionen från sodapannan när en fullskalig PRENOX-anläggning är i drift. Natriumnitrat har tillförts den lut som bränns i sodapannan motsvarande den mängd som skulle kunna överföras från PRENOX-processen. Resultaten visar på en kraftigt förhöjd kväveoxidemission vid tillsats av natriumnitrat. Emissionen av NOx vid normaldrift var ca 57 mg/MJ tillförd energi mot 94-109 mg/MJ vid varierande tillsats av natriumnitrat. Dikväveoxidemissionen (N2O) ökar också men halterna är mycket låga 5 ppm vid normaldrift respektive 13 ppm vid tillsats. Mindre än 10% av tillsatt kväve i form av nitrat emitteras som kväveoxider.
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17.
  • Boström, Gustav, et al. (författare)
  • Aspects in the Agile Toolbox
  • 2005
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • The introduction of agile methodologies promises faster time to market and a flexible, customer-driven software development process. The flexibility with regards to requirements can however also be a risk if new non-functional requirements need to be implemented late in a software development project. In this article we argue that aspect-oriented programming is a technique that can mitigate this risk by providing the means to deal with non-functional, crosscutting requirements. The suggested solution is illustrated by an example where new requirements in the form of quality of service demands on an existing service are implemented by using aspect orientated programming.
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18.
  • Boström, Gustaf, et al. (författare)
  • Different Inflammatory Signatures in Alzheimer's Disease and Frontotemporal Dementia Cerebrospinal Fluid
  • 2021
  • Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 81:2, s. 629-640
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Neuroinflammatory processes are common in neurodegenerative diseases such as Alzheimer's disease (AD) and frontotemporal dementia (FTD), but current knowledge is limited as to whether cerebrospinal fluid (CSF) levels of neuroinflammatory proteins are altered in these diseases.Objective: To identify and characterize neuroinflammatory signatures in CSF from patients with AD, mild cognitive impairment (MCI), and FTD.Methods: We used proximity extension assay and ANOVA to measure and compare levels of 92 inflammatory proteins in CSF from 42 patients with AD, 29 with MCI due to AD (MCI/AD), 22 with stable MCI, 42 with FTD, and 49 control subjects, correcting for age, gender, collection unit, and multiple testing.Results: Levels of matrix metalloproteinase-10 (MMP-10) were increased in AD, MCI/AD, and FTD compared with controls (AD: fold change [FC] = 1.32, 95% confidence interval [CI] 1.14-1.53, q = 0.018; MCI/AD: FC = 1.53, 95% CI 1.20-1.94, q = 0.045; and FTD: FC = 1.42, 95% CI 1.10-1.83, q = 0.020). MMP-10 and eleven additional proteins were increased in MCI/AD, compared with MCI (q < 0.05). In FTD, 36 proteins were decreased, while none was decreased in AD or MCI/AD, compared with controls (q < 0.05).Conclusion: In this cross-sectional multi-center study, we found distinct patterns of CSF inflammatory marker levels in FTD and in both early and established AD, suggesting differing neuroinflammatory processes in the two disorders.
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19.
  • Boström, Martin (författare)
  • Genomic mutational heterogeneity in cancer. lmproved models and tools for driver gene detection
  • 2022
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Cancer is a disease that is strongly related to evolution, as mutations that confer a benefit to individual cells face positive selection and eventually lead to tumorigenesis. As such, the search for genes that drive cancer development entails distinguishing positive selection from other sources of increased mutation rates, which requires detailed knowledge of how normal mutation rates vary across the genome. This thesis aims to improve that knowledge, as well as to provide novel methods of driver detection. In cutaneous melanoma, there are mutational hotspots in promoters that coincide with the sequence motif “TTCCG”. These hotspots could easily be misinterpreted as cancer drivers, but in the first paper of this thesis we show that they are in fact caused by increased UV damage susceptibility upon transcription factor binding, with some contribution from impaired DNA repair. In the second paper, we study how the UV mutational signature varies between different genomic regions and show that the main difference is caused by the level of cytosine methylation, owing to its effect on UV damage formation. We also improve the traditional trinucleotide mutational signature by incorporating longer patterns, capturing the effect of TTCCG-related promoter mutations. In the third paper, we demonstrate a novel method for driver detection that ignores recurrence signals, instead testing the likelihood of observing a particular combination of mutated tumours in a patient cohort. In addition to providing an orthogonal perspective on driver detection, this method is less sensitive to flaws in modelling some forms of mutational heterogeneity, such as the TTCCG hotspots. In summary, this thesis improves our knowledge of mutational heterogeneity in cancer, in addition to describing a new driver detection test that is less sensitive to situations where that knowledge falls short. Both of these advances contribute to the search for genes that drive cancer development.
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20.
  • Boström, Martin, et al. (författare)
  • Promoting sense of security in old-age care
  • 2013
  • Ingår i: Health. - 1949-4998 .- 1949-5005. ; 5:6A2, s. 56-63
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The concept of security is related to the experience of health but has ever so often been argued from a risk perspective rather than from a promotional perspective. The experience of older persons’ sense of security in private homes and in nursing homes seems to be missing when it comes to promote aging well throughout the life span. This study aimed to describe and analyze factors related to the sense of security of older persons receiving care in nursing homes in Sweden. Design and Methods: The study was based on a questionnaire from a total of 495 persons aged ≥ 65 in private homes (n = 350) or nursing homes (n = 145) in Sweden. Results: Secure relationships, sense of control, and perceived health were significantly related to the subjects’ sense of security. No significant relationships were found between sense of security and having a personal emergency response alarm. Implications: Experience of sense of security from the older person perspective differs depending on the context. To promote the sense of security within the care of older persons, methods on how to establish secure relations as well as the sense of control and knowledge need to be further tested, developed and analyzed together with older persons.
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21.
  • Boström, Martin, et al. (författare)
  • Somatic mutation distribution across tumour cohorts provides a signal for positive selection in cancer.
  • 2022
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer gene discovery is reliant on distinguishing driver mutations from a multitude of passenger mutations in tumour genomes. While driver genes may be revealed based on excess mutation recurrence or clustering, there is a need for orthogonal principles. Here, we take advantage of the fact that non-cancer genes, containing only passenger mutations under neutral selection, exhibit a likelihood of mutagenesis in a given tumour determined by the tumour's mutational signature and burden. This relationship can be disrupted by positive selection, leading to a difference in the distribution of mutated cases across a cohort for driver and passenger genes. We apply this principle to detect cancer drivers independently of recurrence in large pan-cancer cohorts, and show that our method (SEISMIC) performs comparably to traditional approaches and can provide resistance to known confounding mutational phenomena. Being based on a different principle, the approach provides a much-needed complement to existing methods for detecting signals of selection.
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22.
  • Boström, Petrus, et al. (författare)
  • Early postoperative pain as a marker of anastomotic leakage in colorectal cancer surgery
  • 2021
  • Ingår i: International Journal of Colorectal Disease. - : Springer-Verlag New York. - 0179-1958 .- 1432-1262. ; 36:9, s. 1955-1963
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Even though anastomotic leakage after colorectal surgery is a major clinical problem in need of a timely diagnosis, early indicators of leakage have been insufficiently studied. We therefore conducted a population-based observational study to determine whether the patient’s early postoperative pain is an independent marker of anastomotic leakage.Methods: By combining the Swedish Colorectal Cancer Registry and the Swedish Perioperative Registry, we retrieved prospectively collected data on 3084 patients who underwent anastomotic colorectal surgery for cancer in 2014–2017. Postoperative pain, measured with the numerical rating scale (NRS), was considered exposure, while anastomotic leakage and reoperation due to leakage were outcomes. We performed logistic regression to evaluate associations, estimating odds ratios (ORs) and 95% confidence intervals (CIs), while multiple imputation was used to handle missing data.Results: In total, 189 patients suffered from anastomotic leakage, of whom 121 patients also needed a reoperation due to leakage. Moderate or severe postoperative pain (NRS 4–10) was associated with an increased risk of anastomotic leakage (OR 1.69, 95% CI 1.21–2.38), as well as reoperation (OR 2.17, 95% CI 1.41–3.32). Severe pain (NRS 8–10) was more strongly related to leakage (OR 2.38, 95% CI 1.44–3.93). These associations were confirmed in multivariable analyses and when reoperation due to leakage was used as an outcome.Conclusion: In this population-based retrospective study on prospectively collected data, increased pain in the post-anaesthesia care unit is an independent marker of anastomotic leakage, possibly indicating a need for further diagnostic measures.
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23.
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24.
  • Boström, Petrus, et al. (författare)
  • High arterial ligation and risk of anastomotic leakage in anterior resection for rectal cancer in patients with increased cardiovascular risk
  • 2015
  • Ingår i: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 17:11, s. 1018-1027
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: Controversy still exists as to whether division of the inferior mesenteric artery close to the aorta influences the risk of anastomotic leakage after anterior resection for rectal cancer. This population-based study was carried out to evaluate the independent association between high arterial ligation and anastomotic leakage in patients with increased cardiovascular risk.Method: All 2673 cases of registered anterior resection for rectal cancer from 2007 to 2010 were identified from the Swedish Colorectal Cancer Registry and cross-referenced with the Prescribed Drugs Registry, rendering a cohort of all patients with increased cardiovascular risk. Operative charts and registered data were reviewed for 722 patients. The association between high tie and anastomotic leakage, as quantified by ORs and 95% CIs, was evaluated in a logistic regression model, with adjustment for confounding, including assessment of interaction.Results: Symptomatic anastomotic leakage occurred in 12.3% (41/334) of patients in the high tie group and in 10.6% (41/388) in the low tie group. The use of high tie was not independently associated with a higher risk of anastomotic leakage (OR = 1.05; 95% CI: 0.61–1.84). In a post-hoc analysis, patients with a history of manifest cardiovascular disease and American Society of Anesthesiologists (ASA) score III–IV seemed to be at greater risk (OR = 3.66; 95% CI: 1.04–12.85).Conclusion: In the present population-based, observational setting, high tie was not independently associated with an increased risk of symptomatic anastomotic leakage after anterior resection for rectal cancer. However, this conclusion may not hold for patients with severe cardiovascular disease.
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25.
  • Boström, Petrus, et al. (författare)
  • Oncological Impact of High Vascular Tie After Surgery for Rectal Cancer : A Nationwide Cohort Study
  • 2021
  • Ingår i: Annals of Surgery. - : Wolters Kluwer. - 0003-4932 .- 1528-1140. ; 274:3, s. e236-e244
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The purpose of this study was to investigate the impact of tie level on oncological outcomes in rectal cancer surgery.Summary background data: Theoretically, a high tie of the inferior mesenteric artery could facilitate removal of apical node metastases and improve tumor staging accuracy. However, no appropriately sized randomized controlled trial exists and results from observational studies are not consistent.Methods: All stage I–III rectal cancer patients who underwent abdominal surgery with curative intention in 2007 to 2014 were identified and followed, using the Swedish Colorectal Cancer Registry. Primary outcome was cancer-specific survival, whereas overall and relative survival, locoregional and distant recurrence, and lymph node harvest were secondary outcomes, with high tie as exposure. We used propensity score matching to emulate a randomized controlled trial, and then performed Cox regression analyses to estimate hazard ratios (HRs) with confidence intervals (CIs).Results: Some 8287 patients remained for analysis, of which 37% had high tie surgery. After propensity score matching, the 5-year cancer-specific survival rate was overall 86% and we found no association between the level of tie and cancer-specific (HR 0.92, 95% CI 0.79–1.07) or overall (HR 0.98, 95% CI 0.89–1.08) survival, nor to locoregional (HR 0.85, 95% CI 0.59–1.23) or distant (HR 1.01, 95% CI 0.88–1.15) recurrence, nor to relative survival (HR 1.05, 95% CI 0.85–1.28). Stratification and sensitivity analyses were similarly insignificant, after adjustment for confounding. Total lymph node harvest was, however, increased after high tie surgery (P < 0.01), but no differences were seen regarding positive nodes (P = 0.72).Conclusion: In this nationwide cohort study, the level of tie did not influence any patient-oriented oncological outcome, neither overall nor in node-positive patients. This would allow the patient's anatomical configuration and the surgeon's preferences to determine the level of tie.
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26.
  • Boström, Petrus, et al. (författare)
  • Population‐based cohort study of the impact on postoperative mortality of anastomotic leakage after anterior resection for rectal cancer
  • 2019
  • Ingår i: BJS Open. - : John Wiley & Sons. - 2474-9842. ; 3:1, s. 106-111
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Anastomotic leakage following anterior resection for rectal cancer may result in death. The aim of this study was to yield an updated, population‐based estimate of postoperative mortality and evaluate possible interacting factors.Methods: This was a retrospective national cohort study of patients who underwent anterior resection between 2007 and 2016. Data were retrieved from a prospectively developed database. Anastomotic leakage constituted exposure, whereas outcome was defined as death within 90 days of surgery. Logistic regression analyses, using directed acyclic graphs to evaluate possible confounders, were performed, including interaction analyses.Results: Of 6948 patients, 693 (10·0 per cent) experienced anastomotic leakage and 294 (4·2 per cent) underwent reintervention due to leakage. The mortality rate was 1·5 per cent in patients without leakage and 3·9 per cent in those with leakage. In multivariable analysis, leakage was associated with increased mortality only when a reintervention was performed (odds ratio (OR) 5·57, 95 per cent c.i. 3·29 to 9·44). Leaks not necessitating reintervention did not result in increased mortality (OR 0·70, 0·25 to 1·96). There was evidence of interaction between leakage and age on a multiplicative scale (P = 0·007), leading to a substantial mortality increase in elderly patients with leakage.Conclusion: Anastomotic leakage, in particular severe leakage, led to a significant increase in 90‐day mortality, with a more pronounced risk of death in the elderly.
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27.
  • Boström, Petrus, 1981- (författare)
  • Rectal cancer : the influence of surgical technique on morbidity, mortality and survival
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Surgery is still the most common treatment for rectal cancer, being the most effective and cost-efficient modality. However, it is not without risk, nor without controversies. This dissertation is an evaluation of the pros and cons of high versus low ligation, whether anastomotic leakage is still prevalent after surgery and associated with increased mortality, and if the risk of leakage could be predicted by early postoperative pain.Study I relied upon case records and registry data to evaluate the causal effect of high ligation on the risk of anastomotic leakage after anterior resection in 722 patients with increased cardiovascular risk. When controlling for confounders, no association was found overall. However, an increased risk for leakage after high ligation was noted for the few patients who suffered from both manifest cardiovascular disease and ASA III–IV (OR 3.66, 95% CI 1.04–12.85) and when performed in a low volume hospital (OR 3.89, 95% 1.58– 9.59). Study II estimated the risk of anastomotic leakage and death after anterior resection today. Among the 6,948 patients, 10.0% suffered from leakage, in whom mortality was 3.9% versus 1.5% for patients without a leak. However, this increased mortality was driven entirely by patients in need of reintervention, who exhibited a 7.5% 90-day mortality, resulting in a significantly increased risk (OR 5.57, 95% CI 3.29–9.44), when controlling for confounders, while conservatively treated leakage was not associated with mortality. Age acted as an effect modifier, as postoperative mortality after leakage was increased in the elderly.Study III returned to high versus low ligation as exposure, to evaluate the long-term oncological benefits of either ligation level, with cancer-specific survival as primary outcome. The final cohort of 8,287 patients who underwent abdominal surgery for rectal cancer, with curative intent, was followed for a minimum of 3.5 years. After propensity score matching, no significant differences were found between high and low ligation for any survival or recurrence analysis, nor in the unmatched cohort, when controlling for confounders. A statistically significant difference was found for lymph node harvest, which was slightly greater in high ligation (17.7 vs 16.7 lymph nodes). Finally, study IV estimated the independent predictive ability of postoperative pain, measured on the numerical rating scale (NRS), on the risk for anastomotic leakage after colorectal cancer surgery. It seems as if increased early pain is an independent predictor for leakage (OR 1.73, 95% CI 1.22– 2.46 for NRS 4–10), with increasing risk of leakage with increasing pain (OR 2.42 for NRS 8–10). In addition, increased pain was more strongly associated with more severe leakage.In summary, the level of ligation seems to be of importance only in a select group of high-risk patients, but offers no obvious oncological advantages. The high incidence and serious sequelae of anastomotic leakage makes it one of the most important clinical challenges in colorectal surgery, with especially detrimental effects in the elderly. A better understanding of the causal pathways behind leakage, and the overall harm and benefit of ligation level and diverting stomas, might allow a better selection of treatment for future patients.
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28.
  • Braun, Madelen, et al. (författare)
  • Levels of inflammatory cytokines MCP-1, CCL4, and PD-L1 in CSF differentiate idiopathic normal pressure hydrocephalus from neurodegenerative diseases
  • 2023
  • Ingår i: Fluids and Barriers of the CNS. - : BioMed Central (BMC). - 2045-8118. ; 20
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Neuroinflammatory processes have been suggested to play a role in the pathophysiology of neurodegenerative diseases and post-hemorrhagic hydrocephalus, but have rarely been investigated in patients with idiopathic normal pressure hydrocephalus (iNPH). The aim of this study was to investigate whether levels of inflammatory proteins in CSF are different in iNPH compared to healthy controls and patients with selected neurodegenerative disorders, and whether any of these markers can aid in the differential diagnosis of iNPH.Methods: Lumbar CSF was collected from 172 patients from a single center and represented iNPH (n = 74), Alzheimer's disease (AD) (n = 21), mild cognitive impairment (MCI) due to AD (n = 21), stable MCI (n = 22), frontotemporal dementia (n = 13), and healthy controls (HC) (n = 21). Levels of 92 inflammatory proteins were analyzed using a proximity extension assay. As a first step, differences between iNPH and HC were investigated, and proteins that differed between iNPH and HC were then compared with those from the other groups. The linear regressions were adjusted for age, sex, and plate number.Results: Three proteins showed higher (MCP-1, p = 0.0013; CCL4, p = 0.0008; CCL11, p = 0.0022) and one lower (PD-L1, p = 0.0051) levels in patients with iNPH compared to HC. MCP-1 was then found to be higher in iNPH than in all other groups. CCL4 was higher in iNPH than in all other groups, except in MCI due to AD. PD-L1 was lower in iNPH compared to all other groups, except in stable MCI. Levels of CCL11 did not differ between iNPH and the differential diagnoses. In a model based on the four proteins mentioned above, the mean area under the receiver operating characteristic curve used to discriminate between iNPH and the other disorders was 0.91.Conclusions: The inflammatory cytokines MCP-1 and CCL4 are present at higher-and PD-L1 at lower-levels in iNPH than in the other investigated diagnoses. These three selected cytokines may have diagnostic potential in the work-up of patients with iNPH.
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29.
  • Cedervall, Johan, et al. (författare)
  • Phase stability and structural transitions in compositionally complex LnMO 3 perovskites
  • 2021
  • Ingår i: Journal of Solid State Chemistry. - : Elsevier BV. - 0022-4596 .- 1095-726X. ; 300
  • Tidskriftsartikel (refereegranskat)abstract
    • Entropy stabilised materials have possibilities for tailoring functionalities to overcome challenges in materials science. The concept of configurational entropy can also be applied to metal oxides, but it is unclear whether these could be considered as solid solutions in the case of perovskite-structured oxides and if the configurational entropy plays a stabilising role. In this study, compositionally complex perovskite oxides, LnMO3 (Ln ​= ​La, Nd, Sm, Ca and Sr, M ​= ​Ti, Cr, Mn, Fe, Co, Ni, and Cu), are investigated for their phase stability and magnetic behaviour. Phase-pure samples were synthesised, and the room temperature structures were found to crystallise in either Pnma or R3¯c space groups, depending on the composition and the resulting tolerance factor, while the structural transition temperatures correlate with the pseudo cubic unit cell volume. The techniques used included diffraction with X-rays and neutrons, both ex- and in-situ, X-ray photoelectron spectroscopy, magnetometry as well as electron microscopy. Neutron diffraction studies on one sample reveal that no oxygen vacancies are found in the structure and that the magnetic properties are ferrimagnetic-like with magnetic moments mainly coupled antiferromagnetically along the crystallographic c-direction. X-ray photoelectron spectroscopy gave indications of the oxidation states of the constituting ions where several mixed oxidation states are observed in these valence-compensated perovskites.
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30.
  • Dorn, Michael, et al. (författare)
  • Logistik 2015-2020 : En framtidsstudie om logistiksimulering: FoT 19 logistik
  • 2006
  • Rapport (populärvet., debatt m.m.)abstract
    • In this study an attempt is made to put forward ideas about how logistic support to the Armed Forces of the future will be dealt with, based on a sur­vey of current social, military and economic trends. The aim is to identify those logistic matters, which it would be relevant to simulate within a 10 to 15-year period. The study has been carried out with the aid of NATO logis­tic doctrine and a qualitative method, which is closely comparable to idea analysis.One of the findings of the study is that the Swedish Armed Forces could be one module, amongst many (e.g. police, rescue services and aid organisa­tions), tailor-made for a particular peace support operation, led by a national HQ. It can also be taken that civilian actors, to a much greater extent than today, will be part of the logistics system and that this system could resem­ble the “IKEA model”, i.e. small stores of equipment that can quickly be put together to meet different needs. All this will require a greater degree of specialisation and coordination, both in Sweden and in other countries.Those logistic matters identified as being relevant for simulation within a 10 to15-year period have been brought together in a summary. The main con­clusion of the study indicates that it is of the utmost importance to simulate a model of the complete logistic chain. In the meantime, in order to carry out the simulation, the collection of experiences and lessons learned must be systemised and recorded. If this does not happen, it is doubtful that the simulation can be used as a system to support decision-making.
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31.
  • Elliott, Kerryn, et al. (författare)
  • Base-resolution UV footprinting by sequencing reveals distinctive damage signatures for DNA-binding proteins
  • 2023
  • Ingår i: Nature Communications. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Decades ago, it was shown that proteins binding to DNA can quantitatively alter the formation of DNA damage by UV light. This established the principle of UV footprinting for non-intrusive study of protein-DNA contacts in living cells, albeit at limited scale and precision. Here, we perform deep base-resolution quantification of the principal UV damage lesion, the cyclobutane pyrimidine dimer (CPD), at select human promoter regions using targeted CPD sequencing. Several transcription factors exhibited distinctive and repeatable damage signatures indicative of site occupancy, involving strong (up to 17-fold) position-specific elevations and reductions in CPD formation frequency relative to naked DNA. Positive damage modulation at some ETS transcription factor binding sites coincided at base level with melanoma somatic mutation hotspots. Our work provides proof of concept for the study of protein-DNA interactions at individual loci using light and sequencing, and reveals widespread and potent modulation of UV damage in regulatory regions. Proteins binding to DNA can locally alter DNA damage formation by UV light. Here, Elliott et al. generate high-resolution quantitative UV damage profiles for genomic regions of interest, revealing distinctive damage signatures for specific proteins and elevated UV damage at melanoma mutation hotspots.
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32.
  • Elliott, Kerryn, et al. (författare)
  • Elevated pyrimidine dimer formation at distinct genomic bases underlies promoter mutation hotspots in UV-exposed cancers.
  • 2018
  • Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 14:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Sequencing of whole cancer genomes has revealed an abundance of recurrent mutations in gene-regulatory promoter regions, in particular in melanoma where strong mutation hotspots are observed adjacent to ETS-family transcription factor (TF) binding sites. While sometimes interpreted as functional driver events, these mutations are commonly believed to be due to locally inhibited DNA repair. Here, we first show that low-dose UV light induces mutations preferably at a known ETS promoter hotspot in cultured cells even in the absence of global or transcription-coupled nucleotide excision repair (NER). Further, by genome-wide mapping of cyclobutane pyrimidine dimers (CPDs) shortly after UV exposure and thus before DNA repair, we find that ETS-related mutation hotspots exhibit strong increases in CPD formation efficacy in a manner consistent with tumor mutation data at the single-base level. Analysis of a large whole genome cohort illustrates the widespread contribution of this effect to recurrent mutations in melanoma. While inhibited NER underlies a general increase in somatic mutation burden in regulatory elements including ETS sites, our data supports that elevated DNA damage formation at specific genomic bases is at the core of the prominent promoter mutation hotspots seen in skin cancers, thus explaining a key phenomenon in whole-genome cancer analyses.
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33.
  • Flank, Peter, et al. (författare)
  • Self-reported physical activity and risk markers for cardiovascular disease after spinal cord injury
  • 2014
  • Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081. ; 46:9, s. 886-890
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective:To examine whether self-reported physical activity of a moderate/vigorous intensity influences risk markers for cardiovascular disease in persons with paraplegia due to spinal cord injury.Design:Descriptive, cross-sectional study.Subjects:A total of 134 wheelchair-dependent individuals (103 men, 31 women) with chronic (>= 1 year) post-traumatic spinal cord injury with paraplegia.Methods:Cardiovascular disease markers (hypertension, blood glucose and a blood lipid panel) were analysed and related to physical activity.Results:One out of 5 persons reported undertaking physical activity >= 30 min/day. Persons who were physically active >= 30 min/day were significantly younger than inactive persons. Systolic and diastolic blood pressures were lower in the physically active group. When adjusting for age, the association between systolic blood pressure and physical activity disappeared. Physical activity >= 30 min/day had a tendency to positively influence body mass index and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio. Men had significantly higher systolic and diastolic blood pressures than women, lower high-density lipoprotein cholesterol, higher low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio and higher triglycerides. No other significant differences between men and women were found.Conclusion:Self-reported physical activity >= 30 min/day in persons with spinal cord injury positively influenced diastolic blood pressure. No other reductions in cardiovascular disease risk markers were seen after controlling for age. These results indicate a positive effect of physical activity, but it cannot be concluded that recommendations about physical activity in cardiovascular disease prevention for the general population apply to wheelchair-dependent persons with spinal cord injury.
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34.
  • Henkel, Martin, et al. (författare)
  • Moving from internal to external services using aspects
  • 2006
  • Ingår i: Interoperability of Enterprise Software and Applications. - London : Springer. - 1846281512 ; , s. 301-310
  • Konferensbidrag (refereegranskat)abstract
    • Service oriented computing and web service technology provide the means to structure an organisation’s internal IT resources into a highly integrated network of services. In e-business and business process integration the internal services are interconnected with other, external organisations’ resources to form virtual organisations. This move from using services internally to external use puts new non-functional requirements on the service implementation. Without any supporting technologies, meeting these new requirements can result in re-writing or changing a large part of the service implementation. In this paper we argue that aspect oriented programming is an important technique that can be used to facilitate the implementation of the new requirements that arises when moving from internal to external services. The suggested solution is illustrated by an example where quality of service metrics is implemented by using aspect oriented programming.
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35.
  • Henkel, Martin, et al. (författare)
  • Moving from Internal to External Services using Aspects
  • 2005
  • Ingår i: Proceedings of the First International Conference on Interoperability of Enterprise Software and Applications (INTEROP-ESA'05), Geneva, Switzerland.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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36.
  • Henning, Martin, 1978, et al. (författare)
  • Den regionala arbetsdelningens anatomi – Perspektiv från yrken, branscher och funktioner
  • 2020
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Regional specialisering är en utmärkande egenskap för ekonomins geografiska fördelning. Att regioner specialiserar sig betyder också att de binds samman och blir delar av en geografisk ekonomisk arbetsdelning. Det innebär att varje regional ekonomi har en distinkt roll i produktionssystemet av varor och tjänster, vilket också skapar beroendeförhållanden mellan regioner, inte minst i dagens rumsligt integrerade ekonomi. Över tid har det vuxit fram en stor litteratur som förklarar varför sådan regional specialisering uppstår, och hur det går till. Men många är idag eniga om att beskrivning på traditionell branschnivå ger en allt för grov bild av regioners specialisering. Denna rapport utforskar idén om att regional specialisering idag är kopplad snarare till olika funktioner i produktionslogiken av varor och tjänster, än till specifika branscher. I rapporten betonar vi att det inte finns ett sätt att beskriva en regional specialisering. Det finns olika metoder med olika styrkor och svagheter. Vilken som är lämpligast att använda beror på ändamålet med analysen. Det funktionella perspektiv som vi beskriver här har dock många fördelar, såväl teoretiskt som empiriskt. Bland annat ger det den bästa beskrivningen av regional specialisering, bland de olika alternativ som vi undersöker. Vår funktionella kategorisering ger alltså en distinkt beskrivning av regionernas specialiseringsprofil. För Västra Götalands del ser man till exempel den regionala specialiseringen inom värdekedjelogiken till logistik, tillverkning, service och inköp, men där Göteborg är högre specialiserad inom teknikutveckling.
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37.
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38.
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39.
  • Henning, Martin, et al. (författare)
  • Strukturomvandling och automatisering : Konsekvenser på regionala arbetsmarknader
  • 2016
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Denna rapport handlar om den regionala ekonomiska strukturomvandling som ägt rum i Västra Götaland och Skåne sedan 1990-talet, och om den fortsatta automatiseringens framtida regionala avtryck på svenska lokala arbetsmarknader. Rapporten beskriver och gör en sammanfattning av den debatt som på senare år varit intensiv om automatiseringens framtida effekter på arbetsmarknaden. Med utgångspunkt i den internationella litteraturen, förs en diskussion om automatiseringens drivkrafter, hinder ocheffekter.Det finns ingen direkt orsakskedja mellan teknisk utveckling av nya automatiseringslösningar, och effekter på arbetsmarknaden. Många hinder och fördröjningseffekter finns också, som påverkar när och hur nya automatiseringslösningar får genomslag. Dessa kan exempelvis vara av institutionell, social, legal eller etisk art. Vi har mycket att lära av historien. Många faktorer känner vi igen från tidigare teknikskiften.
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40.
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41.
  • Ibitokou, Samad A., et al. (författare)
  • Submicroscopic Infections with Plasmodium falciparum during Pregnancy and Their Association with Circulating Cytokine, Chemokine, and Cellular Profiles
  • 2014
  • Ingår i: Clinical and Vaccine Immunology. - 1556-6811 .- 1556-679X. ; 21:6, s. 859-866
  • Tidskriftsartikel (refereegranskat)abstract
    • The immunological consequences of pregnancy-associated malaria (PAM) due to Plasmodium falciparum have been extensively investigated in cross-sectional studies conducted at delivery, but there have been very few longitudinal studies of changes due to PAM during pregnancy. We conducted a prospective study in Benin to investigate the changes associated with PAM in groups of 131 and 111 women at inclusion in the second trimester and at delivery, respectively. Infected women were identified by standard microscopic examinations of blood smears and by quantitative PCR (qPCR) assays and were matched to uninfected control women by age, gestational age, and gravidity. We quantified plasma levels of a panel of soluble immunological mediators and other mediators, as well as the frequencies of peripheral blood mononuclear cell types. Comparisons of these variables in infected and uninfected women used multivariate analyses, and we also assessed the predictive value of variables measured at inclusion for pregnancy outcomes at delivery. In multivariate analyses, peripheral plasma interleukin 10 (IL-10) and gamma interferon-inducible protein 10 (IP-10) levels were associated with PAM at inclusion and at delivery, while higher IL-10 levels distinguished qPCR-detectable submicroscopic infections at inclusion but not at delivery. Maternal anemia at delivery was associated with markers of proinflammatory (increased frequency of monocytes) and anti-inflammatory (increased IL-10 levels and increased activation of regulatory T cells) activity measured at inclusion. Elevated concentrations of IL-10 are associated with the majority of P. falciparum infections during pregnancy, but this marker alone does not identify all submicroscopic infections. Reliably identifying such occult infections will require more sensitive and specific methods.
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42.
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43.
  • Ingvar, Martin, et al. (författare)
  • En bättre skolstart för alla: bedömning och betyg för progression i lärandet
  • 2014
  • Rapport (populärvet., debatt m.m.)abstract
    • Obligatoriska bedömningsstödGrundläggande färdigheter i svenska och matematik är en förutsättning för att klara skolan. Det finns därför anledning att fokusera insatserna av bedömningar och bedömningsstöd under de tidigare årskurserna i grundskolan. Promemorians förslag att införa krav på användning av bedömningsstöd i läs och skrivutveckling i årskurs 1 avspeglar vikten av att alla tidigt ska nå god förmåga i läsning och skrivning. En bred användning av bedömningsstöd kan aktivt bidra till att tidigt identifiera behov och ge möjlighet att sätta in stödåtgärder för de elever som inte bedöms nå kunskapskraven i årskurs 3. Kravet på användning av bedömningsstöd i matematik avspeglar behovet av att förbättra resultaten i matematik genom att en tydlig progression kan dokumenteras för varje elev.Att tillämpa nationellt fastställda bedömningsstöd i skolan främjar likvärdighet i lärarnas bedömningar av elevernas kunskapsutveckling. Nationellt fastställda bedömningsstöd främjar även det kollegiala arbetet genom att gemensamma begrepp och mallar används i bedömningen vilket i sin tur bör kunna ge en högre kvalitet i bedömningarna.Kunskapskrav i läsförståelse i årskurs 1Ett införande av kunskapskrav i läsförståelse i årkurs 1 motiveras av att förmågan att läsa och skriva är starkt förknippad med att lyckas i skolan och därmed även möjligheten att senare etablera sig socialt och på arbetsmarknaden. Varje barn som inte tidigt når tillräcklig automaticitet i läsningen riskerar att under den fortsatta skolgången få kämpa för att hänga med och klara de kunskapskrav som minst ska uppnås i alla ämnen. En löpande uppföljning av i vilken uträckning eleverna når kunskapskravet i läsförståelse kan visa om undervisningen motsvarar kraven enligt skollagen. Införandet av ett sådant kunskapskrav aktualiserar samtidigt skollagens krav på åtgärder på skol, klassrums och elevnivå i de fall elever riskerar att inte nå de kunskapskrav som minst ska uppnås. Förslaget till kunskapskrav i läsförståelse bör konstrueras i samklang med det obligatoriska bedömningsstödet i läs och skrivutveckling liksom kunskapskravet för årskurs 3 i svenska och svenska som andraspråk.Betyg från årskurs 4Betyg föreslås införas i årskurs 4 och 5 i grundskolan och motsvarande skolformer. Detta ska ses som ytterligare en del i det som behövs för att utveckla bedömningskulturen i skolan. Förslaget innebär att svenska elever kommer att få betyg vid samma ålder som i de flesta andra OECDländer. Betyg ger en tydligare kommunikation mellan skola, elev och föräldrar. Ett tidigt införande av betyg ger en tydlighet av målen för utbildningen för eleverna vilket är av särskild betydelse för barn från miljöer med begränsad utbildningstradition. Effekten av tidigare betyg fokuserar skolans process kring vad som ska uppnås och medför att varje lärare blir tvungen förtydliga sin bild av utbildningens resultat. När betyg införs i årskurs 4 och 5 finns inte längre behovet av skriftliga individuella utvecklingsplaner i dessa årskurser.
  •  
44.
  • Karlson, L., et al. (författare)
  • Influence of added surfactant on particle flocculation in waterborne polymer-particle systems
  • 2008
  • Ingår i: Journal of Coatings Technology and Research. - : Springer Science and Business Media LLC. - 1547-0091 .- 1935-3804. ; 5:4, s. 447-454
  • Tidskriftsartikel (refereegranskat)abstract
    • Polymer-particle interactions can cause particle flocculation and phase separation problems in waterborne coatings. The problems can be the result of interactions that are either too weak or too strong. It is known by empirical work that addition of surfactants can minimize these problems. In this study, the authors have investigated how different types of surfactants influence the polymer-particle interactions. Both hydrophobic and hydrophilic particles were included in the study, and nonionic, anionic, and cationic surfactants were used. A simple model is suggested that can be used to predict the surfactant concentration needed to stabilize the system. The model considers the cmc (critical micelle concentration) of the surfactant, the adsorption to the polymer, and the adsorption to the particles.
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45.
  • Karlsson, Dennis, et al. (författare)
  • Binder jetting of the AlCoCrFeNi alloy
  • 2019
  • Ingår i: Additive Manufacturing. - : Elsevier. - 2214-8604 .- 2214-7810. ; 27, s. 72-79
  • Tidskriftsartikel (refereegranskat)abstract
    • High density components of an AlCoCrFeNi alloy, often described as a high-entropy alloy, were manufactured by binder jetting followed by sintering. Thermodynamic calculations using the CALPHAD approach show that the high-entropy alloy is only stable as a single phase in a narrow temperature range below the melting point. At all other temperatures, the alloy will form a mixture of phases, including a sigma phase, which can strongly influence the mechanical properties. The phase stabilities in built AlCoCrFeNi components were investigated by comparing the as-sintered samples with the post-sintering annealed samples at temperatures between 900 °C and 1300 °C. The as-sintered material shows a dominant B2/bcc structure with additional fcc phase in the grain boundaries and sigma phase precipitating in the grain interior. Annealing experiments between 1000 °C and 1100 °C inhibit the sigma phase and only a B2/bcc phase with a fcc phase is observed. Increasing the temperature further suppresses the fcc phase in favor for the B2/bcc phases. The mechanical properties are, as expected, dependent on the annealing temperature, with the higher annealing temperature giving an increase in yield strength from 1203 MPa to 1461 MPa and fracture strength from 1996 MPa to 2272 MPa. This can be explained by a hierarchical microstructure with nano-sized precipitates at higher annealing temperatures. The results enlighten the importance of microstructure control, which can be utilized in order to tune the mechanical properties of these alloys. Furthermore, an excellent oxidation resistance was observed with oxide layers with a thickness of less than 5 μm after 20 h annealing at 1200 °C, which would be of great importance for industrial applications.
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46.
  • Larsson, Martin, et al. (författare)
  • Kemiska bekämpningsmedel i grundvatten 1986–2014 : Sammanställning av resultat och trender i Sverige  under tre decennier, samt internationella utblickar
  • 2014
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Syftet med denna rapport är att sammanställa kunskapsläget när det gäller förekomst av kemiska bekämpningsmedel i svenskt grundvatten. Underlaget utgörs av tillgängliga data från perioden 1986–2014. I rapporten ingår också en kortare genomgång av förändringar inom jordbruket i Sverige och dess användning av bekämpningsmedel, samt en litteraturgenomgång som sammanfattar resultat från undersökningar och det allmänna kunskapsläget om bekämpningsmedel i Danmark, Norge och Storbritannien. För att sammanställa data om bekämpningsmedel i grundvatten har resultat samlats in från undersökningar utförda av många olika instanser; vattenverk, länsstyrelser, kommuner, vattenvårdsförbund och privatpersoner. Extra ansträngningar har gjorts för att samla in data för Skåne som är den mest jordbruks- och bekämpningsmedelsintensiva regionen i Sverige. Resultaten visar att ett eller flera bekämpningsmedel återfanns i 36 % av alla prover tagna i grundvatten under hela perioden. Den vanligast detekterade substansen var BAM (2,6-diklorbensamid) som påvisades i 33 % av de undersökta proverna, följt av atrazin tillsammans med sina nedbrytningsprodukter (5–9 %). BAM är en nedbrytningsprodukt till diklobenil som tillsammans med atrazin hade stor användning som totalbekämpningsmedel mot oönskad vegetation. Tillsammans ingick de bland annat i den tidigare mycket välkända produkten Totex Strö som hade en omfattande användning inom en rad olika sektorer och områden, så som parkförvaltning, banvallar, vägarbeten, tomtmark, industriområden. Både diklobenil och atrazin är förbjudna sedan 1989–1990, men är alltså fortfarande de substanser som förekommer oftast i svenskt grundvatten. Av de växtskyddsmedel som fortfarande är godkända för användning inom jordbruket var det ogräsmedlet bentazon som återfinns oftast i grundvattenprover under den senaste 10-årsperioden (ca 3 %). Övriga i dag godkända växtskyddsmedel har däremot återfunnits mera sporadiskt i olika grundvattenundersökningar under senare år. Sammanfattningsvis visar resultaten att fynden i grundvatten huvudsakligen domineras av substanser som inte längre är tillåtna att användas och av substanser vars främsta användning har varit utanför jordbruket. Ett resultat som kan tillskrivas dels att registreringsprocessen i allt större utsträckning har kommit att beakta miljöaspekterna vid godkännandet och dels en förbättrad hantering av växtskyddsmedel genom utbildning och rådgivning till lantbrukare som minskat risken för punktutsläpp under åren.Gränsvärdet för tjänligt dricksvatten när det gäller bekämpningsmedel är i) att summahalten av alla undersökta bekämpningsmedel inte får överskrida 0,5 µg/l, ii) att halten av ett enskilt bekämpningsmedel inte får överskrida 0,1 µg/l. Samma halter gäller även som riktvärden för grundvattenkvalitet. Resultaten av denna sammanställning visar att summahalter som överskrider 0,5 µg/l har minskat från ca 15 % perioden 1987–1994, till strax under 5 % perioden 2005– 2014 i grundvattenprover, exklusive vattenverk. Motsvarande jämförelse för råvattenprover från vattenverk visar en minskning från ca 5 % till ca 2 %. Andelen prover som har minst en substans i en halt över 0,1 µg/l har varierat under åren med som mest ca 35 % år 2000 i grundvattenprover, exklusive vattenverk, vartefter andelen överskridanden har minskat till <10 % under senare år. Även prover från vattenverk visar samma trend med minskande halter över 0,1 µg/l. En sammanställning av halterna av bekämpningsmedel i brunnar av olika djup indikerar att grunda brunnar har en högre fyndfrekvens av halter över  0,1 µg/l än de djupare brunnarna. I resultaten ingår det dock få brunnar från de djupare intervallen. En jämförelse av bekämpningsmedelsförekomst i brunnar som är borrade respektive grävda visar att de flesta substanserna har en högre fyndfrekvens i halter över 0,1 µg/l i grävda än i borrade brunnar. För atrazin, inklusive dess nedbrytningsprodukter, är det en betydande skillnad mellan grävda och  borrade brunnar, där den större andelen fynd i grävda brunnar sannolikt beror på att atrazin har använts flitigt för att bekämpa ogräs på gårdsplaner som ofta ligger i nära anslutning till gårdens privata dricksvattenbrunn.  Eftersom många får sin dricksvattenförsörjning från enskilda brunnar och dessa kan vara extra känsliga för föroreningar, undersöktes bekämpningsmedelsförekomsten i dessa för sig. I enskilda brunnar låg summahalten av bekämpningsmedel över 0,5 µg/l i ca 10 % av alla prover under hela tidsperioden, men med en minskande trend mot slutet av perioden. BAM är även här den mest frekvent påträffade substansen följt av atrazin och dess nedbrytningsprodukter som har en högre fyndfrekvens i enskilda brunnar jämfört med råvatten till vattenverk. Cirka 10 % av vattenproverna från enskilda brunnar har minst en substans som överskrider 0,1 µg/l.  Halterna i grundvattnet minskar generellt sett och de historiskt höga halterna av BAM, atrazin och dess nedbrytningsprodukter och bentazon är alla på väg ner. Diklobenil (med nedbrytningsprodukten BAM) och atrazin är förbjudna sedan början av 1990-talet och effekten börjar synas nu. Bentazons användningsområde har begränsats och faktorer som bättre utbildning och hantering av bekämpningsmedel under senare årtionden har sannolikt bidragit till de minskande halterna. För att kunna ge en bra bild av grundvattenkvalitén i Sverige framöver vore det önskvärt att insamling av data förbättras när det gäller till exempel yttäckning och vilka substanser som analyseras.  
  •  
47.
  • Lindberg, Markus, 1989, et al. (författare)
  • Intragenomic variability and extended sequence patterns in the mutational signature of ultraviolet light
  • 2019
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 116:41, s. 20411-20417
  • Tidskriftsartikel (refereegranskat)abstract
    • Mutational signatures can reveal properties of underlying mutational processes and are important when assessing signals of selection in cancer. Here, we describe the sequence characteristics of mutations induced by ultraviolet (UV) light, a major mutagen in several human cancers, in terms of extended (longer than trinucleotide) patterns as well as variability of the signature across chromatin states. Promoter regions display a distinct UV signature with reduced TCG > TTG transitions, and genome-wide mapping of UVB-induced DNA photoproducts (pyrimidine dimers) showed that this may be explained by decreased damage formation at hypomethylated promoter CpG sites. Further, an extended signature model encompassing additional information from longer contextual patterns improves modeling of UV mutations, which may enhance discrimination between drivers and passenger events. Our study presents a refined picture of the UV signature and underscores that the characteristics of a single mutational process may vary across the genome.
  •  
48.
  • Lindgren, David, et al. (författare)
  • Isolation and characterization of progenitor-like cells from human renal proximal tubules.
  • 2011
  • Ingår i: American Journal of Pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 178:2, s. 828-837
  • Tidskriftsartikel (refereegranskat)abstract
    • The tubules of the kidney display a remarkable capacity for self-renewal on damage. Whether this regeneration is mediated by dedifferentiating surviving cells or, as recently suggested, by stem cells has not been unequivocally settled. Herein, we demonstrate that aldehyde dehydrogenase (ALDH) activity may be used for isolation of cells with progenitor characteristics from adult human renal cortical tissue. Gene expression profiling of the isolated ALDH(high) and ALDH(low) cell fractions followed by immunohistochemical interrogation of renal tissues enabled us to delineate a tentative progenitor cell population scattered through the proximal tubules (PTs). These cells expressed CD24 and CD133, previously described markers for renal progenitors of Bowman's capsule. Furthermore, we show that the PT cells, and the glomerular progenitors, are positive for KRT7, KRT19, BCL2, and vimentin. In addition, tubular epithelium regenerating on acute tubular necrosis displayed long stretches of CD133(+)/VIM(+) cells, further substantiating that these cells may represent a progenitor cell population. Furthermore, a potential association of these progenitor cells with papillary renal cell carcinoma was discovered. Taken together, our data demonstrate the presence of a previously unappreciated subset of the PT cells that may be endowed with a more robust phenotype, allowing increased resistance to acute renal injury, enabling rapid repopulation of the tubules.
  •  
49.
  • Mak, Jonathan K. L., et al. (författare)
  • Development of an Electronic Frailty Index for Hospitalized Older Adults in Sweden
  • 2022
  • Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press. - 1079-5006 .- 1758-535X. ; 77:11, s. 2311-2319
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Frailty assessment in the Swedish health system relies on the Clinical Frailty Scale (CFS), but it requires training, in-person evaluation, and is often missing in medical records. We aimed to develop an electronic frailty index (eFI) from routinely collected electronic health records (EHRs) and assess its association with adverse outcomes in hospitalized older adults. Methods EHRs were extracted for 18 225 patients with unplanned admissions between 1 March 2020 and 17 June 2021 from 9 geriatric clinics in Stockholm, Sweden. A 48-item eFI was constructed using diagnostic codes, functioning and other health indicators, and laboratory data. The CFS, Hospital Frailty Risk Score, and Charlson Comorbidity Index were used for comparative assessment of the eFI. We modeled in-hospital mortality and 30-day readmission using logistic regression; 30-day and 6-month mortality using Cox regression; and length of stay using linear regression. Results Thirteen thousand one hundred and eighty-eight patients were included in analyses (mean age 83.1 years). A 0.03 increment in the eFI was associated with higher risks of in-hospital (odds ratio: 1.65; 95% confidence interval: 1.54-1.78), 30-day (hazard ratio [HR]: 1.43; 1.38-1.48), and 6-month mortality (HR: 1.34; 1.31-1.37) adjusted for age and sex. Of the frailty and comorbidity measures, the eFI had the highest area under receiver operating characteristic curve for in-hospital mortality of 0.813. Higher eFI was associated with longer length of stay, but had a rather poor discrimination for 30-day readmission. Conclusions An EHR-based eFI has robust associations with adverse outcomes, suggesting that it can be used in risk stratification in hospitalized older adults.
  •  
50.
  • Mak, Jonathan K. L., et al. (författare)
  • Two Years with COVID-19 : The Electronic Frailty Index Identifies High-Risk Patients in the Stockholm GeroCovid Study
  • 2023
  • Ingår i: Gerontology. - : S. Karger. - 0304-324X .- 1423-0003. ; 69:4, s. 396-405
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Frailty, a measure of biological aging, has been linked to worse COVID-19 outcomes. However, as the mortality differs across the COVID-19 waves, it is less clear whether a medical record-based electronic frailty index (eFI) that we have previously developed for older adults could be used for risk stratification in hospitalized COVID-19 patients. Objectives: The aim of the study was to examine the association of frailty with mortality, readmission, and length of stay in older COVID-19 patients and to compare the predictive accuracy of the eFI to other frailty and comorbidity measures. Methods: This was a retrospective cohort study using electronic health records (EHRs) from nine geriatric clinics in Stockholm, Sweden, comprising 3,980 COVID-19 patients (mean age 81.6 years) admitted between March 2020 and March 2022. Frailty was assessed using a 48-item eFI developed for Swedish geriatric patients, the Clinical Frailty Scale, and the Hospital Frailty Risk Score. Comorbidity was measured using the Charlson Comorbidity Index. We analyzed in-hospital mortality and 30-day readmission using logistic regression, 30-day and 6-month mortality using Cox regression, and the length of stay using linear regression. Predictive accuracy of the logistic regression and Cox models was evaluated by area under the receiver operating characteristic curve (AUC) and Harrell's C-statistic, respectively. Results: Across the study period, the in-hospital mortality rate decreased from 13.9% in the first wave to 3.6% in the latest (Omicron) wave. Controlling for age and sex, a 10% increment in the eFI was significantly associated with higher risks of in-hospital mortality (odds ratio = 2.95; 95% confidence interval = 2.42-3.62), 30-day mortality (hazard ratio [HR] = 2.39; 2.08-2.74), 6-month mortality (HR = 2.29; 2.04-2.56), and a longer length of stay (beta-coefficient = 2.00; 1.65-2.34) but not with 30-day readmission. The association between the eFI and in-hospital mortality remained robust across the waves, even after the vaccination rollout. Among all measures, the eFI had the best discrimination for in-hospital (AUC = 0.780), 30-day (Harrell's C = 0.733), and 6-month mortality (Harrell's C = 0.719). Conclusion: An eFI based on routinely collected EHRs can be applied in identifying high-risk older COVID-19 patients during the continuing pandemic.
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