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1.
  • Arvestad, Lars, et al. (författare)
  • Bayesian gene/species tree reconciliation and orthology analysis using MCMC
  • 2003
  • Ingår i: Bioinformatics. - : Oxford Journals. - 1367-4803 .- 1367-4811. ; 19, s. i7-i15
  • Tidskriftsartikel (refereegranskat)abstract
    • Motivation: Comparative genomics in general and orthology analysis in particular are becoming increasingly important parts of gene function prediction. Previously, orthology analysis and reconciliation has been performed only with respect to the parsimony model. This discards many plausible solutions and sometimes precludes finding the correct one. In many other areas in bioinformatics probabilistic models have proven to be both more realistic and powerful than parsimony models. For instance, they allow for assessing solution reliability and consideration of alternative solutions in a uniform way. There is also an added benefit in making model assumptions explicit and therefore making model comparisons possible. For orthology analysis, uncertainty has recently been addressed using parsimonious reconciliation combined with bootstrap techniques. However, until now no probabilistic methods have been available. Results: We introduce a probabilistic gene evolution model based on a birth-death process in which a gene tree evolves ‘inside’ a species tree. Based on this model, we develop a tool with the capacity to perform practical orthology analysis, based on Fitch’s original definition, and more generally for reconciling pairs of gene and species trees. Our gene evolution model is biologically sound (Nei et al., 1997) and intuitively attractive. We develop a Bayesian analysis based on MCMC which facilitates approximation of an a posteriori distribution for reconciliations. That is, we can find the most probable reconciliations and estimate the probability of any reconciliation, given the observed gene tree. This also gives a way to estimate the probability that a pair of genes are orthologs. The main algorithmic contribution presented here consists of an algorithm for computing the likelihood of a given reconciliation. To the best of our knowledge, this is the first successful introduction of this type of probabilistic methods, which flourish in phylogeny analysis, into reconciliation and orthology analysis. The MCMC algorithm has been implemented and, although not yet being in its final form, tests show that it performs very well on synthetic as well as biological data. Using standard correspondences, our results carry over to allele trees as well as biogeography.
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2.
  • Arvestad, Lars, et al. (författare)
  • Gene tree reconstruction and orthology analysis based on an integrated model for duplications and sequence evolution.
  • 2004
  • Ingår i: Proceedings of the Annual International Conference on Computational Molecular Biology, RECOM. - New York, New York, USA : ACM Press. ; , s. 326-335
  • Konferensbidrag (refereegranskat)abstract
    • Gene tree and species tree reconstruction, orthology analysis and reconciliation, are problems important in multigenome-based comparative genomics and biology in general. In the present paper, we advance the frontier of these areas in several respects and provide important computational tools. First, exact algorithms are given for several probabilistic reconciliation problems with respect to the probabilistic gene evolutionmodel, previously developed by the authors. Until now, those problems were solved by MCMC estimation algorithms. Second, we extend the gene evolution model to the genesequence evolution model, by including sequence evolution. Third, we develop MCMC algorithms for the gene sequence evolution model that, given gene sequence data allows: (1) orthology analysis, reconciliation analysis, and gene tree reconstruction, w.r.t. a species tree, that balances a likely/unlikely reconciliation and a likely/unlikely genetree and (2) species tree reconstruction that balance a likely /unlikely reconciliation and a likely/unlikely gene trees. These MCMC algorithms take advantage of the exact algorithms for the gene evolution model. We have successfully tested our dynamical programming algorithms on real data for a biogeography problem. The MCMC algorithms perform very well both on synthetic and biological data.
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3.
  • Bergkvist, Charlotte, et al. (författare)
  • Dietary exposure to polychlorinated biphenyls and risk of myocardial infarction - A population-based prospective cohort study
  • 2015
  • Ingår i: International Journal of Cardiology. - : ELSEVIER IRELAND LTD. - 0167-5273 .- 1874-1754. ; 183, s. 242-248
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Fish consumption may promote cardiovascular health. The role of major food contaminants, such as polychlorinated biphenyls (PCBs) common in fatty fish, is unclear. We assessed the association between dietary PCB exposure and risk of myocardial infarction taking into account the intake of long-chain omega-3 fish fatty acids. Methods: In the prospective population-based Swedish Mammography Cohort, 33,446 middle-aged and elderly women, free from cardiovascular disease, cancer and diabetes at baseline (1997) were followed-up for 12 years. Validated estimates of dietary PCB exposure and intake of fish fatty acids (eicosapentaenoic acid and docosahexaenoic acid; EPA-DHA) were obtained via a food frequency questionnaire at baseline. Results: During follow-up 1386 incident cases of myocardial infarction were ascertained through register-linkage. Women in the highest quartile of dietary PCB exposure (median 286 ng/day) had a multivariable-adjusted RR of myocardial infarction of 1.21 (95% confidence interval [CI], 1.01-1.45) compared to the lowest quartile (median 101 ng/day) before, and 1.58 (95% CI, 1.10-2.25) after adjusting for EPA-DHA. Stratification by low and high EPA-DHA intake, resulted in RRs 2.20 (95% CI, 1.18-4.12) and 1.73 (95% CI, 0.81-3.69), respectively comparing highest PCB tertile with lowest. The intake of dietary EPA-DHA was inversely associated with risk of myocardial infarction after but not before adjusting for dietary PCB. Conclusion: Exposure to PCBs was associated with increased risk of myocardial infarction, while some beneficial effect was associated with increasing EPA and DHA intake. To increase the net benefits of fish consumption, PCB contamination should be reduced to a minimum. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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4.
  • Bergkvist, Charlotte, et al. (författare)
  • Dietary exposure to polychlorinated biphenyls and risk of myocardial infarction in men - A population-based prospective cohort study
  • 2016
  • Ingår i: Environment International. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0160-4120 .- 1873-6750. ; 88, s. 9-14
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Major food contaminants such as polychlorinated biphenyls (PCBs) are proposed to play a role in the etiology of cardiovascular disease (CVD), but to date the impact of PCBs on cardiovascular health need to be explored. Methods and results: We assessed the association between validated food frequency questionnaire-based estimates of dietary PCB exposure and risk of myocardial infarction, ascertained through register-linkage, among 36,759 men from the population-based Swedish Cohort of Men, free of cardiovascular disease, diabetes and cancer at baseline (1997). Relative risks were adjusted for known cardiovascular risk factors, long-chain omega-3 fatty acids (eicosapentaenoic and docosahexaenoic acids) and methyl mercury exposure. During 12 years of follow-up (433,243 person-years), we ascertained 3005 incident cases of myocardial infarction (654 fatal). Compared with the lowest quintile of dietary PCB exposure (median 113 ng/day), men in the highest quintile (median 436 ng/day) had multivariable-adjusted relative risks of 1.74 (95% confidence interval [CI], 1.30-2.33; p-trend < 0.001) for total and 1.97 (95% C11.42-2.75; p-trend < 0.001) for non-fatal myocardial infarction. In mutually adjusted models, dietary PCB exposure was associated with an increased risk of myocardial infarction, while the intake of long-chain omega-3 fish fatty acids was associated with a decreased risk. We also observed an effect modification by adiposity on the association between of dietary PCB exposure and myocardial infarction, with higher risk among lean men (p value for interaction = 0.03). Conclusions: Exposure to PCBs via diet was associated with increased risk of myocardial infarction in men. (C) 2015 Elsevier Ltd. All rights reserved.
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5.
  • Bergkvist, Charlotte, et al. (författare)
  • Exposure to dioxin-like pollutants via different food commodities in Swedish children and young adults.
  • 2008
  • Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 46:11, s. 3360-3367
  • Tidskriftsartikel (refereegranskat)abstract
    • The dietary intake of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs) in terms of toxic equivalents (TEQs) was investigated in Swedish children and young adults. Exposure was estimated from concentration data of six groups of individual food commodities (meat, fish, dairy products, egg, edible fats and other foodstuff) combined with food intake data from a 7-day record book obtained from 670 individuals aged 1-24 years. The results showed that Swedish boys and girls, up to the age of ten, had a median TEQ intake that exceeded the tolerable daily intake (TDI) of 2 pg TEQ/kg body weight. Children exceeding the TDI varied from almost all individuals among the youngest children to about 20% among young men and women. Dairy and fish products were the main sources of exposure for the average child, accounting for 59% of the total TEQ intake. The individuals most highly exposed were, on the other hand, characterized by a high consumption of fish. Since children constitute a vulnerable group, results obtained from the present study show that it is essential to perform age specific dietary intake assessments of pollutants and more carefully consider sensitive and/or highly exposed groups in the population in the risk management processes.
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6.
  • Bergkvist, Charlotte, et al. (författare)
  • Validation of questionnaire-based long-term dietary exposure to polychlorinated biphenyls using biomarkers
  • 2012
  • Ingår i: Molecular Nutrition & Food Research. - : Wiley. - 1613-4125 .- 1613-4133. ; 56:11, s. 1748-1754
  • Tidskriftsartikel (refereegranskat)abstract
    • Scope The health consequences of lifelong low-level exposure to polychlorinated biphenyls (PCBs) via food are largely unknown, mainly due to the lack of large population-based prospective studies addressing this issue. We validated long-term food frequency questionnaire (FFQ)-based dietary PCB exposure against concentrations of six PCB congeners in serum. Methods and results Dietary PCB exposure was estimated in the Swedish Mammography Cohort by constructing a recipe-based database of CB-153, an indicator for total PCBs in food. The Spearman rank correlation (adjusted for within-person variability) was assessed between concurrent (20042006), past (1997), and long-term (mean of 1997 and 20042006) FFQ-based dietary PCB exposure, respectively, and the following serum PCB congeners, CB-118, CB-138, CB-153, CB-156, CB-170, and CB-180, in women (5685 years of age, n = 201). The correlation between FFQ-based dietary PCB exposure and serum CB-153 was 0.41 (p < 0.001) for the concurrent (median 1.6 ng/kg body weight) and 0.34 (p < 0.05) for the past (median 2.6 ng/kg body weight) exposure assessment. Long-term validity of FFQ-based PCB estimates and the six serum PCB congeners ranged from 0.30 to 0.58 (p < 0.05). Conclusion FFQ-based PCB exposure estimates show acceptable validity in relation to PCB concentrations in serum, justifying their use in large-scale epidemiological studies.
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7.
  • Berglund, Ann-Charlotte, et al. (författare)
  • Combining local and grid resources in scientific workflows (for Bioinformatics)
  • 2009
  • Konferensbidrag (refereegranskat)abstract
    • We examine some issues that arise when using both local and Gridresources in scientific workflows. Our previous work addresses and illustratesthe benefits of a light-weight and generic workflow engine that manages andoptimizes Grid resource usage. Extending on this effort, we hereillustrate how a client tool for bioinformatics applications employs the engine tointerface with Grid resources. We also explore how to define data flowsthat transparently integrates local and Grid subworkflows. In addition, the benefits of parameter sweep workflows are examined and a means for describing this type of workflows in an abstract and concise manner is introduced. Finally, the above mechanisms are employed to perform an orthology detection analysis.
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8.
  • Berglund, Ann-Charlotte, et al. (författare)
  • InParanoid 6 : eukaryotic ortholog clusters with inparalogs
  • 2008
  • Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 36, s. D263-D266
  • Tidskriftsartikel (refereegranskat)abstract
    • The InParanoid eukaryotic ortholog database (http://InParanoid.sbc.su.se/) has been updated to version 6 and is now based on 35 species. We collected all available 'complete' eukaryotic proteomes and Escherichia coli, and calculated ortholog groups for all 595 species pairs using the InParanoid program. This resulted in 2 642 187 pairwise ortholog groups in total. The orthology-based species relations are presented in an orthophylogram. InParanoid clusters contain one or more orthologs from each of the two species. Multiple orthologs in the same species, i.e. inparalogs, result from gene duplications after the species divergence. A new InParanoid website has been developed which is optimized for speed both for users and for updating the system. The XML output format has been improved for efficient processing of the InParanoid ortholog clusters.
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9.
  • Berglund, Lisa, et al. (författare)
  • Glucose-Dependent Insulinotropic Polypeptide (GIP) Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB.
  • 2016
  • Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 65:1, s. 239-254
  • Tidskriftsartikel (refereegranskat)abstract
    • Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with extrapancreatic effects beyond glycemic control. Here we demonstrate unexpected effects of GIP signaling in the vasculature. GIP induces the expression of the pro-atherogenic cytokine osteopontin (OPN) in mouse arteries, via local release of endothelin-1 (ET-1) and activation of cAMP response element binding protein (CREB). Infusion of GIP increases plasma OPN levels in healthy individuals. Plasma ET-1 and OPN levels are positively correlated in patients with critical limb ischemia. Fasting GIP levels are higher in individuals with a history of cardiovascular disease (myocardial infarction, stroke) when compared to controls. GIP receptor (GIPR) and OPN mRNA levels are higher in carotid endarterectomies from patients with symptoms (stroke, transient ischemic attacks, amaurosis fugax) than in asymptomatic patients; and expression associates to parameters characteristic of unstable and inflammatory plaques (increased lipid accumulation, macrophage infiltration and reduced smooth muscle cell content). While GIPR expression is predominantly endothelial in healthy arteries from human, mouse, rat and pig; remarkable up-regulation is observed in endothelial and smooth muscle cells upon culture conditions yielding a "vascular disease-like" phenotype. Moreover, a common variant rs10423928 in the GIPR gene associated with increased risk of stroke in type 2 diabetes patients.
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11.
  • Berglund, Per, et al. (författare)
  • Linking Education and Research : A Roadmap for Higher Education Institutions at the Dawn of the Knowledge Society
  • 2019
  • Ingår i: Linking education and research. - Basel, Switzerland : MDPI. ; , s. 11-33
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • In an era characterized by a move towards a “knowledge society”, universities are central in fostering “knowledgeability”, that is the reflexive understanding of knowledge in knowledge societies. The objective of “knowledgeability” can be met through creating a stronger link between education and research. Furthermore, overall student performance, for example in critical thinking and problem solving, can be improved if research-related activities are incorporated into the curriculum.The aim of this paper is to use international examples to discuss the research- education nexus from four different perspectives, namely context, policy, implementation and quality, with case studies from higher education institutions in Singapore and Sweden.We suggest that different integrative technologies can be used to enhance the links, but it will be essential to consider the inputs of training, service and support in using new technology. Interestingly, the act of evaluating the link between education and research will increase awareness of this linkage by stakeholders involved in both education and research. In turn the link can be strengthened, contributing to increased quality in both education and research.
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12.
  • Berglund-Sonnhammer, Ann-Charlotte, et al. (författare)
  • Optimal gene trees from sequences and species trees using a soft interpretation of parsimony
  • 2006
  • Ingår i: Journal of Molecular Evolution. - : Springer Science and Business Media LLC. - 0022-2844 .- 1432-1432. ; 63:2, s. 240-250
  • Tidskriftsartikel (refereegranskat)abstract
    • Gene duplication and gene loss as well as other biological events can result in multiple copies of genes in a given species. Because of these gene duplication and loss dynamics, in addition to variation in sequence evolution and other sources of uncertainty, different gene trees ultimately present different evolutionary histories. All of this together results in gene trees that give different topologies from each other, making consensus species trees ambiguous in places. Other sources of data to generate species trees are also unable to provide completely resolved binary species trees. However, in addition to gene duplication events, speciation events have provided some underlying phylogenetic signal, enabling development of algorithms to characterize these processes. Therefore, a soft parsimony algorithm has been developed that enables the mapping of gene trees onto species trees and modification of uncertain or weakly supported branches based on minimizing the number of gene duplication and loss events implied by the tree. The algorithm also allows for rooting of unrooted trees and for removal of in-paralogues (lineage-specific duplicates and redundant sequences masquerading as such). The algorithm has also been made available for download as a software package, Softparsmap.
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13.
  • Böttcher, Johanna, et al. (författare)
  • Adding a smartphone app to internet-based self-help for social anxiety : A randomized controlled trial
  • 2018
  • Ingår i: Computers in human behavior. - : Elsevier BV. - 0747-5632 .- 1873-7692. ; 87, s. 98-108
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Increasing access to treatment via smartphone apps is an important topic in Social Anxiety Disorder (SAD). ‘Challenger’ is an app promoting exposure exercises in daily life. The present study evaluated the additional benefit of using the app as adjunct to Internet-based unguided self-help for SAD. In a second step, we also tested how the app and the self-help programme (SH) should best be combined.Method: 209 patients diagnosed with SAD were randomly allocated to three groups. Group 1 received the app and the self-help programme for six weeks (parallel treatment), group 2 first received SH for six weeks and then the app for six weeks (sequential treatment). Group 3 was a wait-list group. Comparisons were made at week 7 evaluating the potential add-on effect of the app (SH plus app versus SH only) and at week 14 comparing the parallel to the sequential treatment. Participants filled in questionnaires prior, during, and post treatment, and at 4- and 12- months follow-up.Results: Intention-to-treat analyses showed no significant effect of adding the app to Internet-based self-help. However, among participants actively using the app, adding Challenger to self-help resulted in significantly less social anxiety (d = 0.30). At week 14, decreases in social anxiety were large for both the parallel and the sequential group with no differences between the active groups (dwithin = 1.12–1.19). Changes were maintained throughout the follow-up period.Conclusion: Results of the current study cautiously support the notion of adding a smartphone app to unguided self-help for SAD. Future studies should investigate how patients can be motivated to use the app more frequently.
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14.
  • Carroll, Haley A, et al. (författare)
  • Effects of parental monitoring on alcohol use in the US and Sweden : A brief report
  • 2016
  • Ingår i: Addictive Behaviours. - : Elsevier. - 0306-4603 .- 1873-6327. ; 63, s. 89-92
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Adolescent alcohol use predicts a myriad of negative mental and physical health outcomes including fatality (Midanik, 2004). Research in parental influence on alcohol consumption finds parental monitoring (PM), or knowing where/whom your child is with, is associated with lower levels of alcohol use in adolescents (e.g., Arria et al., 2008). As PM interventions have had only limited success (Koutakis, Stattin, & Kerr, 2008), investigating moderating factors of PM is of importance. Country may serve as one such moderator (Calafat, Garcia, Juan, Becoña, & Fernández-Hermida, 2014). Thus, the purpose of the present report is to assess the relationship between PM and alcohol use in the US and Sweden. Method High school seniors from the US (n = 1181, 42.3% Male) and Sweden (n = 2171, 44.1% Male) completed assessments of total drinks consumed in a typical week, problematic alcohol use, and perceived PM. Results Generalized linear mixed modeling (GLM, Cohen, Cohen, West, & Aiken, 2013; Hilbe, 2011) was used to examine whether country moderated the relationship between PM and alcohol use. Results revealed main effects of country and PM and a significant interaction between country and PM in predicting total drinks per week and PM in predicting problematic alcohol use (p < 0.001). Conclusions While PM is related to lower quantity of alcohol consumed and problematic alcohol use, greater PM appears to be more strongly related to fewer drinks per week and less problematic alcohol use in the US, as compared to Sweden.
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15.
  • Clark, Charlotte, et al. (författare)
  • Psychological restoration, coping strategies and children’s cognitive performance in the RANCH study
  • 2006
  • Ingår i: Proceedings of Inter-Noise 2006, Honolulu, Hawaii, USA, 3-6 December, 2006, Paper no in06_090 (Available on CD). ; :Paper no in06_090
  • Konferensbidrag (refereegranskat)abstract
    • The RANCH study found a linear exposure effect association between chronic aircraft noise exposure at primary school and the impairment of children’s reading comprehension, in the Netherlands, Spain and the United Kingdom. This paper presents multilevel modelling analyses, exploring psychological mechanisms, which may moderate the effect of aircraft noise on children’s cognition. Psychological restoration – the process whereby places which afford tranquility and relaxation are utilized to reduce stress and promote well being – has been shown to reduce the adverse effect of noise on children’s annoyance responses. This paper examines whether having places for psychological restoration at home, moderates the adverse effects of chronic aircraft noise exposure at school on children’s cognition. In addition, the effectiveness of coping strategies in relation to noise exposure at school are examined – are specific coping strategies associated with less impairment of cognition? Multi-level models examining the role of psychological restoration and coping strategies, as part of a broader model of environmental risk and protective factors for children’s cognition are presented. The implication of the findings for interventions for children attending noise exposed schools are discussed.
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16.
  • Danielsson, Henrik, et al. (författare)
  • A Systematic Review of Longitudinal Trajectories of Mental Health Problems in Children with Neurodevelopmental Disabilities
  • 2024
  • Ingår i: Journal of Developmental and Physical Disabilities. - : Springer. - 1056-263X .- 1573-3580. ; 36, s. 203-242
  • Forskningsöversikt (refereegranskat)abstract
    • To review the longitudinal trajectories - and the factors influencing their development - of mental health problems in children with neurodevelopmental disabilities. Systematic review methods were employed. Searches of six databases used keywords and MeSH terms related to children with neurodevelopmental disabilities, mental health problems, and longitudinal research. After the removal of duplicates, reviewers independently screened records for inclusion, extracted data (outcomes and influencing factors), and evaluated the risk of bias. Findings were tabulated and synthesized using graphs and a narrative. Searches identified 94,662 unique records, from which 49 publications were included. The median publication year was 2015. Children with attention deficit hyperactivity disorder were the most commonly included population in retrieved studies. In almost 50% of studies, trajectories of mental health problems changed by < 10% between the first and last time point. Despite multiple studies reporting longitudinal trajectories of mental health problems, greater conceptual clarity and consideration of the measures included in research is needed, along with the inclusion of a more diverse range of populations of children with neurodevelopmental disabilities.
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17.
  • Engström, Gunnar, et al. (författare)
  • The Swedish CArdioPulmonary BioImage Study : objectives and design
  • 2015
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
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18.
  • Eriksson, Matilda, 1981- (författare)
  • Entreprenörskapets tysta(de) röster : En narrativ studie om kvinnor som delar sitt liv med en man som är entreprenör
  • 2021
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Entrepreneurship has come to play a crucial role in developing our society, as has gender equality. However, some conflicting aspects of these two political priorities have to date been overlooked. Taking its point of departure in feminist theory, an entrepreneurial culture and an empirical context supporting companies with high growth potential, this thesis aims to illuminate and analyze narrative constructions of entrepreneurship and gender in relation to the female spouse or partner (S/P) of a male entrepreneur. This means entrepreneurship is studied from a gender perspective and gender from the perspective of entrepreneurship. Reading into a broad literature within the field of entrepreneurship, the epistemology appears to be permeated by a masculine rationality, not least is this disclosed in the field of gender studies on entrepreneurship. This excludes, and silences, the voices and practices of the entrepreneur’s S/P, which is questioned in this thesis by using the metaphor of a hunter-gatherer society.The thesis builds on a narrative method, analyzing the entrepreneurship policy’s normative story of entrepreneurship in parallel to the female S/P’s narratives and experiences of her entrepreneurial journey. The normative narrative includes certain assumptions about entrepreneurship, women and business. One is that entrepreneurial practice takes part in the public sphere. Another that entrepreneurship is practiced by the entrepreneur. A third that equality is only seen to be achieved between women and men who run a business. Understanding policy as a cultural product, constructed by contemporary norms and values, that govern our lives in its broadest sense, these assumptions do not only hide certain silences. They also bear implications for the lives we can live.In order to illustrate and problematize how our lives can be lived, the S/P’s narratives are analyzed and the implications unfolded. These narratives demonstrate how the women, by means of economic and social support, enable the start-up and development of entrepreneurial business by adopting a more traditional role. The fact that women have a more traditional role than men may not be noteworthy. The remarkable thing is rather that men – with the support of the state and women – can build companies where women’s efforts and conditions are discounted, while the reforms that aim to support economic growth and gender equality leave this unproblematized. In order to make their voices heard, these women tend to imitate and reproduce an entrepreneurial and masculine rationale when making sense of their experiences. This, in turn, further silences the experiences of S/Ps whose voices and practices are rendered even more suppressed.By mirroring the normative and parallel narratives, six different constructions of entrepreneurship and gender emerge. At first, the S/P’s invisible participation trains a skilled imitator when positioning herself as entrepreneurial. Secondly, the conditional equality of the policy reform relates to a double subordination in relation to the man and the entrepreneur, who are both superior to the female S/P. Thirdly, equality and economic growth appear to be two incompatible concepts, which can be illustrated by the assumption that a co-ownership requires an active role in the business. This holds a structural discrimination, leaving the role of the majority of women in an entrepreneurial context unacknowledged, both with regards to theory and practice.
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19.
  • Fehniger, Thomas E, et al. (författare)
  • Exploring the context of the lung proteome within the airway mucosa following allergen challenge.
  • 2004
  • Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 3:2, s. 307-320
  • Forskningsöversikt (refereegranskat)abstract
    • The lung proteome is a dynamic collection of specialized proteins related to pulmonary function. Many cells of different derivations, activation states, and levels of maturity contribute to the changing environment, which produces the lung proteome. Inflammatory cells reacting to environmental challenge, for example from allergens, produce and secrete proteins which have profound effects on both resident and nonresident cells located in airways, alveoli, and the vascular tree which provides blood cells to the parenchyma alveolar bed for gas exchange. In an experimental model of allergic airway inflammation, we have compared control and allergen challenged lung compartments to determine global protein expression patterns using 2D-gel electrophoresis and subsequent spot identification by MS/MS mass spectrometry. We have then specifically isolated the epithelial mucosal layer, which lines conducting airways, from control and allergen challenged lungs, using laser capture technology and performed proteome identification on these selected cell samples. A central component of our investigations has been to contextually relate the histological features of the dynamic pulmonary environment to the changes in protein expression observed following challenge. Our results provide new information of the complexity of the submucosa/epithelium interface and the mechanisms behind the transformation of airway epithelium from normal steady states to functionally activated states.
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21.
  • Heijkenskjöld Rentzhog, Charlotte, et al. (författare)
  • Overall and peripheral lung function assessment by spirometry and forced oscillation technique in relation to asthma diagnosis and control.
  • 2017
  • Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 47:12, s. 1546-1554
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Classic spirometry is effort dependent and of limited value in assessing small airways. Peripheral airway involvement, and relation to poor control, in asthma, has been highlighted recently. Forced oscillation technique (FOT) offers an effort-independent assessment of overall and peripheral lung mechanics. We studied the association between lung function variables, obtained either by spirometry or multifrequency (5, 11 and 19 Hz) FOT, and asthma diagnosis and control.METHODS: ), resistance difference between 5-19 Hz (R5-R19) and Asthma Control Test scores were determined in 234 asthmatic and 60 healthy subjects (aged 13-39 years). We used standardized lung function variables in logistic regression analyses, unadjusted and adjusted for age, height, gender and weight.RESULTS: and R5-R19) were associated with uncontrolled asthma (P-values < .05).CONCLUSIONS: /FVC, supporting a complementary role for FOT. Asthma control was related to FOT measures of peripheral airways, suggesting a potential use in identifying such involvement. Further studies are needed to determine a clinical value and relevant reference values in children, for the multifrequency FOT measurements.
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22.
  • Jones, Geraint H., et al. (författare)
  • The Comet Interceptor Mission
  • 2024
  • Ingår i: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 220:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600 ms − 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule.
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23.
  • Keselman, Boris, et al. (författare)
  • Analysis and modelling of mistriage in the Stockholm stroke triage system
  • 2022
  • Ingår i: European Stroke Journal. - : Sage Publications. - 2396-9873 .- 2396-9881. ; 7:2, s. 126-133
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The Stockholm Stroke Triage System (SSTS) is a prehospital triage system for detection of patients eligible for endovascular thrombectomy (EVT). Assessment of hemiparesis combined with ambulance-hospital teleconsultation is used to route patients directly to the thrombectomy centre. Some patients are not identified and require secondary transport for EVT (undertriage) while others taken to the thrombectomy centre do not undergo EVT (overtriage). The aims of this study were to characterize mistriaged patients, model for and evaluate alternative triage algorithms.Patients and methods: Patients with suspected stroke transported by priority 1 ground ambulance between October 2017 and October 2018 (n = 2905) were included. Three triage algorithms were modelled using prehospital data. Decision curve analysis was performed to calculate net benefit (correctly routing patients for EVT without increasing mistriage) of alternative models vs SSTS.Results: Undertriage for EVT occurred in n = 35/2582 (1.4%) and overtriage in n = 239/323 (74.0%). Compared to correct thrombectomy triages, undertriaged patients were younger and had lower median NIHSS (10 vs 18), despite 62.9% with an M1 occlusion. In overtriaged patients, 77.0% had a stroke diagnosis (29.7% haemorrhagic). Hemiparesis and FAST items face and speech were included in all models. Decision curve analysis showed highest net benefit for SSTS for EVT, but lower for large artery occlusion (LAO) stroke.Discussion: Undertriaged patients had lower NIHSS, likely due to better compensated proximal occlusions. SSTS was superior to other models for identifying EVT candidates, but lacked information allowing comparison to other prehospital scales.Conclusion: Using prehospital data, alternative models did not outperform the SSTS in finding EVT candidates.
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24.
  • Keselman, Boris, et al. (författare)
  • The Stockholm Stroke Triage Project : Outcomes of Endovascular Thrombectomy Before and After Triage Implementation
  • 2022
  • Ingår i: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 53:2, s. 473-481
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND PURPOSE: The Stockholm Stroke Triage System (SSTS) is a prehospital algorithm for detection of endovascular thrombectomy (EVT)-eligible patients, combining symptom severity assessment and ambulance-to-hospital teleconsultation, leading to a decision on primary stroke center bypass. In the Stockholm Region (6 primary stroke centers, 1 EVT center), SSTS implementation in October 2017 reduced onset-to-EVT time by 69 minutes. We compared clinical outcomes before and after implementation of SSTS in an observational study.METHODS: We prospectively recruited patients transported by Code Stroke ambulance within the Stockholm region under the SSTS, treated with EVT during October 2017 to October 2019, and compared to EVT patients from 2 previous years.OUTCOMES: shift in modified Rankin Scale (mRS) scores, mRS score 0 to 1, mRS score 0 to 2, and death (all 3 months), National Institutes of Health Stroke Scale (NIHSS) score change 24-hour post-EVT, recanalization (Thrombolysis in Cerebral Infarction 2b-3), and symptomatic intracranial hemorrhage. mRS outcomes were adjusted for age and baseline NIHSS.RESULTS: Patients with EVT in the SSTS group (n=244) were older and had higher baseline NIHSS versus historical controls (n=187): median age 74 (interquartile range, 63-81) versus 71 (61-78); NIHSS score 17 (11.5-21) versus 15 (10-20). During SSTS, median onset-to-puncture time was 136 versus 205 minutes (P<0.001). Adjusted common odds ratio for lower mRS in SSTS patients was 1.7 (95% CI, 1.2-2.3) versus controls. During SSTS, 83/240 (34.6%) versus 44/186 (23.7%) reached 3-month mRS score 0 to 1 (P=0.014), adjusted common odds ratio 2.3 (95% CI, 1.4-3.6). Median NIHSS change 24-hour post-EVT was 6 versus 4 (P=0.005). Differences in Thrombolysis in Cerebral Infarction, symptomatic intracranial hemorrhage, and death were nonsignificant.CONCLUSIONS: With an onset to arterial puncture time reduction by 69 minutes, outcomes in thrombectomy-treated patients improved significantly after region-wide large artery occlusion triage system implementation. These results warrant replication studies in other geographic and organizational circumstances.
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25.
  • Kisiel, Marta A., 1984-, et al. (författare)
  • Quality of life and asthma control related to hormonal transitions in women's lives
  • 2022
  • Ingår i: Journal of Asthma. - : Marcel Dekker. - 0277-0903 .- 1532-4303. ; 59:9, s. 1869-1877
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The aim was to investigate if menstruation and use of exogenous sex hormones influence self-reported asthma related quality of life (QoL) and asthma control.Methods: The study is based on two asthma cohorts randomly selected in primary and secondary care. A total of 622 female patients 18-65 years were included and classified as premenopausal ≤46 years (n = 338) and peri/postmenopausal 47-65 years (n = 284). Questionnaire data from 2012 and 2014 with demographics, asthma related issues and sex hormone status. Outcome measures were Mini Asthma Quality of Life Questionnaire (Mini-AQLQ) and asthma control including Asthma Control Test (ACT) and exacerbations last six months.Results: Premenopausal women with menstruation related asthma worsening, perimenstrual asthma (PMA) (9%), had a clinically relevant lower Mini-AQLQ mean score 4.9 vs. 5.8 (p < 0.001), lower asthma control with ACT score <20, 72% vs. 28% (p < 0.001) and higher exacerbation frequency 44% vs. 20% (p = 0.004) compared with women without PMA. Women with irregular menstruation had higher exacerbation frequency than women with regular menstruation (p = 0.023). Hormonal contraceptives had no impact on QoL and asthma control. Peri/postmenopausal women with menopausal hormone therapy (MHT) had a clinically relevant lower Mini-AQLQ mean score compared to those without MHT, 4.9 vs 5.4 (p < 0.001), but no differences in asthma control.Conclusion: Women with PMA had lower QoL and more uncontrolled asthma than women without PMA. Peri/postmenopausal women with MHT had lower QoL than women without MHT. Individual clinical management of women with asthma may benefit from information about their sex hormone status.
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26.
  • Lilja, Hans, et al. (författare)
  • Long-term prediction of prostate cancer up to 25 years before diagnosis of prostate cancer using prostate kallikreins measured at age 44 to 50 years.
  • 2007
  • Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 25:4, s. 431-436
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose We examined whether prostate-specific antigen (PSA) forms and human kallikrein 2 (hK2) measured at age 44 to 50 years predict long-term risk of incident prostate cancer. Methods From 1974 to 1986, 21,277 men age <= 50 years in Malmo, Sweden, enrolled onto a cardiovascular study (74% participation). The rate of PSA screening in this population is low. According to the Swedish Cancer Registry, 498 were later diagnosed with prostate cancer. We measured hK2, free PSA, and total PSA (tPSA) in archived blood plasma from 462 participants later diagnosed with prostate cancer and from 1,222 matched controls. Conditional logistic regression was used to test for association of prostate cancer with hK2 and PSA forms measured at baseline. Results Median delay between venipuncture and prostate cancer diagnosis was 18 years. hK2 and all PSA forms were strongly associated with prostate cancer (all P < .0005). None of the 90 anthropometric, lifestyle, biochemical, and medical history variables measured at baseline was importantly predictive. A tPSA increase of 1 ng/mL was associated with an increase in odds of cancer of 3.69 (95% CI, 2.99 to 4.56); addition of other PSA forms or hK2 did not add to the predictive value of tPSA. tPSA remained predictive for men diagnosed >= 20 years after venipuncture, and the predictive value remained unchanged in an analysis restricted to palpable disease. Conclusion A single PSA test at age 44 to 50 years predicts subsequent clinically diagnosed prostate cancer. This raises the possibility of risk stratification for prostate cancer screening programs.
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27.
  • Lindqvist, Charlotte, et al. (författare)
  • Male broad-nosed pipefish Syngnathus typhle do not locate females by smell
  • 2011
  • Ingår i: Journal of Fish Biology. - London : Academic Press. - 0022-1112 .- 1095-8649. ; 78:6, s. 1861-1867
  • Tidskriftsartikel (refereegranskat)abstract
    • Broad-nosed pipefish Syngnathus typhle were used to investigate whether males used scent in their search for mates. When the males in an experiment had access to olfactory cues only, they did not locate females better than they located males. Thus, S. typhle, was less successful in mate search when visual cues were absent.
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28.
  • Lundgren Mortensen, Anja Charlotte, et al. (författare)
  • Combination therapy of tyrosine kinase inhibitor sorafenib with the HSP90 inhibitor onalespib as a novel treatment regimen for thyroid cancer
  • 2023
  • Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Thyroid cancer is the most common endocrine malignancy, affecting nearly 600,000 new patients worldwide. Treatment with the BRAF inhibitor sorafenib partially prolongs progression-free survival in thyroid cancer patients, but fails to improve overall survival. This study examines enhancing sorafenib efficacy by combination therapy with the novel HSP90 inhibitor onalespib. In vitro efficacy of sorafenib and onalespib monotherapy as well as in combination was assessed in papillary (PTC) and anaplastic (ATC) thyroid cancer cells using cell viability and colony formation assays. Migration potential was studied in wound healing assays. The in vivo efficacy of sorafenib and onalespib therapy was evaluated in mice bearing BHT-101 xenografts. Sorafenib in combination with onalespib significantly inhibited PTC and ATC cell proliferation, decreased metabolic activity and cancer cell migration. In addition, the drug combination approach significantly inhibited tumor growth in the xenograft model and prolonged the median survival. Our results suggest that combination therapy with sorafenib and onalespib could be used as a new therapeutic approach in the treatment of thyroid cancer, significantly improving the results obtained with sorafenib as monotherapy. This approach has the potential to reduce treatment adaptation while at the same time providing therapeutic anti-cancer benefits such as reducing tumor growth and metastatic potential.
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29.
  • Luthander, Charlotte Millde, et al. (författare)
  • Gaps in obstetric care processes - we can only improve what is being measured
  • 2018
  • Ingår i: Journal of Perinatal Medicine. - : WALTER DE GRUYTER GMBH. - 0300-5577 .- 1619-3997. ; 46:2, s. 139-149
  • Tidskriftsartikel (refereegranskat)abstract
    • A multifaceted intervention at all six obstetric units in the Stockholm Health Region was performed in 2008-2011 in order to increase safety for the newborn infants. Case-controlled criterion-based reviews of care processes during labor and delivery have been used to assess factors associated with suboptimal care during labor and delivery. Categories of increased risk of adverse outcome during labor and delivery were defined. Cases with low Apgar scores and healthy controls were scrutinized and compared to data from a study with an identical design performed before the intervention. The risk of suboptimal care increased twice among controls and three times among cases when reviewing specific criteria after a multifaceted intervention. There are still gaps in care processes that need attention. Improving guidelines is important but not enough alone, and the management of fetal surveillance needs further improvement. The complexity of reviewing care processes using criterion-based research methodology is highlighted.
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30.
  • Lyssenko, Valeriya, et al. (författare)
  • Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes.
  • 2007
  • Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 117:8, s. 2155-2163
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic variants in the gene encoding for transcription factor-7-like 2 (TCF7L2) have been associated with type 2 diabetes (T2D) and impaired beta cell function, but the mechanisms have remained unknown. We therefore studied prospectively the ability of common variants in TCF7L2 to predict future T2D and explored the mechanisms by which they would do this. Scandinavian subjects followed for up to 22 years were genotyped for 3 SNPs (rs7903146, rs12255372, and rs10885406) in TCF7L2, and a subset of them underwent extensive metabolic studies. Expression of TCF7L2 was related to genotype and metabolic parameters in human islets. The CT/TT genotypes of SNP rs7903146 strongly predicted future T2D in 2 independent cohorts (Swedish and Finnish). The risk T allele was associated with impaired insulin secretion, incretin effects, and enhanced rate of hepatic glucose production. TCF7L2 expression in human islets was increased 5-fold in T2D, particularly in carriers of the TT genotype. Overexpression of TCF7L2 in human islets reduced glucose-stimulated insulin secretion. In conclusion, the increased risk of T2D conferred by variants in TCF7L2 involves the enteroinsular axis, enhanced expression of the gene in islets, and impaired insulin secretion.
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31.
  • Lyssenko, Valeriya, et al. (författare)
  • Pleiotropic Effects of GIP on Islet Function Involve Osteopontin
  • 2011
  • Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 60:9, s. 2424-2433
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE-The incretin hormone GIP (glucose-dependent insulinotropic polypeptide) promotes pancreatic beta-cell function by potentiating insulin secretion and beta-cell proliferation. Recently, a combined analysis of several genome-wide association studies (Meta-analysis of Glucose and Insulin-Related Traits Consortium [MAGIC]) showed association to postprandial insulin at the GIP receptor (GIPR) locus. Here we explored mechanisms that could explain the protective effects of GIP on islet function. RESEARCH DESIGN AND METHODS-Associations of GIPR rs10423928 with metabolic and anthropometric phenotypes in both nondiabetic (N = 53,730) and type 2 diabetic individuals (N = 2,731) were explored by combining data from 11 studies.Insulin secretion was measured both in vivo in nondiabetic subjects and in vitro in islets from cadaver donors. Insulin secretion was also measured in response to exogenous GIP. The in vitro measurements included protein and gene expression as well as measurements of beta-cell viability and proliferation. RESULTS-The A allele of GIPR rs10423928 was associated with impaired glucose- and GIP-stimulated insulin secretion and a decrease in BMI, lean body mass, and waist circumference. The decrease in BMI almost completely neutralized the effect of impaired insulin secretion on risk of type 2 diabetes. Expression of GIPR mRNA was decreased in human islets from carriers of the A allele or patients with type 2 diabetes. GIP stimulated osteopontin (OPN) mRNA and protein expression. OPN expression was lower in carriers of the A allele. Both GIP and OPN prevented cytokine-induced reduction in cell viability (apoptosis). In addition, OPN stimulated cell proliferation in insulin-secreting cells. CONCLUSIONS-These findings support beta-cell proliferative and antiapoptotic roles for GIP in addition to its action as an incretin hormone. Identification of a link between GIP and OPN may shed new light on the role of GIP in preservation of functional beta-cell mass in humans. Diabetes 60:2424-2433, 2011
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32.
  • Mazya, Michael V., et al. (författare)
  • Implementation of a Prehospital Stroke Triage System Using Symptom Severity and Teleconsultation in the Stockholm Stroke Triage Study
  • 2020
  • Ingår i: JAMA Neurology. - : American Mathematical Society (AMS). - 2168-6149 .- 2168-6157. ; 77:6, s. 691-699
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: To our knowledge, it is unknown whether a prehospital stroke triage system combining symptom severity and teleconsultation could accurately select patients for primary stroke center bypass and hasten delivery of endovascular thrombectomy (EVT) without delaying intravenous thrombolysis (IVT).Objective: To evaluate the predictive performance of the newly implemented Stockholm Stroke Triage System (SSTS) for large-artery occlusion (LAO) stroke and EVT initiation. Secondary objectives included evaluating whether the Stockholm Stroke Triage System shortened onset-to-puncture time for EVT and onset-to-needle time (ONT) for IVT.Design, Setting, and Participants: This population-based prospective cohort study conducted from October 2017 to October 2018 across the Stockholm region (Sweden) included patients transported by first-priority ("code stroke") ambulance to the hospital for acute stroke suspected by an ambulance nurse and historical controls (October 2016-October 2017). Exclusion criteria were in-hospital stroke and helicopter or private transport. Of 2909 eligible patients, 4 (0.14%) declined participation.Exposures: Patients were assessed by ambulance nurses with positive the face-arm-speech-time test or other stroke suspicion and were evaluated for moderate-to-severe hemiparesis (≥2 National Institutes of Health stroke scale points each on the ipsilateral arm and leg [A2L2 test]). If present, the comprehensive stroke center (CSC) stroke physician was teleconsulted by phone for confirmation of stroke suspicion, assessment of EVT eligibility, and direction to CSC or the nearest primary stroke center. If absent, the nearest hospital was prenotified.Main Outcomes and Measures: Primary outcome: LAO stroke. Secondary outcomes: EVT initiation, onset-to-puncture time, and ONT. Predictive performance measures included sensitivity, specificity, positive and negative predictive values, the overall accuracy for LAO stroke, and EVT initiation.Results: We recorded 2905 patients with code-stroke transports (1420 women [49%]), and of these, 323 (11%) had A2L2+ teleconsultation positive results and were triaged for direct transport to CSC (median age, 73 years [interquartile range (IQR), 64-82 years]; 55 women [48%]). Accuracy for LAO stroke was 87% (positive predictive value, 41%; negative predictive value, 93%) and 91% for EVT initiation (positive predictive value, 26%; negative predictive value, 99%). Endovascular thrombectomy was performed for 84 of 323 patients (26%) with triage-positive results and 35 of 2582 patients (1.4%) with triage-negative results. In EVT cases with a known onset time (77 [3%]), the median OPT was 137 minutes (IQR, 118-180; previous year, 206 minutes [IQR, 160-280]; n = 75) (P < .001). The regional median ONT (337 [12%]) was unchanged at 115 minutes (IQR, 83-164; previous year, 115 minutes [IQR, 85-161]; n = 360) (P = .79). The median CSC IVT door-to-needle time was 13 minutes (IQR, 10-18; 116 [4%]) (previous year, 31 minutes [IQR, 19-38]; n = 45) (P < .001).Conclusions and Relevance: The Stockholm Stroke Triage System, which combines symptom severity and teleconsultation, results in markedly faster EVT delivery without delaying IVT.
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33.
  • Mishchenko, Kateryna, 1973- (författare)
  • Numerical Algorithms for Optimization Problems in Genetical Analysis
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The focus of this thesis is on numerical algorithms for efficient solution of QTL analysis problem in genetics.Firstly, we consider QTL mapping problems where a standard least-squares model is used for computing the model fit. We develop optimization methods for the local problems in a hybrid global-local optimization scheme for determining the optimal set of QTL locations. Here, the local problems have constant bound constraints and may be non-convex and/or flat in one or more directions. We propose an enhanced quasi-Newton method and also implement several schemes for constrained optimization. The algorithms are adopted to the QTL optimization problems. We show that it is possible to use the new schemes to solve problems with up to 6 QTLs efficiently and accurately, and that the work is reduced with up to two orders magnitude compared to using only global optimization.Secondly, we study numerical methods for QTL mapping where variance component estimation and a REML model is used. This results in a non-linear optimization problem for computing the model fit in each set of QTL locations. Here, we compare different optimization schemes and adopt them for the specifics of the problem. The results show that our version of the active set method is efficient and robust, which is not the case for methods used earlier. We also study the matrix operations performed inside the optimization loop, and develop more efficient algorithms for the REML computations. We develop a scheme for reducing the number of objective function evaluations, and we accelerate the computations of the derivatives of the log-likelihood by introducing an efficient scheme for computing the inverse of the variance-covariance matrix and other components of the derivatives of the log-likelihood.
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34.
  • Newton-Cheh, Christopher, et al. (författare)
  • Genome-wide association study identifies eight loci associated with blood pressure
  • 2009
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:6, s. 666-676
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N <= 71,225 European ancestry, N <= 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 x 10(-24)), CYP1A2 (P = 1 x 10(-23)), FGF5 (P = 1 x 10(-21)), SH2B3 (P = 3 x 10(-18)), MTHFR (P = 2 x 10(-13)), c10orf107 (P = 1 x 10(-9)), ZNF652 (P = 5 x 10(-9)) and PLCD3 (P = 1 x 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
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35.
  • Olsson Möller, Ulrika, et al. (författare)
  • Prevalence and predictors of falls and dizziness in people younger and older than 80 years of age-A longitudinal cohort study
  • 2013
  • Ingår i: Archives of gerontology and geriatrics (Print). - : Elsevier Ireland Ltd. - 0167-4943 .- 1872-6976. ; 56:1, s. 160-168
  • Tidskriftsartikel (refereegranskat)abstract
    • The objectives were to investigate the prevalence and predictors for falls and dizziness among people younger and older than 80 years of age. The sample was drawn from the Swedish National study on Aging and Care (SNAC) and comprised 973 and 1273 subjects with data on the occurrence of falls and dizziness respectively at baseline. Follow-ups were made after 3- and 6-years. Data included socio-demographics, physical function, health complaints, cognition, quality of life and medications. The prevalence of falls was 16.5% in those under aged 80 and 31.7% in those 80+ years while dizziness was reported by 17.8% and 31.0% respectively. Predictors for falls in those under aged 80 were neuroleptics, dependency in personal activities of daily living (PADL), a history of falling, vision impairment and higher age, and in those 80+ years a history of falling, dependency in instrumental activities of daily living (IADL), fatigue and higher age. Factors predicting dizziness in those under aged 80 were a history of dizziness, feeling nervous and reduced grip strength and in those 80+ years a history of dizziness and of falling. Predictors for falls and dizziness differed according to age. Specific factors were identified in those under aged 80. In those 80+ years more general factors were identified implying the need for a comprehensive investigation to prevent falls. This longitudinal study also showed that falling and dizziness in many older people are persistent and therefore should be treated as chronic conditions. (c) 2012 Elsevier Ireland Ltd. All rights reserved.
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36.
  • Onufrey, Ksenia, 1985-, et al. (författare)
  • Digital tools for self-study and examination
  • 2019
  • Konferensbidrag (refereegranskat)abstract
    • Digitalization and increased use of information and communication technology (ICT) are major change processes taking place in engineering education today. Self-study and examination are areas with high potential for beneficial use of digital ICT tools. Some advantages with such tools are that students' can continuously assess their own learning in relation to the course objectives while they also can provide an opportunity to meet the teachers' needs to control how the students absorb the course material. Moreover, automatic provision of quick or instant feedback through digital tools can stimulate students’ commitment and active learning and allow students greater flexibility in their learning process, with tests that can be conducted online regardless of time and space and can be repeated as needed. The purpose of this paper is to investigate how different types of ICT-based self-study and examination practices can be implemented in courses on topics such as project management, product development, and entrepreneurship, and build a knowledge base necessary for future systematic implementation of digital examinations. Our study is based on an educational development project at Linköping University, where we tested and evaluated different models and approaches for digital knowledge testing in a number of selected courses.We discuss both positive and potentially problematic aspects of the use of digital tools and conclude that successful implementation is dependent on well-planned integration of such tools into the overall course where different types of activities enhance each other. Thus, this study connects the areas of digital self- study and examination and provides examples of first steps on the way towards implementation of ICT-based examination practices.
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37.
  • Remberger, Mats, et al. (författare)
  • Improved survival after allogeneic hematopoietic stem cell transplantation in recent years : A single-center study
  • 2011
  • Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 17:11, s. 1688-1697
  • Tidskriftsartikel (refereegranskat)abstract
    • We analyzed the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) over the past 2 decades. Between 1992 and 2009, 953 patients were treated with HSCT, mainly for a hematologic malignancy. They were divided according to 4 different time periods of treatment: 1992 to 1995, 1996 to 2000, 2001 to 2005, and 2006 to 2009. Over the years, many factors have changed considerably regarding patient age, diagnosis, disease stage, type of donor, stem cell source, genomic HLA typing, cell dose, type of conditioning, treatment of infections, use of granulocyte-colony stimulating factor (G-CSF), use of mesenchymal stem cells, use of cytotoxic T cells, and home care. When we compared the last period (2006-2009) with earlier periods, we found slower neutrophil engraftment, a higher incidence of acute graft-versus-host disease (aGVHD) of grades II-IV, and less chronic GVHD (cGHVD). The incidence of relapse was unchanged over the 4 periods (22%-25%). Overall survival (OS) and transplant-related mortality (TRM) improved significantly in the more recent periods, with the best results during the last period (2006-2009) and a 100-day TRM of 5.5%. This improvement was also apparent in a multivariate analysis. When correcting for differences between the 4 groups, the hazard ratio for mortality in the last period was 0.59 (95% confidence interval [CI]: 0.44-0.79; P < .001) and for TRM it was 0.63 (CI: 0.43-0.92; P = .02). This study shows that the combined efforts to improve outcome after HSCT have been very effective. Even though we now treat older patients with more advanced disease and use more alternative HLA nonidentical donors, OS and TRM have improved. The problem of relapse still has to be remedied. Thus, several different developments together have resulted in significantly lower TRM and improved survival after HSCT over the last few years.
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38.
  • Rodríguez-Varela, Ricardo, et al. (författare)
  • The genetic history of Scandinavia from the Roman Iron Age to the present
  • 2023
  • Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 186:1, s. 32-46
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigate a 2,000-year genetic transect through Scandinavia spanning the Iron Age to the present, based on 48 new and 249 published ancient genomes and genotypes from 16,638 modern individuals. We find regional variation in the timing and magnitude of gene flow from three sources: the eastern Baltic, the British-Irish Isles, and southern Europe. British-Irish ancestry was widespread in Scandinavia from the Viking period, whereas eastern Baltic ancestry is more localized to Gotland and central Sweden. In some regions, a drop in current levels of external ancestry suggests that ancient immigrants contributed proportionately less to the modern Scandinavian gene pool than indicated by the ancestry of genomes from the Viking and Medieval periods. Finally, we show that a north-south genetic cline that characterizes modern Scandinavians is mainly due to the differential levels of Uralic ancestry and that this cline existed in the Viking Age and possibly earlier.
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39.
  • Romare, Charlotte, et al. (författare)
  • Burden of care related to monitoring patient vital signs during intensive care; a descriptive retrospective database study
  • 2022
  • Ingår i: Intensive & Critical Care Nursing. - : Elsevier. - 0964-3397 .- 1532-4036. ; 71
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aim of this study was to describe burden of care related to monitoring patient vital signs of intensive care unit patients in a Swedish hospital. Setting: Data collected by “The Swedish Intensive Care Registry” from one general category II intensive care unit in a Swedish hospital was included in this study. Data from year 2014 to 2020 was analysed comprising a total of 3617 intensive care episodes and 29,165 work shifts. Research methodology: This is a retrospective database study. Descriptive statistics gave an overview of the dataset. To test for differences between variables related to burden of care for “Documentation of monitoring” Mann Whitney U test and Kruskal Wallis test was performed using STATA. Results: “Documentation of monitoring” was reported to generate a prominent burden of care during intensive care. Nearly all patients had continuous monitoring. Comparison for burden of care related to “Documentation of monitoring” for sexes generated no statistically significant difference. Comparison for burden of care related to “Documentation of monitoring” among age groups, diagnose groups and time of day generated statistically significant differences. Conclusion: Monitoring patient vital signs was clearly present during intensive care, hence impacting intensive care nurses’ clinical practice. Further research is endorsed to improve and facilitate monitoring to keep improving patient safety.
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40.
  • Romare, Charlotte, 1979-, et al. (författare)
  • Nurse anesthetists’ experiences using smart glasses to monitor patients’ vital signs during anesthesia care : A qualitative study
  • 2021
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16:4 April
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose To describe nurse anesthetists’ experiences using smart glasses to monitor patients’ vital signs during anesthesia care. Methods Data was collected through individual semi-structured interviews with seven nurse anesthetists who had used smart glasses, with a customized application for monitoring vital signs, during clinical anesthesia care. Data was analyzed using thematic content analysis. Results An overarching theme became evident during analysis; Facing and embracing responsibility. Being a nurse anesthetist entails a great responsibility, and the participants demonstrated that they shouldered this responsibility with pride. The theme was divided in two sub-themes. The first of these, A new way of working, comprised the categories Adoption and Utility. This involved incorporating smart glasses into existing routines in order to provide safe anesthesia care. The second sub-theme, Encountering side effects, consisted of the categories Obstacles and Personal affect. This sub-theme concerned the possibility to use smart glasses as intended, as well as the affect on nurse anesthetists as users. Conclusion Smart glasses improved access to vital signs and enabled continuous monitoring regardless of location. Continued development and improvement, both in terms of the application software and the hardware, are necessary for smart glasses to meet nurse anesthetists’ needs in clinical practice. Copyright: 
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41.
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42.
  • Sennblad, Bengt, et al. (författare)
  • primetv : a viewer for reconciled trees
  • 2007
  • Ingår i: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 8, s. 148-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Evolutionary processes, such as gene family evolution or parasite-host cospeciation, can often be viewed as a tree evolving inside another tree. Relating two given trees under such a constraint is known as reconciling them. Adequate software tools for generating illustrations of tree reconciliations are instrumental for presenting and communicating results and ideas regarding these phenomena. Available visualization tools have been limited to illustrations of the most parsimonious reconciliation. However, there exists a plethora of biologically relevant non-parsimonious reconciliations. Illustrations of these general reconciliations may not be achieved without manual editing. Results: We have developed a new reconciliation viewer, primetv. It is a simple and compact visualization program that is the first automatic tool for illustrating general tree reconciliations. It reads reconciled trees in an extended Newick format and outputs them as tree-within-tree illustrations in a range of graphic formats. Output attributes, such as colors and layout, can easily be adjusted by the user. To enhance the construction of input to primetv, two helper programs, readReconciliation and reconcile, accompany primetv. Detailed examples of all programs' usage are provided in the text. For the casual user a web-service provides a simple user interface to all programs. Conclusion: With primetv, the first visualization tool for general reconciliations, illustrations of trees-within-trees are easy to produce. Because it clarifies and accentuates an underlying structure in a reconciled tree, e. g., the impact of a species tree on a gene-family phylogeny, it will enhance scientific presentations as well as pedagogic illustrations in an educational setting. primetv is available at http://prime.sbc.su.se/primetv, both as a standalone command-line tool and as a web service. The software is distributed under the GNU General Public License.
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43.
  • Ståhle, Alexander, et al. (författare)
  • Designguide för Smarta gator
  • 2022
  • Bok (övrigt vetenskapligt/konstnärligt)abstract
    • Designguiden för smarta gator konkretiserar hur de fyra megatrenderna urbanisering, digitalisering, samhällsförändringar och miljöförändringar leder till nya krav och utformningsprinciper för framtidens gator. Guiden är tänkt att fungera som en inspiration och ett underlag för att förnya svensk gatupolicy på nationell, regional och kommunal nivå.Guiden innehåller utöver en inledning följande kapitel: en historisk tillbakablick (gatans utveckling), gatans användning, gatans delar, gatans design, designprocessen, guidens genomförande.
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44.
  • Ulmert, David, et al. (författare)
  • Long-term prediction of prostate cancer: Prostate-specific antigen (PSA) velocity is predictive but does not improve the predictive accuracy of a single PSA measurement 15 years or more before cancer diagnosis in a large, representative, unscreened population
  • 2008
  • Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 26:6, s. 835-841
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose We tested whether total prostate-specific antigen velocity (tPSAv) improves accuracy of a model using PSA level to predict long-term risk of prostate cancer diagnosis. Methods During 1974 to 1986 in a preventive medicine study in Sweden, 5,722 men aged <= 50 gave two blood samples about 6 years apart. We measured free (fPSA) and total PSA (tPSA) in archived plasma samples from 4,907 participants. Prostate cancer was subsequently diagnosed in 443 (9%) men. Cox proportional hazards regression was used to evaluate tPSA and tPSAv as predictors of prostate cancer. Predictive accuracy was assessed by the concordance index. Results The median time from second blood draw to cancer diagnosis was 16 years; median follow-up for men without prostate cancer was 21 years. In univariate models, tPSA level at second assessment and tPSAv between first and second assessments were associated with prostate cancer (both P < .001). tPSAv was highly correlated with tPSA level (r = 0.93). Twenty-year probabilities of cancer for men at 50th, 90th, and 95th percentile of tPSA and tPSAv were 10.6%, 17.1%, and 21.2% for tPSA, and 9.1%, 11.8%, and 14.1% for tPSAv, respectively. The concordance index for tPSA level was 0.771. Adding tPSAv, fPSA, % fPSA or velocities of fPSA and % fPSA did not importantly increase accuracy of tPSA to predict prostate cancer. Results were unchanged if the analysis was restricted to patients with advanced cancer at diagnosis. Conclusion Although PSA velocity is significantly increased in men with prostate cancer up to two decades before diagnosis, it does not aid long-term prediction of prostate cancer.
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45.
  • Ulmert, David, et al. (författare)
  • Prostate-specific antigen at or before age 50 as a predictor of advanced prostate cancer diagnosed up to 25 years later: A case-control study
  • 2008
  • Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Based on a large, representative unscreened cohort from Malmo, Sweden, we have recently reported that a single prostate-specific antigen (PSA) measurement at or before age 50 is a strong predictor of prostate cancer occurring up to 25 years subsequently. We aimed to determine whether this association holds for advanced cancers, defined as clinical stage T3 or higher, or skeletal metastasis at the time of the cancer diagnosis. Methods: In 1974-1986 blood samples were obtained from a cohort of 21,277 men aged up to 50. Through 1999, 498 men were diagnosed with prostate cancer, and of these 161 had locally advanced or metastatic prostate cancers. Three controls, matched for age and date of venipuncture, were selected for each case. Conditional logistic regression was used to test associations between molecular markers and advanced cancer. Results: Median time from venipuncture to diagnosis was 17 years. Levels of all PSA forms and hK2 were associated with case status. Total PSA was a strong and statistically significant predictor of subsequent advanced cancer ( area under the curve 0.791; p < 0.0005). Two-thirds of the advanced cancer cases occurred in men with the top 20% of PSA levels (0.9 ng/ml or higher). Conclusion: A single PSA test taken at or before age 50 is a very strong predictor of advanced prostate cancer diagnosed up to 25 years later. This suggests the possibility of using an early PSA test to risk-stratify patients so that men at highest risk are the focus of the most intensive screening efforts.
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46.
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47.
  • Ulmert, David, et al. (författare)
  • Reproducibility and Accuracy of Measurements of Free and Total Prostate-Specific Antigen in Serum vs Plasma after Long-Term Storage at -20 {degrees}C.
  • 2006
  • Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 52:2, s. 235-239
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Long-term frozen storage may alter the results of prostate-specific antigen (PSA) measurements, mainly because of degradation of free PSA (fPSA) in vitro. We compared the effects of long-term storage on fPSA, total PSA (tPSA), and complexed PSA (cPSA) in serum vs EDTA-plasma samples. Methods: We measured fPSA and tPSA concentrations in matched pairs of archival serum and EDTA-plasma samples (stored frozen at -20 degrees C for 20 years) from a large population-based cohort in Malmo, Sweden. We also compared concentrations in age-matched men with those in samples not subjected to long-term storage, obtained from participants in a population-based study of prostate cancer screening in Goteborg, Sweden. These contemporary samples were handled according to standardized preanalytical. and analytical protocols aimed at minimizing in vitro degradation. tPSA and fPSA measurements were performed with a commercial assay (Prostatus Dual Assay; Perkin-Elmer Life Sciences). Results: Concentrations of tPSA and fPSA and calculated cPSA (tPSA-fPSA) in archival plasma were not significantly different from those in contemporary serum from age-matched men. In archival serum, however, random variability of fPSA was higher vs plasma than in contemporary samples, whereas systematic error of fPSA analyses was similarly small in archival and contemporary serum and plasma. Conclusions: Concentrations of tPSA and calculated cPSA were highly stable in plasma and serum samples subjected to long-term storage at -20 degrees C. Greater random variability, rather than a systematic decrease, may explain differences in fPSA analyses observed in archival serum. (c) 2006 American Association for Clinical Chemistry.
  •  
48.
  • van Kempen, Elise E.M.M., et al. (författare)
  • Children's annoyance reactions to aircraft and road traffic noise
  • 2009
  • Ingår i: Journal of the Acoustical Society of America. - : Acoustical Society of America. - 0001-4966 .- 1520-8524. ; 125:2, s. 895-904
  • Tidskriftsartikel (refereegranskat)abstract
    • Since annoyance reactions of children to environmental noise have rarely been investigated, no source specific exposure-response relations are available. The aim of this paper is to investigate children’s reactions to aircraft and road traffic noise and to derive exposure-response relations. To this end, children’s annoyance reactions to aircraft and road traffic noise in both the home and the school setting were investigated using the data gathered in a cross-sectional multicenter study, carried out among 2844 children age 9–11 years attending 89 primary schools around three European airports. An exposure-response relation was demonstrated between exposure to aircraft noise at school LAeq, 7–23 h and severe annoyance in children: after adjustment for confounders, the percentage severely annoyed children was predicted to increase from about 5.1% at 50 dB to about 12.1% at 60 dB. The findings were consistent across the three samples. Aircraft noise at home LAeq,7–23 h demonstrated a similar relation with severe annoyance. Children attending schools with higher road traffic noise LAeq,7–23 h were more annoyed. Although children were less annoyed at levels above 55 dB, the shapes of the exposure-response relations found among children were comparable to those found in their parents.
  •  
49.
  • Zackrisson, Olle, et al. (författare)
  • Nitrogen fixation increases with successional age in boreal forests
  • 2004
  • Ingår i: Ecology. - : Wiley. - 0012-9658. ; 85, s. 3327-3334
  • Tidskriftsartikel (refereegranskat)abstract
    • There is little understanding of successional dynamics of N fixation in northern boreal forests. Recent evidence suggests that N fixation by cyanobacteria in association with the common feather moss Pleurozium schreberi contributes to a significant proportion of the total N economy. The purpose of the work herein was to determine how time since last fire influences N fixation rates in boreal forests. We evaluated seasonal N fixation rates on a total of 12 natural forest preserves varying in time since last fire (35–355 years). Each site was monitored for N fixation activity using a calibrated acetylene reduction assay. Nitrogen fixation rates were found to increase linearly with time since fire. This increase in N fixation with succession is likely a function of degree of colonization by cyanobacteria and site factors such as presence of available N. Surface applications of 4.5 kg N·ha−1·yr−1 as NH4NO3 were found to eliminate N fixation while applications of P resulted in only a slight and temporary increase of N fixation rates. In contrast to common observation our findings suggest that N fixation in boreal forests becomes more important in late succession. Limited N availability in late succession is clearly one of the primary drivers of N fixation rates in boreal forest ecosystems. These findings may help to explain the origin of high rates of net N accumulation in soil unaccounted for at northern boreal sites.
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