| 1. |
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| 2. |
- Sliz, E., et al.
(author)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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| 3. |
- Kurki, MI, et al.
(author)
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FinnGen provides genetic insights from a well-phenotyped isolated population
- 2023
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 613:7944, s. 508-
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Journal article (peer-reviewed)abstract
- Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10–11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants.
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| 4. |
- Shah, S, et al.
(author)
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Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
- 2020
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 163-
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Journal article (peer-reviewed)abstract
- Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
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| 7. |
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| 8. |
- Zhao, J. H., et al.
(author)
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Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets
- 2023
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In: Nature Immunology. - : Springer Nature. - 1529-2908 .- 1529-2916. ; 24:9, s. 1540-1551
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Journal article (peer-reviewed)abstract
- Circulating proteins have important functions in inflammation and a broad range of diseases. To identify genetic influences on inflammation-related proteins, we conducted a genome-wide protein quantitative trait locus (pQTL) study of 91 plasma proteins measured using the Olink Target platform in 14,824 participants. We identified 180 pQTLs (59 cis, 121 trans). Integration of pQTL data with eQTL and disease genome-wide association studies provided insight into pathogenesis, implicating lymphotoxin-alpha in multiple sclerosis. Using Mendelian randomization (MR) to assess causality in disease etiology, we identified both shared and distinct effects of specific proteins across immune-mediated diseases, including directionally discordant effects of CD40 on risk of rheumatoid arthritis versus multiple sclerosis and inflammatory bowel disease. MR implicated CXCL5 in the etiology of ulcerative colitis (UC) and we show elevated gut CXCL5 transcript expression in patients with UC. These results identify targets of existing drugs and provide a powerful resource to facilitate future drug target prioritization. Here the authors identify genetic effectors of the level of inflammation-related plasma proteins and use Mendelian randomization to identify proteins that contribute to immune-mediated disease risk.
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| 9. |
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| 10. |
- Heidegger, A., et al.
(author)
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Development and inter-laboratory validation of the VISAGE enhanced tool for age estimation from semen using quantitative DNA methylation analysis
- 2022
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In: Forensic Science International: Genetics. - : Elsevier BV. - 1872-4973. ; 56
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Journal article (peer-reviewed)abstract
- The analysis of DNA methylation has become an established method for chronological age estimation. This has triggered interest in the forensic community to develop new methods for age estimation from biological crime scene material. Various assays are available for age estimation from somatic tissues, the majority from blood. Age prediction from semen requires different DNA methylation markers and the only assays currently developed for forensic analysis are based on SNaPshot or pyrosequencing. Here, we describe a new assay using massively parallel sequencing to analyse 13 candidate CpG sites targeted in two multiplex PCRs. The assay has been validated by five consortium laboratories of the VISible Attributes through GEnomics (VISAGE) project within a collaborative exercise and was tested for reproducible quantification of DNA methylation levels and sensitivity with DNA methylation controls. Furthermore, DNA extracts and stains on Whatman FTA cards from two semen samples were used to evaluate concordance and mimic casework samples. Overall, the assay yielded high read depths (> 1000 reads) at all 13 marker positions. The methylation values obtained indicated robust quantification with an average standard deviation of 2.8% at the expected methylation level of 50% across the 13 markers and a good performance with 50 ng DNA input into bisulfite conversion. The absolute difference of quantifications from one participating laboratory to the mean quantifications of concordance and semen stains of remaining laboratories was approximately 1%. These results demonstrated the assay to be robust and suitable for age estimation from semen in forensic investigations. In addition to the 13-marker assay, a more streamlined protocol combining only five age markers in one multiplex PCR was developed. Preliminary results showed no substantial differences in DNA methylation quantification between the two assays, indicating its applicability with the VISAGE age model for semen developed with data from the complete 13-marker tool.
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| 11. |
- Jaakonmäki, N., et al.
(author)
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Obesity and the Risk of Cryptogenic Ischemic Stroke in Young Adults
- 2022
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In: Journal of Stroke and Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057. ; 31:5
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Journal article (peer-reviewed)abstract
- Objectives: We examined the association between obesity and early-onset cryptogenic ischemic stroke (CIS) and whether fat distribution or sex altered this association. Materials and Methods: This prospective, multi-center, case-control study included 345 patients, aged 18-49 years, with first-ever, acute CIS. The control group included 345 age- and sex-matched stroke-free individuals. We measured height, weight, waist circumference, and hip circumference. Obesity metrics analyzed included body mass index (BMI), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), and a body shape index (ABSI). Models were adjusted for age, level of education, vascular risk factors, and migraine with aura. Results: After adjusting for demographics, vascular risk factors, and migraine with aura, the highest tertile of WHR was associated with CIS (OR for highest versus lowest WHR tertile 2.81, 95%CI 1.43-5.51; P=0.003). In sex-specific analyses, WHR tertiles were not associated with CIS. However, using WHO WHR cutoff values (>0.85 for women, >0.90 for men), abdominally obese women were at increased risk of CIS (OR 2.09, 95%CI 1.02-4.27; P=0.045). After adjusting for confounders, WC, BMI, WSR, or ABSI were not associated with CIS. Conclusions: Abdominal obesity measured with WHR was an independent risk factor for CIS in young adults after rigorous adjustment for concomitant risk factors. © 2022 The Author(s)
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| 12. |
- Jhun, Mina-A, et al.
(author)
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A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids
- 2021
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust and consistent association with blood lipid levels across multiple racial/ethnic groups. Abnormal blood lipid levels are important risk factors for cardiovascular and other various diseases. Here the authors conduct a large-scale multi-ethnic epigenome-wide association study combined with epigenetic (cis-QTL and eQTM) data, and identify CpG-lipid traits associations that are specific to or common across racial/ethnic groups.
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| 14. |
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| 15. |
- Anttila, V., et al.
(author)
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Direct intramyocardial injection of VEGF mRNA in patients undergoing coronary artery bypass grafting
- 2023
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In: Molecular Therapy. - : Elsevier BV. - 1525-0016. ; 31:3, s. 866-874
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Journal article (peer-reviewed)abstract
- Vascular endothelial growth factor A (VEGF-A) has therapeutic cardiovascular effects, but delivery challenges have impeded clinical development. We report the first clinical study of naked mRNA encoding VEGF-A (AZD8601) injected into the human heart. EPICCURE (ClinicalTrials.gov: NCT03370887) was a randomized, double-blind study of AZD8601 in patients with left ventricular ejection fraction (LVEF) 30%–50% who were undergoing elective coronary artery bypass surgery. Thirty epicardial injections of AZD8601 (total 3 mg) or placebo in citrate-buffered saline were targeted to ischemic but viable myocardial regions mapped using quantitative [15O]-water positron emission tomography. Seven patients received AZD8601 and four received placebo and were followed for 6 months. There were no deaths or treatment-related serious adverse events and no AZD8601-associated infections, immune reactions, or arrhythmias. Exploratory outcomes indicated potential improvement in LVEF, Kansas City Cardiomyopathy Questionnaire scores, and N-terminal pro-B-type natriuretic peptide levels, but the study is limited in size, and significant efficacy conclusions are not possible from the dataset. Naked mRNA without lipid encapsulation may provide a safe delivery platform for introducing genetic material to cardiac muscle, but further studies are needed to confirm efficacy and safety in a larger patient pool. © 2022
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| 16. |
- Hambäck, Peter A., et al.
(author)
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Tradeoffs and synergies in wetland multifunctionality : A scaling issue
- 2023
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In: Science of the Total Environment. - Amsterdam : Elsevier BV. - 0048-9697 .- 1879-1026. ; 862
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Research review (peer-reviewed)abstract
- Wetland area in agricultural landscapes has been heavily reduced to gain land for crop production, but in recent years there is increased societal recognition of the negative consequences from wetland loss on nutrient retention, biodiversity and a range of other benefits to humans. The current trend is therefore to re-establish wetlands, often with an aim to achieve the simultaneous delivery of multiple ecosystem services, i.e., multifunctionality. Here we review the literature on key objectives used to motivate wetland re-establishment in temperate agricultural landscapes (provision of flow regulation, nutrient retention, climate mitigation, biodiversity conservation and cultural ecosystem services), and their relationships to environmental properties, in order to identify potential for tradeoffs and synergies concerning the development of multifunctional wetlands. Through this process, we find that there is a need for a change in scale from a focus on single wetlands to wetlandscapes (multiple neighboring wetlands including their catchments and surrounding landscape features) if multiple societal and environmental goals are to be achieved. Finally, we discuss the key factors to be considered when planning for re-establishment of wetlands that can support achievement of a wide range of objectives at the landscape scale.
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| 17. |
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| 18. |
- Hedman, A. K., et al.
(author)
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Identification of novel pheno-groups in heart failure with preserved ejection fraction using machine learning
- 2020
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In: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 106:5, s. 342-349
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Journal article (peer-reviewed)abstract
- Objective Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. We aimed to derive HFpEF phenotype-based groups ('phenogroups') based on clinical and echocardiogram data using machine learning, and to compare clinical characteristics, proteomics and outcomes across the phenogroups. Methods We applied model-based clustering to 32 echocardiogram and 11 clinical and laboratory variables collected in stable condition from 320 HFpEF outpatients in the Karolinska-Rennes cohort study (56% female, median 78 years (IQR: 71-83)). Baseline proteomics and the composite end point of all-cause mortality or heart failure (HF) hospitalisation were used in secondary analyses. Results We identified six phenogroups, for which significant differences in the prevalence of concomitant atrial fibrillation (AF), anaemia and kidney disease were observed (p<0.05). Fifteen out of 86 plasma proteins differed between phenogroups (false discovery rate, FDR<0.05), including biomarkers of HF, AF and kidney function. The composite end point was significantly different between phenogroups (log-rank p<0.001), at short-term (100 days), mid-term (18 months) and longer-term follow-up (1000 days). Phenogroup 2 was older, with poorer diastolic and right ventricular function and higher burden of risk factors as AF (85%), hypertension (83%) and chronic obstructive pulmonary disease (30%). In this group a third experienced the primary outcome to 100 days, and two-thirds to 18 months (HR (95%CI) versus phenogroups 1, 3, 4, 5, 6: 1.5 (0.8-2.9); 5.7 (2.6-12.8); 2.9 (1.5-5.6); 2.7 (1.6-4.6); 2.1 (1.2-3.9)). Conclusions Using machine learning we identified distinct HFpEF phenogroups with differential characteristics and outcomes, as well as differential levels of inflammatory and cardiovascular proteins.
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| 19. |
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| 20. |
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| 21. |
- Mitselou, Niki, 1982-, et al.
(author)
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Preterm birth and risk of IgE sensitization up to early adulthood : a population-based birth cohort study
- 2021
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In: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:Suppl. 110, s. 397-399
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Journal article (other academic/artistic)abstract
- Background: Immunoglobulin E (IgE) sensitization is associated with asthma and allergic diseases. Gestational age influences early immune system development, thereby potentially affecting the process of tolerance induction to allergens. We aimed to study IgE sensitization to common allergens by gestational age from childhood up to early adulthood. Method: Population-based birth cohort, data from the Swedish BAMSE study was used. Allergen-specific IgE to a mix of common food (fx5) and inhalant (Phadiatop) allergens were analysed at 4, 8, 16 and 24 years. Sensitization was defined as allergen-specific IgE ≥0.35 kU A /l to fx5 and/or Phadiatop at each time-point. Using logistic regression and generalized estimated equations, adjusted odds ratios (aORs) for sensitization in relation to gestational age were calculated. Replication was sought within the Swedish twin study STOPPA.Results: In BAMSE, 3523 participants were screened for IgE anti-bodies during follow-up; of these, 197 (5.6%) were born preterm (<37 gestational weeks), and 330 (9.4%) post-term (≥42 weeks). Preterm birth was inversely associated with sensitization to common food and/or inhalant allergens up to early adulthood; overall aOR = 0.71 (95% CI = 0.51- 0.98). An inverse association was also observed between preterm birth and sensitization to food allergens specifically; overall aOR = 0.59 (95% CI = 0.38- 0.95). No relation was found between post-term birth and IgE sensitization at any time-point. Replication analyses in STOPPA ( N = 675) showed similar risk estimates for sensitization to food and/or inhalant allergens (aOR = 0.76; 95% CI: 0.45- 1.26), which resulted in a combined meta-analysis aOR = 0.72 (95% CI: 0.55- 0.95). Conclusion: Our study suggests an inverse association between preterm birth and later IgE sensitization.
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| 22. |
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Yildiz, B, et al.
(author)
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Live well, die well - an international cohort study on experiences, concerns and preferences of patients in the last phase of life: the research protocol of the iLIVE study
- 2022
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In: BMJ OPEN. - : BMJ. - 2044-6055. ; 12:8
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Journal article (other academic/artistic)abstract
- Adequately addressing the needs of patients at the end of life and their relatives is pivotal in preventing unnecessary suffering and optimising their quality of life. The purpose of the iLIVE study is to contribute to high-quality personalised care at the end of life in different countries and cultures, by investigating the experiences, concerns, preferences and use of care of terminally ill patients and their families.Methods and analysisThe iLIVE study is an international cohort study in which patients with an estimated life expectancy of 6 months or less are followed up until they die. In total, 2200 patients will be included in 11 countries, that is, 200 per country. In addition, one relative per patient is invited to participate. All participants will be asked to fill in a questionnaire, at baseline and after 4 weeks. If a patient dies within 6 months of follow-up, the relative will be asked to fill in a post-bereavement questionnaire. Healthcare use in the last week of life will be evaluated as well; healthcare staff who attended the patient will be asked to fill in a brief questionnaire to evaluate the care that was provided. Qualitative interviews will be conducted with patients, relatives and healthcare professionals in all countries to gain more in-depth insights.Ethics and disseminationThe cohort study has been approved by ethics committees and the institutional review boards (IRBs) of participating institutes in all countries. Results will be disseminated through the project website, publications in scientific journals and at conferences. Within the project, there will be a working group focusing on enhancing the engagement of the community at large with the reality of death and dying.Trial registration numberNCT04271085.
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| 27. |
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| 28. |
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| 30. |
- Gaber, Sophie, et al.
(author)
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Enacting citizenship through participation in a technological society : A longitudinal three-year study among people with dementia in Sweden
- 2023
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In: Ageing & Society. - : Cambridge University Press. - 0144-686X .- 1469-1779. ; 43:2, s. 276-297
-
Journal article (peer-reviewed)abstract
- The role of Everyday Technology (ET) use is presented as subsidiary or neutral in policy for age- and dementia-friendly communities; and yet, research suggests that older people, especially those with dementia, experience increased challenges using ET in their everyday lives. Through the lens of micro-citizenship, the study aims to deepen the knowledge about how use of ET outside the home, including portable ETs, relates to participation in places visited within public space among people with dementia over time. Using a longitudinal study design, 35 people with dementia were recruited at baseline and followed over three years. Data were collected through semi-structured interviews using standardised questionnaires: the Participation in ACTivities and Places OUTside Home Questionnaire (ACT-OUT) and the Everyday Technology Use Questionnaire (ETUQ). Random intercept modelling and descriptive statistics were used to analyse the data. Throughout the three-year study, decreasing use of ET outside the home, including portable ETs, was associated with decreasing participation in places visited within public space, in a statistically significant way when controlling for age (F = 7.59, p = 0.01). The findings indicate that facilitating access and use of ET outside the home, among people with dementia, should be integral to promoting and maintaining participation in age- and dementia-friendly communities.
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| 31. |
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| 32. |
- Hambäck, P.A., et al.
(author)
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Trade-offs and synergies in the design of multifunctional wetlands : A scaling issue
- 2023
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In: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 862
-
Journal article (peer-reviewed)abstract
- Wetland area in agricultural landscapes has been heavily reduced to gain land for crop production, but in recent years there is increased societal recognition of the negative consequences from wetland loss on nutrient retention, biodiversity and a range of other benefits to humans. The current trend is therefore to re-establish wetlands, often with an aim to achieve the simultaneous delivery of multiple ecosystem services, i.e., multifunctionality. Here we review the literature on key objectives used to motivate wetland re-establishment in temperate agricultural landscapes (provision of flow regulation, nutrient retention, climate mitigation, biodiversity conservation and cultural ecosystem services), and their relationships to environmental properties, in order to identify potential for tradeoffs and synergies concerning the development of multifunctional wetlands. Through this process, we find that there is a need for a change in scale from a focus on single wetlands to wetlandscapes (multiple neighboring wetlands including their catchments and surrounding landscape features) if multiple societal and environmental goals are to be achieved. Finally, we discuss the key factors to be considered when planning for re-establishment of wetlands that can support achievement of a wide range of objectives at the landscape scale.
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Smith-Byrne, K, et al.
(author)
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The Blood Proteome of Cancer Risk
- 2022
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In: GENETIC EPIDEMIOLOGY. - 0741-0395. ; 46:7, s. 534-534
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Conference paper (other academic/artistic)
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| 37. |
- Strand, John A., et al.
(author)
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Anlagda våtmarker som flödesbuffrare : Hur skapar vi synergieffekter medbiologisk mångfald och pollinering?
- 2024
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Reports (other academic/artistic)abstract
- Anlagda våtmarker har använts som naturbaserade lösningar på miljöproblem sedan 1990-talet i Sverige, framför allt i jordbrukslandskapet. Inledningsvis var huvudsyftet kostnadseffektiva åtgärder för att minska övergödningseffekter i havet men även våtmarkers positiva effekt på den biologiska mångfalden betonades tidigt. Under det senaste decenniet har anlagda våtmarker också diskuterats som lösning på andra miljönyttor, som flödesbuffring, vattenmagasinering och för att hålla kvar kol i organogena marker. För de senare ekosystemtjänsterna är forskningsläget emellertid osäkert och för vissa, såsom flödesbuffring, har det saknats faktiska mätdata. Denna brist är speciellt tydligt på de större landskapsskalor som behöver studeras för att exempelvis förstå våtmarkers och våtmarkslandskapens förmåga att förhindra översvämning lokalt och av nedströms belägna områden. I frånvaro av mätdata har förväntade positiva effekter i stället modellerats fram genom att utgå från parametrar som nederbörd och avrinningsområdens egenskaper. För att studera betydelsen av anlagda våtmarker i jordbrukslandskapet på flödesbuffring, dvs vattenmagasineringsförmågan, samt hur denna förmåga påverkar biologisk mångfald, har projektet samlat ett konsortium av experter och forskare inom framför allt ekologi och hydrologi. Inom ramen för projektet har en omfattande och strategisk provtagning genomförts under 3 år, av hydrologiska och ekologiska parametrar samt biologisk mångfald. Förutom dessa fältmätningar har även markägarnas åsikter kring värdet av sina anlagda våtmarker undersökts. Resultaten visar att anlagda våtmarker i jordbrukslandskapet har en stor potential att fungera som flödesutjämnare och buffra vatten både i den enskilda våtmarken och på landskapsnivå. Samtidigt gynnas en stor mängd organismgrupper, inklusive specialiserade våtmarksarter på nationella hotlistor. Resultaten visar också att för både flödesbuffring och biologisk mångfald finns flera avgörande parametrar vad gäller placering och design som styr hur väl en våtmark faktiskt levererar dessa ekosystemtjänster. De anlagda våtmarkerna i studien är huvudsakligen grävda dammar optimerade för näringsavskiljning och var därigenom relativt små och tog huvudsakligen emot dräneringsvatten från åkermark. Trots storleken bidrog de undersökta våtmarkerna till att dämpa högflöden med 3–17 %, vilket är i paritet med mätningar från naturliga våtmarker i tidigare studier (cirka 10 %). Det visade sig också att våtmarkerna bibehöll sina buffrande funktioner både under kortare högflödesperioder samt under ett år med hög årsnederbörd, vilket indikerar att de kan fungera med liknande effektivitet i ett framtida klimat med högre avrinning. Vid extremnederbörd framstår dock de buffrade volymerna i dessa små våtmarker som otillräckliga för att kunna fungera som (enskild) åtgärd, både idag och i framtiden. Till skillnad från naturliga våtmarker fanns inga starka samband mellan flödesbuffringen i studiens anlagda våtmarker och deras position i avrinningsområdet. Varken våtmarkens höjd över havet eller nerströms/uppströms placering i avrinningsområdet påverkade buffringsförmågan. Det fanns dock andra faktorer som påverkade våtmarkernas buffring, som att buffringen ökade med storleken på våtmarkens tillrinningsområden. Den effekten var delvis oväntad eftersom våtmarker med stora tillrinningsområde borde fyllas snabbare, vara fulla under längre tid och därmed buffra mindre effektivt. Resultaten tyder dock på att den tekniska utformningen på våtmarkerna ger dem god buffringskapacitet trots hög hydrologisk belastning. Resultaten visar också att det finns marginal för att förbättra buffringen genom tekniska anläggningsmekanismer, särskilt i fråga om tömningsmöjligheterna och reglerbarheten i utloppskonstruktionerna. Våra data visar att endast 47 % av den teoretiska volymförändringspotentialen utnyttjades i våtmarkerna, vilket kan medge ökad buffringspotential genom aktiv tömning/sänkning inför stora nederbördssituationer. De kraftiga vattennivåvariationerna i många av våtmarkerna, i kombination med förekomst av både flacka partier och brantare släntlutning, var positivt för artrikedomen hos flera organismgrupper. Generellt gynnades mångfalden hos flera grupper av större strandvåtmarker och flacka stränder, men det fanns undantag. Till exempel gynnades nätbyggande spindlar av brantare stränder. Ett oväntat resultat var också den begränsade eller till och med negativa effekten av betande djur, vilket går stick i stäv med rekommendationer i manualer för våtmarksanläggning och skötsel. Sannolikt gynnas leddjuren av att vegetationen hålls kort men samtidigt kan de rent fysiska effekterna av trampet missgynna artgrupper som har sin larvutveckling i blöt jord. För att förstå dessa samband behövs mer forskning som går in på mekanismer samt hur effekten påverkas av djurslag, djurtäthet och jordart. För insekter som utvecklas i vatten, som trollsländor, sågs inga samband med hydrologiska parametrar, men det var uppenbart att små, anlagda våtmarker är veritabla artöar för trollsländor. Totalt noterades 68 % av alla Sveriges arter på en yta (800 km2) som motsvarar 0,0015 % av Sveriges yta. Artsammansättning skilde sig mellan våtmarker och för att nå höga artantal på landskapsnivå kan det därför vara en fördel med många olika våtmarker i en region. För pollinatörer, särskilt bin, fanns korrelation mellan förekomst och storleken på våtmarkernas minsta vattenareal (dvs, när de är som mest uttorkade). Markägarenkäten visade att markägarna överlag ser mest nyttor, snarare än problem, med anlagda våtmarker. Mest notabelt var den höga nöjdheten med våtmarker (91 %) samt att en mycket stor andel markägare (83 %) använder sin våtmark för personlig rekreation, där skridskoåkning var populärast. Slutsatsen från studierna är att anlagda våtmarker som konstruerats för näringsavskiljning och i viss mån biologisk mångfald kan fungera bra som flödesbuffrare. Dessutom finns stor potential för ökad buffringskapacitet genom att både utformning (inte minst in- och utloppslösningar och aktiv nivåstyrning i våtmarkerna), läge och skötsel har en stor påverkan på den totala effekten. Dessutom verkar det finnas möjliga synergieffekter mellan vattennivåvariationer och artrikedomen av leddjur, men för att nå en hög biologisk mångfald i anlagda våtmarker bör stränderna vara heterogena eller att olika våtmarker har olika struktur.
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| 39. |
- Anttila, V., et al.
(author)
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Synthetic mRNA Encoding VEGF-A in Patients Undergoing Coronary Artery Bypass Grafting: Design of a Phase 2a Clinical Trial
- 2020
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In: Molecular Therapy-Methods & Clinical Development. - : Elsevier BV. - 2329-0501. ; 18, s. 464-472
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Journal article (peer-reviewed)abstract
- Therapeutic angiogenesis may improve outcomes in patients with coronary artery disease undergoing surgical revascularization. Angiogenic factors may promote blood vessel growth and regenerate regions of ischemic but viable myocardium. Previous clinical trials of vascular endothelial growth factor A (VEGF-A) gene therapy with DNA or viral vectors demonstrated safety but not efficacy. AZD8601 is VEGF-A(165) mRNA formulated in biocompatible citrate-buffered saline and optimized for high-efficiency VEGF-A expression with minimal innate immune response. EPICCURE is an ongoing randomized, double-blind, placebo-controlled study of the safety of AZD8601 in patients with moderately decreased left ventricular function (ejection fraction 30% 50%) undergoing elective coronary artery bypass surgery. AZD8601 3 mg, 30 mg, or placebo is administered as 30 epicardial injections in a 10-min extension of cardioplegia. Injections are targeted to ischemic but viable myocardial regions in each patient using quantitative O-15-water positron emission tomography (PET) imaging (stress myocardial blood flow < 2.3 mL/g/min; resting myocardial blood flow > 0.6 mL/g/min). Improvement in regional and global myocardial blood flow quantified with O-15-water PET is an exploratory efficacy outcome, together with echocardiographic, clinical, functional, and biomarker measures. EPICCURE combines high-efficiency delivery with quantitative targeting and follow-up for robust assessment of the safety and exploratory efficacy of VEGF-A mRNA angiogenesis (ClinicalTrials.gov: NCT03370887).
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| 40. |
- Axelsson, Malin, 1964-, et al.
(author)
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Underdiagnosis and misclassification of COPD in Sweden - A Nordic Epilung study
- 2023
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In: Respiratory Medicine. - : Elsevier. - 0954-6111 .- 1532-3064. ; 217
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Journal article (peer-reviewed)abstract
- Introduction: The prevalence of COPD tends to level off in populations with decreasing prevalence of smoking but the extent of underdiagnosis in such populations needs further investigation.Aim: To investigate underdiagnosis and misclassification of COPD with a focus on socio-economy, lifestyle determinants and healthcare utilization.Method: The 1839 participants were selected from two ongoing large-scale epidemiological research programs: The Obstructive Lung Disease in Northern Sweden Studies and the West Sweden Asthma Study. COPDGOLD was defined according to the fixed post-bronchodilator spirometric criteria FEV1/FVC<0.70 in combination with respiratory symptoms. Results: Among the 128 participants who fulfilled the criteria for COPDGOLD, the underdiagnosis was 83.6% (n = 107) of which 57.9% were men. The undiagnosed participants were younger, had higher FEV1% of predicted and less frequently a family history of bronchitis. One in four of the undiagnosed had utilized healthcare and had more frequently utilized healthcare due to a burden of respiratory symptoms than the general population without COPD. Underdiagnosis was not related to educational level. Misclassification of COPD was characterized by being a woman with low education, ever smoker, having respiratory symptoms and having a previous asthma diagnosis.Conclusion: In the high income country Sweden, the underdiagnosis of COPD was highly prevalent. Reduced underdiagnosis can contribute to risk factor modification, medical treatment and self-management strategies in early stages of the disease, which may prevent disease progression and improve the quality of life among those affected. Therefore, there is a need to increase the use of spirometry in primary care to improve the diagnostic accuracy.
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| 44. |
- Bermúdez Barón, Nicolás, et al.
(author)
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Among respiratory symptoms, wheeze associates most strongly with impaired lung function in adults with asthma: a long-term prospective cohort study
- 2021
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In: BMJ Open Respiratory Research. - : BMJ. - 2052-4439. ; 8:1
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Journal article (peer-reviewed)abstract
- Background Asthma is a common disease and a major public health concern. Respiratory symptoms are related to its prognosis, which in turn associates with lung function. Still this association on a long-term basis is not entirely understood. Aim To study the association of the type and number of respiratory symptoms with FEV1 and FEV1 decline in women and men with asthma. Method A population-based cohort of adults with asthma was examined at study entry between 1986 and 2001 and at follow-up between 2012 and 2014, and n=977 had valid measurements of FEV1 on both occasions. Data regarding respiratory symptoms at study entry (recurrent wheeze, dyspnoea, longstanding cough and productive cough) were analysed in relation to FEV1 and annual decline in FEV1, both unadjusted and adjusted for other potentially associated factors by linear regression. Results For both sexes recurrent wheeze and dyspnoea were associated with lower FEV1 at study entry and follow-up, while productive cough was associated with lower FEV1 only at follow-up. No associations were found between the type of symptoms and annual decline in FEV1. In adjusted analyses, the association between recurrent wheeze and lower FEV1 both at study entry and follow-up remained significant among women. Also, the association between a higher number of symptoms with lower FEV1 both at study entry and follow-up were present for both sexes and remained after adjustment. Conclusions Particularly recurrent wheeze and a higher number of respiratory symptoms may predict lower lung function also in the long run among women and men with asthma.
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| 46. |
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| 47. |
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| 48. |
- Bunne, Joakim, et al.
(author)
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The Majority of Children Sensitized Before School-Age Develop Allergic Disease Before Adulthood: A Longitudinal Population-Based Study
- 2022
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In: Journal of Allergy and Clinical Immunology: In Practice. - : Elsevier BV. - 2213-2198 .- 2213-2201. ; 10:2
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Journal article (peer-reviewed)abstract
- Background: Allergic sensitization increases the risk of asthma and allergic rhinitis, but the impact of age at onset of sensitization is less studied. Objective: To examine the cumulative incidence of asthma and rhinitis up to age 19 years in relation to age at onset of sensitization to airborne allergens. Method: All children in grade 1 and 2 (median age, 8 years) in 2 municipalities in Northern Sweden were invited to undergo skin prick tests and answer a questionnaire about allergic diseases, and 88% participated. At ages 12 and 19 years, the protocol was repeated, and 1510 individuals participated in all 3 examinations. Specific IgE data were collected in a random sample at age 19 years (n = 770). Onset of sensitization was defined: 8 years or less, 8 to 12 years, 12 to 19 years, and never sensitized. Adjusted Poisson regression was used to calculate risk ratios (RRs). Results: At 19 years, those sensitized at 8 years of age or earlier had the highest risk of asthma (RR, 4.68; 95% CI, 3.15-6.97) and rhinitis (RR, 22.3; 95% CI, 13.3-37.6), and 84% had developed either asthma or rhinitis. The combination of sensitization at age 8 years or earlier and family history of allergic diseases rendered high risks for asthma (RR, 10.6; 95% CI, 6.71-16.7) and rhinitis (RR, 36.3; 95% CI, 18.9-69.7). Individuals sensitized at age 8 years or earlier showed significantly highest level of sensitization, as judged by number of positive skin test results and titers of specific IgE. Conclusions: Most individuals with sensitization at age 8 years or earlier developed asthma or rhinitis before young adulthood. The high level of sensitization in those sensitized early contributes to the high incidence of allergic airway conditions. © 2021 The Authors
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| 49. |
- de Melo, A. L. L., et al.
(author)
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Single-molecule array assay reveals the prognostic impact of plasma LRIG1 in ovarian carcinoma
- 2022
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In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 61:11, s. 1425-1433
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Journal article (peer-reviewed)abstract
- Background Ovarian carcinoma is the eighth most common cause of cancer death in women worldwide. The disease is predominantly diagnosed at a late stage. This contributes to high recurrence rates, eventually leading to the development of treatment-resistant disease. Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is a transmembrane protein that functions as a tumor suppressor and regulator of growth factor signaling. LRIG1 levels have not been investigated in human plasma previously. Materials and methods A quantitative LRIG1-specific single molecule array assay was developed and validated. LRIG1 levels were quantified in plasma samples from 486 patients with suspicious ovarian masses. Results Among women with ovarian carcinoma, LRIG1 levels were significantly elevated compared to women with benign or borderline type tumors. High LRIG1 plasma levels were associated with worse overall survival and shorter disease-free survival both in the group of all malignant cases and among the stage 3 cases only. LRIG1 was an independent prognostic factor in patients with stage 3 ovarian carcinoma. Conclusion LRIG1 plasma levels were elevated in patients with ovarian carcinoma, and high levels were associated with poor prognosis, suggesting that LRIG1 might be an etiologic factor and a potentially useful biomarker in ovarian carcinoma.
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