| 1. |
- Cutululis, Nicolaos Antonio, et al.
(författare)
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Challenges Towards the Deployment of Offshore Grids: the OffshoreDC Project
- 2014
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Ingår i: 13th International Workshop on Large-Scale Integration of Wind Power into Power Systems as well as on Transmission Networks for Offshore Wind Plants, Berlin, Germany, 11-13 Nov. 2014. - 9783981387094
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Konferensbidrag (refereegranskat)abstract
- This paper summarizes challenges towards the deployment of offshore grids which are dealt with in the Nordic OffshoreDC project. The OffshoreDC project studies the techno-economic challenges related to assessment of the value and use of optimization in the design of offshore grids. The project also studies the technical challenges related to control, protection and provision of ancillary services from HVDC grids with connected wind power plants. Finally, the transients in the DC grids are studied in the project.
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| 2. |
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| 3. |
- Konki, Mikko, et al.
(författare)
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Peripheral blood DNA methylation differences in twin pairs discordant for Alzheimer's disease.
- 2019
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Ingår i: Clinical Epigenetics. - : BioMed Central. - 1868-7083 .- 1868-7075. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Alzheimer's disease results from a neurodegenerative process that starts well before the diagnosis can be made. New prognostic or diagnostic markers enabling early intervention into the disease process would be highly valuable. Environmental and lifestyle factors largely modulate the disease risk and may influence the pathogenesis through epigenetic mechanisms, such as DNA methylation. As environmental and lifestyle factors may affect multiple tissues of the body, we hypothesized that the disease-associated DNA methylation signatures are detectable in the peripheral blood of discordant twin pairs.RESULTS: Comparison of 23 disease discordant Finnish twin pairs with reduced representation bisulfite sequencing revealed peripheral blood DNA methylation differences in 11 genomic regions with at least 15.0% median methylation difference and FDR adjusted p value ≤ 0.05. Several of the affected genes are primarily associated with neuronal functions and pathologies and do not display disease-associated differences in gene expression in blood. The DNA methylation mark in ADARB2 gene was found to be differentially methylated also in the anterior hippocampus, including entorhinal cortex, of non-twin cases and controls. Targeted bisulfite pyrosequencing of the DNA methylation mark in ADARB2 gene in 62 Finnish and Swedish twin pairs revealed that, in addition to the disease status, DNA methylation of this region is influenced by gender, age, zygosity, APOE genotype, and smoking. Further analysis of 120 Swedish twin pairs indicated that this specific DNA methylation mark is not predictive for Alzheimer's disease and becomes differentially methylated after disease onset.CONCLUSIONS: DNA methylation differences can be detected in the peripheral blood of twin pairs discordant for Alzheimer's disease. These DNA methylation signatures may have value as disease markers and provide insights into the molecular mechanisms of pathogenesis. We found no evidence that the DNA methylation marks would be associated with gene expression in blood. Further studies are needed to elucidate the potential importance of the associated genes in neuronal functions and to validate the prognostic or diagnostic value of the individual marks or marker panels.
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| 4. |
- Laajala, Essi, et al.
(författare)
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Permutation-based significance analysis reduces the type 1 error rate in bisulfite sequencing data analysis of human umbilical cord blood samples
- 2022
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Ingår i: Epigenetics. - : Taylor & Francis. - 1559-2294 .- 1559-2308. ; 17:12, s. 1608-1627
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation patterns are largely established in-utero and might mediate the impacts of in-utero conditions on later health outcomes. Associations between perinatal DNA methylation marks and pregnancy-related variables, such as maternal age and gestational weight gain, have been earlier studied with methylation microarrays, which typically cover less than 2% of human CpG sites. To detect such associations outside these regions, we chose the bisulphite sequencing approach. We collected and curated clinical data on 200 newborn infants; whose umbilical cord blood samples were analysed with the reduced representation bisulphite sequencing (RRBS) method. A generalized linear mixed-effects model was fit for each high coverage CpG site, followed by spatial and multiple testing adjustment of P values to identify differentially methylated cytosines (DMCs) and regions (DMRs) associated with clinical variables, such as maternal age, mode of delivery, and birth weight. Type 1 error rate was then evaluated with a permutation analysis. We discovered a strong inflation of spatially adjusted P values through the permutation analysis, which we then applied for empirical type 1 error control. The inflation of P values was caused by a common method for spatial adjustment and DMR detection, implemented in tools comb-p and RADMeth. Based on empirically estimated significance thresholds, very little differential methylation was associated with any of the studied clinical variables, other than sex. With this analysis workflow, the sex-associated differentially methylated regions were highly reproducible across studies, technologies, and statistical models.
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| 5. |
- Laajala, Essi, et al.
(författare)
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Umbilical cord blood DNA methylation in children who later develop type 1 diabetes
- 2021
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Ingår i: European Journal of Immunology. - : John Wiley & Sons. - 0014-2980 .- 1521-4141. ; 51:Suppl. 1, s. 291-291
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Distinct DNA methylation patterns have recently been observed to precede Type 1 Diabetes in whole blood collected from young children. Our aim was to determine if such methylation patterns are present already at the time of birth. Reduced representation bisulfite sequencing (RRBS) analysis was performed on a unique collection of umbilical cord blood samples collected within the Type 1 Diabetes Prediction and Prevention (DIPP) study. Children later diagnosed with Type 1 Diabetes and/or testing positive for multiple islet autoantibodies (N=43) were compared to control individuals (N=79), who remained autoantibody‐negative throughout the DIPP follow‐up until 15 years of age. Altogether 24 clinical and technical covariates related to the pregnancy and the mother were included in a binomial mixed effects model, which was fit separately for each high‐coverage CpG site, followed by spatial and multiple testing adjustment of P values. We discovered a strong inflation of P values, which was caused by a standard spatial adjustment method. Findings that were based on Benjamini‐Hochberg corrected spatially adjusted P values, could not be validated by Pyrosequencing. We therefore used permutation‐based significance analysis and showed that sex‐associated differentially methylated cytosines could be reproducibly detected with this approach. After empirical type 1 error control, no differences in cord blood methylation patterns were observed between cases and controls. Differences between children who progress to Type 1 Diabetes and those who remain healthy throughout childhood, are not yet present in the perinatal DNA methylome.
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| 6. |
- Laajala, Essi, et al.
(författare)
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Umbilical cord blood DNA methylation in children who later develop type 1 diabetes
- 2022
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 65:9, s. 1534-1540
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Distinct DNA methylation patterns have recently been observed to precede type 1 diabetes in whole blood collected from young children. Our aim was to determine whether perinatal DNA methylation is associated with later progression to type 1 diabetes.METHODS: Reduced representation bisulphite sequencing (RRBS) analysis was performed on umbilical cord blood samples collected within the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Study. Children later diagnosed with type 1 diabetes and/or who tested positive for multiple islet autoantibodies (n = 43) were compared with control individuals (n = 79) who remained autoantibody-negative throughout the DIPP follow-up until 15 years of age. Potential confounding factors related to the pregnancy and the mother were included in the analysis.RESULTS: No differences in the umbilical cord blood methylation patterns were observed between the cases and controls at a false discovery rate <0.05.CONCLUSIONS/INTERPRETATION: Based on our results, differences between children who progress to type 1 diabetes and those who remain healthy throughout childhood are not yet present in the perinatal DNA methylome. However, we cannot exclude the possibility that such differences would be found in a larger dataset.
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| 7. |
- Nielsen-Kudsk, Jens Erik, et al.
(författare)
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Left atrial appendage occlusion versus standard medical care in patients with atrial fibrillation and intracerebral haemorrhage : a propensity score-matched follow-up study
- 2017
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Ingår i: EuroIntervention. - : EUROPA EDITION. - 1774-024X .- 1969-6213. ; 13:3, s. 371-378
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The aim of this study was to investigate the prognosis in patients with atrial fibrillation (AF) and intracerebral haemorrhage (ICH) having a left atrial appendage occlusion (LAAO) versus patients receiving standard medical therapy. Methods and results: A total of 151 patients from the Nordic countries with AF and previous ICH who underwent LAAO using the AMPLATZER Cardiac Plug or the AMPLATZER AMULET were compared to a propensity score-matched group of 151 patients receiving standard medical therapy. The two groups were matched so that their risks for stroke and bleeding were similar (CHA2DS2-VASc and HAS-BLED scores). The standard care patients were identified from the Danish Stroke Registry among 787 patients with AF and ICH. The primary endpoint was a composite of all-cause mortality, ischaemic stroke and major bleeding. Patients with AF and a prior ICH treated with LAAO had a lower risk of the composite outcome as compared to patients treated with standard medical care (events/1,000 years [95% confidence interval]: 53.3 [44.3-64.1] vs. 366.7 [298.2-450.9]; hazard ratio 0.16 [0.07-0.37]). Conclusions: LAAO is suggested to be of major clinical benefit in AF patients having sustained an ICH. These results have to be confirmed in a randomised clinical trial.
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| 8. |
- Petrescu, Ana Maria Roxana, et al.
(författare)
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The uncertain climate footprint of wetlands under human pressure
- 2015
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 112:15, s. 4594-4599
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Tidskriftsartikel (refereegranskat)abstract
- Significant climate risks are associated with a positive carbon-temperature feedback in northern latitude carbon-rich ecosystems, making an accurate analysis of human impacts on the net greenhouse gas balance of wetlands a priority. Here, we provide a coherent assessment of the climate footprint of a network of wetland sites based on simultaneous and quasi-continuous ecosystem observations of CO2 and CH4 fluxes. Experimental areas are located both in natural and in managed wetlands and cover a wide range of climatic regions, ecosystem types, and management practices. Based on direct observations we predict that sustained CH4 emissions in natural ecosystems are in the long term (i.e., several centuries) typically offset by CO2 uptake, although with large spatiotemporal variability. Using a space-for-time analogy across ecological and climatic gradients, we represent the chronosequence from natural to managed conditions to quantify the "cost" of CH4 emissions for the benefit of net carbon sequestration. With a sustained pulse-response radiative forcing model, we found a significant increase in atmospheric forcing due to land management, in particular for wetland converted to cropland. Our results quantify the role of human activities on the climate footprint of northern wetlands and call for development of active mitigation strategies for managed wetlands and new guidelines of the Intergovernmental Panel on Climate Change (IPCC) accounting for both sustained CH4 emissions and cumulative CO2 exchange.
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| 9. |
- Poutanen, Markku, et al.
(författare)
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DynaQlim – Upper Mantle Dynamics and Quaternary Climate in Cratonic Areas
- 2010
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Ingår i: New Frontiers in Integrated Solid Earth Sciences. - Dordrecht : Springer. - 9789048127368 - 9789048127375 ; , s. 349-372
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The isostatic adjustment of the solid Earth to the glacial loading (GIA, Glacial Isostatic Adjustment) with its temporal signature offers a great opportunity to retrieve information of Earth’s upper mantle to the changing mass of glaciers and ice sheets, which in turn is driven by variations in Quaternary climate. DynaQlim (Upper Mantle Dynamics and Quaternary Climate in Cratonic Areas) has its focus to study the relations between upper mantle dynamics, its composition and physical properties, temperature, rheology, and Quaternary climate. Its regional focus lies on the cratonic areas of northern Canada and Scandinavia.Geodetic methods like repeated precise levelling, tide gauges, high-resolution observations of recent movements, gravity change and monitoring of postglacial faults have given information on the GIA process for more than 100 years. They are accompanied by more recent techniques like GPS observations and the GRACE and GOCE satellite missions which provide additional global and regional constraints on the gravity field. Combining geodetic observations with seismological investigations, studies of the postglacial faults and continuum mechanical modelling of GIA, DynaQlim offers new insights into properties of the lithosphere. Another step toward a better understanding of GIA has been the joint inversion of different types of observational data – preferentially connected with geological relative sea-level evidence of the Earth’s rebound during the last 10,000 years.Due to the changes in the lithospheric stress state large faults ruptured violently at the end of the last glaciation in large earthquakes, up to the magnitudes MW = 7–8. Whether the rebound stress is still able to trigger a significant fraction of intraplate seismic events in these regions is not completely understood due to the complexity and spatial heterogeneity of the regional stress field. Understanding of this mechanism is of societal importance.Glacial ice sheet dynamics are constrained by the coupled process of the deformation of the viscoelastic solid Earth, the ocean and climate variability. Exactly how the climate and oceans reorganize to sustain growth of ice sheets that ground to continents and shallow continental shelves is poorly understood. Incorporation of nonlinear feedback in modelling both ocean heat transport systems and atmospheric CO2 is a major challenge. Climate-related loading cycles and episodes are expected to be important, hence also more short-term features of palaeoclimate should be explicitly treated.Within this Chapter View ChapterIntroductionObservational BasisCurrent Models and Problems to be SolvedClimateChallenges with DynaQlimReferencesReferencesOther actionsExport citationsAbout this BookReprints and Permissions
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| 10. |
- Ristiniemi, Noora, et al.
(författare)
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Cystatin C as a predictor of all-cause mortality and myocardial infarction in patients with non-ST-elevation acute coronary syndrome
- 2012
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 1873-2933 .- 0009-9120. ; 45:7-8, s. 535-540
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the predictive value of cystatin C among patients diagnosed with non-ST-elevation acute coronary syndrome (nSTE-ACS). Design and methods: Admission serum samples from 245 nSTE-ACS patients were measured with a novel cystatin C immunoassay based on a dry-reagent, double monoclonal design. Creatinine concentrations, estimated glomerular filtration rates (eGFR) and one-year follow-up data were available for these patients. Results: During the follow-up period, 34 (14%) of patients had myocardial infarction (MI) and 25 (11%) died. Increased serum cystatin C was an independent predictor of all-cause mortality and combined events (all-cause mortality and MI) after adjustment to non-biomarker baseline factors, hazard ratio (HR) 2.19 (per increase of 1 tertile; 95% CI 1.28-3.78, p = 0.0046) and 1.75 (1.22-2.51, p = 0.0024), respectively. Corresponding values for eGFR were 2.56 (1.43-4.59, p = 0.0016) and 1.76 (1.23-2.53, p = 0.0022), respectively. Creatinine was not an independent predictor of endpoints (p > 0.05). Conclusions: Cystatin C was associated with an increased risk of death and combined events in patients with nSTE-ACS. (C) 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
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