| 1. |
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| 2. |
- Abreu, P, et al.
(författare)
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b-tagging in DELPHI at LEP
- 2004
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 32:2, s. 185-208
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Tidskriftsartikel (refereegranskat)abstract
- The standard method used for tagging b-hadrons in the DELPHI experiment at the CERN LEP Collider is discussed in detail. The main ingredient of b-tagging is the impact parameters of tracks, which relies mostly on the vertex detector. Additional information, such as the mass of particles associated to a secondary vertex, significantly improves the selection efficiency and the background suppression. The paper describes various discriminating variables used for the tagging and the procedure of their combination. In addition, applications of b-tagging to some physics analyses, which depend crucially on the performance and reliability of b-tagging, are described briefly.
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| 3. |
- Ahsan, Muhammad, et al.
(författare)
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The relative contribution of DNA methylation and genetic variants on protein biomarkers for human diseases.
- 2017
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 13:9
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Tidskriftsartikel (refereegranskat)abstract
- Associations between epigenetic alterations and disease status have been identified for many diseases. However, there is no strong evidence that epigenetic alterations are directly causal for disease pathogenesis. In this study, we combined SNP and DNA methylation data with measurements of protein biomarkers for cancer, inflammation or cardiovascular disease, to investigate the relative contribution of genetic and epigenetic variation on biomarker levels. A total of 121 protein biomarkers were measured and analyzed in relation to DNA methylation at 470,000 genomic positions and to over 10 million SNPs. We performed epigenome-wide association study (EWAS) and genome-wide association study (GWAS) analyses, and integrated biomarker, DNA methylation and SNP data using between 698 and 1033 samples depending on data availability for the different analyses. We identified 124 and 45 loci (Bonferroni adjusted P < 0.05) with effect sizes up to 0.22 standard units' change per 1% change in DNA methylation levels and up to four standard units' change per copy of the effective allele in the EWAS and GWAS respectively. Most GWAS loci were cis-regulatory whereas most EWAS loci were located in trans. Eleven EWAS loci were associated with multiple biomarkers, including one in NLRC5 associated with CXCL11, CXCL9, IL-12, and IL-18 levels. All EWAS signals that overlapped with a GWAS locus were driven by underlying genetic variants and three EWAS signals were confounded by smoking. While some cis-regulatory SNPs for biomarkers appeared to have an effect also on DNA methylation levels, cis-regulatory SNPs for DNA methylation were not observed to affect biomarker levels. We present associations between protein biomarker and DNA methylation levels at numerous loci in the genome. The associations are likely to reflect the underlying pattern of genetic variants, specific environmental exposures, or represent secondary effects to the pathogenesis of disease.
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| 4. |
- Backhaus, Erik, et al.
(författare)
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Antimicrobial susceptibility of invasive pneumococcal isolates from a region in south-west Sweden 1998-2001.
- 2007
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Ingår i: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 39:1, s. 19-27
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Tidskriftsartikel (refereegranskat)abstract
- Invasive disease caused by antibiotic resistant pneumococci is a worldwide problem. All invasive pneumococcal strains in an area of south-west Sweden with 1.7 million inhabitants were collected prospectively during 1998-2001. Minimum inhibitory concentrations (MICs) were determined by E-test and correlated to serotypes and clinical characteristics. Of 827 strains, 744 (90%) were susceptible (S) to all agents tested and 83 (10%) were indeterminate (I) or resistant (R) to at least 1 agent. 22 isolates (2.7%) were I to penicillin (MIC >0.06 to < or = 1.0 mg/l), but none were R (MIC >1.0 mg/l). Numbers and proportions of decreased susceptibility against other agents tested were as follows: erythromycin R: 30 (3.6%), clindamycin R: 6 (0.7%), tetracycline R: 16 (1.9%), moxifloxacin R: 1 (0.1%), cotrimoxazole I: 17 (2%) and R: 31(4%). Non-susceptibility to at least 1 agent was not correlated with age, clinical manifestation, underlying diseases and outcome. The serotype distribution differed between non-susceptible and susceptible strains. The serotypes in the 7-valent pneumococcal conjugate vaccine covered 42% of all infections and 73% of those caused by non-susceptible strains. In conclusion, the impact of antibiotic resistance in invasive pneumococcal disease remains limited in south-west Sweden.
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| 5. |
- Badia, J. D., et al.
(författare)
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Effect of sisal and hydrothermal ageing on the dielectric behaviour of polylactide/sisal biocomposites
- 2017
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Ingår i: Composites Science And Technology. - : Elsevier. - 0266-3538 .- 1879-1050. ; 149, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- The dielectric properties of virgin polylactide (PLA) and its reinforced composites with different weight amounts of sisal fibres were assessed at broad temperature (from −130 °C to 130 °C) and frequency ranges (from 10−2–107 Hz), before and after being subjected to accelerated hydrothermal ageing. The synergetic effects of both the loading of sisal and hydrothermal ageing were analysed by means of dielectric relaxation spectra. The relaxation time functions were evaluated by the Havriliak-Negami model, substracting the ohmic contribution of conductivity. The intramolecular and intermolecular relaxations were respectively analysed by means of Arrhenius and Vogel-Fulcher-Tammann-Hesse thermal activation models. The addition of fibre increased the number of hydrogen bonds, which incremented the dielectric permittivity and mainly hindered the non-cooperative relaxations of the biocomposites by increasing the activation energy. Hydrothermal ageing enhanced the formation of the crystalline phase at the so-called transcrystalline region along sisal. This fact hindered the movement of the amorphous PLA fraction, and consequently decreased the dielectric permittivity and increased the dynamic fragility.
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| 6. |
- Badia, J. D., et al.
(författare)
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Relevant factors for the eco-design of polylactide/sisal biocomposites to control biodegradation in soil in an end-of-life scenario
- 2017
-
Ingår i: Polymer degradation and stability. - : Elsevier. - 0141-3910 .- 1873-2321. ; 143, s. 9-19
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Tidskriftsartikel (refereegranskat)abstract
- The eco-design considers the factors to prepare biocomposites under an end-of-life scenario. PLA/sisal biocomposites were obtained from amorphous polylactide and sisal loadings of 10, 20 and 30 wt% with and without coupling agent, and subjected to biodegradation in soil according to standard ISO846. Mass-loss, differential scanning calorimetry and size-exclusion chromatography were used for monitoring biodegradation. A statistical factorial analysis based on the molar mass Mn and crystallinity degree XC pointed out the relevance and interaction of amount of fibre and use of coupling agent with the time of burial in soil. During the preparation of biocomposites, chain scission provoked a similar reduction of Mn for coupled and non-coupled biocomposites. The amount of fibre was relevant for the increase of XC due to the increase of nucleation sites. The coupling agent accelerated the evolution of both factors: reduction of Mn and the consequent increase of XC, mainly during biodegradation in soil. Both factors should be balanced to facilitate microbial assimilation of polymer segments, since bacterial digestion is enhanced by chain scission but blocked by the promotion of crystalline fractions.
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| 7. |
- Badia, J. D., et al.
(författare)
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Water absorption and hydrothermal performance of PHBV/sisal biocomposites
- 2014
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Ingår i: Polymer degradation and stability. - : Elsevier BV. - 0141-3910 .- 1873-2321. ; 108, s. 166-174
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Tidskriftsartikel (refereegranskat)abstract
- The performance of biocomposites of poly(hydroxybutyrate-co-valerate) (PHBV) and sisal fibre subjected to hydrothermal tests at different temperatures above the glass transition of PHBV (T-H = 26, 36 and 46 degrees C) was evaluated in this study. The influences of both the fibre content and presence of coupling agent were focused. The water absorption capability and water diffusion rate were considered for a statistical factorial analysis. Afterwards, the physico-chemical properties of water-saturated biocomposites were assessed by Fourier-Transform Infrared Analysis, Size Exclusion Chromatography, Differential Scanning Calorimetry and Scanning Electron Microscopy. It was found that the water diffusion rate increased with both temperature and percentage of fibre, whereas the amount of absorbed water was only influenced by fibre content. The use of coupling agent was only relevant at the initial stages of the hydrothermal test, giving an increase in the diffusion rate. Although the chemical structure and thermal properties of water-saturated biocomposites remained practically intact, the physical performance was considerably affected, due to the swelling of fibres, which internally blew-up the PHBV matrix, provoking cracks and fibre detachment.
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| 8. |
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| 9. |
- Baresel, Christian, et al.
(författare)
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Kompletterande tester för en resurseffektiv avancerad rening av avloppsvatten
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Större delen av de läkemedel och andra mikroföroreningar som används i samhället hamnar i våra avloppsreningsverk. Där bryts en del ner effektivt, men många föroreningar passerar i stort sett opåverkade genom verken. Vid låg utspädning i närrecipienten kan vissa substanser nå så höga halter att man inte kan utesluta effekter på vattenlevande organismer. Kompletterande rening av avloppsvattnet vid avloppsreningsverk kan därför vare ett alternativ för att avlägsna dessa mikroföroreningar. De mest lovande teknikerna för att minska utsläppen av ett brett spektrum av läkemedelssubstanser och andra svårnedbrytbara substanser är behandling med starka oxidationsmedel, främst ozon, adsorption till aktivt kol och en utökad biologisk nedbrytning. Denna rapport redovisar resultat från fortsatta försök med avskiljning av särskilt läkemedelsrester i avloppsvatten inom projektet SystemLäk, och kompletterar tidigare genomförda försök inom samma projekt. I första hand har 24 olika läkemedel, som ofta förekommer i avloppsvatten och som representerar olika läkemedelsgrupper, analyserats. Tekniker som studerats innefattar: § Granulerat aktivt kol som filtermaterial med biologisk aktivitet - BAF(GAK) § Rening med biokol framställt från bioslam/organiskt substrat - BAK § Användning av pulveriserat aktivt kol i MembranBioReaktor (MBR) -PAK § Oxidation med ozon § Oxidation med klordioxid Genomförda tester, i kombination med tidigare försök, visar tydligt på att de flesta studerade teknikerna ger ökad avskiljning av de flesta studerade ämnena. I många fall får man en mycket bra effekt med en rimlig insats. Testerna har även lyft fram begränsningar hos de studerade teknikerna: BAF(GAK) - Granulerat aktivt kol som biofilter, BAK – Biokol framställt från bioslam, PAK-MBR – Pulveriserat aktivt kol (PAK) i membranbioreaktor, Resurseffektiv ozonering, Klordioxid (ClO2) För mer detaljer kring de ämnen som studerats, analysmetoder för dessa, vilken effekt dessa har i recipienten samt till vilken nivå de bör reduceras hänvisas till den första delrapporten i SystemLäk (Baresel m fl., 2015a). För en samlad bedömning av olika reningssystem inklusive miljöpåverkan och kostnader samt vilka av tekniker som rekommenderas hänvisas till slutrapporten i SystemLäk (Baresel m fl., 2017).
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| 10. |
- Baresel, Christian, et al.
(författare)
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Reuse of treated wastewater for non-potable use (ReUse)
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Population growth, increasing living standards, but also environmental hazards with global climate change as the most significant are all contributing to an increasing water stress in many parts of the world. While access to fresh water for drinking water is getting more costly due to environmental pollution, uses of drinking water conflicts with water needs for agricultural and industrial use, which are in need of substantial water quantities. The use of reclaimed wastewater for non-potable purposes provides a solution for this. This is not new and has in fact been applied in many regions as the main water management approach. As water scarcity becomes more severe, also the need for more sustainable and holistic approaches to deal with our limited fresh water resources becomes more and more obvious. The traditional one-way water handling approach, with end-of-pipe treatment releasing “clean” effluent water to nature, has to be converted into a society-internal water reuse scheme where different water qualities and water uses are considered as an integral part of the water cycle. The present report presents activities and results from an international project that aimed at developing and optimizing water treatment processes and systems for sustainable reuse of treated wastewater. The starting point is to combine the sequential batch treatment (SBR, sequencing batch reactors) with different conventional and emerging secondary and tertiary treatment techniques in various combinations, optimized from an overall sustainability perspective. Evaluation and optimization is achieved using life cycle assessment and life cycle cost assessment and their combination. Den här rapporten finns endast på engelska. Svensk sammanfattning finns i rapporten.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Dedic, Dina, 1985-
(författare)
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The warship Vasa : A Study of Lignin, Extractives and Acids in the oak wood
- 2013
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The oak wood timbers of the 17th century Swedish warship Vasa are weak. The weakening has been attributed to cellulose degradation, which is more extensive in the interior of the timbers compared to the surface regions. Further, the mechanism of cellulose degradation was attributed to oxidative reactions involving iron as a catalyst. In this work, the non-cellulosic wood components (lignin and extractives) in the wood of the Vasa have been studied in order to assess the level of degradation possibly caused by oxidative reactions. Because the interior of the wood timbers is more acidic and its cellulose more depolymerized than at the near surface regions, a general study of organic acidand iron concentrations with respect to different depths from the surface was also performed.Characterization of lignin in the wood of the Vasa was done by means of wet chemical degradation (thioacidolysis) and subsequent GC-MS analysis of the degradation products, as well as CP/MAS 13C NMR spectroscopy of the wood. Dry acetone- and water extracts of the wood were analyzed by 13C NMR spectroscopy and MALDI-TOF mass spectroscopy in order to study the presence of gallo- and ellagitannins. No severe lignin degradation and no discernible amounts of hydrolysable tannins in the oak wood of the Vasa were detected, indicating that oxidative reactions are not the primary route to cellulose depolymerization.High amounts of oxalic acid (analyzed by HPIEC) and a low pH have been found in the interior of the wood timbers, supporting acid hydrolysis as the main mechanism of cellulose depolymerization. Analysis of the iron distribution using ICP AES shows that iron is most abundant in the surface of the timbers and decreases as the concentration of oxalic acid increases. Experimental work also shows that some iron species (rust) in the Vasa neutralize oxalic acid, thereby protecting the surface wood from acid hydrolysis.
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| 16. |
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| 17. |
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| 18. |
- Ek, Anders, et al.
(författare)
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Slaughterhouse waste co-digestion - Experiences from 15 years of full-scale operation
- 2011
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Ingår i: World Renewable Energy Congress - Sweden 8-13 May, 2011. - Linköping : Linköping University Electronic Press. - 9789173930703 ; , s. 64-71
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Konferensbidrag (refereegranskat)abstract
- At Tekniska Verken in Linköping AB (TVAB) there is a long time experience of handling and producing biogas from large volumes of slaughterhouse waste. Experiences from research and development and plant operations have lead to the implementation of several process improving technological/biological solutions. We can in this paper describe how the improvements have had several positive effects on the process, including energy savings, better odor control, higher gas quality, increased organic loading rates and higher biogas production with maintained process stability. In addition, it is described how much of the process stability in anaerobic digestion of slaughter house waste relates to the plant operation, which allow the microbiological consortia to adapt to the substrate. Since digestion of proteinaceous substrates like slaughterhouse waste lead to high ammonia loads, special requirements in ammonia tolerance are placed on the microbiota of the anaerobic digestion. Biochemical assays revealed that the main route for methane production proceed through syntrophic acetate oxidation, which require longer retention times than methane production by acetoclastic methanogens. Thus, the long retention time of the plant, accomplished by a low dilution of the substrate, is a vital component of the process stability when treating high protein substrates like slaughterhouse waste.
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| 19. |
- Ek, Kristine, 1975, et al.
(författare)
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A harmonized method for automatable life cycle sustainability performance assessment and comparison of civil engineering works design concepts
- 2020
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Ingår i: IOP Conference Series: Earth and Environmental Science. - : IOP Publishing. - 1755-1307 .- 1755-1315. ; 588:5
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Konferensbidrag (refereegranskat)abstract
- The life cycle sustainability performance of civil engineering works is increasingly important. The possibility to influence the sustainability of a project design is larger in the conceptual stage than in later stages. Better-informed decisions regarding design choices’ impact on sustainability can be made by comparing conceptual project designs based on an assessment of their life cycle sustainability performance. It is essential that concepts are assessed in a harmonized way and compared impartially. Current standards provide the general framework for the assessment of sustainability performance, but do not give detailed guidance on calculation of sustainability indicators and their aggregation. Since design in automated systems is becoming increasingly common, there is a growing need for machine-readable data and automatable assessment methods. Assessment methods which can be applied using open-access data is important to achieve fair competition. This paper aims to provide a method for life cycle sustainability performance assessment and comparison of civil engineering works design concepts, possible to apply using open-access Environmental Product Declarations (EPDs) and life cycle assessment (LCA) data. The purpose is to enable fair and automatable sustainability assessments of design concepts, to facilitate impartial comparisons of such assessments as a basis for choosing sustainable designs. A literature review of relevant standards and scientific papers on sustainability assessment of construction and civil engineering works was performed. A harmonized, fair and automatable method for life cycle sustainability assessment and comparison of civil engineering works design concepts, well-suited for optimization purposes, is presented. However, the aim currently limits categories and indicators possible to include. The proposed method includes guidance on the calculation of environmental, social and economic indicators, based on LCA, life cycle costing (LCC) and external costs, and aggregation using normalisation and weighting factors of the Product Environmental Footprint (PEF). The proposed method allows for an impartial comparison of the sustainability of design concepts, resulting in better-informed decisions.
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| 20. |
- Ek, Kristine, 1975, et al.
(författare)
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Life Cycle Sustainability Performance Assessment Method for Comparison of Civil Engineering Works Design Concepts: Case Study of a Bridge
- 2020
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 17:21, s. 1-34
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Tidskriftsartikel (refereegranskat)abstract
- Standardized and transparent life cycle sustainability performance assessment methods are essential for improving the sustainability of civil engineering works. The purpose of this paper is to demonstrate the potential of using a life cycle sustainability assessment method in a road bridge case study. The method is in line with requirements of relevant standards, uses life cycle assessment, life cycle costs and incomes, and environmental externalities, and applies normalization and weighting of indicators. The case study involves a short-span bridge in a design-build infrastructure project, which was selected for its generality. Two bridge design concepts are assessed and compared: a concrete slab frame bridge and a soil-steel composite bridge. Data available in the contractor’s tender phase are used. The two primary aims of this study are (1) to analyse the practical application potential of the method in carrying out transparent sustainability assessments of design concepts in the early planning and design stages, and (2) to examine the results obtained in the case study to identify indicators in different life cycle stages and elements of the civil engineering works project with the largest impacts on sustainability. The results show that the method facilitates comparisons of the life cycle sustainability performance of design concepts at the indicator and construction element levels, enabling better-informed and more impartial design decisions to be made.
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| 21. |
- Ek, Monica, et al.
(författare)
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CELL 28-Biointeractive fibers with antibacterial properties
- 2008
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Ingår i: ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY. ; , s. 28-CELL-
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Konferensbidrag (refereegranskat)abstract
- Growth of bacteria on various surfaces may cause major concern if encountered in the wrong environment. The ability to impart antimicrobial properties onto surfaces is therefore desirable. Modification of both glass surfaces and cellulose membranes using weak polyelectrolytes as antimicrobial agent is presented. The aim was to incorporate a known carrier of antimicrobial activity into a multilayer structure of adsorbed polyelectolytes at different surfaces and evaluate the antibacterial activities. The approach involved screening for antimicrobial activity in soln. of modified and unmodified polymers. The polymers were evaluated against gram-neg. E. coli and gram-pos. B. subtilis. In order to elucidate the mode of action of the polymers, the charge was detd. This is done since earlier studies have shown that both charge and degree of hydrophobicity are of importance in terms of exerted activity. Results show that the chosen polymers exert activity in the immobilized state. Different techniques have been used to evaluate the mechanisms.
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| 22. |
- Ek, Martin, et al.
(författare)
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Electron Image Series Reconstruction of Twin Interfaces in InP Superlattice Nanowires.
- 2011
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Ingår i: Microscopy and Microanalysis. - 1435-8115. ; 17:5, s. 752-758
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Tidskriftsartikel (refereegranskat)abstract
- The twin interface structure in twinning superlattice InP nanowires with zincblende structure has been investigated using electron exit wavefunction restoration from focal series images recorded on an aberration-corrected transmission electron microscope. By comparing the exit wavefunction phase with simulations from model structures, it was possible to determine the twin structure to be the ortho type with preserved In-P bonding order across the interface. The bending of the thin nanowires away from the intended ⟨110⟩ axis could be estimated locally from the calculated diffraction pattern, and this parameter was successfully taken into account in the simulations.
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| 23. |
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| 24. |
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| 25. |
- Ek, Monica, et al.
(författare)
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New cellulose derivatives from wood for high value products
- 2008
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Ingår i: TAPPSA: Technical Association of the Pulp and Paper Industry of Southern Africa. - 1029-0109. ; :September 2008
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Tidskriftsartikel (refereegranskat)abstract
- Various pre-treatment methods to increase the accessibility of cellulose materials to swelling and reactive agents at different hierarchical levels, has been developed. It was demonstrated that enzymes are very efficient at increasing the cellulose reactivity. A new method to measure the reactivity and accessibility of the hydroxyl groups on cellulose was developed. Reversible addition-fragmentation chain transfer (RAFT) agents were synthesized and used further in esterification reactions with cellulose samples to prepare cellulose based graft-copolymers. MALDI-TOFMS was evaluated for characterization of cellulose derivatives. Methods to prepare electrospun fibres, casings, sponges and beads, were developed with target applications in pharmaceuticals and foods.
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| 26. |
- Ek, Staffan, et al.
(författare)
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Relative Age Effect of Sport Academy Adolescents, a Physiological Evaluation
- 2020
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Ingår i: Sports. - Basel : MDPI. - 2075-4663. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- The relationship between birth quarter distribution and physiological characteristics related to athletic skills, in adolescent sport academy students has not been fully investigated. In a cross-sectional study, we recruited 86 boys and 52 girls aged 12-14 years during their first term at a sport academy school. We measured body size, cardiac size, pulmonary function, body composition, lower body power, cardiorespiratory fitness parameters, and running endurance by standard methods and analyzed these estimates in relation to birth quarter by ANOVA. Birth quarter distribution in our cohort was compared with birth quarter distribution in the same ages in the whole of Sweden and analyzed by logistic regression. The academy had an overrepresentation of students born in the first quartile of the year compared to those born in the last quartile (odds ratio 2.3 (95% CI: 1.1-4.7)). When comparing the physiological characteristics between birth quarters, uniformity is prominent since out of 26 performed physiological and anthropometric tests only four showed statistically significant group differences. We thus believe that the selection process to the sport academy favours athletes with higher chronological age, i.e., a so-called relative age effect is present. © 2020 MDPI (Basel, Switzerland).
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| 27. |
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| 28. |
- Ek, Weronica E, et al.
(författare)
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Causal effects of inflammatory protein biomarkers on inflammatory diseases
- 2021
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:50
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Tidskriftsartikel (refereegranskat)abstract
- Many circulating proteins are associated with the presence or severity of disease. However, whether these protein biomarkers are causal for disease development is usually unknown. We investigated the causal effect of 21 well-known or exploratory protein biomarkers of inflammation on 18 inflammatory diseases using two-sample Mendelian randomization. We identified six proteins to have causal effects on any of 11 inflammatory diseases (FDR < 0.05, corresponding to P < 1.4 x 10(-3)). IL-12B protects against psoriasis and psoriatic arthropathy, LAP-TGF-beta-1 protects against osteoarthritis, TWEAK protects against asthma, VEGF-A protects against ulcerative colitis, and LT-alpha protects against both type 1 diabetes and rheumatoid arthritis. In contrast, IL-18R1 increases the risk of developing allergy, hay fever, and eczema. Most proteins showed protective effects against development of disease rather than increasing disease risk, which indicates that many disease-related biomarkers are expressed to protect from tissue damage. These proteins represent potential intervention points for disease prevention and treatment.
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| 29. |
- Ek, Weronica E, et al.
(författare)
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Genetic variants influencing phenotypic variance heterogeneity
- 2018
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Ingår i: Human Molecular Genetics. - : OXFORD UNIV PRESS. - 0964-6906 .- 1460-2083. ; 27:5, s. 799-810
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Tidskriftsartikel (refereegranskat)abstract
- Most genetic studies identify genetic variants associated with disease risk or with the mean value of a quantitative trait. More rarely, genetic variants associated with variance heterogeneity are considered. In this study, we have identified such variance single-nucleotide polymorphisms (vSNPs) and examined if these represent biological gene x gene or gene x environment interactions or statistical artifacts caused by multiple linked genetic variants influencing the same phenotype. We have performed a genome-wide study, to identify vSNPs associated with variance heterogeneity in DNA methylation levels. Genotype data from over 10 million single-nucleotide polymorphisms (SNPs), and DNA methylation levels at over 430 000 CpG sites, were analyzed in 729 individuals. We identified vSNPs for 7195 CpG sites (P < 9.4 x 10(-11)). This is a relatively low number compared to 52 335 CpG sites for which SNPs were associated with mean DNA methylation levels. We further showed that variance heterogeneity between genotypes mainly represents additional, often rare, SNPs in linkage disequilibrium (LD) with the respective vSNP and for some vSNPs, multiple low frequency variants co-segregating with one of the vSNP alleles. Therefore, our results suggest that variance heterogeneity of DNA methylation mainly represents phenotypic effects by multiple SNPs, rather than biological interactions. Such effects may also be important for interpreting variance heterogeneity of more complex clinical phenotypes.
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| 30. |
- Ek, Weronica E., et al.
(författare)
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Tea and coffee consumption in relation to DNA methylation in four European cohorts
- 2017
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 26:16, s. 3221-3231
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Tidskriftsartikel (refereegranskat)abstract
- Lifestyle factors, such as food choices and exposure to chemicals, can alter DNA methylation and lead to changes in gene activity. Two such exposures with pharmacologically active components are coffee and tea consumption. Both coffee and tea has been suggested to play an important role in modulating disease-risk in humans by suppressing tumour progression, decreasing inflammation and influencing estrogen metabolism. These mechanisms may be mediated by changes in DNA methylation.To investigate if DNA methylation in blood is associated with coffee and tea consumption we performed a genome-wide DNA methylation study for coffee and tea consumption in four European cohorts (N = 3,096). DNA methylation was measured from whole blood at 421,695 CpG sites distributed throughout the genome and analysed in men and women both separately and together in each cohort. Meta-analyses of the results and additional regional-level analyses were performed.After adjusting for multiple testing, the meta-analysis revealed that two individual CpG-sites, mapping to DNAJC16 and TTC17, were differentially methylated in relation to tea consumption in women. No individual sites were associated in men or in the sex-combined analysis for tea or coffee. The regional analysis revealed that 28 regions were differentially methylated in relation to tea consumption in women. These regions contained genes known to interact with estradiol metabolism and cancer. No significant regions were found in the sex-combined and male-only analysis for either tea or coffee consumption.
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| 31. |
- Engström, Maria, 1958-, et al.
(författare)
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Fatigue and cognitive effort in multiple sclerosis: an fMRI study
- 2011
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Despite recent advances in therapy and diagnosis, fatigue remains a mayor challenge in multiple sclerosis (MS). To further the understanding of the neural underpinnings of fatigue, we undertook a study using functional magnetic resonance imaging (fMRI) to investigate neural networks that may be affected by MS-related fatigue. Twelve MS patients and 12 age- and sex matched controls were administered the Fatigue Impact Scale (FIS) to assess clinically significant fatigue, and underwent a neuropsychological examination. The participants performed a working memory task (Daneman’s ‘Reading Span’ task) while being monitored by means of a 1.5 T Philips Achieva MR scanner. We have previously shown that this task triggers an executive network comprising frontal and parietal areas typically involved in working memory. In addition, the task engages a core network involving the anterior insula and the anterior cingulate cortex. This latter network may be implicated in allocation of mental resources and monitoring of the present state of the individual. There were two main findings. MS participants evidenced less activation than controls in the anterior cingulate and the left parietal cortex (Brodmann area 7) and more activation in left hemisphere language areas as well as the anterior insula. The second main finding was that clinical ratings of fatigue were strongly correlated with activity in wide areas of the core network, as well as posterior language areas. We take this finding to indicate that fatigue is related to compensatory involvement of the core network, and that excess activity in the core network possibly could be used as an objective marker of fatigue in MS.
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| 32. |
- Engström, Maria, 1958-, et al.
(författare)
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Thalamo-striato-cortical determinants to fatigue in multiple sclerosis
- 2013
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Ingår i: Brain and Behavior. - : Wiley. - 2162-3279 .- 2162-3279. ; 3:6, s. 715-728
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Tidskriftsartikel (refereegranskat)abstract
- Background The aim was to explore the thalamo-striato-cortical theory of central fatigue in multiple sclerosis (MS) patients with self-reported fatigue. If the theory correctly predicted fatigue based on disruptions of the thalamo-striato-cortical network, we expected altered brain activation in this network in MS participants while performing a complex cognitive task that challenged fatigue. Methods
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| 33. |
- Enoksson, SL, et al.
(författare)
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The inflammatory cytokine IL-18 induces self-reactive innate antibody responses regulated by natural killer T cells
- 2011
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 108:51, s. E1399-E1407
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Tidskriftsartikel (refereegranskat)abstract
- Inflammatory responses initiate rapid production of IL-1 family cytokines, including IL-18. This cytokine is produced at high levels in inflammatory diseases, including allergy and autoimmunity, and is known to induce IgE production in mice. Here we provide evidence that IL-18 is directly coupled to induction of self-reactive IgM and IgG antibody responses and recruitment of innate B2 B cells residing in the marginal zone of the spleen. Moreover, the data suggest that the B-cell activation occurs predominantly in splenic extrafollicular plasma cell foci and is regulated by natural killer T (NKT) cells that prevent formation of mature germinal centers. We also find evidence that NKT cells control this type of B-cell activation via cytotoxicity mediated by both the perforin and CD95/CD178 pathways. Thus, NKT cells regulate innate antibody responses initiated by an inflammatory stimulus, suggesting a general mechanism that regulates B-cell behavior in inflammation and autoreactivity.
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| 34. |
- Gil-Castell, O., et al.
(författare)
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Hydrothermal ageing of polylactide/sisal biocomposites. Studies of water absorption behaviour and Physico-Chemical performance
- 2014
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Ingår i: Polymer degradation and stability. - : Elsevier BV. - 0141-3910 .- 1873-2321. ; 108, s. 212-222
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Tidskriftsartikel (refereegranskat)abstract
- An accelerated hydrothermal degrading test was designed in order to analyse the synergic effect of water and temperature on PLA/sisal biocomposites with and without coupling agent. As well, the physicochemical properties of biocomposites were monitored along the hydrothermal test by means of Scanning Electron Microscopy, Size Exclusion Chromatography and Differential Scanning Calorimetry. The addition of fibre induced higher water absorption capability and promoted physical degradation, as observed in the surface topography. During the processing of biocomposites and throughout the hydrothermal ageing, a reduction of molecular weight due to chain scission was found. As a consequence, a faster formation of crystalline domains in the PIA matrix occurred the higher the amount of fibre was, which acted as a nucleating agent. Higher crystallinity was considered as a barrier against the advance of penetrant and a reduction in the diffusion coefficient was shown. The addition of coupling agent presented a different influence depending on the composition, showing an inflection point around 20% of sisal fibre.
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| 35. |
- Gil-Castell, O., et al.
(författare)
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Impact of hydrothermal ageing on the thermal stability, morphology and viscoelastic performance of PLA/sisal biocomposites
- 2016
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Ingår i: Polymer degradation and stability. - : Elsevier. - 0141-3910 .- 1873-2321.
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Tidskriftsartikel (refereegranskat)abstract
- The influence of the combined exposure to water and temperature on the behaviour of polylactide/sisal biocomposites coupled with maleic acid anhydride was assessed through accelerated hydrothermal ageing. The biocomposites were immersed in water at temperatures from 65 to 85 °C, between the glass transition and cold crystallisation of the PLA matrix. The results showed that the most influent factor for water absorption was the percentage of fibres, followed by the presence of coupling agent, whereas the effect of the temperature was not significant. Deep assessment was devoted to biocomposites subjected to hydrothermal ageing at 85 °C, since it represents the extreme degrading condition. The morphology and crystallinity of the biocomposites were evaluated by means of X-Ray diffraction (XRD) and field emission scanning electron microscopy (FE-SEM). The viscoelastic and thermal performance were assessed by means of dynamic mechanic thermal analysis (DMTA) and thermogravimetry (TGA). The presence of sisal generally diminished the thermal stability of the biocomposites, which was mitigated by the addition of the coupling agent. After composite preparation, the effectiveness of the sisal fibre was improved by the crystallisation of PLA around sisal, which increased the storage modulus and reduced the dampening factor. The presence of the coupling agent strengthened this effect. After hydrothermal ageing, crystallisation was promoted in all biocomposites therefore showing more fragile behaviour evidencing pores and cracks. However, the addition of coupling agent in the formulation of biocomposites contributed in all cases to minimise the effects of hydrothermal ageing.
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| 36. |
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| 37. |
- Hadizadeh, Fatemeh, et al.
(författare)
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Effects of oral contraceptives and menopausal hormone therapy on the risk of rheumatoid arthritis : a prospective cohort study.
- 2023
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Ingår i: Rheumatology. - 1462-0324 .- 1462-0332.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Oral contraceptives (OC) and menopausal hormone therapy (MHT) contain exogenous sex hormones and are used by millions of women around the world. However, their effect on development of rheumatoid arthritis (RA) is still debated and the current literature suggests that they may exert opposite effects on the risk of RA. The present study aimed to estimate the effects of exogenous hormones on development of RA, both during the reproductive lifespan and later in life.METHODS: The association between OC and RA, as well as between MHT and late-onset RA (LORA), was investigated using time-dependent Cox regression modelling in white British women from the UK Biobank (N = 236 602 and N = 102 466, respectively) and replicated in women from all ethnic groups.RESULTS: OC use was associated with a decreased risk of RA in ever-users (hazard ratio [HR]=0.89; 95% CI = 0.82-0.96), as well as in current (HR = 0.81; 0.73-0.91) and former users (HR = 0.92; 0.84 -1.00), compared with never-users. In contrast, MHT use was associated with an increased risk of LORA in ever-users (HR = 1.16; 1.06-1.26) as well as in former users (HR = 1.13; 1.03-1.24) compared with never-users.CONCLUSION: OC use appears to protect against RA, while MHT may increase the risk of LORA. This study provides new insights into the possible inverse effect of exposure to different exogenous sex hormones on the risk of RA.
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| 38. |
- Hagberg, Linus, et al.
(författare)
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Svenska skogsindustrins emissioner och upptag av växthusgaser
- 2008
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I denna studie har upptag och emissioner av växthusgaser för aktiviteter förknippade med den svenska skogsindustrins beräknats för åren 2001-2003. Emissioner och upptag i svensk skog och emissioner vid skogsbruk, vid produktion av skogsprodukter och vid transporter inom Sverige har ingått i inventeringen. Studien kommer fram till att nettoresultatet för svenska skogsindustrin är ett årligt upptag på ca 1,6 milj ton CO2-ekvivalenter. Upptaget i skogsekosystemet beräknades till ca 5,2 milj ton CO2-ekvivalenter och emissionerna i det skogsindustriella produktionssystemet beräknades till 3,5 milj ton CO2-ekvivalenter.
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| 39. |
- Hammarlund, Maria, et al.
(författare)
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The Alpha 7 Nicotinic Acetylcholine Receptor Does Not Affect Neonatal Brain Injury
- 2022
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation plays a central role in the development of neonatal brain injury. The alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) can modulate inflammation and has shown promising results as a treatment target in rodent models of adult brain injury. However, little is known about the role of the alpha 7nAChR in neonatal brain injury. Hypoxic-ischemic (HI) brain injury was induced in male and female C57BL/6 mice, alpha 7nAChR knock-out (KO) mice and their littermate controls on postnatal day (PND) 9-10. C57BL/6 pups received i.p. injections of alpha 7nAChR agonist PHA 568487 (8 mg/kg) or saline once daily, with the first dose given directly after HI. Caspase-3 activity and cytokine mRNA expression in the brain was analyzed 24 h after HI. Motor function was assessed 24 and 48 h after HI, and immunohistochemistry was used to assess tissue loss at 24 h and 7 days after HI and microglial activation 7 days after HI. Activation of alpha 7nAChR with the agonist PHA 568487 significantly decreased CCL2/MCP-1, CCL5/RANTES and IL-6 gene expression in the injured brain hemisphere 24 h after HI compared with saline controls in male, but not female, pups. However, alpha 7nAChR activation did not alter caspase-3 activity and TNF alpha, IL-1 beta and CD68 mRNA expression. Furthermore, agonist treatment did not affect motor function (24 or 48 h), neuronal tissue loss (24 h or 7 days) or microglia activation (7 days) after HI in either sex. Knock-out of alpha 7nAChR did not influence neuronal tissue loss 7 days after HI. In conclusion, targeting the alpha 7nAChR in neonatal brain injury shows some effect on dampening acute inflammatory responses in male pups. However, this does not lead to an effect on overall injury outcome.
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| 40. |
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| 41. |
- Hellman, Jan, et al.
(författare)
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Mechanisms of increased methane production through re-circulation of magnetic biomass carriers in an experimental continuously stirred tank reactor
- 2010
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Konferensbidrag (refereegranskat)abstract
- Magnetite particles were used in a semi-continuous process as magnetic biomass carriers to separate and re-introduce microorganisms in a CSTR reactor. In comparison to a control reactor the methane content during the semi-continuous process was elevated when magnetite particles were used. The difference was most apparent during the fermentative step directly after feeding and upon direct spiking with volatile fatty acids. Total DNA quantification of the separated magnetite particles revealed high association of microorganisms. Furthermore, quantitative real-time PCR analysis of the associated microbial consortia indicated that the hydrogenotrophic Methanobacteriales was overrepresented at the particle surface. Thus, the increased methane production could be coupled to both the crowding and shorter interspecies distances between the groups involved in anaerobic digestion, as well as a preferential adsorption of hydrogenotrophs. By bringing the hydrogenotrophs closer to the primary fermentative bacteria and increasing their relative number the produced hydrogen during acidogenesis is more effectively utilized and more carbon dioxide is converted to methane. Furthermore, by the same cause, the rate of acetogenesis increased as the hydrogenotrophs more effectively could consume the hydrogen produced and thereby keep the hydrogen partial pressure low.
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| 42. |
- Hjelmesaeth, J., et al.
(författare)
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Impact of body weight, low energy diet and gastric bypass on drug bioavailability, cardiovascular risk factors and metabolic biomarkers: protocol for an open, non-randomised, three-armed single centre study (COCKTAIL)
- 2018
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Ingår i: Bmj Open. - 2044-6055. ; 8:5
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Roux-en-Y gastric bypass (GBP) is associated with changes in cardiometabolic risk factors and bioavailability of drugs, but whether these changes are induced by calorie restriction, the weight loss or surgery per se, remains uncertain. The COCKTAIL study was designed to disentangle the short-term (6 weeks) metabolic and pharmacokinetic effects of GBP and a very low energy diet (VLED) by inducing a similar weight loss in the two groups. Methods and analysis This open, non-randomised, three-armed, single-centre study is performed at a tertiary care centre in Norway. It aims to compare the short-term (6 weeks) and long-term (2 years) effects of GBP and VLED on, first, bioavailability and pharmacokinetics (24 hours) of probe drugs and biomarkers and, second, their effects on metabolism, cardiometabolic risk factors and biomarkers. The primary outcomes will be measured as changes in: (1) all six probe drugs by absolute bioavailability area under the curve (AUC(oral)/AUC(iv)) of midazolam (CYP3A4 probe), systemic exposure (AUC(oral)) of digoxin and rosuvastatin and drug:metabolite ratios for omeprazole, losartan and caffeine, levels of endogenous CYP3A biomarkers and genotypic variation, changes in the expression and activity data of the drug-metabolising, drug transport and drug regulatory proteins in biopsies from various organs and (2) body composition, cardiometabolic risk factors and metabolic biomarkers. Ethics and dissemination The COCKTAIL protocol was reviewed and approved by the Regional Committee for Medical and Health Research Ethics (Ref: 2013/2379/REK serest A). The results will be disseminated to academic and health professional audiences and the public via presentations at conferences, publications in peer-reviewed journals and press releases and provided to all participants.
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| 43. |
- Hou, JH, et al.
(författare)
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Polygenic resilience scores capture protective genetic effects for Alzheimer's disease
- 2022
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1, s. 296-
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRSs) can boost risk prediction in late-onset Alzheimer’s disease (LOAD) beyond apolipoprotein E (APOE) but have not been leveraged to identify genetic resilience factors. Here, we sought to identify resilience-conferring common genetic variants in (1) unaffected individuals having high PRSs for LOAD, and (2) unaffected APOE-ε4 carriers also having high PRSs for LOAD. We used genome-wide association study (GWAS) to contrast “resilient” unaffected individuals at the highest genetic risk for LOAD with LOAD cases at comparable risk. From GWAS results, we constructed polygenic resilience scores to aggregate the addictive contributions of risk-orthogonal common variants that promote resilience to LOAD. Replication of resilience scores was undertaken in eight independent studies. We successfully replicated two polygenic resilience scores that reduce genetic risk penetrance for LOAD. We also showed that polygenic resilience scores positively correlate with polygenic risk scores in unaffected individuals, perhaps aiding in staving off disease. Our findings align with the hypothesis that a combination of risk-independent common variants mediates resilience to LOAD by moderating genetic disease risk.
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| 44. |
- Höglund, Julia, et al.
(författare)
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Characterization of the human ABO genotypes and their association to common inflammatory and cardiovascular diseases in the UK Biobank
- 2021
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Ingår i: American Journal of Hematology. - : John Wiley & Sons. - 0361-8609 .- 1096-8652. ; 96:11, s. 1350-1362
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Tidskriftsartikel (refereegranskat)abstract
- The ABO gene contains three major alleles that encodes different antigens; A, B, and O, which determine an individual's blood group. Previous studies have primarily focused on identifying associations between ABO blood groups and diseases risk. Here, we sought to test for association between ABO genotypes (OO, OA, AA; OB, BB, and AB) and a large set of common inflammatory and cardiovascular diseases in UK Biobank as well as disease-related protein biomarkers in NSPHS. We first tested for association by conducting a likelihood ratio test, testing whether ABO contributed significantly to the risk for 24 diseases, and 438 plasma proteins. For phenotypes with FDR < 0.05, we tested for pair-wise differences between genetically determined ABO genotypes using logistic or linear regression. Our study confirmed previous findings of a strong association between ABO and cardiovascular disease, identified associations for both type 1 and type 2 diabetes, and provide additional evidence of significant differences between heterozygous and homozygous allele carriers for pulmonary embolism, deep vein thrombosis, but also for von Willebrand factor levels. Furthermore, the results indicated an additive effect between genotypes, even between the two most common A subgroups, A1 and A2. Additionally, we found that ABO contributed significantly to 39 plasma proteins, of which 23 have never been linked to the ABO locus before. These results show the need of incorporating ABO genotype information in the consultation and management of patients at risk, rather than classifying patients into blood groups.
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| 45. |
- Höglund, Julia, et al.
(författare)
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Gene-based variant analysis of whole-exome sequencing in relation to eosinophil count
- 2022
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils play important roles in the release of cytokine mediators in response to inflammation. Many associations between common genetic variants and eosinophils have already been reported, using single nucleotide polymorphism (SNP) array data. Here, we have analyzed 200,000 whole-exome sequences (WES) from the UK Biobank cohort and performed gene-based analyses of eosinophil count. We defined five different variant weighting schemes to incorporate information on both deleteriousness and frequency. A total of 220 genes in 55 distinct (>10 Mb apart) genomic regions were found to be associated with eosinophil count, of which seven genes (ALOX15, CSF2RB, IL17RA, IL33, JAK2, S1PR4, and SH2B3) are driven by rare variants, independent of common variants identified in genome-wide association studies. Two additional genes, NPAT and RMI1, have not been associated with eosinophil count before and are considered novel eosinophil loci. These results increase our knowledge about the effect of rare variants on eosinophil count, which can be of great value for further identification of therapeutic targets.
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| 46. |
- Höglund, Julia, et al.
(författare)
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Improved power and precision with whole genome sequencing data in genome-wide association studies of inflammatory biomarkers
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified associations between thousands of common genetic variants and human traits. However, common variants usually explain a limited fraction of the heritability of a trait. A powerful resource for identifying trait-associated variants is whole genome sequencing (WGS) data in cohorts comprised of families or individuals from a limited geographical area. To evaluate the power of WGS compared to imputations, we performed GWAS on WGS data for 72 inflammatory biomarkers, in a kinship-structured cohort. When using WGS data, we identified 18 novel associations that were not detected when analyzing the same biomarkers with genotyped or imputed SNPs. Five of the novel top variants were low frequency variants with a minor allele frequency (MAF) of <5%. Our results suggest that, even when applying a GWAS approach, we gain power and precision using WGS data, presumably due to more accurate determination of genotypes. The lack of a comparable dataset for replication of our results is a limitation in our study. However, this further highlights that there is a need for more genetic epidemiological studies based on WGS data.
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| 47. |
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| 48. |
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| 49. |
- Johansson, Therese
(författare)
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Leveraging genetic and population-level data to improve women’s health
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hormonal contraception (HC) and menopausal hormone therapy (MHT) are commonly used medicines, but their safety profiles are uncertain due to conflicting research. This thesis aims to examine the potential risks associated with HC and MHT by utilizing large-scale population-based cohorts.In Paper I, we prospectively examined the link between oral contraceptives (OCs) and MHT use with the risk of stroke in the UK Biobank (UKB). Cox regression with time-varying exposures was used to investigate if treatment effects vary with time and to avoid immortal time bias. We included time-varying covariates to account for potential confounding factors that change over time and might affect the exposure level. Our research showed higher stroke risk during the initial period after initiating both treatments and increased stroke risk with MHT use regardless of menopause timing.In Paper II, we calculated the hazard rate of the first incidence of depression following OC use. To avoid the influence of healthy-user bias, we estimated the risk in first-time users and excluded previous users in the reference group. A unique aspect of our study was the sibling analysis, which explored the causal relationship between OC use and depression by examining female sibling pairs in the UKB. Our findings showed that initiating OC was associated with a higher risk of depression, especially among adolescents and during the initial phase of treatment.Paper III explored the genetic predisposition to venous thromboembolism (VTE) among OC users in the UKB. Using polygenic risk scores, we demonstrated that women with a high genetic liability for VTE have a significantly increased risk when initiating OC. This suggests that genetic screening may be beneficial in personalising contraceptive advice and mitigating the risk of thrombotic events.In Paper IV, we investigated the association between different types of contemporary MHT and the risk of cardiovascular disease, building upon our findings from Paper I. We emulated a target trial using the Swedish nationwide registers to estimate the intention-to-treat and per-protocol effect. We showed that specific MHT treatments, particularly those that combine estrogen and progestin, are linked to an increased risk of ischemic heart disease (IHD) and venous thromboembolism (VTE). Tibolone was positively associated with IHD and cerebral infarction but not VTE. In Paper V, we examined the risk of depression following HC initiation using the Swedish nationwide registers. Our research expanded upon the findings of Paper II by including various types of modern HCs and employing an emulated target trial study design. We observed an increased risk of depression among various HCs and found that the risk of depression is influenced by different dosages and types of progestins rather than the route of administration.Using advanced analytical methods, we identified critical risk periods, variations in risk between different treatments and the interplay between treatment and genetics. While HC and MHT offer significant benefits, their potential side effects warrant careful consideration. Therefore, prescribing HCs and MHT should be approached with nuance, emphasising individual risk assessments and ongoing monitoring to optimise safety.
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| 50. |
- Johansson, Therese, et al.
(författare)
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Oral Contraceptives, Hormone Replacement Therapy, and Stroke Risk
- 2022
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Ingår i: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 53:10, s. 3107-3115
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Millions of women worldwide use exogenous hormones as oral contraceptives or hormone replacement therapy. Still, time-dependent and long-term consequences of exogenous hormones on stroke risk remains unclear.METHODS: We examined the association between self-reported oral contraceptive and hormone replacement therapy use and stroke risk in 257 194 women from the UK Biobank, born between 1939 and 1970. Outcomes included any type of stroke, ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Exposures were analyzed as time-varying variables in Cox regression models.RESULTS: During first year of oral contraceptive use, an increased event rate of any stroke was observed (hazard ratio [HR], 2.49 [95% CI, 1.44-4.30]), while the hazards were found to be comparable during remaining years of use (HR, 1.00 [95% CI, 0.86-1.14]), compared with nonusers. Similarly, first year of hormone replacement therapy use was associated with higher hazard rates of any stroke (HR, 2.12 [95% CI, 1.66-2.70]), as well as cause-specific stroke, including ischemic stroke (HR, 1.93 [95% CI, 1.05-3.57]) and subarachnoid hemorrhage (HR, 2.17 [95% CI, 1.25-3.78]), which remained increased for any stroke during remaining years of use (HR, 1.18 [95% CI, 1.05-1.31]), and after discontinuation (HR, 1.16 [95% CI, 1.02-1.32]).CONCLUSIONS: Oral contraceptive use and hormone replacement therapy were associated with an increased risk of stroke, especially during the first year of use, possibly due to immediate changes in hemostatic balance. This study provides new insights on the effects of hormone exposure on stroke risk and provide evidence of not only an overall risk but also a pronounced effects seen in the beginning of treatment.
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