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| 2. |
- Aulchenko, Yurii S, et al.
(författare)
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Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:1, s. 47-55
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Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 x 10(-11); LDL, P = 2.6 x 10(-10)), TMEM57 (TC, P = 5.4 x 10(-10)), CTCF-PRMT8 region (HDL, P = 8.3 x 10(-16)), DNAH11 (LDL, P = 6.1 x 10(-9)), FADS3-FADS2 (TC, P = 1.5 x 10(-10); LDL, P = 4.4 x 10(-13)) and MADD-FOLH1 region (HDL, P = 6 x 10(-11)). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.
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| 3. |
- Gerber, Sofi, 1973-
(författare)
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Öst är Väst men Väst är bäst : Östtysk identitetsformering i det förenade Tyskland
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the German Democratic Republic (GDR) the overthrow of the socialist regime did not only bring about both an economic and political shift, it resulted also in the inclusion of the GDR into the Federal Republic of Germany. The fall of the Wall brought with it transformations in everyday life as well as changes in social identities.This study examines how people who grew up in the GDR define the East and the West in unified Germany, as well as identifying which concepts play a role in the self-interpretations given by former GDR citizens. Through applying discourse theory, I investigate how identities are partially fixed and change over time, relating this always to historically situated discourses. In the analysis, East and West are considered as floating signifiers, which, through articulations made with other categories such as class, nation, place and gender, come to be filled with meaning. The study is based on twenty-five life story interviews conducted in Eastern Germany. The group of interviewees consisted of fifteen women and ten men born in the GDR between the years of 1970 and 1979, all of whom had different levels of education.The demise of the socialist state and the transition to a capitalist society is central in the interviewees’ life stories. Their narratives about the past are formed in a discursive order other than the one in which the events themselves took place. Conversely, the past is used as a foil against which the present is compared. With the dislocation, the interviewees have developed a reflexive stance to both themselves and the world. The study reveals both how East and West are still used to make the world intelligible in a number of fields and, at the same time, how these same concepts are transcended. It shows in what ways the interviewees employ different strategies to adapt to the new circumstances and to handle a potentially marked position in unified Germany.
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- Kaunitz, Niklas, 1977-
(författare)
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Workers, Firms and Welfare : Four Essays in Economics
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis comprises four chapters, in two parts. The first part examines the result of a Swedish payroll tax reduction; first from the perspective of the worker, then from that of the employer. The second half of the thesis concerns subjective well-being, both from an individual and from an aggregate viewpoint.Payroll Taxes and Youth Labor Demand. In 2007, the Swedish payroll tax was reduced substantially for young workers. This paper examines whether targeted payroll tax reductions are effective in raising youth employment. We estimate a small impact, both on employment and on wages. However, the effect differs markedly across ages, with 4–5 times higher impact on 22–23 year-olds compared to 25-year-olds. Additionally, the employment effects are strongly procyclical, approaching zero in the deep recession. We calculate that the estimated cost per created job is more than four times that of directly hiring workers at the average wage.Payroll Taxes and Firm Performance. The Swedish payroll tax reform of 2007 had the effect that firms' average social fees came to depend on the age structure of their employees. This makes it possible to estimate how firms respond to shocks in labor costs. We find a significant, but very small effect on gross investments, and a negative, but not statistically significant, impact on labor productivity. There are no effects on exit rates or profitability.Beyond Income: The Importance for Life Satisfaction of Having Access to a Cash Margin. We study how life satisfaction among adult Swedes is influenced by having access to a cash margin, i.e. a moderate amount of money that could be acquired on short notice either through own savings, by loan from family or friends, or by other means. We find that cash margin is a strong and robust predictor of life satisfaction, also when controlling for individual fixed-effects and socio-economic conditions, including income. This suggests that cash margin captures something beyond wealth.On Aggregating Subjective Well-Being. This paper discusses the assumptions underlying the aggregation of individually measured well-being. Any aggregation method is associated with measurability assumptions regarding the underlying well-being measure, as well as moral philosophical assumptions with respect to how individual well-being is weighted into a composite metric. I compare welfare across a set of countries, under alternative aggregation methods, and find that countries often can be ranked under comparatively weak measurement assumptions, and, equally important, that aggregation methods can be chosen so as to refrain from strong ethical preconceptions.
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| 5. |
- Lindqvist, Annika, 1983-, et al.
(författare)
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Pharmacokinetic Considerations of Nanodelivery to the Brain : Using Modeling and Simulations to Predict Outcome of Liposomal Formulations
- 2016
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 92, s. 173-182
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Tidskriftsartikel (refereegranskat)abstract
- The use of nanocarriers is an intriguing solution to increase the brain delivery of novel therapeutics. The aim of this paper was to use pharmacokinetic analysis and simulations to identify key factors that determine the effective drug concentration-time profile at the target site in the brain. Model building and simulations were based on experimental data obtained from the administration of the opioid peptide DAMGO in glutathione tagged PEGylated liposomes to rats. Different pharmacokinetic models were investigated to explore the mechanisms of increased brain delivery. Concentration time profiles for a set of formulations with varying compound and carrier characteristics were simulated. By controlling the release rate from the liposome, the time profile and the extent of brain delivery can be regulated. The modeling did not support a mechanism of the liposomes passing the brain endothelial cell membrane in an intact form through endocytosis or transcytosis. The most likely process was found to be fusion of the liposome with the endothelial luminal membrane. The simulations revealed that low permeable compounds, independent on efflux, will gain the most from a nanocarrier formulation. The present model based approach is useful to explore and predict possibilities and limitations of carrier-based systems to the brain.
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| 6. |
- Lindqvist, Annika, 1983-
(författare)
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Quantitative Aspects of Nanodelivery Across the Blood-Brain Barrier : Exemplified with the Opioid Peptide DAMGO
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The use of nanocarriers is an intriguing approach in the development of efficacious treatment for brain disorders. The aim of the conducted research was to evaluate and quantify the impact of a liposomal nanocarrier formulation on the brain drug delivery. A novel approach for investigating the blood-brain barrier transport of liposomal DAMGO is presented, including in vivo microdialysis in rat, a high quality LC-MS/MS bioanalytical method and pharmacokinetic model analysis of the data. Factors limiting the brain distribution of the free peptide DAMGO were also investigated. Microdialysis, in combination with plasma sampling, made it possible to separate the released drug from the encapsulated and to quantify the active substance in both blood and brain interstitial fluid over time.The opioid peptide DAMGO entered the brain to a limited extent, with a clearance out of the brain 13 times higher than the clearance into the brain. The brain to blood ratio of unbound drug was not affected when the efflux transporter inhibitors cyclosporine A and elacridar were co-administered with DAMGO. Nor was the transport affected in the in vitro Caco-2 assay using the same inhibitors. This indicates that DAMGO is not transported by P-glycoprotein (Pgp) or breast cancer resistant protein (Bcrp). The blood-brain barrier transport was significantly increased for DAMGO when formulated in liposomes, resulting in 2-3 fold higher brain to blood ratio of unbound DAMGO. The increased brain delivery was seen both for glutathione tagged PEGylated liposomes, as well as for PEGyalted liposomes without specific brain targeting. The improvement in brain delivery was observed only when DAMGO was encapsulated into the liposomes, thus excluding any effect of the liposomes themselves on the integrity of the blood-brain barrier. Modeling of the data provided additional mechanistic understanding of the brain uptake, showing that endocytosis or transcytosis of intact liposomes across the endothelial cell membranes were unlikely. A model describing fusion of the liposomes with the luminal membrane described the experimental data the best.In conclusion, the studies presented in this thesis all contribute to an increased understanding of how to evaluate and improve brain delivery of CNS active drugs and contribute with important insights to the nanocarrier field.
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| 7. |
- Lindqvist, Markus, et al.
(författare)
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Abdominal aortic aneurysm and the association with serum levels of Homocysteine, vitamins B6, B12 and Folate.
- 2012
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Ingår i: American Journal of Cardiovascular Disease. - 2160-200X. ; 2:4, s. 318-22
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Tidskriftsartikel (refereegranskat)abstract
- Previous investigations have shown hyperhomocysteinemi in patients with abdominal aortic aneurysm (AAA). In the present study we evaluated the circulating level of homocysteine (Hcy) in relation to renal function, vitamins B6, B12 and folate status in AAA patients with special regard to aneurysm size, and rupture. Hcy, Creatinine, B6, B12 and folate were measured in 119 patients with AAA and 36 controls without aneurysm matched by age, gender and smoking habit. As expected there was a weak correlation between Hcy and vitamins B6, B12 or folate. We found similar levels of Hcy, B6 and folic acid in patients with nonruptured AAA compared to the control group matched by age, gender and smoking habit. There was no correlation between maximum diameter of the nonruptured AAA (n=78) and Hcy, B6 or folate. However, the present study shows a significant inverse correlation between maximum diameter of the nonruptured AAA (n=78) and B12 (r = -0.304, p=0.007) with significant higher levels in small AAA compared to large AAA. In conclusion, Hcy does not seem to be a useful biomarker in AAA disease. The unexpected finding of B12 levels correlating to aneurysm diameter warrants urgent further investigation of B12 supplement to prevent progression of small AAA.
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| 8. |
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| 9. |
- Lindqvist, Markus, et al.
(författare)
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Plasma glycosylphosphatidylinositol phospholipase D (GPI-PLD) and abdominal aortic aneurysm.
- 2012
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Ingår i: International Journal of Clinical and Experimental Medicine. - 1940-5901. ; 5:4, s. 306-9
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Tidskriftsartikel (refereegranskat)abstract
- Recent reviews state that a circulating biomarker predicting aortic rupture risk would be a powerful tool to stratify patients with small screen-detected abdominal aortic aneurysm (AAA). In a current proteomic pilot-study elevated levels of the enzyme Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) was shown in patients with small AAA compared with controls without aneurysm. In the present study we investigated the impact of plasma GPI-PLD as a biomarker in patients with AAA in relation to aneurysm size, and rupture. Plasma GPI-PLD was measured in patients with AAA (nonruptured, n=78 and ruptured, n=55) and controls without aneurysm (n=41) matched by age, sex and smoking habit. The plasma GPI-PLD levels were significantly lower in patients with ruptured compared nonruptured AAA which we interpreted as a result of hemodilution due to hemorrhage in patients with ruptured AAA. The plasma GPI-PLD levels were similar in patients with nonruptured AAA compared to the controls without aneurysm. Furthermore, there was no correlation between plasma GPI-PLD and aneurysm size in the group of patients with nonruptured AAA. In conclusion, the present study fails to show a connection between GPI-PLD and AAA. However, the definite role of GPI-PLD as a predictive marker needs to be further clarified in a follow-up cohort study.
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| 10. |
- Lindqvist, Markus, et al.
(författare)
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Soluble urokinase plasminogen activator receptor in patients with abdominal aortic aneurysm
- 2012
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 130:3, s. 511-513
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In the present study we investigated the impact of soluble urokinase plasminogen activator receptor (suPAR) as a biomarker in patients with abdominal aortic aneurysm (AAA) in relation to conventional inflammatory markers, aneurysm size, and rupture. Methods: suPAR and conventional inflammatory markers were measured in 119 patients with AAA and 36 controls without aneurysm matched by age, gender and smoking habit. Results: The results support earlier studies suggesting a state of activated inflammatory response in patients with nonruptured AAA as expressed by elevated CRP and IL-6 compared with the controls. In contrast, suPAR showed similar levels in patients with nonruptured AAA compared with the controls. Unexpectedly, all follow-up patients (n = 16) have significant (p<0.001) elevated suPAR levels three years postoperatively compared preoperatively. Conclusions: suPAR does not seem to be a useful biomarker in the AAA disease. The role of the postoperative elevation of suPAR needs to be further elucidated. (C) 2012 Elsevier Ltd. All rights reserved.
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