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- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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- Sundström, Johan, Professor, 1971-, et al.
(författare)
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Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults
- 2019
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.
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- Andersson, Jenny, et al.
(författare)
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Is it possible to identify patient´s sex when reading blinded illness narratives? An experimental study about gender bias
- 2008
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Ingår i: International Journal for Equity in Health. - : BioMed Central. - 1475-9276. ; 7:21, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Background: In many diseases men and women, for no apparent medical reason, are not offered the same investigations and treatment in health care. This may be due to staff's stereotypical preconceptions about men and women, i.e., gender bias. In the clinical situation it is difficult to know whether gender differences in management reflect physicians' gender bias or male and female patients' different needs or different ways of expressing their needs. To shed some light on these possibilities this study investigated to what extent it was possible to identify patients' sex when reading their blinded illness narratives, i.e., do male and female patients express themselves differently enough to be recognised as men and women without being categorised on beforehand?Methods: Eighty-one authentic letters about being diseased by cancer were blinded regarding sex and read by 130 students of medicine and psychology. For each letter the participants were asked to give the author's sex and to explain their choice. The success rates were analysed statistically. To illuminate the participants' reasoning the explanations of four letters were analysed qualitatively.Results: The patient's sex was correctly identified in 62% of the cases, with significantly higher rates in male narratives. There were no differences between male and female participants. In the qualitative analysis the choice of a male writer was explained by: a short letter; formal language; a focus on facts and a lack of emotions. In contrast the reasons for the choice of a woman were: a long letter; vivid language; mention of emotions and interpersonal relationships. Furthermore, the same expressions were interpreted differently depending on whether the participant believed the writer to be male or female.Conclusion: It was possible to detect gender differences in the blinded illness narratives. The students' explanations for their choice of sex agreed with common gender stereotypes implying that such stereotypes correspond, at least on a group level, to differences in male and female patients' illness descriptions. However, it was also obvious that preconceptions about gender obstructed and biased the interpretations, a finding with implications for the understanding of gender bias in clinical practice.
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- Andersson, Jenny Marie, et al.
(författare)
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Effect of cholesterol on the molecular structure and transitions in a clinical-grade lung surfactant extract
- 2017
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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. - 0027-8424. ; 114:18, s. 3592-3601
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Tidskriftsartikel (refereegranskat)abstract
- The lipid-protein film covering the interface of the lung alveolar in mammals is vital for proper lung function and its deficiency is related to a range of diseases. Here we present a molecular-level characterization of a clinical-grade porcine lung surfactant extract using a multitechnique approach consisting of 1H-13C solid-state nuclear magnetic spectroscopy, small-And wide-Angle X-ray scattering, and mass spectrometry. The detailed characterization presented for reconstituted membranes of a lung extract demonstrates that the molecular structure of lung surfactant strongly depends on the concentration of cholesterol. If cholesterol makes up about 11% of the total dry weight of lung surfactant, the surfactant extract adopts a single liquid-ordered lamellar phase, Lα(o), at physiological temperatures. This Lα(o) phase gradually changes into a liquid-disordered lamellar phase, Lα(d), when the temperature is increased by a few degrees. In the absence of cholesterol the system segregates into one lamellar gel phase and one Lα(d) phase. Remarkably, it was possible to measure a large set of order parameter magnitudes /SCH/ from the liquiddisordered and -ordered lamellar phases and assign them to specific C-H bonds of the phospholipids in the biological extract with no use of isotopic labeling. These findings with molecular details on lung surfactant mixtures together with the presented NMR methodology may guide further development of pulmonary surfactant pharmaceuticals that better mimic the physiological selfassembly compositions for treatment of pathological states such as respiratory distress syndrome.
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| 9. |
- Andersson, Jenny Marie, et al.
(författare)
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The Impact of Nonequilibrium Conditions in Lung Surfactant : Structure and Composition Gradients in Multilamellar Films
- 2018
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Ingår i: ACS Central Science. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 4:10, s. 1315-1325
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Tidskriftsartikel (refereegranskat)abstract
- The lipid-protein mixture that covers the lung alveoli, lung surfactant, ensures mechanical robustness and controls gas transport during breathing. Lung surfactant is located at an interface between water-rich tissue and humid, but not fully saturated, air. The resulting humidity difference places the lung surfactant film out of thermodynamic equilibrium, which triggers the buildup of a water gradient. Here, we present a millifluidic method to assemble multilamellar interfacial films from vesicular dispersions of a clinical lung surfactant extract used in replacement therapy. Using small-angle X-ray scattering, infrared, Raman, and optical microscopies, we show that the interfacial film consists of several coexisting lamellar phases displaying a substantial variation in water swelling. This complex phase behavior contrasts to observations made under equilibrium conditions. We demonstrate that this disparity stems from additional lipid and protein gradients originating from differences in their transport properties. Supplementing the extract with cholesterol, to levels similar to the endogenous lung surfactant, dispels this complexity. We observed a homogeneous multilayer structure consisting of a single lamellar phase exhibiting negligible variations in swelling in the water gradient. Our results demonstrate the necessity of considering nonequilibrium thermodynamic conditions to study the structure of lung surfactant multilayer films, which is not accessible in bulk or monolayer studies. Our reconstitution methodology also opens avenues for lung surfactant pharmaceuticals and the understanding of composition, structure, and property relationships at biological air-liquid interfaces.
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| 10. |
- Andersson, Jenny Marie, et al.
(författare)
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The plant dehydrin Lti30 stabilizes lipid lamellar structures in varying hydration conditions[S]
- 2020
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Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 61:7, s. 1014-1024
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge to plant growth and survival are changes in temperature and diminishing water supply. During acute temperature and water stress, plants often express stress proteins, such as dehydrins, which are intrinsically disordered hydrophilic proteins. In this article, we investigated how the dehydrin Lti30 fromArabidopsis thalianastabilizes membrane systems that are exposed to large changes in hydration. We also compared the effects of Lti30 on membranes with those of the simple osmolytes urea and trimethylamineN-oxide. Using X-ray diffraction and solid-state NMR, we studied lipid-protein self-assembly at varying hydration levels. We made the following observations:1) the association of Lti30 with anionic membranes relies on electrostatic attraction, and the protein is located in the bilayer interfacial membrane region;2) Lti30 can stabilize the lamellar multilayer structure, making it insensitive to variations in water content;3) in lipid systems with a composition similar to those present in some seeds and plants, dehydrin can prevent the formation of nonlamellar phases upon drying, which may be crucial for maintaining membrane integrity; and4) Lti30 stabilizes bilayer structures both at high and low water contents, whereas the small osmolyte molecules mainly prevent dehydration-induced transitions. These results corroborate the idea that dehydrins are part of a sensitive and multifaceted regulatory mechanism that protects plant cells against stress.
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