| 1. |
- Molin, Mikael, 1973, et al.
(författare)
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Protein kinase A controls yeast growth in visible light
- 2020
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Ingår i: BMC Biology. - : Springer Science and Business Media LLC. - 1741-7007. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: A wide variety of photosynthetic and non-photosynthetic species sense and respond to light, having developed protective mechanisms to adapt to damaging effects on DNA and proteins. While the biology of UV light-induced damage has been well studied, cellular responses to stress from visible light (400–700 nm) remain poorly understood despite being a regular part of the life cycle of many organisms. Here, we developed a high-throughput method for measuring growth under visible light stress and used it to screen for light sensitivity in the yeast gene deletion collection. Results: We found genes involved in HOG pathway signaling, RNA polymerase II transcription, translation, diphthamide modifications of the translational elongation factor eEF2, and the oxidative stress response to be required for light resistance. Reduced nuclear localization of the transcription factor Msn2 and lower glycogen accumulation indicated higher protein kinase A (cAMP-dependent protein kinase, PKA) activity in many light-sensitive gene deletion strains. We therefore used an ectopic fluorescent PKA reporter and mutants with constitutively altered PKA activity to show that repression of PKA is essential for resistance to visible light. Conclusion: We conclude that yeast photobiology is multifaceted and that protein kinase A plays a key role in the ability of cells to grow upon visible light exposure. We propose that visible light impacts on the biology and evolution of many non-photosynthetic organisms and have practical implications for how organisms are studied in the laboratory, with or without illumination.
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| 2. |
- Trovik, Clement, et al.
(författare)
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The Scandinavian Sarcoma Group Central Register: 6,000 patients after 25 years of monitoring of referral and treatment of extremity and trunk wall soft-tissue sarcoma
- 2017
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Ingår i: Acta Orthopaedica. - : TAYLOR & FRANCIS LTD. - 1745-3674 .- 1745-3682. ; 88:3, s. 341-347
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Tidskriftsartikel (refereegranskat)abstract
- Purpose - We wanted to examine the potential of the Scandinavian Sarcoma Group (SSG) Central Register, and evaluate referral and treatment practice for soft-tissue sarcomas in the extremities and trunk wall (STS) in the Nordic countries. Background - Based on incidence rates from the literature, 8,150 (7,000-9,300) cases of STS of the extremity and trunk wall should have been diagnosed in Norway, Finland, Iceland, and Sweden from 1987 through 2011. The SSG Register has 6,027 cases registered from this period, with 5,837 having complete registration of key variables. 10 centers have been reporting to the Register. The 5 centers that consistently report treat approximately 90% of the cases in their respective regions. The remaining centers have reported all the patients who were treated during certain time periods, but not for the entire 25-year period. Results - 59% of patients were referred to a sarcoma center untouched, i.e. before any attempt at open biopsy. There was an improvement from 52% during the first 5 years to 70% during the last 5 years. 50% had wide or better margins at surgery. Wide margins are now achieved less often than 20 years ago, in parallel with an increase in the use of radiotherapy. For the centers that consistently report, 97% of surviving patients are followed for more than 4 years. Metastasis-free survival (MFS) increased from 67% to 73% during the 25-year period. Interpretation - The Register is considered to be representative of extremity and trunk wall sarcoma disease in the population of Scandinavia, treated at the reporting centers. There were no clinically significant differences in treatment results at these centers.
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| 3. |
- Andreasson, Jakob, 1975, et al.
(författare)
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Electron-phonon interactions in perovskites containing Fe and Cr studied by Raman scattering using oxygen-isotope and cation substitution
- 2008
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X .- 2469-9950 .- 2469-9969. ; 78:23, s. 235103-
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Tidskriftsartikel (refereegranskat)abstract
- We use temperature-dependent inelastic light scattering to study the origin of the strong multiphonon scattering of a local oxygen breathing mode present in the mixed B-site orthorhombic (space group Pnma) perovskite LaFe0.5Cr0.5O3 but absent in isostructural LaFeO3 and LaCrO3. It is seen that the multiphonon scattering is critically sensitive to the presence of both Fe and Cr ions on the B site. These results support our interpretation that the multiphonon scattering is activated by local electron-phonon interactions according to the Franck-Condon picture following an Fe-Cr charge transfer. Further, O-18 substitution is performed on the x=0, 0.04, and 0.5 compounds and clearly shows that all modes appearing above the first-order phonon-scattering region in these compounds originate from higher-order oxygen stretching vibrations. In particular this is the case for the strong second-order scattering dominating the scattering response in LaFeO3. Accordingly we propose that these modes are generated by infrared-active longitudinal optical (IR LO) two-phonon and combination scattering activated by Frohlich interaction. For x=0.02 and 0.04 the characteristic IR LO two-phonon and Franck-Condon multiphonon-scattering profiles mix. We also study the influence of isovalent cation substitution and Sr doping in AFe(0.5)Cr(0.5)O(3) (A=La, Nd, and Gd) and La1-ySryFe0.5Cr0.5O3-delta (y=0, 0.16, and 0.5) on the strong electron-phonon coupling present in LaFe0.5Cr0.5O3. The Franck-Condon effect in LaFe0.5Cr0.5O3, is not significantly affected by isovalent A-site substitution, despite the increasing orthorhombic distortion associated with decreasing A-site ionic radii. On the contrary, aliovalent Sr doping causes a rapid decrease in the Franck-Condon scattering. This shows that the strong electron-phonon coupling in these compounds is highly sensitive to local lattice and electronic decoherence but insensitive to global lattice distortions. Finally, a preliminary assignment of the A(g) and B-2g phonon modes in AFe(0.5)Cr(0.5)O(3) (A=La, Nd, and Gd) is made based on the present observations and published results for LaCrO3 and AMnO(3). The modes associated with oxygen octahedral tilt and bending vibrations are heavily influenced by the magnitude of the orthorhombic distortion.
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| 4. |
- Damberg, Mattias, et al.
(författare)
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Investigation of transcription factor AP-2 beta genotype in women with premenstrual dysphoric disorder.
- 2005
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Ingår i: Neuroscience letters. - : Elsevier BV. - 0304-3940. ; 377:1, s. 49-52
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Tidskriftsartikel (refereegranskat)abstract
- It has repeatedly been shown that the serotonergic system is involved in the symptomatology of premenstrual dysphoric disorder (PMDD). Women with PMDD are reported to differ from symptom-free controls with regard to serotonin-related biological markers. Evidence from family and twin studies suggests a genetic contribution to the aetiology of PMDD. The expression of human transcription factor AP-2beta in neural crest cell lineages and neuroectodermal cells suggests that this protein may be of importance for functional characteristics of neurons by regulating the expression of target genes. Within the monoaminergic systems, several genes have binding sites for AP-2beta in regulatory regions, suggesting an involvement of AP-2beta in these systems. The gene encoding AP-2beta is located on chromosome 6p12-p21.1 and includes a polymorphic region consisting of a variable number of [CAAA] repeats located in the second intron. We have earlier shown that AP-2beta genotype is associated with serotonergic phenotypes and that brainstem levels of AP-2beta correlate positively to serotonin metabolism in rat frontal cortex. The aim of this study was to investigate the relationship between PMDD and transcription factor AP-2beta genotype. The participants included 176 women with PMDD and 91 healthy controls. Genotyping was performed by polymerase chain reactions. We did not observe any differences in AP-2beta genotype frequencies between PMDD subjects and controls. Our results suggest that AP-2beta genotype is not a risk factor for PMDD. To our knowledge, this is the first study investigating transcription factor AP-2beta genotype in women with PMDD. Hence, these results should be considered preliminary until replicated.
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| 5. |
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| 6. |
- Ekman, Agneta, 1961, et al.
(författare)
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Low density and high affinity of platelet [3H]paroxetine binding in women with bulimia nervosa.
- 2006
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Ingår i: Psychiatry research. - : Elsevier BV. - 0165-1781 .- 1872-7123. ; 142:2-3, s. 219-23
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Tidskriftsartikel (refereegranskat)abstract
- Impaired serotonin transmission has been suggested to be implicated in the pathophysiology of bulimia nervosa. As an indirect measure of brain serotonergic activity, the binding of tritiated ligands to platelet serotonin transporters has been studied in bulimia nervosa as well as in other putatively serotonin-related psychiatric disorders. In this study, the density and affinity of platelet serotonin transporters were assessed in 20 women meeting the DSM-IV criteria for bulimia nervosa and in 14 controls without previous or ongoing eating disorder using [(3)H]paroxetine as a ligand. In comparison to controls, women with bulimia nervosa had a significantly reduced number of platelet binding sites (B(max) = 721 +/- 313 vs. 1145 +/- 293 fmol/mg protein) and an increase in the affinity for the ligand demonstrated by a lower dissociaton constant (K(d) = 33 +/- 10 vs. 44 +/- 10 pM). A significant correlation between B(max) and K(d) values was found in patients but not in controls. Our results support the notion that bulimia nervosa is associated with a reduction in platelet serotonin transporter density. In addition, our study is the first to report that this reduced transporter density in women with bulimia nervosa is accompanied by an increase in the affinity of the transporter for the ligand.
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| 7. |
- Engström, Jens, et al.
(författare)
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Energy absorption from parks of point-absorbing wave energy converters in the Swedish exclusive economic zone
- 2020
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Ingår i: Energy Science & Engineering. - : John Wiley & Sons. - 2050-0505. ; 8:1, s. 38-49
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Tidskriftsartikel (refereegranskat)abstract
- In a future energy system based on renewable energy sources, wave energy will most likely play a role due to its high energy potential and low intermittency. The power production from parks of wave energy converters of point absorber type has been extensively studied. This is also the case for the wave energy resource at many coastal areas around the globe. Wave energy has not yet reached a commercial level, and a large variety of technologies exist; therefore, an established method to calculate the technical potential for wave energy has still not been established. To estimate the technical potential of wave energy conversion, some approximations inevitably need to be taken due to the systems high complexity. In this study, a detailed mapping of the wave climate and simulation of large arrays of hydrodynamically cross‐coupled wave energy converters are combined to calculate the technical potential for wave energy conversion in the Swedish exclusive economic zone. A 16‐year wave data set distributed in a 1.1 km × 1.1 km grid is used to calculate the absorbed energy from a park of 200 generic point absorbers. The areas with best potential have an average annual energy absorption of 16 GWh for the selected wave energy park adapted to 1 km2 when using a constant damping, while the theoretical upper bound is 63 GWh for the same area.
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| 8. |
- Eriksson, Jonas, et al.
(författare)
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Small Molecule Screening for Inhibitors of the YopH Phosphatase of Yersinia pseudotuberculosis
- 2012
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Ingår i: Advances in Yersinia Research. - New York : Springer. - 9781461435600 - 9781461435617 ; , s. 357-363
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Bokkapitel (refereegranskat)abstract
- Bacterial virulence systems are attractive targets for development of new antibacterial agents. Yersinia spp. utilize the type III secretion (T3S) system to secrete and translocate Yersinia outer proteins (Yop effectors) into the cytosol of the target cell and thereby overcome host defenses to successfully establish an infection. Thus, the Yop effectors constitute attractive targets for drug development. In the present study we apply small molecule screening to identify inhibitors of one of the secreted proteins YopH, a tyrosine phosphatase required for virulence. Characterization of seven inhibitors indicated that both competitive and noncompetitive inhibitors were identified with IC50 values of 6–20 μM.
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| 9. |
- Eriksson, K. G. Peter, et al.
(författare)
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A Simple and Reliable Electrical Method for Measuring the Junction Temperature and Thermal Resistance of 4H-SiC Power Bipolar Junction Transistors
- 2009
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Ingår i: Materials Science Forum. - : Trans Tech Publications Inc.. - 0255-5476 .- 1662-9752. ; 600-603, s. 1171-1174
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Tidskriftsartikel (refereegranskat)abstract
- To determine the maximum allowed power dissipation in a power transistor, it is important to determine the relationship between junction temperature and power dissipation. This work presents a new method for measuring the junction temperature in a SiC bipolar junction transistor (BJT) that is self-heated during DC forward conduction. The method also enables extraction of the thermal resistance between junction and ambient by measurements of the junction temperature as function of DC power dissipation. The basic principle of the method is to determine the temperature dependent IN characteristics of the transistor under pulsed conditions with negligible self-heating, and compare these results with DC measurements with self-heating. Consistent results were obtained from two independent temperature measurements using the temperature dependence of the current gain, and the temperature dependence of the base-emitter IN characteristics, respectively.
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| 10. |
- Eriksson, Olle, 1954-, et al.
(författare)
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Ovarian morphology in premenstrual dysphoria
- 2012
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 37:6, s. 742-751
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Tidskriftsartikel (refereegranskat)abstract
- Ovarian cyclicity is a prerequisite for premenstrual dysphoria (PMD), as illustrated by the fact that this condition is effectively eliminated by ovariectomy or by treatment with a GnRH agonist. Despite the possibility of differences in ovarian function between women with and without PMD, no study comparing ovarian morphology in these two groups has ever been published. Fifty-two women were recruited for this study; 26 had premenstrual dysphoria, fulfilling criteria slightly modified from those of the premenstrual dysphoric disorder, and 26 were asymptomatic age-matched controls. Ovarian morphology was assessed using transvaginal 7MHz ultrasonography on day 5 after the start of menses, and venous blood was sampled for hormone analysis on days 3 and 8, the expected day of ovulation, and day -4 of the menstrual cycle. There were no significant differences between the groups with respect to the prevalence of polycystic ovaries (PCO), the total number of follicles, the total ovarian volume or serum levels of androgen hormones. In addition, serum free testosterone levels in late premenstrual phase showed an inverse association to premenstrual symptoms of irritability and a similar inverse association trend to symptoms of depressed mood. Unexpectedly, the prevalence of ovaries with fewer than five antral or growing follicles was significantly higher in women with PMD than in controls (p=0.016). While the results do not support a role for PCO or androgen hormones in eliciting late luteal phase irritability, the possible relationship between oligofollicular ovaries and PMD deserves further study.
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| 11. |
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| 12. |
- Erlinge, D., et al.
(författare)
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Bivalirudin versus Heparin Monotherapy in Myocardial Infarction
- 2017
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 377:12, s. 1132-1142
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Tidskriftsartikel (refereegranskat)abstract
- Background The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. Methods In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y12 inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up. Results A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P=0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P=0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P=0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P=0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P=0.76). Conclusions Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others; VALIDATE-SWEDEHEART ClinicalTrialsRegister.eu number, 2012-005260-10 ; ClinicalTrials.gov number, NCT02311231 .).
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| 13. |
- Gabrielson, Marike, et al.
(författare)
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Inclusion of Endogenous Plasma Dehydroepiandrosterone Sulfate and Mammographic Density in Risk Prediction Models for Breast Cancer
- 2020
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association For Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 29:3, s. 574-581
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Tidskriftsartikel (refereegranskat)abstract
- Background: Endogenous hormones and mammographic density are risk factors for breast cancer. Joint analyses of the two may improve the ability to identify high-risk women.Methods: This study within the KARMA cohort included pre-diagnostic measures of plasma hormone levels of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), and mammographic density in 629 cases and 1,223 controls, not using menopausal hormones. We evaluated the area under the receiver-operating curve (AUC) for risk of breast cancer by adding DHEA, DHEAS, and mammographic density to the Gail or Tyrer-Cuzick 5-year risk scores or the CAD2Y 2-year risk score.Results: DHEAS and percentage density were independently and positively associated with breast cancer risk (P = 0.007 and P < 0.001, respectively) for postmenopausal, but not premenopausal, women. No significant association was seen for DHEA. In postmenopausal women, those in the highest tertiles of both DHEAS and density were at greatest risk of breast cancer (OR, 3.5; 95% confidence interval, 1.9-6.3) compared with the lowest tertiles. Adding DHEAS significantly improved the AUC for the Gail (+2.1 units, P = 0.008) and Tyrer-Cuzick (+1.3 units, P = 0.007) risk models. Adding DHEAS to the Gail and Tyrer-Cuzick models already including mammographic density further increased the AUC by 1.2 units (P = 0.006) and 0.4 units (P = 0.007), respectively, compared with only including density.Conclusions: DHEAS and mammographic density are independent risk factors for breast cancer and improve risk discrimination for postmenopausal breast cancer.Impact: Combining DHEAS and mammographic density could help identify women at high risk who may benefit from individualized breast cancer screening and/or preventive measures among postmenopausal women.
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| 14. |
- Gabrielson, Marike, et al.
(författare)
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Inclusion of Plasma Prolactin Levels in Current Risk Prediction Models of Premenopausal and Postmenopausal Breast Cancer
- 2018
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Ingår i: JNCI CANCER SPECTRUM. - : OXFORD UNIV PRESS. - 2515-5091. ; 2:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Circulating plasma prolactin is associated with breast cancer risk and may improve our ability to identify high-risk women. Mammographic density is a strong risk factor for breast cancer, but the association with prolactin is unclear. We studied the association between breast cancer, established breast cancer risk factors and plasma prolactin, and improvement of risk prediction by adding prolactin. Methods: We conducted a nested case-control study including 721 breast cancer patients and 1400 age-matched controls. Plasma prolactin levels were assayed using immunoassay and mammographic density measured by STRATUS. Odds ratios (ORs) were calculated by multivariable adjusted logistic regression, and improvement in the area under the curve for the risk of breast cancer by adding prolactin to established risk models. Statistical tests were two-sided. Results: In multivariable adjusted analyses, prolactin was associated with risk of premenopausal (OR, top vs bottom quintile = 1.9; 1.88 (95% confidence interval [CI] = 1.08 to 3.26) but not with postmenopausal breast cancer. In postmenopausal cases prolactin increased by 10.6% per cBIRADS category (P-trend = .03). In combined analyses of prolactin and mammographic density, ORs for women in the highest vs lowest tertile of both was 3.2 (95% CI = 1.3 to 7.7) for premenopausal women and 2.44 (95% CI = 1.44 to 4.14) for postmenopausal women. Adding prolactin to current risk models improved the area under the curve of the Gail model (+2.4 units, P = .02), Tyrer-Cuzick model (+3.8, P = .02), and the CAD2Y model (+1.7, P = .008) in premenopausal women. Conclusion: Circulating plasma prolactin and mammographic density appear independently associated with breast cancer risk among premenopausal women, and prolactin may improve risk prediction by current risk models.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Hemeren, Paul, et al.
(författare)
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The Use of Visual Cues to Determine the Intent of Cyclists in Traffic
- 2014
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Ingår i: 2014 IEEE International Inter-Disciplinary Conference on Cognitive Methods in Situation Awareness and Decision Support (CogSIMA). - : IEEE Press. - 9781479935635 - 9781479935642 ; , s. 47-51
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Konferensbidrag (refereegranskat)abstract
- The purpose of this research was to answer the following central questions: 1) How accurate are human observers at predicting the behavior of cyclists as the cyclists approached a crossing? 2) If the accuracy is reliably better than chance, what cues were used to make the predictions? 3) At what distance from the crossing did the most critical cues occur? 4) Can the cues be used in a model that can reliably predict cyclist intent? We present results that show a number of indicators that can be used in to predict the intention of a cyclist, i.e., future actions of a cyclist, e.g., “left turn” or “continue forward” etc.Results of empirical studies show that humans are reasonably good at this type of prediction for a majority of the situations studied. However, some situations seem to contain conflicting information. The results also suggested that human prediction of intention is to a large extent relying on a single “strong” indicator, e.g., that the cyclist makes a clear “head movement”. Several “weaker" indicators that together could be a strong “combined indicator”, or equivalently strong evidence, is likely to be missed or too complex to be handled by humans in real-time. We suggest this line of research can be used to create decision support systems that predict the behavior of cyclists in traffic.
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| 19. |
- Hemeren, Paul, et al.
(författare)
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URBANIST : Signaler som används för att avläsa cyklisters intentioner i trafiken
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Genom att titta på ett fåtal bestämda signaler kan man med god träffsäkerhet förutsäga cyklisters beteende, vilket tyder på att de identifierade signalerna är betydelsefulla. Vetskapen om dessa kan, bland annat, praktiskt användas för att utveckla enkla hjälpmedel – såsom medveten placering av fluorescerande eller reflekterande material på leder och/eller införande av olikfärgade hjälmsidor. Dylika kan förväntas förstärka kommunikationen av viktiga signaler. Vetskapen kan även användas för att utbilda oerfarna bilförare. Båda fallen kan i förlängningen ge en säkrare trafikmiljö för oskyddade trafikanter.
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| 20. |
- Ho, Peh Joo, et al.
(författare)
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Comparison of self-reported and register-based hospital medical data on comorbidities in women
- 2019
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer patients commonly present with comorbidities which are known to influence treatment decisions and survival. We aim to examine agreement between self-reported and register-based medical records (National Patient Register [NPR]). Ascertainment of nine conditions, using individually-linked data from 64,961 women enrolled in the Swedish KARolinska MAmmography Project for Risk Prediction of Breast Cancer (KARMA) study. Agreement was assessed using observed proportion of agreement (overall agreement), expected proportion of agreement, and Cohen's Kappa statistic. Two-stage logistic regression models taking into account chance agreement were used to identify potential predictors of overall agreement. High levels of overall agreement (i.e. ≥86.6%) were observed for all conditions. Substantial agreement (Cohen's Kappa) was observed for myocardial infarction (0.74), diabetes (0.71) and stroke (0.64) between self-reported and NPR data. Moderate agreement was observed for preeclampsia (0.51) and hypertension (0.46). Fair agreement was observed for heart failure (0.40) and polycystic ovaries or ovarian cysts (0.27). For hyperlipidemia (0.14) and angina (0.10), slight agreement was observed. In most subgroups we observed negative specific agreement of >90%. There is no clear reference data source for ascertainment of conditions. Negative specific agreement between NPR and self-reported data is consistently high across all conditions.
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| 21. |
- Holm, Johanna, et al.
(författare)
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Assessment of breast cancer risk factors reveals subtype heterogeneity
- 2017
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Ingår i: Cancer Research. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0008-5472. ; 77:13, s. 3708-3717
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Tidskriftsartikel (refereegranskat)abstract
- Subtype heterogeneity for breast cancer risk factors has been suspected, potentially reflecting etiological differences and implicating risk prediction. Reports are conflicting regarding presence of heterogeneity for many exposures. To examine subtype heterogeneity across known breast cancer risk factors, we conducted a case-control analysis of 2,632 breast cancers and 15,945 controls in Sweden. Molecular subtype was predicted from pathology-record derived immunohistochemistry markers by a classifier trained on PAM50 subtyping. Multinomial logistic regression estimated separate odds ratios for each subtype by the exposures parity, age at first birth, breastfeeding, menarche, HRT use, somatotype at age 18, benign breast disease, mammographic density, polygenic risk score, family history of breast cancer and BRCA mutations. We found clear subtype heterogeneity for genetic factors and breastfeeding. The polygenic risk score was associated with risk of all subtypes except for the basal-like (p heterogeneity < 0.0001). Parous women who never breastfed were at higher risk of basal-like subtype (OR 4.17; 95% CI 1.89 to 9.21) compared to both nulliparous (reference) and breastfeeding women. Breastfeeding was not associated with risk of HER2-overexpressing type, but protective for all other subtypes. The observed heterogeneity in risk of distinct breast cancer subtypes for germline variants supports heterogeneity in etiology and has implications for their use in risk prediction. The increased risk of basal-like subtype among women who never breastfed merits more research into potential causal mechanisms and confounders.
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| 22. |
- Karlsson, Stefan, et al.
(författare)
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“Transparent Intelligence” for Sustainable Development
- 2018
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Ingår i: Abstracts. ; , s. 208-
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Konferensbidrag (refereegranskat)abstract
- Transparent materials are essential in everyone’s life. They enable daylight to reach the interior of buildings, thereby contributing to both our physical and mental well-being; they are the primary component for communication via optical fibers and a key component in electronic devices such as protective cover and/or dielectric material; and they enable clean energy production through solar panels or algae reactors by acting as protective and light transmitting barriers. Adding functions to transparent materials in an intelligent way creates further opportunities to use and enhance the beneficial impacts of transparency. The concept Transparent Intelligence covers transparent materials and products with integral intelligent functions – passive, active or interactive. By using Transparent Intelligence it is possible to embrace many of the societal challenges that we are facing today. The concept can be divided into five broad industrial sectors: Built Environment, Information and Communication Technologies (ICT), Solar Energy, Mobility, and Materials. A perspective on how Transparent Intelligence can improve the sustainable development of our world will be presented, using examples of electrochromic windows for energy-efficient buildings, photocatalytic coatings for improved indoor air quality, transparent conductive coatings for antennas, bandpass filters for mobile phone indoor coverage, UV down-converting components for efficient solar energy, hygienic surfaces for infection mitigation on electronic devices, printed electronics for sustainable glass packaging, and IR-reflecting coatings for fire safety.
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| 23. |
- Klaric, Lucija, et al.
(författare)
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Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.
- 2021
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. ; , s. 1-28
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at the FAS locus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.
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- Landén, Mikael, 1966, et al.
(författare)
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Compounds with affinity for serotonergic receptors in the treatment of premenstrual dysphoria: a comparison of buspirone, nefazodone and placebo.
- 2001
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Ingår i: Psychopharmacology. - 0033-3158. ; 155:3, s. 292-8
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: It is well established that serotonin reuptake inhibitors (SRIs) are effective for the treatment of premenstrual dysphoria (PMD), but the receptor subtype(s) mediating this effect of serotonin have yet not been identified. OBJECTIVE: In this trial, the possible efficacy of buspirone, a partial 5HT1A receptor agonist, and nefazodone, a combined SRI and 5HT2 receptor antagonist, was evaluated in women with PMD. METHODS: After a three-menstrual-cycle screening phase, patients were randomised to buspirone (n=19), nefazodone (n=22) or placebo (n=22). During the first two treatment cycles, patients were taking the drug during the luteal phase only (mean +/- SD daily dose of buspirone: 21 +/- 6 mg; nefazodone: 228 +/- 54 mg). During the subsequent two cycles, the medication was taken each day of the menstrual cycle (mean daily dose of buspirone: 27 +/- 10 mg; nefazodone: 304 +/- 95 mg). RESULTS: With respect to self-rated global improvement, buspirone (P<0.001) but not nefazodone was significantly superior to placebo. While buspirone appeared to reduce self-rated irritability (visual analogue scale) more effectively than placebo, other self-rated symptoms did not differ markedly between the groups. The side-effects were mild, and sexual dysfunction was not significantly more common in patients given buspirone or nefazodone than in those given placebo. CONCLUSION: It is suggested that buspirone is mildly effective for premenstrual irritability. In patients experiencing sexual dysfunction when treated with an SRI, buspirone may be a useful alternative.
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