| 11. |
- Folkersen, Lasse, et al.
(författare)
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Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
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Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
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Tidskriftsartikel (refereegranskat)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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| 12. |
- Froitzheim, Jan, 1981, et al.
(författare)
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Chromium evaporation of Coated and uncoated FE-22CR steels investigated by a novel denuder technique
- 2009
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Ingår i: 3rd European Fuel Cell Technology and Applications - Piero Lunghi Conference, EFC 2009; Rome; Italy; 15 December 2009 through 18 December 2009. - 9788882862114 ; , s. 77-78
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Konferensbidrag (refereegranskat)abstract
- The formation of volatile chromium species is a major problem concerning metallic interconnects for Solid Oxide Fuel Cells (SOFC). This problem is known and a number of routes, usually in the form of coatings, has been presented to overcome this problem. This paper investigates the influence of thin metallic films which can be applied by a low cost process. The measurements are carried out by a novel denuder technique where volatile chromium species are collected as sodium chromate. This technique allows the quantification of chromium evaporation in a time resolved manner. Coated and uncoated samples of ferritic steels developed for SOFC applications are investigated at 850°C in a N2-O2-H2O environment.
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| 13. |
- Froitzheim, Jan, 1981, et al.
(författare)
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Cr evaporation of metallic interconnects: A novel method for quantification
- 2009
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Ingår i: ECS Transactions. - : The Electrochemical Society. - 1938-5862 .- 1938-6737. - 9781566777391 ; 25:2 PART 2, s. 1423-1428
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Konferensbidrag (refereegranskat)abstract
- Chromium evaporation from metallic interconnects in SOFCs is commonly poisoning the cathode of SOFCs. To reduce chromium evaporation, rather thick coatings have been deposited using various coating techniques. In this study, a 22% Cr ferritic steel has been coated with thin films (
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| 14. |
- Froitzheim, Jan, 1981, et al.
(författare)
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Investigation of Chromium Volatilization from FeCr Interconnects by a Denuder Technique
- 2010
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Ingår i: Journal of the Electrochemical Society. - : The Electrochemical Society. - 1945-7111 .- 0013-4651. ; 157:9, s. B1295-B1300
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Tidskriftsartikel (refereegranskat)abstract
- A technique is presented for accurate and time-resolved quantification of chromium volatilization from alloys at high temperature. A denuder tube which is coated with Na2CO3 is placed downstream of the samples. CrO2(OH)(2) that evaporated from the samples is collected on the denuder and converted to the thermally stable Na2CrO4. The chromate is then dissolved in water and determined quantitatively. Three commercially available ferritic 22% Cr steels intended for use as solid oxide fuel cell interconnect materials (Sanergy HT, Crofer 22 APU, and ZMG 232) have been investigated with respect to chromium volatilization and oxidation rate. The effect on chromium volatilization of a submicrometer cobalt coating on the steel surface is reported. Comparisons are made with a conventional thick ceramic coating. The experiments are carried out at 850 degrees C in N-2 - 20% O-2 - 3% H2O atmosphere. The submicrometer Co coatings proved to be very efficient, reducing Cr volatilization by 1 order of magnitude. Microscopic studies show that both uncoated steel and steel coated with a submicrometer cobalt film develop two-layered oxide scales with the bottom part consisting of a Cr-rich corundum-type oxide. The uncoated samples develop a top layer consisting of (Cr, Mn)(3)O-4 oxide, whereas the Co-coated samples exhibit a top layer consisting of Co-rich spinel oxide. (C) 2010 The Electrochemical Society. [DOI: 10.1149/1.3462987] All rights reserved.
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| 15. |
- Heid, Iris M, et al.
(författare)
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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
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Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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| 16. |
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| 17. |
- Johansson, Eva, et al.
(författare)
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Time, Symptom Burden, Androgen Deprivation, and Self-Assessed Quality of Life after Radical Prostatectomy or Watchful Waiting : The Randomized Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) Clinical Trial
- 2009
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 55:2, s. 422-432
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Quality-of-life outcomes are important in the choice of treatment strategy for men with localized prostate cancer.OBJECTIVE: To evaluate how follow-up time, number of physical symptoms, and presence of androgen deprivation affected quality of life among men randomized to radical prostatectomy or watchful waiting.DESIGN, SETTING, AND PARTICIPANTS: The study group was composed of all 376 living men included in the Swedish part of the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) between January 1, 1989, and February 29, 1996. Quality-of-life data were collected after a mean follow-up time of 4.1 yr.INTERVENTION: All patients were randomly assigned to radical prostatectomy or watchful waiting. Forty-five men were androgen deprived.MEASUREMENTS: Data of specific symptoms, symptom-induced stress, sense of well-being, and self-assessed quality of life were obtained by means of a questionnaire. Psychological symptoms were assessed using seven-point visual digital scales.RESULTS AND LIMITATIONS: In analyses stratified on the basis of the numbers of physical symptoms, anxiety and depressed mood were less common, and sense of well-being and self-assessed quality of life were better throughout in the radical prostatectomy group than in the watchful waiting group. As the number of physical symptoms increased, all psychological variables became worse and more prominent in the watchful waiting group. After a follow-up time of 6-8 yr, a significant decrease in quality of life (p=0.03) was seen in the watchful waiting group. Twenty-four percent of androgen-deprived patients assigned to watchful waiting reported high self-assessed quality of life compared with 60% in the radical prostatectomy group. Eighty-eight percent of patients had clinically detected tumors.CONCLUSIONS: Androgen deprivation negatively affected self-assessed quality of life in men assigned to watchful waiting. The number of physical symptoms was associated with the level of quality of life. Quality of life was lower with longer follow-up time in both groups and was statistically significant in the watchful waiting group (p=0.03).
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| 18. |
- Lango Allen, Hana, et al.
(författare)
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Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
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Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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| 19. |
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| 20. |
- Machowicz, Rafal, et al.
(författare)
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Allogeneic hematopoietic stem cell transplantation for adult HLH : a retrospective study by the chronic malignancies and inborn errors working parties of EBMT
- 2022
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Ingår i: Bone Marrow Transplantation. - : Springer Nature. - 0268-3369 .- 1476-5365. ; 57:5, s. 817-823
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Tidskriftsartikel (refereegranskat)abstract
- Hemophagocytic lymphohistiocytosis (HLH; hemophagocytic syndrome) is a rare syndrome of potentially fatal, uncontrolled hyperinflammation. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is indicated in primary, recurrent or progressive HLH, but information about its outcomes in the adult population is limited. We obtained data about 87 adult (>= 18 years of age) patients retrospectively reported to the EBMT. The median survival time was 13.9 months. The three and five-year overall survival (OS) was 44% (95% CI 33-54%). Among 39 patients with a follow-up longer than 15 months, only three died. Relapse rate was 21% (95% CI 13-30%), while NRM reached 36% (95% CI 25-46%). Younger patients (<30 years of age) had better prognosis, with an OS of 59% (95% CI 45-73%) at three and five years vs 23% (95% CI 8-37%) for older ones. No difference in survival between reduced and myeloablative conditioning was found. To our knowledge, this is the largest report of adult HLH patients who underwent allo-HSCT. Patients who survive the first period after this procedure can expect a long disease-free survival. Both reduced intensity and myeloablative conditioning have therapeutic potential in adult HLH.
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