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| 2. |
- Haycock, Philip C., et al.
(författare)
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Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
- 2017
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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- Corvigno, Sara, et al.
(författare)
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Multi-parametric profiling of renal cell, colorectal, and ovarian cancer identifies tumour-type-specific stroma phenotypes and a novel vascular biomarker
- 2017
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Ingår i: The journal of pathology. Clinical research. - : WILEY. - 2056-4538. ; 3:3, s. 214-224
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Tidskriftsartikel (refereegranskat)abstract
- A novel set of integrated procedures for quantification of fibroblast-rich stroma and vascular characteristics has recently been presented allowing discovery of novel perivascular and stromal biomarkers in colorectal, renal cell, and ovarian cancer. In the present study, data obtained through these procedures from clinically well-annotated collections of these three tumour types have been used to address two novel questions. First, data have been used to investigate if the three tumour types demonstrate significant differences regarding features such as vessel diameter, vessel density, and perivascular marker expression. Second, analyses of the cohorts have been used to explore the prognostic significance of a novel vascular metric, 'vessel distance inter-quartile range (IQR)' that describes intra-case heterogeneity regarding vessel distribution. The comparisons between the three tumour types demonstrated a set of significant differences. Vessel density of renal cell cancer was statistically significantly higher than in colorectal and ovarian cancer. Vessel diameter was statistically significantly higher in ovarian cancer. Concerning perivascular status, colorectal cancer displayed significantly higher levels of perivascular PDGFR-beta expression than the other two tumour types. Intra-case heterogeneity of perivascular PDGFR-beta expression was also higher in colorectal cancer. Notably, these fibroblast-dominated stroma phenotypes matched previously described experimental tumour stroma characteristics, which have been linked to differential sensitivity to anti-VEGF drugs. High 'vessel distance IQR' was significantly associated with poor survival in both renal cell cancer and colorectal cancer. In renal cell cancer, this characteristic also acted as an independent prognostic marker according to multivariate analyses including standard clinico-pathological characteristics. Explorative subset analyses indicated particularly strong prognostic significance of 'vessel distance IQR' in T stage 4 of this cancer type. Together, these analyses identified tumour-type-specific vascular-stroma phenotypes of possible functional significance, and suggest 'vessel distance IQR' as a novel prognostic biomarker.
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| 4. |
- Johansson, Boo, et al.
(författare)
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Laxative treatment elevates plasma homocysteine: a study on a population-based Swedish sample of old people
- 2004
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Ingår i: European Journal of Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 60:1, s. 45-49
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Elevated plasma homocysteine might indicate an increased risk of cancer, and cardiovascular and neurological diseases. The homocysteine level depends on the supply of folate and cobalamine, and constipation and/or laxative treatment might compromise this supply. The present study examined the impact of constipation and laxative treatment on the blood levels of homocysteine, folate and cobalamine in a population-based sample of aged people, including consideration of frailty and impaired renal function, both of which may also influence the homocysteine level. METHODS: The study was based on biochemical tests in 341 females and 183 males aged 82 years or older. The concentrations of homocysteine (plasma), folate, cobalamine and urea (serum) were measured in subjects with and without ongoing treatment with laxative drugs. Values were adjusted for age, gender and frailty, as well as for clinical diagnoses and drug therapies known to affect homocysteine levels. RESULTS: Homocysteine levels were increased and those of folate reduced in aged subjects on laxatives. Homocysteine remained elevated after adjusting for frailty and various neurological disorders. There was no significant effect on homocysteine and folate in constipated subjects without laxatives
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| 5. |
- Köttgen, Anna, et al.
(författare)
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New loci associated with kidney function and chronic kidney disease
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:5, s. 376-384
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea < 60 ml/min/1.73 m2; n = 5,807 individuals with CKD (cases)). Follow-up of the 23 new genome-wide–significant loci (P < 5 × 10−8) in 22,982 replication samples identified 13 new loci affecting renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2 and SLC7A9) and 7 loci suspected to affect creatinine production and secretion (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72 and BCAS3). These results further our understanding of the biologic mechanisms of kidney function by identifying loci that potentially influence nephrogenesis, podocyte function, angiogenesis, solute transport and metabolic functions of the kidney.
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| 6. |
- Vermeer, Nina C. A., et al.
(författare)
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Treatment and Survival of Patients with Colon Cancer Aged 80 Years and Older : A EURECCA International Comparison
- 2018
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Ingår i: The Oncologist. - : Wiley-Blackwell. - 1083-7159 .- 1549-490X. ; 23:8, s. 982-990
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Tidskriftsartikel (refereegranskat)abstract
- Background. Colon cancer in older patients represents a major public health issue. As older patients are hardly included in clinical trials, the optimal treatment of these patients remains unclear. The present international EURECCA comparison explores possible associations between treatment and survival outcomes in elderly colon cancer patients.Subjects, Materials, and Methods. National data from Belgium, Denmark, The Netherlands, Norway, and Sweden were obtained, as well as a multicenter surgery cohort from Germany. Patients aged 80 years and older, diagnosed with colon cancer between 2001 and 2010, were included. The study interval was divided into two periods: 2001–2006 and 2007–2010. The proportion of surgical treatment and chemotherapy within a country and its relation to relative survival were calculated for each time frame.Results. Overall, 50,761 patients were included. At least 94% of patients with stage II and III colon cancer underwent surgical removal of the tumor. For stage II–IV, the proportion of chemotherapy after surgery was highest in Belgium and lowest in The Netherlands and Norway. For stage III, it varied from 24.8% in Belgium and 3.9% in Norway. For stage III, a better adjusted relative survival between 2007 and 2010 was observed in Sweden (adjusted relative excess risk [RER] 0.64, 95% confidence interval [CI]: 0.54–0.76) and Norway (adjusted RER 0.81, 95% CI: 0.69–0.96) compared with Belgium.Conclusion. There is substantial variation in the rate of treatment and survival between countries for patients with colon cancer aged 80 years or older. Despite higher prescription of adjuvant chemotherapy, poorer survival outcomes were observed in Belgium. No clear linear pattern between the proportion of chemotherapy and better adjusted relative survival was observed.
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| 9. |
- Babayev, Rafig, et al.
(författare)
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Computational characterization of hydrogen direct injection and nonpremixed combustion in a compression-ignition engine
- 2021
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Ingår i: International Journal of Hydrogen Energy. - : Elsevier BV. - 0360-3199. ; 46:35, s. 18678-18696
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Tidskriftsartikel (refereegranskat)abstract
- With the revived interest in hydrogen (H ) as a direct combustion fuel for engine applications, a computational study is conducted to assess the characteristics of H direct-injection (DI) compression-ignition (CI) non-premixed combustion concept. Development of a CFD modeling using CONVERGE CFD solver focuses on hydrogen's unique characteristics by utilizing a suitable numerical method to reproduce the direct H injection phenomena. A grid sensitivity study is performed to ensure the fidelity of results with optimal cost, and the models are validated against constant-volume optical chamber and diesel engine experimental data. The present study aims to contribute to the future development of DICI H combustion engines, providing detailed characterization of the combustion cycle, and highlighting several distinct aspects of CI nonpremixed H versus diesel combustion. First, unlike the common description of diesel sprays, hydrogen jets do not exhibit significant flame lift-off and air entrainment near injector nozzle, and the fuel-air interface is drastically more stratified with no sign of premixing. It is also found that the DICI H combustion concept is governed first by a free turbulent jet mixing phase, then by an in-cylinder global mixing phase. The former is drastically more dominant with the DICI H engine compared to conventional diesel engines. The free-jet mixing is also found to be more effective that the global mixing, which indicates the need to completely rethink the optimization strategies for CI engines when using H as fuel. 2 2 2 2 2 2 2 2
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| 10. |
- Babayev, Rafig, 1995, et al.
(författare)
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Computational comparison of the conventional diesel and hydrogen direct-injection compression-ignition combustion engines
- 2022
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Ingår i: Fuel. - : Elsevier BV. - 0016-2361. ; 307
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Tidskriftsartikel (refereegranskat)abstract
- Most research and development on hydrogen (H2) internal combustion engines focus on premixed-charge spark ignition (SI) or diesel-hydrogen dual-fuel technologies. Premixed charge limits the engine efficiency, power density, and safety, while diesel injections give rise to CO2 and particulate emissions. This paper demonstrates a non-premixed compression-ignition (CI) neat H2 engine concept that uses H2 pilots for ignition. It compares the CI H2 engine to an equivalent diesel engine to draw fundamental insights about the mixing and combustion processes. The Converge computational fluid dynamics solver is used for all simulations. The results show that the brake thermal efficiency of the CI H2 engine is comparable or higher than diesel, and the molar expansion with H2 injections at TDC constitutes 5–10 % of the total useful work. Fuel-air mixing in the free-jet phase of combustion is substantially higher with H2 due to hydrogen's gaseous state, low density, high injection velocity, and transient vortices, which contribute to the 3 times higher air entrainment into the quasi-steady-state jet regions. However, the H2 jet momentum is up to 4 times lower than for diesel, which leads to not only ineffective momentum-driven global mixing but also reduced heat transfer losses with H2. The short H2 flame quenching distance may also be inconsequential for heat transfer in CI engines. Finally, this research enables future improvements in CI H2 engine efficiency by hypothesizing a new optimization path, which maximizes the free-jet phase of combustion, hence is totally different from that for conventional diesel engines.
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