| 1. |
- Matejcic, M., et al.
(författare)
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Biomarkers of folate and vitamin B12 and breast cancer risk : report from the EPIC cohort
- 2017
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 140:6, s. 1246-1259
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4-Q1=1.26; 95% CI 1.00-1.58; P-trend=0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4-Q1=1.29; 95% CI 1.02-162; P-trend=0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.
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| 2. |
- Finsterle, S., et al.
(författare)
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Conceptual uncertainties in modelling the interaction between engineered and natural barriers of nuclear waste repositories in crystalline rocks
- 2019
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Ingår i: Geological Society Special Publication. - 0305-8719. ; 482:1, s. 261-283
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Tidskriftsartikel (refereegranskat)abstract
- Nuclear waste disposal in geological formations relies on a multi-barrier concept that includes engineered components – which, in many cases, include a bentonite buffer surrounding waste packages – and the host rock. Contrasts in materials, together with gradients across the interface between the engineered and natural barriers, lead to complex interactions between these two subsystems. Numerical modelling, combined with monitoring and testing data, can be used to improve our overall understanding of rock–bentonite interactions and to predict the performance of this coupled system. Although established methods exist to examine the prediction uncertainties due to uncertainties in the input parameters, the impact of conceptual model decisions on the quantitative and qualitative modelling results is more difficult to assess. A Swedish Nuclear Fuel and Waste Management Company Task Force project facilitated such an assessment. In this project, 11 teams used different conceptualizations and modelling tools to analyse the Bentonite Rock Interaction Experiment (BRIE) conducted at the Äspö Hard Rock Laboratory in Sweden. The exercise showed that prior system understanding along with the features implemented in the available simulators affect the processes included in the conceptual model. For some of these features, sufficient characterization data are available to obtain defensible results and interpretations, whereas others are less supported. The exercise also helped to identify the conceptual uncertainties that led to different assessments of the relative importance of the engineered and natural barrier subsystems. The range of predicted bentonite wetting times encompassed by the ensemble results were considerably larger than the ranges derived from individual models. This is a consequence of conceptual uncertainties, demonstrating the relevance of using a multi-model approach involving alternative conceptualizations.
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| 3. |
- Soler, J. M., et al.
(författare)
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Predictive Modeling of a Simple Field Matrix Diffusion Experiment Addressing Radionuclide Transport in Fractured Rock. Is It So Straightforward?
- 2022
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Ingår i: Nuclear Technology. - : Informa UK Limited. - 0029-5450 .- 1943-7471. ; 208:6, s. 1059-1073
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Tidskriftsartikel (refereegranskat)abstract
- The SKB GroundWater Flow and Transport of Solutes Task Force is an international forum in the area of conceptual and numerical modeling of groundwater flow and solute transport in fractured rocks relevant for the deep geological disposal of radioactive waste. Two in situ matrix diffusion experiments in crystalline rock (gneiss) were performed at POSIVA’s ONKALO underground facility in Finland. Synthetic groundwater containing several conservative and sorbing radiotracers was injected at one end of a borehole interval and flowed along a thin annulus toward the opposite end. Several teams performed predictive modeling of the tracer breakthrough curves using “conventional” modeling approaches (constant diffusion and sorption in the rock, no or minimum rock heterogeneity). Supporting information, derived from small-scale laboratory experiments, was provided. The teams were free to implement different concepts, use different codes, and apply the transport and retention parameters that they considered to be most suited (i.e., not a benchmark exercise). The main goal was the comparison of the different sets of results and the analysis of the possible differences for this relatively simple experimental setup with a well-defined geometry. Even though the experiment was designed to study matrix diffusion, the calculated peaks of the breakthrough curves were very sensitive to the assumed magnitude of dispersion in the borehole annulus. However, given the very different timescales for advection and matrix diffusion, the tails of the curves provided information concerning diffusion and retention in the rock matrix regardless of the magnitude of dispersion. In addition, although the task was designed to be a blind modeling exercise, the model results have also been compared to the measured experimental breakthroughs. Experimental results tend to show relatively small activities, wide breakthroughs, and early first arrivals, which are somewhat similar to model results using large dispersivity values.
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| 4. |
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| 5. |
- Sevastianova, K., et al.
(författare)
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Effect of short-term carbohydrate overfeeding and long-term weight loss on liver fat in overweight humans
- 2012
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165. ; 96:4, s. 727-734
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cross-sectional studies have identified a high intake of simple sugars as an important dietary factor predicting nonalcoholic fatty liver disease (NAFLD). Objective: We examined whether overfeeding overweight subjects with simple sugars increases liver fat and de novo lipogenesis (DNL) and whether this is reversible by weight loss. Design: Sixteen subjects [BMI (kg/m(2)): 30.6 +/- 1.2] were placed on a hypercaloric diet (>1000 kcal simple carbohydrates/d) for 3 wk and, thereafter, on a hypocaloric diet for 6 mo. The subjects were genotyped for rs739409 in the PNPLA3 gene. Before and after overfeeding and after hypocaloric diet, metabolic variables and liver fat (measured by proton magnetic resonance spectroscopy) were measured. The ratio of palmitate (16:0) to linoleate (18:2n-6) in serum and VLDL triglycerides was used as an index of DNL. Results: Carbohydrate overfeeding increased weight (+/- SEM) by 2% (1.8 +/- 0.3 kg; P < 0.0001) and liver fat by 27% from 9.2 +/- 1.9% to 11.7 +/- 1.9% (P = 0.005). DNL increased in proportion to the increase in liver fat and serum triglycerides in subjects with PNPLA3-148II but not PNPLA3-148MM. During the hypocaloric diet, the subjects lost 4% of their weight (3.2 +/- 0.6 kg; P < 0.0001) and 25% of their liver fat content (from 11.7 +/- 1.9% to 8.8 +/- 1.8%; P < 0.05). Conclusions: Carbohydrate overfeeding for 3 wk induced a >10-fold greater relative change in liver fat (27%) than in body weight (2%). The increase in liver fat was proportional to that in DNL. Weight loss restores liver fat to normal. These data indicate that the human fatty liver avidly accumulates fat during carbohydrate overfeeding and support a role for DNL in the pathogenesis of NAFLD. This trial was registered at www.hus.fi as 235780. Am J Clin Nutr 2012;96:727-34.
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| 6. |
- Cederberg, H., et al.
(författare)
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Non-Cholesterol Sterol Levels Predict Hyperglycemia and Conversion to Type 2 Diabetes in Finnish Men
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the levels of non-cholesterol sterols as predictors for the development of hyperglycemia (an increase in the glucose area under the curve in an oral glucose tolerance test) and incident type 2 diabetes in a 5-year follow-up study of a population-based cohort of Finnish men (METSIM Study, N = 1,050) having non-cholesterol sterols measured at baseline. Additionally we determined the association of 538,265 single nucleotide polymorphisms (SNP) with non-cholesterol sterol levels in a cross-sectional cohort of non-diabetic offspring of type 2 diabetes (the Kuopio cohort of the EUGENE2 Study, N = 273). We found that in a cross-sectional METSIM Study the levels of sterols indicating cholesterol absorption were reduced as a function of increasing fasting glucose levels, whereas the levels of sterols indicating cholesterol synthesis were increased as a function of increasing 2-hour glucose levels. A cholesterol synthesis marker desmosterol significantly predicted an increase, and two absorption markers (campesterol and avenasterol) a decrease in the risk of hyperglycemia and incident type 2 diabetes in a 5-year follow-up of the METSIM cohort, mainly attributable to insulin sensitivity. A SNP of ABCG8 was associated with fasting plasma glucose levels in a cross-sectional study but did not predict hyperglycemia or incident type 2 diabetes. In conclusion, the levels of some, but not all non-cholesterol sterols are markers of the worsening of hyperglycemia and type 2 diabetes.
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| 7. |
- Gibbs, David Corley, et al.
(författare)
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Association of prediagnostic vitamin D status with mortality among colorectal cancer patients differs by common, inherited vitamin D‐binding protein isoforms
- 2020
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 147:10, s. 2725-2734
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Tidskriftsartikel (refereegranskat)abstract
- Lower prediagnostic circulating 25‐hydroxyvitamin D (25[OH]D)—considered the best marker of total vitamin D exposure—is associated with higher mortality risk among colorectal cancer (CRC) patients. However, it is unknown whether this association differs by the vitamin D‐binding protein (GC) isoform Gc2 (encoded by GC rs4588*C>A, Thr436Lys), which may substantially affect vitamin D metabolism and modify associations of 25(OH)D with colorectal neoplasm risk. Prediagnostic 25(OH)D‐mortality associations according to Gc2 isoform were estimated using multivariable Cox proportional hazards regression among 1281 CRC cases (635 deaths, 483 from CRC) from two large prospective cohorts conducted in the United States (Cancer Prevention Study‐II) and Europe (European Prospective Investigation into Cancer and Nutrition). 25(OH)D measurements were calibrated to a single assay, season standardized, and categorized using Institute of Medicine recommendations (deficient [<30], insufficient [30 ‐ <50], sufficient [≥50 nmol/L]). In the pooled analysis, multivariable‐adjusted hazard ratios (HRs) for CRC‐specific mortality associated with deficient relative to sufficient 25(OH)D concentrations were 2.24 (95% CI 1.44‐3.49) among cases with the Gc2 isoform, and 0.94 (95% CI 0.68‐1.22) among cases without Gc2 (P interaction = .0002). The corresponding HRs for all‐cause mortality were 1.80 (95% CI 1.24‐2.60) among those with Gc2, and 1.12 (95% CI 0.84‐1.51) among those without Gc2 (P interaction = .004). Our findings suggest that the association of prediagnostic vitamin D status with mortality among CRC patients may differ by functional GC isoforms, and patients who inherit the Gc2 isoform (GC rs4588*A) may particularly benefit from higher circulating 25(OH)D for improved CRC prognosis.
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| 8. |
- Gylling, Björn, et al.
(författare)
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Vitamin B-6 and colorectal cancer risk : a prospective population-based study using 3 distinct plasma markers of vitamin B-6 status
- 2017
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 105:4, s. 897-904
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Tidskriftsartikel (refereegranskat)abstract
- Background: Higher plasma concentrations of the vitamin B-6 marker pyridoxal 5#-phosphate (PLP) have been associated with reduced colorectal cancer (CRC) risk. Inflammatory processes, including vitamin B-6 catabolism, could explain such findings. Objective: We investigated 3 biomarkers of vitamin B-6 status in relation to CRC risk. Design: This was a prospective case-control study of 613 CRC cases and 1190 matched controls nested within the Northern Sweden Health and Disease Study (n = 114,679). Participants were followed from 1985 to 2009, and the median follow-up from baseline to CRC diagnosis was 8.2 y. PLP, pyridoxal, pyridoxic acid (PA), 3-hydroxykynurenine, and xanthurenic acids (XAs) were measured in plasma with the use of liquid chromatography-tandem mass spectrometry. We calculated relative and absolute risks of CRC for PLP and the ratios 3-hydroxykynurenine: XA (HK: XA), an inverse marker of functional vitamin B-6 status, and PA:(PLP + pyridoxal) (PAr), a marker of inflammation and oxidative stress and an inverse marker of vitamin B-6 status. Results: Plasma PLP concentrations were associated with a reduced CRC risk for the third compared with the first quartile and for PLP sufficiency compared with deficiency [OR: 0.60 (95% CI: 0.44, 0.81) and OR: 0.55 (95% CI: 0.37, 0.81), respectively]. HK: XA and PAr were both associated with increased CRC risk [OR: 1.48 (95% CI: 1.08, 2.02) and OR: 1.50 (95% CI: 1.10, 2.04), respectively] for the fourth compared with the first quartile. For HK: XA and PAr, the findings were mainly observed in study participants with,10.5 y of follow-up between sampling and diagnosis. Conclusions: Vitamin B-6 deficiency as measured by plasma PLP is associated with a clear increase in CRC risk. Furthermore, our analyses of novel markers of functional vitamin B-6 status and vitamin B-6-associated oxidative stress and inflammation suggest a role in tumor progression rather than initiation.
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| 9. |
- Gylling, H., et al.
(författare)
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Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease
- 2014
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 232:2, s. 346-360
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This EAS Consensus Panel critically appraised evidence relevant to the benefit to risk relationship of functional foods with added plant sterols and/or plant stanols, as components of a healthy lifestyle, to reduce plasma low-density lipoprotein-cholesterol (LDL-C) levels, and thereby lower cardiovascular risk. Methods and results: Plant sterols/stanols (when taken at 2g/day) cause significant inhibition of cholesterol absorption and lower LDL-C levels by between 8 and 10%. The relative proportions of cholesterol versus sterol/stanol levels are similar in both plasma and tissue, with levels of sterols/stanols being 500-/10,000-fold lower than those of cholesterol, suggesting they are handled similarly to cholesterol in most cells. Despite possible atherogenicity of marked elevations in circulating levels of plant sterols/stanols, protective effects have been observed in some animal models of atherosclerosis. Higher plasma levels of plant sterols/stanols associated with intakes of 2g/day in man have not been linked to adverse effects on health in long-term human studies. Importantly, at this dose, plant sterol/stanol-mediated LDL-C lowering is additive to that of statins in dyslipidaemic subjects, equivalent to doubling the dose of statin. The reported 6-9% lowering of plasma triglyceride by 2g/day in hypertriglyceridaemic patients warrants further evaluation. Conclusion: Based on LDL-C lowering and the absence of adverse signals, this EAS Consensus Panel concludes that functional foods with plant sterols/stanols may be considered 1) in individuals with high cholesterol levels at intermediate or low global cardiovascular risk who do not qualify for pharmacotherapy, 2) as an adjunct to pharmacologic therapy in high and very high risk patients who fail to achieve LDL-C targets on statins or are statin- intolerant, 3) and in adults and children (>6 years) with familial hypercholesterolaemia, in line with current guidance. However, it must be acknowledged that there are no randomised, controlled clinical trial data with hard end-points to establish clinical benefit from the use of plant sterols or plant stanols. © 2013 The Authors.
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| 10. |
- Lankinen, Maria A., et al.
(författare)
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Dietary carbohydrate modification alters serum metabolic profiles in individuals with the metabolic syndrome
- 2010
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Ingår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier. - 0939-4753 .- 1590-3729. ; 20:4, s. 249-57
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Whole-grain cereals and diets with a low glycemic index may protect against the development of type 2 diabetes and heart disease, but the mechanisms are poorly understood. We studied the effect of carbohydrate modification on serum metabolic profiles, including lipids and branched chain amino acids, and dependencies between these and specific gene expression pathways in adipose tissue.METHODS AND RESULTS: Twenty subjects with metabolic syndrome were selected from the larger FUNGENUT study population, randomized either to a diet high in oat and wheat bread and potato (OWP) or rye bread and pasta (RP). Serum metabolomics analyses were performed using ultra-performance liquid chromatography coupled to electrospray ionization mass spectrometry (UPLC/MS), gas chromatography (GC) and UPLC. In the OWP group multiple proinflammatory lysophosphatidylcholines increased, while in the RP group docosahexaenoic acid (DHA 22:6n-3) increased and isoleucine decreased. mRNA expression of stress reactions- and adipose tissue differentiation-related genes were up-regulated in adipose tissue in the OWP group. In the RP group, however, pathways related to stress reactions and insulin signaling and energy metabolism were down-regulated. The lipid profiles had the strongest association with the changes in the adipose tissue differentiation pathway when using the elastic net regression model of the lipidomic profiles on selected pathways.CONCLUSION: Our results suggest that the dietary carbohydrate modification alters the serum metabolic profile, especially in lysoPC species, and may, thus, contribute to proinflammatory processes which in turn promote adverse changes in insulin and glucose metabolism.
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| 11. |
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| 12. |
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| 13. |
- Murphy, Neil, et al.
(författare)
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Heterogeneity of Colorectal Cancer Risk Factors by Anatomical Subsite in 10 European Countries : A Multinational Cohort Study
- 2019
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 17:7, s. 1323-1331
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Colorectal cancer located at different anatomical subsites may have distinct etiologies and risk factors. Previous studies that have examined this hypothesis have yielded inconsistent results, possibly because most studies have been of insufficient size to identify heterogeneous associations with precision.Methods: In the European Prospective Investigation into Cancer and Nutrition study, we used multivariable joint Cox proportional hazards models, which accounted for tumorsat different anatomical sites (proximal colon, distal colon, and rectum) as competing risks, to examine the relationships between 14 established/suspected lifestyle, anthropometric, and reproductive/menstrual risk factors with colorectal cancer risk. Heterogeneity across sites was tested using Wald tests.Results: After a median of 14.9 years of follow-up of 521,330 men and women, 6291 colorectal cancer cases occurred. Physical activity was related inversely to proximal colon and distal colon cancer, but not to rectal cancer (P heterogeneity = .03). Height was associated positively with proximal and distal colon cancer only, but not rectal cancer (P heterogeneity = .0001). For men, but not women, heterogeneous relationships were observed for body mass index (P heterogeneity = .008) and waist circumference (P heterogeneity = .03), with weaker positive associations found for rectal cancer, compared with proximal and distal colon cancer. Current smoking was associated with a greater risk of rectal and proximal colon cancer, but not distal colon cancer (P heterogeneity = .05). No heterogeneity by anatomical site was found for alcohol consumption, diabetes, nonsteroidal anti-inflammatory drug use, and reproductive/menstrual factors.Conclusions: The relationships between physical activity, anthropometry, and smoking with colorectal cancer risk differed by subsite, supporting the hypothesis that tumors in different anatomical regions may have distinct etiologies.
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| 14. |
- Soler, Josep M., et al.
(författare)
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Predictive and Inverse Modeling of a Radionuclide Diffusion Experiment in Crystalline Rock at ONKALO (Finland)
- 2023
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Ingår i: Nuclear Technology. - : Informa UK Limited. - 0029-5450 .- 1943-7471. ; 209:11, s. 1765-1784
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Tidskriftsartikel (refereegranskat)abstract
- The REPRO-TDE test was performed at a depth of about 400 m in the ONKALO underground research facility in Finland. Synthetic groundwater containing radionuclide tracers [tritiated water tracer (HTO), 36Cl, 22Na, 133Ba, and 134Cs] was circulated for about 4 years in a packed-off interval of the injection borehole. Tracer activities were additionally monitored in two observation boreholes. The test was the subject of a modeling exercise by the SKB GroundWater Flow and Transport of Solutes Task Force. Eleven teams participated in the exercise, using different model concepts and approaches. Predictive model calculations were based on laboratory-based information concerning porosities, diffusion coefficients, and sorption partition coefficients. After the experimental results were made available, the teams were able to revise their models to reproduce the observations. General conclusions from these back-analysis calculations include the need for reduced effective diffusion coefficients for 36Cl compared to those applicable to HTO (anion exclusion), the need to implement weaker sorption for 22Na compared to results from laboratory batch sorption experiments, and the observation of large differences between the theoretical initial concentrations for the strongly sorbing 133Ba and 134Cs, and the first measured values a few hours after tracer injection. Different teams applied different concepts, concerning mainly the implementation of isotropic versus anisotropic diffusion, or the possible existence of borehole disturbed zones around the different boreholes. The role of microstructure was also addressed in two of the models.
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| 15. |
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