Comparison and Uncertainty Quantification of Two-Fluid Models forBubbly Flows with NEPTUNE_CFD and STAR-CCM+

International audienceThe nuclear industry is interested in better understanding the behavior of turbulent boiling flowsand in using modern computational tools for the design and analysis of advanced fuels and reactorsand for simulation and study of mitigation strategies in accident scenarios. Such interests serve asdrivers for the advancement of the 3-dimensional multiphase Computational Fluid Dynamicsapproach. A pair of parallel efforts have been underway in Europe and in the United States, theNEPTUNE and CASL programs respectively, that aim at delivering advanced simulation tools thatwill enable improved safety and economy of operations of the reactor fleet. Results from acollaboration between these two efforts, aimed at advancing the understanding of multiphaseclosures for pressurized water reactor (PWR) application, are presented. Particular attention is paidto the assessment and analysis of the different physical models implemented in NEPTUNE_CFDand STAR-CCM+ codes used in the NEPTUNE and the CASL programs respectively, forapplication to turbulent two-phase bubbly flows. The experiments conducted by Liu and Bankoff(Liu, 1989; Liu and Bankoff 1993a and b) are selected for benchmarking, and predictions from thetwo codes are presented for a broad range of flow conditions and with void fractions varyingbetween 0 and 50percent. Comparison of the CFD simulations and experimental measurements revealsthat a similar level of accuracy is achieved in the two codes. The differences in both sets of closuremodels are analyzed, and their capability to capture the main features of the flow over a wide rangeof experimental conditions are discussed. This analysis paves the way for future improvements ofexisting two-fluid models. The benchmarks are further leveraged for a systematic study of thepropagation of model uncertainties. This provides insights into mechanisms that lead to complexinteractions between individual closures (of the different phenomena) in the multiphase CFDapproach. As such, it is seen that the multi-CFD-code approach and the principled uncertaintyquantification approach are both of great value in assessing the limitations and the level of maturityof multiphase hydrodynamic closures

Epigenome-wide association study reveals decreased average methylation levels years before breast cancer diagnosis

Interest in the potential of DNA methylation in peripheral blood as a biomarker of cancer risk is increasing. We aimed to assess whether epigenome-wide DNA methylation measured in peripheral blood samples obtained before onset of the disease is associated with increased risk of breast cancer. We report on three independent prospective nested case-control studies from the European Prospective Investigation into Cancer and Nutrition (EPIC-Italy; n = 162 matched case-control pairs), the Norwegian Women and Cancer study (NOWAC; n = 168 matched pairs), and the Breakthrough Generations Study (BGS; n = 548 matched pairs). We used the Illumina 450k array to measure methylation in the EPIC and NOWAC cohorts. Whole-genome bisulphite sequencing (WGBS) was performed on the BGS cohort using pooled DNA samples, combined to reach 50× coverage across ~16 million CpG sites in the genome including 450k array CpG sites. Mean β values over all probes were calculated as a measurement for epigenome-wide methylation

Segmentation of Retinal Ganglion Cells From Fluorescent Microscopy Imaging

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Acrylamide and Glycidamide Hemoglobin Adducts and Epithelial Ovarian Cancer: A Nested Case-Control Study in Nonsmoking Postmenopausal Women from the EPIC Cohort

Background: Acrylamide was classified as “probably carcinogenic to humans (group 2A)” by the International Agency for Research on Cancer. Epithelial ovarian cancer (EOC) is the fourth cause of cancer mortality in women. Five epidemiological studies have evaluated the association between EOC risk and dietary acrylamide intake assessed using food frequency questionnaires, and one nested case–control study evaluated hemoglobin adducts of acrylamide (HbAA) and its metabolite glycidamide (HbGA) and EOC risk; the results of these studies were inconsistent. Methods: A nested case–control study in nonsmoking postmenopausal women (334 cases, 417 controls) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Unconditional logistic regression models were used to estimate ORs and 95% confidence intervals (CI) for the association between HbAA, HbGA, HbAA+HbGA, and HbGA/HbAA and EOC and invasive serous EOC risk. Results: No overall associations were observed between biomarkers of acrylamide exposure analyzed in quintiles and EOC risk; however, positive associations were observed between some middle quintiles of HbGA and HbAA+HbGA. Elevated but nonstatistically significant ORs for serous EOC were observed for HbGA and HbAA+HbGA (ORQ5vsQ1, 1.91; 95% CI, 0.96–3.81 and ORQ5vsQ1, 1.90; 95% CI, 0.94–3.83, respectively); however, no linear dose–response trends were observed. Conclusion: This EPIC nested case–control study failed to observe a clear association between biomarkers of acrylamide exposure and the risk of EOC or invasive serous EOC. Impact: It is unlikely that dietary acrylamide exposure increases ovarian cancer risk; however, additional studies with larger sample size should be performed to exclude any possible association with EOC risk

An epidemiological model for prediction of endometrial cancer risk in Europe

Endometrial cancer (EC) is the fourth most frequent cancer in women in Europe, and as its incidence is increasing, prevention strategies gain further pertinence. Risk prediction models can be a useful tool for identifying women likely to benefit from targeted prevention measures. On the basis of data from 201,811 women (mostly aged 30–65 years) including 855 incident EC cases from eight countries in the European Prospective Investigation into Cancer and Nutrition cohort, a model to predict EC was developed. A step-wise model selection process was used to select confirmed predictive epidemiologic risk factors. Piece-wise constant hazard rates in 5-year age-intervals were estimated in a cause-specific competing risks model, five-fold-cross-validation was applied for internal validation. Risk factors included in the risk prediction model were body-mass index (BMI), menopausal status, age at menarche and at menopause, oral contraceptive use, overall and by different BMI categories and overall duration of use, parity, age at first full-term pregnancy, duration of menopausal hormone therapy and smoking status (specific for pre, peri- and post-menopausal women). These variables improved the discriminating capacity to predict risk over 5 years from 71 % for a model based on age alone to 77 % (overall C statistic), and the model was well-calibrated (ratio of expected to observed cases = 0.99). Our model could be used for the identification of women at increased risk of EC in Western Europe. To achieve an EC-risk model with general validity, a large-scale cohort-consortium approach would be needed to assess and adjust for population variation

Insulin-like growth factor I and risk of epithelial invasive ovarian cancer by tumour characteristics: results from the EPIC cohort

Background: Prospective studies on insulin-like growth factor I (IGF-I) and epithelial ovarian cancer (EOC) risk are inconclusive. Data suggest risk associations vary by tumour characteristics. Methods: We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate IGF-I concentrations and EOC risk by tumour characteristics (n=565 cases). Multivariable conditional logistic regression models were used to estimate associations. Results: We observed no association between IGF-I and EOC overall or by tumour characteristics. Conclusions: In the largest prospective study to date was no association between IGF-I and EOC risk. Pre-diagnostic serum IGF-I concentrations may not influence EOC risk

Blood DNA methylation and breast cancer risk: a meta-analysis of four prospective cohort studies

BACKGROUND: Environmental and genetic factors play an important role in the etiology of breast cancer. Several small blood-based DNA methylation studies have reported risk associations with methylation at individual CpGs and average methylation levels; however, these findings require validation in larger prospective cohort studies. To investigate the role of blood DNA methylation on breast cancer risk, we conducted a meta-analysis of four prospective cohort studies, including a total of 1663 incident cases and 1885 controls, the largest study of blood DNA methylation and breast cancer risk to date. METHODS: We assessed associations with methylation at 365,145 CpGs present in the HumanMethylation450 (HM450K) Beadchip, after excluding CpGs that did not pass quality controls in all studies. Each of the four cohorts estimated odds ratios (ORs) and 95% confidence intervals (CI) for the association between each individual CpG and breast cancer risk. In addition, each study assessed the association between average methylation measures and breast cancer risk, adjusted and unadjusted for cell-type composition. Study-specific ORs were combined using fixed-effect meta-analysis with inverse variance weights. Stratified analyses were conducted by age at diagnosis ( 10 years). The false discovery rate (q value) was used to account for multiple testing. RESULTS: The average age at blood draw ranged from 52.2 to 62.2 years across the four cohorts. Median follow-up time ranged from 6.6 to 8.4 years. The methylation measured at individual CpGs was not associated with breast cancer risk (q value > 0.59). In addition, higher average methylation level was not associated with risk of breast cancer (OR = 0.94, 95% CI = 0.85, 1.05; P = 0.26; P for study heterogeneity = 0.86). We found no evidence of modification of this association by age at diagnosis (P = 0.17), ER status (P = 0.88), time since blood collection (P = 0.98), or CpG location (P = 0.98). CONCLUSIONS: Our data indicate that DNA methylation measured in the blood prior to breast cancer diagnosis in predominantly postmenopausal women is unlikely to be associated with substantial breast cancer risk on the HM450K array. Larger studies or with greater methylation coverage are needed to determine if associations exist between blood DNA methylation and breast cancer risk

Intérêt écologique des galeries de drainage

Artificial subterranean habitats can be of important ecological interest. Draining galleries are a typology of artificial springs with underground development characterized by an almost horizontal tunnel that penetrates the side of a slope, to catch the subterranean water and bring it outward. They are a very ancient spring catching technique and provide interesting unstudied subterranean habitats. In this study we surveyed 18 draining galleries in NW Italy. We provide specific environmental data that can help to support broad conclusions on the ecological features and value of these habitats. We found that they house permanent waterbodies, have lengths up to 120 m, are characterized by climatic conditions similar to those of natural caves. We collected several taxa of organisms, adapted to subterranean life as well as coming from outside environment, which find inside draining galleries shelter, roosting and breeding sites. We tested the role of accessibility in determining galleries biodiversity and we found that the latter is scarcely affected. From a conservationist point of view draining galleries can have important ecological value, particularly in areas devoid of natural subterranean habitatsLes environnements souterrains artificiels peuvent être très intéressants d'une point de vue écologique. Les galeries drainantes sont des sources artificielles avec un développement hypogé constitué par une galerie presque horizontale qui s'étend à l'intérieur d'un relief. Il s'agit d'une technique de captage très ancienne qui a créé des habitats souterrains non ou peu étudiés et qui sont potentiellement très intéressants d'un point de vue écologique. Nous avons étudié 18 galeries drainantes dans le nord-ouest de l'Italie. Nous présentons des données écologiques spécifiques qui peuvent aider à formuler des conclusions générales sur les caractéristiques écologiques de ces habitats hypogés. Les galeries drainantes, qui dans la région d'étude atteignent 120 m de longueur, offrent la présence de biotopes humides permanents et ont des caractéristiques climatiques semblables à celles des grottes. Elles constituent des refuges et des sites de reproduction tant à des organismes typiques de la faune cavernicole qu'à beaucoup de taxons provenant de l'extérieur. Nous n'avons pas observé d'influence statistiquement significative de l'accessibilité des sites sur leur niveau de biodiversité. Du point de vue de la conservation les galeries de drainage présentent une valeur écologique certaine, surtout dans les zones dépourvues d'environnements souterrains naturels