BIOMARKERS OF MATERNAL SMOKING AND THE RISK OF RETINOBLASTOMA IN OFFSPRING.

PURPOSE: Previous studies examining the risk of retinoblastoma with maternal smoking were inconclusive, likely due in part to the reliance on self-reported maternal smoking. This study uses biomarkers of tobacco smoking in neonatal dried blood spots to investigate associations between maternal smoking and retinoblastoma in offspring. METHODS: The authors randomly selected 498 retinoblastoma cases and 895 control subjects born between 1983 and 2011 from a population-based case-control study in California. Maternal pregnancy-related smoking was measured using the following three metrics: provider or self-reported smoking during pregnancy, cotinine, and hydroxycotinine in neonatal blood. The authors used multivariable logistic regression to estimate the effects of maternal tobacco smoking on retinoblastoma. RESULTS: Using all metrics (biomarkers or self-report), maternal smoking late in pregnancy or early postpartum was related to retinoblastoma (all types; odds ratio = 1.44, 95% confidence interval: 1.00-2.09). Relying on cotinine or hydroxycotinine to ascertain smoking, maternal smoking was related to unilateral retinoblastoma (odds ratio = 1.66, 95% confidence interval: 1.08-2.57). CONCLUSION: The results indicate that maternal smoking during pregnancy may be a risk factor for retinoblastoma, particularly among unilateral cases.

Upscaling of hydraulic conductivity and telescopic mesh refinement.

Performance assessments of repositories for the underground disposal of nuclear fuel and waste include models of ground water flow and transport in the host rocks. Estimates of hydraulic conductivity, K, based on field measurements may require adjustment (upscaling) for use in numerical models, but the choice of upscaling approach can be complicated by the use of nested modeling, large-scale fracture zones, and a high degree of heterogeneity. Four approaches to upscaling K are examined using a reference case based on exhaustive site data and an application of nested modeling to evaluate performance assessment of a waste repository. The upscaling approaches are evaluated for their effects on the flow balance between nested modeling domains and on simple measures of repository performance. Of the upscaling approaches examined in this study, the greatest consistency of boundary flows was achieved using the observed scale dependence for the rock domains, measured values from the large-scale interference test for the conductor domain, and a semivariogram regularization based on the Moye model for packer test interpretation. Making the assumption that large fracture zones are two-dimensional media results in the greatest changes to the median of travel time and improves the flow balance between the nested models. The uncertainty of upscaling methods apparently has a small impact on median performance measures, but a significant impact on the variances and earliest arrival times.

Modeling dispersion in three-dimensional heterogeneous fractured media at Yucca Mountain.

Highly resolved numerical simulations are conducted to evaluate the longitudinal and transverse dispersivities proposed for use in the larger-scale Yucca Mountain saturated zone (SZ) site-scale model. Two different stochastic continuum models (SCM) that define the spatial variability of permeability are inferred from the observed fracture characteristics and the measured permeabilities. These models are created with a combination of indicator geostatistics and boolean simulation that allow for modeling different correlation lengths and anisotropy ratios at different permeability thresholds as well as the inclusion of large, high-permeability features. Longitudinal and transverse (horizontal and vertical) dispersion through the permeability realizations is evaluated for both distributed and focused source geometries using groundwater flow and streamline particle tracking. These numerical results are compared to behavior predicted by an analytical solution and to dispersivities estimated by an expert panel. Early time transport results are significantly non-Gaussian due to the strong heterogeneity of the fractured medium. At late times, travel distances of 23 correlation lengths, the longitudinal and transverse horizontal dispersivity results are well approximated by the analytical solution and the expert elicitation estimates. The calculated transverse vertical dispersivity values are smaller than those estimated from the analytical solution. Inclusion of high-permeability features of the same size as the model domain with a distributed planar source creates extreme values of the longitudinal and transverse horizontal dispersivity.