Prognostic value of histological grading of oligodendroglial tumors is controversial and interobserver reproducibility in grading of these tumors is unknown. Seven neuropathologists and 6 surgical pathologists experienced in brain tumor-diagnosis assessed 124 oligodendroglial tumors operated at the Mayo Clinic (1960-1990). Among histologic parameters upon which current oligodendroglioma grading systems are based, only high cellularity, presence of mitoses, microcalcifications, endothelial hypertrophy, endothelial proliferation, and necrosis appeared to be reproducible. Reproducible histologic features, based on consensus ratings among neuropathologists (defined as > 60%), were evaluated for the association with cause-specific survival by fitting Cox regression models. By univariate analysis, a significant association with survival was found for age, high cellularity, presence of mitoses, endothelial hypertrophy and proliferation and necrosis. On multivariable analysis with a stepwise variable selection method, only age and presence of endothelial proliferation were found to be independently associated with survival with a discriminatory index of the model of 0.68. Mitotic index was significantly associated with survival based on the grading from each separate neuropathologist, but it was not based on consensus, most likely because this was classified as indeterminate in 54% of cases. Alternatively, "models fit" considering the assessment of single neuropathologists, identified a model based on age and on mitotic index with similar discriminatory indices of 0.69-0.7. Our study found few factors independently associated with cause specific-survival among morphological parameters. These findings are consistent with the present WHO stratification of oligodendrogliomas into low- and high-grade variants.
This work illustrates the use of Physiologically-Based Toxicokinetic (PBTK) modelling for the healthy Caucasian population in in vitro-to-in vivo correlation of kinetic measures of caffeine skin penetration and liver clearance (based on literature experiments), as well as dose metrics of caffeine-induced measured HepaRG toxicity. We applied a simple correlation factor to quantify the in vitro and in vivo differences in the amount of caffeine permeated through the skin and concentration-time profiles of caffeine in the liver. We developed a multi-scale computational approach by linking the PBTK model with a Virtual Cell-Based Assay to relate an external oral and dermal dose with the measured in vitro HepaRG cell viability. The results revealed higher in vivo skin permeation profiles than those determined in vitro using identical exposure conditions. Liver clearance of caffeine derived from in vitro metabolism rates was found to be much slower than the optimised in vivo clearance with respect to caffeine plasma concentrations. Finally, HepaRG cell viability was shown to remain almost unchanged for external caffeine doses of 5-400 mg for both oral and dermal absorption routes. We modelled single exposure to caffeine only.
IntroductionThis report relays the methodology and presents results of an ongoing study of the performance of residential structures in the State of Florida. Specifically, site built single family homes constructed after Andrew-related changes to the standard building code were in effect were targeted for a detailed investigation of damage as a result of the 2004 hurricane season. The purpose of this study is to provide a quantitative statistical comparison of the relative performance of homes built between 1994 and 2001 with those built after the 2001 Florida Building Code replaced the Standard Building Code.
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