Edward L. Frome

Intratracheal versus intravenous administration of bleomycin in mice: Acute effects

We examined whether intratracheal instillation (IT) of bleomycin would produce similar or dissimilar lesions when compared to lung damage following intravenous (iv) injection of the drug. BALB/c mice were treated with either 4 U/kg IT or 100 U iv bleomycin and killed at intervals up to 21 days after treatment. Cell proliferation, histopathology, lung lavage, and hydroxyproline content were examined. There was a biphasic response in the cell proliferation in the IT-treated mice, while the iv-treated mice showed a single delayed peak in proliferation. The histopathologic features of interstitial pneumonitis, elevation of lung lavage enzyme activities, and lung hydroxyproline content were qualitatively similar between the two routes of administration, although the IT mice response was always greater in magnitude. Differences exist between the lung reaction to these two routes of administration, but these differences reflect nonspecific inflammatory response and magnitude of initial injury. We conclude that the response to bleomycin administered IT is basically similar to the changes produced by intravenous injection of the drug.

Asymmetric tensile and compressive creep deformation of hot-isostatically-pressed Y2O3-doped -Si3N4

Abstract The uniaxial tensile and compressive creep rates of an yttria-containing hot-isostatically-pressed silicon nitride were examined at several temperatures between 1316 and 1399°C and found to have different stress dependencies. Minimum creep rates were always faster in tension than compression for an equal magnitude of stress. An empirical model was formulated which represented the minimum creep rate as a function of temperature for both tensile and compressive stresses. The model also depicted the asymmetric creep deformation using exponential and linear dependence on tensile and compressive stress, respectively. Unlike other models which represent either tensile or compressive creep deformation as a respective function of tensile or compressive stress, the model in the present study predicted creep deformation rate for both tensile and compressive stresses without conditional or a priori knowledge of the sign of stress. A statistical weight function was introduced to improve the correlation of the model’s regressed fit to the experimental data. Post-testing TEM microstructural analysis revealed that differences in the amount of tensile- and compressive-stress-induced cavitation accounted for the creep strain asymmetry between them, and that cavitation initiated in tensile and compressively crept specimens for magnitudes of creep strain in excess of 0·1%.

Poisson regression analysis of the mortality among a cohort of World War II nuclear industry workers.

A historical cohort mortality study was conducted among 28,008 white male employees who had worked for at least 1 month in Oak Ridge, Tennessee, during World War II. The workers were employed at two plants that were producing enriched uranium and a research and development laboratory. Vital status was ascertained through 1980 for 98.1% of the cohort members and death certificates were obtained for 96.8% of the 11,671 decedents. A modified version of the traditional standardized mortality ratio (SMR) analysis was used to compare the cause-specific mortality experience of the World War II workers with the U.S. white male population. An SMR and a trend statistic were computed for each cause-of-death category for the 30-year interval from 1950 to 1980. The SMR for all causes was 1.11, and there was a significant upward trend of 0.74% per year. The excess mortality was primarily due to lung cancer and diseases of the respiratory system. Poisson regression methods were used to evaluate the influence of duration of employment, facility of employment, socioeconomic status, birth year, period of follow-up, and radiation exposure on cause-specific mortality. Maximum likelihood estimates of the parameters in a main-effects model were obtained to describe the joint effects of these six factors on cause-specific mortality of the World War II workers. We show that these multivariate regression techniques provide a useful extension of conventional SMR analysis and illustrate their effective use in a large occupational cohort study.

Collection, Validation, and Treatment of Data for a Mortality Study of Nuclear Industry Workers

Abstract To investigate the long-term health effects of protracted occupational exposure to low levels of ionizing radiation, a combined facility mortality study was initiated for 118,588 workers hired between 1942 and 1982 by three Department of Energy facilities in Oak Ridge, Tennessee. The primary objectives of the study were: (1) to evaluate and compare the mortality experience of separate subcohorts delineated by facility of employment, and (2) to conduct detailed dose-response analyses of the combined facilities subcohort having potential for external radiation exposure. Presented here are issues involving validation and treatment of data for study members, and characteristics of their radiation exposure. To verify data accuracy a stratified random sample was chosen, and original source documents containing demographic and radiation exposure data were reviewed. Health physicists investigated monitoring policies and practices in place at each facility over the 42 years of follow-up (1943 to 1984) bef...

Evaluating goodness of fit of poisson regression models in cohort studies

Abstract Relative and absolute risk models are often used in epidemiologic studies to describe the effect of exposure on age-specific mortality rates. Poisson regression analysis is used to obtain maximum likelihood estimates of unknown parameters and to assess goodness of fit of the models. It is common practice to base both estimation and the evaluation of goodness of fit on certain marginal totals. This approach is potentially misleading for relative risk models and is totally inappropriate for absolute risk models. To illustrate the situation, we present an example using data on smoking and lung cancer. In the example, the goodness-of-fit tests based on the marginal totals indicate that neither the absolute risk nor the relative risk model can be rejected, whereas the age-specific test statistics strongly reject both models. The validity of the marginal test is based on an assumption (i.e., of no exposure by age interaction) that is not satisfied in the example. We describe a more general approach to ...

A model search procedure for hierarchical models

Abstract Large data sets cross-classified according to multiple factors are available in epidemiology and other disciplines. Their analysis often calls for finding a small set of best hierarchical models to serve as a basis for further analysis. This selection can be based on some well defined model optimality criterion. Fitting all possible models to find a best set is usually not feasible for as few as five factors (7581 possible models). We note that the set of hierarchical models and their relationships can be represented by a graph and develop an algorithm to generate it efficiently. We further develop a graph traversal algorithm that requires fitting of only fraction of all models to find exactly a best subset of the models. The algorithm classifies as many models as possible on the basis of each fit. A data structure implementing the graph of model nodes keeps track of the information required by the model search algorithm.

Adjusting external doses from the ORNL and Y-12 facilities for the Oak Ridge Nuclear Facilities mortality study

This report presents specific procedures used for adjusting radiation doses to radiation personnel at the ORNL and Y-12 plants during the early years. Topics discussed include: background information; selection of employment years to be considered; hardcopy monitoring methods and records; pocket meter data; and replacement of 1943 unmonitored employment years. These topics were discussed for both years.