Ram C. Tripathi

PHARMACOKINETICS OF TCDD IN VETERANS OF OPERATION RANCH HAND: 10-YEAR FOLLOW-UP

Using multiple measurements from serum collected over 10 yr (1982, 1987, and 1992), we estimated the half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in 213 veterans of Operation Ranch Hand, the Air Force unit responsible for the aerial spraying of Agent Orange in Vietnam. The potential influences of age, percent body fat, and changes in percent body fat on the half-life estimate were also examined. The mean decay rate of TCDD for these veterans is 0.0797 per year with 95% confidence interval 0.0727 to 0.0868 per year; the corresponding half-life estimate is 8.7 yr with 95% confidence interval 8.0-9.5 yr. Half-life increased significantly with increasing body fat, but not with age or relative changes in percent body fat.

Analysis of zero-adjusted count data

Abstract In this paper a zero adjusted discrete model is developed. Such a situation arises when the proportion of zeros in the data is higher (lower) than that predicted by the original model. The effect of such an adjustment is studied. The failure rates and the survival functions of the adjusted and the non-adjusted models are compared. The relative error incurred by ignoring the adjustment is studied and it is shown that the relative error is a decreasing function of the count. An adjusted generalized Poisson distribution is studied and the three parameters of this model are estimated by the maximum likelihood method. Finally, two examples are presented. In both the examples, it is shown that the zero adjusted generlized Poisson distribution fits very well and the estimates of the parameters are obtained by simple and straight-forward methods.

Score Test for Zero Inflated Generalized Poisson Regression Model

Abstract In certain applications involving count data, it is sometimes found that zeros are observed with a frequency significantly higher (lower) than predicted by the assumed model. Examples of such applications are cited in the literature from engineering, manufacturing, economics, public health, epidemiology, psychology, sociology, political science, agriculture, road safety, species abundance, use of recreational facilities, horticulture and criminology. In this article, a zero adjusted generalized Poisson distribution is studied and a score test is developed, with and without covariates, to determine whether such an adjustment is necessary. Examples, with and without covariates, are provided to illustrate the results.

Pharmacokinetics of 2,3,7,8-tetrachlorodibenzo- p -dioxin in Seveso adults and veterans of operation Ranch Hand

A combined analysis of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) elimination in Seveso adults and Ranch Hand veterans found a period of fast elimination within the first 0.27 years after exposure in Seveso, followed by a period of slower elimination between 3 and 16.35 years from exposure. The mean TCDD elimination rate within the first 0.27 years after exposure among six adult males in the Seveso cohort was 2.0646 year−1 (half-life=0.34 years). The mean rate from 3 to 16.35 years was 0.1011 year−1 (half-life=6.9 years). The mean Ranch Hand elimination rate, 00924 year−1 (half-life=6.9 years), measured between 9 and 33 years after exposure, was significantly less than the Seveso mean in the first 0.27 years after exposure, but not significantly different from the Seveso mean between 3 and 16.35 years after exposure. The fast elimination within the first 0.27 years followed by a slower rate after 3 years is consistent with the expected pattern in a two-compartment open model, with a distribution phase of rapid elimination followed by a slower elimination phase.

On the monotonic properties of discrete failure rates

Abstract As is well known, the monotonicity of failure rate of a life distribution plays an important role in modeling failure time data. In this paper, we develop techniques for the determination of increasing failure rate (IFR) and decreasing failure rate (DFR) property for a wide class of discrete distributions. Instead of using the failure rate, we make use of the ratio of two consecutive probabilities. The method developed is applied to various well known families of discrete distributions which include the binomial, negative binomial and Poisson distributions as special cases. Finally, a formula is presented to determine explicitly the failure rate of the families considered. This formula is used to determine the failure rate of various classes of discrete distributions. These formulas are explicit but complicated and cannot normally be used to determine the monotonicity of the failure rates.

Diabetes mellitus and 2,3,7,8-tetrachlorodibenzo-p-dioxin elimination in veterans of Operation Ranch Hand.

Using multivariate statistical models, no significant relationship was found between the rate of 2,3,7,8-tetrachlorodibenzo-p-dioxin ( TCDD) elimination and the occurrence or time to onset of diabetes in 343 veterans of Operation Ranch Hand, the unit responsible for the aerial spraying of Agent Orange and other TCDD-contaminated herbicides during the Vietnam War. Without adjustment for age, body mass index, family history of diabetes, and smoking history, the time to onset of diabetes decreased and the risk of diabetes increased with a diminished elimination rate. However, after adjustment, diabetes time to onset and occurrence were not significantly associated with TCDD elimination. Analyses of covariance found no significant difference between the average elimination rates of diabetic and nondiabetic veterans, without or with adjustment for risk factors. To our knowledge, this is the only study to date to examine TCDD elimination and diabetes.

Estimation of parameters in the beta binomial model

This paper contains some alternative methods for estimating the parameters in the beta binomial and truncated beta binomial models. These methods are compared with maximum likelihood on the basis of Asymptotic Relative Efficiency (ARE). For the beta binomial distribution a simple estimator based on moments or ratios of factorial moments has high ARE for most of the parameter space and it is an attractive and viable alternative to computing the maximum likelihood estimator. It is also simpler to compute than an estimator based on the mean and zeros, proposed by Chatfield and Goodhart (1970,Appl. Statist.,19, 240–250), and has much higher ARE for most part of the parameter space. For the truncated beta binomial, the simple estimator based on two moment relations does not behave quite as well as for the BB distribution, but a simple estimator based on two linear relations involving the first three moments and the frequency of “ones” has extremely high ARE. Some examples are provided to illustrate the procedure for the two models.

Inflated modified power series distributions with applications

In certain applications involving discrete data, it is sometimes found that X = 0 is observed with a frequency significantly higher than predicted by the assumed model. Zero inflated Poisson, binomial and negative binomial models have been employed in some clinical trials and in some regression analysis problems. In this paper, we study the zero inflated modified power series distributions (IMPSD) which include among others the generalized Poisson and the generalized negative binomial distributions and hence the Poisson, binomial and negative binomial distributions. The structural properties along with the distribution of the sum of independent IMPSD variables are studied. The maximum likelihood estimation of the parameters of the model is examined and the variance-covariance matrix of the estimators is obtained. Finally, examples are presented for the generalized Poisson distribution to illustrate the results.

Investigation of TCDD half-life heterogeneity in veterans of Operation Ranch Hand.

The half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the contaminant of Agent Orange, has been recently estimated in 36 members of Operation Ranch Hand, the Air Force unit responsible for the aerial spraying of Agent Orange in Vietnam, as 7.1 yr with a 95% [corrected] confidence interval of 5.8-9.6 yr. We investigated the variability of TCDD half-life with percent body fat in these 36 Ranch Hand veterans who have two TCDD assay results from serum drawn in 1982 and 1987. Using a repeated measures linear model, we found a marginally significant change in half-life with percentage of body fat (p = .09) and no statistically significant change in half-life with relative changes in percentage of body fat from 1982 to 1987 (p = .60).

The Effect of Errors in Diagnosis and Measurement on the Estimation of the Probability of an Event

Abstract This article investigates the effect of misclassification and measurement error in the basic data on the asymptotic bias and efficiency of the logistic regression (LR) and normal discrimination (ND) classification procedures. The effect of misclassification in a single binary independent variable on the bias and efficiency of both procedures is also presented. Typically, asymptotic bias increases and efficiency decreases as misclassification and measurement error increase. The performance of LR relative to ND is shown to be better in the presence of error than without error.