Cancer Risk Assessment with Intermittent Exposure

Applications of methods for carcinogenic risk assessment often focus on estimating lifetime cancer risk. With intermittent or time-dependent exposures, lifetime risk is often approximated on the basis of a lifetime average daily dose (LADD). In this article, we show that there exists a lifetime equivalent constant dose (LECD) which leads to the same lifetime risk as the actual time-dependent exposure pattern. The ratio C = LECD/LADD then provides a measure of accuracy of risk estimates based on the LADD, as well as a basis for correcting such estimates. Theoretical results derived under the classical multistage model and the two-stage birth-death-mutation model suggest that the maximum value of C, which represents the factor by which the LADD may lead to underestimates of risk, will often lie in the range of 2- to 5-fold. The practical application of these results is illustrated in the case of astronauts subjected to relatively short-term exposure to volatile organics in a closed space station environment, and in the case of the ingestion of pesticide residues in food where consumption patterns vary with age.     

Estimation of Dietary Exposure to Chemicals: A Case Study Illustrating Methods of Distributional Analyses for Food Consumption Data

There are a number of sources of variability in food consumption patterns and residue levels of a particular chemical (e.g., pesticide, food additive) in commodities that lead to an expected high level of variability in dietary exposures across a population. This paper focuses on examples of consumption pattern survey data for specific commodities, namely that for wine and grape juice, and demonstrates how such data might be analyzed in preparation for performing stochastic analyses of dietary exposure. Data from the NIAAA/NHIS wine consumption survey were subset for gender and age group and, with matched body weight data from the survey database, were used to define empirically-based percentile estimates for wine intake (μl wine/kg body weight) for the strata of interest. The data for these two subpopulations were analyzed to estimate 14-day consumption distributional statistics and distributions for only those days on which wine was consumed. Data subsets for all wine-consuming adults and wine-consuming females ages 18 through 45, were determined to fit a lognormal distribution ( R ²= 0.99 for both datasets). Market share data were incorporated into estimation of chronic exposures to hypothetical chemical residues in imported table wine. As a separate example, treatment of grape juice consumption data for females, ages 18–40, as a simple lognormal distribution resulted in a significant underestimation of intake, and thus exposure, because the actual distribution is a mixture (i.e., multiple subpopulations of grape juice consumers exist in the parent distribution). Thus, deriving dietary intake statistics from food consumption survey data requires careful analysis of the underlying empirical distributions.     

Consideration of Background Exposures in the Management of Hazardous Waste Sites: A New Approach to Risk Assessment

The current approach to health risk assessment of toxic waste sites in the U.S. may lead to considerable expenditure of resources without any meaningful reduction in population exposure. Risk assessment methods used generally ignore background exposures and consider only incremental risk estimates for maximally exposed individuals. Such risk estimates do not address true public health risks to which background exposures also contribute. The purpose of this paper is to recommend a new approach to risk assessment and risk management concerning toxic waste sites. Under this new approach, which we have called public health risk assessment, chemical substances would be classified into a level of concern based on the potential health risks associated with typical national and regional background exposures. Site assessment would then be based on the level of concern for the particular pollutants involved and the potential contribution of site contaminants to typical background human exposures. While various problems can be foreseen with this approach, the key advantage is that resources would be allocated to reduce the most important sources of human exposure, and site remediation decisions could be simplified by focussing on exposure assessment rather than questionable risk extrapolations.     

Public Distrust and Hazard Management Success at the Rocky Flats Nuclear Weapons Plant

Based on experience gained while serving a public oversight commission appointed by the governor of Colorado, hazard management at the Department of Energy's Rocky Flats nuclear weapons plant is reviewed. Specific reference is made to the plant's history of controversy, its defense-in-depth strategy of hazard control, occupational health issues, public exposure to plutonium, and the assessment of low-probability, high-consequence risks. This leads to the conclusion that Rocky Flats is, by any objective standard, a hazard management success. It follows that public distrust of Rocky Flats arises as much from fear and loathing of nuclear weapons themselves as from the manufacturing process by which they are made.     

Field Measurement of Dermal Soil Loading Attributable to Various Activities: Implications for Exposure Assessment

Estimates of soil adherence to skin are required for assessment of dermal exposures to contaminants in soils. Previously available estimates depend heavily on indirect measurements and/or artificial activities and reflect sampling of hands only. Results are presented here from direct measurement of soil loading on skin surfaces of volunteers before and after normal occupational and recreational activities that might reasonably be expected to lead to soil contact. Skin surfaces assayed included hands, forearms, lower legs, faces and/or feet. Observed hand loadings vary over five orders of magnitude (roughly from 10^–3 to 10² mg/cm²) and are dependent upon type of activity. Hand loadings within the current default range of 0.2 to 1.0 mg/cm² were produced by activities providing opportunity for relatively vigorous soil contact (rugby, farming). Loadings less than 0.2 mg/cm² were found on hands following activities presenting less opportunity for direct soil contact (soccer, professional grounds maintenance) and on other body parts under many conditions. The default range does not, however, represent a worst case. Children playing in mud on the shore of a lake generated geometric mean loadings well in excess of 1 mg/cm² on hands, arms, legs, and feet. Post-activity average loadings on hands were typically higher than average loadings on other body parts resulting from the same activity. Hand data from limited activities cannot, however, be used to conservatively predict loadings that might occur on other body surfaces without regard to activity since non-hand loadings attributable to higher contact activities exceeded hand loadings resulting from lower contact activities. Differences between pre- and post-activity loadings also demonstrate that dermal contact with soil is episodic. Typical background (pre-activity) geometric mean loadings appear to be on the order of 10^-2 mg/cm² or less. Because exposures are activity dependent, quantification of dermal exposure to soil will remain inadequate until data describing relevant human behavior (type of activity, frequency, duration including interval before bathing, clothing worn, etc.) are generated.     

组合证券投资有效边界的进一步研究

研究了不允许卖空情况下有效证券组合的结构特征，证明了其有效边界由一系列开口向上的抛物线段光滑连接而成，给出了连续确定有效证券组合构成变动及相应的有效边界的方法，并将有关结果推广到考虑外汇套期保值的国际组合证券投资决策中。     

Using the Biological Two-Stage Model to Assess Risk from Short-Term Exposures

Two assumptions used in risk assessment are investigated: (1) the assumption of fraction of lifetime dose rate assumes that the risk from a fractional lifetime exposure at a given dose rate is equal to the risk from full lifetime exposure at that same fraction of the given dose rate; (2) the assumption of fraction of lifetime risk assumes that the risk from a fractional lifetime exposure at a given dose rate is equal to that same fraction of the risk from full lifetime exposure at the same dose rate. These two assumptions are equivalent when risk is a linear function of dose. Thus both can be thought of as generalizations of the assumption that cancer risk is proportional to the total accumulated lifetime dose (or average daily dose), which is often made to assess the risk from short-term exposures. In this paper, the age-specific cumulative hazard functions are derived using the two-stage model developed by Moolgavkar, Venzon, and Knudson for situations when the exposure occurs during a single period or a single instant. The two assumptions described above are examined for three types of carcinogens, initiator, completer, and promoter, in the context of the model. For initiator and completer, these two assumptions are equivalent in the low-dose region; for a promoter, using the fraction of lifetime risk assumption is generally more conservative than that of the fraction of lifetime dose rate assumption. Tables are constructed to show that the use of either the fraction of lifetime dose rate assumption or the fraction lifetime risk assumption can both underestimate and overestimate the true risk for the three types of carcinogens.     

Armitage-Doll Two-Stage Model: Implications and Extension

The objective of this paper is twofold: (1) to provide insight on the simplified MVK model of carcinogenesis (a model proposed by Moolgavkar and colleagues) by revealing the relationship between the Armitage-Doll two-stage model and the simplified MVK model; and (2) to extend the Armitage-Doll two-stage model to one with time-varying (piece-wise constant) parameters. It is shown that the simplified MVK model is a special case of the Armitage-Doll two-stage model, and many applications of the simplified MVK model involving intermittent exposures or exposures to different compounds in different time periods can be derived easily from the Armitage-Doll two-stage model with piece-wise constant parameters. The limitations of the Armitage-Doll two-stage model are discussed.     

Inference for a Simple Step-Stress Model with Type-I Censoring and Lognormally Distributed Lifetimes

Accelerated life-testing (ALT) is a very useful technique for examining the reliability of highly reliable products. It allows the experimenter to obtain failure data more quickly at increased stress levels than under normal operating conditions. A step-stress model is one special class of ALT, and in this article we consider a simple step-stress model under the cumulative exposure model with lognormally distributed lifetimes in the presence of Type-I censoring. We then discuss inferential methods for the unknown parameters of the model by the maximum likelihood estimation method. Some numerical methods, such as the Newton–Raphson and quasi-Newton methods, are discussed for solving the corresponding non-linear likelihood equations. Next, we discuss the construction of confidence intervals for the unknown parameters based on (i) the asymptotic normality of the maximum likelihood estimators (MLEs), and (ii) parametric bootstrap resampling technique. A Monte Carlo simulation study is carried out to examine the performance of these methods of inference. Finally, a numerical example is presented in order to illustrate all the methods of inference developed here.     

Media Exposure to Terrorism and Perception of Immigrants as a Threat: The Role of Emotional Intelligence and Psychophysiological Self-Regulation

To better understand how media exposure to terrorism-related images can lead to perceiving immigrants as more threatening, in the present study we manipulated participants’ exposure to media coverage of terrorist attacks and investigated how this may influence people's perception of Arab immigrants. Considering the important role of regulatory abilities when facing stressful events like terrorist attacks, we measured individual differences in both trait emotional intelligence and resting heart rate variability (HRV). Results showed that participants perceived Arab immigrants as more threatening in the media exposure condition than in the control condition. Importantly, there were moderating effects of both trait emotional intelligence and HRV. People with lower trait emotional intelligence or lower HRV at rest felt more threatened in the media exposure condition compared to the control condition, whereas this effect was not observed among participants with higher trait emotional intelligence or higher resting HRV. The present study highlights some of the complexities related to how media exposure to terrorism-related images influences people's reactions to, and evaluations of, an outgroup that is related to the perpetrators of the attacks.