A Stochastic Two-Stage Model for Cancer Risk Assessment. I. The Hazard Function and the Probability of Tumor

We present a mathematical treatment of a two-mutation model for carcinogenesis with time-dependent parameters. This model has previously been shown to be consistent with epidemiologic and experimental data. An approximate hazard function used in previous papers is critically evaluated.     

Calculating the Hazard Function and Probability of Tumor for Cancer Risk Assessment When the Parameters Are Time-Dependent

The probability of tumor and hazard function are calculated in a stochastic two-stage model for carcinogenesis when the parameters of the mode are time-dependent. The method used is called the method of characteristics.     

Price Setting With Menu Cost for Multiproduct Firms

We model the decisions of a multiproduct firm that faces a fixed “menu” cost: once it is paid, the firm can adjust the price of all its products. We characterize analytically the steady state firm's decisions in terms of the structural parameters: the variability of the flexible prices, the curvature of the profit function, the size of the menu cost, and the number of products sold. We provide expressions for the steady state frequency of adjustment, the hazard rate of price adjustments, and the size distribution of price changes, all in terms of the structural parameters. We study analytically the impulse response of aggregate prices and output to a monetary shock. The size of the output response and its duration both increase with the number of products; they more than double as the number of products goes from 1 to 10, quickly converging to the response of Taylor's staggered price model.     

Semiparametric Estimation of a Proportional Hazard Model with Unobserved Heterogeneity

The proportional hazard model with unobserved heterogeneity gives the hazard function of a random variable conditional on covariates and a second random variable representing unobserved heterogeneity. This paper shows how to estimate the baseline hazard function and the distribution of the unobserved heterogeneity nonparametrically. The baseline hazard function and heterogeneity distribution are assumed to satisfy smoothness conditions but are not assumed to belong to known, finite-dimensional, parametric families. Existing estimators assume that the baseline hazard function or heterogeneity distribution belongs to a known parametric family. Thus, the estimators presented here are more general than existing ones.     

Priority Setting for the Distribution of Localized Hazard Protection

We address the problem of distributing safety-enhancing devices across a region, where each identical device provides for only local protection of the population. The devices protect nonidentical sectors of the population. The sectors of population are exposed to nonidentical intensities of hazard. A method for the screening and prioritizing of needs for the protective devices is described. An approach of risk-benefit-cost analysis under uncertainty is recommended as follows. Measures of hazard intensity and population exposure are identified. Exogenous parameters that influence assessments of risks, benefits, and costs are identified. Uncertainties of the exogenous parameters are propagated by interval analysis. Several tiers of the plausibility of need for protection are identified. The tiers are useful in setting priorities for the distribution of the safety devices. The method is demonstrated in an engineering application to roadway lighting, but has implications for disaster preparedness, anti-terrorism, transportation safety, and other arenas of public safety.     

Fitting the Two-Stage Clonal Expansion Model Based on Exact Hazard to the ED01 Data Using SAS NLIN

The two-stage clonal expansion model is a popular model for carcinogenesis data. One common form of this model is based on the approximate hazard function. In certain situations, this formulation is not appropriate, and the exact hazard should be applied. However, the difficulty of implementing the model based on the exact hazard has deterred many from using it. This paper presents a program implementing the exact hazard model for piecewise constant dosing using SAS, a package that is readily available to most that are interested in this type of analysis. Also, an analysis of the ED₀₁ data is presented using this program, and comparisons are made to an earlier analysis based on the approximate hazard. By allowing for an independent background tumor mechanism, an excellent fit to the bladder tumor incidence data was obtained.     

An Alternative Exact Solution of the Two-Stage Clonal Growth Model of Cancer

The approximate solution of the two-stage clonal expansion model of cancer may substantially deviate from the exact solution, and may therefore lead to erroneous conclusions in particular applications. However, for time-varying parameters the exact solution (method of characteristics) is not easy to implement, hampering the accessibility of the model to nonmathematicians. Based on intuitive reasoning, Clewell et al. (1995) proposed an improved approximate solution that is easy to implement whatever time-varying behavior the parameters may have. Here we provide the mathematical foundation for the approximation suggested by Clewell et al. (1995) and show that, after a slight modification, it is in fact an exact solution for the case of time-constant parameters. We were not able to prove that it is an exact solution for time-varying parameters as well. However, several computer simulations showed that the numerical results do not differ from the exact solution as proposed by Moolgavkar and Luebeck (1990). The advantage of this alternative solution is that the hazard rate of the first malignant cell can be evaluated by numerically integrating a single differential equation.     

MORAL HAZARD AND DYNAMIC INSURANCE DATA

This paper exploits dynamic features of insurance contracts in the empirical analysis of moral hazard. We first show that experience rating implies negative occurrence dependence under moral hazard: individual claim intensities decrease with the number of past claims. We then show that dynamic insurance data allow to distinguish this moral‐hazard effect from dynamic selection on unobservables. We develop nonparametric tests and estimate a flexible parametric model. We find no evidence of moral hazard in French car insurance. Our analysis contributes to a recent literature based on static data that has problems distinguishing between moral hazard and selection and dealing with dynamic features of actual insurance contracts. Methodologically, this paper builds on and extends the literature on state dependence and heterogeneity in event‐history data. (JEL: D82, G22, C41, C14)     

An Analysis of Changes in the Risk of Mortality from Chronic Obstructive Lung Disease, 1968-1977

Nonlinear hazard models are used to examine temporal trends in the age-specific mortality risks of chronic obstructive lung diseases for the U.S. population. These hazard functions are fit to age-specific mortality rates for 1968 and 1977 for four race/sex groups. Changes in the parameters of these models are used to assess two types of differences in the age pattern of the rates between 1968 and 1977. The first measure of trend in the age-specific mortality rates is the temporal change in the proportionality constant in the function used to model their age variation. By allowing only this proportionality parameter to vary between 1968 and 1977, it is possible to determine an age-constant percentage increase or decrease. The second measure reflects the absolute displacement in terms of years of life of the fitted mortality curves for the two time points. This second index can be interpreted as the acceleration or deceleration of mortality risks over the life span, i.e., the number of years that is needed for mortality rates to achieve the same level as in the comparison group. The analysis showed that the age changes in chronic obstructive lung disease mortality rates differed by race/sex group and for both measures of change over the period. Adjustment of the fitted curves for the effects of individual variability in risk was significant for three of four groups.     

On the Exact Hazard and Survival Functions of the MVK Stochastic Carcinogenesis Model

The MVK two-stage carcinogenesis model is one of the most widely accepted mechanistic models in carcinogenesis modeling. However, due to a perceived difficulty in obtaining analytic solutions for the hazard and survival functions, approximations and numerical methods have been used to calculate these two fundamental quantities. This paper focuses on a special case of the homogeneous MVK model where the number of normal cells is constant. The probability generating function (pgf) for the number of tumor cells is derived, and the exact analytic solutions to the hazard and survival functions are obtained from the pgf.     

供应链质量管理中的最优合同设计

本文研究在供应链质量管理过程中合同设计问题对供应商质量预防决策和制造商质量检测决策的影响.在合同设计过程中分析了各种行动隐匿情况下的道德风险问题,以及如何通过限定合同参数的取值来激励制造商和供应商的行动,在实现供应商和制造商利益最大化的同时,保证供应链整体质量收益(质量成本)的优化.     

失业保险给付期限差异下的失业持续时间研究

本文对享受不同失业保险给付期限的失业者的失业持续时间差异进行了实证研究。根据工作搜寻理论,应用存活分析方法建立了含有失业保险给付期限因素的失业持续时间模型,并对青岛市失业者登记数据进行了实证研究。结果表明:享受失业保险者的失业持续时间明显长于不享受失业保险者的失业持续时间,在失业保险给付额度相同的条件下,失业保险给付期限与失业持续时间成同向变动关系。     

Do People Believe Combined Hazards Can Present Synergistic Risks?

The risk attributable to some hazard combinations can be greater than the sum of the risk attributable to each constituent hazard. Such "synergistic risks" occur in several domains, can vary in magnitude, and often have harmful, even life-threatening, outcomes. Yet, the extent to which people believe that combined hazards can present synergistic risks is unclear. We present the results of two experimental studies aimed at addressing this issue. In both studies, participants examined synergistic and additive risk scenarios, and judged whether these were possible. The results indicate that the proportion of people who believe that synergistic risks can occur declines linearly as the magnitude of the synergistic risk increases. We also find that people believe, despite scientific evidence to the contrary, that certain hazard combinations are more likely to present additive or weakly synergistic risks than synergistic risks of higher magnitudes. Furthermore, our findings did not vary as a simple function of hazard domain (health vs. social), but varied according to the characteristics of the specific hazards considered (specified vs. unspecified drug combinations). These results suggest that many people's beliefs concerning the risk attributable to combined hazards could lead them to underestimate the threat posed by combinations that present synergistic risks, particularly for hazard combinations that present higher synergistic risk magnitudes. These findings highlight a need to develop risk communications that can effectively increase awareness of synergistic risks.     

An Exact Analysis of the Multistage Model Explaining Dose-Response Concavity

The traditional multistage (MS) model of carcinogenesis implies several empirically testable properties for dose-response functions. These include convex (linear or upward-curving) cumulative hazards as a function of dose; symmetric effects on lifetime tumor probability of transition rates at different stages; cumulative hazard functions that increase without bound as stage-specific transition rates increase without bound; and identical tumor probabilities for individuals with identical parameters and exposures. However, for at least some chemicals, cumulative hazards are not convex functions of dose. This paper shows that none of these predicted properties is implied by the mechanistic assumptions of the MS model itself. Instead, they arise from the simplifying "rare-tumor" approximations made in the usual mathematical analysis of the model. An alternative exact probabilistic analysis of the MS model with only two stages is presented, both for the usual case where a carcinogen acts on both stages simultaneously, and also for idealized initiation-promotion experiments in which one stage at a time is affected. The exact two-stage model successfully fits bioassay data for chemicals (e.g., 1,3-butadiene) with concave cumulative hazard functions that are not well-described by the traditional MS model. Qualitative properties of the exact two-stage model are described and illustrated by least-squares fits to several real datasets. The major contribution is to show that properties of the traditional MS model family that appear to be inconsistent with empirical data for some chemicals can be explained easily if an exact, rather than an approximate model, is used. This suggests that it may be worth using the exact model in cases where tumor rates are not negligible (e.g., in which they exceed 10%). This includes the majority of bioassay experiments currently being performed.     

Estimation of Semiparametric Models when the Criterion Function Is Not Smooth

We provide easy to verify sufficient conditions for the consistency and asymptotic normality of a class of semiparametric optimization estimators where the criterion function does not obey standard smoothness conditions and simultaneously depends on some nonparametric estimators that can themselves depend on the parameters to be estimated. Our results extend existing theories such as those of Pakes and Pollard (1989), Andrews (1994a), and Newey (1994). We also show that bootstrap provides asymptotically correct confidence regions for the finite dimensional parameters. We apply our results to two examples: a ‘hit rate’ and a partially linear median regression with some endogenous regressors.     

The effect of capacity management strategies on employees' well-being: A quantitative investigation into the long-term healthcare industry

The aim of this study is to understand the effects of different capacity management strategies on the well-being of employees in long-term healthcare organizations. Such strategies may produce psychological effects in terms of job satisfaction and well-being among employees, namely frontline employees, thus affecting service quality. We collected 2158 observations from 42 nursing homes in Italy. Our results show that all capacity management strategies addressed in this study can influence the perceived degree of fatigue or of job hazard, and some of them can influence both. Moreover, a better perception of job hazard and fatigue leads to a higher degree of reported well-being from employees, although with the former, it is only through the mediation of job satisfaction. We conclude our paper by discussing theoretical contributions and policy implications.     

SEPARATING MORAL HAZARD FROM ADVERSE SELECTION AND LEARNING IN AUTOMOBILE INSURANCE: LONGITUDINAL EVIDENCE FROM FRANCE

The identification of information problems in different markets is a challenging issue in the economic literature. In this paper, we study the identification of moral hazard from adverse selection and learning about risk within the context of a multi‐period dynamic model. We extend the model of Abbring, Chiappori, and Pinquet (2003, Journal of the European Economic Association, 1, 767–820) to include learning about risk and insurance coverage choice over time. We derive testable empirical implications for panel data. We then perform tests using longitudinal data from France during the period 1995–1997. We find evidence of moral hazard among a sub‐group of policyholders with less driving experience (less than 15 years). Policyholders with fewer than five years of experience have a combination of learning about risk and moral hazard, whereas no residual information problem is found for policyholders with more than 15 years of experience.     

Atmospheric Dispersion of Inflammable Substances for Estimating Vulnerable Zones in Hydrocarbon Industry

The present study utilizes an operational model as well as simple empirical relationships for estimating hazard zones due to fire, explosion, and toxic vapor cloud dispersion. The empirical relationships are based on giving appropriate weightage to each of the parameters on which the hazard in question (viz, fire, explosion, toxic vapour dispersion) is dependent. Results from these two approaches [i.e., an operational model FLAMCALC of U.K. Health and Safety Executive (HSE) and an empirical model named FIREX] have been compared with the data obtained from the Mexico City disaster in 1984. In general, results from the empirical approach and FLAMCALC are comparable to the observed effects.     

Securing Passenger Aircraft from the Threat of Man‐Portable Air Defense Systems (MANPADS)

In this article, we develop a model for the expected maximum hit probability of an attack on a commercial aircraft using MANPADS, as a function of the (random) location of the attacker. We also explore the sensitivity of the expected maximum hit probability to the parameters of the model, including both attacker parameters (such as weapon characteristics) and defender parameters (such as the size of the secure region around the airport). We conclude that having a large secure region around an airport offers some protection against MANPADS, and that installing onboard countermeasures reduces the success probability of a MANPADS attack.     

Nonparametric Identification of a Contract Model With Adverse Selection and Moral Hazard

This paper studies the nonparametric identification of a contract model with adverse selection and moral hazard. Specifically, we consider the false moral hazard model developed by Laffont and Tirole (1986). We first extend this model to allow for general random demand and cost functions. We establish the nonparametric identification of the demand, cost, deterministic transfer, and effort disutility functions as well as the joint distribution of the random elements of the model, which are the firm's type and the demand, cost, and transfer shocks. The cost of public funds is identified with the help of an instrument. Testable restrictions of the model are characterized.