A Comparative Pharmacokinetic Estimate of Mercury in U.S. Infants Following Yearly Exposures to Inactivated Influenza Vaccines Containing Thimerosal

The use of thimerosal preservative in childhood vaccines has been largely eliminated over the past decade in the United States because vaccines have been reformulated in single‐dose vials that do not require preservative. An exception is the inactivated influenza vaccines, which are formulated in both multidose vials requiring preservative and preservative‐free single‐dose vials. As part of an ongoing evaluation by USFDA of the safety of biologics throughout their lifecycle, the infant body burden of mercury following scheduled exposures to thimerosal preservative in inactivated influenza vaccines in the United States was estimated and compared to the infant body burden of mercury following daily exposures to dietary methylmercury at the reference dose established by the USEPA. Body burdens were estimated using kinetic parameters derived from experiments conducted in infant monkeys that were exposed episodically to thimerosal or MeHg at identical doses. We found that the body burden of mercury (AUC) in infants (including low birth weight) over the first 4.5 years of life following yearly exposures to thimerosal was two orders of magnitude lower than that estimated for exposures to the lowest regulatory threshold for MeHg over the same time period. In addition, peak body burdens of mercury following episodic exposures to thimerosal in this worst‐case analysis did not exceed the corresponding safe body burden of mercury from methylmercury at any time, even for low‐birth‐weight infants. Our pharmacokinetic analysis supports the acknowledged safety of thimerosal when used as a preservative at current levels in certain multidose infant vaccines in the United States.     

Perceptions of Randomized Security Schedules

Security of infrastructure is a major concern. Traditional security schedules are unable to provide omnipresent coverage; consequently, adversaries can exploit predictable vulnerabilities to their advantage. Randomized security schedules, which randomly deploy security measures, overcome these limitations, but public perceptions of such schedules have not been examined. In this experiment, participants were asked to make a choice between attending a venue that employed a traditional (i.e., search everyone) or a random (i.e., a probability of being searched) security schedule. The absolute probability of detecting contraband was manipulated (i.e., 1/10, 1/4, 1/2) but equivalent between the two schedule types. In general, participants were indifferent to either security schedule, regardless of the probability of detection. The randomized schedule was deemed more convenient, but the traditional schedule was considered fairer and safer. There were no differences between traditional and random schedule in terms of perceived effectiveness or deterrence. Policy implications for the implementation and utilization of randomized schedules are discussed.     

Point Estimates of Test Sensitivity and Specificity from Sample Means and Variances

In a wide variety of biomedical and clinical research studies, sample statistics from diagnostic marker measurements are presented as a means of distinguishing between two populations, such as with and without disease. Intuitively, a larger difference between the mean values of a marker for the two populations, and a smaller spread of values within each population, should lead to more reliable classification rules based on this marker. We formalize this intuitive notion by deriving practical, new, closed-form expressions for the sensitivity and specificity of three different discriminant tests defined in terms of the sample means and standard deviations of diagnostic marker measurements. The three discriminant tests evaluated are based, respectively, on the Euclidean distance and the Mahalanobis distance between means, and a likelihood ratio analysis. Expressions for the effects of measurement error are also presented. Our final expressions assume that the diagnostic markers follow independent normal distributions for the two populations, although it will be clear that other known distributions may be similarly analyzed. We then discuss applications drawn from the medical literature, although the formalism is clearly not restricted to that application.     

Longitudinal Links between Adolescent and Peer Conduct Problems and Moderation by a Sensitivity Genetic Index

The most extensively studied influence on adolescent conduct problem behaviors is peers, and the literature points to genetics as one source of individual differences in peer influence. The purpose of this study was to test the hypothesis that an environmental sensitivity genetic index comprised of DRD4, 5‐HTTLPR, and GABRA2 variation would moderate the association between peer and adolescent conduct problems. Latent growth modeling was applied to PROSPER project longitudinal data from adolescents and their peers. Results showed the hypothesis was supported; adolescents with more copies of putative sensitivity alleles were more strongly influenced by their peers. The interaction form was consistent with differential susceptibility in follow‐up analyses. Strengths and weaknesses of genetic aggregates for sensitivity research are discussed.     

Identifying Changing Aviation Threat Environments Within an Adaptive Homeland Security Advisory System

A critical component of aviation security consists of screening passengers and baggage to protect airports and aircraft from terrorist threats. Advancements in screening device technology have increased the ability to detect these threats; however, specifying the operational configurations of these devices in response to changes in the threat environment can become difficult. This article proposes to use Fisher information as a statistical measure for detecting changes in the threat environment. The perceived risk of passengers, according to prescreening information and behavior analysis, is analyzed as the passengers sequentially enter the security checkpoint. The alarm responses from the devices used to detect threats are also analyzed to monitor significant changes in the frequency of threat items uncovered. The key results are that this information‐based measure can be used within the Homeland Security Advisory System to indicate changes in threat conditions in real time, and provide the flexibility of security screening detection devices to responsively and automatically adapt operational configurations to these changing threat conditions.     

An Additive–Multiplicative Restricted Mean Residual Life Model

The mean residual life measures the expected remaining life of a subject who has survived up to a particular time. When survival time distribution is highly skewed or heavy tailed, the restricted mean residual life must be considered. In this paper, we propose an additive–multiplicative restricted mean residual life model to study the association between the restricted mean residual life function and potential regression covariates in the presence of right censoring. This model extends the proportional mean residual life model using an additive model as its covariate dependent baseline. For the suggested model, some covariate effects are allowed to be time‐varying. To estimate the model parameters, martingale estimating equations are developed, and the large sample properties of the resulting estimators are established. In addition, to assess the adequacy of the model, we investigate a goodness of fit test that is asymptotically justified. The proposed methodology is evaluated via simulation studies and further applied to a kidney cancer data set collected from a clinical trial.     

Emotional Climate in Families Experiencing Homelessness: Associations with Child Affect and Socioemotional Adjustment in School

This study examined associations among family‐level risks, emotional climate, and child adjustment in families experiencing homelessness. Emotional climate, an indirect aspect of emotion socialization, was indexed by parents’ expressed emotion while describing their children. Sociodemographic risk and parent internalizing distress were hypothesized to predict more negativity and less warmth in the emotional climate. Emotional climate was expected to predict observer‐rated child affect and teacher‐reported socioemotional adjustment, mediating effects of risk. Participants were 138 homeless parents (64 percent African‐American) and their four‐ to six‐year‐old children (43.5 percent male). During semi‐structured interviews, parents reported demographic risks and internalizing distress and completed a Five Minute Speech Sample about their child, later rated for warmth and negativity. Children's positive and negative affect were coded from videotapes of structured parent‐child interaction tasks. Socioemotional adjustment (externalizing behavior, peer acceptance, and prosocial behavior) was reported by teachers a few months later. Hypotheses were partially supported. Parent internalizing distress was associated with higher parent negativity, which was linked to more negative affect in children, and parent warmth was associated with children's positive affect. Neither emotional climate nor child affect predicted teacher‐reported externalizing behavior or peer acceptance, but parental negativity and male sex predicted lower prosocial behavior in the classroom. Future research directions and clinical implications are discussed.     

Improved bridge constructs for stochastic differential equations

We consider the task of generating discrete-time realisations of a nonlinear multivariate diffusion process satisfying an Itô stochastic differential equation conditional on an observation taken at a fixed future time-point. Such realisations are typically termed diffusion bridges. Since, in general, no closed form expression exists for the transition densities of the process of interest, a widely adopted solution works with the Euler–Maruyama approximation, by replacing the intractable transition densities with Gaussian approximations. However, the density of the conditioned discrete-time process remains intractable, necessitating the use of computationally intensive methods such as Markov chain Monte Carlo. Designing an efficient proposal mechanism which can be applied to a noisy and partially observed system that exhibits nonlinear dynamics is a challenging problem, and is the focus of this paper. By partitioning the process into two parts, one that accounts for nonlinear dynamics in a deterministic way, and another as a residual stochastic process, we develop a class of novel constructs that bridge the residual process via a linear approximation. In addition, we adapt a recently proposed construct to a partial and noisy observation regime. We compare the performance of each new construct with a number of existing approaches, using three applications.