Comparisons of outlier tests for potency bioassays

Potency bioassays are used to measure biological activity. Consequently, potency is considered a critical quality attribute in manufacturing. Relative potency is measured by comparing the concentration‐response curves of a manufactured test batch with that of a reference standard. If the curve shapes are deemed similar, the test batch is said to exhibit constant relative potency with the reference standard, a critical requirement for calibrating the potency of the final drug product. Outliers in bioassay potency data may result in the false acceptance/rejection of a bad/good sample and, if accepted, may yield a biased relative potency estimate. To avoid these issues, the USP<1032> recommends the screening of bioassay data for outliers prior to performing a relative potency analysis. In a recently published work, the effects of one or more outliers, outlier size, and outlier type on similarity testing and estimation of relative potency were thoroughly examined, confirming the USP<1032> outlier guidance. As a follow‐up, several outlier detection methods, including those proposed by the USP<1010>, are evaluated and compared in this work through computer simulation. Two novel outlier detection methods are also proposed. The effects of outlier removal on similarity testing and estimation of relative potency were evaluated, resulting in recommendations for best practice.     

An Instrument for Person-of-the-Therapist Supervision

This article introduces a tool that serves as a guide for building an effective bridge between the personal and technical aspects of therapy in supervision. The instrument is based on a model of clinical supervision that emphasizes the purposeful utilization of self—in the moment, with both flaws and strengths—in the therapeutic relationship in combination with the technical interventions with clients. The article also offers some aid to promote a personal integration of the philosophy underlying this supervisory model into a therapist's clinical thinking and practice .     

Testing drug additivity based on monotherapies

Under the Loewe additivity, constant relative potency between two drugs is a sufficient condition for the two drugs to be additive. Implicit in this condition is that one drug acts like a dilution of the other. Geometrically, it means that the dose‐response curve of one drug is a copy of another that is shifted horizontally by a constant over the log‐dose axis. Such phenomenon is often referred to as parallelism. Thus, testing drug additivity is equivalent to the demonstration of parallelism between two dose‐response curves. Current methods used for testing parallelism are usually based on significance tests for differences between parameters in the dose‐response curves of the monotherapies. A p‐value of less than 0.05 is indicative of non‐parallelism. The p‐value‐based methods, however, may be fundamentally flawed because an increase in either sample size or precision of the assay used to measure drug effect may result in more frequent rejection of parallel lines for a trivial difference. Moreover, similarity (difference) between model parameters does not necessarily translate into the similarity (difference) between the two response curves. As a result, a test may conclude that the model parameters are similar (different), yet there is little assurance on the similarity between the two dose‐response curves. In this paper, we introduce a Bayesian approach to directly test the hypothesis that the two drugs have a constant relative potency. An important utility of our proposed method is in aiding go/no‐go decisions concerning two drug combination studies. It is illustrated with both a simulated example and a real‐life example. Copyright © 2015 John Wiley & Sons, Ltd.     

The Unmaking of Management? Change and Continuity in British Management in the 1990s

In the late 1980s, a series of reports —notably, The Making of Managers by CharlesHandy-outlined a development path for management in theU.K. This was to be based on the development of aneducation and training base and the model set by leadingcorporations. A decade later, this paper reviews currenttrends in managerial work and employment against theexpectations of the late 1980s. In doing so, it distinguishes between the objectivecondition of British management and itsinstitutionalized meaning within wider British society.It argues that recent accounts of changes in managerialwork and employment have focused solely on incremental changes inthe empirical domain and have neglected importantdiscursive shifts in the way management is understoodand enacted within organizations. These shifts have been catalyzed by the emergence of a series oforganizational initiatives-first, Total QualityManagement (TQM) and, latterly, lean production andBusiness Process Reengineering (BPR)-which aim tosystematically deconstruct management by emphasizing workerempowerment, delayering, downsizing, and theredistribution of managerial functions. In short,initiatives such as these are contributing to theunmaking of management. Managerial groups aresubject to intensification and polarization, whilemanagerial practices are diffused throughout the workprocess.     

Risk Analysis of Terrorist Attacks

A quantitative probabilistic/systems analysis model is described which is useful for allocating resources to safeguard valuable documents or materials in either a fixed-site facility or a moving convoy against an overt terrorist attack. The model is also useful for ranking the sensitive areas at a site according to their survivability of a given hypothesized terrorist attempt. To compare various defense strategies and security configurations, the probability of a successful terrorist activity is computed based on event tree models of the site/security configuration. This calculation incorporates a realistic engagement model (in the event a guard force engages the terrorists prior to completion of their objective) and information on barrier penetration times (for example, distribution of the time to defeat a chain link fence or vault door, traverse an open area, and so forth). Two security analyses are described to illustrate the methodology. One example considers a terrorist attack on a convoy transporting a missile from a storage to a launch facility. The second example involves an attack on a munitions storage facility.     

Social capital and women's reduced vulnerability to HIV infection in rural Zimbabwe

Social capital—especially through its “network” dimension (high levels of participation in local community groups)—is thought to be an important determinant of health in many contexts. We investigate its effect on HIV prevention, using prospective data from a general population cohort in eastern Zimbabwe spanning a period of extensive behavior change (1998–2003). Almost half of the initially uninfected women interviewed were members of at least one community group. In an analysis of 88 communities, individuals with higher levels of community group participation had lower incidence of new HIV infections and more of them had adopted safer behaviors, although these effects were largely accounted for by differences in socio-demographic composition. Individual women in community groups had lower HIV incidence and more extensive behavior change, even after controlling for confounding factors. Community group membership was not associated with lower HIV incidence in men, possibly refecting a propensity among men to participate in groups that allow them to develop and demonstrate their masculine identities—often at the expense of their health. Support for women's community groups could be an effective HIV prevention strategy in countries with large-scale HIV epidemics.