The time‐dependent “cure‐death” model investigating two equally important endpoints simultaneously in trials treating high‐risk patients with resistant pathogens

A variety of primary endpoints are used in clinical trials treating patients with severe infectious diseases, and existing guidelines do not provide a consistent recommendation. We propose to study simultaneously two primary endpoints, cure and death, in a comprehensive multistate cure‐death model as starting point for a treatment comparison. This technique enables us to study the temporal dynamic of the patient‐relevant probability to be cured and alive. We describe and compare traditional and innovative methods suitable for a treatment comparison based on this model. Traditional analyses using risk differences focus on one prespecified timepoint only. A restricted logrank‐based test of treatment effect is sensitive to ordered categories of responses and integrates information on duration of response. The pseudo‐value regression provides a direct regression model for examination of treatment effect via difference in transition probabilities. Applied to a topical real data example and simulation scenarios, we demonstrate advantages and limitations and provide an insight into how these methods can handle different kinds of treatment imbalances. The cure‐death model provides a suitable framework to gain a better understanding of how a new treatment influences the time‐dynamic cure and death process. This might help the future planning of randomised clinical trials, sample size calculations, and data analyses.     

Statistical modeling for Bayesian extrapolation of adult clinical trial information in pediatric drug evaluation

Children represent a large underserved population of “therapeutic orphans,” as an estimated 80% of children are treated off‐label. However, pediatric drug development often faces substantial challenges, including economic, logistical, technical, and ethical barriers, among others. Among many efforts trying to remove these barriers, increased recent attention has been paid to extrapolation; that is, the leveraging of available data from adults or older age groups to draw conclusions for the pediatric population. The Bayesian statistical paradigm is natural in this setting, as it permits the combining (or “borrowing”) of information across disparate sources, such as the adult and pediatric data. In this paper, authored by the pediatric subteam of the Drug Information Association Bayesian Scientific Working Group and Adaptive Design Working Group, we develop, illustrate, and provide suggestions on Bayesian statistical methods that could be used to design improved pediatric development programs that use all available information in the most efficient manner. A variety of relevant Bayesian approaches are described, several of which are illustrated through 2 case studies: extrapolating adult efficacy data to expand the labeling for Remicade to include pediatric ulcerative colitis and extrapolating adult exposure‐response information for antiepileptic drugs to pediatrics.     

The Politics of Women's Economic Independence

We identify the political conditions that shape the economicposition of married/cohabiting women and of the economicallymost vulnerable group of women—single mothers. Specifically,we examine the determinants of reductions in single mothers'poverty rate due to taxes and transfers, and women's wages relativeto spouses'/ partners' wages. The Luxembourg Income Study archiveyields an unbalanced panel with 71 observations on 15 countries.The principal determinants of poverty reduction due to taxesand transfers are left government, constitutional veto points,and welfare generosity. The relative wage of women in couplesis a function mainly of female labor force participation, parttime work among women, and women's mobilization. In explainingthe causal pathways to these outcomes, we highlight the interrelationshipsof welfare state, care, and labor market policies.     

DETERMINING THE APPROPRIATE DISCOUNT RATES IN PURE CAPITAL RATIONING

This paper proposes an interpretation of the pure capital rationing problem as it is faced by many managers in decentralized firms in which budgets serve as the principal means of control. It is argued that the appropriate objective for situations such as these is the maximization of either undiscounted earnings over the planning horizon or total value of the investments at the horizon. When either objective function is used in conjunction with the frequently encountered linear programming models for the capital rationing problem, shadow prices result which give rise to discount rates that will reproduce the optimal solution using discounted cash flow as a criterion. These results are then used as a means for clarifying several confusing and misleading statements that have appeared in the literature.     

Electronic Access to Agricultural Journals: An Agronomy Case Study

Abstract

This study examines the electronic availability of agronomy journals at eight ARL (Association of Research Libraries) member institutions with doctoral programs in agronomy. Of the forty-seven journals examined, twelve were not available electronically at any of the institutions. On average, institutions provided access to thirty of the titles, with twenty-seven of these being unembargoed. In terms of depth of access, much of the older literature which is important to the agricultural sciences was not available electronically. Librarians can use these results to communicate to researchers the importance of not relying solely on electronically available research materials.     

Children Selectively Trust Individuals Who Have Imitated Them

We investigated the influence of being imitated on children's subsequent trust. Five‐ to six‐year‐olds interacted with one experimenter who mimicked their choices and another experimenter who made different choices. Children were then presented with two tests. In a preference test, the experimenters offered conflicting preferences for the contents of two opaque boxes, and children were asked to choose a box. In a factual claims test, the experimenters offered conflicting claims about the referent for a novel word, and children were asked to state which object the word referred to. Children were significantly more likely to endorse both the preferences and the factual claims of the experimenter who had mimicked them. These results demonstrate that imitation is a powerful means of social influence in development.     

Can Heterosexism Harm Organizations? Predicting the Perceived Organizational Citizenship Behaviors of Gay and Lesbian Employees

An initial test and validation of a model predicting perceived organizational citizenship behaviors (OCBs) of lesbian and gay employees were conducted using structural equation modeling. The proposed structural model demonstrated acceptable goodness of fit and structural invariance across 2 samples (ns = 311 and 295), which suggested that altruistic OCB performance is precipitated by workplace outness. Furthermore, stigmatization salience and organizational climate for heterosexism predict levels of workplace outness. Organizational climate for heterosexism is negatively related to stigmatization salience. When the model was tested on 2 samples, all structural paths except 1 were significant.     

Dynamic Graphics for Exploring Spatial Data with Application to Locating Global and Local Anomalies

We explore the application of dynamic graphics to the exploratory analysis of spatial data. We introduce a number of new tools and illustrate their use with prototype software, developed at Trinity College, Dublin. These tools are used to examine local variability—anomalies—through plots of the data that display its marginal and multivariate distributions, through interactive smoothers, and through plots motivated by the spatial auto-covariance ideas implicit in the variogram. We regard these as alternative and linked views of the data. We conclude that the most important single view of the data is the Map View: All other views must be cross-referred to this, and the software must encourage this. The view can be enriched by overlaying on other pertinent spatial information. We draw attention to the possibilities of one-many linking, and to the use of line-objects to link pairs of data points. We draw attention to the parallels with work on Geographical Information Systems.     

Expectations, alienation, and drinking motives among college men and women

Relationships among three motivational variables (negative-personal functions of drinking, alienation, and perceived discrepancies between valued goals and expected success toward valued goals) were evaluated in a group of 257 college drinkers. As predicted, a positive relationship between alienation scores and the extent of discrepancies between values and expectations for academic and social success was found. Negative-personal drinking functions were positively associated with both alienation and value-expectation discrepancies. Results are discussed in terms of heuristic consistency and potential applications.