Bayesian adaptive dose‐escalation designs for simultaneously estimating the optimal and maximum safe dose based on safety and efficacy

The main purpose of dose‐escalation trials is to identify the dose(s) that is/are safe and efficacious for further investigations in later studies. In this paper, we introduce dose‐escalation designs that incorporate both the dose‐limiting events and dose‐limiting toxicities (DLTs) and indicative responses of efficacy into the procedure. A flexible nonparametric model is used for modelling the continuous efficacy responses while a logistic model is used for the binary DLTs. Escalation decisions are based on the combination of the probabilities of DLTs and expected efficacy through a gain function. On the basis of this setup, we then introduce 2 types of Bayesian adaptive dose‐escalation strategies. The first type of procedures, called “single objective,” aims to identify and recommend a single dose, either the maximum tolerated dose, the highest dose that is considered as safe, or the optimal dose, a safe dose that gives optimum benefit risk. The second type, called “dual objective,” aims to jointly estimate both the maximum tolerated dose and the optimal dose accurately. The recommended doses obtained under these dose‐escalation procedures provide information about the safety and efficacy profile of the novel drug to facilitate later studies. We evaluate different strategies via simulations based on an example constructed from a real trial on patients with type 2 diabetes, and the use of stopping rules is assessed. We find that the nonparametric model estimates the efficacy responses well for different underlying true shapes. The dual‐objective designs give better results in terms of identifying the 2 real target doses compared to the single‐objective designs.     

Using Work Values to Predict Post‐Retirement Work Intentions

Work values might be proximal predictors of individuals' late‐career intentions because they serve as guiding principles for the selection, evaluation, and justification of vocational behavior. The purpose of this study was to examine the relationship between work values and post‐retirement work intentions. The authors investigated individual work values within the structure of 4 higher order values elaborated on by Schwartz et al. ( 2012 ). Relationships between work values and 4 types of post‐retirement work intentions were examined. Data from 1,071 employees of a German logistics company were used to test the hypotheses. The results of a structural equation model indicated that work values were differentially related to the 4 types of post‐retirement work intentions. The identified work value–work type combinations add to the literature on post‐retirement work. Practice implications for promoting positive individual and organizational outcomes are drawn from the results.     

Micro‐investment perspective and the potential of the universal basic income

The article evaluates prospects of the Basic Income (BI) as a development policy tool. While BI is a relatively new initiative within development policy, the article argues that it should be seen as a serious option in the future, given the changing geography of poverty and the findings from existing cash transfer schemes. The analysis is carried out as a synthesis of existing findings on BI pilot programmes, along with cash transfer instruments more generally. While not including new empirical data, the synthesis allows preliminary estimates on the likely impacts of abolishing conditioning and targeting in cash transfer schemes. Particular attention is paid to the notion of micro‐investment and the psychological conditions of micro‐investment.     

Nonparametric Shrinkage Estimation for Aalen's Additive Hazards Model

Aalen's nonparametric additive model in which the regression coefficients are assumed to be unspecified functions of time is a flexible alternative to Cox's proportional hazards model when the proportionality assumption is in doubt. In this paper, we incorporate a general linear hypothesis into the estimation of the time‐varying regression coefficients. We combine unrestricted least squares estimators and estimators that are restricted by the linear hypothesis and produce James‐Stein‐type shrinkage estimators of the regression coefficients. We develop the asymptotic joint distribution of such restricted and unrestricted estimators and use this to study the relative performance of the proposed estimators via their integrated asymptotic distributional risks. We conduct Monte Carlo simulations to examine the relative performance of the estimators in terms of their integrated mean square errors. We also compare the performance of the proposed estimators with a recently devised LASSO estimator as well as with ridge‐type estimators both via simulations and data on the survival of primary billiary cirhosis patients.     

Who is a Distracted Driver? Associations between Mobile Phone Use while Driving,Domain‐Specific Risk Taking,and Personality

Mobile phone use while driving (MPUWD) is an increasingly common form of distracted driving. Given its widespread prevalence, it is important for researchers to identify factors that may predict who is more likely to engage in this risky behavior. The current study investigates associations between MPUWD risk behaviors, domain‐specific risk perceptions, and broad personality dimensions. An Italian community sample (n = 804) completed a survey regarding MPUWD risk perceptions and engagement in MPUWD, in addition to the HEXACO‐PI‐R, a broad six‐factor personality inventory (honesty‐humility, emotionality, extraversion, agreeableness, conscientiousness, openness to experience), and the DOSPERT, a six‐factor domain‐specific self‐report risk‐taking measure (health/safety, recreational, social, ethical, gambling, and investment). With respect to domain‐specific risk taking, greater frequency of SMS use while driving most strongly was associated with greater risk taking for the health/safety, gambling, and ethical risk domains. Further, greater honesty‐humility and conscientiousness, two traits related to cognitive control and risk behaviors, and to a lesser extent openness to experience, were associated with less frequent MPUWD, and positively associated with MPUWD risk perceptions. With growing public safety concern surrounding MPUWD, understanding associated personality factors is not only important for identifying psychological mechanisms underlying risk behavior, but also for more effective prevention and intervention programs.     

And I Still Love Them: On Touching Loss

In this article, the author performs a re‐membering practice that incorporates a relational materialist theory. It traces the disturbances that follow in the wake of three deaths in her family. Written in an autoethnographic voice, the article is a polyphonic composition of the narrative therapy approach of re‐membering entangled with the spacetimematter of silence, speaking, sitting, staying, presence, absence, loss of momentum, dreams, trees, books, cardiac pace‐makers, writing, breath, ashes, murmuring, suffering. Thus, the dispersed agencies of bodies, human and non‐human, reinvigorate a linguistic practice and the author's personal and professional life.     

Need,well‐being and outcomes: the development of policy‐thinking for children's services 1989–2004

This paper describes how government policy thinking about the well‐being of children and young people developed between the Children Act 1989 and the Children Act 2004. These two Acts are milestone statements about how services to children in England and Wales should be delivered. It is an account informed by the author's own experience as a government adviser on children's social care over much of this period and supporting documentation. It traces the strands of government policy thinking about how to deliver services for children from children in need to the articulation of the five Every Child Matters outcomes. It argues that attempts to achieve coordinated service planning for children and young people played a significant role in the formulation of shared objectives and the articulation of child outcomes. However, it argues that looking at real outcomes exposes how children in the UK do relatively badly compared with other rich nations. It questions whether we can realistically expect our services to deliver significantly improved outcomes given the impact of enduring inequality in our society. This paper is dedicated to the memory of David Lambert CBE, former Assistant Chief Inspector of the Social Services Inspectorate in London, who died suddenly on 7 October 2010. He lent me articles to assist me in writing this paper.     

New Data,Strategies, and Insights for Listeria monocytogenes Dose‐Response Models: Summary of an Interagency Workshop, 2011

Listeria monocytogenes is a leading cause of hospitalization, fetal loss, and death due to foodborne illnesses in the United States. A quantitative assessment of the relative risk of listeriosis associated with the consumption of 23 selected categories of ready‐to‐eat foods, published by the U.S. Department of Health and Human Services and the U.S. Department of Agriculture in 2003, has been instrumental in identifying the food products and practices that pose the greatest listeriosis risk and has guided the evaluation of potential intervention strategies. Dose‐response models, which quantify the relationship between an exposure dose and the probability of adverse health outcomes, were essential components of the risk assessment. However, because of data gaps and limitations in the available data and modeling approaches, considerable uncertainty existed. Since publication of the risk assessment, new data have become available for modeling L. monocytogenes dose‐response. At the same time, recent advances in the understanding of L. monocytogenes pathophysiology and strain diversity have warranted a critical reevaluation of the published dose‐response models. To discuss strategies for modeling L. monocytogenes dose‐response, the Interagency Risk Assessment Consortium (IRAC) and the Joint Institute for Food Safety and Applied Nutrition (JIFSAN) held a scientific workshop in 2011 (details available at http://foodrisk.org/irac/events/ ). The main findings of the workshop and the most current and relevant data identified during the workshop are summarized and presented in the context of L. monocytogenes dose‐response. This article also discusses new insights on dose‐response modeling for L. monocytogenes and research opportunities to meet future needs.     

Does Fatherhood Matter for Men?

Ignored in the flurry of new research on fathers is that fatherhood may have consequences for men. This article explores possible effects on the lives and well‐being of men for a range of fatherhood experiences. Data are drawn from the National Survey of Families and Households. The first part of this article examines whether men's varied associations with children (no children, coresident, non‐coresident, and stepfatherhood) are associated with men's psychological health and behavior, social connections, intergenerational family relations, and work behavior. We found strong evidence that fathers differ from nonfathers in their social connections, family relationships, and work behavior. There is significant variation in effects among the father types as well. The second section of this article focuses attention only on men who are fathers and examines whether fathering behavior (e.g., the amount of time and nature of the activities that fathers are reported to be spending with their children) is associated with men's well‐being. The effects of father involvement on men was found to be most significant for those who were living with their own children.