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.     

The next forty years in public health

In this article an attempt is made to assess the major health problems of the second half of the twentieth century in developed countries, the methods appropriate to these problems, and the pattern of medical services necessary to deal with them. From an examination of mortality and morbidity trends it is suggested that the most important problems are likely to be the mortality, malformation and disability established before birth, mental illness, and the disease and disability associated with ageing. Reasons are given for doubting whether control of breeding, the method which has contributed greatly to the improvement of plants and other animals, can be expected to be effective in the case of man, and hence reliance must continue to be placed on modifications of the environment to which achievement hitherto has been entirely due. The methods likely to be significant are: an extension of measures already in use for control ofthe physical environment; discovery and application of knowledge concerning the social environment; and elaboration of more effective methods of preventing and treating disease in the individual. Profound changes will be needed in the pattern of services through which medical knowledge is applied, the most important being unification ofthe major classes ofhospitals - acute, mental and chronic; association ofthe preventive personal health services with curative services (rather than with environmental services); and the strengthening of domiciliary medical care, particularly through a new and more intimate relationship between general practitioner and hospital services.     

Predictive factors of acculturation attitudes and social support among Asian immigrants in the USA

This study examines acculturation attitude and its relation to social support among Asian immigrants. The data were collected from 242 Korean, Indian and Filipino immigrants in the USA using the Acculturation Attitude Scale and the Social Support Index. Findings showed that Koreans had a less positive attitude toward acculturation than did Indian and Filipino participants. Acculturation attitude was positively correlated with educational level and English fluency. This study also found a negative correlation between acculturation attitude and social support. Social support from friends and English fluency were identified as significant predictor variables in determining the level of acculturation attitude. These findings not only contribute to social work education and practice, but also increase cultural sensitivity and awareness in working with these populations.     

Resolving conflict over salespeople’s brand adoption in franchised channels of distribution

Many franchise-based retail outlets offer both the franchisor-owned brand and brands of competitors or independent suppliers. As salespeople may influence customers’ brand choices considerably, an important concern for franchisors is how to raise salespeople’s selling preferences for the franchisor-owned brand. However, the channel administration literature suggests that salespeople may not automatically favor the franchisor’s brand over other brand lines. While a large body of research examines franchise–channel relationships, previous investigations have conspicuously overlooked this channel conflict. In proposing a conceptual model grounded in the behavioral sciences, this study analyzes how franchisors can induce salespeople to advocate their brand by fostering the intention to promote the franchisor-owned brand (IFOB) in customer interaction. The results of an empirical field study show that individual brand promotion depends on factors such as salespeople’s identification with the franchisor and their tenure with the organization, as well as on the franchisor’s prestige and administration of the franchise. Moreover, we find that franchisees’ IFOB transfers to salespeople, but only if franchisees display a charismatic leadership style. We discuss these findings in light of extant theory and empirical evidence and derive several managerially relevant implications for the administration of franchised retail channels.     

The Eating Disorders NOS Diagnostic Profile Among College Women

Abstract

The authors examined a proposed profile of eating-related behaviors, associated features, developmental issues, and help-seeking behavior among college women, using an eating disorder response program. The most common symptom scenario was a pattern of regular binge eating, together with daily exercise and occasional purging. The most common associated features were distressing or dysfunctional overconcern about body image and self-esteem, usually with day-to-day stress and intermittent depression. The women who fit this pattern also presented developmental issues of perfectionism, conflictual relationships with parents, and struggles for independence; and they tended to be ambivalent about seeking services. Implications for practice, including the need to develop a framework for eating disorder responses on campus that includes preventive programs and developmental interventions to target emerging and moderate concerns are discussed; limitations and the preliminary nature of the findings are explicated.     

Assessing the Concept of the ‘Insecure‐Other’ Category in the Cassidy–Marvin Scheme: Changes Between 4 and 6 Years in the English and Romanian Adoptee Study

We set out to explore the meaning of the attachment categories in the Cassidy/Marvin strange situation procedure, as employed in the home, using data from a longitudinal study of children adopted into UK families up to the age of 42 months from Romanian institutions, and of adopted children without the experience of institutional care––both groups being assessed at 4 and 6 years of age. Inter‐rater reliability was found to be good. Security (meaning the use of the parent as a secure base and no negative behavior on reunion) was the modal categorical rating in both the institution‐reared and comparison groups, but the category of anomalous non‐normative behavior (meaning a lack of any ordered attachment behavior as covered by the standard ratings), previously labeled ‘insecure‐other’, was more common in the institution‐reared children. Because this was unassociated with the usual manifestations of insecurity (such as avoidance or resistance) and because it was largely evident in interactions with the stranger, it is concluded that the adjective ‘insecure’ was not appropriate. Although this ‘insecure‐other’ category was associated with disinhibited attachment as reported by parents (meaning a lack of differentiation among adults, a willingness to go off with strangers and a lack of checking back with parents in anxiety‐provoking situations), it did not prove to be a good index of disinhibited attachment because changes over time in the ‘insecure‐other’ category were not associated with changes in the rate of disinhibited attachment. Also, whereas the rate of ‘insecure‐other’ fell markedly in the institution‐reared group between 4 and 6 years of age, it rose in the comparison group, raising queries over its meaning.     

Voting Technology,Political Responsiveness,and Infant Health: Evidence From Brazil

This paper studies the introduction of electronic voting technology in Brazilian elections. Estimates exploiting a regression discontinuity design indicate that electronic voting reduced residual (error‐ridden and uncounted) votes and promoted a large de facto enfranchisement of mainly less educated citizens. Estimates exploiting the unique pattern of the technology's phase‐in across states over time suggest that, as predicted by political economy models, it shifted government spending toward health care, which is particularly beneficial to the poor. Positive effects on both the utilization of health services (prenatal visits) and newborn health (low‐weight births) are also found for less educated mothers, but not for the more educated.     

Benefits of Hybrid Lateral Transshipments in Multi‐Item Inventory Systems under Periodic Replenishment

Lateral transshipments are a method of responding to shortages of stock in a network of inventory‐holding locations. Conventional reactive approaches only seek to meet immediate shortages. The study proposes hybrid transshipments which exploit economies of scale by moving additional stock between locations to prevent future shortages in addition to meeting immediate ones. The setting considered is motivated by retailers who operate networks of outlets supplying car parts via a system of periodic replenishment. It is novel in allowing non‐stationary stochastic demand and general patterns of dependence between multiple item types. The generality of our work makes it widely applicable. We develop an easy‐to‐compute quasi‐myopic heuristic for determining how hybrid transshipments should be made. We obtain simple characterizations of the heuristic and demonstrate its strong cost performance in both small and large networks in an extensive numerical study.