Examples of option values in drug development

The option to stop a project is fundamental in drug development. The majority of drugs do not reach the market. Furthermore, many marketed drugs do not repay their development costs. It is therefore crucial to optimize the value of the option to stop. We formulate two examples of statistical models. One is based on success/failure in a series of trials; the other assumes that the commercial value evolves as a stochastic process as more information becomes available. These models are used to study a number of issues: the number and timing of decision points; value of information; speed of development; and order of trials. The results quantify the value of options. They show that early information that can change key decisions is most valuable. That is, we should nip bad projects in the bud. Modelling is also useful to analyse more complex decisions, for example, weighting the value of decision points against the cost of information or the speed of development. Copyright © 2003 John Wiley & Sons, Ltd.     

Health benefits of volunteering in the Wisconsin longitudinal study

We investigate positive effects of volunteering on psychological well-being and self-reported health using all four waves of the Wisconsin Longitudinal Study. Confirming previous research, volunteering was positively related to both outcome variables. Both consistency of volunteering over time and diversity of participation are significantly related to well-being and self-reported health. The relationship of volunteering to psychological well-being was moderated by level of social integration, such that those who were less well integrated benefited the most. Mattering appears to mediate the link between volunteering and wellbeing. Controls for other forms of social participation and for the predictors of volunteering are employed in analyses of well-being in 1992. We find volunteering effects on psychological well-being in 2004, controlling for 1992 wellbeing, thus providing strong evidence for a causal effect.     

The Roles of Parenting Styles and Social Capital in the School Performance of Immigrant Asian and Hispanic Adolescents*

Objective. This study investigates the role of parenting styles and social capital (parental involvement, intergenerational closure, expectation, and trust) in accounting for school performance among ethnic groups and across immigrant generations. Methods. Using data from the Adolescent Health Survey, we estimate fixed‐effects models to analyze students' grade‐point averages. We compare three generations of Asian students and three generations of Hispanic students to the third‐generation (native born with native parents) white students. Results. We find significant differences by both race/ethnicity and generational status in parenting styles and forms of social capital. However, while family socioeconomic status (SES) accounts for the achievement gap between foreign‐born Hispanic and the third‐generation white students, parenting styles and forms of social capital do not moderate any ethnic‐generational differences. Conclusions. Family influences, apart from SES, cannot explain ethnicity‐generation differences in school grades among Hispanic and Asian adolescents. This study provides conceptual clarification and empirical evidence for the significant but independent association between students' school grades and parenting styles on the one hand, and social capital on the other.     

Psychometric Evaluation of the Affect Regulation Checklist: Clinical and Community Samples,Parent-Reports and Youth Self-Reports

The Affect Regulation Checklist (ARC) was designed to capture affect dysregulation, suppression, and reflection. Importantly, affect dysregulation has been established as a transdiagnostic mechanism underpinning many forms of psychopathology. We tested the ARC psychometric properties across clinical and community samples and through both parent-report and youth self-report information. Clinical sample: Participants included parents (n = 814; M_age = 43.86) and their child (n = 608; M_age = 13.98). Community sample: Participants included independent samples of parents (n = 578; M_age = 45.12) and youth (n = 809; M_age = 15.67). Exploratory structural equation modeling supported a three-factor structure across samples and informants. Dysregulation was positively associated with all forms of psychopathology. In general, suppression was positively associated with many forms of psychopathology, and reflection was negatively associated with externalizing problems and positively associated with internalizing problems.     

Women's expectations and experiences with labour pain in medical and midwifery models of birth in the United States

BackgroundThis research focuses on how women understand and experience labour as related to two competing views of childbirth pain. The biomedical view is that labour pain is abnormal and anaesthesia/analgesia use is encouraged to relieve the pain. The midwifery view is that pain is a normal part of labour that should be worked with instead of against.AimsTo determine differences in the preparation for and experiences with labour pain by women choosing midwives versus obstetricians.MethodsPrenatal and postpartum in-depth semi-structured interviews were conducted with a convenience sample of 80 women in Florida (United States): 40 who had chosen an obstetrician and 40 who had chosen a licensed midwife as their birth practitioner.FindingsWomen in both groups were concerned with the pain of childbirth before and after their labour experiences. Women choosing midwives discussed preparing for pain through various non-pharmaceutical coping methods, while women choosing physicians discussed pharmaceutical and non-pharmaceutical pain relief.ConclusionsEqual numbers of women expressed concerns with childbirth pain during the prenatal interviews, while more women choosing doctors spoke about pain after their births. Women had negative experiences when their planned pain relief method, either natural or medical, did not occur. The quandary facing women when it comes to labour pain relief is not choosing what they desire, but rather preparing themselves for the possibility that they may have to accept alternatives to their original preferences.     

Adverse Childhood Experiences and Substance Use History among Vulnerable Older Adults Living in Public Housing

ABSTRACT

Previous research shows strong correlations between adverse childhood experiences (ACE) and later life health. The current study examines the relationship between ACEs and substance use among older adults living in public housing. Results show that about one-third of participants had four or more ACEs, and ACE score predicted likelihood of substance use history. Over half of older adults with four or more ACEs experienced substance abuse in their lifetime compared to one out of ten older adults with less than four ACEs. Findings shed light on a vulnerable group and point to next steps in research and practice.     

Binary Mixtures of Polycyclic Aromatic Hydrocarbons Display Nonadditive Mixture Interactions in an In Vitro Liver Cell Model

Polycyclic aromatic hydrocarbons (PAHs) have been labeled contaminants of concern due to their carcinogenic potential, insufficient toxicological data, environmental ubiquity, and inconsistencies in the composition of environmental mixtures. The Environmental Protection Agency is reevaluating current methods for assessing the toxicity of PAHs, including the assumption of toxic additivity in mixtures. This study was aimed at testing mixture interactions through in vitro cell culture experimentation, and modeling the toxicity using quantitative structure‐activity relationships (QSAR). Clone‐9 rat liver cells were used to analyze cellular proliferation, viability, and genotoxicity of 15 PAHs in single doses and binary mixtures. Tests revealed that many mixtures have nonadditive toxicity, but display varying mixture effects depending on the mixture composition. Many mixtures displayed antagonism, similar to other published studies. QSARs were then developed using the genetic function approximation algorithm to predict toxic activity both in single PAH congeners and in binary mixtures. Effective concentrations inhibiting 50% of the cell populations were modeled, with R² = 0.90, 0.99, and 0.84, respectively. The QSAR mixture algorithms were then adjusted to account for the observed mixture interactions as well as the mixture composition (ratios) to assess the feasibility of QSARs for mixtures. Based on these results, toxic addition is improbable and therefore environmental PAH mixtures are likely to see nonadditive responses when complex interactions occur between components. Furthermore, QSAR may be a useful tool to help bridge these data gaps surrounding the assessment of human health risks that are associated with PAH exposures.