Testing for bioequivalence of highly variable drugs from TR‐RT crossover designs with heterogeneous residual variances

Traditional bioavailability studies assess average bioequivalence (ABE) between the test (T) and reference (R) products under the crossover design with TR and RT sequences. With highly variable (HV) drugs whose intrasubject coefficient of variation in pharmacokinetic measures is 30% or greater, assertion of ABE becomes difficult due to the large sample sizes needed to achieve adequate power. In 2011, the FDA adopted a more relaxed, yet complex, ABE criterion and supplied a procedure to assess this criterion exclusively under TRR‐RTR‐RRT and TRTR‐RTRT designs. However, designs with more than 2 periods are not always feasible. This present work investigates how to evaluate HV drugs under TR‐RT designs. A mixed model with heterogeneous residual variances is used to fit data from TR‐RT designs. Under the assumption of zero subject‐by‐formulation interaction, this basic model is comparable to the FDA‐recommended model for TRR‐RTR‐RRT and TRTR‐RTRT designs, suggesting the conceptual plausibility of our approach. To overcome the distributional dependency among summary statistics of model parameters, we develop statistical tests via the generalized pivotal quantity (GPQ). A real‐world data example is given to illustrate the utility of the resulting procedures. Our simulation study identifies a GPQ‐based testing procedure that evaluates HV drugs under practical TR‐RT designs with desirable type I error rate and reasonable power. In comparison to the FDA's approach, this GPQ‐based procedure gives similar performance when the product's intersubject standard deviation is low (≤0.4) and is most useful when practical considerations restrict the crossover design to 2 periods.     

Staff Development as a School Climate Intervention to Support Transgender and Gender Nonconforming Students: An Integrated Research Partnership Model for School Counselors and Counselor Educators

ABSTRACT

This article posits that an integrative research partnership model can assist school counselors in addressing the marginalization of transgender students in schools through staff development. A methodological integration of action research and program evaluation through quantitative and qualitative data collection is explained, and a collaborative process is highlighted. A case example is provided to demonstrate the use of the design.     

Generating a smallest binary tree by proper selection of the longest edges to bisect in a unit simplex refinement

In several areas like global optimization using branch-and-bound methods for mixture design, the unit n-simplex is refined by longest edge bisection (LEB). This process provides a binary search tree. For \(n>2\), simplices appearing during the refinement process can have more than one longest edge (LE). The size of the resulting binary tree depends on the specific sequence of bisected longest edges. The questions are how to calculate the size of one of the smallest binary trees generated by LEB and how to find the corresponding sequence of LEs to bisect, which can be represented by a set of LE indices. Algorithms answering these questions are presented here. We focus on sets of LE indices that are repeated at a level of the binary tree. A set of LEs was presented in Aparicio et al. (Informatica 26(1):17–32, 2015), for \(n=3\). An additional question is whether this set is the best one under the so-called \(m_k\)-valid condition.     

Changing Trends of Mothers’ Active and Passive Childcare Times

This paper explores how mothers’ allocation of types of time with children and the determinants of this allocation have changed during 1981–1997 in the United States, using Time Use Longitudinal Panel Study and Family Interaction, Social Capital and Trends in Time Use. Data reveal that active time with children has increased for the case of educated working mothers with young children. Estimations also provide evidence that although different uses of time are substitutes; active time is less sensitive than passive. Moreover, the relationship between active and passive time with children has changed over time.     

Infant Distress and Regulatory Behaviors Vary as a Function of Attachment Security Regardless of Emotion Context and Maternal Involvement

Differences in infant distress and regulatory behaviors based on the quality of attachment to mother, emotion context (frustration versus fear), and whether or not mothers were actively involved in the emotion-eliciting tasks were examined in a sample of 98 16-month-old infants and their mothers. Dyads participated in the Strange Situation, a limiting task designed to elicit infant frustration, and a novelty task designed to elicit infant fear. Mothers were asked to remain uninvolved during the first minute of each task, and then instructed to engage with their infants as they wished for the remaining three minutes. Independent of concurrent maternal sensitivity, resistant infants were significantly more distressed than secure and avoidant infants. Avoidant infants engaged in fewer active mother-oriented regulation behaviors than secure and resistant infants and engaged in more self-soothing in the mother involved condition than the mother uninvolved condition. Resistant infants engaged in more physical comfort with their mothers and more venting than both secure and avoidant infants, and exhibited a smaller variety of adaptive non-mother-oriented strategies than did secure infants. There were few differences in infant distress and regulatory behaviors as a function of emotion task and maternal involvement. Limitations and implications for future research are discussed.     

Climate change and population migration in Brazil’s Northeast: scenarios for 2025–2050

This research contributes to an understanding of the relationship between climate change, economic impacts and migration. We model the long-term relationship (up to 45 years of projection) between demographic dynamics—particularly migration—driven by changes in the performance of the economy due to climate changes in the Northeast region of Brazil. The region is of particular relevance to the study of climate change impacts given its large human population (28% of Brazil’s population) and high levels of impoverishment, having an extensive semi-dry area which will be severely impacted by growing temperatures. Ultimately, the integrated model generates state- and municipal-level migration scenarios based on climate change impacts on the primary economic sectors and their articulations with other sectors. Results suggest that the predicted climate changes will impact severely the agriculture sector in the region, acting as a potential migration push factor to other regions in the country. Finally, we discuss how the increased vulnerability of some groups, particularly migrants, can be factored into Brazilian public policy and planning.     

An Analysis of Student Satisfaction: Full-Time vs. Part-Time Students

This paper examines how full-time or part-time status affects students’ level of satisfaction with their degree programs. For our analysis, we obtained data from a survey of graduate students. The survey was conducted at a public university in Spain from 2001 to 2004. The decision to undertake paid employment while studying emerges as one of the key determinants of student satisfaction. In particular, our findings indicate that students who hold a part-time job while studying are more likely to express less satisfaction with their college experience.