Methods for exploring treatment effect heterogeneity in subgroup analysis: an application to global clinical trials

Multi‐country randomised clinical trials (MRCTs) are common in the medical literature, and their interpretation has been the subject of extensive recent discussion. In many MRCTs, an evaluation of treatment effect homogeneity across countries or regions is conducted. Subgroup analysis principles require a significant test of interaction in order to claim heterogeneity of treatment effect across subgroups, such as countries in an MRCT. As clinical trials are typically underpowered for tests of interaction, overly optimistic expectations of treatment effect homogeneity can lead researchers, regulators and other stakeholders to over‐interpret apparent differences between subgroups even when heterogeneity tests are insignificant. In this paper, we consider some exploratory analysis tools to address this issue. We present three measures derived using the theory of order statistics, which can be used to understand the magnitude and the nature of the variation in treatment effects that can arise merely as an artefact of chance. These measures are not intended to replace a formal test of interaction but instead provide non‐inferential visual aids, which allow comparison of the observed and expected differences between regions or other subgroups and are a useful supplement to a formal test of interaction. We discuss how our methodology differs from recently published methods addressing the same issue. A case study of our approach is presented using data from the Study of Platelet Inhibition and Patient Outcomes (PLATO), which was a large cardiovascular MRCT that has been the subject of controversy in the literature. An R package is available that implements the proposed methods. Copyright © 2014 John Wiley & Sons, Ltd.     

Persistent symptoms of maternal post-traumatic stress following childbirth across the first months postpartum: Associations with perturbations in maternal behavior and infant avoidance of social gaze toward mother

Recent literature identifies childbirth as a potentially traumatic event, following which mothers may develop symptoms of Post-Traumatic-Stress-Following-Childbirth (PTS-FC). The current study examines whether stable symptoms of PTS-FC during the early postpartum period may impose risk for perturbations in maternal behavior and infant social-engagement with mother, controlling for comorbid postpartum internalizing symptoms. Mother-infant dyads (N = 192) were recruited from the general population, during the third trimester of pregnancy. 49.5% of the mothers were primipara, and 48.4% of the infants were girls. Maternal PTS-FC was assessed at 3-day, 1-month and 4-month postpartum, via self-report and clinician-administered interview. Latent Profile Analysis generated two profiles of symptomology: “Stable-High-PTS-FC” (17.0%), and “Stable-Low-PTS-FC” (83%). Membership in the “Stable-High-PTS-FC” profile associated with perturbed maternal sensitivity, which was in turn significantly associated with infant avoidance of social gaze toward mother (Indirect effect β = −0.15). Results suggest the need for early screening and inform the planning of early preventive interventions.     

Early socialization of hostile attribution bias: The roles of parental attributions,parental discipline,and child attributes

The goal of this study was to examine child and parent predictors of children's hostile attribution bias (HAB) with a particular focus on exploring the associations between parents’ early attribution of child misbehavior and children's HAB in the transition to school age. Participants were 241 children (118 girls) of middle‐income families who were at risk for school‐age conduct problems. Multi‐method, multi‐informant data were collected on maternal attributions of child misbehavior, parental use of corporal punishment, and child attributes (i.e., verbal IQ, effortful control, theory of mind, and emotional understanding) at 3 years, and child HAB in ambiguous situations at 6 years. Results indicated that mothers’ internal explanations for children's misconduct may either reduce or increase children's later HAB depending on the specific content of attributions, such that mothers’ belief that children misbehave because of their internal state (i.e., emotional state or temperament) was associated with lower levels of child HAB, whereas attributing power‐based motives (i.e., manipulative, controlling intentions) in children was associated with higher levels of HAB. The findings are discussed with respect to appreciating the complexity of parents’ explanations for children's behavior, and considering parental cognition as a potential target for early identification and prevention of child HAB and related problems.     

Relational Aggression in Middle Childhood: Predictors and Adolescent Outcomes

This study examined gender differences in the level and developmental course of relational aggression in middle childhood, as well as early predictors and outcomes of relational aggression, after controlling for concurrent physical aggression. Relational (RAgg) and Physical aggression (PAgg) scores for 558 boys and 545 girls at the ages of eight to 11 in the NICHD Study of Early Child Care and Youth Development (SECCYD) were created by combining the highest rating for each item across mother and teacher reports. Longitudinal analyses were conducted using latent curve models of RAgg with PAgg as a time‐varying covariate, with all parameters allowed to vary by gender. Boys and girls had different growth parameters of RAgg. Girls' RAgg intercept was higher, and the slope was not different from zero; boys' RAgg intercept was lower, and the slope declined. Mother–child conflict in early childhood predicted RAgg intercept for both boys and girls, but maternal harsh control and sensitivity were also uniquely predictive for girls whereas center care was uniquely predictive for boys. RAgg intercept predicted adolescent self‐reports of depression for girls and delinquency and risk‐taking for both boys and girls; the magnitude of the association with risk taking was significantly greater for boys.     

Audience effects on solitary faces during imagery: Displaying to the people in your head

Subjects imagined situations in which they reported enjoying themselves either alone or with others. Electromyographic (EMG) activity was recorded bilaterally from regions overlying thezygomatic major muscles responsible for smiling. Controlling for equal rated happiness in the two conditions, subjects showed more smiling in high-sociality than low-sociality imagery. In confirming imaginary audience effects during imagery, these data corroborate hypotheses that solitary facial displays are mediated by the presence of imaginary interactants, and suggest caution in employing them as measures of felt emotion.Avery Gilbert and Amy Jaffey had compelling insights throughout the course of study. We thank Paul Ekman, Carroll Izard, and Paul Rozin for extensive comments on earlier drafts. We also thank Bernard Apfelbaum, Jon Baron, Janet Bavelas, John Cacioppo, Linda Camras, Dean Delis, Rob DeRubeis, Alan Fiske, Stephen Fowler, Greg McHugo, Harriet Oster, David Premack, W. John Smith, and David Williams for their valuable comments and suggestions.     

Soil microbial community of urban green infrastructures in a polar city

Urban and technogenic landscapes in subarctic zones are not considered comfortable habitats for soil microbiota. However, green infrastructures in polar cities can provide a new niche for the development of a microbial soil community. Soil microbial biomass and the diversity of cultivable microfungi have been studied in relation to the chemical and morphological properties of urban soils in the polar city of Apatity. The quantitative indicators based on fluorescence microscopy and PCR real-time methods as well as the qualitative composition of the cultivable microfungal community were used to characterize the microbial community. Changes in the morphological and chemical composition of urban soils included a shift in pH and increased C and N content compared with forest soil. Studies have shown that the biomass of microfungi and actinomycetes in urban soils was lower than in forest soils and equals 0.12–0.19 mg/g and 0.06–0.44?×?10^?3 mg/g, respectively. Bacterial biomass, on the contrary, increased in urban soils up to 2.6?×?10^–3 – 5.6?×?10^–3 mg/g. The number of ITS gene copies of fungi in urban soils varied from 5.0?×?10⁹ to 1.45?×?10¹⁰ copies/g of soil, reaching the highest values in the courtyard. The number of rRNA gene copies of bacteria and archaea in urban soils increased compared with forest soil and amounted to 2.37?×?10¹⁰ – 9.99?×?10¹⁰ and 0.4?×?10¹⁰ – 0.8?×?10¹⁰ copies/g of soil, respectively. In urban soils, morphological changes in microfungi, including the predominance of small spores, were revealed in comparison with forest soils, where mycelium prevailed. An increase in the diversity of microfungi in urban soil and changes in the structure of their communities compared with forest soil was noted. Microfungi found in urban soils are not typical of the background soils of the region and would be expected in more southern conditions. Among them, opportunistic fungi species have been identified in humans, which increases the risk of diseases in residents of the northern region.

     

Coalition-building and the forging of solidarity across difference and inequality

Diverse coalitions hold great potential for social movements, but they also face tremendous challenges. In this article, I review the literature on diverse alliances with a focus on how trust, commitment, and ultimately, solidarity can be developed and sustained across divides. The article begins by discussing the needs of diverse alliances to build trust and commitment, and the coalitional characteristics deemed vital for doing so, with a focus on shared neutral space, ongoing interaction, and social ties and bridgebuilders. Five coalitional processes and practices are identified and discussed that have been empirically found or theorized to be imperative for cultivating solidarity across difference and inequality. These processes include (a) uniting around shared principles while engaging difference; (b) acknowledging and managing inequalities; (c) making space for each other; (d) attention to managing conflicts; and (e) actions that confirm the shared commitments and negotiated identity. I conclude by evaluating the state of research on developing and sustaining alliances across divides.