Testing the Impact of the Whole-Day Good Behavior Game on Aggressive Behavior: Results of a Classroom-Based Randomized Effectiveness Trial.

Three generations of developmental epidemiologically based randomized field trials of the Good Behavior Game (GBG) have been delivered to Baltimore elementary schools. With the collaboration of family and community partners, all three trials were directed at decreasing proximal targets of aggressive behavior and improving learning in first-grade classrooms with distal mental health and substance abuse outcomes. GBG is a group-contingent classroom behavior management strategy that promotes classmate/peer concern for each child's positive behavior by rewarding teams with below-criterion levels of aggressive, disruptive behavior. GBG targets early risk factors for the above distal outcomes: aggressive, disruptive behavior, family/school relationships, and school failure. Here, we report on the third-generation randomized prevention trial of the GBG (whole-day first grade program (WD)), including 12 elementary schools. WD enhanced the standard curriculum in the areas of classroom behavior management; academic instruction, particularly reading; and family-classroom partnerships. Using a within-school classroom randomized trial design, we: 1) evaluate the effectiveness of the WD program by sex and cohort and 2) measure variation in WD impact by the quality of teachers' behavior management practices. Data from 961 first graders were used in general growth mixture modeling that accounts for classroom randomization to identify distinct developmental trajectories of aggressive, disruptive behavior and GBG impact on these trajectories. In the chronic high aggression trajectory of males, ratings of aggression after WD implementation and to the end of third grade were significantly lower in the WD condition than in controls in classrooms with a higher WD dosage (Cohort 2) and especially in classrooms with higher quality of WD implementation. For females, we found a modest but significant benefit of GBG in the low trajectory class when cohorts were combined. Regarding policy implications, embedding GBG into the curricula in teacher's colleges could better support student learning and behavior. Clinical Trials Registration number: NCT00257088.

Polygenic Score × Intervention Moderation: an Application of Discrete-Time Survival Analysis to Model the Timing of First Marijuana Use Among Urban Youth.

The present study examines the interaction between a polygenic score and an elementary school-based universal preventive intervention trial and its effects on a discrete-time survival analysis of time to first smoking marijuana. Research has suggested that initiation of substances is both genetically and environmentally driven (Rhee et al., Archives of general psychiatry 60:1256-1264, 2003; Verweij et al., Addiction 105:417-430, 2010). A previous work has found a significant interaction between the polygenic score and the same elementary school-based intervention with tobacco smoking (Musci et al., in press). The polygenic score reflects the contribution of multiple genes and has been shown in prior research to be predictive of smoking cessation, tobacco use, and marijuana use (Uhl et al., Molecular Psychiatry 19:50-54, 2014). Using data from a longitudinal preventive intervention study (N = 678), we examined age of first marijuana use from sixth grade to age 18. Genetic data were collected during emerging adulthood and were genotyped using the Affymetrix 6.0 microarray (N = 545). The polygenic score was computed using these data. Discrete-time survival analysis was employed to test for intervention main and interaction effects with the polygenic score. We found main effect of the polygenic score approaching significance, with the participants with higher polygenic scores reporting their first smoking marijuana at an age significantly later than controls (p = .050). We also found a significant intervention × polygenic score interaction effect at p = .003, with participants at the higher end of the polygenic score benefiting the most from the intervention in terms of delayed age of first use. These results suggest that genetics may play an important role in the age of first use of marijuana and that differences in genetics may account for the differential effectiveness of classroom-based interventions in delaying substance use experimentation.

Testing moderation in network meta-analysis with individual participant data.

Meta-analytic methods for combining data from multiple intervention trials are commonly used to estimate the effectiveness of an intervention. They can also be extended to study comparative effectiveness, testing which of several alternative interventions is expected to have the strongest effect. This often requires network meta-analysis (NMA), which combines trials involving direct comparison of two interventions within the same trial and indirect comparisons across trials. In this paper, we extend existing network methods for main effects to examining moderator effects, allowing for tests of whether intervention effects vary for different populations or when employed in different contexts. In addition, we study how the use of individual participant data may increase the sensitivity of NMA for detecting moderator effects, as compared with aggregate data NMA that employs study-level effect sizes in a meta-regression framework. A new NMA diagram is proposed. We also develop a generalized multilevel model for NMA that takes into account within-trial and between-trial heterogeneity and can include participant-level covariates. Within this framework, we present definitions of homogeneity and consistency across trials. A simulation study based on this model is used to assess effects on power to detect both main and moderator effects. Results show that power to detect moderation is substantially greater when applied to individual participant data as compared with study-level effects. We illustrate the use of this method by applying it to data from a classroom-based randomized study that involved two sub-trials, each comparing interventions that were contrasted with separate control groups. Copyright © 2016 John Wiley & Sons, Ltd.

Higher Childhood Peer Reports of Social Preference Mediates the Impact of the Good Behavior Game on Suicide Attempt.

The Good Behavior Game (GBG) is a universal classroom-based preventive intervention directed at reducing early aggressive, disruptive behavior and improving children's social adaptation into the classroom. The GBG is one of the few universal preventive interventions delivered in early elementary school that has been shown to reduce the risk for future suicide attempts. This paper addresses one potential mechanism by which the GBG lowers the risk of later suicide attempt. In this study, we tested whether the GBG, by facilitating social adaptation into the classroom early on, including the level of social preference by classmates, thereby lowers future risk of suicide attempts. The measure of social adaptation is based on first and second grade peer reports of social preference ("which children do you like best?"; "which children don't you like?"). As part of the hypothesized meditational model, we examined the longitudinal association between childhood peer social preference and the risk of future suicide attempt, which has not previously been examined. Data were from an epidemiologically based randomized prevention trial, which tested the GBG among two consecutive cohorts of first grade children in 19 public schools and 41 classrooms. Results indicated that peer social preference partially mediated the relationship between the GBG and the associated reduction of risk for later suicide attempts by adulthood, specifically among children characterized by their first grade teacher as highly aggressive, disruptive. These results suggest that positive childhood peer relations may partially explain the GBG-associated reduction of risk for suicide attempts and may be an important and malleable protective factor for future suicide attempt.

Polygenic score × intervention moderation: an application of discrete-time survival analysis to modeling the timing of first tobacco use among urban youth.

The present study examines the interaction between a polygenic score and an elementary school-based universal preventive intervention trial. The polygenic score reflects the contribution of multiple genes and has been shown in prior research to be predictive of smoking cessation and tobacco use (Uhl et al., 2014). Using data from a longitudinal preventive intervention study, we examined age of first tobacco use from sixth grade to age 18. Genetic data were collected during emerging adulthood and were genotyped using the Affymetrix 6.0 microarray. The polygenic score was computed using these data. Discrete-time survival analysis was employed to test for intervention main and interaction effects with the polygenic score. We found a main effect of the intervention, with the intervention participants reporting their first cigarette smoked at an age significantly later than controls. We also found an Intervention × Polygenic Score interaction, with participants at the higher end of the polygenic score benefitting the most from the intervention in terms of delayed age of first use. These results are consistent with Belsky and colleagues' (e.g., Belsky, Bakermans-Kranenburg, & van IJzendoorn, 2007; Belsky & Pleuss, 2009, 2013; Ellis, Boyce, Belsky, Bakermans-Kranenburg, & van IJzendoorn, 2011) differential susceptibility hypothesis and the concept of "for better or worse," wherein the expression of genetic variants are optimally realized in the context of an enriched environment, such as provided by a preventive intervention.

Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263 (navitoclax).

The anti-apoptotic protein MCL-1 is a key regulator of cancer cell survival and a known resistance factor for small-molecule BCL-2 family inhibitors such as ABT-263 (navitoclax), making it an attractive therapeutic target. However, directly inhibiting this target requires the disruption of high-affinity protein-protein interactions, and therefore designing small molecules potent enough to inhibit MCL-1 in cells has proven extremely challenging. Here, we describe a series of indole-2-carboxylic acids, exemplified by the compound A-1210477, that bind to MCL-1 selectively and with sufficient affinity to disrupt MCL-1-BIM complexes in living cells. A-1210477 induces the hallmarks of intrinsic apoptosis and demonstrates single agent killing of multiple myeloma and non-small cell lung cancer cell lines demonstrated to be MCL-1 dependent by BH3 profiling or siRNA rescue experiments. As predicted, A-1210477 synergizes with the BCL-2/BCL-XL inhibitor navitoclax to kill a variety of cancer cell lines. This work represents the first description of small-molecule MCL-1 inhibitors with sufficient potency to induce clear on-target cellular activity. It also demonstrates the utility of these molecules as chemical tools for dissecting the basic biology of MCL-1 and the promise of small-molecule MCL-1 inhibitors as potential therapeutics for the treatment of cancer.

Reducing aggression and impulsivity through school-based prevention programs: a gene by intervention interaction.

A variety of school-based, universal preventive interventions have been developed to address behavioral and mental health problems. Unfortunately, few have been evaluated within the context of randomized controlled trials with long-term follow-up. Even fewer still have examined the potential genetic factors that may drive differential impact of the intervention. In the present analysis, we examine the extent to which the longitudinal effects of two elementary school-based interventions were moderated by the brain-derived neurotrophic factor (BDNF) gene, which has been linked with aggression and impulsive behaviors. The sample included 678 urban, primarily African American children who were randomly assigned along with their teachers to one of three first grade classroom conditions: classroom-centered (CC) intervention, Family School Partnership (FSP), or a control condition. The teacher ratings of the youth's aggressive and impulsive behavior were obtained at baseline and in grades 6-12. Single-nucleotide polymorphisms (SNPs) from the BDNF gene were extracted from the genome-wide data. Longitudinal latent trait-state-error models indicated a significant interaction between a particular profile of the BDNF SNP cluster (46 % of sample) and CC intervention on impulsivity (ß = -.27, p < .05). A similar interaction was observed for the BDNF SNP cluster and the CC intervention on aggression (ß = -.14, p < .05). The results suggest that the impacts of preventive interventions in early elementary school on late adolescent outcomes of impulsivity and aggression can be potentially modified by genetic factors, such as BDNF. However, replication of these results is necessary before firm conclusions can be drawn.

The impact of the Good Behavior Game, a universal classroom-based preventive intervention in first and second grades, on high-risk sexual behaviors and drug abuse and dependence disorders into young adulthood.

The Good Behavior Game (GBG), a method of teacher classroom behavior management, was tested in first- and second-grade classrooms in 19 Baltimore City Public Schools beginning in the 1985-1986 school year. The intervention was directed at the classroom as a whole to socialize children to the student role and reduce aggressive, disruptive behaviors, confirmed antecedents of a profile of externalizing problem outcomes. This article reports on the GBG impact on the courses and interrelationships among aggressive, disruptive behavior through middle school, risky sexual behaviors, and drug abuse and dependence disorders through ages 19-21. In five poor to lower-middle class, mainly African American urban areas, classrooms within matched schools were assigned randomly to either the GBG intervention or the control condition. Balanced assignment of children to classrooms was made, and teachers were randomly assigned to intervention or control. Analyses involved multilevel growth mixture modeling. By young adulthood, significant GBG impact was found in terms of reduced high-risk sexual behaviors and drug abuse and dependence disorders among males who in first grade and through middle school were more aggressive, disruptive. A replication with the next cohort of first-grade children with the same teachers occurred during the following school year, but with minimal teacher mentoring and monitoring. Findings were not significant but generally in the predicted direction. A universal classroom-based prevention intervention in first- and second-grade classrooms can reduce drug abuse and dependence disorders and risky sexual behaviors.

A computational future for preventing HIV in minority communities: how advanced technology can improve implementation of effective programs.

African Americans and Hispanics in the United States have much higher rates of HIV than non-minorities. There is now strong evidence that a range of behavioral interventions are efficacious in reducing sexual risk behavior in these populations. Although a handful of these programs are just beginning to be disseminated widely, we still have not implemented effective programs to a level that would reduce the population incidence of HIV for minorities. We proposed that innovative approaches involving computational technologies be explored for their use in both developing new interventions and in supporting wide-scale implementation of effective behavioral interventions. Mobile technologies have a place in both of these activities. First, mobile technologies can be used in sensing contexts and interacting to the unique preferences and needs of individuals at times where intervention to reduce risk would be most impactful. Second, mobile technologies can be used to improve the delivery of interventions by facilitators and their agencies. Systems science methods including social network analysis, agent-based models, computational linguistics, intelligent data analysis, and systems and software engineering all have strategic roles that can bring about advances in HIV prevention in minority communities. Using an existing mobile technology for depression and 3 effective HIV prevention programs, we illustrated how 8 areas in the intervention/implementation process can use innovative computational approaches to advance intervention adoption, fidelity, and sustainability.

Partnerships for the design, conduct, and analysis of effectiveness, and implementation research: experiences of the prevention science and methodology group.

What progress prevention research has made comes through strategic partnerships with communities and institutions that host this research, as well as professional and practice networks that facilitate the diffusion of knowledge about prevention. We discuss partnership issues related to the design, analysis, and implementation of prevention research and especially how rigorous designs, including random assignment, get resolved through a partnership between community stakeholders, institutions, and researchers. These partnerships shape not only study design, but they determine the data that can be collected and how results and new methods are disseminated. We also examine a second type of partnership to improve the implementation of effective prevention programs into practice. We draw on social networks to studying partnership formation and function. The experience of the Prevention Science and Methodology Group, which itself is a networked partnership between scientists and methodologists, is highlighted.

The effect of two elementary school-based prevention interventions on being offered tobacco and the transition to smoking.

AIMS: This study sought to more precisely delineate the mechanisms by which two early elementary school-based, universal (i.e., applied to the entire population regardless of risk status) preventive interventions increased survival to first tobacco cigarette smoked. Specifically, we examined whether the interventions' effect on survival to first use was via the reduction of offers to smoke and/or through preventing the transition from first offer to smoking. METHODS: A total of 678 urban first-graders were assigned randomly to the classroom-centered (CC), or the family-school partnership (FSP), or a control classroom condition. Youth were followed annually until 1 year beyond their anticipated high school graduation (mean age ∼18 years). Discrete-time survival analyses on 628 youth evaluated the impact of the CC and FSP interventions on first tobacco offer and initial tobacco smoking once offered. FINDINGS: The risk of being offered tobacco was reduced among both CC and FSP intervention groups relative to the control group, although the reduction was only statistically significant for the CC intervention. Neither intervention condition reduced the transition to smoking once offered tobacco to smoke. CONCLUSION: The CC intervention appeared to have its effect on survival to first cigarette smoked by delaying the first offer to smoke. Preventive interventions focused on refusal skills during the middle school years may be necessary to reduce the likelihood of the transition to smoking once offered.

The good behavior game and the future of prevention and treatment.

The Good Behavior Game (GBG), a universal classroom behavior management method, was tested in first- and second-grade classrooms in Baltimore beginning in the 1985-1986 school year. Followup at ages 19-21 found significantly lower rates of drug and alcohol use disorders, regular smoking, antisocial personality disorder, delinquency and incarceration for violent crimes, suicide ideation, and use of school-based services among students who had played the GBG. Several replications with shorter followup periods have provided similar early results. We discuss the role of the GBG and possibly other universal prevention programs in the design of more effective systems for promoting children's development and problem prevention and treatment services.

Depressed mood and the effect of two universal first grade preventive interventions on survival to the first tobacco cigarette smoked among urban youth.

INTRODUCTION: As part of an evaluation of two first-grade, universal preventive interventions whose proximal targets were early learning and behavior, we investigated the influence of depressed mood, the interventions, and their interaction on survival to the first tobacco cigarette smoked through age 19. One intervention focused on improving teacher behavior management and instructional skills (Classroom-Centered, CC) as a means of improving student behavior and learning and the other on the family-school partnership (FSP). Variation in the relationship between depressed mood and first cigarette smoked by gender and grade was also examined. METHODS: Self-reports of smoking behavior and depressed mood were collected on an annual basis from grade 6 through age 19. The present analyses were restricted to the 563 youth who had never smoked by grade 6, or 83% of the original sample of first grade participants. Discrete-time survival analysis was used to examine the effects of depressed mood and the interventions on survival to the first tobacco cigarette smoked. RESULTS: Depressed mood was associated with reduced survival time to the first cigarette smoked (adjusted hazard ratio, aHR: 1.4; 95% CI: 1.1-1.9), whereas the CC intervention prolonged survival time (aHR: 0.8; 95% CI: 0.7-0.9). No significant variation in the effect of depressed mood on survival was found by gender or grade, nor was the effect of the CC intervention moderated by depressed mood. CONCLUSIONS: Strategies to prevent tobacco cigarette smoking should include both a focus on depressed mood in adolescence as well as on early success in elementary school.

Longitudinal Impact of Two Universal Preventive Interventions in First Grade on Educational Outcomes in High School.

This study examined the longitudinal effects of 2 first-grade universal preventive interventions on academic outcomes (e.g., achievement, special education service use, graduation, postsecondary education) through age 19 in a sample of 678 urban, primarily African American children. The classroom-centered intervention combined the Good Behavior Game (H. H. Barrish, Saunders, & Wolfe, 1969) with an enhanced academic curriculum, whereas a second intervention, the Family-School Partnership, focused on promoting parental involvement in educational activities and bolstering parents' behavior management strategies. Both programs aimed to address the proximal targets of aggressive behavior and poor academic achievement. Although the effects varied by gender, the classroom-centered intervention was associated with higher scores on standardized achievement tests, greater odds of high school graduation and college attendance, and reduced odds of special education service use. The intervention effects of the Family-School Partnership were in the expected direction; however, only 1 effect reached statistical significance. The findings of this randomized controlled trial illustrate the long-term educational impact of preventive interventions in early elementary school.

Effects of a universal classroom behavior management program in first and second grades on young adult behavioral, psychiatric, and social outcomes.

BACKGROUND: The Good Behavior Game (GBG), a method of classroom behavior management used by teachers, was tested in first- and second-grade classrooms in 19 Baltimore City Public Schools beginning in the 1985-1986 school year. The intervention was directed at the classroom as a whole to socialize children to the student role and reduce aggressive, disruptive behaviors, confirmed antecedents of later substance abuse and dependence disorders, smoking, and antisocial personality disorder. This article reports on impact to ages 19-21. METHODS: In five poor to lower-middle class, mainly African American urban areas, three or four schools were matched and within each set randomly assigned to one of three conditions: (1) GBG, (2) a curriculum-and-instruction program directed at reading achievement, or (3) the standard program. Balanced assignment of children to classrooms was made, and then, within intervention schools, classrooms and teachers were randomly assigned to intervention or control. RESULTS: By young adulthood significant impact was found among males, particularly those in first grade who were more aggressive, disruptive, in reduced drug and alcohol abuse/dependence disorders, regular smoking, and antisocial personality disorder. These results underline the value of a first-grade universal prevention intervention. REPLICATION: A replication was implemented with the next cohort of first-grade children with the same teachers during the following school year, but with diminished mentoring and monitoring of teachers. The results showed significant GBG impact for males on drug abuse/dependence disorders with some variation. For other outcomes the effects were generally smaller but in the predicted direction.

The impact of two universal randomized first- and second-grade classroom interventions on young adult suicide ideation and attempts.

OBJECTIVE: This paper reports the impact of two first- and second-grade classroom based universal preventive interventions on the risk of Suicide Ideation (SI) and Suicide Attempts (SA) by young adulthood. The Good Behavior Game (GBG) was directed at socializing children for the student role and reducing aggressive, disruptive behavior. Mastery Learning (ML) was aimed at improving academic achievement. Both were implemented by the teacher. METHODS: The design was epidemiologically based, with randomization at the school and classroom levels and balancing of children across classrooms. The trial involved a cohort of first-grade children in 19 schools and 41 classrooms with intervention at first and second grades. A replication was implemented with the next cohort of first grade children with the same teachers but with little mentoring or monitoring. RESULTS: In the first cohort, there was consistent and robust GBG-associated reduction of risk for suicide ideation by age 19-21 years compared to youths in standard setting (control) classrooms regardless of any type of covariate adjustment. A GBG-associated reduced risk for suicide attempt was found, though in some covariate-adjusted models the effect was not statistically robust. No statistically significant impact on these outcomes was found for ML. The impact of the GBG on suicide ideation and attempts was greatly reduced in the replication trial involving the second cohort. CONCLUSIONS: A universal preventive intervention directed at socializing children and classroom behavior management to reduce aggressive, disruptive behavior may delay or prevent onset of suicide ideation and attempts. The GBG must be implemented with precision and continuing support of teachers.

Impact of the Good Behavior Game, a universal classroom-based behavior intervention, on young adult service use for problems with emotions, behavior, or drugs or alcohol.

BACKGROUND: The Good Behavior Game (GBG) is a classroom behavior management strategy focused on socializing children to the role of student and aimed at reducing early aggressive, disruptive behavior, a confirmed antecedent to service use. The GBG was tested in a randomized field trial in 19 elementary schools with two cohorts of children as they attended first and second grades. This article reports on the impact of the GBG on service use through young adulthood. METHODS: Three or four schools in each of five urban areas were matched and randomly assigned to one of three conditions: (1) GBG, (2) an intervention aimed at academic achievement, or (3) the standard program of the school system. Children were assigned to classrooms to ensure balance, and teachers and classrooms were randomly assigned to intervention conditions. RESULTS: This study provides evidence of a positive impact of a universal preventive intervention on later service use by males, although not by females, for problems with emotions, behavior, or drugs or alcohol. For both cohorts, males in GBG classrooms who had been rated as highly aggressive, disruptive by their teachers in the fall of first grade had a lower rate of school-based service use than their counterparts in control classrooms. REPLICATION: The design employed two cohorts of students. Although both first- and second-grade teachers received less training and support with the second cohorts of students than with the first cohort, the impact of GBG was similar across both cohorts.

Developmental epidemiological courses leading to antisocial personality disorder and violent and criminal behavior: effects by young adulthood of a universal preventive intervention in first- and second-grade classrooms.

BACKGROUND: Antisocial personality disorder (ASPD), violent and criminal behavior, and drug abuse disorders share the common antecedent of early aggressive, disruptive behavior. In the 1985-1986 school year teachers implemented the Good Behavior Game (GBG), a classroom behavior management strategy targeting aggressive, disruptive behavior and socializing children to the student role. From first through seventh grade the developmental trajectories of 2311 students from 19 Baltimore City Public Schools were examined. We report the GBG impact on these trajectories and ASPD and violent and criminal behavior by age 19-21. METHODS: In five urban, poor to lower middle class predominately African-American areas, three to four schools were matched and within each set randomly assigned to one of three conditions: (1) GBG, (2) a reading achievement program, or (3) the standard program. Classrooms and teachers were randomly assigned to intervention or control. Measures at 19-21 included self reports and juvenile court and adult incarceration records. GBG impact was assessed via General Growth Mixture Modeling based on repeated measures of aggressive, disruptive behavior. RESULTS: Three trajectories of aggressive, disruptive behavior were identified. By young adulthood, GBG significantly reduced the rates of ASPD and violent and criminal behavior among males in the persistent high aggressive, disruptive trajectory. REPLICATION: A replication was implemented with the following cohort of first-grade children using the same teachers, but with diminished mentoring and monitoring. Beneficial impact was found among persistent high males through seventh grade. By young adulthood GBG effects on ASPD and violent and criminal behavior were non-significant, but generally in the hypothesized direction.