The Impact of Old Age Pension Eligibility on Alcohol Consumption: Evidence From a Population-Based Study in Rural South Africa.

Background and Objectives: Alcohol causes more than 3 million deaths a year globally and contributes to over 5% of global disease and injury. Heavy drinking and alcohol use disorders among older adults have increased in the last 10-15 years. For individuals living in low-income countries, where wages are low and unemployment is high, old age pensions may provide a significant increase in household income. In turn, the receipt of supplementary income may increase spending on alcohol. Earlier life factors and socioeconomic status may affect alcohol consumption, making it difficult to directly assess the impact of income on alcohol consumption. This study reduces the potential for endogeneity with other life factors by exploiting an exogenous increase in income from old age pensions to isolate the impact of extra income on alcohol consumption for older adults. Research Design and Methods: We used a regression discontinuity design to assess changes in drinking patterns among rural, low-income adults who were 3 years below and 3 years above South Africa's Old Age Pension Grant eligibility threshold (age 60). We assessed this relationship separately by gender and for employed and unemployed individuals. Results: We observed a significantly increased alcohol use associated with the Old Age Pension Grant eligibility for employed men (ß = 4.57, 95% confidence interval: 1.72-12.14). We did not observe this same trend for unemployed men or for women. Discussion and Implications: The analysis in this study indicates that increased income from reaching the pension eligibility age may contribute to an increase in alcohol consumption for employed men. Interventions, such as informational campaigns on the risks of alcohol consumption for older adults or age-appropriate health interventions to help individuals reduce alcohol consumption, targeted around the time of pension eligibility age for employed men may help to reduce alcohol-related harms in low-income, rural sub-Saharan African settings.

Child support grant expansion and cognitive function among women in rural South Africa: Findings from a natural experiment in the HAALSI cohort.

BACKGROUND: Cash transfers are a promising but understudied intervention that may protect cognitive function in adults. Although South Africa has a rapidly ageing population, little is known about the nature of association between cash transfers and cognitive function in this setting. OBJECTIVES: We leveraged age-eligibility expansions to South Africa's Child Support Grant (CSG) to investigate the association between duration of CSG eligibility and cognitive function of biological mothers of child beneficiaries in South Africa. METHODS: We analysed 2014/2015 baseline data from 944 women, aged 40-59 years with at least one CSG-eligible child, enrolled in the population-representative HAALSI cohort in Agincourt, South Africa. Duration of CSG eligibility for each mother was calculated based on the birth dates of all their children and the CSG age-eligibility expansion years (2003-2012). Cognitive function was measured using a cognitive battery administered at the HAALSI baseline interview. Linear regression was used to estimate the association between duration of CSG eligibility, dichotomized as low (≤10 years) and high (>10 years) eligibility, and cognitive function z-scores of the mothers. RESULTS: High vs. low duration of CSG eligibility, was associated with higher cognitive function z-scores in the full sample [ß: 0.15 SD units; 95% CI: 0.04, 0.26; p-value = 0.01]. In mothers with one to four lifetime children, but not five or more, high vs. low duration of CSG eligibility, was associated with higher cognitive function z-scores [ß: 0.19 SD units; 95% CI: 0.05, 0.34, p-value = 0.02]. CONCLUSION: Government cash transfers given to support raising children may confer substantial protective effects on the subsequent cognitive function of mothers. Further studies are needed to understand how parity may influence this relationship. Our findings bring evidence to policymakers for designing income supplementation programmes to promote healthy cognitive ageing in low-income settings.

Disease awareness and healthcare utilization in rural South Africa: a comparative analysis of HIV and diabetes in the HAALSI cohort.

BACKGROUND: Studies from rural South Africa indicate that people living with HIV (PLHIV) may have better health outcomes than those without, potentially due to the frequent healthcare visits necessitated by infection. Here, we examined the association between HIV status and healthcare utilization, using diabetes as an illustrative comparator of another high-burden, healthcare-intensive disease. METHODS: Our exposure of interest was awareness of positive disease status for both HIV and diabetes. We identified 742 individuals who were HIV-positive and aware of their status and 305 who had diabetes and were aware of their status. HIV-positive status was further grouped by viral suppression. For each disease, we estimated the association with (1) other comorbid, chronic conditions, (2) health facility visits, (3) household-level healthcare expenditure, and (4) per-visit healthcare expenditure. We used log-binomial regression models to estimate prevalence ratios for co-morbid chronic conditions. Linear regression models were used for all other outcomes. RESULTS: Virally suppressed PLHIV had decreased prevalence of chronic conditions, increased public clinic visits [ß = 0.59, 95% CI: 0.5, 0.7], and reduced per-visit private clinic spending [ß = -60, 95% CI: -83, -6] compared to those without HIV. No differences were observed in hospitalizations and per-visit spending at hospitals and public clinics between virally suppressed PLHIV and non-PLHIV. Conversely, diabetic individuals had increased prevalence of chronic conditions, increased visits across facility types, increased household-level expenditures (ß = 88 R, 95% CI: 29, 154), per-visit hospital spending (ß = 54 R, 95% CI: 7, 155), and per-visit public clinic spending (ß = 31 R, 95% CI: 2, 74) compared to those without diabetes. CONCLUSIONS: Our results suggest that older adult PLHIV may visit public clinics more often than their HIV-negative counterparts but spend similarly on a per-visit basis. This provides preliminary evidence that the positive health outcomes observed among PLHIV in rural South Africa may be explained by different healthcare engagement patterns. Through our illustrative comparison between PLHIV and diabetics, we show that shifting disease burdens towards chronic and historically underfunded diseases, like diabetes, may be changing the landscape of health expenditure inequities.

Child Support Grant expansion and cognitive function among women in rural South Africa: findings from a natural experiment in HAALSI cohort.

Cash transfers are a promising but understudied intervention that may protect cognitive function in adults by promoting their cognitive reserve. South Africa has a rapidly ageing population, however, less is known about the nature of association between cash transfers and cognitive function in this setting. We leveraged natural experiments from Child Support Grant (CSG) age-eligibility expansions to investigate the association between duration of CSG eligibility and cognitive function among biological mothers of child beneficiaries in South Africa. We analysed 2014/2015 baseline data from 944 women, aged 40 - 59 years with at least one CSG-eligible child, enrolled in the HAALSI cohort in Agincourt, South Africa. Duration of CSG eligibility for each mother was calculated based on the birth dates of all their children and the CSG age eligibility expansion years. Cognitive function was measured using a cognitive battery administered to the mothers at baseline interview. Linear regression was used to estimate the association between duration of CSG eligibility, dichotomized as low (≤10 years) and high (>10 years) eligibility, and cognitive function z-scores of the mothers. Our study finds that high duration of CSG eligibility, compared to low, was associated with higher cognitive function z-scores in the full sample [ß: 0.15 SD; 95% CI: 0.04, 0.26; p-value = 0.01]. In mothers with one to four lifetime children, but not five or more, high duration of CSG eligibility, compared to low, was associated with higher cognitive function z-scores [ß: 0.19 SD; 95% CI: 0.05, 0.34, p-value = 0.02]. Government cash transfers given to support raising children may confer substantial protective effect on cognitive function of mothers in their mid-life. Further studies are needed to understand how parity may influence this relationship. Our findings bring evidence to policymakers for designing income supplementation programmes to promote healthy cognitive ageing in low-income settings.

Outcome of the AVID College Preparatory Program on Adolescent Health: A Randomized Trial.

BACKGROUND AND OBJECTIVES: Academic tracking is a widespread practice, separating students by prior academic performance. Clustering lower performing students together may unintentionally reinforce risky peer social networks, school disengagement, and risky behaviors. If so, mixing lower performing with high performing youth ("untracking") may be protective, leading to better adolescent health. METHODS: Advancement via Individual Determination (AVID), a nationally-disseminated college preparatory program, supports placing middle-performing students in rigorous college-preparatory classes alongside high-performing peers. We conducted the first randomized, controlled trial of AVID in the United States, randomizing 270 students within 5 large public high schools to receive AVID (AVID group) versus usual school programming (control group). Participants completed surveys at the transition to high school (end of eighth grade/ beginning of ninth grade) and the end of ninth grade. Intent-to-treat analyses tested whether AVID resulted in healthier social networks (primary outcome), health behaviors, and psychosocial wellbeing. RESULTS: At follow-up, AVID students had lower odds of using any substance (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.48-0.89) and associating with a substance-using peer (OR 0.74, 95% CI 0.45-0.98), and higher odds of associating with a peer engaged in school (OR 1.73, 95% CI 1.11-2.70). Male AVID students had lower stress and higher self-efficacy, grit, and school engagement than control students (P < .05 for all). No adverse health effects among high-performing peers were observed. CONCLUSIONS: AVID positively impacts social networks, health behaviors, and psychosocial outcomes suggesting academic untracking may have substantial beneficial spillover effects on adolescent health.

Associations between Cortical Thickness and Metamemory in Alzheimer's Disease.

Metacognitive deficits affect Alzheimer's disease (AD) patient safety and increase caregiver burden. The brain areas that support metacognition are not well understood. 112 participants from the Imaging and Genetic Biomarkers for AD (ImaGene) study underwent comprehensive cognitive testing and brain magnetic resonance imaging. A performance-prediction paradigm was used to evaluate metacognitive abilities for California Verbal Learning Test-II learning (CVLT-II 1-5) and delayed recall (CVLT-II DR); Visual Reproduction-I immediate recall (VR-I Copy) and Visual Reproduction-II delayed recall (VR-II DR); Rey-Osterrieth Complex Figure Copy (Rey-O Copy) and delayed recall (Rey-O DR). Vertex-wise multivariable regression of cortical thickness was performed using metacognitive scores as predictors while controlling for age, sex, education, and intracranial volume. Subjects who overestimated CVLT-II DR in prediction showed cortical atrophy, most pronounced in the bilateral temporal and left greater than right (L > R) frontal cortices. Overestimation of CVLT-II 1-5 prediction and DR performance in postdiction showed L > R associations with medial, inferior and lateral temporal and left posterior cingulate cortical atrophy. Overconfident prediction of VR-I Copy performance was associated with right greater than left medial, inferior and lateral temporal, lateral parietal, anterior and posterior cingulate and lateral frontal cortical atrophy. Underestimation of Rey-O Copy performance in prediction was associated with atrophy localizing to the temporal and cingulate areas, and in postdiction, with diffuse cortical atrophy. Impaired metacognition was associated to cortical atrophy. Our results indicate that poor insight into one's cognitive abilities is a pervasive neurodegenerative feature associated with AD across the cognitive spectrum.

Acceptability of an mHealth App for Youth With Substance Use and Mental Health Needs: Iterative, Mixed Methods Design.

BACKGROUND: Treating substance use disorders (SUDs) during adolescence can prevent adult addiction and improve youth outcomes. However, it can be challenging to keep adolescents with SUDs engaged in ongoing services, thus limiting potential benefits. Developmentally appropriate tools are needed to improve treatment engagement during and between sessions for youth with SUDs and mental health disorders. Mobile health apps may augment or replace psychotherapy components; however, few have been developed specifically for youth with SUDs following user-guided design principles, which may limit their appropriateness and utility. Formative research on acceptability to intended end users is needed before the efficacy of such tools can be examined. OBJECTIVE: This study involves user-centered, iterative development and initial user testing of a web-based app for adolescents with SUDs and mental health concerns. METHODS: Adolescents aged 14 to 17 years with past-year involvement in outpatient psychotherapy and behavioral health clinicians with adolescent SUD treatment caseloads were recruited. Across 2 assessment phases, 40 participants (alpha: 10 youths and 10 clinicians; beta: 10 youths and 10 clinicians) viewed an app demonstration and completed semistructured interviews and questionnaires about app content and functionality. RESULTS: Participants expressed positive impressions of the app and its potential utility in augmenting outpatient therapy for youth with SUDs and mental health concerns. Noted strengths included valuable educational content, useful embedded resources, and a variety of activities. Adolescents and clinicians favored the app over conventional (paper-and-pencil) modalities, citing convenience and familiarity. The app was found to be user-friendly and likely to improve treatment engagement. Adolescents suggested the inclusion of privacy settings, and clinicians recommended more detailed instructions and simplified language. CONCLUSIONS: The novel app developed here appears to be a promising, acceptable, and highly scalable resource to support adolescents with SUDs and mental health concerns. Future studies should test the efficacy of such apps in enhancing adolescent behavioral health treatment engagement and outcomes.

Peer review reduces spin in PCORI research reports.

BACKGROUND: The Patient-Centered Outcomes Research Institute (PCORI) is obligated to peer review and to post publicly "Final Research Reports" of all funded projects. PCORI peer review emphasizes adherence to PCORI's Methodology Standards and principles of ethical scientific communication. During the peer review process, reviewers and editors seek to ensure that results are presented objectively and interpreted appropriately, e.g., free of spin. METHODS: Two independent raters assessed PCORI peer review feedback sent to authors. We calculated the proportion of reports in which spin was identified during peer review, and the types of spin identified. We included reports submitted by April 2018 with at least one associated journal article. The same raters then assessed whether authors addressed reviewers' comments about spin. The raters also assessed whether spin identified during PCORI peer review was present in related journal articles. RESULTS: We included 64 PCORI-funded projects. Peer reviewers or editors identified spin in 55/64 (86%) submitted research reports. Types of spin included reporting bias (46/55; 84%), inappropriate interpretation (40/55; 73%), inappropriate extrapolation of results (15/55; 27%), and inappropriate attribution of causality (5/55; 9%). Authors addressed comments about spin related to 47/55 (85%) of the reports. Of 110 associated journal articles, PCORI comments about spin were potentially applicable to 44/110 (40%) articles, of which 27/44 (61%) contained the same spin that was identified in the PCORI research report. The proportion of articles with spin was similar for articles accepted before and after PCORI peer review (63% vs 58%). DISCUSSION: Just as spin is common in journal articles and press releases, we found that most reports submitted to PCORI included spin. While most spin was mitigated during the funder's peer review process, we found no evidence that review of PCORI reports influenced spin in journal articles. Funders could explore interventions aimed at reducing spin in published articles of studies they support.

Neurodegenerative changes in early- and late-onset cognitive impairment with and without brain amyloidosis.

BACKGROUND: A substantial number of patients clinically diagnosed with Alzheimer's disease do not harbor amyloid pathology. We analyzed the presence and extent of tau deposition and neurodegeneration in amyloid-positive (AD) and amyloid-negative (nonAD) ADNI subjects while also taking into account age of onset (< or > 65 years) as we expected that the emerging patterns could vary by age and presence or absence of brain amyloidosis. METHODS: One hundred and ten early-onset AD (EOAD), 121 EOnonAD, 364 late-onset AD (LOAD), and 175 LOnonAD mild cognitive impairment (MCI) and dementia (DEM) subjects were compared to 291 ADNI amyloid-negative control subjects using voxel-wise regression in SPM12 with cluster-level family-wise error correction at pFWE < 0.05). A subset of these subjects also received 18F-flortaucipir scans and allowed for analysis of global tau burden. RESULTS: As expected, relative to LOAD, EOAD subjects showed more extensive neurodegeneration and tau deposition in AD-relevant regions. EOnonADMCI showed no significant neurodegeneration, while EOnonADDEM showed bilateral medial and lateral temporal, and temporoparietal hypometabolism. LOnonADMCI and LOnonADDEM showed diffuse brain atrophy and a fronto-temporo-parietal hypometabolic pattern. LOnonAD and EOnonAD subjects failed to show significant tau binding. CONCLUSIONS: LOnonAD subjects show a fronto-temporal neurodegenerative pattern in the absence of tau binding, which may represent underlying hippocampal sclerosis with TDP-43, also known as limbic-predominant age-related TDP-43 encephalopathy (LATE). The hypometabolic pattern observed in EOnonADDEM seems similar to the one observed in EOADMCI. Further investigation into the underlying etiology of EOnonAD is warranted.

ZMIZ1 Variants Cause a Syndromic Neurodevelopmental Disorder.

ZMIZ1 is a coactivator of several transcription factors, including p53, the androgen receptor, and NOTCH1. Here, we report 19 subjects with intellectual disability and developmental delay carrying variants in ZMIZ1. The associated features include growth failure, feeding difficulties, microcephaly, facial dysmorphism, and various other congenital malformations. Of these 19, 14 unrelated subjects carried de novo heterozygous single-nucleotide variants (SNVs) or single-base insertions/deletions, 3 siblings harbored a heterozygous single-base insertion, and 2 subjects had a balanced translocation disrupting ZMIZ1 or involving a regulatory region of ZMIZ1. In total, we identified 13 point mutations that affect key protein regions, including a SUMO acceptor site, a central disordered alanine-rich motif, a proline-rich domain, and a transactivation domain. All identified variants were absent from all available exome and genome databases. In vitro, ZMIZ1 showed impaired coactivation of the androgen receptor. In vivo, overexpression of ZMIZ1 mutant alleles in developing mouse brains using in utero electroporation resulted in abnormal pyramidal neuron morphology, polarization, and positioning, underscoring the importance of ZMIZ1 in neural development and supporting mutations in ZMIZ1 as the cause of a rare neurodevelopmental syndrome.

Neurodegenerative Patterns of Cognitive Clusters of Early-Onset Alzheimer's Disease Subjects: Evidence for Disease Heterogeneity.

BACKGROUND/AIMS: Alzheimer's disease (AD) with onset before 65 (early-onset AD [EOAD]) occurs in approximately 6% of cases and can affect nonmemory domains. Here, we analyze patterns of impairment in amnestic EOAD individuals using data-driven statistical analyses. METHODS: Cognitive data of 146 EOAD subjects were Z-normalized to 395 cognitively normal (CN) individuals. Domain-averaged Z-scores were adjusted for age, sex, and education followed by Wald cluster analysis of residuals. Magnetic resonance imaging and positron emission tomography comparisons of EOAD clusters to age-matched CN were done using Statistic Parametric Mapping 8. Cluster-level-family-wise error (p < 0.05) correction was applied. Mixed-effect models were used to compute longitudinal change across clusters. RESULTS: Scree plot using the pseudo-T-squared suggested a 4-cluster solution. Cluster 1 (memory-predominant impairment) showed atrophy/hypometabolism in medial/lateral temporal, lateral parietal, and posterior cingulate regions. Cluster 2 (memory/visuospatial-predominant) showed atrophy/hypometabolism of medial temporal, temporoparietal, and frontal cortices. Cluster 3 (memory, language, and executive function) and Cluster 4 (globally impaired) manifested atrophy and hypometabolism throughout the brain. Longitudinally between-cluster differences in the visuospatial and language/executive domains were significant, suggesting phenotypic variation. CONCLUSION: We observed significant heterogeneity in cognitive presentation among amnestic EOAD subjects and patterns of atrophy/hypometabolism in each cluster in agreement with the observed cognitive phenotype.

Associations of the Top 20 Alzheimer Disease Risk Variants With Brain Amyloidosis.

Importance: Late-onset Alzheimer disease (AD) is highly heritable. Genome-wide association studies have identified more than 20 AD risk genes. The precise mechanism through which many of these genes are associated with AD remains unknown. Objective: To investigate the association of the top 20 AD risk variants with brain amyloidosis. Design, Setting, and Participants: This study analyzed the genetic and florbetapir F 18 data from 322 cognitively normal control individuals, 496 individuals with mild cognitive impairment, and 159 individuals with AD dementia who had genome-wide association studies and 18F-florbetapir positron emission tomographic data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a prospective, observational, multisite tertiary center clinical and biomarker study. This ongoing study began in 2005. Main Outcomes and Measures: The study tested the association of AD risk allele carrier status (exposure) with florbetapir mean standard uptake value ratio (outcome) using stepwise multivariable linear regression while controlling for age, sex, and apolipoprotein E ε4 genotype. The study also reports on an exploratory 3-dimensional stepwise regression model using an unbiased voxelwise approach in Statistical Parametric Mapping 8 with cluster and significance thresholds at 50 voxels and uncorrected P < .01. Results: This study included 977 participants (mean [SD] age, 74 [7.5] years; 535 [54.8%] male and 442 [45.2%] female) from the ADNI-1, ADNI-2, and ADNI-Grand Opportunity. The adenosine triphosphate-binding cassette subfamily A member 7 (ABCA7) gene had the strongest association with amyloid deposition (χ2 = 8.38, false discovery rate-corrected P < .001), after apolioprotein E ε4. Significant associations were found between ABCA7 in the asymptomatic and early symptomatic disease stages, suggesting an association with rapid amyloid accumulation. The fermitin family homolog 2 (FERMT2) gene had a stage-dependent association with brain amyloidosis (FERMT2 × diagnosis χ2 = 3.53, false discovery rate-corrected P = .05), which was most pronounced in the mild cognitive impairment stage. Conclusions and Relevance: This study found an association of several AD risk variants with brain amyloidosis. The data also suggest that AD genes might differentially regulate AD pathologic findings across the disease stages.

Missense Variants in RHOBTB2 Cause a Developmental and Epileptic Encephalopathy in Humans, and Altered Levels Cause Neurological Defects in Drosophila.

Although the role of typical Rho GTPases and other Rho-linked proteins in synaptic plasticity and cognitive function and dysfunction is widely acknowledged, the role of atypical Rho GTPases (such as RHOBTB2) in neurodevelopment has barely been characterized. We have now identified de novo missense variants clustering in the BTB-domain-encoding region of RHOBTB2 in ten individuals with a similar phenotype, including early-onset epilepsy, severe intellectual disability, postnatal microcephaly, and movement disorders. Three of the variants were recurrent. Upon transfection of HEK293 cells, we found that mutant RHOBTB2 was more abundant than the wild-type, most likely because of impaired degradation in the proteasome. Similarly, elevated amounts of the Drosophila ortholog RhoBTB in vivo were associated with seizure susceptibility and severe locomotor defects. Knockdown of RhoBTB in the Drosophila dendritic arborization neurons resulted in a decreased number of dendrites, thus suggesting a role of RhoBTB in dendritic development. We have established missense variants in the BTB-domain-encoding region of RHOBTB2 as causative for a developmental and epileptic encephalopathy and have elucidated the role of atypical Rho GTPase RhoBTB in Drosophila neurological function and possibly dendrite development.

The effect of the top 20 Alzheimer disease risk genes on gray-matter density and FDG PET brain metabolism.

INTRODUCTION: We analyzed the effects of the top 20 Alzheimer disease (AD) risk genes on gray-matter density (GMD) and metabolism. METHODS: We ran stepwise linear regression analysis using posterior cingulate hypometabolism and medial temporal GMD as outcomes and all risk variants as predictors while controlling for age, gender, and APOE ε4 genotype. We explored the results in 3D using Statistical Parametric Mapping 8. RESULTS: Significant predictors of brain GMD were SLC24A4/RIN3 in the pooled and mild cognitive impairment (MCI); ZCWPW1 in the MCI; and ABCA7, EPHA1, and INPP5D in the AD groups. Significant predictors of hypometabolism were EPHA1 in the pooled, and SLC24A4/RIN3, NME8, and CD2AP in the normal control group. DISCUSSION: Multiple variants showed associations with GMD and brain metabolism. For most genes, the effects were limited to specific stages of the cognitive continuum, indicating that the genetic influences on brain metabolism and GMD in AD are complex and stage dependent.

Using Research to Improve College Readiness: A Research Partnership Between the Los Angeles Unified School District and the Los Angeles Education Research Institute.

The Los Angeles Unified School District (LAUSD) serves a large majority of socioeconomically disadvantaged students who are struggling academically and are underprepared for high school graduation and college. This article describes the partnership between LAUSD and the Los Angeles Education Research Institute, and how this collaboration endeavors to produce accessible and high-quality research to inform pressing problems of practice. The article also presents findings from an ongoing partnership research project analyzing a district policy focused on improving college readiness by aligning high school graduation and college-eligibility requirements. In a cohort that went through high school before the policy became mandatory for all students, less than 1/5 of all students (and 30% of graduates) met the college eligibility criteria. Our findings indicate that academic and behavioral indicators from 8th and 9th grade can help identify for possible intervention students who are not on track to meet these new graduation requirements.

Some ways in which neighborhoods, nuclear families, friendship groups, and schools jointly affect changes in early adolescent development.

This study assessed some ways in which schools, neighborhoods, nuclear families, and friendship groups jointly contribute to positive change during early adolescence. For each context, existing theory was used to develop a multiattribute index that should promote successful development. Descriptive analyses showed that the four resulting context indices were only modestly intercorrelated at the individual student level (N = 12,398), but clustered more tightly at the school and neighborhood levels (N = 23 and 151 respectively). Only for aggregated units did knowing the developmental capacity of any one context strongly predict the corresponding capacity of the other contexts. Analyses also revealed that each context facilitated individual change in a success index that tapped into student academic performance, mental health, and social behavior. However, individual context effects were only modest in size over the 19 months studied and did not vary much by context. The joint influence of all four contexts was cumulatively large, however, and because it was generally additive in form, no constellation of contexts was identified whose total effect reliably surpassed the sum of its individual context main effects. These results suggest that achieving significant population changes in multidimensional student growth during early adolescence most likely requires both theory and interventions that are explicitly pan-contextual.