Alterations in EGFR, KRAS, and ALK are oncogenic drivers in lung cancer, but how oncogenic signaling influences immunity in the tumor microenvironment is just beginning to be understood. Immunosuppression likely contributes to lung cancer, because drugs that inhibit immune checkpoints like PD-1 and PD-L1 have clinical benefit. Here, we show that activation of the AKT-mTOR pathway tightly regulates PD-L1 expression in vitro and in vivo. Both oncogenic and IFNg-mediated induction of PD-L1 was dependent on mTOR. In human lung adenocarcinomas and squamous cell carcinomas, membranous expression of PD-L1 was significantly associated with mTOR activation. These data suggest that oncogenic activation of the AKT-mTOR pathway promotes immune escape by driving expression of PD-L1, which was confirmed in syngeneic and genetically engineered mouse models of lung cancer where an mTOR inhibitor combined with a PD-1 antibody decreased tumor growth, increased tumor-infiltrating T cells, and decreased regulatory T cells.

This study examined the association between 3 components of ethnic identity (exploration, resolution, and affirmation) and factors related to family, neighborhood, and individual characteristics. The purpose was to identity factors that are positively associated with adolescent ethnic identity among a sample of 187 Latino adolescents with a mean age of 14.61. The findings suggested that family ethnic socialization was directly associated with exploration and resolution, but not ethnic affirmation. Analyses with moderator variables suggested that associations between family ethnic socialization and ethnic affirmation varied based on parental behaviors and neighborhood characteristics. The results also suggested that ethnic affirmation, but not exploration or resolution, was positively associated with teacher reports of school performance.

There is relatively little research on the role of teacher expectations in the early school years or on the importance of teacher expectations as a predictor of future academic achievement. The current study investigated these issues in the reading and mathematic domains for young children. Data from nearly 1,000 children and families at first, third, and fifth grades were included. Child sex and social skills emerged as consistent predictors of teacher expectations of reading and, to a lesser extent, math ability. In predicting actual future academic achievement, results showed that teacher expectations were differentially related to achievement in reading and math. There was no evidence that teacher expectations accumulate but some evidence that they remain durable over time for math achievement. Additionally, teacher expectations were more strongly related to later achievement for groups of children who may be considered to be at risk.

Objective Anti-HMGCR antibodies are found in patients with statin-associated immune-mediated necrotizing myopathy and, less commonly, in statin-unexposed subjects with autoimmune myopathy. The main objective of this study is to define the association of anti-HMGCR antibody levels with disease activity. Methods Anti-HMGCR levels, creatine kinase (CK) levels, and strength were assessed in anti-HMGCR positive subjects. Associations of antibody level with CK and strength at visit 1 were analyzed in 55 subjects, 40 of whom were statin-exposed. In 12 statin-exposed and 5 statin-unexposed subjects with serum from 5 serial visits, the evolution of antibody levels, CK levels, and strength was investigated. Results Antibody levels were associated with CK levels (p < 0.001), arm strength (p < 0.05), and leg strength (p < 0.05) at visit 1 but these associations were only significant amongst statin-exposed patients in stratified analyses. With treatment over 26.2 +/− 12.6 months, antibody levels declined (p < 0.05) and arm abduction strength improved (p < 0.05) in 17 subjects followed longitudinally. When analyzed separately, statin-exposed subjects developed decreased antibody levels (p < 0.01), decreased CK levels (p < 0.001), improved arm strength (p < 0.05), and improved hip flexion strength (p < 0.05) with treatment. Anti-HMGCR antibody levels did not normalize in any subject. Conclusion In the entire cohort, initial anti-HMGCR levels correlated with indicators of disease activity; with treatment, antibody levels declined and arm strength improved. Statin-exposed but not statin-unexposed subjects had significant improvements in CK and strength, suggesting a phenotypic difference between statin-exposed and -unexposed anti-HMGCR patients.

BACKGROUND AND OBJECTIVE: Many urban youth experiencesignificant and unremitting negative stressors, including those associated with community violence, multigenerational poverty, failing educational systems, substance use, limited avenues for success, health risks, and trauma. Mindfulness instruction improves psychological functioning in a variety of adult populations; research on mindfulness for youth is promising, but has been conducted in limited populations. Informed by implementation science, we evaluated an adapted mindfulness-based stress reduction (MBSR) program to ameliorate the negative effects of stress and trauma among low-income, minority, middle school public school students.

Introduction: Teen dating violence is a serious public health problem with few effective prevention strategies. This study examines whether the Dating Matters comprehensive prevention model, compared with a standard of care intervention, prevented negative relationship behaviors and promoted positive relationship behaviors. Study design: This longitudinal, cluster-RCT compared the effectiveness of Dating Matters with standard of care across middle school. Standard of care was an evidence-based teen dating violence prevention curriculum (Safe Dates) implemented in eighth grade. Setting/participants: Forty-six middle schools in high-risk urban neighborhoods in four U.S. cities were randomized. Schools lost to follow-up were replaced with new schools, which were independently randomized (71% school retention). Students were surveyed in fall and spring of sixth, seventh, and eighth grades (2012−2016). The analysis sample includes students from schools implementing Dating Matters or standard of care for >2 years who started sixth grade in the fall of 2012 or 2013 and had dated (N=2,349 students, mean age 12 years, 49% female, and 55% black, non-Hispanic, 28% Hispanic, 17% other). Intervention: Dating Matters is a comprehensive, multicomponent prevention model including classroom-delivered programs for sixth to eighth graders, training for parents of sixth to eighth graders, educator training, a youth communications program, and local health department activities to assess capacity and track teen dating violence−related policy and data. Main outcome measures: Self-reported teen dating violence perpetration and victimization, use of negative conflict resolution strategies, and positive relationship skills were examined as outcomes. Imputation and analyses were conducted in 2017. Results: Latent panel models demonstrated significant program effects for three of four outcomes; Dating Matters students reported 8.43% lower teen dating violence perpetration, 9.78% lower teen dating violence victimization, and 5.52% lower use of negative conflict resolution strategies, on average across time points and cohorts, than standard of care students. There were no significant effects on positive relationship behaviors.

Background: Perinatal intimate partner violence (IPV) is common and has significant negative health outcomes for mothers and infants. This study evaluated the effectiveness of an IPV intervention in reducing violence among abused women in perinatal home visiting programs. Materials and Methods: This assessor-blinded multisite randomized control trial of 239 women experiencing perinatal IPV was conducted from 2006 to 2012 in U.S. urban and rural settings. The Domestic Violence Enhanced Home Visitation Program (DOVE) intervention group (n = 124) received a structured abuse assessment and six home visitor-delivered empowerment sessions integrated into home visits. All participants were screened for IPV and referred appropriately. IPV was measured by the Conflicts Tactics Scale2 at baseline through 24 months postpartum. Results: There was a significant decrease in IPV over time (F = 114.23; p < 0.001) from baseline to 1, 3, 6, 12, 18, and 24 months postpartum (all p < 0.001). Additional models examining change in IPV from baseline indicated a significant treatment effect (F = 6.45; p < 0.01). Women in the DOVE treatment group reported a larger mean decrease in IPV scores from baseline compared to women in the usual care group (mean decline 40.82 vs. 35.87). All models accounted for age and maternal depression as covariates. Conclusions: The DOVE intervention was effective in decreasing IPV and is brief, thereby facilitating its incorporation within well-woman and well-child care visits, as well as home visiting programs, while satisfying recommendations set forth in the Affordable Care Act for IPV screening and brief counseling.

Using a risk and resiliency theoretical framework, the association between interparental conflict and academic achievement was examined. The sample consisted of 2,297 6th grade youth with a mean age of 11.92. Participants were mostly European American (81.8%) and 52% were girls. Results demonstrated that interparental conflict is a risk factor for lower academic achievement, suggesting that family interactions play a significant role in how youth perform in the academic setting. Youth self-blame acted as a significant mediator, providing some explanation for how interparental conflict affects academic achievement. Maternal acceptance and monitoring knowledge partially buffered the association between interparental conflict and youth self-blame. Additionally, the positive association between interparental conflict and perceived threat was stronger for youth who perceived relationships with mothers as more supportive, connected, and involved. Results from this study underscore the need for continued focus on the link between family and school environments with respect to youth developmental outcomes.