A Panel-Based Mutational Signature of Mismatch Repair Deficiency is Associated With Durable Response to Pembrolizumab in Metastatic Castration-Resistant Prostate Cancer.

INTRODUCTION/BACKGROUND: Immune checkpoint inhibitors (ICIs) have limited efficacy in prostate cancer (PCa). Better biomarkers are needed to predict responses to ICIs. We sought to demonstrate that a panel-based mutational signature identifies mismatch repair (MMR) deficient (MMRd) PCa and is a biomarker of response to pembrolizumab. PATIENTS AND METHODS: Clinico-genomic data was obtained for 2664 patients with PCa sequenced at Dana-Farber Cancer Institute (DFCI) and Memorial Sloan Kettering (MSK). Clinical outcomes were collected for patients with metastatic castration-resistant PCa (mCRPC) treated with pembrolizumab at DFCI. SigMA was used to characterize tumors as MMRd or MMR proficient (MMRp). The concordance between MMRd with microsatellite instability (MSI-H) was assessed. Radiographic progression-free survival (rPFS) and overall survival (OS) were collected for patients treated with pembrolizumab. Event-time distributions were estimated using Kaplan-Meier methodology. RESULTS: Across both cohorts, 100% (DFCI: 12/12; MSK: 43/43) of MSI-H tumors were MMRd. However, 14% (2/14) and 9.1% (6/66) of MMRd tumors in the DFCI and MSK cohorts respectively were microsatellite stable (MSS), and 26% (17/66) were MSI-indeterminate in the MSK cohort. Among patients treated with pembrolizumab, those with MMRd (n = 5) versus MMRp (n = 14) mCRPC experienced markedly improved rPFS (HR = 0.088, 95% CI: 0.011-0.70; P = .0064) and OS (HR = 0.11, 95% CI: 0.014-0.80; P = .010) from start of treatment. Four patients with MMRd experienced remissions of >= 2.5 years. CONCLUSION: SigMA detects additional cases of MMRd as compared to MSI testing in PCa and identifies patients likely to experience durable response to pembrolizumab.

Co-occurring BRCA2/SPOP Mutations Predict Exceptional Poly (ADP-ribose) Polymerase Inhibitor Sensitivity in Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND AND OBJECTIVE: BRCA2 mutations in metastatic castration-resistant prostate cancer (mCRPC) confer sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors. However, additional factors predicting PARP inhibitor efficacy in mCRPC are needed. Preclinical studies support a relationship between speckle-type POZ protein (SPOP) inactivation and PARP inhibitor sensitivity. We hypothesized that SPOP mutations may predict enhanced PARP inhibitor response in BRCA2-altered mCRPC. METHODS: We conducted a multicenter retrospective study involving 13 sites. We identified 131 patients with BRCA2-altered mCRPC treated with PARP inhibitors, 14 of which also carried concurrent SPOP mutations. The primary efficacy endpoint was prostate-specific antigen (PSA) response rate (≥50% PSA decline). The secondary endpoints were biochemical progression-free survival (PSA-PFS), clinical/radiographic progression-free survival (PFS), and overall survival (OS). These were compared by multivariable Cox proportional hazard models adjusting for age, tumor stage, baseline PSA level, Gleason sum, prior therapies, BRCA2 alteration types, and co-occurring mutations. KEY FINDINGS AND LIMITATIONS: Baseline characteristics were similar between groups. PSA responses were observed in 60% (70/117) of patients with BRCA2mut/SPOPwt disease and in 86% (12/14) of patients with BRCA2mut/SPOPmut disease (p = 0.06). The median time on PARP inhibitor treatment was 24.0 mo (95% confidence interval [CI] 19.2 mo to not reached) in this group versus 8.0 mo (95% CI 6.1-10.9 mo) in patients with BRCA2 mutation alone (p = 0.05). In an unadjusted analysis, patients with BRCA2mut/SPOPmut disease experienced longer PSA-PFS (hazard ratio [HR] 0.33 [95% CI 0.15-0.72], p = 0.005) and clinical/radiographic PFS (HR 0.4 [95% CI 0.18-0.86], p = 0.02), and numerically longer OS (HR 0.4 [95% CI 0.15-1.12], p = 0.08). In a multivariable analysis including histology, Gleason sum, prior taxane, prior androgen receptor pathway inhibitor, stage, PSA, BRCA2 alteration characteristics, and other co-mutations, patients with BRCA2mut/SPOPmut disease experienced longer PSA-PFS (HR 0.16 [95% CI 0.05-0.47], adjusted p = 0.001), clinical/radiographic PFS (HR 0.28 [95% CI 0.1-0.81], adjusted p = 0.019), and OS (HR 0.19 [95% CI 0.05-0.69], adjusted p = 0.012). In a separate cohort of patients not treated with a PARP inhibitor, there was no difference in OS between patients with BRCA2mut/SPOPmut versus BRCA2mut/SPOPwt disease (HR 0.97 [95% CI 0.40-2.4], p = 0.94). In a genomic signature analysis, Catalog of Somatic Mutations in Cancer (COSMIC) SBS3 scores predictive of homologous recombination repair (HRR) defects were higher for BRCA2mut/SPOPmut than for BRCA2mut/SPOPwt disease (p = 0.04). This was a retrospective study, and additional prospective validation cohorts are needed. CONCLUSIONS AND CLINICAL IMPLICATIONS: In this retrospective analysis, PARP inhibitors appeared more effective in patients with BRCA2mut/SPOPmut than in patients with BRCA2mut/SPOPwt mCRPC. This may be related to an increase in HRR defects in coaltered disease. PATIENT SUMMARY: In this study, we demonstrate that co-alteration of both BRCA2 and SPOP predicts superior clinical outcomes to treatment with poly (ADP-ribose) polymerase (PARP) inhibitors than BRCA2 alteration without SPOP mutation.

Nucleosome Patterns in Circulating Tumor DNA Reveal Transcriptional Regulation of Advanced Prostate Cancer Phenotypes.

Advanced prostate cancers comprise distinct phenotypes, but tumor classification remains clinically challenging. Here, we harnessed circulating tumor DNA (ctDNA) to study tumor phenotypes by ascertaining nucleosome positioning patterns associated with transcription regulation. We sequenced plasma ctDNA whole genomes from patient-derived xenografts representing a spectrum of androgen receptor active (ARPC) and neuroendocrine (NEPC) prostate cancers. Nucleosome patterns associated with transcriptional activity were reflected in ctDNA at regions of genes, promoters, histone modifications, transcription factor binding, and accessible chromatin. We identified the activity of key phenotype-defining transcriptional regulators from ctDNA, including AR, ASCL1, HOXB13, HNF4G, and GATA2. To distinguish NEPC and ARPC in patient plasma samples, we developed prediction models that achieved accuracies of 97% for dominant phenotypes and 87% for mixed clinical phenotypes. Although phenotype classification is typically assessed by IHC or transcriptome profiling from tumor biopsies, we demonstrate that ctDNA provides comparable results with diagnostic advantages for precision oncology. SIGNIFICANCE: This study provides insights into the dynamics of nucleosome positioning and gene regulation associated with cancer phenotypes that can be ascertained from ctDNA. New methods for classification in phenotype mixtures extend the utility of ctDNA beyond assessments of somatic DNA alterations with important implications for molecular classification and precision oncology. This article is highlighted in the In This Issue feature, p. 517.

Differential responses to taxanes and PARP inhibitors in ATM- versus BRCA2-mutated metastatic castrate-resistant prostate cancer.

BACKGROUND: PARP (poly(ADP-ribose) polymerase) inhibitors (PARPi) are now standard of care in metastatic castrate-resistant prostate cancer (mCRPC) patients with select mutations in DNA damage repair (DDR) pathways, but patients with ATM- and BRCA2 mutations may respond differently to PARPi. We hypothesized that differences may also exist in response to taxanes, which may inform treatment sequencing decisions. METHODS: mCRPC patients (N = 158) with deleterious ATM or BRCA2 mutations who received taxanes, PARPi, or both were retrospectively identified from 11 US academic centers. Demographic, treatment, and survival data were collected. Kaplan-Meier analyses were performed and Cox hazard ratios (HR) were calculated for progression-free survival (PFS) as well as overall survival (OS), from time of first taxane or PARPi therapy. RESULTS: Fifty-eight patients with ATM mutations and 100 with BRCA2 mutations were identified. Fourty-four (76%) patients with ATM mutations received taxane only or taxane before PARPi, while 14 (24%) received PARPi only or PARPi before taxane. Patients with ATM mutations had longer PFS when taxane was given first versus PARPi given first (HR: 0.74 [95% confidence interval [CI]: 0.37-1.50]; p = 0.40). Similarly, OS was longer in patients with ATM mutations who received taxane first (HR: 0.56 [CI: 0.20-1.54]; p = 0.26). Among patients with BRCA2 mutations, 51 (51%) received taxane first and 49 (49%) received PARPi first. In contrast, patients with BRCA2 mutations had longer PFS when PARPi was given first versus taxane given first (HR: 0.85 [CI: 0.54-1.35]; p = 0.49). Similarly, OS was longer in patients with BRCA2 mutations who received PARPi first (HR: 0.75 [CI: 0.41-1.37]; p = 0.35). CONCLUSIONS: Our retrospective data suggest differential response between ATM and BRCA2 mutated prostate cancers in terms of response to PARPi and to taxane chemotherapy. When considering the sequence of PARPi versus taxane chemotherapy for mCRPC with DDR mutations, ATM, and BRCA2 mutation status may be helpful in guiding choice of initial therapy.

Addition of Germline Testing to Tumor-Only Sequencing Improves Detection of Pathogenic Germline Variants in Men With Advanced Prostate Cancer.

PURPOSE: Guidelines recommend somatic and germline testing for men with advanced prostate cancer (PCa). Barriers to widespread implementation result in underutilization of germline testing. Somatic testing alone risks missing pathogenic germline variants (PGVs). We sought to determine whether the addition of germline testing to tumor-only sequencing improves detection of PGVs in men with advanced PCa. Secondarily, we sought to define the added value of combining somatic and germline testing to optimize detection of clinically actionable alterations. PATIENTS AND METHODS: We analyzed results of independent germline testing and tumor-only sequencing from 100 men with advanced PCa from a prospective clinical trial (ClinicalTrials.gov identifier: NCT03328091). The primary outcome was the proportion of PGVs not reported with tumor-only sequencing. The secondary outcome was the association of locus-specific loss of heterozygosity for PGVs in homologous recombination genes with clinical-genomic features. RESULTS: In the 100 men who underwent germline testing and tumor-only sequencing, 24 PGVs were identified, 17 of which were clinically actionable, in 23 patients. Tumor-only sequencing failed to report four (17%) of the PGVs. One additional PGV (4.2%) had variant allele frequency on tumor-sequencing below the threshold for follow-up germline testing. When integrating tumor-only sequencing with germling testing results, 33% of patients harbored clinically actionable alterations. Rates of locus-specific loss of heterozygosity were higher for BRCA2 PGVs in castration-resistant PCa than PGVs in other homologous recombination genes in hormone-sensitive PCa (P = .029). CONCLUSION: Tumor-only sequencing failed to report more than 20% of PGVs in men with advanced PCa. These findings strongly support guideline recommendations for universal germline and somatic testing in this population. Combining tumor and germline sequencing doubled the chance of detecting a clinically actionable alteration.

The Prostate Cancer Androgen Receptor Cistrome in African American Men Associates with Upregulation of Lipid Metabolism and Immune Response.

African-American (AA) men are more likely to be diagnosed with and die from prostate cancer than European American (EA) men. Despite the central role of the androgen receptor (AR) transcription factor in prostate cancer, little is known about the contribution of epigenetics to observed racial disparities. We performed AR chromatin immunoprecipitation sequencing on primary prostate tumors from AA and EA men, finding that sites with greater AR binding intensity in AA relative to EA prostate cancer are enriched for lipid metabolism and immune response genes. Integration with transcriptomic and metabolomic data demonstrated coinciding upregulation of lipid metabolism gene expression and increased lipid levels in AA prostate cancer. In a metastatic prostate cancer cohort, upregulated lipid metabolism associated with poor prognosis. These findings offer the first insights into ancestry-specific differences in the prostate cancer AR cistrome. The data suggest a model whereby increased androgen signaling may contribute to higher levels of lipid metabolism, immune response, and cytokine signaling in AA prostate tumors. Given the association of upregulated lipogenesis with prostate cancer progression, our study provides a plausible biological explanation for the higher incidence and aggressiveness of prostate cancer observed in AA men. SIGNIFICANCE: With immunotherapies and inhibitors of metabolic enzymes in clinical development, the altered lipid metabolism and immune response in African-American men provides potential therapeutic opportunities to attenuate racial disparities in prostate cancer.

Detecting Neuroendocrine Prostate Cancer Through Tissue-Informed Cell-Free DNA Methylation Analysis.

PURPOSE: Neuroendocrine prostate cancer (NEPC) is a resistance phenotype that emerges in men with metastatic castration-resistant prostate adenocarcinoma (CR-PRAD) and has important clinical implications, but is challenging to detect in practice. Herein, we report a novel tissue-informed epigenetic approach to noninvasively detect NEPC. EXPERIMENTAL DESIGN: We first performed methylated immunoprecipitation and high-throughput sequencing (MeDIP-seq) on a training set of tumors, identified differentially methylated regions between NEPC and CR-PRAD, and built a model to predict the presence of NEPC (termed NEPC Risk Score). We then performed MeDIP-seq on cell-free DNA (cfDNA) from two independent cohorts of men with NEPC or CR-PRAD and assessed the accuracy of the model to predict the presence NEPC. RESULTS: The test cohort comprised cfDNA samples from 48 men, 9 with NEPC and 39 with CR-PRAD. NEPC Risk Scores were significantly higher in men with NEPC than CR-PRAD (P = 4.3 × 10-7) and discriminated between NEPC and CR-PRAD with high accuracy (AUROC 0.96). The optimal NEPC Risk Score cutoff demonstrated 100% sensitivity and 90% specificity for detecting NEPC. The independent, multi-institutional validation cohort included cfDNA from 53 men, including 12 with NEPC and 41 with CR-PRAD. NEPC Risk Scores were significantly higher in men with NEPC than CR-PRAD (P = 7.5×10-12) and perfectly discriminated NEPC from CR-PRAD (AUROC 1.0). Applying the predefined NEPC Risk Score cutoff to the validation cohort resulted in 100% sensitivity and 95% specificity for detecting NEPC. CONCLUSIONS: Tissue-informed cfDNA methylation analysis is a promising approach for noninvasive detection of NEPC in men with advanced prostate cancer.

Promoting Strong Latino Families Within an Emerging Immigration Context: Results of a Replication and Extension Trial of a Culturally Adapted Preventive Intervention.

We conducted a randomized controlled trial (RCT) of Nuestras Familias: Andando Entre Culturas, a culturally adapted evidence-based parent management training (PMT) preventive intervention, with a sample of 241 Spanish-speaking Latino parents and their middle-school-aged children residing in an emerging immigration context. Scientifically rigorous studies of programs designed for this setting are rare. The intervention was designed to promote prosocial parenting practices and to prevent youth substance use and related problem behaviors. The RCT was designed as an extension and replication of a prior trial (Martinez & Eddy in Journal of Consulting and Clinical Psychology, 73, 841-851, 2005) which was also conducted in an emerging immigration context. Two key issues were of primary interest: intervention feasibility and intervention efficacy. Intervention feasibility was assessed through weekly session attendance, participation, and parent-reported session satisfaction as well as overall program satisfaction. Intervention efficacy was assessed by comparing changes within the intervention and control groups on parenting practices and youth adjustment from pre-intervention baseline to post-intervention termination 6 months later. Results provided support for the feasibility of delivering the intervention on a large scale within communities. Consistent with the prior trial, positive effects of the intervention were detected on parenting practices and on youth outcomes. Differential effects of the intervention were detected based on youth gender and nativity status, such that girls benefited the most with respect to tobacco use likelihood, and foreign-born youth benefited the most with respect to decreased depressive symptoms.Findings provide additional evidence for Nuestras Familias as an efficacious family-based intervention for Latino families within communities that are sites of emerging immigration in terms of both improving parenting practices and decreasing risk for youth substance use and related problem behaviors.

Suppression of Kv3.3 channels by antisense oligonucleotides reverses biochemical effects and motor impairment in spinocerebellar ataxia type 13 mice.

Mutations in KCNC3, the gene that encodes the Kv3.3 voltage dependent potassium channel, cause Spinocerebellar Ataxia type 13 (SCA13), a disease associated with disrupted motor behaviors, progressive cerebellar degeneration, and abnormal auditory processing. The Kv3.3 channel directly binds Hax-1, a cell survival protein. A disease-causing mutation, Kv3.3-G592R, causes overstimulation of Tank Binding Kinase 1 (Tbk1) in the cerebellum, resulting in the degradation of Hax-1 by promoting its trafficking into multivesicular bodies and then to lysosomes. We have now tested the effects of antisense oligonucleotides (ASOs) directed against the Kv3.3 channel on both wild type mice and those bearing the Kv3.3-G592R-encoding mutation. Intracerebroventricular infusion of the Kcnc3-specific ASO suppressed both mRNA and protein levels of the Kv3.3 channel. In wild-type animals, this produced no change in levels of activated Tbk1, Hax-1 or Cd63, a tetraspanin marker for late endosomes/multivesicular bodies. In contrast, in mice homozygous for the Kv3.3-G592R-encoding mutation, the same ASO reduced Tbk1 activation and levels of Cd63, while restoring the expression of Hax-1 in the cerebellum. The motor behavior of the mice was tested using a rotarod assay. Surprisingly, the active ASO had no effects on the motor behavior of wild type mice but restored the behavior of the mutant mice to those of age-matched wild type animals. Our findings indicate that, in mature intact animals, suppression of Kv3.3 expression can reverse the deleterious effects of a SCA13 mutation while having little effect on wild type animals. Thus, targeting Kv3.3 expression may prove a viable therapeutic approach for SCA13.

Alcohol use severity, depressive symptoms, and optimism among Hispanics: Examining the immigrant paradox in a serial mediation model.

OBJECTIVE: Hispanic immigrants exhibit more positive outcomes than U.S.-born Hispanics across educational, psychological, and physical health indices, a phenomenon called the immigrant paradox. We examined the immigrant paradox in relation to alcohol use severity among Hispanic young adults while considering both positive (optimism) and negative (depressive symptoms) processes. METHOD: Among 200 immigrant and U.S.-born Hispanic young adults (Mage = 21.30; 49% male) in Arizona and Florida, we tested whether optimism and depressive symptoms statistically mediated the relationship between nativity and alcohol use severity. Specifically, we examined whether Hispanic immigrants reported greater optimism than their U.S.-born counterparts, and whether such optimism was, in turn, associated with less depressive symptoms and thus lower alcohol use severity. RESULTS: Indirect effects were significant in hypothesized directions (nativity → optimism → depressive symptoms → alcohol use severity). CONCLUSIONS: Both positive and negative psychological processes are important to consider when accounting for the immigrant paradox vis-à-vis alcohol use severity among Hispanic young adults.

Impaired motor skill learning and altered seizure susceptibility in mice with loss or gain of function of the Kcnt1 gene encoding Slack (KNa1.1) Na+-activated K+ channels.

Gain-of-function mutations in KCNT1, the gene encoding Slack (KNa1.1) channels, result in epilepsy of infancy with migrating focal seizures (EIMFS) and several other forms of epilepsy associated with severe intellectual disability. We have generated a mouse model of this condition by replacing the wild type gene with one encoding Kcnt1R455H, a cytoplasmic C-terminal mutation homologous to a human R474H variant that results in EIMFS. We compared behavior patterns and seizure activity in these mice with those of wild type mice and Kcnt1-/- mice. Complete loss of Kcnt1 produced deficits in open field behavior and motor skill learning. Although their thresholds for electrically and chemically induced seizures were similar to those of wild type animals, Kcnt1-/- mice were significantly protected from death after maximum electroshock-induced seizures. In contrast, homozygous Kcnt1R455H/R455H mice were embryonic lethal. Video-EEG monitoring of heterozygous Kcnt1+/R455H animals revealed persistent interictal spikes, spontaneous seizures and a substantially decreased threshold for pentylenetetrazole-induced seizures. Surprisingly, Kcnt1+/R455H mice were not impaired in tasks of exploratory behavior or procedural motor learning. These findings provide an animal model for EIMFS and suggest that Slack channels are required for the development of procedural learning and of pathways that link cortical seizures to other regions required for animal survival.

Latinx Immigrant Farmworker Community Health Promotion: A Needs Assessment.

The present study examined the health promotion intervention needs of Latinx immigrant farmworker families residing in Oregon. Grounded theory qualitative procedures were used to analyze the needs assessment data from 31 Latinx immigrant farmworker residents and key informant interviews as well as four focus groups with resident youth and parents. A theoretical model of how key family-based health behaviors can both confer risk for and protection against negative physical, mental, and social health outcomes among Latinx farmworking communities emerged. Six primary areas of concern emerged from these data, leading to the identification of primary health promotion intervention needs with three foci: (a) the provision of sustainable supports and resources, (b) skill development so that individuals could successfully negotiate identified challenges, and (c) greater community efficacy. Findings underscore the importance of social support and resource accessibility for Latinx immigrant populations.

The Effects of Cooperative Learning on Peer Relations, Academic Support, and Engagement in Learning Among Students of Color.

Despite Brown vs. Board of Education, prejudice still exists in the American school system. These attitudes can give rise to negative social experiences for students of color (i.e., discrimination), negatively impacting their mental and physical health and creating disparities in educational outcomes. Rather than seeking to ameliorate these negative experiences, our approach attempts to address the underlying prejudices and, in so doing, reduce these disparities. Using 4 waves of data from a cluster randomized trial (N = 15 middle schools, 1,890 students, 47.1% female, 75.2% White), we hypothesized that cooperative learning, which has been shown to reduce prejudice in previous research, would create positive gains in peer relatedness, perceptions of academic support, and engagement in learning, and that gains would be larger for students of color; our results confirmed these hypotheses. Our findings highlight the potential role of cooperative learning in reducing disparities and creating greater equity in education.

Climbing the ladder of decline: Income and acculturation associated with chronic inflammation among Mexican immigrants.

OBJECTIVES: Financial hardship and immigrant status are often associated with poorer health as immigrant groups acculturate to life in the US. Known as the Latino health paradox, studies have shown that Latino/a immigrants in particular often experience declines in health the more they embrace ways of life considered "dominant" by US society. At present, critical biological pathways linking socioeconomic and acculturative processes remain to be better explained. The present study investigates associations among financial strain, acculturation, and chronic inflammation. METHODS: In our study of 129 Mexican-born immigrants living in the US, we used Pearson's correlations and multiple regression analyses to investigate links among income-to-poverty ratio (an indicator of financial strain), English language engagement (acculturation), and C-reactive protein (CRP), a measure of systemic inflammation. RESULTS: Results showed that for men, but not women, acculturation as defined by English language engagement moderated the association between an income-to-poverty ratio and CRP levels. CONCLUSIONS: Consistent with the Latino health paradox, more acculturated men with relatively higher income levels (compared with the study sample) had significantly higher levels of CRP.

Mind the Gap: Bridging the Divide Between Current Binge Drinking Prevention and the Needs of Hispanic Underage Emerging Adults.

In this article, we highlight the urgent public health need for prevention of heavy episodic drinking among underage Hispanic emerging adults in the USA. We outline the current state of binge drinking prevention programming and contrast it with the unique cultural, social, and developmental realities of this population using an ecodevelopmental framework (Szapocznik and Coatsworth 1999). Finally, we advance specific recommendations for the development and delivery of culturally tailored, multisystemic binge drinking prevention programs for underage Hispanic emerging adults.

Longitudinal effects of acculturation and enculturation on mental health: Does the measure matter?

A great deal of research has focused on acculturation and enculturation, which represent the processes of adapting to a new culture. Despite this growing literature, results have produced inconsistent findings that may be attributable to differences in terms of the instruments used to assess acculturation and enculturation. Utilizing a 3-year longitudinal data set (with 1-year lags between assessments), the present study explored the psychometric properties of the Bicultural Involvement Questionnaire-Short Version (BIQ-S) and the Acculturation Rating Scale for Mexican Americans II (ARSMA-II) and examined the overlap between changes in these measures as they relate to internalizing and externalizing problem behavior. The present sample consisted of 216 immigrant Latino youth (43% boys; mean age 13.6 years at baseline; SD = 1.44 years, range 10 to 17). Exploratory structural equation modeling identified factor structures for the BIQ-S and ARSMA-II that diverged from their hypothesized structure. Growth curve models also indicate divergence between the BIQ-S and ARSMA-II in terms of change in acculturation and enculturation processes. Finally, the present findings emphasized that measures of acculturation and enculturation are not equivalent in terms of their effects on internalizing and externalizing problems.

A tale of two measures: Concordance between the ARSMA-II and the BIQ acculturation scales among Latino immigrant families.

Acculturation refers to the extent to which an individual immigrant (or immigrant group) acquires the customs and characteristics of a new receiving society and/or retains the customs and characteristics of the person's or group's cultural heritage. Different acculturation measures are often assumed to be interchangeable, although this assumption is rarely tested empirically. The purpose of the present study was to examine the overlap between 2 commonly used measures of acculturation among individuals of Latino/Hispanic ancestry in the United States, the Acculturation Rating Scale for Mexican Americans II (ARSMA-II) and the Bicultural Involvement Questionnaire-Short Version (BIQ-S). Specifically, we examined the ways in which scores from the 2 measures relate to one another, as well as similarities versus differences in the ways they predict external variables of interest (e.g., family functioning, parenting, and youth adjustment) that acculturation is known to influence. Findings indicate distinct patterns of results for the 2 measures. For instance, though the BIQ-S focuses entirely on language use and other cultural practices, the ARSMA-II more consistently relates to language variables. Further, adolescent BIQ-S cultural heritage scores related negatively to risks for and engagement in alcohol use-supporting prior findings-whereas ARSMA-II scores were unrelated to alcohol use. Given the largely nonoverlapping set of relationships of the BIQ-S and the ARSMA-II subscale scores with measures of language dominance and conflict, measures of parenting, and measures of youth outcomes, we recommend that studies utilize both of these measures to fully appraise acculturation in this population. (PsycINFO Database Record

Food insecurity partially mediates associations between social disadvantage and body composition among older adults in india: Results from the study on global AGEing and adult health (SAGE).

OBJECTIVE: Our objective was to test whether food insecurity mediates cross-sectional associations between social disadvantage and body composition among older adults (aged 50+) in India (n = 6556). METHODS: Adjusting for key sociodemographic and dietary variables, we examined whether markers of social disadvantage (lower educational attainment, lower household wealth, belonging to a disadvantaged caste/tribe, and belonging to a minority religion) were associated with food insecurity. We then examined whether food insecurity, in turn, was associated with anthropometric measures of body composition, body mass index (BMI), and waist circumference (WC). We also tested whether food insecurity mediated the relationship between social disadvantage and body composition. RESULTS: In adjusted models, lower household wealth [lowest quintile (Q5) vs highest quintile (Q1): odds ratio (OR) = 13.57, P < .001], having less than a high-school education (OR = 2.12. P < .005), being Muslim (OR = 1.82, P < .001), and being in a scheduled caste (historically marginalized) (OR = 1.49, P < .005) were associated with greater food insecurity. Those who were severely food insecure had greater odds of being underweight (OR = 1.36, P < .01) and lower odds of high WC (OR = 0.70, P < .01). Mediation analyses estimated that food insecurity explained 4.7%-29.7% of the relationship between social disadvantage and body composition, depending on the variables considered. CONCLUSIONS: Our results are consistent with the hypothesis that food insecurity is a mechanism linking social disadvantage and body composition among older adults in India. These analyses contribute to a better understanding of processes leading to variation in body composition, which may help enhance the design of interventions aimed at improving population nutritional status.

Informed consent training improves surgery resident performance in simulated encounters with standardized patients.

BACKGROUND: Although informed consent is vital to patient-physician communication, little training is provided to surgical trainees. We hypothesized that highlighting critical aspects of informed consent would improve resident performance. METHODS: Eighty (out of 88) surgical postgraduate year 1 surgical residents were randomly assigned to one of the 2 cases (laparoscopic cholecystectomy or ventral herniorrhaphy) and instructed to obtain and document informed consent with a standardized patient (SP) followed by a didactic training session. The residents then obtained and documented informed consent with the other case with the other SP. SPs graded encounters ("Checklist"); trained raters graded notes. Repeated measures multivariate analysis of variance (MANOVA) was used to determine differences between pre- and post-training and Checklist versus "Note" scores. RESULTS: Statistically significant pre- to post differences for Note (P < .01) and Checklist (P < .01) along with significant differences between Note and Checklist (P < .01) were noted. CONCLUSIONS: Training improved surgery residents' ability to discuss and document informed consent. Despite this improvement, significant differences between discussion and documentation persisted. Documentation training is a future area for improvement.