The NYCKidSeq randomized controlled trial: Impact of GUÍA digitally enhanced genetic results disclosure in diverse families.

Digital solutions are needed to support rapid increases in the application of genetic/genomic tests (GTs) in diverse clinical settings and patient populations. We developed GUÍA, a bilingual digital application that facilitates disclosure of GT results. The NYCKidSeq randomized controlled trial enrolled diverse children with neurologic, cardiac, and immunologic conditions who underwent GTs. The trial evaluated GUÍA's impact on understanding the GT results by randomizing families to results disclosure genetic counseling with GUÍA (intervention) or standard of care (SOC). Parents/legal guardians (participants) completed surveys at baseline, post-results disclosure, and 6 months later. Survey measures assessed the primary study outcomes of participants' perceived understanding of and confidence in explaining their child's GT results and the secondary outcome of objective understanding. The analysis included 551 diverse participants, 270 in the GUÍA arm and 281 in SOC. Participants in the GUÍA arm had significantly higher perceived understanding post-results (OR = 2.8, CI[1.004, 7.617], p = 0.049) and maintained higher objective understanding over time (OR = 1.1, CI[1.004, 1.127], p = 0.038) compared to SOC. There was no impact on perceived confidence. Hispanic/Latino(a) individuals in the GUÍA arm maintained higher perceived understanding (OR = 3.9, CI[1.603, 9.254], p = 0.003), confidence (OR = 2.7, CI[1.021, 7.277], p = 0.046), and objective understanding (OR = 1.1, CI[1.009, 1.212], p = 0.032) compared to SOC. This trial demonstrates that GUÍA positively impacts understanding of GT results in diverse parents of children with suspected genetic conditions and builds a case for utilizing GUÍA to deliver complex results. Continued development and evaluation of digital applications in diverse populations are critical for equitably scaling GT offerings in specialty clinics.

Physician services and costs after disclosure of diagnostic sequencing results in the NYCKidSeq program.

PURPOSE: To better understand the effects of returning diagnostic sequencing results on clinical actions and economic outcomes for pediatric patients with suspected genetic disorders. METHODS: Longitudinal physician claims data after diagnostic sequencing were obtained for patients aged 0 to 21 years with neurologic, cardiac, and immunologic disorders with suspected genetic etiology. We assessed specialist consultation rates prompted by primary diagnostic results, as well as marginal effects on overall 18-month physician services and costs. RESULTS: We included data on 857 patients (median age: 9.6 years) with a median follow-up of 17.3 months after disclosure of diagnostic sequencing results. The likelihood of having ≥1 recommendation for specialist consultation in 155 patients with positive findings was high (72%) vs 23% in 443 patients with uncertain findings and 21% in 259 patients with negative findings (P < .001). Follow-through consultation occurred in 30%. Increases in 18-month physician services and costs following a positive finding diminished after multivariable adjustment. Also, no significant differences between those with uncertain and negative findings were demonstrated. CONCLUSION: Our study did not provide evidence for significant increases in downstream physician services and costs after returning positive or uncertain diagnostic sequencing findings. More large-scale longitudinal studies are needed to confirm these findings.

Interactions among stress, behavioral inhibition, and delta-beta coupling predict adolescent anxiety during the COVID-19 pandemic.

The COVID-19 pandemic brought about unprecedented changes and uncertainty to the daily lives of youth. The range of adjustment in light of a near-universal experience of COVID restrictions highlights the importance of identifying factors that may render some individuals more susceptible to heightened levels of anxiety during stressful life events than others. Two risk factors to consider are temperamental behavioral inhibition (BI) and difficulties in emotion regulation (ER). As such, the current paper focused on BI examined prior to COVID, because of its developmental link to anxiety and ER, as difficulties may be associated with differences in anxiety. We examined a neurocognitive marker of ER processes, delta-beta coupling (DBC). The current paper had two goals: (1) to examine BI in relation to COVID-related worry and social anxiety experienced during the pandemic, and (2) to explore the role of individual differences in early DBC in the relationship between BI and anxiety outcomes 6 months apart during COVID-19 (n = 86; T1 Mage  = 15.95, SD = 1.73; T6 Mage  = 16.43, SD = 1.73). We found support for the moderating role of DBC in the relationship between BI levels and social anxiety disorder (SAD) symptom severity during the pandemic. Here, high BI was predictive of increased SAD symptom levels in adolescents with stronger DBC.

Molecular diagnostic yield of genome sequencing versus targeted gene panel testing in racially and ethnically diverse pediatric patients.

PURPOSE: Adoption of genome sequencing (GS) as a first-line test requires evaluation of its diagnostic yield. We evaluated the GS and targeted gene panel (TGP) testing in diverse pediatric patients (probands) with suspected genetic conditions. METHODS: Probands with neurologic, cardiac, or immunologic conditions were offered GS and TGP testing. Diagnostic yield was compared using a fully paired study design. RESULTS: A total of 645 probands (median age 9 years) underwent genetic testing, and 113 (17.5%) received a molecular diagnosis. Among 642 probands with both GS and TGP testing, GS yielded 106 (16.5%) and TGPs yielded 52 (8.1%) diagnoses (P < .001). Yield was greater for GS vs TGPs in Hispanic/Latino(a) (17.2% vs 9.5%, P < .001) and White/European American (19.8% vs 7.9%, P < .001) but not in Black/African American (11.5% vs 7.7%, P = .22) population groups by self-report. A higher rate of inconclusive results was seen in the Black/African American (63.8%) vs White/European American (47.6%; P = .01) population group. Most causal copy number variants (17 of 19) and mosaic variants (6 of 8) were detected only by GS. CONCLUSION: GS may yield up to twice as many diagnoses in pediatric patients compared with TGP testing but not yet across all population groups.

Identification of copy number variants with genome sequencing: Clinical experiences from the NYCKidSeq program.

Copy number variations (CNVs) play a significant role in human disease. While chromosomal microarray has traditionally been the first-tier test for CNV detection, use of genome sequencing (GS) is increasing. We report the frequency of CNVs detected with GS in a diverse pediatric cohort from the NYCKidSeq program and highlight specific examples of its clinical impact. A total of 1052 children (0-21 years) with neurodevelopmental, cardiac, and/or immunodeficiency phenotypes received GS. Phenotype-driven analysis was used, resulting in 183 (17.4%) participants with a diagnostic result. CNVs accounted for 20.2% of participants with a diagnostic result (37/183) and ranged from 0.5 kb to 16 Mb. Of participants with a diagnostic result (n = 183) and phenotypes in more than one category, 5/17 (29.4%) were solved by a CNV finding, suggesting a high prevalence of diagnostic CNVs in participants with complex phenotypes. Thirteen participants with a diagnostic CNV (35.1%) had previously uninformative genetic testing, of which nine included a chromosomal microarray. This study demonstrates the benefits of GS for reliable detection of CNVs in a pediatric cohort with variable phenotypes.

Detection of mosaic variants using genome sequencing in a large pediatric cohort.

The increased use of next-generation sequencing has expanded our understanding of the involvement and prevalence of mosaicism in genetic disorders. We describe a total of eleven cases: nine in which mosaic variants detected by genome sequencing (GS) and/or targeted gene panels (TGPs) were considered to be causative for the proband's phenotype, and two of apparent parental mosaicism. Variants were identified in the following genes: PHACTR1, SCN8A, KCNT1, CDKL5, NEXMIF, CUX1, TSC2, GABRB2, and SMARCB1. In addition, we identified one large duplication including three genes, UBE3A, GABRB3, and MAGEL2, and one large deletion including deletion of ARFGAP1, EEF1A2, CHRNA4, and KCNQ2. All patients were enrolled in the NYCKidSeq study, a research program studying the communication of genomic information in clinical care, as well as the clinical utility and diagnostic yield of GS for children with suspected genetic disorders in diverse populations in New York City. We observed variability in the correlation between reported variant allele fraction and the severity of the patient's phenotype, although we were not able to determine the mosaicism percentage in clinically relevant tissue(s). Although our study was not sufficiently powered to assess differences in mosaicism detection between the two testing modalities, we saw a trend toward better detection by GS as compared with TGP testing. This case series supports the importance of mosaicism in childhood-onset genetic conditions and informs guidelines for laboratory and clinical interpretation of mosaic variants detected by GS.

Latent profile analysis of adolescent temperament: Relations to happiness and health in adulthood.

INTRODUCTION: This study provides long-term evidence that profiles of temperament during adolescence are associated with happiness and health over two decades later. METHODS: Data are based on the ongoing Fullerton Longitudinal Study, a community-based sample in the United States. At 14 and 16 years, adolescents (N = 111; 52% male, 90% Euro-American) and their mothers (N = 105) completed the Dimensions of Temperament Survey-Revised, a scale designed specifically to assess adolescents' temperament across a set of attributes. When adolescents reached age 38 years in 2017, they completed scales measuring comprehensive happiness and global health. RESULTS: Latent profile analysis (LPA), a person-centered approach, was conducted for adolescents' and for mothers' temperament ratings separately. Distinct two-profile solutions, labeled more regulated and less regulated, emerged for each informant. These were comparable in features across informants. Only the adolescents' self-rated profiles, controlling for sex and family SES, revealed a conceptually meaningful and statistically significant relation to the distal outcomes of health and happiness two decades later. CONCLUSIONS: Adolescents with temperament profiles characterized as more regulated, in contrast to less regulated, reported being happier and healthier upon entering middle adulthood. Implications for intervention are presented.

Integration of stakeholder engagement from development to dissemination in genomic medicine research: Approaches and outcomes from the CSER Consortium.

PURPOSE: There is a critical need for genomic medicine research that reflects and benefits socioeconomically and ancestrally diverse populations. However, disparities in research populations persist, highlighting that traditional study designs and materials may be insufficient or inaccessible to all groups. New approaches can be gained through collaborations with patient/community stakeholders. Although some benefits of stakeholder engagement are recognized, routine incorporation into the design and implementation of genomics research has yet to be realized. METHODS: The National Institutes of Health-funded Clinical Sequencing Evidence-Generating Research (CSER) consortium required stakeholder engagement as a dedicated project component. Each CSER project planned and carried out stakeholder engagement activities with differing goals and expected outcomes. Examples were curated from each project to highlight engagement strategies and outcomes throughout the research lifecycle from development through dissemination. RESULTS: Projects tailored strategies to individual study needs, logistical constraints, and other challenges. Lessons learned include starting early with engagement efforts across project stakeholder groups and planned flexibility to enable adaptations throughout the project lifecycle. CONCLUSION: Each CSER project used more than 1 approach to engage with relevant stakeholders, resulting in numerous adaptations and tremendous value added throughout the full research lifecycle. Incorporation of community stakeholder insight improves the outcomes and relevance of genomic medicine research.

Observed parent-adolescent coalitions and family hostilities during family discussions: Associations with marital aggression.

This study investigated bidirectional associations between observed parent-youth coalitions-wherein one parent and a child align themselves against the other parent-and family hostilities as they evolved in real-time during triadic family conflict discussions. Participants were 102 families with an adolescent child (50% girls, Mage  = 15.3 years, SD = 0.8). Using time-lagged, multilevel models, we tested immediate, temporal influences from hostility (within marital and mother-youth and father-youth relationships) to parent-youth coalitions and vice versa. Guided by sensitization theories, we also investigated whether a history of marital aggression moderated these links. Results indicated multiple concurrent links supporting the interconnectedness of cross generational coalitions and angry, critical exchanges within multiple family relationships. Moreover, time-linked effects demonstrated that hostility within both the marital and parent-adolescent domains preceded subsequent coalitions, and also that coalitions preceded hostility, particularly in the parent-adolescent domain. Findings further demonstrated that marital aggression moderates temporal associations between fathers' marital hostility and father-youth coalitions. These patterns highlight the dynamic links between hostilities and coalitions, how such patterns spill over across family subsystems, and how these two insidious influences in parents' interactions with their adolescent youth may mutually reinforce each other. This study informs intervention efforts by identifying patterns and sequences of family hostilities surrounding parent-youth coalitions during adolescence.

En este estudio se investigaron las asociaciones bidireccionales entre las alianzas observadas entre padres y adolescentes -en las cuales un padre y un hijo se alinean contra el otro padre- y las hostilidades familiares a medida que se desarrollaban en tiempo real durante discusiones triádicas por conflictos familiares. Los participantes fueron 102 familias con un hijo adolescente (el 50% niñas, edad promedio = 15.3 años, desviación típica = 0.8). Utilizando modelos multinivel con tiempo de retardo, evaluamos las influencias inmediatas y temporales de la hostilidad (dentro de las relaciones conyugales y de las relaciones entre madre y adolescente y padre y adolescente) en las alianzas entre padres y adolescentes y viceversa. Guiados por las teorías de sensibilización, también investigamos si los antecedentes de agresión conyugal moderaron estas asociaciones. Los resultados indicaron varias asociaciones simultáneas que respaldaron la interconexión de las alianzas intergeneracionales y los intercambios agresivos y críticos dentro de las relaciones de varias familias. Además, los efectos asociados con el tiempo demostraron que la hostilidad dentro del área conyugal y de padres y adolescentes precedió a alianzas posteriores, y también que las alianzas precedieron a la hostilidad, particularmente en el área de padres y adolescentes. Los resultados también demostraron que la agresión conyugal modera las asociaciones temporales entre la hostilidad conyugal de los padres y las alianzas entre los padres y los jóvenes. Estos patrones destacan las asociaciones dinámicas entre las hostilidades y las alianzas, las maneras en la que dichos patrones se desbordan entre los subsistemas familiares, y cómo estas dos influencias insidiosas en las interacciones de los padres con sus hijos adolescentes pueden reforzarse mutuamente. Este estudio sirve como base para los esfuerzos de intervención, ya que identifica los patrones y las secuencias de las hostilidades familiares que rodean a las alianzas entre los padres y los adolescentes durante la adolescencia.

GUÍA: a digital platform to facilitate result disclosure in genetic counseling.

PURPOSE: Use of genomic sequencing is increasing at a pace that requires technological solutions to effectively meet the needs of a growing patient population. We developed GUÍA, a web-based application, to enhance the delivery of genomic results and related clinical information to patients and families. METHODS: GUÍA development occurred in five overlapping phases: formative research, content development, stakeholder/community member input, user interface design, and web application development. Development was informed by formative qualitative research involving parents (N = 22) whose children underwent genomic testing. Participants enrolled in the NYCKidSeq pilot study (N = 18) completed structured feedback interviews post-result disclosure using GUÍA. Genetic specialists, researchers, patients, and community stakeholders provided their perspectives on GUÍA's design to ensure technical, cultural, and literacy appropriateness. RESULTS: NYCKidSeq participants responded positively to the use of GUÍA to deliver their children's results. All participants (N = 10) with previous experience with genetic testing felt GUÍA improved result disclosure, and 17 (94%) participants said the content was clear. CONCLUSION: GUÍA communicates complex genomic information in an understandable and personalized manner. Initial piloting demonstrated GUÍA's utility for families enrolled in the NYCKidSeq pilot study. Findings from the NYCKidSeq clinical trial will provide insight into GUÍA's effectiveness in communicating results among diverse, multilingual populations.

Establishing the value of genomics in medicine: the IGNITE Pragmatic Trials Network.

PURPOSE: A critical gap in the adoption of genomic medicine into medical practice is the need for the rigorous evaluation of the utility of genomic medicine interventions. METHODS: The Implementing Genomics in Practice Pragmatic Trials Network (IGNITE PTN) was formed in 2018 to measure the clinical utility and cost-effectiveness of genomic medicine interventions, to assess approaches for real-world application of genomic medicine in diverse clinical settings, and to produce generalizable knowledge on clinical trials using genomic interventions. Five clinical sites and a coordinating center evaluated trial proposals and developed working groups to enable their implementation. RESULTS: Two pragmatic clinical trials (PCTs) have been initiated, one evaluating genetic risk APOL1 variants in African Americans in the management of their hypertension, and the other to evaluate the use of pharmacogenetic testing for medications to manage acute and chronic pain as well as depression. CONCLUSION: IGNITE PTN is a network that carries out PCTs in genomic medicine; it is focused on diversity and inclusion of underrepresented minority trial participants; it uses electronic health records and clinical decision support to deliver the interventions. IGNITE PTN will develop the evidence to support (or oppose) the adoption of genomic medicine interventions by patients, providers, and payers.

Risk factors for and protective factors against breastfeeding interruption before 2 years: a birth cohort study.

BACKGROUND: Little is known about the factors associated with the World Health Organization (WHO) recommendation of breastfeeding for at least 2 years. The objective of this study was to identify risk factors for and protective factors against breastfeeding interruption before 2 years of age. METHODS: In this live birth cohort, mother and infant dyads were followed for 2 years. Data collection was performed at the maternity ward and subsequently at the children's homes, monthly during the first 6 months of life and then at 9, 12, 18, and 24 months. The outcome of interest was breastfeeding interruption before 2 years of age. Median duration of breastfeeding was estimated using Kaplan-Meier's survival analysis, and the associations were tested using Cox's hierarchical multivariate model. Significance was set at 5%. RESULTS: Data from a total of 1344 dyads were assessed. Median breastfeeding duration was 385 days. The following risk factors for breastfeeding interruption were identified: white skin color (adjusted hazard ratio [HRa]: 1.31; 95% confidence interval [95%CI]: 1.10-1.56), primiparity (HRa: 1.21; 95%CI: 1.05-1.40), working outside the home (HRa: 1.52; 95%CI: 1.30-1.77), child sex male (HRa: 1.18; 95%CI: 1.03-1.35) and use of a pacifier (HRa: 3.46; 95%CI: 2.98-4.01). Conversely, the following protective factors were identified: lower family income (HRa: 0.81; 95%CI: 0.71-0.94), mother-infant bed-sharing (HRa:0.61, 95%CI: 0.52-0.73), on-demand breastfeeding in the first month (HRa: 0.64; 95%CI: 0.47-0.89) and exclusive breastfeeding at 4 months (HRa: 0.58, 95%CI: 0.48-0.70). CONCLUSIONS: The findings allowed to identify both risk factors for and protective factors against breastfeeding interruption before 2 years of age. Knowledge of these factors may help prevent this event and aid in the development of programs that help women maintain breastfeeding for at least 2 years, as recommended by the WHO.

Correction: Developing a common framework for evaluating the implementation of genomic medicine interventions in clinical care: the IGNITE Network's Common Measures Working Group.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Correction: Opportunities to implement a sustainable genomic medicine program: lessons learned from the IGNITE Network.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Colostrum oropharyngeal immunotherapy for very low birth weight preterm infants: protocol of an intervention study.

BACKGROUND: The oropharyngeal colostrum administration protocol to treat premature newborns is a possible and plausible strategy in neonatal health services, since the immunoprotective components of colostrum can be absorbed by the lymphoid tissues of the oropharynx. In this context, this study aims to describe the implementation of oropharyngeal colostrum immunotherapy in very low birth weight preterm newborns in a neonatal unit, as well as to test an algorithm in a public hospital. METHODS: The protocol is applied in a non-randomized, superiority clinical trial with historical control. In the treatment group, 0.2 mL of raw colostrum is dripped into the right and left oropharyngeal mucosa, totaling 8 administrations every 24 h until the 7th complete day of life interruptedly. The control group consists of very low birth weight preterm newborns born in the same hospital in previous years (historical control). The clinical progression of 60 newborns until hospital discharge is recorded on standardized forms. A total of 350 participants are estimated to complete the survey in 4 years. The occurrence of continuous outcomes between the groups are compared through the paired t-test or Wilcoxon's two-sample test. The chi-square test or Fisher's exact test, and survival analysis are used for binary outcomes. The nutritional status is assessed through Intergrowth-21st growth curves for preterm newborns. DISCUSSION: The flows of the protocol's actions is sorted by an algorithm, compatible with the Brazilian reality of a public hospital. This measure facilitates and systematizes clinical care, organizes the team's work process, speeds up the intervention steps, standardizes decision-making and unifies the quality of care, besides showing the feasibility of oropharyngeal colostrum immunotherapy. TRIAL REGISTRATION: ReBEC, U1111-1222-0598 , Registered 09 October 2018, http://www.ensaiosclinicos.gov.br/rg/RBR-2cyp7c/ .

Successful recruitment and retention of diverse participants in a genomics clinical trial: a good invitation to a great party.

PURPOSE: African ancestry (AA) individuals are inadequately included in translational genomics research, limiting generalizability of findings and benefits of genomic discoveries for populations already facing disproportionately poor health outcomes. We aimed to determine the impact of stakeholder-engaged strategies on recruitment and retention of AA adult patients into a clinical trial testing them for renal risk variants nearly exclusive to AAs. METHODS: Our academic-clinical-community team developed ten key strategies that recognize AAs' barriers and facilitators for participation. Using electronic health records (EHRs), we identified potentially eligible patients. Recruiters reached out through letters, phone calls, and at medical visits. RESULTS: Of 5481 AA patients reached, 51% were ineligible, 37% enrolled, 4% declined, 7% were undecided when enrollment finished. We retained 93% at 3-month and 88% at 12-month follow-up. Those enrolled are more likely female, seen at community sites, and reached through active strategies, than those who declined. Those retained are more likely female, health-literate, and older. While many patients have low income, low clinician trust, and perceive racism in health care, none of these attributes correlate with retention. CONCLUSION: With robust stakeholder engagement, recruiters from patients' communities, and active approaches, we successfully recruited and retained AA patients into a genomic clinical trial.

Opportunities to implement a sustainable genomic medicine program: lessons learned from the IGNITE Network.

PURPOSE: While there is growing scientific evidence for and significant advances in the use of genomic technologies in medicine, there is a significant lag in the clinical adoption and sustainability of genomic medicine. Here we describe the findings from the National Human Genome Research Institute's (NHGRI) Implementing GeNomics In pracTicE (IGNITE) Network in identifying key constructs, opportunities, and challenges associated with driving sustainability of genomic medicine in clinical practice. METHODS: Network members and affiliates were surveyed to identify key drivers associated with implementing and sustaining a genomic medicine program. Tallied results were used to develop and weigh key constructs/drivers required to support sustainability of genomic medicine programs. RESULTS: The top three driver-stakeholder dyads were (1) genomic training for providers, (2) genomic clinical decision support (CDS) tools embedded in the electronic health record (EHR), and (3) third party reimbursement for genomic testing. CONCLUSION: Priorities may differ depending on healthcare systems when comparing the current state of key drivers versus projected needs for supporting genomic medicine sustainability. Thus we provide gap-filling guidance based on IGNITE members' experiences. Although results are limited to findings from the IGNITE network, their implementation, scientific, and clinical experience may be used as a road map by others considering implementing genomic medicine programs.

Correction: Opportunities to implement a sustainable genomic medicine program: lessons learned from the IGNITE Network.

The original version of this Article contained an error in the spelling of the author Geoffrey S. Ginsburg, which was incorrectly given as Geoffrey Ginsburg. This has now been corrected in both the PDF and HTML versions of the Article.

Monitoring of air quality before the Olympic Games Rio 2016.

For the accomplishment of Olympic and Paralympic Games in Rio de Janeiro city (Rio 2016), the government of the Rio de Janeiro state has undertaken to monitor air quality before and during the events. In Beijing, China, and Athens, Greece, the air quality was monitored in Olympic venues in order to evaluate the athletes' performance in relation to the environment in which they were exposed. This study has the same proposal to Rio de Janeiro, Brazil. The air quality scenario of the three previous years (2013, 2014, 2015) of Rio 2016 was considered. Coarse (PM10) and fine (PM2.5) particles and O3 were monitored continuously on the stations located near to competition venues, as required by International Olympic Committee (IOC). The levels registered ranged from 6 to 96 µg m-3 for PM10, 1 to 44 µg m-3 for PM2.5 and 121 to 269 µg m-3 for O3. These concentrations exceeded the national and international air quality standards. These high concentrations are associated with uncountable civil works to build Olympic arenas and the urban mobility´s improvement. However, the concentrations for all the pollutants monitored in Rio de Janeiro city were in lower concentrations than in Beijing Olympic Games 2008.

Deviant Peers and Adolescent Risky Behaviors: The Protective Effect of Nonverbal Display of Parental Warmth.

This study examines whether nonverbal displays of parents' warmth during an in-lab conflict discussion mitigate the links between affiliation with deviant peers and risky behaviors. A sample of 107 youth and their parents participated in a study spanning from mid-adolescence (T1) to late adolescence (T2). At T1, family members discussed a contentious issue, which was coded for parents' nonverbal warmth. At T1 and T2, youth reported on their friends' and their own risky behaviors. Fathers' warmth moderated each prospective association between deviant peers and risky behaviors. Mothers' warmth did not emerge as a significant moderator. Girls, in particular, benefitted from fathers' warmth as a buffer in the trajectory from T1 risky behaviors to T2 risky behaviors and deviant peers.