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Although the Research Diagnostic Criteria (RDoC) framework proposes biological and environmental mechanisms intersect in the etiology of psychopathology, there is no guidance on how to define or measure experiences in the environment within the RDoC matrix. Interpersonal dynamics during caregiver-child interactions involve temporal coordination of interacting partners biobehavioral functioning; repeated experiences of signaling to caregivers and responding to caregivers signals shape childrens subsequent socioemotional and brain development. We begin with a review of the extant literature on caregiver-child dynamics, which reveals that RDoCs units of analysis (brain circuits, physiology, behavior, and self-report) are inextricably linked with moment-to-moment changes in the caregiving environment. We then offer a proof-of-concept for integrating biobehavioral RDoC units and environmental components via caregiver-child dynamics. Our approach uses dynamic structural equation models to estimate within-dyad dynamics involving arousal, social, cognitive, and negative or positive affective processes based on second-by-second changes in parasympathetic activity (RSA) during a conflict discussion and a positive event-planning task. Our results illustrate variation in parent-child RSA synchrony, suggesting differences depending on the driver (i.e., child- or parent-led) and on the unique and intersecting domains involved (e.g., positive or negative affect valence systems). We conclude with recommendations for conducting robust, methodologically rigorous studies of interpersonal dynamics that advance the RDoC framework and provide a summary of the clinical implications of this research. Examining caregiver-child dynamics during and across multiple dyadic interaction paradigms that differentially elicit key domains of functioning can deepen understanding of how caregiver- and child-led interpersonal dynamics contribute to child psychopathology risk.

ObjectivesSurveys can assist in screening oral diseases in populations to enhance the early detection of disease and intervention strategies for children in need. This paper aims to develop short forms of child-report and proxy-report survey screening instruments for active dental caries and urgent treatment needs in school-age children.MethodsThis cross-sectional study recruited 497 distinct dyads of children aged 8-17 and their parents between 2015 to 2019 from 14 dental clinics and private practices in Los Angeles County. We evaluated responses to 88 child-reported and 64 proxy-reported oral health questions to select and calibrate short forms using Item Response Theory. Seven classical Machine Learning algorithms were employed to predict children's active caries and urgent treatment needs using the short forms together with family demographic variables. The candidate algorithms include CatBoost, Logistic Regression, K-Nearest Neighbors (KNN), Naïve Bayes, Neural Network, Random Forest, and Support Vector Machine. Predictive performance was assessed using repeated 5-fold nested cross-validations.ResultsWe developed and calibrated four ten-item short forms. Naïve Bayes outperformed other algorithms with the highest median of cross-validated area under the ROC curve. The means of best testing sensitivities and specificities using both child-reported and proxy-reported responses were 0.84 and 0.30 for active caries, and 0.81 and 0.31 for urgent treatment needs respectively. Models incorporating both response types showed a slightly higher predictive accuracy than those relying on either child-reported or proxy-reported responses.ConclusionsThe combination of Item Response Theory and Machine Learning algorithms yielded potentially useful screening instruments for both active caries and urgent treatment needs of children. The survey screening approach is relatively cost-effective and convenient when dealing with oral health assessment in large populations. Future studies are needed to further leverage the customize and refine the instruments based on the estimated item characteristics for specific subgroups of the populations to enhance predictive accuracy.

Given that noncompliance is the most common externalizing problem during middle childhood and reliably predicts significant conduct problems, innovations in elucidating its etiology are sorely needed. Evaluation of in-the-moment antecedents and consequences of child noncompliance improves traction on this goal, given that multiple theories contend that child noncompliance and parent behavior mutually influence each other through negative reciprocation as well as contingent praise processes. Among a sample of 140 families (child age: 6-10 years; 32.1% female), the present study capitalized on intensive repeated measures of observed child noncompliance and parent negative talk and praise objectively coded during three unique tasks. We employed dynamic structural equation modeling to evaluate within-dyad parent-child behavioral dynamics and between-dyad differences therein. Results provided mixed support for hypotheses and suggested that antecedents and consequences of child noncompliance differed according to task demands and child ADHD symptoms. Contrary to models of coercive cycles, during child-led play, parent negative talk was more likely following prior child noncompliance, but child noncompliance was less likely following prior parent negative talk. As expected, during parent-led play, parent praise was less likely following prior child noncompliance, which was also less likely following prior parent praise. Relative to youth with fewer symptoms, for children with elevated ADHD symptoms, during a challenging clean-up task, child noncompliance was less stable and less contingent on prior parent negative talk. Results are discussed in terms of their implications of real-time parent-child interactions for typical and atypical development of externalizing problems.

Attention bias confers risk for anxiety development, however, the influence of sociodemographic variables on the relationship between attention bias and anxiety remains unclear. We examined the association between attention bias and anxiety among rural Latinx youth and investigated potential moderators of this relationship. Clinical symptoms, demographic characteristics, and a performance-based measure of attention bias were collected from 66 rural Latinx youth with clinical levels of anxiety (33.3% female; Mage = 11.74; 92.4% Latinx, 7.6% Mixed Latinx). No moderating effects for age or gender were found. Youth below the poverty line displayed an attention bias away from threat in comparison to youth above the poverty line, who displayed an attention bias towards threat. Among youth below the poverty line, this bias away from threat was associated with increased anxiety. Findings highlight the importance of economic adversity in understanding the relationship between attention bias and anxiety.

Conduct problems are increasingly prevalent in girls and they uniquely predict negative outcomes. Yet, few reliable risk factors for aggression and violence in girls and women have been identified. Although preliminary evidence suggests peer relationships may be central to the development of youth conduct problems, especially in girls, rigorous interactive models of peer risk and protective factors for conduct problems are lacking. Based on 3104 10-13-year-old girls in the Adolescent Brain and Cognitive Development study, we tested the independent associations of separate peer risk factors (i.e., relational aggression victimization, physical aggression victimization, and deviant peer affiliation) with multidimensional conduct problems, including their moderation by peer support. Being the victim of relational aggression, being the victim of physical aggression, and deviant peer affiliation were each positively associated with conduct problems and perpetration of aggression whereas peer support was negatively associated with youth report conduct problems and perpetration of physical aggression. Further, elevated peer support significantly attenuated the association of being the victim of relational aggression with teacher-rated conduct problems. These results highlight the sensitivity of conduct problems to peer risk factors and suggest that peer support designates important configurations of risk that differentially relate to conduct problems in girls.

Given the increasing prevalence of adolescent depression, identification of its early predictors and elucidation of the mechanisms underlying its individual differences is imperative. Controlling for baseline executive functioning (EF), we tested separate ADHD dimensions (i.e., inattention, hyperactivity-impulsivity) as independent predictors of early adolescent depression, including temporally-ordered causal mediation by academic functioning and social problems, using structural equation modeling. At baseline, participants consisted of 216 children (67% male) ages 6-9 years old with (n = 112) and without (n = 104) ADHD who subsequently completed Wave 2 and 3 follow-ups approximately two and four years later, respectively. Predictors consisted of separate parent and teacher ratings of childhood ADHD and laboratory-based assessments of key EF domains. At Wave 2, parents and teachers completed normed rating scales of youth academic and social functioning; youth completed standardized assessments of academic achievement. At Wave 3, youth self-reported depression. Baseline inattention positively predicted early adolescent depression whereas childhood hyperactivity-impulsivity and EF did not. Neither academic nor social functioning significantly mediated predictions of depression from baseline ADHD and EF. We consider prediction of early adolescent depression from inattention, including directions for future intervention and prevention research.

Increased tumor infiltrating lymphocytes (TIL) are associated with improved patient responses to immunotherapy. As a result, there is interest in enhancing lymphocyte trafficking particularly to colon cancers since the majority are checkpoint blockade-resistant and microsatellite stable. Here, we demonstrate that activated T-cells (ATC) armed with anti-CD3 x anti-EGFR bispecific antibody increases TIL and mediate anti-tumor cytotoxicity while decreasing tumor cell viability. Furthermore, treatment induces endogenous anti-tumor immunity that resisted tumor rechallenge and increased memory T-cell subsets in the tumor. When combined with targeted tumor expression of the tumor necrosis factor superfamily member LIGHT, activated T-cell proliferation and infiltration were further enhanced, and human colorectal tumor regressions were observed. Our data indicate that tumor-targeted armed bispecific antibody increases TIL trafficking and is a potentially potent strategy that can be paired with combination immunotherapy to battle microsatellite stable colon cancer. SIGNIFICANCE: Enhancing trafficking of tumor infiltrating lymphocytes (TILs) to solid tumors has been shown to improve outcomes. Unfortunately, few strategies have been successful in the clinical setting for solid tumors, particularly for "cold" microsatellite stable colon cancers. In order to address this gap in knowledge, this study combined TNFSF14/LIGHT immunomodulation with a bispecific antibody armed with activated T-cells targeted to the tumor. This unique T-cell trafficking strategy successfully generated anti-tumor immunity in a microsatellite stable colon cancer model, stimulated T-cell infiltration, and holds promise as a combination immunotherapy for treating advanced and metastatic colorectal cancer.

This study reports the results of focus groups with school nurses and teachers from elementary, middle, and high schools to explore their perceptions of child and adolescent oral health. Participants included 14 school nurses and 15 teachers (83% female; 31% Hispanic; 21% White; 21% Asian; 14% African American; and 13% Others). Respondents were recruited from Los Angeles County schools and scheduled by school level for six one-hour focus groups using Zoom. Audio recordings were transcribed, reviewed, and saved with anonymization of speaker identities. NVivo software (QSR International, Melbourne, Australia) was used to facilitate content analysis and identify key themes. The nurses' rate of "Oral Health Education" comments statistically exceeded that of teachers, while teachers had higher rates for "Parental Involvement" and "Mutual Perception" comments. "Need for Care" was perceived to be more prevalent in immigrants to the United States based on student behaviors and complaints. "Access to Care" was seen as primarily the nurses' responsibilities. Strong relationships between community clinics and schools were viewed by some as integral to students achieving good oral health. The results suggest dimensions and questions important to item development for oral health surveys of children and parents to address screening, management, program assessment, and policy planning.

While the main goal in the management of an EHM outbreak focuses on identifying early clinical disease in order to physically separate infected horses, little effort is placed towards monitoring healthy horses. The assumption that EHV-1 shedding parallels clinical disease is erroneous, as subclinical shedders have been shown to be actively involved in viral spread. In an attempt to document the frequency of EHV-1 shedders and their impact on environmental contamination, we collected nasal swabs from 231 healthy horses and 203 environmental samples for the testing of EHV-1 by qPCR. Six horses and 28 stalls tested qPCR-positive for EHV-1. There was no association in the EHV-1 qPCR-positive status between nasal and stall swabs. While testing nasal secretions of healthy at-risk horses can detect active shedding at a specific time point, the testing of stall swabs allows to assess the temporal EHV-1 shedding status of a horse. The study results highlight the risk of subclinical EHV-1 shedders and stalls occupied by these horses as sources of infection for susceptible horses. The testing of individual stalls for the presence of EHV-1 may be a more practical approach than the collection of individual nasal swabs for the monitoring and early detection of the circulating virus. The results also highlight the need to improve the cleanliness and disinfection of stalls utilized by performance horses during show events.

Although childhood aggression is typically associated with peer rejection, some children concurrently employ coercive and socially skilled behavior and successfully avoid negative peer outcomes. However, research on children's dual use of coercive and social behavior has largely employed cross-sectional designs with nonclinical populations and, as a result, little is known about the covariation of aggression with social skills, particularly among high-risk samples. We directly addressed this limitation by testing childhood aggression and social skills as separate time-varying predictors of prospective change in peer rejection in a sample of children with and without attention-deficit/hyperactivity disorder (ADHD). Two hundred and two 5-10-year-old children (M = 7.9 years, SD = 1.2) with and without ADHD were followed prospectively for 6 years. Key constructs, including children's overt aggression, social skills, and peer rejection, were collected at each of the three waves using multiple methods and informants. Controlling for demographic factors and time-varying ADHD symptoms, longitudinal change in child-, parent-, and teacher-reported aggression positively predicted prospective change in parent- and teacher-reported peer rejection. Importantly, predictions were moderated by parent- and teacher-reported social skills, such that aggression inversely predicted peer rejection for children with high social skills. These results demonstrate that social skills meaningfully alter trajectories of peer rejection predicted from cross-time variation in aggression. We discuss the theoretical and empirical implications of these findings within a developmental psychopathology framework, including recommendations for directions for future research.

Simple Summary: Head and neck cancer disparities in outcomes for Black Americans have been well recognized. However, the specific drivers of the inferior outcomes remain poorly understood. We investigated the biologic features of patient oral cancers and performed a follow-up study of the patient post-surgery recurrences and metastases aiming to explore potential mechanisms that might underpin the poorer outcomes among Black American patients. It was found that high levels of tumor stemness and tumor-promoting stromal characteristics were linked to patient recurrence and metastasis. There were more cases of Black American than White American exhibiting high stemness traits and strong tumor-promoting stromal features associated with tumor recurrences and metastases, although the investigated cases displayed comparable clinical diagnoses. Our findings revealed that the differences in tumor stemness and stromal property among cancers with similar diagnoses contribute to patient outcome disparities. Black Americans (BAs) with head and neck cancer (HNC) have worse survival outcomes compared to the White patients. While HNC disparities in patient outcomes for BAs have been well recognized, the specific drivers of the inferior outcomes remain poorly understood. Here, we investigated the biologic features of patient tumor specimens obtained during the surgical treatment of oral cancers and performed a follow-up study of the patients' post-surgery recurrences and metastases with the aim to explore whether tumor biologic features could be associated with the poorer outcomes among BA patients compared with White American (WA) patients. We examined the tumor stemness traits and stromal properties as well as the post-surgery recurrence and metastasis of oral cancers among BA and WA patients. It was found that high levels of tumor self-renewal, invasion, tumorigenesis, metastasis, and tumor-promoting stromal characteristics were linked to post-surgery recurrence and metastasis. There were more BA than WA patients demonstrating high stemness traits and strong tumor-promoting stromal features in association with post-surgery tumor recurrences and metastases, although the investigated cases displayed clinically comparable TNM stages and histological grades. These findings demonstrated that the differences in tumor stemness and stromal property among cancers with comparable clinical diagnoses contribute to the outcome disparity in HNCs. More research is needed to understand the genetic and molecular basis of the biologic characteristics underlying the inferior outcomes among BA patients, so that targeting strategies can be developed to reduce HNC disparity. [ABSTRACT FROM AUTHOR]

The current study examined cross‐cultural differences in perceptions of certain externalizing symptoms, such as those of attention deficit hyperactivity disorder – hyperactivity impulsivity (ADHD‐HI) and oppositional defiant disorder (ODD) as described in the Diagnostic and Statistical Manual of Mental Disorders (DSM‐5). For this study, 39 American and 34 Japanese college students rated the acceptability of externalizing symptoms. The results showed cross‐cultural patterns of perceptions for externalizing symptoms. In terms of ADHD‐HI symptoms, Americans were less accepting of "often interrupts or intrudes on others" and "often has difficulty awaiting his or her turn" while Japanese individuals were less accepting of "often fidgets with or taps hands or feet or squirms in seat" and "often on the go, acting as if driven by motor." For ODD symptoms, Americans were less accepting of "often blames others," "often actively defies or refuses to comply with request," "is often angry and resentful," "often loses temper," and "often deliberately annoys others." This study showed the possible perceptual differences of symptoms between Japanese and American populations, which may be the first step in testing the nonequivalence of DSM‐5 constructs of externalizing disorders. [ABSTRACT FROM AUTHOR]