Faculty Bibliography

Separability (a Kronecker product) of a scatter matrix is one of favorable structures when multivariate heavy-tailed data are collected in a matrix form, due to its parsimonious representation. However, little attempt has been made to test separability beyond Gaussianity. In this paper, we present nonparametric separability tests that can be applied to a larger class of multivariate distributions not only including elliptical distributions but also generalized elliptical distributions and transelliptical distributions. The proposed test statistic exploits robustness of Tyler's M (or Kendall's tau) estimator and a likelihood function of a scaled variable. Since its distribution is hard to specify, we approximate the p-value using a permutation procedure, whose unbiasedness is obtained from the permutation invariance of multivariate paired data. Our simulation study demonstrates the efficacy of our method against other alternatives, and we apply it to rhesus monkey data and corpus callosum data.

IMPORTANCE:Early behavior problems in children with developmental delay (DD) are prevalent and impairing, but service barriers persist. Controlled studies examining telehealth approaches are limited, particularly for children with DD. OBJECTIVE:To evaluate the efficacy of a telehealth parenting intervention for behavior problems in young children with DD. DESIGN, SETTING, AND PARTICIPANTS:A randomized clinical trial was conducted from March 17, 2016, to December 15, 2020, in which children with DD and externalizing behavior problems were recruited from early intervention and randomly assigned to a telehealth parenting intervention or control group and evaluated through a 12-month follow-up. Most children were from ethnic or racial minoritized backgrounds. Over one-half of children were in extreme poverty or low income-need ratio categories. INTERVENTIONS:Internet-delivered parent-child interaction therapy (iPCIT), which leverages videoconferencing to provide live coaching of home-based caregiver-child interactions. Families received 20 weeks of iPCIT (provided in English or in Spanish) or referrals as usual (RAU). MAIN OUTCOMES AND MEASURES:Observational and caregiver-report measures of child and caregiver behaviors and caregiving stress were examined at preintervention, midtreatment, and postintervention and at 6- and 12-month follow-ups. RESULTS:The sample included a total of 150 children (mean [SD] age, 36.2 [1.0] months; 111 male children [74%]) and their caregivers with 75 each randomly assigned to iPCIT or RAU groups. Children receiving iPCIT relative to RAU displayed significantly lower levels of externalizing problems (postintervention Cohen d = 0.48; 6-month Cohen d = 0.49; 12-month Cohen d = 0.50) and significantly higher levels of compliance to caregiver direction after treatment. Of those children with data at postintervention, greater clinically significant change was observed at postintervention for children in the iPCIT group (50 [74%]) than for those in the RAU group (30 [42%]), which was maintained at the 6-month but not the 12-month follow-up. iPCIT did not outperform RAU in reducing caregiving stress, but caregivers receiving iPCIT, relative to RAU, showed steeper increases in proportion of observed positive parenting skills (postintervention odds ratio [OR], 1.10; 95% CI, 0.53-2.21; 6-month OR, 1.31; 95% CI, 0.61-2.55; 12-month OR, 1.64; 95% CI, 0.70-3.07) and sharper decreases in proportion of observed controlling/critical behaviors (postintervention OR, 1.40; 95% CI, 0.61-1.52; 6-month OR, 1.72; 95% CI, 0.58-1.46; 12-month OR, 2.23; 95% CI, 0.53-1.37). After treatment, iPCIT caregivers also self-reported steeper decreases in harsh and inconsistent discipline than did than RAU caregivers (postintervention Cohen d = 0.24; 6-month Cohen d = 0.26; 12-month Cohen d = 0.27). CONCLUSIONS AND RELEVANCE:Results of this randomized clinical trial provide evidence that a telehealth-delivered parenting intervention with real-time therapist coaching led to significant and maintained improvements for young children with DD and their caregivers. Findings underscore the promise of telehealth formats for expanding scope and reach of care for underserved families. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT03260816.

Fetal motor behavior is an important clinical indicator of healthy development. However, our understanding of associations between fetal behavior and fetal brain development is limited. To fill this gap, this study introduced an approach to automatically and objectively classify long durations of fetal movement from a continuous four-dimensional functional magnetic resonance imaging (fMRI) data set, and paired behavior features with brain activity indicated by the fMRI time series. Twelve-minute fMRI scans were conducted in 120 normal fetuses. Postnatal motor function was evaluated at 7 and 36 months age. Fetal motor behavior was quantified by calculating the frame-wise displacement (FD) of fetal brains extracted by a deep-learning model along the whole time series. Analyzing only low motion data, we characterized the recurring coactivation patterns (CAPs) of the supplementary motor area (SMA). Results showed reduced motor activity with advancing gestational age (GA), likely due in part to loss of space (r = -.51, p < .001). Evaluation of individual variation in motor movement revealed a negative association between movement and the occurrence of coactivations within the left parietotemporal network, controlling for age and sex (p = .003). Further, we found that the occurrence of coactivations between the SMA to posterior brain regions, including visual cortex, was prospectively associated with postnatal motor function at 7 months (r = .43, p = .03). This is the first study to pair fetal movement and fMRI, highlighting potential for comparisons of fetal behavior and neural network development to enhance our understanding of fetal brain organization.

INTRODUCTION AND OBJECTIVES/OBJECTIVE:The opioid overdose epidemic is exacerbated by the emergence of Xylazine as an illicit drug adulterant. Xylazine, a veterinary sedative, can potentiate opioid effects while also causing toxic and potentially fatal side effects. This systematic review aims to assess the impact of Xylazine use and overdoses within the opioid epidemic context. METHOD/METHODS:A systematic search was conducted following PRISMA guidelines to identify relevant case reports, and case series related to Xylazine use. A comprehensive literature search included databases like Web of Science, PubMed, Embase, and Google Scholar, utilizing keywords and Medical Subject Headings (MeSH) terms related to Xylazine. Thirty-four articles met the inclusion criteria for this review. RESULTS:Intravenous (IV) administration was a common route for Xylazine use among various methods, including subcutaneous (SC), intramuscular (IM), and inhalation, with overall doses ranging from 40 mg to 4300 mg. The average dose in fatal cases was 1,200 mg, compared to 525 mg in non-fatal cases. Concurrent administration of other drugs, primarily opioids, occurred in 28 cases (47.5%). Intoxication was identified as a notable concern in 32 out of 34 studies, and treatments varied, with the majority experiencing positive outcomes. Withdrawal symptoms were documented in one case study, but the low number of cases with withdrawal symptoms may be attributed to factors such as a limited number of cases or individual variation. Naloxone was administered in eight cases (13.6%), and all patients recovered, although it should not be misconstrued as an antidote for Xylazine intoxication. Of the 59 cases, 21 (35.6%) resulted in fatal outcomes, with 17 involving Xylazine use in conjunction with other drugs. The IV route was a common factor in six out of the 21 fatal cases (28.6%). CONCLUSION/CONCLUSIONS:This review highlights the clinical challenges associated with Xylazine use and its co-administration with other substances, particularly opioids. Intoxication was identified as a major concern, and treatments varied across the studies, including supportive care, naloxone, and other medications. Further research is needed to explore the epidemiology and clinical implications of Xylazine use. Understanding the motivations and circumstances leading to Xylazine use, as well as its effects on users, is essential for developing effective psychosocial support and treatment interventions to address this public health crisis.

INTRODUCTION:The novel coronavirus disease 2019 (COVID-19) significantly disrupted therapy service delivery for children with disabilities and their families. Parents of children with disabilities have been particularly impacted as a large degree of responsibility has been placed on them to both manage and deliver therapies remotely. However, little is known regarding whether sociodemographic factors are associated with parents' perceptions of therapy service delivery during COVID-19. This study explored the relationship between sociodemographic factors and parents' satisfaction with therapies for children with disabilities during COVID-19. METHOD:Two hundred seven parents of children with disabilities completed an online survey battery that included the Family-Provider Partnership Scale and sociodemographic characteristics and assessed their satisfaction with their child[ren]'s therapies during COVID-19. RESULTS:Access to telehealth, receipt of only school-based therapies, parent education, number of household essential workers, and total number of children were associated with satisfaction with therapy service and/or the family-provider partnership. DISCUSSION:By better understanding the association between sociodemographic factors and parent perception of therapy service delivery, providers can better support families in optimizing service delivery during the remainder of COVID-19 mitigation efforts and during future periods of service disruption. This study provides insight into the sociodemographic characteristics that are associated with lower levels of satisfaction and thus require more tailored support from providers. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Characterizing the developmental trajectories of children with autism spectrum disorder (ASD) throughout adolescence and across different domains of functioning offers opportunities to improve long-term outcomes. This prospective study explored, for the first time, the evolution of children with ASD-without intellectual disability (ID) in terms of socio-adaptative skills, learning behaviors, executive functioning (EF), and internalizing/externalizing problems, compared to typically developing (TD) peers. Forty-five children with ASD-without ID and 37 matched TD children (aged 7-11) were assessed at baseline and after 5 years. Parents and teachers completed measures on theory of mind (ToM), socialization, daily living skills, learning style, EF, and emotional/behavioural difficulties at both time points. On all the domains assessed, the ASD group performed significantly worse than the TD group, both in childhood and adolescence. Specific changes were noted between baseline and follow-up assessment on adaptive skills, prosocial behavior, emotional control, inhibit, working memory and monitoring. Group membership (ASD/TD) was influenced by peer relationships and inhibit EF variables. These findings have implications for clinical and school settings.

Cognition in preverbal human infants must be inferred from overt motor behaviors such as gaze shifts, head turns, or reaching for objects. However, infant mammals - including human infants - show protracted postnatal development of cortical motor outflow. Cortical control of eye, face, head, and limb movements is absent at birth and slowly emerges over the first postnatal year and beyond. Accordingly, the neonatal cortex in humans cannot generate the motor behaviors routinely used to support inferences about infants' cognitive abilities, and thus claims of developmental continuity between infant and adult cognition are suspect. Recognition of the protracted development of motor cortex should temper rich interpretations of infant cognition and motivate more serious consideration of the role of subcortical mechanisms in early cognitive development.

Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous disorder with a high degree of psychiatric and physical comorbidity, which complicates its diagnosis in childhood and adolescence. We analyzed registry data from 238,696 persons born and living in Sweden between 1995 and 1999. Several machine learning techniques were used to assess the ability of registry data to inform the diagnosis of ADHD in childhood and adolescence: logistic regression, random Forest, gradient boosting, XGBoost, penalized logistic regression, deep neural network (DNN), and ensemble models. The best fitting model was the DNN, achieving an area under the receiver operating characteristic curve of 0.75, 95% CI (0.74-0.76) and balanced accuracy of 0.69. At the 0.45 probability threshold, sensitivity was 71.66% and specificity was 65.0%. There was an overall agreement in the feature importance among all models (τ > .5). The top 5 features contributing to classification were having a parent with criminal convictions, male sex, having a relative with ADHD, number of academic subjects failed, and speech/learning disabilities. A DNN model predicting childhood and adolescent ADHD trained exclusively on Swedish register data achieved good discrimination. If replicated and validated in an external sample, and proven to be cost-effective, this model could be used to alert clinicians to individuals who ought to be screened for ADHD and to aid clinicians' decision-making with the goal of decreasing misdiagnoses. Further research is needed to validate results in different populations and to incorporate new predictors.

BACKGROUND:NEUROD2, encoding the neurogenic differentiation factor 2, is essential for neurodevelopment. To date, heterozygous missense variants in this gene have been identified in eight patients (from six unrelated families) with epileptic encephalopathy and developmental delay. CASE REPORT/METHODS:We describe a child with initial clinical suspicion of Rett/Rett-like syndrome, in whom exome sequencing detected a novel de novo variant (c.388G > A, p.Glu130Lys) in NEUROD2. Interestingly, a missense change affecting the same codon, c.388G > C (p.Glu130Gln), was previously identified in other two patients. CONCLUSIONS:Our results suggest that Glu130 might represent a potential mutational hotspot of NEUROD2. Furthermore, the clinical findings (especially the absence of clinically overt seizures) strengthen the NEUROD2-phenotypic spectrum, implying that developmental delay may also manifest isolatedly. We suggest inclusion of NEUROD2-associated developmental and epileptic encephalopathies (DEEs) in the differential diagnosis of atypical Rett syndrome as well as gene panels related to autism spectrum disorder.