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1. This study compared serum concentrations of morphine after administration of a buccal tablet (25mg) with those after intramuscular injection (10mg). 2. Buccal morphine was administered to eleven healthy volunteers and intramuscular morphine was given to five preoperative surgical patients. Serum morphine concentrations were assayed by high performance liquid chromatography (h.p.l.c.) in samples taken up to 8 h after drug administration. 3. Mean maximum morphine concentrations were eight times lower after buccal administration than after intramuscular injection and occurred at a mean of 4 h later. Individual morphine concentration-time profiles showed marked interindividual variability after administration of the buccal tablet, consistent with considerable variation in tablet persistence time on the buccal mucosa. [ABSTRACT FROM AUTHOR]

Objectives: To assess changes in trainees' knowledge and application of Diversity, Equity, Inclusion, and Justice (DEIJ) concepts after participating in a midwestern academic medical center Leadership Education in Neurodevelopmental and Related Disabilities (LEND) program. LEND is a federally funded year-long program training individuals of various disciplines (e.g., speech pathology, family advocacy, psychology) to better support the health of individuals with disabilities., Methods: Trainees ( n  = 46) answered questions about their knowledge and application of DEIJ topics before and after program participation in 2021-2022 and 2022-2023. Changes in trainees' responses were examined using paired-samples t -tests., Results: Thirty-six (78%) participants identified as White, 7 (15%) as Black, 2 (4%) as Asian, and 2 (4%) as more than one race. Three (7%) participants identified as Hispanic/Latino. Over the one-year program, trainees' perceived knowledge increased [ t (45) = 5.84, p  < .001, M diff  = .59, Cohen's D  = 0.86]. Regarding articulating definitions of DEIJ terms, trainees' summed scores following program participation also improved [ t (45) = 4.71, p  < .001, M diff  = 2.37, Cohen's D  = 0.70]. However, their comfort with addressing prejudicial statements and discussing and combating "-isms" (application of DEIJ skills) did not increase [ t (45) = 1.74, p  = .09, M diff  = 0.17, Cohen's D = 0.26]., Conclusions for Practice: LEND program participation positively impacted trainees' perceived DEIJ knowledge and ability to define DEIJ terms. However, future refinements to the curriculum will be needed to improve trainees' application of skills and to develop a more nuanced understanding of equity, intersectionality, inclusion, and belonging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Fisher, Gies, Weber, Froehlich, Abimosleh, Ravindran and Smith.)

Purpose: Pediatric brain tumor survivors (PBTS) commonly experience mental health challenges, which can be exacerbated during adolescence and emerging adulthood (AEA). We examined survivors and caregivers' perceived need for mental health services and barriers to receiving mental health care. Methods: Families completed surveys to assess perceived need for mental health services, socioemotional impairment, and barriers to mental health services. Survivors were between 13 and 25 years of age and were at least 5 years from diagnosis. Results: Sixty-nine caregiver-PBTS dyads participated, as well as 18 survivors and 20 caregivers who participated individually. Approximately half of survivors were male ( n  = 57, 52.3%), 85% ( n  = 93) were White, and their average age was 19.31. Most caregivers ( n  = 63, 70.8%) and survivors ( n  = 55, 63.2%) endorsed need for services for the survivors. Adolescents endorsed more barriers related to perceived helpfulness, t (18) = 2.3, p  = 0.03, d  = 0.54, and effects of services, t (18) = 3.8, p  < 0.001, d  = 0.88, than their caregivers. Emerging adults, t (34) = 2.4, p  = 0.02, d  = 0.41, endorsed more content barriers than their caregivers.. Discussion: Both survivors and their caregivers reported obstacles to accessing mental health services such as perceived lack of need, concerns regarding the effectiveness and usefulness of services, and limited knowledge about the content of services. Psychoeducation and psychosocial screening can support families in understanding survivors' need for mental health services.

Background: Black families of children with autism spectrum disorder have less access to high quality, culturally responsive care for their children., Method: We assessed satisfaction and service utilization among fifty (29%) Black caregivers and 124 (71%) White caregivers of children with autism spectrum disorder. We also examined whether race moderated the association between satisfaction and service utilization., Results: We did not identify racial differences in satisfaction or service utilization. Race moderated the association between satisfaction and total service use, F(170) = 5.29, p =.02, therapy service use, F(163) = 3.59, p =.046, and community service use, F(169) = 4.76, p =.046. For Black families, there was a positive association between satisfaction and service use. There was no association between satisfaction and service use among White families., Discussion: Satisfaction may be particularly important among Black families, who have been mistreated by the healthcare system and frequently face discrimination. Our results suggest the importance of culturally responsive care for Black families., (© 2024. The Author(s).)

Background: Preterm birth is associated with adverse mental health outcomes, including internalizing problems, social difficulties and inattention. Interventions are needed beyond infancy and toddlerhood to support children and their families. We examined the feasibility and acceptability of the I-InTERACT Preterm pilot study, an online parenting intervention for preterm children ages 3-8., Method: Families participated in a weekly intervention comprised of seven sessions with online modules followed by videoconference coaching sessions with a therapist. Following completion of the study, caregivers completed a survey to assess their satisfaction and were asked to participate in a voluntary semi-structured interview to provide feedback. We anticipated greater than a 50% participation rate (enrollment feasibility) and 75% completion rate (adherence feasibility). We also hypothesized that at least 80% of participants would be satisfied with the intervention (acceptability)., Results: Nineteen of 32 families (59%) enrolled in the study, suggesting adequate enrollment feasibility. Feasibility of programme completion (adherence) was lower than anticipated (59%). Regarding satisfaction, all caregivers agreed that the programme's information was relevant to them and their family. Nearly all participants (92%) indicated that they had a better understanding of the effects of preterm birth on behaviour, that they enjoyed the programme, that it met their expectations and that they recommend the programme to others. In qualitative interviews, caregivers expressed satisfaction with the content, skills they learned, and receiving direct coaching. Caregivers suggested improvements to increase intervention feasibility and skill implementation, including offering biweekly sessions and more hands-on coaching., Conclusion: Our largely satisfactory acceptability rates suggest the value of and need for a parenting intervention for children born preterm past the initial period of early development. Future directions include modifying the intervention in response to caregiver feedback to improve recruitment, engagement and adherence., (© 2023 The Authors. Child: Care, Health and Development published by John Wiley & Sons Ltd.)

Lay Abstract: Children of color are diagnosed with autism later than White children. Caregivers of color are also more likely than White caregivers to report that their child's healthcare providers do not treat them as a partner, spend enough time with them, or respect their culture and values. We wanted to better understand the experiences of caregivers of color with the diagnostic process of autism spectrum disorder, from the time they discuss developmental concerns with their child's primary care provider to when the diagnosis is shared with them. We systematically reviewed the literature and found 15 articles that explored the experiences of caregivers of color. Caregivers of color described that they faced large-scale barriers, such as the cost of appointments, transportation, and long wait lists. They also reported negative experiences with providers, including providers not taking their concerns seriously, making assumptions about caregivers, and delaying referrals for an evaluation. Caregivers stated that their own lack of knowledge of autism spectrum disorder, stigma, their family's thoughts and opinions, and cultural differences between providers and caregivers served as barriers during the diagnostic process. Communication challenges were discussed and included use of medical and technical jargon, a lack of follow-up, language barriers, and difficulty obtaining high-quality interpreters. Some families described providers, other individuals, community networks, and self-advocacy as helpful during the diagnostic process. Large-scale changes are needed, such as increases in the number of providers who are trained in diagnosing Autism. Provider-level changes (e.g. implicit bias training) are also important for improving caregivers' experiences.

Background: Pediatric brain tumor survivors (PBTS) are at risk of worse quality of life (QOL) due to the impact of neurotoxic treatments on the developing nervous system. Parenting factors such as protectiveness have been linked to worse QOL in childhood cancer survivors generally, but have yet to be explored for PBTS. We examined whether parenting behaviors moderated the association between neurotoxic treatment and QOL for PBTS., Methods: PBTS ( n  = 40; ages 10-25) and their caregivers ( n  = 47) completed measures of parenting behaviors including warmth (support/connectedness) and psychological control (protectiveness) and QOL. We divided the sample into moderate/high and low neurotoxicity groups based on chart review using the Pediatric Neuro-Oncology Rating of Treatment Intensity and examined moderator effects., Results: Survivor-reported primary caregiver warmth moderated the relationship between neurotoxicity and caregiver-reported QOL. Moderate/high neurotoxicity was associated with lower caregiver-reported QOL only when survivor-reported primary caregiver warmth was low, P  = .02. Similar results were found for survivor-reported QOL. Caregiver-reported psychological control moderated the association between neurotoxicity and caregiver-reported QOL such that neurotoxicity only affected QOL at high levels of psychological control, P  = .01., Conclusions: Heightened associations between parenting and QOL in the context of neurotoxic treatments underscore the need to better support PBTS. Findings are consistent with research suggesting that family factors may be particularly important for children with other neurological insults. Limitations include cross-sectional design and a small/heterogeneous clinical sample with low ethnic/racial diversity. Prospective studies are needed to refine evidence-based screening and develop psychosocial intervention strategies to optimize QOL for PBTS and their families., Competing Interests: None., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective Pediatric traumatic brain injury (TBI) is associated with long-term cognitive and behavioral deficits. Social communication impairments are common and impact functional outcomes, such as social engagement and academic performance. There are many barriers to identifying social communication deficits following TBI, including the absence of a standardized parent-reported communication measure for use in this population. The Children's Communication Checklist-Second Edition (CCC-2) has demonstrated utility in identifying communication deficits in diagnoses other than TBI. This study investigated the clinical utility of the CCC-2's social communication scales in children with TBI. Method: 203 children who sustained TBI or orthopedic injuries between the ages of 36 and 83 months were recruited as part of a larger, longitudinal study. We analyzed social communication subscale scores from the CCC-2 an average of 3.5 years postinjury. We used binary logistic regression analyses to examine the measure's accuracy in classifying children with and without social communication deficits on other measures of pragmatic language and social competence. Correlation analyses and linear mixed models were used to examine the construct validity of the CCC-2. Results: The CCC-2 was able to accurately classify those with and without pragmatic language impairments on the Comprehensive Assessment of Spoken Language 92% of the time (sensitivity = 55%) and 96% of the time on the Home and Community Social Behavior scale (sensitivity = 72%). The CCC-2 demonstrated strong correlations with and predictive validity for measures of social communication and competence. Conclusions: The findings offer support for the clinical utility of the CCC-2 in the pediatric TBI population.

For young children with autism spectrum disorder (ASD), early intensive intervention is imperative. The Bridge Skill Development Program is a parent-mediated intervention designed to "bridge the gap" during the period after a diagnosis of ASD while children wait for intensive intervention. This program introduces applied behavior analysis (ABA) teaching techniques, including the use of parent-mediated discrete trial teaching (DTT), to promote skill acquisition of target behaviors. Significant improvements were observed across four target behaviors taught to all participants. The program also aims to connect participants to intensive ABA programming., Competing Interests: Conflicts of InterestThe authors have no financial or nonfinancial interests that are directly or indirectly related to the work submitted for publication., (© Association for Behavior Analysis International 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Purpose :To understand child and family needs following TBI in early childhood, 22 caregivers of children who were hospitalized for a moderate to severe TBI between the ages of 0 and 4 within the past 10 years ( M  = 3.27 years; Range = 3 months to 8 years) participated in a needs assessment. Methods: Through a convergent study design, including focus groups (FG), key informant interviews (KII), and standardized questionnaires, caregivers discussed challenges and changes in their child's behaviors and functioning in addition to resources that would be helpful post-injury. Standardized questionnaires assessing current psychological distress and parenting stress in addition to open-ended questions about their general experience were completed. Results: Results indicated some families continue to experience unresolved concerns relating to the child's injury, caregiver wellbeing, and the family system after early TBI, including notable variation in caregiver reported psychological distress and parenting stress. Caregivers noted unmet needs post-injury, such as child behavior management and caregiver stress and coping. Conclusion: Early TBI can have a long-term impact on the child, caregivers, and family system. Addressing the needs of the whole family system in intervention and rehabilitation efforts may optimize outcomes following early TBI. Study results will inform intervention development to facilitate post-injury coping and positive parenting.IMPLICATIONS FOR REHABILITATIONEarly TBI can result in unmet needs that have a lingering impact on the child, caregiver, and family.Caregivers need information and resources that address their own distress and stressors related to changes in the child post-injury.Our study suggests that stress management and self-care skills are possible targets of intervention for caregivers of children who experienced an early TBI.

Objective: To examine professional stakeholders' perspectives of barriers to behavioral health care (BHC) follow-up and telepsychology after pediatric traumatic brain injury (TBI)., Methods: Twenty-nine professionals participated in a focus group (FG) or key informant interview (KII) between January and March 2020. Professionals answered questions about facilitators and barriers to BHC follow-up and telepsychology. Given widespread telepsychology implementation since COVID-19, a follow-up survey assessing telehealth perceptions since the pandemic was sent out in December 2020. Nineteen professionals completed the survey., Results: Professionals identified individual (e.g., family factors, insurance coverage/finances, transportation/distance, availability, planning follow-up care) and system-level (e.g., lack of access to BHC providers) barriers to BHC post-injury. Possible solutions, like collaborative follow-up care, were also identified. Generally, clinical professionals have favorable impressions of telepsychology and utilized services as a delivery modality for clinical care. Though telepsychology could reduce barriers to care, professionals also expressed concerns (e.g., technology issues, security/safety) and challenges (e.g., funding, accessibility, training/licensure for clinicians) with implementing telepsychology., Conclusion: Barriers identified highlight the need for context-specific solutions to increase BHC access, with telepsychology generally recognized as a beneficial modality for BHC. Future work should continue to focus on understanding barriers to BHC and potential solutions after pediatric TBI.

Objective: We examined parent- and adolescent-reported executive functioning (EF) behaviors following pediatric traumatic brain injury (TBI) in the context of Online Family Problem-Solving Therapy (OFPST) and moderators of change in EF behaviors., Method: In total, 274 families were randomized to OFPST or an internet resource comparison group. Parents and adolescents completed the Behavior Rating Inventory of Executive Function at four time points. Mixed models were used to examine EF behaviors, assessing the effects of visit, treatment group, rater, TBI severity, age, socioeconomic status, and family functioning., Results: Parents rated their adolescents' EF as poorer (F(3,1156) = 220.15, p < .001; M = 58.11, SE = 0.73) than adolescents rated themselves (M = 51.81, SE = 0.73). Across raters, EF behaviors were poorer for adolescents whose parents had less education (F(3,1156) = 8.60, p = .003; M = 56.76, SE = 0.98) than for those with more education (M = 53.16, SE = 0.88). Age at baseline interacted with visit (F(3,1156) = 5.05, p = .002), such that families of older adolescents reported improvement in EF behaviors over time. Family functioning also interacted with visit (F(3, 1156) = 2.61, p = .049), indicating more improvement in EF behaviors over time in higher functioning families. There were no effects of treatment or TBI severity., Conclusion: We identified a discrepancy between parent- and adolescent-reported EF, suggesting reduced awareness of deficits in adolescents with TBI. We also found that poorer family functioning and younger age were associated with poorer recovery after TBI, whereas adolescents of parents with less education were reported as having greater EF deficits across time points.

Objective: Neuropsychological testing is often recommended for pediatric brain tumor survivors, yet little is known about perceptions of testing and resources. The purpose of this study is to examine survivor and caregiver perceptions about neuropsychology and resources and identify factors associated with receipt of neuropsychological testing., Method: Survivors and their families (N = 55) completed questionnaires on demographics and family functioning. The Neurological Predictive Scale was used to rate treatment intensity and expected impact on neuropsychological functioning. Chi squares and logistic regression were used to examine the associations between demographic, disease, and treatment factors and receipt of neuropsychological testing. Qualitative interviews (N = 25) were completed with a subset of families and coded with thematic content analysis and a multicoder consensus process with high inter-rater reliability (kappas .91-.93)., Results: The majority of survivors received neuropsychological testing. Survivors were more likely to receive neuropsychological testing if they were younger and if their caregivers had less than a college education and lower income. Qualitatively, families identified neurocognitive concerns. Some families reported that neuropsychological testing was helpful in clarifying deficits or gaining accommodations, while other families had difficulty recalling results or identified barriers to services. To mitigate the impact of deficits, families implemented metacognitive strategies and advocated for their survivor at school. Families desired more resources around the transition to adulthood and more opportunities for connection with other survivors., Conclusions: Many families valued insights from neuropsychological services yet identified room for further improvement to address barriers and ensure accessibility and comprehensibility of neuropsychological findings., (Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications 2021.)

Background: The COVID-19 pandemic has prompted unprecedented challenges, contributing to greater difficulties among families of children with special health care needs, such as pediatric brain tumor survivors. We examined the impact of the pandemic on psychosocial functioning of adolescent and emerging adult survivors and their parents. We hypothesized that COVID-19 disruptions and survivor social connectedness would be associated with survivor-reported posttraumatic stress and family outcomes, including family functioning, parenting, and parent mental health., Procedure: Fifty-five families (44 survivors, 48 parents) were recruited via phone and email to participate in the study. Survivors were ages 13-25 (M = 19.62, SD = 3.47) and at least 5 years post diagnosis. Parents completed the COVID-19 Exposure and Family Impact Survey (CEFIS), and survivors completed the Environmental influences on Child Health Outcomes (ECHO) COVID-19 child self-report form, which assessed pandemic impacts on their psychosocial functioning., Results: Parents reported a mean of 7.52 (SD = 2.83) disruptions to their families' lives. The pandemic negatively affected survivors' life satisfaction (M diff  = 0.46, t(44) = 3.96, p < .001), with 92% reporting reduced social connectedness (n = 39). Total disruptions due to COVID-19 and survivor social connectedness predicted survivor-reported posttraumatic stress, above and beyond survivors' pre-pandemic psychosocial risk. Most parents reported positive changes in their parenting (n = 31, 67.4%) and family cohesion (n = 30, 66.7%). However, they also reported worsened mood (n = 28, 62.3%) and increased anxiety (n = 31, 71.1%)., Conclusions: Parents and survivors reported positive and negative impacts of COVID-19, which had downstream consequences on survivor psychosocial functioning. Follow-up care should consider potential adverse effects on social connectedness and stress symptoms., (© 2021 Wiley Periodicals LLC.)

Stem cells give rise to the entirety of cells within an organ. Maintaining stem cell identity and coordinately regulating stem cell divisions is crucial for proper development. In plants, mobile proteins, such as WUSCHEL-RELATED HOMEOBOX 5 (WOX5) and SHORTROOT (SHR), regulate divisions in the root stem cell niche. However, how these proteins coordinately function to establish systemic behaviour is not well understood. We propose a non-cell autonomous role for WOX5 in the cortex endodermis initial (CEI) and identify a regulator, ANGUSTIFOLIA (AN3)/GRF-INTERACTING FACTOR 1, that coordinates CEI divisions. Here, we show with a multi-scale hybrid model integrating ordinary differential equations (ODEs) and agent-based modeling that quiescent center (QC) and CEI divisions have different dynamics. Specifically, by combining continuous models to describe regulatory networks and agent-based rules, we model systemic behaviour, which led us to predict cell-type-specific expression dynamics of SHR, SCARECROW, WOX5, AN3 and CYCLIND6;1, and experimentally validate CEI cell divisions. Conclusively, our results show an interdependency between CEI and QC divisions., Competing Interests: The authors declare no conflict of interest., (© The Author(s) 2021.)

Given sparse literature examining receipt of behavioral health service in children and caregivers following traumatic brain injury (TBI), we sought to identify predictors of unmet need. We performed an individual participant data meta-analysis using generalized linear mixed-effect models to examine predictors of behavioral health service use and unmet need. We included 572 children, ages 3 to 18, who were hospitalized overnight following complicated mild to severe TBI between 2002 and 2015. Caregivers completed ratings of depression and distress, child behavior problems, family functioning, and behavioral health service utilization. For children, unmet behavioral health service need was defined as an elevation on one or more child behavior problem scales without receipt of behavioral health services. For caregivers, unmet need was defined as an elevation on either a depression or distress scale without behavioral health service utilization. Among those with behavioral health needs, rates of unmet need were high for both children (77.8%) and caregivers (71.4%). Poorer family functioning was related to more unmet need in children (F(1, 497) = 6.57, p = 0.01; OR = 1.8) and caregivers (F(1, 492) = 17.54, p < 0.001; OR = 2.7). Children with unmarried caregivers also had more unmet behavioral health service need than those with married caregivers (F(1, 497) = 12.14, p < 0.001; OR = 2.2). In conclusion, unmet needs are common after pediatric TBI and relate to family factors. The findings underscore the importance of monitoring service needs following pediatric TBI and point to disparities in service use.

Mild Traumatic Brain Injury (mTBI) is a significant cause of morbidity for adolescents. Currently, there is a lack of evidence-based interventions to address common sequelae of mTBI. To address this gap, we designed a program to promote recovery for adolescents following mTBI. Preliminary testing of the Self-Monitoring Activity Regulation and Relaxation Treatment (SMART) program demonstrated good usability but indicated a need for modifications to the program. The SMART application was redesigned with the addition of more interactive and gamified components. Content was also reframed to specifically target and engage adolescents with mTBI. We describe the usability evaluation of the updated SMART application. Children aged 11-18 years diagnosed with mTBI who were 1 to 6 months post mTBI were recruited to participate in a 1-2-hour usability session in which they thought aloud and responded to targeted usability-related questions during their interaction with the SMART program. After completing the session, participants rated their usability experience using the System Usability Scale (SUS) and rated the overall user-friendliness of the program. Participants' responses during the session were qualitatively coded and analyzed. Six adolescents participated in a usability session (average age = 13.7 years). On the SUS, participants rated the program as highly usable (M = 85.6, SD = 3.24). They also had overwhelmingly positive feedback regarding the content, design and structure of the program. Overall, findings suggest that the redesigned SMART program was usable, acceptable, and relevant to adolescents with mTBI. Based on adolescents' feedback, additional modifications were made before the program undergoes efficacy testing., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Background: Survivors of childhood brain tumors experience persistent health concerns across their lifespan. In the current study, the authors evaluated changes in symptom burden over the course of 12 months using pediatric Patient-Reported Outcomes Measurement Information System (PROMIS) measures., Methods: Data from 202 survivors aged 8 to 21 years and 262 parents of survivors who were aged 5 to 21 years were analyzed. All completed a PROMIS Cognition short form and computerized adaptive tests of pediatric Anxiety, Depressive Symptoms, Fatigue, Mobility, Upper Extremity Function, and Peer Relationships. Approximately one-half of participants (223 participants: 97 survivors of childhood brain tumors and 126 parents) completed the 12-month follow-up. Linear mixed-effects models evaluated group-level symptoms over time. Cox proportional hazard models explored whether symptoms predicted survival, and latent class growth analysis investigated patterns of individual-level symptom changes over time., Results: Linear mixed-effects models demonstrated that patient-reported Cognition and parent-reported Anxiety worsened over time. Latent class growth analysis results indicated that patient and parent reports diverged, both with regard to the number of classes identified and in the trends of these classes. Parents and patients reported similar patterns of depression over time. For the other areas, parents either were more likely to observe different patterns (Peer Relationships and Mobility) or less likely to observe different patterns (Upper Extremity Function, Cognition, Anxiety, and Fatigue). Baseline patient-reported Mobility and Upper Extremity Function were found to be associated with survival., Conclusions: Survivors of childhood brain tumors demonstrated different trajectory patterns of symptom burden. Along with baseline functioning status and days since treatment, patient-reported Mobility and Upper Extremity Function were associated with survival, suggesting a possible role for patient-reported outcomes in clinical care, especially individualized, tailored assessments such as PROMIS., (© 2020 American Cancer Society.)

Objective: This study examined whether carrying dopamine-related "risk" genes-either the dopamine transporter (DAT1) 10-repeat allele or dopamine receptor-4 (DRD4) 7-repeat allele-moderated the association of family environment and executive function (EF) following traumatic brain injury (TBI) in early childhood., Methods: Caregivers of children with TBI or orthopedic injury (OI) completed the Behavior Rating Inventory of Executive Function (BRIEF) at postinjury visits. General linear models examined gene by environment interactions as moderators of the effects of TBI on EF at 12 months and 7 years postinjury., Results: At 12 months, we did not find any significant gene by environment interactions. At 7 years, we found a significant 3-way interaction among combined carrier status, level of permissive parenting, and injury type. For children exposed to more optimal parenting, carriers of DAT1 and/or DRD4 risk alleles with TBI showed significantly worse parent-reported EF than carriers with OI. In those with less optimal parenting, carriers and noncarriers with TBI, as well as carriers with OI, showed significantly worse parent-reported EF than noncarriers with OI, with medium to large effect sizes., Conclusions: The findings highlight the importance of considering polygenetic and environmental factors in future studies of recovery following TBI and other injuries in childhood.

Stem cells divide and differentiate to form all of the specialized cell types in a multicellular organism. In the Arabidopsis root, stem cells are maintained in an undifferentiated state by a less mitotically active population of cells called the quiescent center (QC). Determining how the QC regulates the surrounding stem cell initials, or what makes the QC fundamentally different from the actively dividing initials, is important for understanding how stem cell divisions are maintained. Here we gained insight into the differences between the QC and the cortex endodermis initials (CEI) by studying the mobile transcription factor SHORTROOT (SHR) and its binding partner SCARECROW (SCR). We constructed an ordinary differential equation model of SHR and SCR in the QC and CEI which incorporated the stoichiometry of the SHR-SCR complex as well as upstream transcriptional regulation of SHR and SCR. Our model prediction, coupled with experimental validation, showed that high levels of the SHR-SCR complex are associated with more CEI division but less QC division. Furthermore, our model prediction allowed us to propose the putative upstream SHR regulators SEUSS and WUSCHEL-RELATED HOMEOBOX 5 and to experimentally validate their roles in QC and CEI division. In addition, our model established the timing of QC and CEI division and suggests that SHR repression of QC division depends on formation of the SHR homodimer. Thus, our results support that SHR-SCR protein complex stoichiometry and regulation of SHR transcription modulate the division timing of two different specialized cell types in the root stem cell niche., Competing Interests: The authors declare no competing interest.

We piloted a patient-reported screener in a clinic for survivors of childhood cancers to facilitate detection of late effects, psychosocial needs, and distress. The mean number of patient-reported survivorship concerns endorsed per patient was 3.2; most frequent were difficulties with body weight, sleep, work/school, and fertility. Few individuals reported clinically significant distress or fear of recurrence. Electronic health record data produced an average of 2.3 late effects. Administration of a brief screener was effective in identifying additional current medical and psychosocial care needs among adult survivors of childhood cancers in a survivorship clinic.

The novel coronavirus, COVID-19, has led to sweeping changes in psychological practice and the concomitant rapid uptake of telepsychotherapy. Although telepsychotherapy is new to many clinical psychologists, there is considerable research on telepsychotherapy treatments. Nearly 2 decades of clinical research on telepsychotherapy treatments with children with neurological conditions has the potential to inform emerging clinical practice in the age of COVID-19. Toward that end, we synthesized findings from 14 clinical trials of telepsychotherapy problem-solving and parent-training interventions involving more than 800 children and families with diverse diagnoses, including traumatic brain injury, epilepsy, brain tumors, congenital heart disease, and perinatal stroke. We summarize efficacy across studies and clinical populations and report feasibility and acceptability data from the perspectives of parents, children, and psychotherapists. We describe adaptation for international contexts and strategies for troubleshooting technological challenges and working with families of varying socioeconomic strata. The extensive research literature reviewed and synthesized provides considerable support for the utility of telepsychotherapy with children with neurological conditions and their families and underscores its high level of acceptability with both diverse clinical populations and providers. During this period of heightened vulnerability and stress and reduced access to usual supports and services, telepsychotherapy approaches such as online family problem-solving treatment and online parenting skills training may allow psychologists to deliver traditional evidence-based treatments virtually while preserving fidelity and efficacy.

Predicting gene regulatory networks (GRNs) from expression profiles is a common approach for identifying important biological regulators. Despite the increased use of inference methods, existing computational approaches often do not integrate RNA-sequencing data analysis, are not automated or are restricted to users with bioinformatics backgrounds. To address these limitations, we developed tuxnet, a user-friendly platform that can process raw RNA-sequencing data from any organism with an existing reference genome using a modified tuxedo pipeline (hisat 2 + cufflinks package) and infer GRNs from these processed data. tuxnet is implemented as a graphical user interface and can mine gene regulations, either by applying a dynamic Bayesian network (DBN) inference algorithm, genist, or a regression tree-based pipeline, rtp-star. We obtained time-course expression data of a PERIANTHIA (PAN) inducible line and inferred a GRN using genist to illustrate the use of tuxnet while gaining insight into the regulations downstream of the Arabidopsis root stem cell regulator PAN. Using rtp-star, we inferred the network of ATHB13, a downstream gene of PAN, for which we obtained wild-type and mutant expression profiles. Additionally, we generated two networks using temporal data from developmental leaf data and spatial data from root cell-type data to highlight the use of tuxnet to form new testable hypotheses from previously explored data. Our case studies feature the versatility of tuxnet when using different types of gene expression data to infer networks and its accessibility as a pipeline for non-bioinformaticians to analyze transcriptome data, predict causal regulations, assess network topology and identify key regulators., (© 2019 The Authors The Plant Journal © 2019 John Wiley & Sons Ltd.)

Background: This study evaluated pre-defined aspects of content validity of the 18-item NCCN FACT-Ovarian Symptom Index (NFOSI-18) and its Disease-Related Symptoms-Physical (DRS-P) subscale, as clinical trial outcome tools for patients with advanced ovarian cancer., Methods: Twenty-one women (mean age 59.5 years) diagnosed with advanced ovarian cancer completed the NFOSI-18 and participated in a cognitive interview to explore: (1) whether 'pain' and 'cramps' are considered redundant; (2) whether 'fatigue' and 'lack of energy' are overlapping concepts; (3) whether patients consider severity when responding to the item "I am bothered by constipation;" and (4) factors considered when responding to the item "I am sleeping well." Interviews were audio-recorded, transcribed, and analyzed qualitatively., Results: Pain was associated with discomfort, hurt, and life interference; 'cramps' was associated with pain, muscle tightening, and menstrual or digestive issues. Most (81%) considered the items "I have pain" and "I have cramps in my stomach area" to be more different than similar. Participants associated 'fatigue' with intense tiredness and 'lack of energy' with motivation and capability to complete daily activities. Item comparisons revealed a majority (65%) considered the items to be more different than similar. When responding to "I am bothered by constipation," patients indicated constipation severity was related to bother. Finally, patients considered disease, treatment, and other factors when responding to "I am sleeping well.", Conclusions: Findings support content validity of the NFOSI-18 and its DRS-P as originally constructed. We propose an alternative scoring option that excludes the item "I am sleeping well" from the DRS-P when used as a symptom-focused index for clinical research in a regulatory context.

Stem cells are responsible for generating all of the differentiated cells, tissues, and organs in a multicellular organism and, thus, play a crucial role in cell renewal, regeneration, and organization. A number of stem cell type-specific genes have a known role in stem cell maintenance, identity, and/or division. Yet, how genes expressed across different stem cell types, referred to here as stem-cell-ubiquitous genes, contribute to stem cell regulation is less understood. Here, we find that, in the Arabidopsis root, a stem-cell-ubiquitous gene, TESMIN-LIKE CXC2 (TCX2), controls stem cell division by regulating stem cell-type specific networks. Development of a mathematical model of TCX2 expression allows us to show that TCX2 orchestrates the coordinated division of different stem cell types. Our results highlight that genes expressed across different stem cell types ensure cross-communication among cells, allowing them to divide and develop harmonically together.

Objectives: We conducted joint analyses from five randomized clinical trials (RCTs) of online family problem-solving therapy (OFPST) for children with traumatic brain injury (TBI) to identify child and parent outcomes most sensitive to OFPST and trajectories of recovery over time., Methods: We examined data from 359 children with complicated mild to severe TBI, aged 5-18, randomized to OFPST or a control condition. Using profile analyses, we examined group differences on parent-reported child (internalizing and externalizing behavior problems, executive function behaviors, social competence) and family outcomes (parental depression, psychological distress, family functioning, parent-child conflict)., Results: We found a main effect for measure for both child and family outcomes [F(3, 731) = 7.35, p < .001; F(3, 532) = 4.79, p = .003, respectively], reflecting differing degrees of improvement across measures for both groups. Significant group-by-time interactions indicated that children and families in the OFPST group had fewer problems than controls at both 6 and 18 months post baseline [t(731) = -5.15, p < .001, and t(731) = -3.90, p = .002, respectively, for child outcomes; t(532) = -4.81, p < .001, and t(532) = -3.80, p < .001, respectively, for family outcomes]., Conclusions: The results suggest limited differences in the measures' responsiveness to treatment while highlighting OFPST's utility in improving both child behavior problems and parent/family functioning. Group differences were greatest at treatment completion and after extended time post treatment.

Background: Children with brain tumors can experience symptom burden throughout their disease continuum. The aim of the study was to evaluate symptom burden reported by children with brain tumors and factors that potentially were associated with their symptoms., Methods: Data from 199 children with brain tumors aged 7-22 (mean age = 14 years; 52% males; 76% white) were analyzed. Symptom burden was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) via computerized adaptive testing (CAT)-anxiety, depression, fatigue, mobility, upper extremity function, peer relationship, and cognition. Patients and parents completed Symptom Distress Scales (SDS). Test statistics and ANOVA were used to evaluate relationships between PROMIS measures and potentially influential variables., Results: Significant results (P < 0.01) showing impact of symptom burden included: PROMIS measures correlated with SDSs reported by patients and parents on all comparisons. Fatigue, mobility, and upper extremity function were associated with Karnofsky functional performance status, number of treatment modalities (0-3), and time since last treatment (≤1 year, >1 year). Fatigue and cognition were associated with educational program (regular classroom without an individualized education plan vs those that had an individualized education plan); mobility and upper extremity function were associated with time since last radiation. Mobility, upper extremity function, and anxiety were associated with time since last chemotherapy., Conclusions: Significant associations were found between PROMIS and SDS as well as clinical and demographic characteristics. Brief-yet-precise PROMIS CATs can be used to systematically assess symptom burden experienced by children with brain tumors., (© 2018 Wiley Periodicals, Inc.)

Cell type-specific gene expression profiles are useful for understanding genes that are important for the development of different tissues and organs. Here, we describe how to perform fluorescence-activated cell sorting (FACS) on Arabidopsis root protoplasts to isolate specific cell types in the root. We then detail how to extract and process RNA from a very low number of cells (≥40 cells) for RNA sequencing (RNA seq). Finally, we describe how to process RNA seq data using TopHat and how to identify differentially expressed genes using PoissonSeq.

Identifying the transcription factors (TFs) and associated networks involved in stem cell regulation is essential for understanding the initiation and growth of plant tissues and organs. Although many TFs have been shown to have a role in the Arabidopsis root stem cells, a comprehensive view of the transcriptional signature of the stem cells is lacking. In this work, we used spatial and temporal transcriptomic data to predict interactions among the genes involved in stem cell regulation. To accomplish this, we transcriptionally profiled several stem cell populations and developed a gene regulatory network inference algorithm that combines clustering with dynamic Bayesian network inference. We leveraged the topology of our networks to infer potential major regulators. Specifically, through mathematical modeling and experimental validation, we identified PERIANTHIA ( PAN ) as an important molecular regulator of quiescent center function. The results presented in this work show that our combination of molecular biology, computational biology, and mathematical modeling is an efficient approach to identify candidate factors that function in the stem cells., Competing Interests: The authors declare no conflict of interest.

To understand complex regulatory processes in multicellular organisms, it is critical to be able to quantitatively analyze protein movement and protein-protein interactions in time and space. During Arabidopsis development, the intercellular movement of SHORTROOT (SHR) and subsequent interaction with its downstream target SCARECROW (SCR) control root patterning and cell fate specification. However, quantitative information about the spatio-temporal dynamics of SHR movement and SHR-SCR interaction is currently unavailable. Here, we quantify parameters including SHR mobility, oligomeric state, and association with SCR using a combination of Fluorescent Correlation Spectroscopy (FCS) techniques. We then incorporate these parameters into a mathematical model of SHR and SCR, which shows that SHR reaches a steady state in minutes, while SCR and the SHR-SCR complex reach a steady-state between 18 and 24 hr. Our model reveals the timing of SHR and SCR dynamics and allows us to understand how protein movement and protein-protein stoichiometry contribute to development.

Stem cells are the source of different cell types and tissues in all multicellular organisms. In plants, the balance between stem cell self-renewal and differentiation of their progeny is crucial for correct tissue and organ formation. How transcriptional programs precisely control stem cell maintenance and identity, and what are the regulatory programs influencing stem cell asymmetric cell division (ACD), are key questions that researchers have sought to address for the past decade. Successful efforts in genetic, molecular, and developmental biology, along with mathematical modeling, have identified some of the players involved in stem cell regulation. In this review, we will discuss several studies that characterized many of the genetic programs and molecular mechanisms regulating stem cell ACD and their identity in the Arabidopsis root. We will also highlight how the growing use of mathematical modeling provides a comprehensive and quantitative perspective on the design rules governing stem cell ACDs., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A 41-year-old man developed acute respiratory failure in association with thoracotomy and decortication for a persisting pleural collection secondary to a stab injury. The use of veno-venous extracorporeal membrane gas exchange proved life-saving.

In a prospective study, 218 cardiothoracic patients, in whom 'Abbocath-T' cannulae had been inserted preoperatively into the internal jugular vein, were randomized to receive skin preparation of the insertion site with tincture of iodine (108 controls) or tincture of iodine followed by application of sterile 2% calcium mupirocin ointment (110 test patients). Cannulae were usually removed within 48 h of the operation. Patients receiving mupirocin were less likely to develop significant colonization of one or more of their cannulae as judged by Maki's criterion of a yield of greater than 15 colony forming units (cfu) from a cannula segment rolled on an agar plate (17% of mupirocin treated patients compared with 54% of the controls, P less than 0.001). Coagulase-negative staphylococci, micrococci, or both, were the commonest isolates and were cultured from 70% of the 186 control cannulae compared with 24% of 172 cannulae inserted through mupirocin-treated skin (P less than 0.001). A count of more than 15 cfu was found on the tips of 25% control cannulae compared with 5% of the cannulae from mupirocin-treated patients, an effect which was independent of in-situ time (P less than 0.001). For cannulae with colonized tips, the same species was isolated from the skin of the insertion site in 67%, from the exterior of the hub in 61% and from the lumen in only 15%. There were no side effects attributed to mupirocin or superinfection with resistant organisms. We conclude that in cardiothoracic patients the application of mupirocin after standard skin preparation with tincture of iodine significantly reduces the colonization of central venous cannulae by organisms derived from the skin insertion site.

Fifty patients were admitted to a double-blind, double-dummy study comparing buccal morphine 10 mg tablets and intramuscular morphine sulphate 13.5 mg as premedication. This investigation was performed on the basis of favourable results obtained in an earlier 25 patient pilot study designed to examine the efficacy, safety and patient acceptability of buccal morphine 10 mg tablets as pre-anaesthetic medication. Both studies and sets of results are presented and show that, whilst buccal morphine is a safe alternative means of delivering opioid premedication, which is acceptable to the majority of patients, an equivalent intramuscular morphine dose is nevertheless a more effective premedicant in terms of anxiolysis and wakefulness, as assessed by linear analogue scores. Pharmacokinetic considerations are advanced both to explain the differing clinical efficacies of the two means of morphine administration and to indicate that improved per- and immediate postoperative analgesia might be obtainable in patients premedicated with buccal morphine.

1. The prior addition of non-aggregating concentrations of the divalent cation ionophore, A-23187, causes human platelets to aggregate in response to a subsequent addition of the 2',3'-dialdehyde and 2',3'-dialcohol derivatives of ADP (oADP and or ADP). Previous studies [Pearce et al. (1978) Eur. J. Biochem. 88, 543--555] have shown that these derivatives act as partial agonists at the platelet ADP receptor inducing only the transition from discoid to globular morphology ('shape change'). A secretion response is also observed on addition of a low concentration of ionophore A-23187 prior to orADP. These responses are not observed if ionophore A-23187 is added prior to the 2',3'-dialdehyde and 2',3'-dialcohol derivatives of ATP (oATP and or ATP) and are markedly inhibited by prior addition of the ADP antagonist, adenosine 5'-[beta, gamma-methylene]triphosphate. 2. The aggregation response to oADP in the presence of ionophore A-23187 is reduced but not eliminated by addition of 3 mM EGTA when studies are performed in heparinised platelet-rich plasma. Additions of 3 mM EGTA in citrated platelet-rich plasma, or of 4 mM EDTA in either system completely inhibits this response. Inhibitors which are reported to elevate the intracellular concentration of adenosine 3':5'-monophosphate (cyclic AMP) or to prevent Ca2+ movement also inhibit the aggregation response to oADP which is observed in the presence of ionophore A-23187. 3. Prior addition of inhibitors of adenylate cyclase fails to cause an aggregation response to subsequent addition of oADP or orADP. Certain of these inhibitors enhance and prolong the shape change response to oADP or orADP but only at concentrations an order of magnitude in excess of those required to antagonise inhibition by agents such as prostaglandin E1, which act by increasing the concentration of cyclic AMP. 4. The concentration of prostaglandin E1, adenosine or papaverine required to inhibit shape change induced by oADP is one to two orders of magnitude lower than that required to inhibit shape change induced by ADP. 5. Prior addition of oADP decreases the lag phase in the response of human platelets to arachidonate while also increasing the concentration required to observe half-maximal response, and causing a decrease in the extent of the response. Prior addition of oATP also diminishes the extent of this response and increases the concentration of arachidonate required but has no effect on the lag phase. 6. The data suggest that oADP and orADP are capable only of acting as partial agonists at the ADP receptor because of a defective ability to increase cytosolic Ca2+ concentration. The defect is rectified by the presence of low concentrations of ionophore A-23187, which promotes mobilisation of Ca2+ from an intracellular store. The results do not appear consistent with the thesis that a decrease in platelet cyclic AMP is an initiating event in aggregation induced by ADP, but do support a model which implicates cyclic AMP in depletion of cytosolic Ca2+.

The absorption of buccal morphine was compared with that of slow-release morphine sulphate in human volunteers. Morphine concentration was assayed by high pressure liquid chromatography in serum samples obtained at intervals up to 8 hours after administration of morphine 20 mg. Similar mean maximum concentrations were obtained by either route, but the mean time to maximum concentration was longer after buccal than after enteral administration.