Development of stratified epithelia, such as the epidermis, requires p63 expression. The p63 gene encodes isoforms that contain (TA) or lack (⌬N) a transactivation domain. We demonstrate that TAp63 isoforms are the first to be expressed during embryogenesis and are required for initiation of epithelial stratification. In addition, TAp63 isoforms inhibit terminal differentiation, suggesting that TAp63 isoforms must be counterbalanced by ⌬Np63 isoforms to allow cells to respond to signals required for maturation of embryonic epidermis. Our data demonstrate that p63 plays a dual role: initiating epithelial stratification during development and maintaining proliferative potential of basal keratinocytes in mature epidermis.

This article presents psychometric characteristics of the UCLA PTSD Reaction Index for DSM IV (PTSD-RI) derived from a large sample of children and adolescents (N = 6,291) evaluated at National Child Traumatic Stress Network centers. Overall mean total PTSD-RI score for girls was significantly higher as compared with boys. Age-related differences were found in that overall mean total PTSD-RI scores and within sex groups were higher among those aged 7-9 years and 16-18 years. There were no significant differences in mean total PTSD-RI scores across racial/ethnic groups. The PTSD-RI total scale displayed good to excellent internal consistency reliability across age ranges, sex, and racial/ethnic groups (α = .88-.91). Correlations of PTSD-RI scores with PTS subscale scores on the TSCC-A for the entire sample and within sex, age, and ethnic/racial groups provided evidence of convergent validity, although not discriminant validity. In contradistinction to previously reported 4-factor models, an exploratory factor analysis revealed 3 factors that mostly reflected the underlying dimensions of PTSD in DSM IV. PTSD-RI scores were associated with increased odds ratios for functional/behavior problems (odds ratio [OR] = 1-1.80). These findings are striking in light of the wide range of trauma exposures, age, and race/ethnicity among subjects.

There is an increasing need to deliver effective mental health services to refugee children and adolescents across the United States; however, the evidence base needed to guide the design and delivery of services is nascent. We investigated the trauma history profiles, psychopathology, and associated behavioral and functional indicators among war-affected refugee children presenting for psychological treatment. From the National Child Traumatic Stress Network's Core Data Set, 60 war-affected refugee children were identified (51.7% males, mean age = 13.1 years, SD = 4.13). Clinical assessments indicated high rates of probable posttraumatic stress disorder (30.4%), generalized anxiety (26.8%), somatization (26.8%), traumatic grief (21.4%), and general behavioral problems (21.4%). Exposure to war or political violence frequently co-occurred with forced displacement; traumatic loss; bereavement or separation; exposure to community violence; and exposure to domestic violence. Academic problems and behavioral difficulties were prevalent (53.6% and 44.6%, respectively); however, criminal activity, alcohol/drug use, and self-harm were rare (all < 5.45%). These findings highlight the complex trauma profiles, comorbid conditions, and functional problems that are important to consider in providing mental health interventions for refugee children and adolescents. Given the difficulties associated with access to mental health services for refugees, both preventive and community-based interventions within family, school, and peer systems hold particular promise.

Although links between adverse childhood experiences (ACEs) and problems in adulthood are wellestablished, less is known regarding links between exposure to trauma during childhood and adolescence and high-risk behavior in adolescence. We tested the hypothesis that cumulative exposure to up to 20 different types of trauma and bereavement/loss incrementally predicts high-risk adolescent behavior beyond demographic variables. Adolescents reporting exposure to at least 1 type of trauma (n ϭ 3,785; mean age ϭ 15.3 years; 62.7% girls) were selected from the National Child Traumatic Stress Network Core Data Set (CDS). Logistic regression analyses tested associations among both demographic variables and number of types of trauma and loss exposure as predictors, and 9 types of high-risk adolescent behavior and functional impairment (attachment difficulties, skipping school, running away from home, substance abuse, suicidality, criminality, self-injury, alcohol use, and victim of sexual exploitation) as criterion variables. As hypothesized, hierarchical logistic regression analyses revealed that each additional type of trauma exposure significantly increased the odds ratios for each problem behavior (range ϭ 1.06 -1.22) after accounting for demographic variables. Some demographic variables (female gender, public insurance eligibility, and older age) were also associated with increased likelihood for some outcomes. Study findings extend previously identified links between childhood trauma and problems later in life to include high-risk behavior and functional impairment during adolescence. The findings underscore the need for a trauma-informed public health approach to systematic screening, prevention, and early intervention for traumatized and bereaved youth in child service systems.

Objective-To compare modafinil to placebo for reducing methamphetamine (MA) use, improving retention, and reducing depressive symptoms and MA cravings. Rates of adverse events and cigarette smoking with modafinil versus placebo were also compared.Methods-Following a 2-week, non-medication lead-in period, 71 treatment-seeking MA dependent participants were randomly assigned to modafinil (400 mg once daily; N= 34) or placebo (once daily; N= 37) for 12-weeks under double-blind conditions. Participants attended clinic thrice weekly to provide urine samples analyzed for MA-metabolite, to complete research assessments, and to receive contingency management and weekly cognitive behavioral therapy (CBT) sessions.Results-There were no statistically significant effects for modafinil on MA use, retention, depressive symptoms, or MA cravings in pre-planned analyses. Outcomes for retention and MA use favored modafinil in a post hoc analysis among participants with low CBT attendance and among participants with baseline high frequency of MA use (MA use on >18 of past 30 days), but did not reach statistical significance in these small subgroups. Modafinil was safe and well tolerated and did not increase cigarette smoking.Conclusions-Modafinil was no more effective than placebo at 400 mg daily in a general sample of MA users. A post hoc analysis showing a trend favoring modafinil among subgroups with baseline high frequency MA use and low CBT attendance suggests that further evaluation of modafinil in MA users is warranted.

Epidermal morphogenesis begins with the commitment of the single-layered surface ectoderm to initiate a stratification program, a process that requires the expression of the transcription factor TAp63alpha. To determine the molecular mechanism by which TAp63alpha induces genes associated with the commitment to stratification, such as K14, we have used a combination of in vitro and in vivo approaches. Our initial gene expression profiling studies suggested that TAp63alpha could regulate one or more AP-2 genes, which have been implicated in development and maintenance of the epidermis. We now demonstrate that TAp63alpha directly induces AP-2gamma expression in embryonic epidermis, when commitment to stratification occurs. Furthermore, we show that, in the absence of AP-2gamma, TAp63alpha fails to induce K14 expression in vitro. Our data identify AP-2gamma as the first in vivo target gene of TAp63alpha, and provide novel insights into the molecular mechanisms associated with early events in epidermal morphogenesis.

The present study focused on identifying risk factors for early readmission of patients discharged from an urban community hospital. Retrospective chart reviews were conducted on 207 consecutive inpatient psychiatric admissions that included patients who were readmitted within 15 days, within 3 to 6 months, and not admitted for at least 12 months post-discharge. Findings indicated that a diagnosis of schizophrenia/schizoaffective disorder (OR = 18; 95% CI 2.70-117.7; p < 0.05), history of alcohol abuse (OR = 9; 95% CI 1.80-40.60; p < 0.05), number of previous psychiatric hospitalizations (OR = 2; 95% CI 1.28-3.73; p < 0.05), and type of residence at initial admission (e.g., homeless, OR = 29; 95% CI 3.99-217; p < 0.05) were significant risk factors for early readmission, where OR compares readmission group 1 versus group 3 in the multinomial logistic regression. Initial positive urine drug screen, history of drug abuse or incarceration, and legal status at initial admission did not predict early readmission. Reducing the risk factors associated with psychiatric readmissions has the potential to lead to the identification and development of preventative intervention strategies that can significantly improve patient safety, quality of care, well-being, and contain health care expenditures.

Imputation strategies are widely used in settings that involve inference with incomplete data. However, implementation of a particular approach always rests on assumptions, and subtle distinctions between methods can have an impact on subsequent analyses. In this paper we are concerned with regression models in which the true underlying relationship includes interaction terms. We focus in particular on a linear model with one fully observed continuous predictor, a second partially observed continuous predictor, and their interaction. We derive the conditional distribution of the missing covariate and interaction term given the observed covariate and the outcome variable, and examine the performance of a multiple imputation procedure based on this distribution. We also investigate several alternative procedures that can be implemented by adapting multivariate normal multiple imputation software in ways that might be expected to perform well despite incompatibilities between model assumptions and true underlying relationships among the variables. The methods are compared in terms of bias, coverage and confidence interval width. As expected, the procedure based on the correct conditional distribution (CCD) performs well across all scenarios. Just as importantly for general practitioners, several of the approaches based on multivariate normality perform comparably to the CCD in a number of circumstances, although, interestingly, procedures that seek to preserve the multiplicative relationship between the interaction term and the main-effects are found to be substantially less reliable. For illustration, the various procedures are applied to an analysis of post-traumatic-stress-disorder symptoms in a study of childhood trauma.