Pathways from Caregiver Problematic Substance Use to Child Harm: A Secondary Data Analysis of the National Survey of Child and Adolescent Well-Being II

Caregiver problematic substance use is a prevalent problem within the child protective services (CPS) system that is associated with negative outcomes for children. Utilizing path analysis models, this dissertation deepens our understanding of the direct and indirect (mediating and moderating) pathways from caregiver problematic substance use to indicators of child harm in two CPS populations: all families investigated for maltreatment (Aim 1) and a sub-group of families in which the children remained in the home after the investigation (Aim 2). Data for these analyses came from the National Survey of Child and Adolescent Well-Being II (NSCAW II), a landmark, longitudinal national probability study of families investigated for child maltreatment. Caregiver problematic substance use was measured in two ways. In Aim 1, caregiver problematic substance use was measured by caseworker-identified problematic drug or alcohol use. In Aim 2, caregiver problematic substance use was measured by caregiver self-report of problematic drug or alcohol use available only in this sub-group. Using the child welfare goals of safety, permanency, and well-being, child harm was operationalized as CPS referrals for services and subsequent reports of maltreatment (safety), having children removed from the home (permanency), and child levels of depression, trauma, internalizing behaviors, or externalizing behaviors (well-being). Mediators included in the models are parental monitoring, harsh discipline, emotional maltreatment, and exposure to violence. Moderators included in the models are caregiver depression, domestic violence, and criminal involvement. Among other findings, this dissertation indicates that emotional maltreatment and caregiver depression are strong pathways through which caregiver problematic substance use is associated with child harm. Bivariate analyses also indicate a need to strengthen training around caregiver problematic substance use for CPS caseworkers. By utilizing the CPS goals of safety, permanency, and well-being, the results of this dissertation have direct implications for national child welfare policies and inform how caregiver problematic substance use is addressed in CPS agencies. Emotional maltreatment and caregiver depression are risk factors that should be targeted in interventions aimed at promoting the safety, permanency, and well-being of children when caregiver problematic substance use is present

ISG15 Is Critical in the Control of Chikungunya Virus Infection Independent of UbE1L Mediated Conjugation

Chikungunya virus (CHIKV) is a re-emerging alphavirus that has caused significant disease in the Indian Ocean region since 2005. During this outbreak, in addition to fever, rash and arthritis, severe cases of CHIKV infection have been observed in infants. Challenging the notion that the innate immune response in infants is immature or defective, we demonstrate that both human infants and neonatal mice generate a robust type I interferon (IFN) response during CHIKV infection that contributes to, but is insufficient for, the complete control of infection. To characterize the mechanism by which type I IFNs control CHIKV infection, we evaluated the role of ISG15 and defined it as a central player in the host response, as neonatal mice lacking ISG15 were profoundly susceptible to CHIKV infection. Surprisingly, UbE1L−/− mice, which lack the ISG15 E1 enzyme and therefore are unable to form ISG15 conjugates, displayed no increase in lethality following CHIKV infection, thus pointing to a non-classical role for ISG15. No differences in viral loads were observed between wild-type (WT) and ISG15−/− mice, however, a dramatic increase in proinflammatory cytokines and chemokines was observed in ISG15−/− mice, suggesting that the innate immune response to CHIKV contributes to their lethality. This study provides new insight into the control of CHIKV infection, and establishes a new model for how ISG15 functions as an immunomodulatory molecule in the blunting of potentially pathologic levels of innate effector molecules during the host response to viral infection