Faculty Bibliography

Background. Traditionally a hospital-acquired pathogen, Clostridium difficile is increasingly recognized as an important cause of diarrhea in community settings. Health disparities in C. difficileinfection (CDI) have been reported, but little is known about the social determinants of health that influence community-associated (CA) CDI incidence. We sought to identify socioeconomic status (SES) factors associated with increased CA-CDI incidence. Methods. Population-based CDI surveillance is conducted in 35 U.S. counties through the Centers for Disease Control and Prevention's Emerging Infections Program. A CA-CDI case is defined as a positive C. difficile stool specimen collected as an outpatient or within three days of hospitalization in a person aged >= 1 year who did not have a positive test in the prior 8 weeks or an overnight stay in a healthcare facility in the prior 12 weeks. ArcGIS software was used to geocode 2014-2015 CA-CDI case addresses to a 2010 census tract (CT). Incidence rate was calculated using 2010 Census population denominators. CT-level SES factors were obtained from the 2011-2015 American Community Survey 5-year estimates and divided into deciles. To account for CT-level clustering effects, separate generalized linear mixed models with negative binomial distribution were used to evaluate the association between each SES factor and CA-CDI incidence, adjusted by age, sex and race. Results. Of 9686 CA-CDI cases, 9417 (97%) had addresses geocoded to a CT; of these, 62% were female, 82% were white, and 35% were aged >=65 years. Annual CA-CDI incidence was 42.9 per 100,000 persons. After adjusting for age, sex and race, CT-level SES factors significantly associated with increased CA-CDI incidence included living under the poverty level (rate ratio [RR] 1.12; 95% confidence interval [CI] 1.09-1.53), crowding in homes (RR 1.11; 95% CI 1.01-1.21), low education (RR 1.11; 95% CI 1.07-1.15), low income (RR 1.15; 95% CI 1.12-1.17), having public health insurance (RR 1.21; 95% CI 1.18-1.24), receiving public assistance income (RR 1.69; 95% CI 1.55-1.84), and unemployment (RR 1.14; 95% CI 1.07-1.22). Conclusion. Areas with lower SES have modestly increased CA-CDI incidence. Understanding the mechanisms by which SES factors impact CA-CDI incidence could help guide prevention efforts in these higher-risk areas

Discrepancy in perception of bullying experiences may lead to later internalizing or externalizing behavior in adolescents. A 1,663 South Korean 7th and 8th graders (mean age: 13.1 and 14.1 years old), were seen for a follow-up study to examine the relationships between the discrepancy in perception of their bullying experiences (defined as discrepancy between self- and peer-reports of bullying experiences) and internalizing or externalizing behavior at follow-up. Bullying was assessed by self- and peer-report. The discrepancy in perception of bullying experiences was defined by the concordance or discordance between self- and peer-reports. Internalizing and externalizing behavior was evaluated using the Youth Self Report and Child Behavior Checklist, at baseline and follow-up. Two by two ANCOVA was performed with a factorial design, categorizing discrepancy in perception of bullying experiences based on the agreement between self-report and peer-report. Internalizing/externalizing behavior-at-follow-up was used as an outcome, adjusting for other known risk factors for internalizing/externalizing behavior, including baseline internalizing/externalizing behavior, and bullying experiences. Adolescents with perceptions of bullying experiences discrepant from peer-reports showed increased internalizing/externalizing behavior at follow-up. Bullying also stands out as an independent risk factor for the development of future externalizing behavior even among adolescents with accurate perceptions of bullying experiences. These specific groups of youth warrant more focused assessment and intervention.

Gender inequalities shape the experience of food insecurity among women living with HIV (WLHIV). We systematically reviewed the impact of food insecurity on sexual risk behaviors and antiretroviral therapy (ART) adherence among WLHIV. We included qualitative or quantitative peer-reviewed articles, extracted data in duplicate, and assessed rigor. Seven studies, from sub-Saharan Africa, North America, and Europe, met inclusion criteria. Food insecurity was associated with increased sexual risk through transactional sex and inability to negotiate safer sex. Hunger and food insecurity were barriers to ART initiation/adherence. Multidimensional programming and policies should simultaneously address poverty, gender inequality, food insecurity, and HIV.

Prosocial behavior emerges in the second year of life, yet it is typical for children in this period not to share, comfort, or help. We compared toddlers (18, 30 months) who helped with those who did not help on two tasks (instrumental helping; empathic helping). More than half of children failed to help on one or both tasks. Nonhelpers engaged in more hypothesis testing on the instrumental helping task, but more security-seeking, wariness, and playing on the empathic helping task. Across tasks, children who tended to engage in nonhelping behaviors associated with negative emotional arousal also tended to seek comfort from a parent. In contrast, children who tended to play instead of helping were less likely to exhibit negative emotional arousal or hypothesis testing, suggesting a focus on their own interests. Parents of 18-month-old nonhelpers on the instrumental task were less engaged in socializing prosocial behavior in their toddlers than were the parents of helpers. On the empathic helping task, 18-month-old nonhelpers had less mature self-other understanding than did helpers. By examining how the predominant reasons for failing to help vary with age and task, we gain a fuller perspective on the factors involved in the early development of prosocial behavior.

The youth health indicator (YHI) program was developed to improve health and reduce risk behaviors for youth treated in clinic and day treatment psychiatric settings. This study examined implementation of the YHI program and factors associated with BMI % change for youth participating in the program. Outpatient facilities which implemented the YHI program were surveyed (N = 10) and lessons learned were summarized. Mixed random effects repeated measures analysis was used to examine BMI % trajectory for youth admitted during 2010-2014 with BMI % measured (N = 6403). Treatment settings indicated a variety of strategies to undertake and sustain the YHI program. Factors associated with BMI % change over time were identified. The YHI program resulted in the development of a wide variety of programmatic innovations targeted at improving youth health. Continued work needs to be done to improve the health outcomes for youth in these treatment settings.

Latent class models are widely used to identify unobserved subgroups (i.e., latent classes) based upon one or more manifest variables. The probability of belonging to each subgroup is typically modeled as a function of a set of measured covariates. In this paper, we extend existing latent class models to incorporate matrix covariates. This research is motivated by a randomized placebo-controlled depression clinical trial. One study goal is to identify a subgroup of subjects who experience symptoms improvement early on during antidepressant treatment, which is considered to be an indication of a placebo rather than a true pharmacological response. We want to relate the likelihood of belonging to this subgroup of early responders to baseline electroencephalography (EEG) measurement that takes the form of a matrix. The proposed method is built upon a low rank Candecomp/Parafac (CP) decomposition of the target coefficient matrix through low-dimensional latent variables, which effectively reduces the model dimensionality. We adopt a Bayesian hierarchical modeling approach to estimate the latent variables, which allows a flexible way to incorporate prior knowledge about covariate effect heterogeneity and offers a data-driven method of regularization. Simulation studies suggest that the proposed method is robust against potentially misspecified rank in the CP decomposition. With the motivating example we show how the proposed method can be applied to extract valuable information from baseline EEG measurements that explains the likelihood of belonging to the early responder subgroup, helping to identify placebo responders and suggesting new targets for the study of placebo response.

Youth with psychiatric and behavioral complaints commonly present to emergency departments (EDs), which often lack dedicated mental health staff. This article addresses techniques EDs can use to better care for children in need of psychiatric assessment and medical clearance, specifically addressing the evaluation of youth with suicidal ideation and coexisting medical and psychiatric needs. The evaluation and management of youth with agitation and aggression are also discussed. The article concludes with a discussion of systems changes needed to truly improve emergency care for psychiatrically ill youth.

The immediate and long-term effects of exposure to early life stress (ELS) have been documented in humans and animal models. Even relatively brief periods of stress during the first 10 days of life in rodents can impact later behavioral regulation and the vulnerability to develop adult pathologies, in particular an impairment of cognitive functions and neurogenesis, but also modified social, emotional, and conditioned fear responses. The development of preclinical models of ELS exposure allows the examination of mechanisms and testing of therapeutic approaches that are not possible in humans. Here, we describe limited bedding and nesting (LBN) procedures, with models that produce altered maternal behavior ranging from fragmentation of care to maltreatment of infants. The purpose of this paper is to discuss important issues related to the implementation of this chronic ELS procedure and to describe some of the most prominent endpoints and consequences, focusing on areas of convergence between laboratories. Effects on the hypothalamic-pituitary adrenal (HPA) axis, gut axis and metabolism are presented in addition to changes in cognitive and emotional functions. Interestingly, recent data have suggested a strong sex difference in some of the reported consequences of the LBN paradigm, with females being more resilient in general than males. As both the chronic and intermittent variants of the LBN procedure have profound consequences on the offspring with minimal external intervention from the investigator, this model is advantageous ecologically and has a large translational potential. In addition to the direct effect of ELS on neurodevelopmental outcomes, exposure to adverse early environments can also have intergenerational impacts on mental health and function in subsequent generation offspring. Thus, advancing our understanding of the effect of ELS on brain and behavioral development is of critical concern for the health and wellbeing of both the current population, and for generations to come.

What an animal needs to learn to survive is altered dramatically as they change from dependence on the parent for protection to independence and reliance on self-defense. This transition occurs in most altricial animals, but our understanding of the behavioral neurobiology has mostly relied on the infant rat. The transformation from dependence to independence occurs over three weeks in pups and is accompanied by complex changes in responses to both natural and learned threats and the supporting neural circuitry. Overall, in early life, the threat system is quiescent and learning is biased towards acquiring attachment related behaviors to support attachment to the caregiver and proximity seeking. Caregiver-associated cues learned in infancy have the ability to provide a sense of safety throughout lifetime. This attachment/safety system is activated by learning involving presumably pleasurable stimuli (food, warmth) but also painful stimuli (tailpinch, moderate shock). At about the midway point to independence, pups begin to have access to the adult-like amygdala-dependent threat system and amygdala-dependent responses to natural dangers such as predator odors. However, pups have the ability to switch between the infant and adult-like system, which is controlled by maternal presence and modification of stress hormones. Specifically, if the pup is alone, it will learn fear but if with the mother it will learn attachment (10-15 days of age). As pups begin to approach weaning, pups lose access to the attachment system and rely only on the amygdala-dependent threat system. However, pups learning system is complex and exhibits flexibility that enables the mother to override the control of the attachment circuit, since newborn pups may acquire threat responses from the mother expressing fear in their presence. Together, these data suggest that the development of pups' threat learning system is not only dependent upon maturation of the amygdala, but it is also exquisitely controlled by the environment. Most notably the mother can switch pup learning between attachment to threat learning in a moment's notice. This enables the mother to navigate pup's learning about the world and what is threatening and what is safe.