Faculty Bibliography

PURPOSE:To provide estimates for the prevalence of parent-reported speech-language difficulties in U.S. children, and to describe the levels of health care access and material hardship in this population. METHOD:We tabulated descriptive and bivariate statistics using cross-sectional data from the 2007 and 2011/2012 iterations of the National Survey of Children's Health, the 2005/2006 and 2009/2010 iterations of the National Survey of Children with Special Health Care Needs, and the 2004 and 2008 panels of the Survey of Income and Program Participation. RESULTS:Prevalence estimates ranged from 1.8% to 5.0%, with data from two of the three surveys preliminarily indicating increased prevalence in recent years. The largest health care challenge was in accessing care coordination, with 49%-56% of children with parent-reported speech-language difficulties lacking full access. Children with parent-reported speech-language difficulties were more likely than peers without any indications of speech-language difficulties to live in households experiencing each measured material hardship and participating in each measured public benefit program (e.g., 20%-22% experiencing food insecurity, compared to 11%-14% of their peers without any indications of speech-language difficulties). CONCLUSIONS:We found mixed preliminary evidence to suggest that the prevalence of parent-reported speech-language difficulties among children may be rising. These children face heightened levels of material hardship and barriers in accessing health care.

BACKGROUND:Women with intellectual and developmental disabilities (IDD) are bearing children at increasing rates. However, there is very little research about pregnancy experiences and birth outcomes among women with IDD. No studies to date have examined birth outcomes with a US population-based sample. OBJECTIVE:The main objective was to estimate the national occurrence of deliveries in women with IDD and to compare their birth outcomes to women without IDD. METHODS:We examined the 2007-2011 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project to compare birth outcomes in women with and without IDD. Birth outcomes included preterm birth, low birth weight, and stillbirth. Multivariable regression analyses compared birth outcomes between women with and without IDD controlling for race/ethnicity, maternal age, household income, health insurance status and type, comorbidity, region and hospital location, teaching status, ownership, and year. RESULTS:Of an estimated 20.6 million deliveries identified through the HCUP 2007-2011 data 10,275 occurred in women with IDD. In adjusted regression analyses, women with IDD compared to those without IDD were significantly more likely to have preterm birth (OR = 1.46; 95%CI: 1.26-1.69, p < 0.001), low birth weight (OR = 1.61, 95%CI: 1.27-2.05, p < 0.001), and stillbirth (OR = 2.40, 95% CI: 1.70-3.40, p < 0.001). CONCLUSION:This study provides a first examination of the birth outcomes among women with IDD in the United States using a largest population-based sample. There are significant differences in birth outcomes between women with and without IDD. Understanding the causes of these differences and addressing these causes are critical to improving pregnancy outcomes among women with IDD.

BACKGROUND/AIMS:Pain is common in cancer patients and results in lower quality of life, depression, poor physical functioning, financial difficulty, and decreased survival time. Behavioral pain interventions are effective and nonpharmacologic. Traditional randomized controlled trials (RCT) test interventions of fixed time and dose, which poorly represent successive treatment decisions in clinical practice. We utilize a novel approach to conduct a RCT, the sequential multiple assignment randomized trial (SMART) design, to provide comparative evidence of: 1) response to differing initial doses of a pain coping skills training (PCST) intervention and 2) intervention dose sequences adjusted based on patient response. We also examine: 3) participant characteristics moderating intervention responses and 4) cost-effectiveness and practicality. METHODS/DESIGN:Breast cancer patients (N=327) having pain (ratings≥5) are recruited and randomly assigned to: 1) PCST-Full or 2) PCST-Brief. PCST-Full consists of 5 PCST sessions. PCST-Brief consists of one 60-min PCST session. Five weeks post-randomization, participants re-rate their pain and are re-randomized, based on intervention response, to receive additional PCST sessions, maintenance calls, or no further intervention. Participants complete measures of pain intensity, interference and catastrophizing. CONCLUSIONS:Novel RCT designs may provide information that can be used to optimize behavioral pain interventions to be adaptive, better meet patients' needs, reduce barriers, and match with clinical practice. This is one of the first trials to use a novel design to evaluate symptom management in cancer patients and in chronic illness; if successful, it could serve as a model for future work with a wide range of chronic illnesses.

Biofilm formation by pathogenic Burkholderia species is a serious complication as it renders the bacteria resistant to antibiotics and host defenses. Using B. thailandensis, we report here a novel redox-sensitive member of the multiple antibiotic resistance regulator (MarR) protein family, BifR, which represses biofilm formation. BifR is encoded as part of the emrB-bifR operon; emrB-bifR is divergent to ecsC, which encodes a putative LasA protease. In Pseudomonas aeruginosa, LasA has been implicated in virulence by contributing to cleavage of elastase. BifR repressed the expression of ecsC and emrB-bifR, and expression was further repressed under oxidizing conditions. BifR bound two sites in the intergenic region between ecsC and emrB-bifR with nanomolar affinity under both reducing and oxidizing conditions; however, oxidized BifR formed a disulfide-linked dimer-of-dimers, a covalent linkage that was absent in BifR-C104A in which the redox-active cysteine was replaced with alanine. BifR also repressed an operon encoding enzymes required for synthesis of phenazine antibiotics, which function as alternate respiratory electron receptors, and inactivation of bifR resulted in enhanced biofilm formation. Taken together, our data suggest that BifR functions to control LasA production and expression of genes involved in biofilm formation, in part by regulating synthesis of alternate electron acceptors that promote survival in the oxygen-limiting environment of a biofilm. The correlation between increased repression of emrB-bifR under oxidative conditions and the formation of a covalently linked BifR dimer-of-dimers suggests that BifR may modulate gene activity in response to cellular redox state.

Although both gene- and temperament-environment interactions contribute to the development of youth externalizing problems, it is unclear how these factors jointly affect environmental sensitivity over time. In a 7-year longitudinal study of 232 children (aged 5-10) with and without ADHD, we employed moderated mediation to test a developmentally sensitive mechanistic model of genetic and temperamental sensitivity to prenatal and postnatal environmental factors. Birth weight, a global measure of the prenatal environment, moderated predictions of child negative emotionality from a composite of dopaminergic polymorphisms (i.e., DRD4 and DAT1), such that birth weight inversely predicted negative emotionality only for children with genetic plasticity. Negative emotionality, in turn, predicted externalizing behavior 4-5 years later, beyond genetic and postnatal parenting effects. Finally, birth weight moderated the indirect effect of dopaminergic genotypes on externalizing problems through negative emotionality, partially supporting a prenatal programming model. We discuss theoretical and empirical implications for models of environmental sensitivity.

OBJECTIVE:To evaluate the impact of erythropoiesis-stimulating agents (ESAs) administered during initial hospitalization and family demographic factors on behavior at 3.5-4 years of age. STUDY DESIGN:Children were enrolled who had previously participated in a randomized study of ESAs (n = 35) or placebo (n = 14) in infants born preterm with birth weights of 500-1250 g. A term healthy control group (n = 22) also was recruited. Behavior was evaluated by parent report with the Behavioral Assessment System of Children-2. Principal component analyses identified 2 demographic factors, a Socioeconomic Composite (SEC) and a Family Stress Composite. A multivariate general linear model evaluated the impact of study group and sex on the 4 composite scales of the Behavioral Assessment System of Children-2. Demographic factors were treated as covariates and interactions with study group (ESA, placebo, and term) were examined. RESULTS:The ESA group had significantly better scores than the placebo group on behavioral symptoms (P = .04) and externalizing scales (P = .04). An interaction was observed between study group and SEC (P = .001). A beneficial effect of ESAs was maximal in the children with lower SEC scores. CONCLUSIONS:The beneficial effects of ESAs on childhood behavior were maximal in children with lower SEC scores. ESAs seemed to ameliorate the adverse impact of lower SEC on behavioral domains seen in the placebo group. This effect was independent of the beneficial effect of ESAs on global cognition we reported previously. TRIAL REGISTRATION:ClinicalTrials.gov: NCT01207778 and NCT00334737.

OBJECTIVE This study identifies quantitative imaging-based measures in patients with Chiari malformation Type I (CM-I) that are associated with positive outcomes after suboccipital decompression with duraplasty. METHODS Fifteen patients in whom CM-I was newly diagnosed underwent MRI preoperatively and 3 months postoperatively. More than 20 previously described morphological and physiological parameters were derived to assess quantitatively the impact of surgery. Postsurgical clinical outcomes were assessed in 2 ways, based on resolution of the patient's chief complaint and using a modified Chicago Chiari Outcome Scale (CCOS). Statistical analyses were performed to identify measures that were different between the unfavorable- and favorable-outcome cohorts. Multivariate analysis was used to identify the strongest predictors of outcome. RESULTS The strongest physiological parameter predictive of outcome was the preoperative maximal cord displacement in the upper cervical region during the cardiac cycle, which was significantly larger in the favorable-outcome subcohorts for both outcome types (p < 0.05). Several hydrodynamic measures revealed significantly larger preoperative-to-postoperative changes in the favorable-outcome subcohort. Predictor sets for the chief-complaint classification included the cord displacement, percent venous drainage through the jugular veins, and normalized cerebral blood flow with 93.3% accuracy. Maximal cord displacement combined with intracranial volume change predicted outcome based on the modified CCOS classification with similar accuracy. CONCLUSIONS Tested physiological measures were stronger predictors of outcome than the morphological measures in patients with CM-I. Maximal cord displacement and intracranial volume change during the cardiac cycle together with a measure that reflects the cerebral venous drainage pathway emerged as likely predictors of decompression outcome in patients with CM-I.

It is generally accepted that women tend to ruminate more than men do and these thought patterns are often associated with depressive symptoms (Nolen-Hoeksema et al., ). Based on these findings, we considered whether the relationship between rumination and depression is stronger in women than in men and if so, whether this might explain the higher prevalence of major depressive disorder (MDD) in women and finally, whether the association can be disrupted through a mind/body intervention. Adult men and women, most of whom were clinically depressed, participated in an intervention known as MAP Training, which combines "mental" training with silent meditation and "physical" training with aerobic exercise (Shors et al., ). After eight weeks of training, both men and women reported significantly fewer symptoms of depression and fewer ruminative thoughts (Alderman et al., ). Statistical correlations between depressive symptoms and ruminative thoughts were strong and significant (rho > 0.50; p < 0.05) for both men and women before and after MAP Training. However, only in women did depressive symptoms relate to "reflective" ruminations, which involve analyses of past events, feelings, and behaviors. This is also the only relationship that dissipated after the intervention. In general, these analyses suggest that the strength of the relationship between depressive symptoms and rumination does not necessarily explain sex differences in depression; but because the relationship is strong, targeting rumination through intervention can reduce the incidence of MDD, which is more prevalent among women. © 2016 Wiley Periodicals, Inc.

Multiple epidemiological studies suggest a relationship between advanced paternal age (APA) at conception and adverse neurodevelopmental outcomes in offspring, particularly with regard to increased risk for autism and schizophrenia. Conclusive evidence about how age-related changes in paternal gametes, or age-independent behavioral traits affect neural development is still lacking. Recent evidence suggests that the origins of APA effects are likely to be multidimensional, involving both inherited predisposition and de novo events. Here we provide a review of the epidemiological and molecular findings to date. Focusing on the latter, we present the evidence for genetic and epigenetic mechanisms underpinning the association between late fatherhood and disorder in offspring. We also discuss the limitations of the APA literature. We propose that different hypotheses relating to the origins of the APA effects are not mutually exclusive. Instead, multiple mechanisms likely contribute, reflecting the etiological complexity of neurodevelopmental disorders.