Faculty Bibliography

BACKGROUND: One strategy to address health problems related to insufficient physical activity is to examine modifiable neighborhood characteristics associated with active transportation. PURPOSE: The aim of this study is to evaluate whether neighborhoods with more aesthetic amenities (sidewalk cafes, street trees, and clean sidewalks) and fewer safety hazards (pedestrian-auto fatalities and homicides) are associated with active transportation. METHODS: The 2003 Community Health Survey in New York City, which asked about active transportation (walking or bicycling >10 blocks) in the past 30 days, was linked to ZIP-code population census and built environment characteristics. Adjusted associations were estimated for dichotomous (any active transportation versus none) and continuous (trip frequency) active transportation outcomes. RESULTS: Among 8,034 adults, those living near sidewalk cafes were 10 % more likely to report active transportation (p = 0.01). Homicide rate was associated with less frequent active transportation among those reporting any active transportation (p = 0.002). CONCLUSIONS: Investments in aesthetic amenities or homicide prevention may help to promote active transportation.

We examined factors influencing informed assent, initial involvement, and ongoing involvement in HIV-focused CBPR research for African American children. Study participants (n = 170) were recruited from the Collaborative HIV and Adolescent Mental Health Project and completed an interview format designed to assess attitudes about research activities. Data were analyzed using a mixed-methods approach. Three themes emerged via quantitative and qualitative data analysis: (1) motivation for the child to participate in the research; (2) trust in researchers; and (3) understanding of the informed assent process. Findings from this study can help researchers develop procedures facilitating ethics boards to assess the appropriateness of child assent in HIV-focused community-based participatory research.

Aim Difficulties in neurocognition and social interaction are the most prominent causes of morbidity and long-term disability in children with neurofibromatosis type 1 (NF1). Symptoms of attention-deficit-hyperactivity disorder (ADHD) have also been extensively recognized in NF1. However, systematic evaluation of symptoms of autism spectrum disorder (ASD) in children with NF1 has been limited. Method We present a retrospective, cross-sectional study of the prevalence of symptoms of ASD and ADHD and their relationship in a consecutive series of 66 patients from our NF1 clinic. The Social Responsiveness Scale and the Vanderbilt ADHD Diagnostic Parent Rating Scale were used to assess symptoms of ASD and ADHD. Results Sixty-six participants (42 males, 24 females) were included in this study. Mean age at assessment was 10 years 11 months (SD 5y 4mo). Forty percent of our NF1 sample had raised symptom levels reaching clinical significance on the Social Responsiveness Scale (T >/= 60), and 14% reached levels consistent with those seen in children with ASDs (T >/= 75). These raised levels were not explained by NF1 disease severity or externalizing/internalizing behavioral disorders. There was a statistically significant relationship between symptoms of ADHD and ASD (chi(2) =9.11, df=1, p=0.003, phi=0.56). Particularly salient were the relationships between attention and hyperactivity deficits, with impairments in social awareness and social motivation. Interpretation We found that symptoms of ASD in our NF1 population were raised, consistent with previous reports. Further characterization of the specific ASD symptoms and their impact on daily function is fundamental to the development and implementation of effective interventions in this population, which will probably include a combination of medical and behavioral approaches.

Attention-deficit/hyperactivity disorder (ADHD) and Asperger's Syndrome (AS) share a heterogeneous cognitive profile. Studies assessing executive functions (EF) and social cognition in both groups have found preserved and impaired performances. These inconsistent findings would be partially explained by the cognitive variability reported in these disorders. First, the present study explored the inter-individual variability in EF and social cognition in both patient groups. Second, we compared differential characteristics and commonalities in the cognitive profiles of EF and social cognition between ADHD, AS and control adults. We assessed 22 patients with ADHD, 23 adults with AS and 21 matched typically developing subjects using different measures of EF (working memory, cognitive flexibility and multitasking) and social cognition (theory of mind and decision-making). Group comparisons and multiple case series analyses (MCSA) were conducted. The between-group comparisons showed an EF deficit in working memory in ADHD and a theory of mind (ToM) impairment in AS. The MCSA evidenced that, compared to controls, ADHD patients had a higher inter-individual variability in EF, while individuals with AS had a more heterogeneous profile in social cognition tasks compared to both groups. Finally, the AS and ADHD groups presented higher task-related variability compared to controls and shared a common heterogeneous profile in EF. This is the first study to compare variability in EF and social cognition profiles of ADHD and AS. We propose that heterogeneity in EF performance is a link between ADHD and AS which may explain the overlap of symptomatology between both diagnoses. In addition, patients with AS seem to show a unique heterogeneous profile in ToM which may explain the low probability of finding AS symptoms in patients with ADHD.

Epigenetic mechanisms mediate heritable control of cell identity in normal cells and cancer. We sought to identify epigenetic regulators driving the pathogenesis of pancreatic ductal adenocarcinoma (PDAC), one of the most lethal human cancers. We found that KDM2B (also known as Ndy1, FBXL10, and JHDM1B), an H3K36 histone demethylase implicated in bypass of cellular senescence and somatic cell reprogramming, is markedly overexpressed in human PDAC, with levels increasing with disease grade and stage, and highest expression in metastases. KDM2B silencing abrogated tumorigenicity of PDAC cell lines exhibiting loss of epithelial differentiation, whereas KDM2B overexpression cooperated with KrasG12D to promote PDAC formation in mouse models. Gain- and loss-of-function experiments coupled to genome-wide gene expression and ChIP studies revealed that KDM2B drives tumorigenicity through 2 different transcriptional mechanisms. KDM2B repressed developmental genes through cobinding with Polycomb group (PcG) proteins at transcriptional start sites, whereas it activated a module of metabolic genes, including mediators of protein synthesis and mitochondrial function, cobound by the MYC oncogene and the histone demethylase KDM5A. These results defined epigenetic programs through which KDM2B subverts cellular differentiation and drives the pathogenesis of an aggressive subset of PDAC.

OBJECTIVE:A growing multicultural society presents healthcare providers with a difficult task of providing appropriate care for individuals who have different life experiences, beliefs, value systems, religions, languages, and notions of healthcare. This is especially vital when end-of-life care is needed during childhood. There is a dearth of literature addressing cultural considerations in the pediatric palliative care field. As members of a specific culture often do not ascribe to the same religious traditions, the purpose of this article was to explore and review how culture and religion informs and shapes pediatric palliative care. METHOD/METHODS:Comprehensive literature searches were completed through an online search of nine databases for articles published between 1980 and 2011: PsychINFO, MEDLINE®, Journal of Citation Reports-Science Edition, Embase, Scopus, CINAHL®, Social Sciences Citation Index (SSCI), EBSCO, and Ovid. Key terms included: culture, transcultural, spiritual, international, ethnic, customs or religion AND end-of-life, palliative care, death, dying, cancer, or hospice, and children, pediatrics, or pediatric oncology. Reference lists in the retrieved articles were examined for additional studies that fit the inclusion criteria, and relevant articles were included for review. In addition, web-based searches of specific journals were conducted. These included, but were not limited to: Qualitative Health Research, Psycho-Oncology, Journal of Psychosocial Oncology, Journal of Pediatric Psychology, Journal of Pediatric Health Care, Journal of Pediatric Oncology Nursing, Omega, Social Work in Health Care, and Journal of Palliative Medicine. RESULTS:Thirty-seven articles met eligibility criteria. From these, seven distinct themes emerged that have implications for pediatric palliative care. These include the role of culture in decision-making, faith and the involvement of clergy, communication (spoken and unspoken language), communicating to children about death (truth telling), the meaning of pain and suffering, the meaning of death and dying, and location of end-of-life care. SIGNIFICANCE OF RESULTS/CONCLUSIONS:The review of the literature provides insight into the influence of religion and how culture informs lifestyle and shapes the experiences of illness, pain, and end-of-life care. Recommendations for providing culturally sensitive end-of-life care are offered through the framework outlined in the Initiative for Pediatric Palliative Care Quality Improvement Project of 2002. Cultural traditions are dynamic, never static, and cannot be generalized to all families. Guidelines to aid in approaches to palliative care are provided, and providers are encouraged to define these important differences for each family under their care.

OBJECTIVE: This study has been specifically designed to investigate very low frequency neuronal oscillations (VLFO, <0.5 Hz) during resting states and during goal-directed tasks of graded difficulty levels, quantify the changes that the slow waves undergo in these conditions and compare them with those for higher frequency bands (namely delta, theta and alpha). METHODS: To this end we developed a multistage signal processing methodology comprising blind source separation coupled with a neural network based feature extraction and classification method. RESULTS: Changes in the amplitude and phase of brain sources estimates in the VLF band between rest and task were enhanced with increased task difficulty, but remained lower than those experienced in higher frequency bands. The slow wave variations were also significantly correlated with task performance measures, and hence with the level of task-directed attention. CONCLUSIONS: These findings suggest that besides their prominent sensitivity to external stimulation, VLFOs also contribute to the cortical ongoing background activity which may not be specifically related to task-specific attention and performance. SIGNIFICANCE: Our work provides important insight into the association between VLF brain activity and conventional EEG frequency bands, and presents a novel framework for assessing neural activity during various mental conditions and psychiatric states.

OBJECTIVE: Minimal research links anxiety disorders in adolescents to regional gray matter volume (GMV) abnormalities and their modulation by genetic factors. Prior research suggests that a brain-derived neurotrophic factor (BNDF) Val(66)Met polymorphism may modulate such brain morphometry profiles. METHOD: Using voxel-based morphometry and magnetic resonance imaging, associations of BDNF and clinical anxiety with regional GMVs of anterior cingulate cortex, insula, amygdala, and hippocampus were examined in 39 affected (17 Met allele carriers, 22 Val/Val homozygotes) and 63 nonaffected adolescents (27 [corrected] Met allele carriers, 36 [corrected] Val/Val homozygotes). RESULTS: Amygdala and anterior hippocampal GMVs were significantly smaller in patients than in healthy comparison adolescents, with a reverse pattern for the insula. Post-hoc regression analyses indicated a specific contribution of social phobia to the GMV reductions in the amygdala and hippocampus. In addition, insula and dorsal-anterior cingulate cortex (ACC) GMVs were modulated by BDNF genotype. In both regions, and GMVs were larger in the Val/Val homozygote patients than in individuals carrying the Met allele. CONCLUSIONS: These results implicate reduced GMV in the amygdala and hippocampus in pediatric anxiety, particularly social phobia. In addition, the data suggest that genetic factors may modulate differences in the insula and dorsal ACC.

The present study is the first to assess whether the neural correlates of cognitive control processes differ in adults with and without a behaviorally inhibited temperament during early childhood. Adults with and without childhood behavioral inhibition completed an emotional conflict task while undergoing functional magnetic resonance imaging scanning. While no group differences in behavior were observed, adults with childhood behavioral inhibition, relative to adults without childhood behavioral inhibition, exhibited greater dorsomedial prefrontal cortex activity during conflict detection and greater putamen activity during conflict adaptation. Lifetime psychopathology predicted behavioral, but not brain-related, differences in conflict adaptation. These data suggest that the brain regions underlying cognitive control processes are differentially influenced by childhood behavioral inhibition, and may be differently related to psychopathology.