Faculty Bibliography

CONTEXT/BACKGROUND:Dual-energy X-ray absorptiometry (DXA) is a cornerstone of pediatric bone health assessment, yet differences in height-for-age confound the interpretation of areal bone mineral density (aBMD) measures. To reduce the confounding of short stature on spine bone density, use of bone mineral apparent density (BMAD) and height-for-age Z-score (HAZ)‒adjusted aBMD (aBMDHAZ) are recommended. However, spine BMAD reference data are sparse, and the degree to which BMAD and aBMDHAZ account for height-related artifacts in bone density remains unclear. OBJECTIVE:We developed age-, sex-, and population ancestry‒specific spine BMAD reference ranges; compared height-adjustment methods in accounting for shorter stature; and assessed the stability of these measures over time. DESIGN/METHODS:Secondary analysis of data from a previous longitudinal study. PARTICIPANTS/METHODS:Children and adolescents aged 5 to 19 years at baseline (n = 2014; 922 males; 22% black) from the Bone Mineral Density in Childhood Study. MAIN OUTCOME MEASURES/METHODS:Lumbar spine BMAD and aBMDHAZ from DXA. RESULTS:Spine BMAD increased nonlinearly with age and was greater in blacks and females (all P < 0.001). Age-specific spine BMAD z-score reference curves were constructed for black and non‒black males and females. Overall, both BMAD and aBMDHAZz scores reduced the confounding influence of shorter stature, but neither was consistently unbiased across all age ranges. Both BMAD and aBMDHAZz scores tracked strongly over 6 years (r = 0.70 to 0.80; all P < 0.001). CONCLUSION/CONCLUSIONS:This study provided robust spine BMAD reference ranges and demonstrated that BMAD and aBMDHAZ partially reduced the confounding influence of shorter stature on bone density.

Human brain anatomical and resting-state functional connectivity have been comprehensively portrayed using MRI, which are termed anatomical and functional connectomes. A systematic examination of tasks modulated whole brain functional connectivity, which we term as task connectome, is still lacking. We analyzed 6 block-designed and 1 event-related designed functional MRI data, and examined whole-brain task modulated connectivity in various task domains, including emotion, reward, language, relation, social cognition, working memory, and inhibition. By using psychophysiological interaction between pairs of regions from the whole brain, we identified statistically significant task modulated connectivity in 4 tasks between their experimental and respective control conditions. Task modulated connectivity was found not only between regions that were activated during the task but also regions that were not activated or deactivated, suggesting a broader involvement of brain regions in a task than indicated by simple regional activations. Decreased functional connectivity was observed in all the 4 tasks and sometimes reduced connectivity was even between regions that were both activated during the task. This suggests that brain regions that are activated together do not necessarily work together. The current study demonstrates the comprehensive task connectomes of 4 tasks, and suggested complex relationships between regional activations and connectivity changes.

The LENA system was designed and validated to provide information about the language environment in children 0 to 4 years of age and its use has been expanded to populations with a number of communication profiles. Its utility in children 5 years of age and older is not yet known. The present study used acoustic data from two samples of children with autism spectrum disorders (ASD) to evaluate the reliability of LENA automated analyses for detecting speech utterances in older, school age children, and adolescents with ASD, in clinic and home environments. Participants between 5 and 18 years old who were minimally verbal (study 1) or had a range of verbal abilities (study 2) completed standardized assessments in the clinic (study 1 and 2) and in the home (study 2) while speech was recorded from a LENA device. We compared LENA segment labels with manual ground truth coding by human transcribers using two different methods. We found that the automated LENA algorithms were not successful (<50% reliable) in detecting vocalizations from older children and adolescents with ASD, and that the proportion of speaker misclassifications by the automated system increased significantly with the target-child's age. The findings in children and adolescents with ASD suggest possibly misleading results when expanding the use of LENA beyond the age ranges for which it was developed and highlight the need to develop novel automated methods that are more appropriate for older children. Autism Research 2019, 12: 628-635. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Current commercially available speech detection algorithms (LENA system) were previously validated in toddlers and children up to 48 months of age, and it is not known whether they are reliable in older children and adolescents. Our data suggest that LENA does not adequately capture speech in school age children and adolescents with autism and highlights the need to develop new automated methods for older children.

Over the past two decades, a low frequency variant (rs1800012) within the first intron of the type I collagen alpha 1 (COLIA1) gene has been implicated in lower areal BMD (aBMD) and increased risk of osteoporotic fracture. This association is particularly strong in postmenopausal women, in whom net bone loss arises in the context of high bone turnover. High bone turnover also accompanies childhood linear growth; however, the role of rs1800012 in this stage of net bone accretion is less well understood. Thus, we assessed the association between rs1800012 and aBMD and bone mineral content (BMC) Z-scores for the 1/3 distal radius, lumbar spine, total hip, and femoral neck total body less head in the Bone Mineral Density in Childhood Study, a mixed-longitudinal cohort of children and adolescents (total n = 804 girls and 771 boys; n = 19 girls and 22 boys with the TT genotype). Mixed effects modeling, stratified by sex, was used to test for associations between rs1800012 and aBMD or BMC Z-scores and for pubertal stage interactions. Separately, SITAR growth modeling of aBMD and BMC in subjects with longitudinal data reduced the complex longitudinal bone accrual curves into three parameters representing a-size, b-timing, and c-velocity. We tested for differences in these three parameters by rs1800012 genotype using t-tests. Girls with the TT genotype had significantly lower aBMD and BMC Z-scores prior to puberty completion (e.g. spine aBMD-Z P-interaction = 1.0 × 10^-6), but this association was attenuated post-puberty. SITAR models revealed that TT girls began pubertal bone accrual later (b-timing; e.g. total hip BMC, P = 0.03). BMC and aBMD Z-scores also increased across puberty in TT homozygous boys. Our data, along with previous findings in post-menopausal women, suggest that rs1800012 principally affects female bone density during periods of high turnover. Insights into the genetics of bone gain and loss may be masked during the relatively quiescent state in mid-adulthood, and discovery efforts should focus on early and late life.

Sézary syndrome (SS) is the leukemic form of cutaneous T-cell lymphoma (CTCL) and can be associated with various nail irregularities, though they are infrequently reported. In this retrospective study, we reviewed medical records from a CTCL clinic database at the University of Texas MD Anderson Cancer Center (Houston, Texas) for reported nail abnormalities in patients with a diagnosis of SS. Findings for 2 select cases are described in more detail and are compared to prior case reports to establish a comprehensive list of nail irregularities that have been associated with SS.

Undiagnosed asthma adds to the burden of asthma and is an especially significant public health concern among urban adolescents. While much is known about individual-level demographic and neighborhood-level factors that characterize those with diagnosed asthma, limited data exist regarding these factors and undiagnosed asthma. This observational study evaluated associations between undiagnosed asthma and individual and neighborhood factors among a large cohort of urban adolescents. We analyzed data from 10,295 New York City adolescents who reported on asthma symptoms and diagnosis; a subset (n = 6220) provided addresses that we were able to geocode into US Census tracts. Multivariable regression models estimated associations between undiagnosed asthma status and individual-level variables. Hierarchical linear modeling estimated associations between undiagnosed asthma status and neighborhood-level variables. Undiagnosed asthma prevalence was 20.2%. Females had higher odds of being undiagnosed (adjusted odds ratio (AOR) = 1.25; 95% confidence interval (CI) = 1.13-1.37). Compared to White, non-Hispanic adolescents, Asian-Americans had higher risk of being undiagnosed (AOR = 1.41; 95% CI = 1.01-1.95); Latinos (AOR = 0.67; 95% CI = 0.45-0.83); and African-Americans/Blacks (AOR = 0.66; 95% CI = 0.52-0.87) had lower risk; Latinos and African-Americans/Blacks did not differ significantly. Living in a neighborhood with a lower concentration of Latinos relative to White non-Latinos was associated with lower risk of being undiagnosed (AOR = 0.66; CI = 0.43-0.95). Living in a neighborhood with health care provider shortages was associated with lower risk of being undiagnosed (AOR = 0.80; 95% CI =0.69-0.93). Public health campaigns to educate adolescents and their caregivers about undiagnosed asthma, as well as education for health care providers to screen adolescent patients for asthma, are warranted.

We conducted a systematic review of studies that have evaluated invariance of the construct of posttraumatic stress disorder (PTSD) to summarize their conclusions related to invariance/noninvariance and sources of noninvariance. In November 2017, we searched Pubmed, PSYCINFO, PILOTS Web of Science, CINAHL, Medline, and Psychological and Behavioral Science Collection for abstracts and articles with these inclusionary criteria: peer-reviewed, including DSM-IV or DSM-5 PTSD invariance as a main study aim, use of multigroup confirmatory factor analyses, and use of an independent PTSD instrument or module. In total, 45 articles out of 1,169 initially identified abstracts met inclusion criteria. Research assistants then followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to complete a secondary search and independently extract data. Results indicated that DSM-IV dysphoric arousal and DSM-5 hybrid model factors demonstrated the most stability; sources of instability were some intrusion (distress to trauma cues), dysphoria/numbing (traumatic amnesia, foreshortened future, emotional numbness, detachment), and arousal (hypervigilance) items. The PTSD Checklist and PTSD Reaction Index were most often used to assess PTSD in studies investigating its invariance; however, these measures demonstrated partial conceptual equivalence of PTSD across subgroups. Instead, clinician-administered measures demonstrated more conceptual equivalence across subgroups. Age, gender, cultural/linguistic factors, and sample diversity had the least moderating effect on PTSD's symptom structure. Our review demonstrates the need to examine invariance of the PTSD construct following recommended guidelines for each empirical and clinical trial study to draw meaningful multigroup comparative conclusions.

Introduction: Short sleep duration promotes metabolic dysregulation and obesity. We have previously shown that acute sleep restriction increases neuronal activity in response to food stimuli in areas of interoception and reward, such as the insula and orbitofrontal cortex. However, whether chronic mild sleep restriction impacts food reward valuation in the brain remains unknown. In an ongoing study, we assess the effects of mild 6-week sleep restriction on intrinsic functional connectivity (iFC) across reward and interoception- related brain circuitry.
Method(s): To date, 16 adult men and women (age 29.0+/-5.3 years and BMI 26.9+/-2.6 kg/m²at study entry) took part in this randomized, crossover, outpatient trial of 2 phases: habitual sleep (HS; >=7 h/night) and sleep restriction (SR; -1.5 h/night relative to HS). All participants were screened with actigraphy over a two-week period to ensure adequate sleep duration of 7-9 h/night (average screening total sleep time: 7.65+/-0.58 h/night). Two resting-state (task-free) functional MRI scans (Siemens Skyra 3T, TR=2.5s, two 5-min runs) were collected during the final week of each phase. Here we report preliminary analyses using the Data Processing & Analysis of Brain Imaging V2.3-170105 toolbox with paired-sample t-tests across the whole brain.
Result(s): Average sleep duration in the HS phase was 7.55+/-0.55 h/ night vs. 6.10+/-0.49 h/night during SR (p<0.0001). Examining iFC of 17 previously studied regions-of-interest relevant to food valuation and interoception yielded two significant results after correction for Gaussian Random Field (p<0.001 at voxel level, cluster p<0.05). iFC was greater following SR than HS for (1) left inferior frontal gyrus with medial prefrontal cortex (mPFC); and (2) mPFC with bilateral superior temporal gyrus.
Conclusion(s): This study provides preliminary evidence of decreased segregation between a key anterior node of the default mode network (mPFC) and nodes of the salience and somatosensory (auditory) networks under prolonged mild SR. Such iFC changes, suggesting atypical network coupling, if confirmed in the completed sample, will be examined in the future in relation to key measures of metabolism and cardiovascular risks

Although prior research suggests that children show rapid change in socioemotional functioning and aggression throughout early childhood, little is known about how these factors may be associated with the development of callous-unemotional (CU) features. This study investigated the parallel development of, and reciprocal relationships between, emotion understanding (EU) and aggression across early childhood, as well as how they play a role in the development of CU features. Parallel latent growth curve modeling was used to examine longitudinal reciprocal relationships between EU and aggression in a sample of 498 primarily Black (i.e., African-American or Afro-Caribbean) preschoolers (49.5% male, 89.2% Black, M_age = 4.1), followed with six waves over a 45-month period from pre-kindergarten through grade 2. CU features were included as a baseline covariate, as well as an outcome, of EU and aggression growth factors. Children with lower levels of EU at age 4 displayed higher linear increases in aggression over time. EU at age 4 had a significant indirect effect on CU features at age 8 via its association with linear increases in aggression. Findings suggest that EU is influential in the early development of aggression, which may in turn influence the development or exacerbation of CU features. Children's EU in early childhood, especially concerning others' distress, may be an important component of preventive intervention efforts for young children at risk for serious antisocial behavior.