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Physical activity (PA) estimated by a wearable sensor may reflect clinical status in pediatric pulmonary hypertension (PH). Prior studies used research‐grade hip‐anchored sensors or commercial wrist sensors with proprietary scoring algorithms. Wrist sensors may offer better acceptability in children; however, their ability to detect associations between PA and clinical characteristics is unknown. Youth 8–18 years with PH [Groups 1–4, functional class (FC) I‐II] and healthy controls wore a GENEActiv accelerometer on the non‐dominant wrist for 14 days. Raw acceleration data were processed using the open‐source GGIR R‐package. Participants completed a 6‐min walk distance (6MWD) and quality‐of‐life questionnaire. Muscle mass and strength were assessed by densitometry and handgrip dynamometry. The most recent cardiac testing was extracted from the medical record. Groups were compared by Fisher's exact test, unpaired t‐test, or Wilcoxon rank sum test. Multivariate regression models assessed for associations between PA and clinical metrics. Thirty PH participants (median 13.9 years, 57% female, 57% Group 1, 50% FC I) and 29 controls were included. Total PA was similar. PH participants demonstrated fewer and shorter bouts of moderate‐to‐vigorous PA ≥ 10 min and more time spent at lower PA intensities. In PH participants, muscle mass was positively associated with PA but 6MWD was negatively associated with PA. PA was not associated with quality of life. Within the PH group, worse PA traits were associated with lower FC and worse clinical testing. Wrist sensors reveal deficits in PA traits including reduced moderate‐to‐vigorous activity bouts and lower intensity gradients in pediatric PH.

ObjectivesAs a common form of sedentary behaviour, television viewing is associated with an increase in body mass index (BMI) as well as overall cardiovascular disease (CVD) risk. This study examined the extent to which meeting the recommended volume of weekly physical activity (PA) reduced the association between television viewing with the outcomes of BMI and CVD risk. A second aim was to determine the number of hours (ie, cut-point) of daily television viewing that conferred a higher BMI and CVD risk for a large population-based sample of adults.DesignPopulation-based, cross-sectional study.SettingUK Biobank recruited across 35 centres in the UK between 2006 and 2010.Primary outcomeCVD risk, as measured by the 30-year Framingham risk score.ResultsLinear regression models indicated that every additional hour of television viewing per day was associated with a 3% increase in CVD risk (aCoeff=0.03, d=0.16, p<0.0001); the interaction between television viewing with meeting PA guidelines was marginally associated with CVD risk (aCoeff=0.0010, d=0.01, p=0.014). Each additional hour of television viewing per day was associated with a 0.54 increase in BMI (aCoeff=0.54, d=0.13, p<0.0001); the interaction between television viewing with meeting PA guidelines was not significantly associated with BMI. Regression tree models of the study outcomes revealed that 2.5 hours of television viewing was associated with pronounced increases in BMI and CVD risk.ConclusionsThese data underscore the independent association between television viewing with cardiovascular risk and suggest that reducing television viewing to less than 2.5 hours per day, even in physically active adults, is a clinical and public health priority.

Children with pulmonary hypertension (PH) often demonstrate limited exercise capacity. Data support exercise as an effective nonpharmacologic intervention among adults with PH. However, data on exercise training in children and adolescents are limited, and characteristics of the optimal exercise program in pediatric PH have not been identified. Exercise programs may have multiple targets, including muscle deficits which are associated with exercise limitations in both adult and pediatric PH. Wearable accelerometer sensors measure physical activity volume and intensity in the naturalistic setting and can facilitate near continuous data transfer and bidirectional communication between patients and the study team when paired with informatics tools during exercise interventions. To address the knowledge gaps in exercise training in pediatric PH, we designed a prospective, single arm, nonrandomized pilot study to determine feasibility and preliminary estimates of efficacy of a 16‐week home exercise intervention, targeting lower extremity muscle mass and enriched by wearable mobile health technology. The exercIse Training in pulmONary hypertEnsion (iTONE) trial includes (1) semistructured exercise prescriptions tailored to the participant's baseline level of activity and access to resources; (2) interval goal setting fostering self‐efficacy; (3) real time monitoring of activity via wearable devices; (4) a digital platform enabling communication and feedback between participant and study team; (5) multiple avenues to assess participant safety. This pilot intervention will provide information on the digital infrastructure needed to conduct home‐based exercise interventions in PH and will generate important preliminary data on the effect of exercise interventions in youth with chronic cardiorespiratory conditions to power larger studies in the future.

The combined effect of modifiable health factors on the risk of cardiovascular disease (CVD) mortality has not been well established. The objective of this study was to determine the association between 5 modifiable health factors in combination on the risk of CVD mortality in a sample of adult men. A cohort of 38,110 men (aged 20-84 years and of middle and upper socioeconomic strata) was followed over time until their date of death or December 31, 2003. A health profile score (unweighted and weighted) was developed based on cardiorespiratory fitness (CRF; moderate or high vs low), self-reported physical activity (active vs inactive), smoking status (not current vs current), alcohol consumption (1-14 drinks per week vs 0 or >14 drinks per week), and body mass index (BMI; 18.5-24.9 vs ≥25.0 kg/m2). During 16.1 ± 8.4 years of follow-up and 613,571 man-years of exposure, there were 949 deaths from CVD. High CRF, normal BMI, being physically active, and not currently smoking were individually associated with reduced risk of CVD mortality after adjusting for confounders. When considered in combination, a minimum of 2 of 5 positive health factors reduced the risk of CVD mortality (hazard ratio = 0.67, 95% CI 0.49-0.91). The weighted score indicated that a combination of high CRF, not currently smoking, and normal BMI is of most clinical importance to CVD mortality (hazard ratio = 0.31, 95% CI 0.24-0.39). Exposure to increasing numbers of beneficial health factors in adulthood reduced the risk of CVD mortality in men, and multibehavioral prevention efforts in adulthood should be encouraged.

Abstract Study Objectives Over 75% of US high school students obtain insufficient sleep, placing them at risk for adverse health outcomes. Identification of modifiable determinants of adolescent sleep is needed to inform prevention strategies, yet little is known about the influence of the built environment on adolescent sleep. Methods In this prospective study, actigraphy was used to assess sleep outcomes among 110 adolescents for 14 days each in eighth and ninth grades: duration (hours/night), onset and offset, and sleeping ≥8 hours. Home addresses were linked to built environment exposures: sound levels, tree canopy cover, street density, intersection density, population density, and housing density. Mixed-effects regression estimated associations of built environment measures with sleep outcomes, adjusting for sex, race, parent education, household income, household size, grade, weeknight status, and neighborhood poverty. Results A 1-standard deviation (SD) increase in neighborhood sound was associated with 16 minutes later sleep onset (β = 0.28; 95% confidence interval (CI): 0.06, 0.49) and 25% lower odds of sleeping for ≥8 hours (odds ratio (OR) = 0.75, 95% CI: 0.59, 0.96). A 1-SD increase in neighborhood tree canopy was associated with 18 minutes earlier sleep onset (β = −0.31, 95% CI: −0.49, −0.13) and 10 minutes earlier sleep offset (β= −0.17, 95% CI: −0.28, −0.05). No associations were observed for density-based exposures. Conclusions Higher neighborhood sound level was associated with lower odds of sufficient sleep, while higher tree canopy cover was associated with more favorable sleep timing. Neighborhood sound levels and tree canopy cover are potential targets for policies and interventions to support healthier sleep among adolescents.

Abstract Study Objectives To examine associations between 24-hour rest–activity patterns and body mass index (BMI) among community-dwelling US adults. Rest–activity patterns provide a field method to study exposures related to circadian rhythms. Methods Adults (N = 578) wore an actigraph on their nondominant wrist for 7 days. Intradaily variability and interdaily stability (IS), M10 (most active 10-hours), L5 (least active 5-hours), and relative amplitude (RA) were derived using nonparametric rhythm analysis. Mesor, acrophase, and amplitude were calculated from log-transformed count data using the parametric cosinor approach. Results Participants were 80% female and mean (standard deviation) age was 52 (15) years. Participants with higher BMI had lower values for magnitude, RA, IS, total sleep time (TST), and sleep efficiency. In multivariable analyses, less robust 24-hour rest–activity patterns as represented by lower RA were consistently associated with higher BMI: comparing the bottom quintile (least robust) to the top quintile (most robust 24-hour rest–activity pattern) of RA, BMI was 3-kg/m2 higher (p = .02). Associations were similar in magnitude to an hour less of TST (1-kg/m2 higher BMI) or a 10% decrease in sleep efficiency (2-kg/m2 higher BMI), and independent of age, sex, race, education, and the duration of rest and/or activity. Conclusions Lower RA, reflecting both higher night activity and lower daytime activity, was associated with higher BMI. Independent of the duration of rest or activity during the day or night, 24-hour rest, and activity patterns from actigraphy provide aggregated measures of activity that associate with BMI in community-dwelling adults.

Background Bone accrual impacts lifelong skeletal health, but genetic discovery has been primarily limited to cross-sectional study designs and hampered by uncertainty about target effector genes. Here, we capture this dynamic phenotype by modeling longitudinal bone accrual across 11,000 bone scans in a cohort of healthy children and adolescents, followed by genome-wide association studies (GWAS) and variant-to-gene mapping with functional follow-up. Results We identify 40 loci, 35 not previously reported, with various degrees of supportive evidence, half residing in topological associated domains harboring known bone genes. Of several loci potentially associated with later-life fracture risk, a candidate SNP lookup provides the most compelling evidence for rs11195210 (SMC3). Variant-to-gene mapping combining ATAC-seq to assay open chromatin with high-resolution promoter-focused Capture C identifies contacts between GWAS loci and nearby gene promoters. siRNA knockdown of gene expression supports the putative effector gene at three specific loci in two osteoblast cell models. Finally, using CRISPR-Cas9 genome editing, we confirm that the immediate genomic region harboring the putative causal SNP influences PRPF38A expression, a location which is predicted to coincide with a set of binding sites for relevant transcription factors. Conclusions Using a new longitudinal approach, we expand the number of genetic loci putatively associated with pediatric bone gain. Functional follow-up in appropriate cell models finds novel candidate genes impacting bone accrual. Our data also raise the possibility that the cell fate decision between osteogenic and adipogenic lineages is important in normal bone accrual.

Study Objectives Pediatricians lack tools to support families at home for the promotion of childhood sleep. We are using the Multiphase Optimization Strategy (MOST) framework to guide the development of a mobile health platform for childhood sleep promotion. The objective of this study is to demonstrate feasibility of a mobile health platform towards treating children with insufficient sleep. Methods Children aged 10–12 years were enrolled (Study #1: N = 30; Study #2: N = 43). Participants wore a sleep tracker to measure sleep duration. Data were retrieved by a mobile health platform, programmed to send introductory messages during run-in (2 weeks) and goal achievement messages during intervention (7 weeks) periods. In study #1, participants were randomized to control, gain-framed incentive or loss-framed incentive arms. In study #2, participants were randomized to control, loss-framed incentive, normative feedback or loss-framed incentive plus normative feedback arms. Results In study #1, 1514 nights of data were captured (69%) and sleep duration during the intervention was higher by an average of 21 (95% CI: −8, 51) and 34 (95% CI: 7, 61) minutes per night for the gain-framed and loss-framed arms, respectively, compared to controls. In study #2, 2,689 nights of data were captured (81%), with no major differences in average sleep duration between the control and the loss-framed or normative feedback arms. Conclusions We have developed and deployed a mobile health platform that can capture sleep data and remotely communicate with families. Promising candidate intervention components will be further investigated under the optimization phase of the MOST framework. Clinical Trials Both studies included in this manuscript were registered at clinicaltrials.gov: -Study #1: NCT03263338 -Study #2: NCT03426644

Osteoporosis is one of the most common chronic forms of disability in postmenopausal women and represents a major health burden around the world. Bone fragility is affected by bone mineral density (BMD), and, one of the most important factors in preventing osteoporosis is optimizing peak bone mass, which is achieved during growth in childhood and adolescence. BMD is a complex trait resulting from environmental and genetic factors. Genome-wide association studies have discovered robust genetic signals influencing BMD in adults, and similar studies have also been conducted to investigate the genetics of BMD in the pediatric setting. These latter studies have revealed that many adult osteoporosis-related loci also regulate BMD during growth. These investigations have the potential to profoundly impact public health and will allow for the eventual development of effective interventions for the prevention of osteoporosis.

Background Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank. Results Large-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide significant loci and leverage trans-ancestry data to perform fine-mapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with different growth trajectories correlated with different outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fibrillation. Conclusion We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single “optimal” pubertal growth pattern.