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Beta distributions are commonly used to model proportion valued response variables, often encountered in longitudinal studies. In this article, we develop semi-parametric Beta regression models for proportion valued responses, where the aggregate covariate effect is summarized and flexibly modeled, using a interpretable monotone time-varying single index transform of a linear combination of the potential covariates. We utilize the potential of single index models, which are effective dimension reduction tools and accommodate link function misspecification in generalized linear mixed models. Our Bayesian methodology incorporates the missing-at-random feature of the proportion response and utilize Hamiltonian Monte Carlo sampling to conduct inference. We explore finite-sample frequentist properties of our estimates and assess the robustness via detailed simulation studies. Finally, we illustrate our methodology via application to a motivating longitudinal dataset on obesity research recording proportion body fat. [ABSTRACT FROM AUTHOR]

Purpose: Impact of lifestyle modification on obesity control during adolescence, a period of significant physical growth and development, is less quantitatively evaluated. Therefore, we investigated the impact of changes in reported energy intake and physical activity on anthropometrics and body composition in adolescents. Methods: Participants were obese adolescents aged 11-18 years. All of them have a body mass index (BMI) ≥ 95th percentile specific for age and gender according to the 2000 CDC Growth Charts. The intervention consists of supervised physical activity, structured nutrition education and dietary modification, and behavioral support in 6 months. Hundred and forty-five obese adolescents completed the study. Results: Compared to baseline, significant reductions in body weight (−1.4 kg, p < 0.001) and BMI (−0.1 kg/m, p < 0.001) were observed at 6 months. When compared to expected growth trajectories on the 2000 CDC Growth Charts, body weight and BMI were reduced by 3.6 kg and 1.5 kg/m, respectively, in boys and 5.6 kg and 1.9 kg/m in girls. Age was inversely associated with changes in weight ( β = −1.48 kg, p < 0.01) and BMI ( β = −0.32 kg/m, p = 0.03). There was a dose-response relationship between reduction in energy intake and weight loss. A decrease of 100 kcal/day was significantly associated with reductions in body weight 0.30 kg, BMI 0.09 kg/m, and BMI Z score 0.01 (all p < 0.01). Physical activity was not significantly associated with changes in anthropometrics or body composition. Conclusions: Reduction in energy intake was a significant predictor of obesity reduction in these adolescents. A quantitative evaluation of adolescent weight loss programs should account for natural growth and development. [ABSTRACT FROM AUTHOR]

Purpose: In a prospective study, Consequences of Prolonged Febrile Seizures in Childhood (FEBSTAT), we determined the frequency of human herpesvirus (HHV)-6 and HHV-7 infection as a cause of febrile status epilepticus (FSE). Methods: Children ages 1 month to 5 years presenting with FSE were enrolled within 72 h and received a comprehensive assessment including specimens for HHV-6 and HHV-7. The presence of HHV-6A, HHV-6B, or HHV-7 DNA and RNA (amplified across a spliced junction) determined using quantitative polymerase chain reaction (qPCR) at baseline indicated viremia. Antibody titers to HHV-6 and HHV-7 were used in conjunction with the PCR results to distinguish primary infection from reactivated or prior infection Key Findings: Of 199 children evaluated, HHV-6 or HHV-7 status could be determined in 169 (84.9%). HHV-6B viremia at baseline was found in 54 children (32.0%), including 38 with primary infection and 16 with reactivated infection. No HHV-6A infections were identified. HHV-7 viremia at baseline was observed in 12 children (7.1%), including eight with primary infection and four with reactivated infection. Two subjects had HHV-6/HHV-7 primary coinfection at baseline. There were no differences in age, characteristics of illness or fever, seizure phenomenology or the proportion of acute EEG or imaging abnormalities in children presenting with FSE with or without HHV infection. Significance: HHV-6B infection is commonly associated with FSE. HHV-7 infection is less frequently associated with FSE. Together, they account for one third of FSE, a condition associated with an increased risk of both hippocampal injury and subsequent temporal lobe epilepsy. [ABSTRACT FROM AUTHOR]

Background: Evidence shows that some causes of the metabolic syndrome (MS) begin in childhood, which could indicate a familial association, through either genetic inheritance or cohabitation. Objective: This study examined associations between parents and adult offspring diagnoses of the MS and its risk factors. Design: Measurements were obtained from adult participants and their adult offspring enrolled in the Fels Longitudinal Study, with simultaneous waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides, HDL, and glucose observations used for diagnosis. On the basis of repeated measurements (in some cases), adult participants were classified as having the MS at least once or as never having the MS. Chi-square tests, ORs, and mixed-effects models were used to study familial associations. Results: Maternal (OR: 2.5; 95% CI: 1.1, 5.5) and paternal (OR: 4.1; 95% CI: 1.4, 12.1) MS classifications were significantly associated with MS classification in sons. MS classification in mothers and daughters (OR: 2.7; 95% CI: 0.9, 8.7; P = 0.08) was similar to that in sons but was not significant, whereas fathers and daughters were not associated (OR: 1.1; 95% CI: 0.4, 3.5). Maternal MS diagnoses were significantly and positively associated with triglycerides in male offspring and were significantly associated with SBP, DBP, and triglycerides in females. Paternal diagnoses were significantly associated only with DBP and HDL in male offspring. Conclusions: Parental MS diagnosis is significantly associated with MS diagnosis in adult male offspring, and adverse levels of certain risk factors are associated between offspring and parents, although these associations vary across risk factors and child sex. [ABSTRACT FROM AUTHOR]

Objectives: To determine secular trends by birth decade in body mass index (BMI), waist circumference/height (W/Ht), percent body fat (PBF), and fat-free mass adjusted for height squared (FFM/Ht2) in children and adolescents aged 8-18 years. Methods: Serial data were analyzed from 628 boys and 591 girls aged 8-18 years who participated in the Fels Longitudinal Study. Subjects were stratified by birth decade from 1960 to 1999. Means and standard deviations were computed for all measurements by birth decade, age, and sex. A repeated-measures analysis of variance was used data to ascertain secular trends separately for boys and girls. Results: Boys and girls born in the 1990s had significantly higher mean BMI, W/Ht, and PBF than did children born in previous decades. Mean FFM/Ht2 was significantly smaller in boys born in the 1990s than boys of the same age born in earlier decades. No secular trend was noted in FFM/Ht2 in girls by decade of birth. Conclusion: Our analysis of serial data collected over 4 decades confirms the secular trend in childhood BMI previously observed in successive cross-sectional studies. Our analysis discloses significant positive secular trends in W/Ht and PBF in both boys and girls and a significant negative secular trend in FFM/Ht2 in boys over the last 4 decades of the 20th century. The secular changes presage increases in the prevalence of conditions associated with childhood and adolescent obesity-such as hypertension, glucose intolerance, and dyslipidemia-that may appear as early as the second decade of life. Am. J. Hum. Biol., 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The effects of adding fiber to the tolerance of a peptide-based formula have not been studied. The objective of this study was to evaluate the tolerance of a peptide-based formula with insoluble and prebiotic fiber in children with compromised gut function. During January 2005 to June 2006, a 6-week randomized, double-blind, cross-over clinical study was conducted to compare stool frequency, stool consistency, and tolerance (abdominal pain, abdominal distension, vomiting, weight gain, and intake) between a formula with or without 3.5 g fructo-oligosaccharides and 3.8 g insoluble fiber/L. Fourteen children with gastrointestinal dysmotility (n=9), Crohn''s disease (n=3), or mild short bowel syndrome (n=2) were randomized to receive one of two formulas for 2 weeks followed by a 5-day washout period and then the second diet for another 2 weeks. Means and standard deviations of daily stool frequency and consistency were calculated and compared using intent-to-treat analysis. Linear mixed models were applied to each outcome variable. Stool frequency did not differ by formula. Stool consistency did differ with more soft “mushy” stools (less hard stools) occurring with use of fiber (P<0.001) and more watery stools occurring with control formula (P<0.01). The extremes of stool consistency were normalized with the fiber formula. No significant differences were observed in vomiting, abdominal pain, feeding intakes, or weight gain between the two formulas. This study showed that a peptide-based formula containing fiber was as well-tolerated as a fiber-free formula in a small population of children with gastrointestinal impairments. Longer-term effects of the fiber formula need to be studied. [Copyright &y& Elsevier]

Abstract: The genetic influences on bone mass likely change throughout the life span, but most genetic studies of bone mass regulation have focused on adults. There is, however, a growing awareness of the importance of genes influencing the acquisition of bone mass during childhood on lifelong bone health. The present investigation examines genetic influences on childhood bone mass by estimating the residual heritabilities of different measures of second metacarpal bone mass in a sample of 600 10-year-old participants from 144 families in the Fels Longitudinal Study. Bivariate quantitative genetic analyses were conducted to estimate genetic correlations between cortical bone mass measures, and measures of bone growth and development. Using a maximum likelihood-based variance components method for pedigree data, we found a residual heritability estimate of 0.71 for second metacarpal cortical index. Residual heritability estimates for individual measures of cortical bone (e.g., lateral cortical thickness, medial cortical thickness) ranged from 0.47 to 0.58, at this pre-pubertal childhood age. Low genetic correlations were found between cortical bone measures and both bone length and skeletal age. However, after Bonferonni adjustment for multiple testing, ρ G was not significantly different from 0 for any of these pairs of traits. Results of this investigation provide evidence of significant genetic control over bone mass largely independent of maturation while bones are actively growing and before rapid accrual of bone that typically occurs during puberty. [Copyright &y& Elsevier]

Abstract: Quantitative ultrasound (QUS) measurements of bone have been reported to predict osteoporotic fracture risk in postmenopausal women and older men. Although many studies have examined the heritability of bone mineral density (BMD), few studies have estimated the heritability of calcaneal QUS phenotypes. In the present study, we examined the genetic regulation of calcaneal QUS parameters in individuals from nuclear and extended families. The study population includes 260 men and 295 women aged 18–91 years (mean ± SD: 46 ± 16 years) who belong to 111 pedigrees in the Fels Longitudinal Study. Three measures of calcaneal structure were collected from both the right and left heel using the Sahara® bone sonometer. These measures included broadband ultrasound attenuation (BUA), speed of sound (SOS), and the quantitative ultrasound index (QUI). We used a variance components based maximum likelihood method to estimate the heritability of QUS parameters while simultaneously adjusting for covariate effects. Additionally, we used bivariate extensions of these methods to calculate additive genetic and random environmental correlations among QUS measures. All phenotypes demonstrated statistically significant heritabilities (P < 0.0000001). Heritabilities in the right heel (h2 ± SE) were h2 = 0.59 ± 0.10 for BUA, h2 = 0.73 ± 0.09 for SOS, and h2 = 0.72 ± 0.09 for QUI. Similarly, heritabilities for the left heel were h2 = 0.52 ± 0.10, h2 = 0.75 ± 0.10, and h2 = 0.70 ± 0.10, respectively. There was evidence for significant genetic and environmental correlations among these six QUS measures. Combinations of QUS measures in the right and left heel demonstrated genetic correlations of 0.94–0.99 and all were significantly different from one indicating at least a partially unique genetic architecture for each of these measures. This study demonstrates that QUS measures of the calcaneus among healthy men and women are heritable, and there are large shared additive genetic effects among all of the traits examined. [Copyright &y& Elsevier]