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AbstractOur primary objectives are to empirically identify distinct childhood groups based on trajectories of waist circumference (WC) and waist circumference index measurements, and then to estimate associations between these groups and adult diabetes incidence, as well as other outcomes, including blood pressure, body size, body composition, and hemoglobin levels. Childhood WC and height measurements as well as various adult measurements are taken from participants in the Fels Longitudinal Study. Childhood groups are identified using group-based trajectory modeling. Associations between the resulting group probabilities and adult outcomes are examined using mixed models. Our results show that distinct childhood groups are identifiable for both waist size measurements, with growth curves exhibited by these groups becoming distinguishably separate at around 4 years of age. Higher probabilities for groups exhibiting the larger waist size for either measurement were estimated to have higher risks of developing diabetes in adulthood. Associations were also observed between group probabilities and systolic blood pressure, diastolic blood pressure, and various anthropomorphic measurements, with most associations consistently occurring in early adulthood. These findings expand upon the existing literature, showing that childhood trends in waist size, distinguishable at ages as early as 4 years, are associated with adult Type-2 diabetes.

Background: Despite the recognition that central obesity plays a critical role in chronic disease, few large-scale imaging studies have documented human variation in abdominal adipose tissue patterning. Objective: We aimed to compare the associations between abdominal subcutaneous adipose tissue (ASAT) and visceral abdominal tissue (VAT), which were measured at different locations across the abdomen, and the presence of the metabolic syndrome (MS; National Cholesterol Education Program Adult Treatment Panel III definition) and individual cardiometabolic risk factors. Design: This study included 713 non-Hispanic whites aged 18- 86 y, in whom VAT and ASAT were assessed by using multiple-image magnetic resonance imaging. The anatomical position of the magnetic resonance image containing the maximum VAT area for each subject was used as a measure of VAT patterning. Multivariate linear and logistic regression analyses were used to examine the relation of VAT, ASAT, and VAT patterning to cardiometabolic risk. Results: VAT mass was a stronger predictor of the MS than was ASAT mass, but ASAT mass (and other measures of subcutaneous adiposity) had signification interactions with VAT mass, whereby elevated ASAT reduced the probability of MS among men with high VAT (P = 0.0008). There was variation across image locations in the association of VAT area with the MS in men, and magnetic resonance images located 4-8 cm above L4-L5 provided the strongest correlations between VAT area and cardiometabolic risk factors. Subjects whose maximum VAT area was higher in the abdomen had higher LDL-cholesterol concentrations ([R.sup.2] = 0.07, P < 0.0001), independent of age and adiposity. Conclusion: Further studies are needed to confirm the effects of VAT patterning on cardiometabolic risk.

Background: A decline in the age at menarche was recently reported for US girls. Although it is possible that this recent drop stems from the concurrent increase in childhood obesity, few longitudinal studies of growth and development have been undertaken to specifically address the temporal relation between growth, adiposity, and the age at menarche. Objective: The objective was to simultaneously examine the effects of birth cohort (secular trend) and rate of maturation (age at menarche) on the timing and pattern of increases in body mass index (BMI) during adolescence in girls. Design: We applied mixed-effects polynomial models to serial BMI data, spanning from 6 y before menarche to 6 y after menarche, obtained from 211 girls enrolled in the Fels Longitudinal Study. We examined the effects of birth cohort (defined as girls born 1929-1946, 1947-1964, and 1965-1983) and age at menarche (defined as [less than or equal to] 11.9 y, 12.0-13.1 y, and [greater than or equal to] 13.2 y) on the magnitude and velocity of BMI during adolescence. Results: BMI and BMI velocity in girls born after 1965 were significantly greater than those of girls of earlier birth cohorts, despite stability in the mean age at menarche. Although girls with early menarche tended to have significantly higher BMIs than did girls with average or later menarche, these differences did not emerge until after menarche. Conclusion: These data suggest that increases in relative weight are a consequence, rather than a determinant, of the age at menarche and that secular changes in BMI and in the mean age at menarche could be independent phenomena. KEY WORDS Body mass index, menarche, longitudinal studies, cohort effect, body composition, growth, sex maturation, female children, adolescence, United States

Background: Previous studies to develop and validate bioelectrical impedance analysis (BIA) equations to predict body composition were limited by small sample sizes, sex specificity, and reliance on reference methods that use a 2-component model. Objective: This study was designed to develop sex-specific BIA equations to predict total body water (TBW) and fat-free mass (FFM) with the use of a multicomponent model for children and adults. Design: Data from 5 centers were pooled to create a sample of 1474 whites and 355 blacks aged 12-94 y. TBW was measured by dilution, and FFM was estimated with a multicomponent model based on densitometry, isotope dilution, and dual-energy X-ray absorptiometry. Results: The final race-combined TBW prediction equations included [stature.sup.2]/resistance and body weight ([R.sup.2] = 0.84 and 0.79 and root mean square errors of 3.8 and 2.6 L for males and females, respectively; CV: 8%) and tended to underpredict TBW in black males (2.0 L) and females (1.4 L) and to overpredict TBW in white males (0.5 L) and females (0.3 L). The race-combined FFM prediction equations contained the same independent variables ([R.sup.2] = 0.90 and 0.83 and root mean square errors of 3.9 and 2.9 kg for males and females, respectively; CV: [approximately equal to] 6%) and tended to underpredict FFM in black males (2.1 kg) and females (1.6 kg) and to overpredict FFM in white males (0.4 kg) and females (0.3 kg). Conclusion: These equations have excellent precision and are recommended for use in epidemiologic studies to describe normal levels of body composition. KEY WORDS Bioelectrical impedance analysis, prediction equations, total body water, fat-free mass, multicomponent model, epidemiologic surveys

The evaporation of molecules from water–organic solute binary mixtures is key for both atmospheric and industrial processes such as aerosol formation and distillation. Deviations from ideal evaporation energetics can be assigned to intermolecular interactions in solution, yet evaporation occurs from the interface, and the poorly understood interfacial, rather than the bulk, structure of binary mixtures affects evaporation kinetics. Here we determine the interfacial structure of nonideal binary mixtures of water with methanol, ethanol, and formic acid, by combining surface-specific vibrational spectroscopy with molecular dynamics simulations. We find that the free, dangling OH groups at the interfaces of these differently behaving nonideal mixtures are essentially indistinguishable. In contrast, the ordering of hydrogen-bonded interfacial water molecules differs substantially at these three interfaces. Specifically, the interfacial water molecules become more disordered (ordered) in mixtures with methanol and ethanol (formic acid), showing higher (lower) vapor pressure than that predicted by Raoult’s law.

Electronic nicotine delivery systems (ENDSs) are used by some smokers to reduce cigarette consumption, but their effectiveness is uncertain. We aimed to examine the extent to which ENDSs or a non-nicotine cigarette substitute influence tobacco-related toxicant exposure and cigarette consumption in smokers interested in smoking reduction.

The origin of the sum-frequency generation (SFG) signal of the water bending mode has been controversially debated in the past decade. Unveiling the origin of the signal is essential, because different assignments lead to different views on the molecular structure of interfacial water. Here, we combine collinear heterodyne-detected SFG spectroscopy at the water-charged lipid interfaces with systematic variation of the salt concentration. The results show that the bending mode response is of a dipolar, rather than a quadrupolar, nature and allows us to disentangle the response of water in the Stern and the diffuse layers. While the diffuse layer response is identical for the oppositely charged surfaces, the Stern layer responses reflect interfacial hydrogen bonding. Our findings thus corroborate that the water bending mode signal is a suitable probe for the structure of interfacial water.

Understanding the interfacial molecular structure of acidic aqueous solutions is important in the context of, e.g., atmospheric chemistry, biophysics, and electrochemistry. The hydration of the interfacial proton is necessarily different from that in the bulk, given the lower effective density of water at the interface, but has not yet been elucidated. Here, using surface-specific vibrational spectroscopy, we probe the response of interfacial protons at the water–air interface and reveal the interfacial proton continuum. Combined with spectral calculations based on ab initio molecular dynamics simulations, the proton at the water–air interface is shown to be well-hydrated, despite the limited availability of hydration water, with both Eigen and Zundel structures coexisting at the interface. Notwithstanding the interfacial hydrated proton exhibiting bulk-like structures, a substantial interfacial stabilization by −1.3 ± 0.2 kcal/mol is observed experimentally, in good agreement with our free energy calculations. The surface propensity of the proton can be attributed to the interaction between the hydrated proton and its counterion.

Ions containing iodine atoms at the vapor-aqueous solution interfaces critically affect aerosol growth and atmospheric chemistry due to their complex chemical nature and multivalency. While the surface propensity of iodide ions has been intensely discussed in the context of the Hofmeister series, the stability of various ions containing iodine atoms at the vapor–water interface has been debated. Here, we combine surface-specific sum-frequency generation (SFG) vibrational spectroscopy with ab initiomolecular dynamics simulations to examine the extent to which iodide ions cover the aqueous surface. The SFG probe of the free O–D stretch mode of heavy water indicates that the free O–D group density decreases drastically at the interface when the bulk NaI concentration exceeds ∼2 M. The decrease in the free O–D group density is attributed to the spontaneous appearance of triiodide that covers the topmost interface rather than to the surface adsorption of iodide. This finding demonstrates that iodide is not surface-active, yet the highly surface-active triiodide is generated spontaneously at the water–air interface, even under dark and oxygen-free conditions. Our study provides an important first step toward clarifying iodine chemistry and pathways for aerosol formation.

Phase-sensitive sum-frequency spectroscopy is a unique tool to interrogate the vibrational structure of interfaces. A precise understanding of the interfacial structure often relies on accurately determining the phase of χ(2), which has recently been demonstrated using a nonlinear interferometer in conjunction with a frequency-scanning picosecond laser system. Here, we implement nonlinear interferometry using a femtosecond laser system for broadband sum-frequency generation. The phase of the vibrational response from a self-assembled monolayer of octadecanethiol on gold is determined using the nonlinear femtosecond interferometer. The results are compared to those obtained using the more traditional heterodyne-detected phase measurements. Both methods give a similar phase spectrum and phase uncertainty. We also discuss the origin of the phase uncertainties and provide guidelines for further improvement.

A previous study showed that quercetin inhibits astrogliosis in a scratch-wound model, but did not identify the underlying mechanisms. Here, we show that quercetin exerts no effect on apoptosis or the viability of astrocytes, but significantly inhibits their proliferation, arresting them in the G1phase and decreasing the percentage of cells in the S and G2phase. In addition, we found that quercetin significantly decreased the phosphorylation of ERK12 and FAK, a downstream ERK signaling protein. Inhibition of this pathway with U0126, an inhibitor of MAP kinase, retarded wound closure, whereas sustained p-ERK12 activation, induced by vanadate, restored astrocyte migration. Our findings thus indicate that quercetin inhibits healing in the scratch-wound model of primary astrocytes in two ways: blockade of the G1to S phase cell cycle transition and inhibition of the ERKFAK signaling pathway, which may contribute toward decreasing astroglial scar formation in vivo.

Information processing of radiotherapy systems has become an important research area for sophisticated radiation treatment methodology. Geometrically precise delivery of radiotherapy in the thorax and upper abdomen is compromised by respiratory motion during treatment. Accurate prediction of the respiratory motion would be beneficial for improving tumor targeting. However, a wide variety of breathing patterns can make it difficult to predict the breathing motion with explicit models. We proposed a respiratory motion predictor, that is, customized prediction with multiple patient interactions using neural network (CNN). For the preprocedure of prediction for individual patient, we construct the clustering based on breathing patterns of multiple patients using the feature selection metrics that are composed of a variety of breathing features. In the intraprocedure, the proposed CNN used neural networks (NN) for a part of the prediction and the extended Kalman filter (EKF) for a part of the correction. The prediction accuracy of the proposed method was investigated with a variety of prediction time horizons using normalized root mean squared error (NRMSE) values in comparison with the alternate recurrent neural network (RNN). We have also evaluated the prediction accuracy using the marginal value that can be used as the reference value to judge how many signals lie outside the confidence level. The experimental results showed that the proposed CNN can outperform RNN with respect to the prediction accuracy with an improvement of 50%.

The FEBSTAT (Consequences of Prolonged Febrile Seizures) study is prospectively addressing the relationships among serial EEG, MRI, and clinical follow-up in a cohort of children followed from the time of presentation with febrile status epilepticus (FSE).

The FEBSTAT study is a prospective study that seeks to determine the acute and long-term consequences of febrile status epilepticus (FSE) in childhood.

Sum-frequency generation (SFG) spectroscopy provides a unique optical probe for interfacial molecules with interface-specificity and molecular specificity. SFG measurements can be further carried out at different polarization combinations, but the target of the polarization-dependent SFG is conventionally limited to investigating the molecular orientation. Here, we explore the possibility of polarization-dependent SFG (PD-SFG) measurements with heterodyne detection (HD-PD-SFG). We stress that HD-PD-SFG enables accurate determination of the peak amplitude, a key factor of the PD-SFG data. Subsequently, we outline that HD-PD-SFG can be used not only for estimating the molecular orientation but also for investigating the interfacial dielectric profile and studying the depth profile of molecules. We further illustrate the variety of combined simulation and PD-SFG studies.

Despite significant progress in understanding the mechanisms by which the prenatal/maternal environment can alter development and adult health, genetic influences on normal variation in growth are little understood. This work examines genetic and nongenetic contributions to body weight and weight change during infancy and the relationships between weight change and adult body composition. The dataset included 501 white infants in 164 nuclear and extended families in the Fels Longitudinal Study, each with 10 serial measures of weight from birth to age 3 years and 232 with body composition data in mid‐adulthood. Heritability and covariate effects on weight and weight z‐score change from birth to 2 years of age were estimated using a maximum likelihood variance decomposition method. Additive genetic effects explained a high proportion of the variance in infant weight status (h2= 0.61–0.95), and change in weight z‐score (h2= 0.56–0.82). Covariate effects explained 27% of the phenotypic variance at 0–1 month of age and declined in effect to 6.9% of phenotypic variance by 36 months. Significant sex, gestational age, birth order, birth year, and maternal body mass index effects were also identified. For both sexes, a significant increase in weight z‐score (≫2 SD units) (upward centile crossing) was associated with greater adulthood stature, fat mass, and percent body fat than decrease or stability in weight z‐score. Understanding genetic influences on growth rate in a well‐nourished, nutritionally stable population may help us interpret the causes and consequences of centile crossing in nutritionally compromised contexts. Am. J. Hum. Biol., 2007. © 2007 Wiley‐Liss, Inc.

Objective.To evaluate the effects of habitual physical activity (PA) on the metabolic syndrome (MS) in young adult men and women. Research methods and procedures.Cross‐sectional PA data were utilized from 249 women and 237 men, aged 18–40 years in the Fels Longitudinal Study. MS components—abdominal circumference (AC), triglycerides (TG), HDL, blood pressure (BP), and fasting glucose (FG)—were dichotomized according to the National Cholesterol Education Program's Adult Treatment Panel III revised criteria. Leisure, sport, work, and total PA scores were calculated using the Baecke Questionnaire of Habitual Physical Activity. Multiple logistic regression modeling assessed the effects of PA, age, smoking, and BMI on MS status. Results.26.9% of men and 19.3% of women had MS. For men, MS risk was reduced with increases in both total PA [OR = 0.65 (95% CI: 0.47, 0.90)] and sport PA [OR = 0.40 (95% CI: 0.23, 0.70)]. AC, TG, and HDL values also improved with total and sport PA. Among women, the risk for MS was marginally reduced by total PA [OR = 0.72 (95% CI: 0.50, 1.02)] and HDL levels were increased by both total PA [OR = 0.79 (95% CI: 0.63, 0.98)] and sport PA [OR = 0.54 (95% CI: 0.35, 0.84)]. Discussion.Increased total and sport PA reduces risk for the MS in young men, though not as clearly in young women. Am. J. Hum. Biol. 19:544–550, 2007. © 2007 Wiley‐Liss, Inc.

Symptomatic patients with Gaucher disease (GD) (acid β-glucosidase [Gcase] deficiency) are treated with injectable human recombinant GCase. Treatment results in significant decreases in lipid storage in liver, spleen, and bone marrow, but the generalized osteopenia and focal bone lesions present in many adult patients are refractory to treatment. A double-blind, 2-arm, placebo-controlled trial of alendronate (40 mg/d) was performed in adults with GD who had been treated with enzyme for at least 24 months. Primary therapeutic endpoints were improvements in (1) bone mineral density (BMD) and content (BMC) at the lumbar spine, and (2) focal lesions in x-rays of long bones assessed by a blinded reviewer. There were 34 patients with GD type 1 (age range, 18-50 years) receiving enzyme therapy who were randomized for this study. After 18 months, ΔBMD at the lumbar spine was 0.068 ± 0.21 and 0.015 ± 0.034 for alendronate and placebo groups, respectively (P = .001). Long-bone x-rays showed no change in focal lesions or bone deformities in any subject in either arm. Alendronate is a useful adjunctive therapy in combination with enzyme replacement therapy (ERT) for the treatment of GD-related osteopenia in adults, but it cannot be expected to improve focal lesions.

A number of recent reports suggest that the average age at menarche of US girls has declined over the past 20 years. Because the putative declines in the age at menarche are concurrent with increases in childhood body mass index (BMI), it has been suggested that these two trends may be causally linked. We examined differences in mean age of menarche in Fels Longitudinal Study girls who were born in six 10‐year birth cohorts (1930s, 1940s, 1950s, 1960s, 1970s, and 1980s) and simultaneous cohort changes in mean BMI measured cross‐sectionally at selected ages from 3–35 years (n = 371). Girls born in the 1980s had a mean age at menarche of 12.34 years, which was ∼3–6 months earlier than that of girls born previously (P< 0.001). While the mean BMI values at ages 25 and 35 generally increased from the 1930s to the 1970s, the mean BMI during childhood and adolescence remained constant across the six birth cohorts. In summary, we found no evidence that the recent decline in the age at menarche in the Fels Longitudinal Study girls was reflected in concurrent increases in BMI at any point in childhood or adolescence. Conversely, girls born in the 1960s and 1970s have subsequently become heavier in young and mid‐adulthood than were girls from earlier birth cohorts, without any concurrent change in the mean age at menarche over that time period. These two findings suggest that population‐level shifts in BMI and the timing of menarche are largely independent, although sometimes coincident, processes. Am. J. Hum. Biol. 16:453–457, 2004. © 2004 Wiley‐Liss, Inc.

Body composition during puberty is a marker of metabolic changes that occur during this period of growth and maturation, and, thus, holds key information regarding current and future health. During puberty, the main components of body composition (total body fat, lean body mass, bone mineral content) all increase, but considerable sexual dimorphism exists. Methods for measuring body composition (e.g. densitometry and dual-energy X-ray absorptiometry) and degree of maturity will be discussed in this review. Components of body composition show age-to-age correlations (i.e. ‘tracking’), especially from adolescence onwards. Furthermore, adipose tissue is endocrinologically active and is centrally involved in the interaction between adipocytokines, insulin and sex-steroid hormones, and thus influences cardiovascular and metabolic disease processes. In conclusion, pubertal body composition is important, not only for the assessment of contemporaneous nutritional status, but also for being linked directly to the possible onset of chronic disease later in life and is, therefore, useful for disease risk assessment and intervention early in life.

Early menarche (EM), in the lowest quartile of menarcheal age, is associated with cardiovascular disease-related outcomes among which are proximal and long-term hyperinsulinemia and insulin resistance. An increased body mass index (BMI) and increased adiposity in adolescence also have been described. This study examined the influence of menarcheal age on changes in blood insulin and glucose levels, lipid levels, and blood pressure during adolescence. Subjects were 391 females 8 to 21 years of age who participated in the Fels Longitudinal Study. Early menarche occurred at 11.9 years or less; average menarche between the 25th and 75th percentiles at ages 11.9 to 13.2 years; and late menarche at above the 75th percentile or older than 13.2 years. Nearly one fourth of participants, 23%, had EM; 42% had average menarche; and 35% had late menarche.