Comparing the activPAL software's Primary Time in Bed Algorithm against Self-Report and van der Berg's Algorithm.

The purpose of this study was to compare activPAL algorithm-estimated values for time in bed (TIB), wake time (WT) and bedtime (BT) against self-report and an algorithm developed by van der Berg and colleagues. Secondary analyses of baseline data from the Community Activity for Prevention Study (CAPS) were used in which adults ≥ 18 years wore the activPAL for seven days. Mixed-effects models compared differences between TIB, WT, and BT for all three methods. Bland-Altman plots examined agreement and the two-one-sided test examined equivalence. activPAL was not equivalent to self-report or van der Berg in estimating TIB, but was equivalent to self-report for estimating BT, and was equivalent to van der Berg for estimating WT. The activPAL algorithm requires adjustments before researchers can use it to estimate TIB. However, researchers can use activPAL's option to manually enter self-reported BT and WT to estimate TIB and better understand 24-hour movement patterns.

CAPS on the move: Crafting an approach to recruitment for a randomized controlled trial of community gardening.

OBJECTIVE: To describe and evaluate recruitment approaches for a randomized controlled trial (RCT) of community gardening in Denver, Colorado. (ClinicalTrials.gov: NCT03089177). METHODS: We used community and staff feedback to adapt our recruitment approach from year 1 to year 2 of a multi-year RCT to address health behaviors related to cancer prevention. In year 2, we added a full-time recruitment coordinator, designed and implemented a tracking spreadsheet, and engaged advisory committee members, local garden leaders, and health partners in planning and outreach. Screening and consent rates, staff time and costs for years 1 and 2 are compared. RESULTS: In year 1, recruitment methods yielded 136 initial contacts, 106 screenings and 64 consented participants. In year 2, enhanced staffing and outreach yielded 257 initial contacts, 193 screenings, and 123 consented participants. Personal referrals, health fairs, NextDoor, and fliers yielded the highest percentage of consented participants. School and community meetings yielded the lowest yield for potential participants. Spanish-speaking participants were mostly recruited by direct methods. Compared to year 1 recruitment, which required 707 h of staff time and cost $14,446, year 2 recruitment required 1224 h of staff time and cost $22,992. Average cost for retained participants was $226 (year 1) and $186 (year 2). DISCUSSION: Those planning pragmatic clinical trials with recruitment in multi-ethnic communities can use the results from this study to understand the efficacy of techniques, and to budget costs for recruitment. While our culturally-tailored recruitment methods cost more, they provided more effective and efficient ways to reach recruitment goals.

On the Distribution of Summary Statistics for Missing Data.

Under an assumption that missing values occur randomly in a matrix, formulae are developed for the expected value and variance of six statistics that summarize the number and location of the missing values. For a seventh statistic, a regression model based on simulated data yields an estimate of the expected value. The results can be used in the development of methods to control the Type I error and approximate power and sample size for multilevel and longitudinal studies with missing data.

Calculating Power for the General Linear Multivariate Model With One or More Gaussian Covariates.

We describe a noncentral ℱ power approximation for hypotheses about fixed predictors in general linear multivariate models with one or more Gaussian covariates. The results apply to both single and multiple parameter hypotheses. The approach extends power approximations for models with only fixed predictors, and for models with a single Gaussian covariate. The new method approximates the noncentrality parameter under the alternative hypothesis using a Taylor series expansion for the matrix-variate beta distribution of type I. We used a Monte Carlo simulation to evaluate the accuracy of both the novel power approximation, and published power approximations. The simulation study accounted for randomness in both the predictors and the errors. We varied the number of outcomes, the number of parameters in the hypothesis, the per-treatment sample size, and the correlations between the random predictors and the outcomes. We demonstrate that our approximation is more accurate than published methods, both in small and large samples. We show that the run time for a single power calculation with the new method is on the order of milliseconds, compared to an average empirical simulation time of roughly three minutes. Approximate and simulated power can be calculated using the free, open-source rPowerlib package. (http://github.com/SampleSizeShop/rPowerlib).

Rationale and design for the community activation for prevention study (CAPs): A randomized controlled trial of community gardening.

BACKGROUND: Engaging in health-promoting behaviors (e.g., healthy fruit- and vegetable-rich diet, physical activity) and living in supportive social and built environments are consistently and significantly associated with reductions in cancer, heart disease, diabetes, and other chronic diseases. Interventions to change diet and physical activity behaviors should aim to educate individuals, change the environments in which people live, work and recreate, improve access, availability, and affordability of healthy foods, and create safe places the facilitate active lifestyles. This trial will assess whether community gardening increases fruit and vegetable consumption and physical activity, improves social support and mental health, and reduces age-associated weight gain and sedentary time among a multi-ethnic, mixed-income population. METHODS/DESIGN: A randomized controlled trial of community gardening began in Denver, Colorado in January 2017. Over 3 years, we will recruit 312 consenting participants on Denver Urban Gardens' waitlists and randomize them to garden or remain on the waitlist. At baseline (pre-gardening), harvest time, and post-intervention, study participants will complete three 24-hour dietary recalls, a 7-day activity monitoring period using accelerometry, a health interview and physical anthropometry. DISCUSSION: This project addresses health-promoting behaviors among a multi-ethnic, mixed-income adult population in a large metropolitan area. If successful, this trial will provide evidence that community gardening supports and sustains healthy and active lifestyles, which can reduce risk of cancer and other chronic diseases. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03089177: Registered on 03/17/17.

Exposure to secondhand smoke, exclusive breastfeeding and infant adiposity at age 5 months in the Healthy Start study.

BACKGROUND: Infant adiposity may be influenced by several environmental risk factors, but few studies have explored these interactions. OBJECTIVE: To examine the interaction between exposure to secondhand smoke and breastfeeding exclusivity on adiposity at age 5 months. METHODS: We studied 813 mother-offspring pairs from the longitudinal Healthy Start study. Fat mass and fat-free mass were measured by air displacement plethysmography. Linear regression analyses were used to estimate the association between household smokers (none, any) with fat mass, fat-free mass, percent fat mass, weight-for-age z-score, weight-for-length z-score and BMI-for-age z-score as separate outcomes. Interaction terms between household smokers and breastfeeding exclusivity (<5 months, ≥5 months) were added to separate models. RESULTS: The combination of exposure to secondhand smoke and a lack of exclusive breastfeeding was associated with increased adiposity at age 5 months. For example, within the not exclusively breastfed strata, exposure to secondhand smoke was associated with increased fat mass (0.1 kg; 95% CI: 0.0-0.2; P = 0.05). Conversely, within the exclusively breastfed strata, there was virtually no difference in fat mass between exposed and non-exposed infants (coefficient: -0.1; 95% CI: -0.3-0.1; P = 0.25). CONCLUSIONS: Our findings may inform new public health strategies with potential relevance for both smoking cessation and obesity prevention.

Fetal overnutrition and offspring insulin resistance and ß-cell function: the Exploring Perinatal Outcomes among Children (EPOCH) study.

AIMS: To examine the associations of intrauterine exposure to maternal diabetes and obesity with offspring insulin resistance, ß-cell function and oral disposition index in a longitudinal observational study of ethnically diverse offspring. METHODS: A total of 445 offspring who were exposed (n=81) or not exposed (n=364) to maternal diabetes in utero completed two fasting blood measurements at mean (sd) ages of 10.5 (1.5) and 16.5 (1.2) years, respectively, and an oral glucose tolerance test at the second visit. We used linear mixed models and general linear univariate models to evaluate the associations of maternal diabetes and pre-pregnancy BMI with offspring outcomes. RESULTS: Maternal diabetes in utero predicted increased insulin resistance [18% higher updated homeostatic model assessment of insulin resistance (HOMA2-IR), P=0.01; 19% lower Matsuda index, P=0.01 and 9% greater updated homeostatic model assessment of ß-cell function (HOMA2-ß), P=0.04]. Each 5-kg/m2 increase in pre-pregnancy BMI predicted increased insulin resistance (11% greater HOMA2-IR, P<0.001; 10% lower Matsuda index, P<0.001; 6% greater HOMA2-ß, P<0.001). Similar results were obtained in a combined model with both exposures. After adjustment for offspring BMI, only maternal diabetes was associated with higher HOMA2-IR (ß=1.12, P=0.03) and lower Matsuda index (ß=0.83, P=0.01). Neither exposure was associated with early insulin response or oral disposition index. CONCLUSIONS: Intrauterine exposure to diabetes or obesity is associated with greater offspring insulin resistance than non-exposure, supporting the hypothesis that fetal overnutrition results in metabolic abnormalities during childhood and adolescence.

Blood pressure during pregnancy, neonatal size and altered body composition: the Healthy Start study.

OBJECTIVE: The objective of this study is to estimate associations between changes in maternal arterial pressure during normotensive pregnancies and offspring birth weight and body composition at birth. STUDY DESIGN: Prospective study of 762 pregnant normotensive Colorado women, recruited from outpatient obstetrics clinics. Repeated arterial pressure measurements during pregnancy were averaged within the second and third trimesters, respectively. Multivariable regression models estimated associations between second to third trimester changes in arterial pressure and small-for-gestational-age birth weight, fat mass, fat-free mass and percent body fat. RESULTS: A greater second to third trimester increase in maternal arterial pressure was associated with greater odds of small-for-gestational-age birth weight. Greater increases in maternal diastolic blood pressure were associated with reductions in offspring percent body fat (-1.1% in highest vs lowest quartile of increase, 95% confidence interval: -1.9%, -0.3%). CONCLUSION: Mid-to-late pregnancy increases in maternal arterial pressure, which do not meet clinical thresholds for hypertension are associated with neonatal body size and composition.

Maternal diet quality in pregnancy and neonatal adiposity: the Healthy Start Study.

BACKGROUND/OBJECTIVES: Poor maternal diet in pregnancy can influence fetal growth and development. We tested the hypothesis that poor maternal diet quality during pregnancy would increase neonatal adiposity (percent fat mass (%FM)) at birth by increasing the fat mass (FM) component of neonatal body composition. METHODS: Our analysis was conducted using a prebirth observational cohort of 1079 mother-offspring pairs. Pregnancy diet was assessed via repeated Automated Self-Administered 24-h dietary recalls, from which Healthy Eating Index-2010 (HEI-2010) scores were calculated for each mother. HEI-2010 was dichotomized into scores of ⩽57 and >57, with low scores representing poorer diet quality. Neonatal %FM was assessed within 72 h after birth with air displacement plethysmography. Using univariate and multivariate linear models, we analyzed the relationship between maternal diet quality and neonatal %FM, FM, and fat-free mass (FFM) while adjusting for prepregnancy body mass index (BMI), physical activity, maternal age, smoking, energy intake, preeclampsia, hypertension, infant sex and gestational age. RESULTS: Total HEI-2010 score ranged between 18.2 and 89.5 (mean: 54.2, s.d.: 13.6). An HEI-2010 score of ⩽57 was significantly associated with higher neonatal %FM (ß=0.58, 95% confidence interval (CI) 0.07-1.1, P<0.05) and FM (ß=20.74; 95% CI 1.49-40.0; P<0.05) but no difference in FFM. CONCLUSIONS: Poor diet quality during pregnancy increases neonatal adiposity independent of maternal prepregnancy BMI and total caloric intake. This further implicates maternal diet as a potentially important exposure for fetal adiposity.

Diet, physical activity and mental health status are associated with dysglycaemia in pregnancy: the Healthy Start Study.

AIMS: To examine the association between dysglycaemia and multiple modifiable factors measured during pregnancy. METHODS: The Healthy Start Study collected self-reported data on modifiable factors in early and mid-pregnancy (median 17 and 27 weeks gestation, respectively) from 832 women. Women received one point for each modifiable factor for which they had optimum scores: diet quality (Healthy Eating Index score ≥64), physical activity level (estimated energy expenditure ≥170 metabolic equivalent task-h/week), and mental health status (Perceived Stress Scale score <6 and Edinburgh Postnatal Depression Scale score <13). Dysglycaemia during pregnancy was defined as an abnormal glucose challenge result, ≥1 abnormal results on an oral glucose tolerance test, or a clinical diagnosis of gestational diabetes. Logistic regression models estimated odds ratios for dysglycaemia as a function of each factor and the total score, adjusted for age, race/ethnicity, pre-pregnancy BMI, history of gestational diabetes, and family history of Type 2 diabetes. RESULTS: In individual analyses, only physical activity was significantly associated with a reduced risk of dysglycaemia (adjusted odds ratio 0.67, 95% CI 0.44-1.00). We observed a significant, dose-response association between increasing numbers of optimal factors and odds of dysglycaemia (adjusted P=0.01). Compared with having no optimal modifiable factors, having all three was associated with a 73% reduced risk of dysglycaemia (adjusted odds ratio 0.27, 95% CI 0.08-0.95). CONCLUSIONS: An increasing number of positive modifiable factors in pregnancy was associated with a dose-response reduction in risk of dysglycaemia. Our results support the hypothesis that modifiable factors in pregnancy are associated with the risk of prenatal dysglycaemia.

Exploring the association between maternal prenatal multivitamin use and early infant growth: The Healthy Start Study.

BACKGROUND: Prenatal multivitamin supplementation is recommended to improve offspring outcomes, but effects on early infant growth are unknown. OBJECTIVES: We examined whether multivitamin supplementation in the year before delivery predicts offspring mass, body composition and early infant growth. METHODS: Multivitamin use was assessed longitudinally in 626 women from the Healthy Start Study. Offspring body size and composition was measured with air displacement plethysmography at birth (<3 days) and postnatally (median 5.2 months). Separate multiple linear regressions assessed the relationship of weeks of daily multivitamin use with offspring mass, body composition and postnatal growth, after adjustment for potential confounders (maternal age, race, pre-pregnant body mass index; offspring gestational age at birth, sex; breastfeeding exclusivity). RESULTS: Maternal multivitamin use was not related to offspring mass or body composition at birth, or rate of change in total or fat-free mass in the first 5 months. Multivitamin use was inversely associated with average monthly growth in offspring percent fat mass (ß = -0.009, p = 0.049) between birth and postnatal exam. Offspring of non-users had a monthly increase in percent fat mass of 3.45%, while offspring at the top quartile of multivitamin users had a monthly increase in percent fat mass of 3.06%. This association was not modified by exclusive breastfeeding. CONCLUSIONS: Increased multivitamin use in the pre-conception and prenatal periods was associated with a slower rate of growth in offspring percent fat mass in the first 5 months of life. This study provides further evidence that in utero nutrient exposures may affect offspring adiposity beyond birth.

Associations of maternal weight status prior and during pregnancy with neonatal cardiometabolic markers at birth: the Healthy Start study.

BACKGROUND: Maternal obesity increases adult offspring risk for cardiovascular disease; however, the role of offspring adiposity in mediating this association remains poorly characterized. OBJECTIVE: To investigate the associations of maternal pre-pregnant body mass index (maternal BMI) and gestational weight gain (GWG) with neonatal cardiometabolic markers independent of fetal growth and neonatal adiposity. METHODS: A total of 753 maternal-infant pairs from the Healthy Start study, a large multiethnic pre-birth observational cohort were used. Neonatal cardiometabolic markers included cord blood glucose, insulin, glucose-to-insulin ratio (Glu/Ins), total and high-density lipoprotein cholesterol (HDL-c), triglycerides, free fatty acids and leptin. Maternal BMI was abstracted from medical records or self-reported. GWG was calculated as the difference between the first pre-pregnant weight and the last weight measurement before delivery. Neonatal adiposity (percent fat mass) was measured within 72 h of delivery using whole-body air-displacement plethysmography. RESULTS: In covariate adjusted models, maternal BMI was positively associated with cord blood insulin (P=0.01) and leptin (P<0.001) levels, and inversely associated with cord blood HDL-c (P=0.05) and Glu/Ins (P=0.003). Adjustment for fetal growth or neonatal adiposity attenuated the effect of maternal BMI on neonatal insulin, rendering the association nonsignificant. However, maternal BMI remained associated with higher leptin (P<0.0011), lower HDL-c (P=0.02) and Glu/Ins (P=0.05), independent of neonatal adiposity. GWG was positively associated with neonatal insulin (P=0.02), glucose (P=0.03) and leptin levels (P<0.001) and negatively associated with Glu/Ins (P=0.006). After adjusting for neonatal adiposity, GWG remained associated with higher neonatal glucose (P=0.02) and leptin levels (P=0.02) and lower Glu/Ins (P=0.048). CONCLUSIONS: Maternal weight prior and/or during pregnancy is associated with neonatal cardiometabolic makers including leptin, glucose and HDL-c at delivery, independent of neonatal adiposity. Our results suggest that intrauterine exposure to maternal obesity influences metabolic processes beyond fetal growth and fat accretion.

Leptin levels at birth and infant growth: the EPOCH study.

OBJECTIVE: To examine the association of cord blood leptin with body mass index (BMI) growth velocity from birth to 12 months of age among infants exposed and not exposed to over-nutrition in utero (defined as maternal overweight/obesity or presence of gestational diabetes). METHODS: 185 infants enrolled in the Exploring Perinatal Outcomes among Children study (76 exposed and 109 not exposed) had leptin and insulin measured in cord blood. Longitudinal weight and length measures in the first 12 months of life (average 4 per participant) obtained from medical records were used to compute BMI growth rates. Mixed models were used to examine associations of cord blood leptin with growth. RESULTS: Compared with unexposed infants, those exposed had significantly higher cord blood insulin (8.64 v. 6.97 uU/ml, P<0.01) and leptin levels (8.89 v. 5.92 ng/ml, P=0.05) as well as increased birth weights (3438.04 v. 3306.89 g, P=0.04). There was an inverse relationship between cord leptin levels and BMI growth from birth to 12 months of age (P=0.005); however, exposure to over-nutrition in utero did not significantly modify this association (P=0.59). CONCLUSION: We provide support of a possible operational feedback mechanism by which lower cord blood leptin levels are associated with faster infant growth in the first year of life. Our data do not tend to support the hypothesis that this mechanism is altered in infants exposed to over-nutrition in utero; however our sample is too small to provide sufficient evidence. Larger epidemiological studies are needed to elucidate the mechanisms responsible for increased propensity for obesity in exposed offspring.

Probabilities for separating sets of order statistics.

Consider a set of order statistics that arise from sorting samples from two different populations, each with their own, possibly different distribution functions. The probability that these order statistics fall in disjoint, ordered intervals and that of the smallest statistics, a certain number come from the first populations is given in terms of the two distribution functions. The result is applied to computing the joint probability of the number of rejections and the number of false rejections for the Benjamini-Hochberg false discovery rate procedure.

Fast Computation by Block Permanents of Cumulative Distribution Functions of Order Statistics from Several Populations.

The joint cumulative distribution function for order statistics arising from several different populations is given in terms of the distribution functions of the populations. The computational cost of our formula in the case of two populations is still exponential in the worst case, but it is a dramatic improvement compared to the general formula by Bapat and Beg. In the case when only the joint distribution function of a subset of the order statistics of fixed size is needed, the complexity is polynomial, for the case of two populations.

Expected Power for the False Discovery Rate with Independence.

The Benjamini-Hochberg procedure is widely used in multiple comparisons. Previous power results for this procedure have been based on simulations. This article produces theoretical expressions for expected power. To derive them, we make assumptions about the number of hypotheses being tested, which null hypotheses are true, which are false, and the distributions of the test statistics under each null and alternative. We use these assumptions to derive bounds for multiple dimensional rejection regions. With these bounds and a permanent based representation of the joint density function of the largest p-values, we use the law of total probability to derive the distribution of the total number of rejections. We derive the joint distribution of the total number of rejections and the number of rejections when the null hypothesis is true. We give an analytic expression for the expected power for a false discovery rate procedure that assumes the hypotheses are independent.

Fat distribution and metabolic changes are strongly correlated and energy expenditure is increased in the HIV lipodystrophy syndrome.

OBJECTIVE: To examine the relationships between protease inhibitor (PI) therapy, body fat distribution and metabolic disturbances in the HIV lipodystrophy syndrome. DESIGN: Cross-sectional study. SETTING: HIV primary care practices. PATIENTS: PI-treated patients with lipodystrophy (n= 14) and PI-treated (n= 13) and PI-naive (n= 5) patients without lipodystrophy. MAIN OUTCOME MEASURES: Body composition was assessed by physical examination, dual-energy X-ray absorptiometry and computed tomography. Insulin sensitivity (SI) was measured using the insulin-modified frequently sampled intravenous glucose tolerance test. Lipid profiles, other metabolic parameters, duration of HIV infection, CD4 lymphocyte counts, HIV-1 RNA load and resting energy expenditure (REE) were also assessed. RESULTS: PI-treated patients with lipodystrophy were significantly less insulin sensitive than PI-treated patients and PI-naive patients without any changes in fat distribution (SI(22) x 10(-4) (min(-1)/microU/ml) versus 3.2 x 10(-4) and 4.6 x 10(-4) (min(-1)/microU/ml), respectively; P < 0.001). Visceral adipose tissue area and other measures of central adiposity correlated strongly with metabolic disturbances as did the percent of total body fat present in the extremities; visceral adipose tissue was an independent predictor of insulin sensitivity and high density lipoprotein cholesterol levels. REE per kg lean body mass was significantly higher in the group with lipodystrophy compared to the groups without lipodystrophy (36.9 versus 31.5 and 29.4 kcal/kg lean body mass; P < 0.001), and SI was strongly correlated with and was an independent predictor of REE in this population. CONCLUSIONS: Body fat distribution and metabolic disturbances are strongly correlated in the HIV lipodystrophy syndrome and REE is increased.

Phosphorylation of eIF-4E on Ser 209 in response to mitogenic and inflammatory stimuli is faithfully detected by specific antibodies.

Phosphorylation of Ser 209 is thought to modulate the activity of the cap-binding factor eIF-4E which is a crucial component in the initiation complex for cap-dependent translation of mRNA. We report here the full reconstitution of the p38 Map kinase cascade leading to phosphorylation of eIF-4E in vitro and the generation of antibodies specific for phospho-serine 209 in eIF-4E. These antibodies were used to probe the phosphorylation of eIF-4E in mammalian cells stimulated with mitogens and pro-inflammatory cytokines. Treatment of human dermal fibroblasts with FCS led to a transient hyperphosphorylation, followed by hypophosphorylation and return to normal state phosphorylation at 16 h after the initial stimulation. By using a potent small molecular weight inhibitor of Mnk1, the upstream kinase for eIF-4E, we observed a rapid dephosphorylation of eIF-4E within 45 min after addition of the inhibitor, suggesting a high turnover of phosphate on eIF-4E mediated by Mnk1 and a yet unidentified phosphatase.

A field comparison of two methods for sampling lead in household dust.

Comparability of dust lead measurements has been a difficult problem due to different sampling and analysis techniques. This paper compares two dust sampling techniques, the U.S. Department of Housing and Urban Development (HUD) dust wipe method and the Lioy, Wainman, Weisel (LWW) sampler. The HUD method specifies using a moist towelette to pick up as much dust as possible in a specified area and estimates total lead loading. The LWW sampler collects the dust on preweighed wetted filter media, and provides greater standardization of the sampling path and pressure applied. LWW samples were analyzed using inductively coupled plasma mass spectronomy (no samples below minimum detection limit), while HUD samples were analyzed using flame atomic absorption (32% of samples below minimum detection limit). A bootstrapping technique was used in the analysis to contend with those HUD samples below the minimum detection limit. Mixed model equations were generated to predict HUD values from LWW results, and to examine the effects of sampling location, time, and method. The results indicate that the two samplers performed similarly under field conditions, although the LWW sampler produced consistently lower lead loading estimates. LWW values that predicted HUD lead clearance values of 100 micrograms/ft2 for floors and 500 micrograms/ft2 for window sills were 72 micrograms/ft2 and 275 micrograms/ft2, respectively. To examine internal reproducibility, duplicate samples were taken using both the HUD and LWW methods. Correlation results within paired samples indicated a statistically significantly higher (p < 0.001) internal reproducibility for lead loading, for the LWW sampler (r = 0.87), than for the HUD method (r = 0.71). Some of the differences appeared to be related to the analytical methods.