Evaluation of the Portable HealthWear Armband: a device to measure total daily energy expenditure in free-living type 2 diabetic individuals.
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Calorimetry, Indirect↗
Biomedical subjects
David B Allison
Publications and source records attributed to David B Allison.
Insufficient production and tissue delivery of CD4+ memory T cells in rapidly progressive simian immunodeficiency virus infection.
The mechanisms linking human immunodeficiency virus replication to the progressive immunodeficiency of acquired immune deficiency syndrome are controversial, particularly the relative contribution of CD4+ T cell destruction. Here, we used the simian immunodeficiency virus (SIV) model to investigate the relationship between systemic CD4+ T cell dynamics and rapid disease progression. Of 18 rhesus macaques (RMs) infected with CCR5-tropic SIVmac239 (n=14) or CXCR4-tropic SIVmac155T3 (n=4), 4 of the former group manifested end-stage SIV disease by 200 d after infection. In SIVmac155T3 infections, naive CD4+ T cells were dramatically depleted, but this population was spared by SIVmac239, even in rapid progressors. In contrast, all SIVmac239-infected RMs demonstrated substantial systemic depletion of CD4+ memory T cells by day 28 after infection. Surprisingly, the extent of CD4+ memory T cell depletion was not, by itself, a strong predictor of rapid progression. However, in all RMs destined for stable infection, this depletion was countered by a striking increase in production of short-lived CD4+ memory T cells, many of which rapidly migrated to tissue. In all rapid progressors (P <0.0001), production of these cells initiated but failed by day 42 of infection, and tissue delivery of new CD4+ memory T cells ceased. Thus, although profound depletion of tissue CD4+ memory T cells appeared to be a prerequisite for early pathogenesis, it was the inability to respond to this depletion with sustained production of tissue-homing CD4+ memory T cells that best distinguished rapid progressors, suggesting that mechanisms of the CD4+ memory T cell generation play a crucial role in maintaining immune homeostasis in stable SIV infection.
Analysis of Variance↗
Overweight, obesity, and colorectal cancer screening: disparity between men and women.
BACKGROUND: To estimate the association between body-mass index (BMI: kg/m2) and colorectal cancer (CRC) screening among US adults aged >or= 50 years. METHODS: Population-based data from the 2001 Behavioral Risk Factor Surveillance Survey. Adults (N = 84,284) aged >or= 50 years were classified by BMI as normal weight (18.5-<25), overweight (25-<30), obesity class I (30-<35), obesity class II (35-<40), and obesity class III (>or= 40). Interval since most recent screening fecal occult blood test (FOBT): (0 = >1 year since last screening vs. 1 = screened within the past year), and screening sigmoidoscopy (SIG): (0 = > 5 years since last screening vs. 1 = within the past 5 years) were the outcomes. RESULTS: Results differed between men and women. After adjusting for age, health insurance, race, and smoking, we found that, compared to normal weight men, men in the overweight (odds ratio [OR] 1.25, 95% CI = 1.05-1.51) and obesity class I (OR = 1.21, 95% CI = 1.03-1.75) categories were more likely to have obtained a screening SIG within the previous 5 years, while women in the obesity class I (OR = 0.86, 95%CI = 0.78-0.94) and II (OR = 0.88, 95%CI = 0.79-0.99) categories were less likely to have obtained a screening SIG compared to normal weight women. BMI was not associated with FOBT. CONCLUSION: Weight may be a correlate of CRC screening behavior but in a different way between men and women.
Aged↗
Clinical implications of obesity with specific focus on cardiovascular disease: a statement for professionals from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation.
Obesity adversely affects cardiac function, increases the risk factors for coronary heart disease, and is an independent risk factor for cardiovascular disease. The risk of developing coronary heart disease is directly related to the concomitant burden of obesity-related risk factors. Modest weight loss can improve diastolic function and affect the entire cluster of coronary heart disease risk factors simultaneously. This statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism reviews the relationship between obesity and the cardiovascular system, evaluates the effect of weight loss on coronary heart disease risk factors and coronary heart disease, and provides practical weight management treatment guidelines for cardiovascular healthcare professionals. The data demonstrate that weight loss and physical activity can prevent and treat obesity-related coronary heart disease risk factors and should be considered a primary therapy for obese patients with cardiovascular disease.
Anti-Obesity Agents↗
Empirical Bayes estimation of gene-specific effects in micro-array research.
Micro-array technology allows investigators the opportunity to measure expression levels of thousands of genes simultaneously. However, investigators are also faced with the challenge of simultaneous estimation of gene expression differences for thousands of genes with very small sample sizes. Traditional estimators of differences between treatment means (ordinary least squares estimators or OLS) are not the best estimators if interest is in estimation of gene expression differences for an ensemble of genes. In the case that gene expression differences are regarded as exchangeable samples from a common population, estimators are available that result in much smaller average mean-square error across the population of gene expression difference estimates. We have simulated the application of such an estimator, namely an empirical Bayes (EB) estimator of random effects in a hierarchical linear model (normal-normal). Simulation results revealed mean-square error as low as 0.05 times the mean-square error of OLS estimators (i.e., the difference between treatment means). We applied the analysis to an example dataset as a demonstration of the shrinkage of EB estimators and of the reduction in mean-square error, i.e., increase in precision, associated with EB estimators in this analysis. The method described here is available in software that is available at http://www.soph.uab.edu/ssg.asp?id=1087.
Bayes Theorem↗
A simple significance test for quantile regression.
Where OLS regression seeks to model the mean of a random variable as a function of observed variables, quantile regression seeks to model the quantiles of a random variable as functions of observed variables. Tests for the dependence of the quantiles of a random variable upon observed variables have only been developed through the use of computer resampling or based on asymptotic approximations resting on distributional assumptions. We propose an exceedingly simple but heretofore undocumented likelihood ratio test within a logistic regression framework to test the dependence of a quantile of a random variable upon observed variables. Simulated data sets are used to illustrate the rationale, ease, and utility of the hypothesis test. Simulations have been performed over a variety of situations to estimate the type I error rates and statistical power of the procedure. Results from this procedure are compared to (1) previously proposed asymptotic tests for quantile regression and (2) bootstrap techniques commonly used for quantile regression inference. Results show that this less computationally intense method has appropriate type I error control, which is not true for all competing procedures, comparable power to both previously proposed asymptotic tests and bootstrap techniques, and greater computational ease. We illustrate the approach using data from 779 adolescent boys age 12-18 from the Third National Health and Nutrition Examination Survey (NHANES III) to test hypotheses regarding age, ethnicity, and their interaction upon quantiles of waist circumference.
Adolescent↗
Epistatic interaction between two nonstructural loci on chromosomes 7 and 3 influences hepatic lipase activity in BSB mice.
BSB mice exhibit a wide range of obesity despite being produced by a backcross of lean C57BL/6J (B) x lean Mus spretus (SPRET/Pt) F1 animals x B. Previous linkage studies identified a quantitative trait locus (QTL) on mouse chromosome 7 with coincident peaks for hepatic lipase activity, obesity, and plasma cholesterol. However, these mice were not analyzed for gene x gene epistasis. Hepatic lipase activity is correlated with obesity and plasma cholesterol levels. In this study, we identified QTLs for plasma hepatic lipase activity with three statistical mapping methods: maximum likelihood interval mapping, Bayesian nonepistatic mapping, and Bayesian epistatic mapping. Bayesian epistatic mapping detected not only the QTL on chromosome 7 but also an additional QTL on chromosome 3, which has a weak main effect but a strong interaction with chromosome 7. SPRET/Pt alleles of the QTL on each chromosome promote hepatic lipase activity. The proportion of phenotypic variance explained by the epistatic effect is higher than that explained by the main effect of the QTL on chromosome 7.
Alleles↗
The impact of alpha-lipoic acid, coenzyme Q10 and caloric restriction on life span and gene expression patterns in mice.
We evaluated the efficacy of three dietary interventions started at middle age (14 months) to retard the aging process in mice. These were supplemental alpha-lipoic acid (LA) or coenzyme Q(10) (CQ) and caloric restriction (CR, a positive control). LA and CQ had no impact on longevity or tumor patterns compared with control mice fed the same number of calories, whereas CR increased maximum life span by 13% (p <.0001) and reduced tumor incidence. To evaluate these interventions at the molecular level, we used microarrays to monitor the expression of 9977 genes in hearts from young (5 months) and old (30 months) mice. LA, CQ, and CR inhibited age-related alterations in the expression of genes involved in the extracellular matrix, cellular structure, and protein turnover. However, unlike CR, LA and CQ did not prevent age-related transcriptional alterations associated with energy metabolism. LA supplementation lowered the expression of genes encoding major histocompatibility complex components and of genes involved in protein turnover and folding. CQ increased expression of genes involved in oxidative phosphorylation and reduced expression of genes involved in the complement pathway and several aspects of protein function. Our observations suggest that supplementation with LA or CQ results in transcriptional alterations consistent with a state of reduced oxidative stress in the heart, but that these dietary interventions are not as effective as CR in inhibiting the aging process in the heart.
Algorithms↗
Novel tumor necrosis factor alpha-regulated genes in rheumatoid arthritis.
OBJECTIVE: To determine novel genes regulated by tumor necrosis factor alpha (TNFalpha) signaling in primary rheumatoid arthritis synovial fibroblasts (RASFs). METHODS: Oligonucleotide microarrays were used to measure gene expression levels in 6 independent replicate samples of RASFs. RASFs were transfected for 18 hours with AdIkappaB-dominant negative (AdIkappaB-DN) (n = 3) or with control AdTet expressing the reverse tetracycline trans-activator (n = 3). The cells were stimulated for 3 hours with TNFalpha, and total RNA was prepared. Several novel parametric and nonparametric methods were used to rank genes in terms of the magnitude and significance of intergroup differences. Microarray expression differences were confirmed by real-time quantitative reverse transcription-polymerase chain reaction. Small interfering RNA (siRNA) was used to specifically down-modulate microarray-identified genes to demonstrate their role in the promotion of apoptosis, proliferation, or matrix metalloproteinase (MMP) expression. RESULTS: Blocking of NF-kappaB by AdIkappaB-DN was associated with a down-modulation of antiapoptosis genes, including BIRC-3, and several novel genes, including GG2-1, a TNFalpha-inducible FLIP-like gene. Other families of genes that were significantly down-regulated by AdIkappaB-DN included cytokines/chemokines (interleukin-1beta [IL-1beta], IL-8, IL-15, and RANTES), adhesion molecule (vascular cell adhesion molecule 1, intercellular adhesion molecule 1), and unique genes that have not previously been reported to be regulated by TNFalpha in RA. Inhibition of the GG2-1 gene using the siRNA technique resulted in significantly enhanced apoptosis, decreased proliferation, and decreased production of MMP-1 in TNFalpha-stimulated RASFs. CONCLUSION: These studies provide a comprehensive analysis of genes that are differentially regulated by TNFalpha signaling and NF-kappaB nuclear translocation in RASFs and demonstrate methods for confirming the expression and functional significance of such genes.
Apoptosis↗
Waist circumference percentiles in nationally representative samples of African-American, European-American, and Mexican-American children and adolescents.
OBJECTIVE: To describe and provide estimates of the distribution of waist circumference (WC) according to percentiles in African-, European-, and Mexican-American children, and to test for group differences at different percentiles. STUDY DESIGN: Cross-sectional data from the Third National Health and Nutrition Examination Survey (NHANES III) were examined. The sample evaluated included 9713 nonpregnant persons 2 to 18 years of age with measured values of WCs. Age-, sex-, and ethnicity-specific percentiles were estimated via percentile regression. RESULTS: WC measurements increased in a monotonic fashion across ages but at nonconstant rates and in a manner that varied across age and sex. At higher percentiles of the distribution, estimates of WC differ between Mexican-American (MA) and European-American (EA) and between African-American (AA) and European-American (EA), and, in some cases, exceeded the adult cutoff value for obesity-related disease risk at as early as 13 years of age. CONCLUSION: Age-, sex-, and ethnicity-specific WC percentiles are available for US children and adolescents and can be used as an assessment tool that could impact public health recommendations. Results suggest concern with respect to high WC values among certain ethnic groups.
Adolescent↗
Statistical methods for testing effects on "maximum lifespan".
It has been noted that certain interventions such as caloric restriction may increase maximum lifespan, whereas other interventions may increase mean or median lifespan but not maximum lifespan. Here the term "maximum lifespan" is used to refer to the upper percentiles of the distribution of lifespan. This is of great interest because increasing maximum lifespan may be an indicator that an intervention is slowing the general process of aging and not merely retarding the development of specific diseases. However, formal methods for testing maximum lifespan have not been elucidated. Herein, we show via simulation that conditional t-test (CTT), a method that is sometimes used, is invalid. We then offer a new method based on quantile regression and we show that this method is, at worst, conservative and remains powerful and valid.
Animals↗
Individual differences in the response to ingested nutrients.
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Energy Metabolism↗
Mapping multiple quantitative trait Loci for ordinal traits.
Many complex traits in humans and other organisms show ordinal phenotypic variation but do not follow a simple Mendelian pattern of inheritance. These ordinal traits are presumably determined by many factors, including genetic and environmental components. Several statistical approaches to mapping quantitative trait loci (QTL) for such traits have been developed based on a single-QTL model. However, statistical methods for mapping multiple QTL are not well studied as continuous traits. In this paper, we propose a Bayesian method implemented via the Markov chain Monte Carlo (MCMC) algorithm to map multiple QTL for ordinal traits in experimental crosses. We model the ordinal traits under the multiple threshold model, which assumes a latent continuous variable underlying the ordinal phenotypes. The ordinal phenotype and the latent continuous variable are linked through some fixed but unknown thresholds. We adopt a standardized threshold model, which has several attractive features. An efficient sampling scheme is developed to jointly generate the threshold values and the values of latent variable. With the simulated latent variable, the posterior distributions of other unknowns, for example, the number, locations, genetic effects, and genotypes of QTL, can be computed using existing algorithms for normally distributed traits. To this end, we provide a unified approach to mapping multiple QTL for continuous, binary, and ordinal traits. Utility and flexibility of the method are demonstrated using simulated data.
Algorithms↗
Effect of winsorization on power and type 1 error of variance components and related methods of QTL detection.
Variance components analysis provides an efficient method for performing linkage analysis for quantitative traits. However, power and type 1 error of variance components-based likelihood ratio testing may be affected when phenotypic data are nonnormally distributed (especially with high values of kurtosis) and there is moderate to high correlation among the siblings. Winsorization can reduce the effect of outliers on statistical analyses. Here, we considered the effect of winsorization on variance components-based tests. We considered the likelihood ratio test (LRT), the Wald test, and some robust variance components tests. We compared these tests with Haseman-Elston least squares-based tests. We found that power to detect linkage is significantly increased after winsorization of the nonnormal phenotypes. Winsorization does not greatly diminish the type 1 error for the variance components-based tests for markedly nonnormal data. A robust version of the LRT that adjusts for sample kurtosis showed the best power for nonnormal data. Finally, phenotype winsorization of nonnormal data reduces the bias in estimation of the major gene variance component.
Alleles↗
Towards sound epistemological foundations of statistical methods for high-dimensional biology.
A sound epistemological foundation for biological inquiry comes, in part, from application of valid statistical procedures. This tenet is widely appreciated by scientists studying the new realm of high-dimensional biology, or 'omic' research, which involves multiplicity at unprecedented scales. Many papers aimed at the high-dimensional biology community describe the development or application of statistical techniques. The validity of many of these is questionable, and a shared understanding about the epistemological foundations of the statistical methods themselves seems to be lacking. Here we offer a framework in which the epistemological foundation of proposed statistical methods can be evaluated.
Genetic Techniques↗
Combination of BMI and Waist Circumference for Identifying Cardiovascular Risk Factors in Whites.
OBJECTIVE: BMI (kilograms per meters squared) and waist circumference (WC) (measured in centimeters) are each associated with the risk of developing cardiovascular disease (CVD). Therefore, a combination of the two may be more effective in identifying subjects at risk than either alone. The present study sought to identify the combination of BMI and WC that has the strongest association with CVD risk factors in whites. RESEARCH METHODS AND PROCEDURES: Subjects were 8712 white men and women from the Third National Health and Nutrition Examination Survey. The optimal combination of BMI and WC was developed using logistic regression models with BMI and WC as predictors and CVD risk factors as outcomes. The combined measure of BMI and WC using current cut-off points was also examined. Sensitivity, specificity, and receiver operating characteristics curves were compared between the combined measures and BMI alone. RESULTS: For white men, the optimal combination of BMI and WC for identifying CVD risk factors was 0.68 x BMI + 0.32 x WC. This combination generated a score that better estimated the odds of having CVD risk factors than either alone. For white women, WC alone largely determined the likelihood of having CVD risks. The combination of BMI and WC using current cut-off points may provide an improved measure of CVD risk. Combined measures showed a higher sensitivity or a shorter distance in receiver operating characteristic curves in the identification of CVD risk factors. DISCUSSION: Combined measures of BMI and WC may provide a higher overall test performance for CVD risk factors and may be useful in some ethnic groups as an improved means of screening subjects for further evaluation in the clinical setting.
Body Constitution↗
Familial aggregation of energy intake in children.
BACKGROUND: Uncompensated overnutrition promotes obesity, but the controls of children's eating behavior are poorly understood. Insights may be achieved by testing whether the eating patterns of children are associated with demographic variables or whether they aggregate among family members. OBJECTIVE: We tested whether children's total energy intake and macronutrient intake and their ability to compensate for earlier energy intake were associated with sociodemographic variables and anthropometric indexes. We also tested whether these behavioral traits aggregate among siblings. DESIGN: Thirty-two sibling pairs aged 3-7 y consumed a multi-item lunch preceded by a low-energy (12.55 kJ) or high-energy (627.60 kJ) preload drink. Mixed-models regression tested the associations between children's energy intake, demographic variables, and anthropometric measures. An intraclass correlation coefficient quantified the family correlation of the measures of children's eating. RESULTS: Children consumed significantly more total energy after consuming the low-energy preload ( +/- SD: 2237.39 +/- 1176.45 kJ) than after consuming the high-energy preload (1601.18 +/- 930.65 kJ). Compensation ability was unrelated to the children's age, sex, or ethnicity. Total energy and macronutrient intake, but not compensation propensity, were associated among siblings. CONCLUSIONS: The familial association of total energy and macronutrient intakes, independent of anthropometric measures, suggests genetic or home environmental influences specific to these behaviors. Short-term energy compensation, although very accurate within this sample, showed no significant familial correlation.
Appetite Regulation↗
Quantitative trait Loci specifying the response of body temperature to dietary restriction.
Dietary restriction (DR) retards aging and mortality across a variety of taxa. In homeotherms, one of the hallmarks of DR is lower mean body temperature (T(b)), which might be directly responsible for some aspects of DR-mediated life extension. We conducted a quantitative trait locus (QTL) analysis of the response of T(b) to DR in mice using a panel of 22 LSXSS recombinant inbred strains, tested in two cohorts. T(b) in response to DR had a significant genetic component, explaining approximately 35% of the phenotypic variation. We mapped a statistically significant QTL to chromosome 9 and a provisional QTL to chromosome 17, which together accounted for about two thirds of the genetic variation. Such QTLs could be used to critically test whether the response of T(b) to DR also affects the response of life extension. In addition, this study demonstrates the feasibility of trying to map QTLs that affect other physiological responses to DR, including the life extension response. Importantly, the genes underlying such QTLs would be causal factors affecting these responses and could be identified by positional cloning.
Aging↗