A unified modeling framework for metabonomic profile development and covariate selection for acute trauma subjects.

Acute trauma is often associated with progressive deterioration of multiple organ systems in humans and is the leading cause of death in trauma care units. Identification of specific organ failure in a non-invasive manner and the contribution of different demographic factors on the casual progression of acute trauma are of supreme interests for successful diagnosis, prognosis or monitoring of trauma status. Recently, electrospray ionization and matrix-assisted laser desorption time-of-flight mass spectrometry have been used to identify biomarkers in both proteomics and metabonomics studies. Data sets generated from mass spectrometers in such studies are generally very large in size and thus require the use of sophisticated statistical techniques to glean useful information. In a recent development, Ghosh et al. (BMC Bioinformatics 2008; 9:38) suggested a unified semiparametric approach to distinguish urinary metabolic profiles in a group of traumatic subjects from those of a control group consisting of normal individuals. In this study we have extended their approach by combining available covariate information in the development of metabonomic profile of acute trauma. We have shown that age is a statistically significant covariate across trauma and control group, thus pointing out the fact that prognosis of trauma may be acutely linked with subjects' age.

Relationship between MNA and SF-36 in a free-living elderly population aged 70 to 75.

BACKGROUND: Within a larger study of social network and nutrition, we investigated measurements of nutritional status and health related quality of life. OBJECTIVE: To relate a well-established questionnaire of nutritional status (MNA) to a likewise well-established questionnaire of health related quality of life (SF-36) in community dwelling, free-living and, healthy 70-75 years old persons. DESIGN: Before an interview, the MNA and SF-36 questionnaires were filled in by 128 participants from a sample of 262 subjects. RESULTS: The MNA worked well as a measurement in this sample. Many MNA aspects correlated with the SF-36 scales. The correlations between MNA total score and the eight SF-36 scales varied from .27 to .62. DISCUSSION: This correlation was partly due to the fact that MNA has questions of health but also to the fact that there is an empirical relation between nutrition and health. CONCLUSION: The MNA measurement is applicable to a healthy, free-living elderly population and parts of the MNA can be interpreted as measurements of health related quality of life. Low values of SF-36 could also be used as predictors of risk of malnutrition, although further studies are required to confirm this result.

Obesity in 70-year-old Swedes: secular changes over 30 years.

OBJECTIVE: Secular increases in obesity have been widely reported in middle-aged adults, but less is known about such trends among the elderly. The primary purpose of this paper is to document the most recent wave of the obesity epidemic in population-based samples of 70-y-old men and women from Göteborg. Additionally, we will investigate the influences of physical activity, smoking and education on these secular trends. POPULATIONS AND METHODS: Five population-based samples of 3702 70-y-olds (1669 men and 2033 women) in Göteborg, Sweden, born between 1901 and 1930, were examined in the Gerontological and Geriatric Population Studies (H70) between 1971 and 2000. Cohort differences in anthropometric measures were the main outcomes studied. Physical activity, smoking habits and education were assessed by comparable methods in all cohorts. Subsamples of the women in the latest two cohorts (birth years 1922 and 1930) were also part of the Prospective Population Study of Women in Göteborg. In these women, it was possible to examine body mass index (BMI) and waist-to-hip circumference ratio (WHR) longitudinally since 1968. RESULTS AND CONCLUSIONS: Significant upward trends were found for height, weight, BMI, waist circumference (WC), WHR, prevalence of overweight (BMI> or =25 kg/m(2)) and obesity (BMI> or =30 kg/m(2)) across cohorts in both sexes. In 2000, 20% of the 70-y-old men born in 1930 were obese, and the largest increment (almost doubling) had occurred between the early 1980s and the early 1990s. In 70-y-old women the prevalence of obesity was 24% in 2000, a 50% increase compared to the cohort born 8 y earlier. BMI increased over time in all physical activity, smoking and education groups, with the exception of never-smoking men. Although 70-y-old women in 2000 were heavier than cohorts examined 8 y previously, data from the women studied longitudinally revealed that these differences were already present in earlier adulthood. In conclusion, the elderly population is very much part of the obesity epidemic, although secular trends in BMI were detected slightly earlier in men than in women. The health implications of these secular trends should be focused on in future gerontological research.

Percent body fat estimation from skin fold thickness in the elderly. Development of a population-based prediction equation and comparison with published equations in 75-year-olds.

OBJECTIVE: To develop a prediction equation for percent body fat (BF%) from skin fold thickness in a random sample of free-living 75-year-olds and to compare with published equations for the elderly. SETTING: Goteborg part of the Nordic Research on Aging (NORA) study in 1991/92. SUBJECTS & METHODS: Anthropometric measurements were performed in 286 participants (125 males,161 females) and body composition was estimated by four compartment model (4C) from total body water (TBW) and total body potassium (TBK) in every alternative subjects. BF % predicted from skin fold thickness (BFSF) was validated against BF % estimated from 4C model (BF4C) and was compared with BFSF and BF % predicted from equations by Durnin and Womersley, 1974 (BFDW), Deurenberg et al.,1989 (BFPD) and, Visseretal.,1994(BFMV), respectively. RESULTS: The BFSF correlated well with BF4C (r = 0.86, SEE = 4.05). Compared to BF4C, both BFPD and BFMV over estimated BF % by 3.26 and 3.63 in males and 9.56 and 9.23 in females, respectively. BFDW underestimated BF % in females by 1.06 and overestimated by 3.12 in males. BFSF showed best agreement with BF4C, where the 95 % of differences lie between +/- 7.4 in males and +/- 8.7 in females, respectively. CONCLUSION: BF % predicted from skin fold thickness correlated well with estimated BF % in 75-year-olds. Different prediction equations gave different values for BF % and population-specific prediction equations seem preferable in the elderly population.

Effects of a natural extract of (-)-hydroxycitric acid (HCA-SX) and a combination of HCA-SX plus niacin-bound chromium and Gymnema sylvestre extract on weight loss.

AIM: The efficacy of optimal doses of highly bioavailable (-)-hydroxycitric acid (HCA-SX) alone and in combination with niacin-bound chromium (NBC) and a standardized Gymnema sylvestre extract (GSE) on weight loss in moderately obese subjects was evaluated by monitoring changes in body weight, body mass index (BMI), appetite, lipid profiles, serum leptin and excretion of urinary fat metabolites. HCA-SX has been shown to reduce appetite, inhibit fat synthesis and decrease body weight without stimulating the central nervous system. NBC has demonstrated its ability to maintain healthy insulin levels, while GSE has been shown to regulate weight loss and blood sugar levels. METHODS: A randomized, double-blind, placebo-controlled human study was conducted in Elluru, India for 8 weeks in 60 moderately obese subjects (ages 21-50, BMI >26 kg/m(2)). Subjects were randomly divided into three groups. Group A was administered HCA-SX 4667 mg, group B was administered a combination of HCA-SX 4667 mg, NBC 4 mg and GSE 400 mg, while group C was given placebo daily in three equally divided doses 30-60 min before meals. All subjects received a 2000 kcal diet/day and participated in supervised walking. RESULTS: At the end of 8 weeks, body weight and BMI decreased by 5-6% in both groups A and B. Food intake, total cholesterol, low-density lipoproteins, triglycerides and serum leptin levels were significantly reduced in both groups, while high-density lipoprotein levels and excretion of urinary fat metabolites increased in both groups. A marginal or non-significant effect was observed in all parameters in group C. CONCLUSION: The present study shows that optimal doses of HCA-SX and, to a greater degree, the combination of HCA-SX, NBC and GSE can serve as an effective and safe weight-loss formula that can facilitate a reduction in excess body weight and BMI, while promoting healthy blood lipid levels.

Body composition estimated by bioelectrical impedance in the Swedish elderly. Development of population-based prediction equation and reference values of fat-free mass and body fat for 70- and 75-y olds.

OBJECTIVE: To develop a bioelectrical impedance (BIA) prediction equation for fat-free mass (FFM(BIA)) and present reference values of FFM and body fat (BF) for healthy Swedish elderly from population-based representative samples. SUBJECTS: This study is based on 823 (344 males, 479 females) participants from two systematic samples of birth cohorts in Göteborg aged 70 (cohort H70V, 201 males and 299 females) and 75 (cohort NORA75, 143 males and 180 females). METHODS: Body composition was measured with BIA (BIA-101, RJL system, Detroit) in both cohorts and was estimated by a four-compartment (4C) model from total body water (TBW) and total body potassium (TBK) in a sub-sample of the NORA75 cohort. The FFM(BIA) was validated against the FFM from the 4C model (FFM(4C)). RESULTS: The FFM(BIA) correlated well with FFM(4C) (r=0.95, SEE=2.64 kg). The FFM(BIA) (kg) in 70-y-old males and females were 58.5+/-5.4 and 43.4+/-4.4, and for 75-y-old males and females were 56.1+/-4.7 and 42.5+/-4, respectively. The body fat in kg (FM) among 70-y-old males and females were 25.2+/-8.1 and 25.7+/-8.4, and for 75-y-old males and females were 21.7+/-7.1 and 22.8+7.2, respectively. The percent body fat (BF%) among 70-y-old males and females were 29.5+/-5.8 and 36.3+/-6.4, and for 75-y-old males and females were 27.3+/-6 and 34.1+/-6.1, respectively. CONCLUSION: The FFM, FM and BF% from this study might be used as reference values for Swedish elderly aged 70 and 75 y.

Height and body weight in elderly adults: a 21-year population study on secular trends and related factors in 70-year-olds.

BACKGROUND: Body size in elderly adults is partly due to aging and partly to secular trends. This study describes secular trends in three anthropometric measures (i.e., height, body weight [BW], and body mass index [BMI]) of 70-year-olds over a period of 21 years and their relation to social and lifestyle factors. METHODS: A total of 3128 70-year-olds from four birth cohorts born between 1901 and 1922 in Gothenburg, Sweden, were examined between 1971 and 1992 in the Geriatric Medicine Department, Göteborg University. Trends in anthropometric measures were examined by permutation test. Influence of the subjects' birth year, physical activity, smoking habits, and education on anthropometric measures were investigated by multiple linear regression. RESULTS: Individuals in later-born cohorts were found to be 1 to 2 cm taller and 1.5 to 6.3 kg heavier than earlier-born cohorts. For BMI, a positive trend was significant only in 70-year-old male participants. "Year of birth" was a positive predictor for BW (p <.001) and BMI (p <.001) in male participants and for height (p <.05) and BW (p <.01) in female participants. Physical inactivity was a positive (p <.01) and "current smoking" a negative (p <.001) predictor for BMI in both sexes. "More than basic education" was a positive predictor for height (p <.001) in both sexes and a negative predictor for body weight (p <.01) and BMI (p <.001) in female participants only. CONCLUSIONS: Trends of increasing height, BW, and BMI were found among the Swedish elderly participants. This may be partly due to differences in smoking habits, physical activity, education, food habits, childhood nutrition, and living conditions between the cohorts.

Body mass index, weight change and mortality in the elderly. A 15 y longitudinal population study of 70 y olds.

OBJECTIVE: To examine the relationship between body mass index (BMI) at age 70, weight change between age 70 and 75, and 15 y mortality. DESIGN: Cohort study of 70-y-olds. SETTING: Geriatric Medicine Department, Göteborg University, Sweden. SUBJECTS: A total of 2628 (1225 males and 1403 females) 70-y-olds examined in 1971--1981 in Gothenburg, Sweden. RESULTS: The relative risks (RRs) for 15 y mortality were highest in the lowest BMI quintiles of males 1.20 (95% CI 0.96--1.51) and females 1.49 (95% CI 1.14--1.96). In non-smoking males, no significant differences were observed across the quintiles for 5, 10 and 15 y mortality. In non-smoking females, the highest RR (1.58, 95% CI 1.15--2.16) for 15 y mortality was in the lowest quintile. After exclusion of first 5 y death, no excess risks were found in males for following 5 and 10 y mortality across the quintiles. In females, a U-shaped relation was observed after such exclusions. BMI ranges with lowest 15 y mortality were 27--29 and 25--27 kg/m(2) in non-smoking males and females, respectively. A weight loss of > or = 10% between age 70 and 75 meant a significantly higher risk for subsequent 5 and 10 y mortality in both sexes relative to individuals with 'stable' weights. CONCLUSION: Low BMI and weight loss are risk factors for mortality in the elderly and smoking habits did not significantly modify that relationship. The BMI ranges with lowest risks for 15 y mortality are relatively higher in elderly. Exclusion of early deaths from the analysis modified the weight-mortality relationship in elderly males but not in females.

A comparison of frailty and other models for bivariate survival data.

Multivariate survival data arise when each study subject may experience multiple events or when study subjects are clustered into groups. Statistical analyses of such data need to account for the intra-cluster dependence through appropriate modeling. Frailty models are the most popular for such failure time data. However, there are other approaches which model the dependence structure directly. In this article, we compare the frailty models for bivariate data with the models based on bivariate exponential and Weibull distributions. Bayesian methods provide a convenient paradigm for comparing the two sets of models we consider. Our techniques are illustrated using two examples. One simulated example demonstrates model choice methods developed in this paper and the other example, based on a practical data set of onset of blindness among patients with diabetic Retinopathy, considers Bayesian inference using different models.

Height and body weight in the elderly. I. A 25-year longitudinal study of a population aged 70 to 95 years.

OBJECTIVE: To describe longitudinal changes in height and body weight between the ages of 70 and 95 y. DESIGN: Longitudinal cohort study with representative sample of 70-y-olds. SETTING: Department of Geriatric Medicine, Göteborg University, Sweden. SUBJECTS: 449 males and 524 females, aged 70 y, living in Göteborg were examined in 1971-72 and this study population participated on 11 occasions during a 25-year follow-up. RESULTS: Mean height decreased 4 and 4.9 cm in males and females respectively and the trend was significant between the ages of 70 and 95 y in both sexes. Between 70 and 75 y of age, a significant difference was found between quintiles of body height where in the highest quintile height was lowered by 0.4 and 0. 3 cm/y, in males and females respectively, and in the lowest quintile by 0.1 cm/y in both sexes. Mean body weight decreased 3.2 and 5.1 kg in males and females respectively, from age 70 to 95 y. The trend was significant over 22 and 20 y for males and females, respectively. Between the ages of 70 and 80 y, individuals in highest quintile of body weight decreased at a rate of 0.8 and 0.6 kg/y, three times higher than those in lowest quintile. Due to the decrease in both height and weight over time, body mass index (BMI) was less affected. CONCLUSION: Height, body weight and BMI decreased significantly in both sexes after age 70 y, and there was a gender difference in the trend. The results can be used as reference data for Swedish elderly and might be of importance to the understanding of anthropometry with the ageing process. SPONSORSHIP: See acknowledgements.

Multivariate survival analysis with positive stable frailties.

In this paper, we describe Bayesian modeling of dependent multivariate survival data using positive stable frailty distributions. A flexible baseline hazard formulation using a piecewise exponential model with a correlated prior process is used. The estimation of the stable law parameter together with the parameters of the (conditional) proportional hazards model is facilitated by a modified Gibbs sampling procedure. The methodology is illustrated on kidney infection data (McGilchrist and Aisbett, 1991).

Grouped random effects models for Bayesian meta-analysis.

Meta-analysis refers to quantitative methods to combine results from independent studies so as to draw overall conclusions. Frequently, results from dissimilar studies are inappropriately combined, resulting in suspect inferential synthesis. We present a straightforward method to identify and address this problem through the development of grouped random effect models for meta-analysis. We examine 15 comparative studies that investigate the efficacy of a new anti-epileptic drug, progabide. The flexibility of this modelling scheme is exemplified by the result that the open studies support the efficacy of progabide while the closed studies support the reverse hypothesis. Bayesian approaches for meta-analysis are preferable because of the small number of studies prevalent in meta-analysis. We specify diffuse proper prior and hyperprior distributions to assure posterior propriety. We investigate sensitivity of the posterior to choice of prior. We use Gibbs sampling and the Metropolis algorithm to generate samples from the relevant posteriors. We analyse posterior summaries and plots of model parameters to suggest solutions to questions of interest.

A Weibull regression model with gamma frailties for multivariate survival data.

Frequently in the analysis of survival data, survival times within the same group are correlated due to unobserved co-variates. One way these co-variates can be included in the model is as frailties. These frailty random block effects generate dependency between the survival times of the individuals which are conditionally independent given the frailty. Using a conditional proportional hazards model, in conjunction with the frailty, a whole new family of models is introduced. By considering a gamma frailty model, often the issue is to find an appropriate model for the baseline hazard function. In this paper a flexible baseline hazard model based on a correlated prior process is proposed and is compared with a standard Weibull model. Several model diagnostics methods are developed and model comparison is made using recently developed Bayesian model selection criteria. The above methodologies are applied to the McGilchrist and Aisbett (1991) kidney infection data and the analysis is performed using Markov Chain Monte Carlo methods.

Mutagenicity of 4-nitrodiphenyl ether and its metabolites.

The mutagenic potential of 4-nitrodiphenyl ether (NDE) an intermediate of herbicides and an anthelmintic drug, and its reduced products (-NO, -NHOH) were investigated in the Ames test. All the three compounds were potent direct-acting base-pair and frameshift mutagens with activity order -NHOH greater than -NO greater than -NO2. The -NHOH compound has been considered to be the penultimate/ultimate mutagen.

Structure-mutagenicity relationships within a series of para-alkoxynitrosobenzenes.

The mutagenic potential of para-alkoxynitrosobenzenes (para substituents, -OCH3, -OC2H5, n-OC4H9, n-OC5H11 and n-OC12H25) and p-phenoxynitrosobenzene was investigated in the Ames test. The order of mutagenic activity within a series of p-alkoxynitrosobenzenes was as follows: p-ethoxy greater than p-methoxy greater than p-butoxy (n) greater than p-pentyloxy (n) greater than p-dodecyloxy (n), the last being inactive. A relationship between mutagenic activity and electronic property of different substituents indicated in the alkoxy series, that as the Hammett constant decreased or bulk of the substituent (except methoxy) increased, the activity was found to decrease.