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PubMed1991

Longitudinal Gompertzian analysis of pancreatic cancer mortality in the U.S., 1962-1987: distinguishing between competitive and environmental influences upon evolving mortality patterns.

Pancreatic cancer (PanC) is an extraordinarily lethal neoplasm that is currently the fifth leading cause of cancer death in the United States. Annual age-specific mortality rates for PanC in the U.S. from 1962 to 1987 were subjected to longitudinal Gompertzian analysis. Age-specific PanC mortality rate distributions between age 30 and 60 years were determined by a common fixed intersect point and a variable competitive factor. The intersect point for PanC occurred at age 59.5 years and mortality rate 37.4 per 100,000 for men, and at age 53.2 years and mortality rate 7.9 per 100,000 for women. These intersect points are determined by genetic and environmental influences upon mortality. The observation that these points have remained fixed suggests that there has been no significant alteration in environmental etiopathogenic influences upon PanC mortality. Longitudinal Gompertzian analysis suggests that the emergence of PanC in the U.S. as a significant cause of cancer mortality has been the consequence of competitive influences upon PanC mortality dynamics.

Adult↗

PubMed2006

Monitoring individual morphological changes over time in ovariectomized rats by in vivo micro-computed tomography.

The ovariectomized (OVX) rat is a well established model for osteoporosis research. The recent development of in vivo micro-computed tomography (micro-CT) provides new possibilities to monitor individual bone changes over time. The purpose of this study was to establish the normal time course of bone loss in the OVX rat model, and to determine the ability to detect morphological changes in vivo compared to cross-sectional study designs where animals are sacrificed at each time point. Eight-month-old female Wistar rats were randomly assigned to one of two groups: OVX (N = 10) or sham-operated (N = 10). In vivo micro-CT scanning of the right proximal tibial metaphyses occurred at 1-month intervals for 6 months. Morphological analyses were performed at each time step for every animal, and a two-way ANOVA with repeated measures was used to analyze the data. A second statistical analysis was performed without repeated measures for analysis as a cross-sectional study design. The repeated measures analysis was more sensitive to early changes than the cross-sectional study analysis. Changes were detected by longitudinal analysis in the sham-operated and OVX animals over time (P < 0.001) with the exception of trabecular separation in the sham animals. The OVX animals had decreases of bone volume ratio of 33% after 1 month, and 72% after 3 months relative to baseline measurements. Significant changes in bone volume ratio, trabecular number and separation were detected early using a longitudinal analysis, thus in vivo assessment is well poised to enable the study of early treatment protocols on the effects of bone architecture. The in vivo analysis found significant changes in the sham animals which were not detected by the cross-sectional analysis, and the changes to the OVX animal morphology was detected sooner. A substantial variation of baseline morphometry within the homogenous group of rats and response to OVX was observed, thus emphasizing the advantage of performing in vivo analysis where each animal acts as its own control. These data provide new insight into individual bone changes following OVX, and can be used as baseline information upon which future in vivo studies can be designed.

Age Factors↗

PubMed1998

Nonrandom sequence of slope-intercept estimates in longitudinal gompertzian analysis suggests biological relevance.

The significance of intersections in age-specific mortality rate distributions could be attributed to a fundamental statistical relationship between estimates of slope and intercept. A strong negative correlation between estimates of slope and intercept is often observed in simple linear regression problems. The net result is that the family of lines generated by repetitive estimates of slope and intercept in a static experimental situation will tend to intersect at a common point. This statistical relationship between slope and intercept, however, should be random with respect to the time-ordered sequence of slope and intercept estimates. Annual paired slope and intercept estimates derived using the method of longitudinal Gompertzian analysis of age-specific mortality rates for men and women in the United States from 1900 to 1988 were analyzed to determine if they varied randomly. The probability that the observed sequence in these annual paired slope-intercept estimates was random is less than 10(-50) for both men and women. This finding essentially excludes the possibility that intersections in age-specific mortality rate distributions reflect a fundamental statistical relationship between slope and intercept and further suggests biological relevance for the method of longitudinal Gompertzian analysis.

Female↗

PubMed1990

Fingernail growth rate as a biomarker of aging in the pigtailed macaque (Macaca nemestrina).

Rate of fingernail growth (FNG) of the middle digit of the right hand was assessed in 46 healthy pigtailed macaques at approximately 6-month intervals for 4 to 6 years. Mean FNG for 24 females, ranging in mean age at measurement from 7 to 24 years, was 104 mu/day; the mean for 22 males, ranging from 7 to 20 years, was 111 mu/day. Longitudinal analysis showed that FNG declined in animals of both sexes and that the rate of decline (-4.8 mu/day/year) did not differ between them, i.e., the mean regression coefficients (beta) of the two sexes were significantly different from zero and not significantly different from each other. Results of cross-sectional analysis differed from those of longitudinal analysis in that the mean FNG appeared to be more rapid in males than in females, particularly in the older animals. Inter- and intra-individual variability in FNG did not increase with age. FNG appears to be an excellent functional marker of the rate of aging because the direction of change is essentially decremental, a significant degree of change can be detected in a few years, and the rate of change is relatively constant across the adult lifespan. In addition, measurement of FNG is innocuous, quantitative, inexpensive, and simple.

Aging↗

PubMedDate not supplied

Longitudinal case analysis in atopic dermatitis.

The current knowledge on atopic dermatitis comes mainly from cross-sectional studies, which are not suited to establish time-courses or causal links in complex diseases. As an alternative approach, the method of longitudinal case analysis by the autoregressive integrated moving average (ARIMA) method has been introduced to investigate the pathogenesis of atopic dermatitis. The method was applied to the investigation of 2 patients suffering from severe and moderate atopic dermatitis. Disease activity, peripheral blood parameters (differential blood count, lymphocyte subpopulations, immunoglobulin E, eosinophilic cationic protein, soluble interleukin-2 receptor), mental stress and environmental factors were determined daily for 50 days. Both patients showed a positive correlation between CD4+ and CD25+ T-cells, a negative correlation between CD16/56+ natural killer cells and CD4+ T-cells, a negative correlation between eosinophils and polymorphonuclear leukocytes, and a time-shifted positive correlation of up to 2 days between scores quantifying mental stress and disease activity. A positive correlation between T-cells and polymorphonuclear leukocytes, CD4+ T-cells and the CD45RA+ subtype, as well as a negative correlation between stress and eosinophils, sports and eosinophils, and sports and disease activity were found only in one patient with more severe atopic dermatitis. In conclusion, longitudinal time-series analysis might represent an interesting and adequate method to generate and test new hypotheses on biomedical problems which cannot be addressed by cross-sectional studies.

Adult↗

PubMed1998

Two-year follow-up study of elderly residents in S. Paulo, Brazil: methodology and preliminary results.

INTRODUCTION: Previous cross-sectional studies have shown a high prevalence of chronic disease and disability among the elderly. Given Brazil's rapid aging process and the obvious consequences of the growing number of old people with chronic diseases and associated disabilities for the provision of health services, a need was felt for a study that would overcome the limitations of cross-sectional data and shed some light on the main factors determining whether a person will live longer and free of disabling diseases, the so-called successful aging. The methodology of the first follow-up study of elderly residents in Brazil is presented. METHOD: The profile of the initial cohort is compared with previous cross-sectional data and an in-depth analysis of nonresponse is carried out in order to assess the validity of future longitudinal analysis. The EPIDOSO ('Epidemiologia do Idoso') Study conducted a two-year follow-up of 1,667 elderly people (65+), living in S. Paulo. The study consisted of two waves, each consisting of household, clinical, and biochemical surveys. RESULTS AND CONCLUSIONS: In general, the initial cohort showed a similar profile to previous cross-sectional samples in S. Paulo. There was a majority of women, mostly widows, living in multigenerational households, and a high prevalence of chronic illnesses, psychiatric disturbances, and physical disabilities. Despite all the difficulties inherent in follow-up studies, there was a fairly low rate of nonresponse to the household survey after two years, which did not actually affect the representation of the cohort at the final household assessment, making unbiased longitudinal analysis possible. Concerning the clinical and blood sampling surveys, the respondents tended to be younger and less disabled than the nonrespondents, limiting the use of the clinical and laboratory data to longitudinal analysis aimed at a healthier cohort. It is worth mentioning that gender, education, family support, and socioeconomic status were not important determinants of nonresponse, as is often the case.

Aged↗

PubMedDate not supplied

EM-REML estimation of covariance parameters in Gaussian mixed models for longitudinal data analysis.

This paper presents procedures for implementing the EM algorithm to compute REML estimates of variance covariance components in Gaussian mixed models for longitudinal data analysis. The class of models considered includes random coefficient factors, stationary time processes and measurement errors. The EM algorithm allows separation of the computations pertaining to parameters involved in the random coefficient factors from those pertaining to the time processes and errors. The procedures are illustrated with Pothoff and Roy's data example on growth measurements taken on 11 girls and 16 boys at four ages. Several variants and extensions are discussed.

Journal Article↗

PubMed1996

Longitudinal Gompertzian analysis of mortality from pancreatic cancer in Japan, 1955-1993.

Age-specific mortality rates from pancreatic cancer (PanC) in Japan from 1955 through 1993 were subjected to longitudinal Gompertzian analysis. Age-specific PanC mortality rate distributions between age 30 and 70 years were highly Gompertzian for each and every year for both men and women. Between 1955 and 1993, age-adjusted PanC mortality rates increased 5.1 times for men and 4.3 times for women. The environmental factor for PanC mortality increased 68% for men and 89% for women over this period. Gompertzian analysis suggests that rising mortality from PanC in Japan may be related to rapidly changing lifestyles among Japanese. Pure alcohol consumption was the identified environmental factor most strongly correlated with PanC mortality.

Adult↗

PubMed1996

Meta-analysis with longitudinal studies: controlling for analytical bias.

A recent study published in an international medical journal presented an opportunity to demonstrate the difficulties of interpreting meta-analysis results with longitudinal data. We conducted a new meta-analysis using identical data from the published study and showed contradictory results.

Bias↗

PubMed1999

Self and identity in advanced old age: validation of theory through longitudinal case analysis.

Case studies drawn from a 20-year longitudinal study of aging were examined for the support they provide to two theoretical viewpoints on the self in later life: one focusing on management of self-esteem, the other on development of identity as story. The five cases selected for scrutiny represented diverse trajectories of self-esteem. They furnished ample illustrations of certain key aspects of both theories, including assimilative processes of coping, depression related to absence of accommodation, maintenance of life story themes, and life review processes. They did not, however, give strong support to the dichotomy, drawn within both theoretical models, between younger and older old age. Examples of accommodation, disengagement, and self-transcendence, hypothesized to typify advanced old age, were relatively few in number and emerged only toward the very end of life. It is argued that examination of prototypical cases provides a useful approach to validating and developing theory. A conclusion drawn from this study is that more analysis should be carried out on the lives of persons who exemplify the theoretically ideal characteristics of advanced old age.

Aged↗

PubMed1994

Effect of prednisone and hydroxychloroquine on coronary artery disease risk factors in systemic lupus erythematosus: a longitudinal data analysis.

PURPOSE: To determine the effect of prednisone dose and hydroxychloroquine dose on the coronary artery disease risk factors serum cholesterol level, mean arterial blood pressure, and weight in patients with systemic lupus erythematosus. PATIENTS AND METHODS: A longitudinal cohort study of 264 patients with systemic lupus erythematosus was conducted. For all patients in the cohort, serum cholesterol, mean arterial pressure, weight, prednisone dose, hydroxychloroquine dose, and other potential confounding variables were recorded at each visit. Regression analysis appropriate for longitudinal data was used to assess the effect of prednisone on serum cholesterol and mean arterial pressure. To assess the effect of prednisone on weight, patients' weights were compared 90 days before and after a 10-mg or 20-mg increase in prednisone. RESULTS: A total of 3,027 patient visits were analyzed. In the regression model for serum cholesterol, a change in prednisone dose of 10 mg was associated with a change in cholesterol of 7.5 +/- 1.46 (SE) mg% after adjustment for the other significant variables in the model, including sex, race, hydroxychloroquine dose, and proteinuria. In the regression model for hydroxychloroquine, the 200-mg and the 400-mg dose were both associated with lower serum cholesterol (8.9 +/- 3.44 SE mg%). In the regression model for mean arterial blood pressure, a 10-mg change in prednisone dose led to a change in mean arterial blood pressure of 1.1 mm Hg after adjustment for age, weight, and antihypertensive drug use. A 10-mg increase in prednisone dose was associated with a mean weight change of 5.50 +/- 1.23 (SE) lb. CONCLUSIONS: Changes in prednisone dose led to definable changes in risk factors for coronary artery disease, even after adjustment for other variables known to affect these risk factors. According to longitudinal regression analysis, hydroxychloroquine therapy was associated with lower serum cholesterol.

Adult↗

PubMed2006

An application of a two-level non-Gaussian state-space model in the analysis of longitudinal papilloma count data.

In this study, a dynamic Bayesian two-level non-Gaussian state-space model is applied in the statistical analysis of longitudinal detectable papilloma count data. This two-level model is established on the basis of the state and hyper-state parameters that depend on the model parameters of biological significance, namely, the initiation rate of normal cells and the birth- and death-rates of initiated cells. As the time-dependent model parameters fluctuate dynamically and stochastically over time, so will the state and hyper-state parameters; thus, smoothness priors that allow a wide range of shapes with no specific forms required on the state/hyper-state parameters can be employed in this model. Gibbs sampler, a Markov chain Monte Carlo approach, is used to implement the Bayesian inferences on the state as well as the hyper-state parameters; and the estimates of the model parameters can be obtained thereon. Illustrations of the Bayesian inference procedure are given by using the datasets from a simulation study as well as a laboratory experiment by Brook et al. [E.A. Brooks, C.M. Kohn, P.J.M. van Birgelen, G.W. Lucier, C.J. Portier, Stochastic models for papilloma formation following exposure to TCDD, Organohalogen Compd. 41 (1999) 521]. Comparing to the parametric approach that assigns specific forms on the time-dependent model parameters, different conclusions are drawn by the two-level state-space modeling approach considered in this study.

Animals↗

PubMed2000

Longitudinal gompertzian analysis of mortality from prostate cancer in Japan, 1955-1996.

The purpose of this study was to determine whether prostate cancer mortality conforms to gompertzian analysis and, if so, what conclusions can be made regarding increasing prostate cancer mortality in Japan by the application of longitudinal gompertzian analysis. Data regarding 77,492 prostate cancer deaths reported during the period 1955 to 1996 were obtained from death certificate records in Japan. Age-adjusted prostate cancer mortality rates increased 6.4-fold during that period. The changing patterns in the mortality rate was explained by a constantly increasing number of elderly people. Age-specific mortality rate distributions between the ages of 50 and 84 years were highly gompertzian for each year during that period. The environmental factor for prostate cancer mortality increased 80% for that period. Gompertzian analysis suggests that rising mortality from prostate cancer may be related to rapidly changing lifestyles among Japanese. Intake of animal proteins was the most strongly correlated parameter considered with the mortality from prostate cancer.

Age Distribution↗

PubMed1995

Longitudinal gompertzian analysis of mortality from stomach cancer in Japan, 1950-1993.

Age-specific mortality rates from stomach cancer (SC) in Japan from 1950 through 1993 were subjected to longitudinal Gompertzian analysis. Age-specific SC mortality rate distributions between ages 45 and 75 years were highly Gompertzian for each- and every year for both men and women. Between 1950 and 1993, age-adjusted SC mortality rates decreased 48.6% for men and 59.6% for women. Gompertzian analysis might suggest that declining SC mortality rates can be attributed to beneficial environmental influences during that period, especially after 1970. This suggests that the environmental factor has changed to account for the dramatic decline in the incidence of, and mortality from SC. The environment was 32.3 and 14.4 times less conducive to mortality from SC in 1993 as compared to 1950 for men and women respectively. Reduced salt consumption was considered as the decline in the SC mortality rate. Intake of green-yellow vegetables, fruits, and vitamin A were also considered as factors for reducing SC mortality. The mass-screening for SC may effectively enhance survival for SC patients, which might partially contribute to a dramatic decline in SC mortality.

Adolescent↗

PubMedDate not supplied

Non-linear models for the analysis of longitudinal data.

Given the importance of longitudinal studies in biomedical research, it is not surprising that considerable attention has been given to linear and generalized linear models for the analysis of longitudinal data. A great deal of attention has also been given to non-linear models for repeated measurements, particularly in the field of pharmacokinetics. In this article, a brief overview of non-linear models for the analysis of repeated measures is given. Particular emphasis is placed on mixed-effects non-linear models and on various estimation procedures proposed for such models. Several of these estimation procedures are compared via a simulation study. In addition, simulation is used to investigate the effects of model misspecification, particularly with respect to one's choice of random-effects. A relatively straightforward measure useful in selecting an appropriate set of random effects is investigated and found to perform reasonably well.

Humans↗

PubMed2002

Testing model fit in longitudinal data analysis against alternatives with omitted covariates.

Several types of common model misspecifications can be re-formulated as problems of omitted covariates. These include situations with unmeasured confounders, measurement errors in observed covariates and informative censoring. Longitudinal data present special opportunities for detecting omitted covariates that are related to the observed ones differently across time than across individuals. This situation arises with period and cohort effects, as well as with usual formulations of classical measurement error in observed covariates. In this article we focus on testing for the existence of omitted covariates in longitudinal data analysis when models are fit by generalized estimation equations. When omitted covariates are present, specification of the correct link function conditionally on only observed covariates under the alternative usually involves complicated numerical integration. We propose a quasi-score test statistic that avoids the need to fit such alternative models. The statistic is asymptotically chi-square distributed under the null hypothesis of no omitted covariates with degrees of freedom determined by the assumed alternative structure. We study the significance level and the power of the quasi-score test in linear and logistic regression models. The test is then applied to an analysis of excessive daytime sleepiness.

Cohort Studies↗

PubMed2004

Analysis of longitudinal multispin orders in strongly coupled spin systems.

Longitudinal multispin orders provide an effective way for measurement of scalar couplings and also to probe molecular interactions and dynamics. Analysis of longitudinal orders has been made in strongly coupled AB and ABX spin systems to determine the dependence of strong coupling parameter on these orders. Experimental and simulated spectra of various longitudinal orders are illustrated for these spin systems. This general procedure can be extended to broad range of spin systems to understand the influence of strong coupling on longitudinal orders.

Journal Article↗

PubMed2003

Genome-wide linkage analysis of longitudinal phenotypes using sigma2A random effects (SSARs) fitted by Gibbs sampling.

The study of change in intermediate phenotypes over time is important in genetics. In this paper we explore a new approach to phenotype definition in the genetic analysis of longitudinal phenotypes. We utilized data from the longitudinal Framingham Heart Study Family Cohort to investigate the familial aggregation and evidence for linkage to change in systolic blood pressure (SBP) over time. We used Gibbs sampling to derive sigma-squared-A-random-effects (SSARs) for the longitudinal phenotype, and then used these as a new phenotype in subsequent genome-wide linkage analyses. Additive genetic effects (sigma2A.time) were estimated to account for approximately 9.2% of the variance in the rate of change of SBP with age, while additive genetic effects (sigma2A) were estimated to account for approximately 43.9% of the variance in SBP at the mean age. The linkage results suggested that one or more major loci regulating change in SBP over time may localize to chromosomes 2, 3, 4, 6, 10, 11, 17, and 19. The results also suggested that one or more major loci regulating level of SBP may localize to chromosomes 3, 8, and 14. Our results support a genetic component to both SBP and change in SBP with age, and are consistent with a complex, multifactorial susceptibility to the development of hypertension. The use of SSARs derived from quantitative traits as input to a conventional linkage analysis appears to be valuable in the linkage analysis of genetically complex traits. We have now demonstrated in this paper the use of SSARs in the context of longitudinal family data.

Adult↗