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PubMed1993

A computer program for regression analysis of repeated measures using generalized estimating equations.

RMGEE is an easy-to-use FORTRAN program for the analysis of repeated binary, count, and normally-distributed response variables using the generalized estimating equations approach of Liang and Zeger [1]. The program can be used when measurements are obtained at multiple time points from each subject or experimental unit, and also when the basic sampling unit is a group or cluster of subjects, and the response variable of interest is obtained from each subject within the cluster. It is not necessary for the number of repeated measurements to be the same for every experimental unit and missing data are easily accommodated. Both time-independent (cluster-specific) and time-dependent (occasion- or subject-specific) covariates are permitted. The program can be run on microcomputers, workstations, and mainframe computers. Three examples illustrating the usage and features of RMGEE are provided.

Algorithms↗

PubMed2001

Goodness-of-fit of the distribution of time-to-first-occurrence in recurrent event models.

Imperfect repair models are a class of stochastic models that deal with recurrent phenomena. This article focuses on the Block, Borges, and Savits (1985) age-dependent minimal repair model (the BBS model) in which a system that fails at time t undergoes one of two types of repair: with probability p(t), a perfect repair is performed, or with probability 1-p(t), a minimal repair is performed. The goodness-of-fit problem of interest concerns the initial distribution of the failure ages. In particular, interest is on testing the null hypothesis that the hazard rate function of the time-to-first-event-occurrence, lambda(.), is equal to a prespecified hazard rate function lambda 0(.). This paper extends the class of hazard-based smooth goodness-of-fit tests introduced in Peña (1998a) to the case where data accrual is from a BBS model. The goodness-of-fit tests are score tests derived by reformulating Neyman's idea of smooth tests in terms of hazard functions. Omnibus as well as directional tests are developed and simulation results are presented to illustrate the sensitivities of the proposed tests for certain types of alternatives.

Air Conditioning↗

PubMed1998

Variation in the measurements of basement membrane thickness and inflammatory cell number in bronchial biopsies.

We do not have an estimate of how much tissue is needed for a reliable measure of bronchial epithelial reticular basement membrane (RBM) thickness or for counts of inflammatory cells. An assessment of the frequency distribution and variance of data from repeat measurements of RBM thickness and biopsy section inflammatory cell counts in cases with asthma (n=6), chronic obstructive pulmonary disease (COPD; n=5), and normal healthy subjects (n=7) was made. Tissue sections were stained with haematoxylin and eosin or by immunohistochemistry for EG2, mast cell tryptase and CD3-positive cells. Measurements of RBM thickness in individuals followed a log-normal distribution. For a precision of approximately +/-15%, 31-45 measurements were required. In contrast, inflammatory cell counts for each individual did not follow a normal distribution. There was high variance such that the cumulative weighted mean did not become stable until at least 5-10 mm of tissue underlying the RBM had been included. In conclusion multiple measurements of reticular basement membrane thickness or tissue section cell counts should be made for each individual in studies of bronchial biopsies. It is recommended that reticular basement membrane thickness should be measured at 20 mm intervals over a 1 mm reticular basement membrane length and that a zone beneath it of at least 5-10 mm of reticular basement membrane should be included for counts of inflammatory cells.

Adult↗

PubMed1997

Estimating a delay distribution from incomplete data, with application to reporting lags for AIDS cases.

Statistical inference for the probability distribution of a reporting delay is considered when delays are recorded only after a certain point in time tau. A method is proposed which utilizes data on incidences arising prior to tau. By a suitable choice of parameters we find explicit expressions for maximum likelihood estimates and standard errors. An application to reporting delay data on Australian AIDS diagnoses demonstrates that inclusion of data on AIDS diagnoses made prior to tau results in significant gains in the precision of estimates. A simulation study indicates for this data set that there is minimal bias in the estimates and the large sample formulae for the standard errors give good estimates of the standard deviation of the estimators.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Biological dosimetry in simulated in vitro partial irradiations.

The assessment by biological dosimetry of the dose received in cases of partial-body exposure to ionizing radiation can be underestimated because irradiated lymphocytes are mixed with non-irradiated ones. To determine if the exposure affects the whole body or only part of it, it may be useful to know the distribution of cells with more than one dicentric chromosome. We established a dose-effect calibration curve for X-rays by analysis of chromosome aberrations. Moreover, in the present work, 20 partial irradiations for four different doses of X-rays (2, 3, 4 and 5 Gy) have been simulated by mixing irradiated and non-irradiated blood in different proportions. In all cases, the 95% confidence intervals of the estimated dose included the real dose of irradiation. However, some difficulties were found for the estimation of the fraction of irradiated cells. In the present study, D0 = 3.8 allows to obtain the best fit between the estimated and the real fraction of irradiated cells.

Cells, Cultured↗

PubMed1996

A population-based study of the incidence of malignant small bowel tumours: SEER, 1973-1990.

BACKGROUND: Little is known about the incidence of cancers of the small bowel. METHODS: Data from cancer registries participating in the Surveillance, Epidemiology, and End-Results (SEER) Program from 1973 to 1990 were analysed to determine the incidence of the four major histological types of cancer occurring in the small intestine: adenocarcinomas, malignant carcinoid tumours, lymphomas and sarcomas. In addition, the incidence rate of lymphomas arising from the small intestine and stomach and adenocarcinomas from the small intestine, stomach and colon were compared over time. RESULTS: Small bowel tumours occurred rarely, with an average annual incidence rate of 9.9 per million people. Carcinoid tumours and adenocarcinomas were the most common histological subtypes, with average annual incidence rates of 3.8 and 3.7 per million people respectively, followed by lymphomas (1.1 per million people) and sarcomas (1.3 per million people). For all histological subtypes, men had higher rates than women. Most tumours occurred in older adults; over 90% of cases occurred in people over the age of 40. During the 18-year study period, the incidence of small bowel tumours has risen slowly. In white men, black men and black women, rises in the incidence of adenocarcinomas, malignant carcinoids and lymphomas contributed to this trend. In white women, the incidence of adenocarcinomas, was stable while malignant carcinoids and lymphomas rose. The incidence of sarcomas was steady for all groups except black women, for which it fell. The histological types were distributed by anatomical subsite: adenocarcinomas were distributed more proximally on average whereas lymphomas were more common distally. In addition, there was an association between the incidence trends of adenocarcinomas occurring in the duodenum and colon suggesting similar risk factors for cancers in these regions. There was no similar correlation for tumours in the jejunum and ileum. The incidence of lymphomas over time rose in all areas of the small intestine, paralleling a similar rise in lymphomas of the stomach. CONCLUSIONS: Cancers of the small bowel are rare despite a slow increase over the past two decades, especially among lymphomas. Higher rates in males and whites deserve further investigation.

Adenocarcinoma↗

PubMed1993

Breast cancer after treatment of Hodgkin's disease.

BACKGROUND: Most studies of survivors of Hodgkin's disease have shown a low risk for subsequent breast cancer, even though much lower doses of radiation than those used for Hodgkin's disease have been shown to induce breast cancer in other settings. PURPOSE: This study quantifies the risk of breast cancer following Hodgkin's disease treatment according to age at treatment and type of treatment. METHODS: To evaluate the risk of breast cancer from irradiation, we reviewed records of 885 women treated for Hodgkin's disease between 1961 and 1990 (mean follow-up, 10 years). Risks for breast cancer incidence and mortality were calculated by comparison with expected rates for a general female population matched by age and race. RESULTS: Twenty-five patients have developed invasive breast cancer, yielding a relative risk (RR) of 4.1 (95% confidence interval [CI] = 2.5-5.7). An additional patient developed multifocal carcinoma in situ. Age at irradiation strongly influenced risk: RR was 136 for women treated before 15 years of age (95% CI = 34-371). RR declined with age at irradiation (P for trend < .0001), but the elevation remained statistically significant for subjects less than 30 years old at the time of irradiation (for those 15-24, RR = 19 [95% CI = 10.3-32]; for those 24-29, RR = 7 [95% CI = 3.2-14.4]). In women above 30 years of age, the risk was not elevated (RR = 0.7; 95% CI = 0.2-1.8). Risk of breast cancer increased significantly with time since treatment (P for trend < .0001). The RR was 2.0 (95% CI = 1.0-3.5) with follow-up under 15 years and 13.6 (95% CI = 7.9-18.2) with follow-up equal to or exceeding 15 years. The addition of mechlorethamine, vincristine, procarbazine, and prednisone chemotherapy to irradiation increased the risk within the first 15 years. Most breast cancers (22 of 26) arose within or at the margin of the radiation field and were infiltrating ductal carcinomas. Stage distribution and outcome suggest that the increased incidence was not solely attributable to vigilant screening. RR of death from breast cancer was 5.1 (95% CI = 2.2-10.0). CONCLUSIONS: Women treated for Hodgkin's disease with radiation before 30 years of age are at markedly increased risk for breast cancer, with risk increasing dramatically more than 15 years after therapy. IMPLICATIONS: The high RR for development of breast cancer in women exposed to therapeutic radiation under 30 years of age raises important issues about optimal treatment strategies for patients with Hodgkin's disease, breast cancer, and other cancers.

Adolescent↗

PubMed2002

Daily birth numbers in Passo Fundo, South Brazil, 1997-1999: trends and periodicities.

Between October 6, 1997 and April 30, 1999, 5011 births (mean: 8.76 per day) were registered in the city of Passo Fundo, South Brazil. The sequence of 572 daily birth numbers was not random (iteration test). Neyman distribution (m = yen ) showed the best fit. Clusters of days with higher birth numbers alternated with days with low numbers of births. Periodogram analysis revealed a significant periodicity of 6.98 days. The cosinor regression, testing 10 a priori supposed period lengths, found significant seasonality peaking in August-September and significantly highest birth numbers on Thursdays. Among the lunar and solar rotation cycles, the tropic lunar cycle and its 4th harmonic were most pronounced, in agreement with results concerning natality in Germany obtained by Svante Arrhenius in the 19th century. These findings confirm Derer-Halberg's concept of multiseptans. In addition to cycling, a significantly increasing linear trend with a daily increase of 0.0045 births was encountered. This documents a growth of the population in agreement with national statistical data.

Birth Rate↗

PubMed2006

Sampling properties of homozygosity-based statistics for linkage disequilibrium.

Homozygosity-based statistics such as Ohta's identity-in-state (IIS) excess offer the potential to measure linkage disequilibrium for multiallelic loci in small samples. However, previous observations have suggested that for independent loci, in small samples these statistics might produce values that more frequently lie on one side rather than on the other side of zero. Here we investigate the sampling properties of the IIS excess. We find that for any pair of independent polymorphic loci, as sample size n approaches infinity, the sampling distribution of the IIS excess approaches a normal distribution. For large samples, the IIS excess tends towards symmetry around zero, and the probabilities of positive and of negative IIS excess both approach 1/2. Surprisingly, however, we also find that for sufficiently large n, independent loci can be chosen so that the probability of a sample having positive IIS excess is arbitrarily close to either 0 or 1. The results are applied to interpretation of data from human populations, and we conclude that before employing homozygosity-based statistics to measure LD in a particular sample, especially for loci with either very small or very large homozygosities, it is useful to verify that loci with the observed homozygosity values are not likely to produce a large bias in IIS excess in samples of the given size.

Algorithms↗

PubMed2002

Micronucleus distribution in human peripheral blood lymphocytes treated in vitro with cadmium chloride in G0 and S phase of the cell cycle.

Cadmium chloride (CdCl2 x H2O) in concentrations 10(-3) - 10(-6) M was tested for genotoxicity in human lymphocytes in vitro. The DNA damage was expressed through the occurrence of micronuclei (MN) and was detected using the cytochalasin-B-blocked MN assay. Human blood was treated in the G0 and S phase of the cell cycle. All except the highest concentration of cadmium chloride of 10(-3) M applied in the G0 phase of the cell cycle resulted in the increase in MN cells, but it was not statistically significant. Cadmium chloride added to the cultures in the concentration of 10(-3) M affected the cell growth regardless of the phase. Cadmium chloride added to cultures 24 h after their initiation (early S phase) was found to significantly increase the MN frequency in 10(-4) - 10(-6) M concentrations (P > 0.05).

Adult↗

PubMed1992

A numerical study of the shape of the surface separating flow into branches in microvascular bifurcations.

The shape of the separating surface formed by the streamlines entering the branches of microvascular bifurcations plays a major role in determining the distribution of red blood cells and other blood constituents downstream from the bifurcation. Using the finite element method, we determined the shape of the surface through numerical solution of three dimensional Navier-Stokes equations for fluid flow at low Reynolds numbers in a T-type bifurcation of circular tubes. Calculations were done for a wide range of daughter branch to parent vessel diameter ratios and flow ratios. The effect of Reynolds number was also studied. Our numerical results are in good agreement with previously reported experimental data of Rong and Carr (Microvascular Research, Vol. 39, pp. 186-202, 1990). The numerical results of this study will be used to predict the concentration of blood constituents downstream from microvascular bifurcations providing that the inlet concentration profile is known.

Blood Flow Velocity↗

PubMed2005

Effect of chain stiffness and entanglements on the elastic behavior of end-linked elastomers.

The effect of chain stiffness and entanglements on the elastic behavior and microscopic structure of cross-linked polymer networks was studied using Monte Carlo simulations. We investigated the behavior of entangled and entanglement-free networks at various degrees of chain stiffness and densities. Based on previous results that indicated that trapped entanglements prevent strain-induced order-disorder transitions in semiflexible chain networks, we prepared the entangled networks by end-linking the chains in very dilute conditions so as to minimize the extent of trapped entanglements. We also considered the entanglement-free case by using a "diamond" structure. We found that the presence of even a very small amount of trapped entanglements is enough to prevent a discontinuous strain-induced transition to an ordered phase. In these mildly entangled networks, a nematiclike order is eventually attained at high extensions but the elastic response remains continuous and the cross-links remain uniformly distributed through the simulation box. The entanglement-free diamond networks on the other hand show discontinuities in their stress-strain data. Networks at higher densities exhibit a more stable ordered phase and show an unusual staircaselike stress-strain curve. This is the result of a stepwise extension mechanism in which the chains form ordered domains that exclude the cross-links. Extension is achieved by increasing the number of these ordered domains in the strain direction. Cross-links aggregate in the spaces between these ordered domains and form periodic bands. Each vertical upturn in the stress-strain data corresponds to the existence of an integer number of ordered domains. This stepwise elastic behavior is found to be similar to that exhibited by some tough natural materials.

Anisotropy↗

PubMed2004

[Study of improvement in X-ray computed tomography images with a radiation treatment planning system: image noise and slice thickness].

In radiotherapy, dose distribution and calculation of dose monitor units (DMU) are generally performed by a radiation treatment planning system using CT images. Therefore, differences in calculation can arise as a result of the quality of the CT image data. The quality of CT images involves contrast resolution, resolution, noise, slice thickness, and other factors. Among these factors, we examined noise and slice thicknesses. Results demonstrated that, even if noise increased, CT value did not change, and, therefore, did not influence DMU. Examination of slice thickness showed that, when the radiation field was rectangular, it was not influenced by slice thickness. However, when a multi-leaf collimator (MLC) was used, if slice thickness was thicker than the size of the MLC, a difference arose in the position of the MLC, and, therefore, some difference arose in dose. Therefore, slice thickness should be thinner than the size of the MLC.

Phantoms, Imaging↗

PubMed2006

A cortical potential imaging study from simultaneous extra- and intracranial electrical recordings by means of the finite element method.

In the present study, we have validated the cortical potential imaging (CPI) technique for estimating cortical potentials from scalp EEG using simultaneously recorded electrocorticogram (ECoG) in the presence of strong local inhomogeneity, i.e., Silastic ECoG grid(s). The finite element method (FEM) was used to model the realistic postoperative head volume conductor, which includes the scalp, skull, cerebrospinal fluid (CSF) and brain, as well as the Silastic ECoG grid(s) implanted during the surgical evaluation in epilepsy patients, from the co-registered magnetic resonance (MR) and computer tomography (CT) images. A series of computer simulations were conducted to evaluate the present FEM-based CPI technique and to assess the effect of the Silastic ECoG grid on the scalp EEG forward solutions. The present simulation results show that the Silastic ECoG grid has substantial influence on the scalp potential forward solution due to the distortion of current pathways in the presence of the extremely low conductive materials. On the other hand, its influence on the estimated cortical potential distribution is much less than that on the scalp potential distribution. With appropriate numerical modeling and inverse estimation techniques, we have demonstrated the feasibility of estimating the cortical potentials from the scalp EEG with the implanted Silastic ECoG gird(s), in both computer simulations and in human experimentation. In an epilepsy patient undergoing surgical evaluation, the cortical potentials were reconstructed from the simultaneously recorded scalp EEG, in which main features of spatial patterns during interictal spike were preserved and over 0.75 correlation coefficient value was obtained between the recorded and estimated cortical potentials. The FEM-based CPI technique provides a means of connecting the simultaneous recorded ECoG and the scalp EEG and promises to become an effective tool to evaluate and validate CPI techniques using clinic data.

Algorithms↗

PubMed1997

Effective size and F-statistics of subdivided populations. II. Dioecious species.

For a dioecious diploid population subdivided into an arbitrary number of subpopulations, we have derived recurrence equations for the inbreeding coefficient and coancestries between individuals within and among subpopulations and formulas for effective size and F-statistics. Stable population size and structure, discrete generations, autosomal inheritance, and the island migration model are assumed, and arbitrary distributions of the numbers of male and female progeny per family, different numbers and variable migration rates of males and females are incorporated in our derivation. Some published equations for effective size and F-statistics for a subdivided population are shown to be incorrect because several incorrect probabilities are used in the derivation. A more general equation for effective size is obtained by finding eigenvalue solutions to the recurrence equations for inbreeding coefficient and coancestry in this article, which reduces to the simple and familiar expressions derived by previous authors for the special case of a single unsubdivided population. Our general expressions for F-statistics also reduce to the classical results of WRIGHT's infinite island model and its extensions. It is shown that population structure is important in determining effective size and F-statistics and should be recognized and incorporated into programs for genetic conservation and evolution.

Biological Evolution↗

PubMed2003

Slow fiber cluster pattern in pig longissimus thoracis muscle: implications for myogenesis.

Recent evidence implicates fiber type proportions as playing a role in meat eating quality, and in pigs it has been suggested that the slow oxidative fibers contribute to both juiciness and tenderness. The fiber distribution in pigs is different from that found in most other species, in which the various types of skeletal muscle fiber are distributed in a "checkerboard" pattern, because in pigs the slow oxidative fibers have a clustered distribution. The initial processes leading to fiber clustering are likely to occur during myogenesis, but the precise mechanistic aetiology of this patterning and whether the slow oxidative fiber clusters occur in a random or ordered fashion is unknown. In the present study longissimus thoracis muscle from Large White crossbred pigs was sampled at the 10th rib, 48 h postmortem. Transverse cryo-sections were cut and histochemically stained to allow the identification of the main muscle fiber types: slow oxidative, fast glycolytic, and fast oxidative glycolytic. Images of the sections were captured and analyzed using point processes and Voronoi Tesselations to examine the randomness and spatial distribution of the clusters of slow oxidative fibers found in pig longissimus thoracis muscle. The results showed that an assumption of complete spatial randomness can be rejected and that a mathematical model incorporating a minimum distance of 1.7 to 2.0 microm between cluster centers produced fiber patterns similar to those observed in the original transverse sections of the muscle. In addition, if it assumed that the central fiber in each cluster is derived from primary myoblast progenitors, these results suggest that there may be some degree of repulsion between the primary fibers during the initial stages of cluster formation. The mechanistic basis of such repulsion is not clear, but it is speculated that secreted factors, such as sonic hedgehog or myostatin may play a role.

Algorithms↗

PubMedDate not supplied

A general model for stochastic SIR epidemics with two levels of mixing.

This paper is concerned with a general stochastic model for susceptible-->infective-->removed epidemics, among a closed finite population, in which during its infectious period a typical infective makes both local and global contacts. Each local contact of a given infective is with an individual chosen independently according to a contact distribution 'centred' on that infective, and each global contact is with an individual chosen independently and uniformly from the whole population. The asymptotic situation in which the local contact distribution remains fixed as the population becomes large is considered. The concepts of local infectious clump and local susceptibility set are used to develop a unified approach to the threshold behaviour of this class of epidemic models. In particular, a threshold parameter R(*) governing whether or not global epidemics can occur, the probability that a global epidemic occurs and the mean proportion of initial susceptibles ultimately infected by a global epidemic are all determined. The theory is specialised to (i) the households model, in which the population is partitioned into households and local contacts are chosen uniformly within an infective's household; (ii) the overlapping groups model, in which the population is partitioned in several ways, with local uniform mixing within the elements of the partitions; and (iii) the great circle model, in which individuals are equally spaced on a circle and local contacts are nearest-neighbour.

Communicable Diseases↗

PubMed1996

Finite element analysis of the effect of cantilever and implant length on stress distribution in an implant-supported fixed prosthesis.

This study investigated the stress distribution at the bone/implant interface with a three-dimensional finite element stress analysis by using three different cantilever and implant lengths in an implant-supported fixed partial denture. Simulation models were created as a bilateral distal cantilever fixed partial denture supported with six implants embedded in a model of the mandibular bone. Nine different simulation models had three different cantilevers (7, 14, and 28 mm) and implant lengths (7, 15, and 20 mm). Vertical forces of 75 N and horizontal forces of 25 N were applied to the distal end of the cantilever. Analysis of the von Mises stresses for the bone/implant interfaces revealed that the maximum stresses occurred at the most distal bone/ implant interface located on the loaded side and significantly increased with the length of the cantilever. However, there was no statistically significant change associated with the length of implants.

Computer Simulation↗