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PubMed2006

Efficacy and cost-effectiveness of nationwide cervical cancer screening in Taiwan.

The annual cervical screening programme using the Papanicolaou (Pap) smear test was launched for women aged 30 years and over from 1995 in Taiwan. This study aimed to evaluate the Taiwanese cervical screening policy and to make recommendations based on the empirical findings from cervical screening data between 1995 and 1998. We used a stochastic process to model the natural history of precancerous lesions and cervical cancer. Based on the estimated results, Monte-Carlo computer simulation was used to evaluate the effectiveness in terms of the reduction in incidence of and mortality from cervical cancer for screening regimes with different screening intervals. Annual Pap smear screening with 100% compliance was estimated to lead to an approximate 80% reduction in deaths from cervical cancer. With 50% compliance, around a 40% reduction was expected. Triennial screening with high compliance was as effective as annual screening with low compliance, and more cost-effective. Based on the observed Taiwan Pap smear-screening programme between 1995 and 1998, with 44.5% women attending at least once, there was an estimated reduction of 16% in deaths from cervical carcinoma. The estimated effectiveness was greater when the period was extended to 2001, in which period 61% of women attended at least once. The screening programme by 2001 was estimated to reduce cervical cancer mortality by 50% (95% confidence interval: 29-65%). The incremental cost-effectiveness was estimated as 8174 dollars per additional life-year gained. In conclusion, triennial screening targeting women aged 30-69 is recommended, along with efforts to enhance the compliance rate.

Adult↗
PubMed1991

Are cohort mortality rates autocorrelated?

In this paper the author examines the proposition that heterogeneity in individual frailty leads to autocorrelation in cohort mortality rates. A simple model is used to construct analytic expressions for the covariance of cohort mortality rates at different ages under a number of alternative assumptions about the stochastic process generating shocks in mortality. The model then is used to construct a procedure that uses correlations in cohort mortality rates to estimate the extent of heterogeneity in a population without relying on strong assumptions about the distribution of frailty or the shape of the underlying hazard. The procedure then is used to show that cohort mortality data from France are consistent with a generalized random-effects model in which frailty is gamma-distributed.

Age Factors↗
PubMed1991

[Problem solving, or: what is my real contribution as a helper?].

A helper's most important task is helping a client find his own solution although it often seems strange how it comes about. In doing this he enters the client's internal and external conversational field and with that into a stochastic process decisive for human life and development. There are however some well defined steps which he can do to reach his goal as the author tries to demonstrate by means of a longer therapy-example.

Adult↗
PubMed1990

Fundamentals of EEG spectral analysis.

Recent progress in the fields of informatics and engineering has enabled a large diffusion of computers in clinical practice too. Availability of these computing facilities has introduced several quantitative methods to analyze electrophysiological signals. Among these techniques spectral analysis is the most used in quantitative electroencephalography. This article introduces some fundamental concepts of the theory of stochastic processes. The power density function and its descriptors useful in EEG analysis are also presented. The various possibilities of the appropriate application of this methodology are discussed.

Electroencephalography↗
PubMed1988

Stochastic humoral expression of human growth hormone epitopes.

Competition experiments between insolubilized monoclonal antibodies (mAb) and polyclonal antisera has led to the description of the humoral expression of human growth hormone (hGH) epitopes. This study was carried out with sera from mice and hamsters submitted to different immunization schedules: chronic administration of the antigen, secondary response and conventional hyperimmunization. The results indicated the absence of a unique immunodominant epitope in hGH; a significant individual variation of antibody (Ab) population titres with time; changes with time in the relative proportion of one Ab population with respect to the others; and the occurrence of Ab enhancing the 125I-hGH binding to five mAb depending upon the individuals and the time of immunization. Heterocliticity towards non-human GH was also detected. Although most of the animals showed cross-reacting Ab, two out of 12 mice, chronically injected, developed heteroclitic Ab. The data suggest that the humoral response to different epitopes of a protein antigen during the maturation of the immune response is a stochastic process leading to transient humoral immunodominance, enhancing Ab populations and heterocliticity, depending upon individual characteristics, either in outbred or inbred populations.

Animals↗
PubMed1989

[The antigenic topography of human growth hormone and the humoral expression of its various epitopes].

Twenty monoclonal antibodies (MAb) against human growth hormone (hGH) were used to establish the antigenic topography of this protein. Mapping experiments were carried out by testing the ability of paired MAb to bind simultaneously or separately to 126I-hGH. Since the specificity of the MAb versus hGH, human placental lactogen, animal prolactins and growth hormones was known, consideration of the whole set of results obtained supported the proposal of a tridimensional model for the antigenic structure of hGH. Further work correlated some of the mapped epitopes with particular regions within the primary structure of the hormone. In addition, it could be demonstrated that certain MAb may induce conformational changes in the antigen as a result of its binding. The humoral expression of various hGH epitopes during the maturation of the immune response was studied in human patients therapeutically treated with hGH and in mice and hamsters submitted to different immunization schemes: chronic administration of the antigen, secondary response and conventional hyperimmunization. The results indicated temporal and individual variations in the titers of each class of Ab as well as the existence of enhancer and heteroclitic Ab. Hence, the expression of the various epitopes of a protein antigen during the immune response is quite probably a stochastic process which depends on individual variations.

Antibodies, Monoclonal↗
PubMed1989

[Phylogenetic analysis of genes of the influenza virus. Relationship between adaptability and neutrality].

Detailed phylogenetic analysis of the gene family of hemagglutinin H3 of influenza A-type virus was fulfilled, taking into account the domain structure of protein and positions of antigen determinants. The densities of distribution of fixed synonimic replacements between domains HA1 and HA2 were shown to be actually equal (rho (HA1) = rho (HA2], and those of nonsynonimic ones to be unequal: their ratios were rho (HA1): rho (HA2) = 2.8 for nonepidemic branches, and rho (HA1): rho (HA2) = 7.7 for epidemic ones. For the positions of antigen determinants (agd) these densities differ still stronger from HA2: rho (agd): rho (HA2) = 10 for nonepidemic branches, and rho (agd): rho (HA2) = 36 for epidemic ones. In total, the rate of fixation of nonsynonimic replacements per position of antigen determinants for epidemic branches is 32 times higher than for nonepidemic ones. The absolute value of this estimation is K(ns)d = (9.1 +/- 0.7).10(-3) of nonsynonimic replacements per nonsynonimic position per year and seems to be twice as much as the maximum rate of neutral fixations Ks = (4.28 +/- 0.68).10(-3). Therefore, the epidemic reproduction of influenza virus is highly adaptive, exactly being focused on positions of antigen determinants. The evolution of influenza virus is stochastic process, both with the neutral and adaptive fixations.

Genes, Viral↗
PubMed1989

[Study on genetic polymorphism of isozyme in natural populations of Drosophila virilis].

Using techniques of polyacrylamide slab electrophoresis and agarose electrophoresis, we have detected genetic variation at 6 loci which coding for enzymes in 4 local samples from natural population of Drosophila virilis. We found 50% of the loci detected are polymorphic, depending on the criterion of polymorphism used. An individual is heterozygotes on the average at 27.13% of its loci. The amount of genetic variation fluctuates widely from locus to locus. At Est-alpha, Est-beta, Amy, most of the individuals are heterozygotes. At the other extreme , Mdh, aGpdh, Acph, few individuals are heterozygotes. For Mdh, we have measured the thermostability at 53 degrees C. No more genetic variation was found. We have measured the amount of genetic differentiation between different local populations. The result showed that there is no relationship between geographical distance and genetic distance. The results are discussed in the light of the continuing controversy over selection and natural theories of genetic variation. We think that both selection and stochastic processes must operate simultaneously in most systems.

Animals↗
PubMed1988

Repopulation of the seminiferous epithelium of the rhesus monkey after X irradiation.

Repopulation of the seminiferous epithelium became evident from Day 75 postirradiation onward after doses of 0.5, 1.0, and 2.0 Gy of X rays. Cell counts in cross sections of seminiferous tubules revealed that during this repopulation the numbers of Apale (Ap) spermatogonia, Adark (Ad) spermatogonia, and B spermatogonia increased simultaneously. After 0.5 Gy the number of spermatogonia increased from approximately 10% of the control level at Day 44 to 90% at Day 200. After 1.0 and 2.0 Gy the numbers of spermatogonia increased from less than 5% at Day 44 to 70% at Days 200 and 370. The number of Ad and B spermatogonia, which are considered to be resting and differentiating spermatogonia, respectively, already had increased when the number of proliferating Ap spermatogonia was still very low. This early inactivation and differentiation of a large part of the population of Ap spermatogonia slows down repopulation of the seminiferous epithelium of the primates. By studying repopulating colonies in whole mounts of seminiferous tubules various types of colonies were found. In colonies consisting of only A spermatogonia, 40% of the A spermatogonia were found to be of the Ad type, which indicates that even before the colony had differentiated, 40% of the A spermatogonia were inactivated into Ad. Differentiating colonies were also found in which one or two generations of germ cells were missing. In some of those colonies it was found that the Ap spermatogonia did not form any B spermatogonia during one or two cycles of the seminiferous epithelium, while in other colonies all Ap spermatogonia present had differentiated into B spermatogonia. This indicates that the differentiation of Ap into B spermatogonia is a stochastic process. When after irradiation the density of the spermatogonia in the epithelium was very low, it could be seen that the populations of Ap and Ad spermatogonia are composed of clones of single, paired, and aligned spermatogonia, which are very similar to the clones of undifferentiated spermatogonia in non-primates.

Animals↗
PubMed1986

CH isotype switching in B cell differentiation.

We have functionally defined a number of B cell subsets that likely represent B cells at different stages of development, based on the pattern of CH isotypes expressed by their clones in splenic fragment or microcultures and on those factors necessary in culture to support the growth of a clone displaying a particular isotype or set of isotypes. Our observations are consistent with isotype switching being a stochastic process which results in the occurrence of progressive isotype restriction in members of a diversifying clone. The surface marker best predictive of the pattern of isotypes a clone may secrete is the sIg isotype of its B cell precursor. Those B cells that have switched to the expression of non-IgM isotypes in vivo can be stimulated in vitro in splenic fragments to give an antibody-secreting clonal culture but so far cannot be stimulated in a microculture of dispersed cells that supports clones secreting IgM alone or with other isotypes.

Animals↗
PubMed1987

The natural history of lung cancer in a periodically screened population.

A mathematical model of the progression kinetics of lung cancer in a periodically screened population is proposed and data collected by the Memorial Sloan-Kettering Cancer Center in New York are used for parameter estimation. It is assumed that the development of adenocarcinoma of lung is a stochastic process with two stages, early and advanced, characterized by mean times, detection probabilities, and cure probabilities. Confidence regions of these parameters are estimated using a number of novel techniques. It is found, surprisingly, that the mean duration of the early stage is at least 4 years, the detectability less than .2, and the curability less than .5. These estimates imply that annual radiographic screening from age 45 to 80 might decrease mortality from adenocarcinoma of lung by something less than 20%.

Adenocarcinoma↗
PubMed1986

On three methods for estimating mutation rates indirectly.

Methods for estimating a mutation rate mu has been proposed by Kimura and Ohta; Nei; and Rothman and Adams. It is shown here that all three methods are best applied to rare alleles and that they are all based upon the assumption that all alleles ultimately become extinct. If there is a neutral allele in a growing population, there is conditioning on ultimate extinction, which implies that the underlying stochastic process can be approximated by a branching process for which the mean number of offspring is less than 1. The low numerical values of t0, the mean time to extinction of a line descended from a single mutant, found in two simulation studies, can be attributed to two features. First, the data on which these studies were based came from a fairly rapidly growing population. In such a population, we would expect that extinction, if it does occur, takes place quickly. A second factor is that the effective population size is somewhat lower than the actual number of adults. Population subdivision and migration does not seem to play a significant role. Conservative high and low estimates of mutation rates are computed, and an estimate is obtained for the standard deviation of the estimate of mu. These allow a rough estimate of a 95% confidence interval, which contains estimates of mu found by Neel and Rothman.

Gene Frequency↗
PubMed1986

Investigations of the time series structure of the EMG during sustained isometric contractions of back muscles.

The experiment aimed at elucidating electromyographic signs of fatigue of lumbar muscles. On two days, 4 subjects had to hold 4 different target forces to fatigue. Bipolar surface EMG's were derived at the L3 level. The time series structure of the EMG's was characterized by means of autoregressive models. The r.m.s.- value did not reveal uniform time-dependent changes, except for an increase during the highest force level. The variance explained by a linear stochastic process systematically increased during the sustained contractions. The mean power frequencies exhibited similar changes.

Adult↗
PubMed1985

Quantitation of the rate of spontaneous generation and carcinogen-induced frequency of anchorage-independent variants of rat tracheal epithelial cells in culture.

The rate of spontaneous generation and the frequency of carcinogen-induced anchorage-independent variants of preneoplastic rat tracheal epithelial (RTE) cells in culture were quantitated. Anchorage-independent variants of different RTE cell lines arose spontaneously by a stochastic process at rates of 0.5 X 10(-4) to 5.4 X 10(-4) variants/cell/generation, as determined by fluctuation analyses. These variants were also induced by the mutagen N-methyl-N'-nitro-N-nitrosoguanidine with a frequency of approximately 10(-3) variants/surviving cell. The rates of spontaneous change and the frequencies of induction are the first reported for epithelial cells and are similar to some, although not all, rates and frequencies of change to anchorage independence for fibroblast-like cells in culture. In addition, these rates and frequencies are similar to those for mutations at some known gene loci. The induced frequency of this late change in neoplastic progression is, however, considerably lower than the frequency of induction of the initial, preneoplastic changes in RTE cells in culture (approximately 3 X 10(-2)/surviving cell). These quantitative determinations are useful in defining the mechanisms of late changes occurring during the progression of RTE cells to the neoplastic state.

Animals↗
PubMed1983

Fibrous intimal thickening and atheronecrosis of the thoracic aorta. Some background for mathematical theory.

Paraffin sections from the lateral walls of the thoracic aorta, stained with a nigrosin-Gomori trichrome combination, were used to separate subjects into those having (Yes-A) and not having (No-A) atheronecrosis, as operationally defined. In 174 of the 211 No-A subjects, the dispersal of fibrous intimal thickening (FIT) over a carefully selected set of loci was fitted well (goodness of fit p greater than 0.05) by the negative binomial distribution. In 99 of the 125 Yes-A subjects, negative binomial forms were fitted well to the data. The Poisson and positive binomial forms also fitted well in most aortas. In some aortas, departures from the negative binomial, positive binomial, or Poisson forms could be attributed to the presence (among a total of 40 points) of a set of one to five points having accelerated fibroplasia. Atheronecrosis and accelerated fibroplasia tended to coexist in the same subjects and also to be found together in the same loci within aortas. Both features of advanced plaques were characteristic of older subjects. These results taken together affirm that several decades of progression of FIT precede an abrupt emergence of the two features of late phase atherogenesis. The findings suggest that atherosclerosis progresses by a two-phase stochastic process. In phase one, FIT evolves such that a form resembling the negative binomial is generated with approximations of the mean as a linear function of time and the standard deviation as a quadratic function of the mean. In phase two the set of points with greatest FIT acquires either atheronecrosis, or accelerated fibroplasia, or both.

Adult↗
PubMedDate not supplied

[Diffusion model for the dynamics of fibroblast initial attachment].

The simplest model for the formation of initial cell--substrate contact from the discrete multitude of the contacts of small cell surface projections named spheropodia (SP) is presented. The main points of the model are: 1) the multitude of SP is homogenous; 2) there are at least two states of SP, S0--free SP, S1--attached SP; 3) transitions between the states are stochastic and independent. There were two criteria for the selection of concrete models. Firstly it must assume the great number of microcontacts. Secondly the parameters of the model function v(t, x) must coincide with the parameters of experimental function v(t, x). The model function is the probability that at the moment t the cell has the attachment force not smaller than the threshold value x. It is shown that the diffusion model satisfied these criteria. In this model the stochastic process of cell attachment is described as a diffusion process with positive drift in the one-dimensional space of the summing cell attachment force.

Animals↗
PubMed1982

[clonal analysis of the independence of tumor cell multiplication from the substrate].

The clone of near-diploid mouse transformed CAK-25AGr cells is characterized by the stable cloning efficiency in a semi-solid medium (about 10(-5) per cell plated in methylcellulose). It was shown that colonies in the semi-solid medium were formed by rare single cells and did not arise as a result of slow multiplication of all cells in the population. These cells are not genetical variants different from other cells in the culture. This is assumed on the basis of following data. First, the majority of the subclones arising in methylcellulose (9 of 12) retained parental cloning efficiency in the semi-solid medium. Second, all 6 subclones picked from the solid substratum had the ability to form colonies in methylcellulose with the frequency not lower than that of the parental clone. Apparently, the proliferation in methylcellulose of the transformed cells studied is a stochastic process. Each cell in the culture has the ability to initiate a colony in the semi-solid medium with the certain probability. This probability is a heritable characteristic of the cloned cell line. It is possible that this characteristic reflects the norm of reaction of the cells to some environmental factors.

Animals↗