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PubMed1993

The development of alcoholics' and heavy drinkers' consumption: a longitudinal study.

Results are reported from two prospective longitudinal studies of heavy drinkers and alcoholics who have received treatment. The present study focuses on the drinking habits of subjects who have been interviewed four times after the end of treatment. The data uncover substantial changes in heavy drinkers' and alcoholics' consumption level over time, and these observed changes are only partly explainable in terms of measurement error and short-term fluctuations. Changes show signs of accumulation over time. This suggests that heavy drinkers' and alcoholics' consumption level is very unstable over longer periods. The signs of systematic progression are weak. No convincing evidence for loss of control is found, and neither is there convincing evidence for a strong and persistent progression towards heavier drinking. At all levels substantial changes are found, and these are nearly equally strong in both directions. It is concluded that the observed pattern of change more resembles an indeterministic (or stochastic) process than a systematic natural history of a disease.

Adult↗
PubMed1978

A study on the irregularity of the sequence of R-R intervals in chronic atrial fibrillation in man based on the time series analysis and the information theory.

The mechanism of the irregularity of R-R intervals and especially the genesis of the long R-R intervals in atrial fibrillation were clarified. From the point of view of the present study, the sequence of successive R-R intervals can be regarded as a stochastic process, and consequently mathematical analyses can be applied, and the following conclusion could be obtained: the stability of the data, mathematically called stationarity, is present in the sequence of R-R intervals, and these intervals are independently and identically distributed. The probability density function is an Erlangian distribution with phase k of 20 to 26. Namely, as soon as, on the average, 20 to 26 atrial excitatory stimuli have arrived at the AV node, a threshold value of the AV node is reached and ventricular activation is induced. However, if we examine the mathematical structure of the sequence of successive R-R intervals in more detail, the following results can be evidently obtained: during atrial fibrillation with rapid ventricular response, the sequence of R-R intervals is completely independent, but with intermediate or slow ventricular response the adjacent R-R intervals correclate with each other and these adjacent intervals have at least the first order Markov property, which seems to be caused by the concealed conduction. Because of this Markow property due to the prolongation of the refractory period of the AV node, slow ventricular response results.

Aged↗
PubMed2006

A robust procedure for removing background damage in assays of radiation-induced DNA fragment distributions.

The non-random distribution of DNA breakage in PFGE (pulsed-field gel electrophoresis) experiments poses a problem of proper subtraction of the background DNA damage to obtain a fragment-size distribution due to radiation only. A naive bin-to-bin subtraction of the background signal will not result in the right DNA mass distribution histogram. This problem could become more pronounced for high-LET (linear energy transfer) radiation, because the fragment-size distribution manifests a higher frequency of smaller fragments. Previous systematic subtraction methods have been based on random breakage, appropriate for low-LET radiation. Moreover, an investigation is needed to determine whether the background breakage is itself random or non-random. We consider two limiting cases: (1) the background damage is present in all cells, and (2) it is present in only a small subset of cells, while other cells are not contributing to the background DNA fragmentation. We give a generalized formalism based on stochastic processes for the subtraction of the background damage in PFGE experiments for any LET and apply it to two sets of PFGE data for iron ions.

Algorithms↗
PubMed1998

An introduction to Markov modelling for economic evaluation.

Markov models are often employed to represent stochastic processes, that is, random processes that evolve over time. In a healthcare context, Markov models are particularly suited to modelling chronic disease. In this article, we describe the use of Markov models for economic evaluation of healthcare interventions. The intuitive way in which Markov models can handle both costs and outcomes make them a powerful tool for economic evaluation modelling. The time component of Markov models can offer advantages of standard decision tree models, particularly with respect to discounting. This paper gives a comprehensive description of Markov modelling for economic evaluation, including a discussion of the assumptions on which the type of model is based, most notably the memoryless quality of Markov models often termed the 'Markovian assumption'. A hypothetical example of a drug intervention to slow the progression of a chronic disease is employed to demonstrate the modelling technique and the possible methods of analysing Markov models are explored. Analysts should be aware of the limitations of Markov models, particularly the Markovian assumption, although the adept modeller will often find ways around this problem.

Economics, Pharmaceutical↗
PubMed2006

Apoptosis in Alzheimer disease: a mathematical improbability.

Neuronal cell dysfunction and death are cardinal features of Alzheimer disease and a great deal of effort is being expended not only to understand factors involved in the cause and progression of disease (i.e., disease initiators and propagators) but, ultimately, the precise mechanism by which neurons die (for want of a better word, the terminators). Understanding each and every component of the complex pathway that ultimately leads to disease (a clinical phenotype) is clearly of paramount importance for the development of effective therapeutic strategies. Of particular intrigue for many scientists, perhaps the more macabre among us, has been to decipher the final event - namely cell death. Broadly speaking, cell death falls into two categories, apoptotic and necrotic. The former, apoptosis, by definition, is a controlled event; thereby offering the potential for intervention, whereas necrosis is a more stochastic process. Since many of the propagators and exacerbators involved in Alzheimer disease are pro-apoptotic, it is not surprising that certain aspects of apoptosis are evident. However, it would be a mistake to call this apoptosis. In fact, as reviewed herein, the chronic course of disease together with the necessarily slow rate of neuronal death makes apoptotic cell death in Alzheimer disease a mathematical improbability. The numbers simply do not add up.

Alzheimer Disease↗
PubMed1983

A note on the use of serial measures in spike train analysis and their relation to the corresponding moments.

A spike train is a sequence of interspike intervals and should be described in terms of random variables. So, in order to recognize the information of the spike train, one usually calculates the sample mean (as the normalized sum of all intervals in one realization) or the means (of outcomes of respective intervals), an approximation of which is the PSTH. Further, the sample variance and variance, the serial correlation, and the autocovariance are utilized for evaluation. In this paper it is shown that these notions, which seem to be very similar, have little to do one with another, except for some cases (stationarity, ergodicity), which rarely occur in neurobiology. Finally, it is proposed to rename the term stationarity in spike train analysis, because it differs considerably from the definition which is used in the theory of random variables and stochastic processes.

Action Potentials↗
PubMed1984

Coordination of neuronal signals as structures in state space.

This paper expresses difficulties we have in interpreting neuronal activities by means of information and probability theory: until now there is no general agreement about the alphabet used by the neurons and, consequently, the first step in information theory is actually a conjecture. Further, electrophysiological single unit records can often be shown to be not stationary (because of trends, facilitations, inhibitions, transient reactions or oscillations). Thus they would not appear to be ergodic. But then, how does the system succeed in recognizing certain patterns by only one realization of a stochastic process? These difficulties do not arise if an appropriate multiunit system is considered, the dynamics of which are determined by a set of differential equations. The asymptotic (t----infinity) solutions of these equations define a number of state space structures (fixed points, limit cycles or strange attractors). According to this concept, information is related to the special shape of a state space structure and its probability, and information flow means the filtering of these structures.

Animals↗
PubMed1992

The brain in fractal time: 1/f-like power spectrum scaling of the human electroencephalogram.

"1/f-like" power spectrum scaling is a ubiquitous feature of complex systems. In such scaling, the power spectrum of a given time series is dominated by an inverse power law, resulting in an inverse linear relation between log power and log frequency. The 1/f-like power spectrum scaling properties of human, resting eyes-closed and eyes-open EEG were examined. For both eyes-closed and eyes-open EEG, log power had a significant inverse linear relation with log frequency. The slope of this relation was not correlated with previously-calculated Grassberger-Procaccia dimension estimates for the same data, indicating that the EEG is not a 1/f-like stochastic process. Further, the degree of deviation from perfect log power versus log frequency linearity was related to power in the 8-12 Hz alpha frequency band. It is speculated that this deviation may be related to the low dimension of a chaotic alpha rhythm relative to other EEG rhythms.

Adult↗
PubMed1992

Assembly of IgH CDR3: mechanism, regulation, and influence on antibody diversity.

The most variable portion of immunoglobulin molecules is the third complementarity determining region (CDR3) of the heavy chain. This is simply because CDR3 encompasses the region of the rearranged gene where the three gene segments (VH-DH-JH) are joined. Since imprecisions exist in the recombinase reaction, significant differences can be generated at the sites of recombination. This results in the generation of antigen receptor molecules which can differ in their antigen specificity even though they derive from the same germline information. In sum, the significance of the inaccuracy in recombination is that antibodies which are reactive to different antigens can be derived from identical genetic information. This explains how the immune system (using only a limited amount of genetic information) can generate antibodies to virtually any antigen. Though the basic phenomenon of VH-DH-JH assembly has been appreciated for years, two recent findings demonstrate that the generation of CDR3 is more complex than originally believed. First, junctional modification is not a stochastic process as was initially presumed, but is in part developmentally regulated. Second, it has now been well documented that more complex recombinations (for example VH-DH-DH-JH, VH-DH-invDH-JH, etc.) are involved in generating the third hypervariable region of the heavy chain. Not only do these unusual rearrangements--which break the so-called "12/23" recombination rule--occur, but interestingly, certain predicted rearrangements (even some which do follow the "12/23" recombination rule) cannot be demonstrated and apparently do not occur. To date, there is no adequate explanation for the lack of these predicted recombinations. These results have important implications for both the generation of antibody diversity and the recombinase reaction itself.

Animals↗
PubMed2005

Computational analysis of tumor angiogenesis patterns using a two-dimensional model.

Tumor angiogenesis was simulated using a two-dimensional computational model. The equation that governed angiogenesis comprised a tumor angiogenesis factor (TAF) conservation equation in time and space, which was solved numerically using the Galerkin finite element method. The time derivative in the equation was approximated by a forward Euler scheme. A stochastic process model was used to simulate vessel formation and vessel elongation towards a paracrine site, i.e., tumor-secreted basic fibroblast growth factor (bFGF). In this study, we assumed a two-dimensional model that represented a thin (1.0 mm) slice of the tumor. The growth of the tumor over time was modeled according to the dynamic value of bFGF secreted within the tumor. The data used for the model were based on a previously reported model of a brain tumor in which four distinct stages (multicellular spherical, first detectable lesion, diagnosis, and death of the virtual patient) were modeled. In our study, computation was not continued beyond the 'diagnosis' time point to avoid the computational complexity of analyzing numerous vascular branches. The numerical solutions revealed that no bFGF remained within the region in which vessels developed, owing to the uptake of bFGF by endothelial cells. Consequently, a sharp declining gradient of bFGF existed near the surface of the tumor. The vascular architecture developed numerous branches close to the tumor surface (the brush-border effect). Asymmetrical tumor growth was associated with a greater degree of branching at the tumor surface.

Computer Simulation↗
PubMed2000

Determination of the relationship between T cell responsiveness and the number of MHC-peptide complexes using specific monoclonal antibodies.

We describe the generation of three mAbs that recognize the complex of the class II MHC molecule IEk bound to a peptide derived from the carboxyl terminus of moth cytochrome c (residues 95-103). Reactivities of these mAbs are sensitive to single alterations in the sequence of both helices of the MHC molecule and to the bound peptide. The epitopes of these reagents are distinct but overlap substantially. One of these mAbs specifically blocks lymphokine release by T cells responsive to this complex but not others. We have used another to examine how the number of complexes on an APC is related to its ability to stimulate T cells. We find that 200-400 complexes per cell are necessary and sufficient to induce a degree of stimulation, whereas maximum stimulation is achieved only if more than 5000 complexes are present. The analysis indicates that T cell activation is a stochastic process.

Amino Acid Sequence↗
PubMed1986

A population dynamics simulation model with application to health planning.

Despite the increasing emphasis on computers and quantitative methods in health services programs, health services administration students are denied access to many of the most powerful tools of systems analysis, including discrete event simulation, because they lack the necessary background in computer programming, simulation methodology, and stochastic processes. This article presents an approach to the modeling of the growth and decline of population groups and their attributes that can be used by students who do not have the extensive quantitative background required to develop the usual discrete event simulation models. The underlying theory, which is based on the behavior of the expectation process of vector Galton-Watson branching processes, can be explained quite easily. An example is presented that uses an age and sex specific model of population growth to investigate policy questions related to the feasibility of the construction of a long-term care facility for a defined population group. Planning decisions are based on the growth and decline of the numbers of individuals in the various age and sex groups. Extensions of the basic methodology are possible that would include projections of the variance-covariance matrix of the population sizes for each year of the projection process. In addition, the model can be extended to include projections of the impact of infectious and communicable diseases on a defined population group together with the effect of categorical disease screening and control programs. Given the basic data utilized in the model, the implementation of the calculations required by the model can be made on modern microcomputer hardware using any of the standard spreadsheet programs.

Health Planning↗
PubMed2000

The population structure of ten Newfoundland outports.

Island populations are most informative in the study of the genetic structure of human aggregates. These populations are often of small size, thus violating the Hardy-Weinberg assumption of infinite size. Some geographically isolated island populations are further subdivided by religion, ethnicity, and socioeconomic factors, reducing their effective sizes and facilitating genetic changes due to stochastic processes. Because of extreme geographic and social isolation, fishing communities or outports of Newfoundland have been investigated for genetic microdifferentiation through the founder effect and genetic drift (Crawford et al. 1995). The purpose of this paper is to examine the population structure of 10 Newfoundland outports using the allelic frequencies derived from 12 red cell antigens. To achieve this goal, first we calculated gene frequencies using maximum-likelihood estimation procedures. Second, we used R-matrix methods to explore population differentiation. Third, we regressed mean per-locus heterozygosity on genetic distance from the gene frequency centroid to identify the most isolated populations. On the basis of this information, the three outports of Seal Cove, Island Harbor, and Tilting were found to be genetically differentiated from the other small populations. Moreover, religious and geographic subdivisions appear to explain the observed genetic variation.

Blood Group Antigens↗
PubMed2001

Formation of retinal pigment epithelium in vitro by transdifferentiation of neural retina cells.

Chick embryonic neural retina (NR) dedifferentiates in culture and can transdifferentiate spontaneously into retinal pigment epithelium (RPE). Both, primary RPE and transdifferentiated RPE (RPEt), are characterized by pigmentation, expression of RPE-specific protein, eRPEAG and lack of expression of the neural cell adhesion molecule, NCAM. In contrast, NR cells are unpigmented and express NCAM but not eRPE(AG). Functionally, both primary RPE and the RPEt cells display a pH(i) response to bFGF, which is different from that of the NR. We used these characteristics to distinguish cell types in primary cultures of chick NR and follow the changes in phenotype that occur during transdifferentiation. We show that the RPEt forms as small "islands" in the packed regions of the primary, "mother" NR cell sheets, in a stochastic process. Because of a small number of cells involved in the initiation of the transdifferentiation we refer to it as a "leader effect" to contrast it with the "community effect" which requires many competent cells to be present in a group to be able to respond to an inductive signal. The RPEt then expands centrifugally and underneath the surrounding NR sheet. To determine if the RPEt maintains its identity in isolation while displaying the RPE-typical phenotypic plasticity, we explanted the islands of RPEt and treated half of them with bFGF. The untreated RPEt maintained its closely packed, polygonal pigmented phenotype but the bFGF-treated RPEt transdifferentiated into a non-pigmented, NR-like phenotype, indicating that RPEt encompasses the full differentiation repertoire of native RPE.

Animals↗
PubMed1975

A procedure for the detection of pollution by fish movements.

An "alarm" system using fish movements has recently been developed to provide rapid information about accidental spills of pollutants. The data are the realization of a non-stationary stochastic process which takes on discrete values. By the use of the Camp-Paulson approximation, the process is transformed to a strictly stationary one for which calculations are tractable. A procedure is then presented to detect the presence of pollutants. Tests with real data indicate that it detects them sooner than the method used previously.

Animals↗
PubMedDate not supplied

[Geographical variability and subpopulational genetic organization of oak leafroller moth].

Geographically distant populations of oak leafroller moth (Tortrix viridana L.) were characterized by the frequency uniformity for most often alleles and differentiation for rare ones in the esterase and protease loci. Opposite tendency was observed at the subpopulational level. It was supposed that the distinctive spatial distribution of the often and rare alleles was due to different sensitivity of the given groups to the factors of a dynamics. Natural selection and stochastic processes play a major role in the dynamics of often and rare alleles, respectively.

Animals↗
PubMed1992

Testing the Gaussianity of the human EEG during anesthesia.

The Gaussian properties of human EEGs, which were measured over various stages of general anesthesia, were tested. The basis of the method was to describe the EEG signals by autoregressive models and to test the normality of the regression residuals with the Shapiro-Wilk statistic. The results show that in general the human EEG during anesthesia can be considered as a realization of a Gaussian stochastic process.

Anesthesia, General↗
PubMed2005

[A comprehensive quantitative assessment model for arid area's basin water-soil environment quality].

The existing assessment models for water-soil environment quality are usually established on the relationships between assessment indicators and their assessment criteria. Such kinds of models are varied with regional scale, and always need a mass of calculation work. This paper tried to find a general assessment model based on a given water-soil quality assessment criteria. In this process, stochastic technology was used to simulate enough assessment indictor series, and then, assessment model was built up by using artificial neural network to assess these series. This model could reduce work load, and needn't construct functional relations between assessment indicators and their criteria and calculate weigh value. A case study in a basin with the highest level of water resources utilization showed that the model was practical and convenient, and could be used in basin water-soil quality assessment.

Conservation of Natural Resources↗