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Stability of heartbeat interval distributions in chronic high altitude hypoxia.

Recent studies of nonlinear dynamics of the long-term variability of heart rate have identified nontrivial long-range correlations and scale-invariant power-law characteristics (l/f noise) that were remarkably consistent between individuals and were unrelated to external or environmental stimuli (Meyer et al., 1998a). The present analysis of complex nonstationary heartbeat patterns is based on the sequential application of the wavelet transform for elimination of local polynomial nonstationary behavior and an analytic signal approach by use of the Hilbert transform (Cumulative Variation Amplitude Analysis). The effects of chronic high altitude hypoxia on the distributions and scaling functions of cardiac intervals over 24 hr epochs and 4 hr day/nighttime subepochs were determined from serial heartbeat interval time series of digitized 24 hr ambulatory ECGs recorded in 9 healthy subjects (mean age 34 yrs) at sea level and during a sojourn at high altitude (5,050 m) for 34 days (Ev-K2-CNR Pyramid Laboratory, Sagarmatha National Park, Nepal). The results suggest that there exists a hidden, potentially universal, common structure in the heterogeneous time series. A common scaling function with a stable Gamma distribution defines the probability density of the amplitudes of the fluctuations in the heartbeat interval time series of individual subjects. The appropriately rescaled distributions of normal subjects at sea level demonstrated stable Gamma scaling consistent with a single scaled plot (data collapse). Longitudinal assessment of the rescaled distributions of the 24 hr recordings of individual subjects showed that the stability of the distributions was unaffected by the subject's exposure to a hypobaric (hypoxic) environment. The rescaled distributions of 4 hr subepochs showed similar scaling behavior with a stable Gamma distribution indicating that the common structure was unequivocally applicable to both day and night phases and, furthermore, did not undergo systematic changes in response to high altitude. In contrast, a single function stable over a wide range of time scales was not observed in patients with congestive heart failure or patients after cardiac transplantation. The functional form of the scaling in normal subjects would seem to be attributable to the underlying nonlinear dynamics of cardiac control. The results suggest that the observed Gamma scaling of the distributions in healthy subjects constitutes an intrinsic dynamical property of normal heart function that would not undergo early readjustment or late acclimatization to extrinsic environmental physiological stress, e.g., chronic hypoxia.

Acclimatization↗

The effects of radiotherapy treatment uncertainties on the delivered dose distribution and tumour control probability.

Uncertainty in the precise quantity of radiation dose delivered to tumours in external beam radiotherapy is present due to many factors, and can result in either spatially uniform (Gaussian) or spatially non-uniform dose errors. These dose errors are incorporated into the calculation of tumour control probability (TCP) and produce a distribution of possible TCP values over a population. We also study the effect of inter-patient cell sensitivity heterogeneity on the population distribution of patient TCPs. This study aims to investigate the relative importance of these three uncertainties (spatially uniform dose uncertainty, spatially non-uniform dose uncertainty, and inter-patient cell sensitivity heterogeneity) on the delivered dose and TCP distribution following a typical course of fractionated external beam radiotherapy. The dose distributions used for patient treatments are modelled in one dimension. Geometric positioning uncertainties during and before treatment are considered as shifts of a pre-calculated dose distribution. Following the simulation of a population of patients, distributions of dose across the patient population are used to calculate mean treatment dose, standard deviation in mean treatment dose, mean TCP, standard deviation in TCP, and TCP mode. These parameters are calculated with each of the three uncertainties included separately. The calculations show that the dose errors in the tumour volume are dominated by the spatially uniform component of dose uncertainty. This could be related to machine specific parameters, such as linear accelerator calibration. TCP calculation is affected dramatically by inter-patient variation in the cell sensitivity and to a lesser extent by the spatially uniform dose errors. The positioning errors with the 1.5 cm margins used cause dose uncertainty outside the tumour volume and have a small effect on mean treatment dose (in the tumour volume) and tumour control.

Humans↗

A computer program for the graphical and iterative fitting of probability density functions to biological data.

A tutorially-assisted, interactive program, written for a Digital Equipment Corporation LAB-11 minicomputer (PDP-11/20, is described which allows a user to fit (with or without automatic estimation of initial parameter values), by a method of nonlinear least squres, any one of seven different types of probability density functions (p.d.f.'s) to an empirical frequency distribution; the latter of which may be input to the program or formed by the program whenever it is furnished a series of times between events. The iteratively-obtained, "best fit" p.d.f. is displayed on a two color, point-plot display against the background of a point-plot histogram. By selecting any one of nine output modes, the user is allowed: (1) to view histograms successively on the point-plot display, (2) to generate selected p.d.f.'s (3) to "force" p.d.f.'s having known parameters through the histogram data, (4) to obtain Chi-square (x2) and Kolmogorov-Smionov estimates of the goodness of fit to the data, and (5) to apply a special test [Williams and Kloot, 1953] in order to determine whether the least squares estimates of two candidate models are statistically different. The resident driver program and the four overlayable program segments are written in standard FORTRAN IV; except for two plot routines, which are written in PDP-11 assembly language.

Computers↗

A new approach to the computation of indices of paternity.

This paper describes an algorithm to calculate several indices of paternity (combination frequency, paternity likelihood (Y/X) and paternity exclusion probability (E) for father-mother-child combination (trio) as well as father-child combination (duo). This program is written in FORTRAN IV and applicable to any kinds of blood group systems such as Rh and HLA. The characteristic points of the present method are as follows: First, the relation between genotypes and phenotypes is given in a straightforward way by introducing a translational matrix. Secondly, by a unit run on a computer, several indices of paternity are tabulated for all kinds of combinations of trio as well as duo. Finally, the efficiency of diagnosis of a certain system is listed by calculating the distribution of log (Y/X).

Child↗

A computer calculation of probability of monozygosity for twins.

A general algorithm is described to calculate the probability of monozygosity of concordant twins on the basis of blood type tests. Frequencies of all combinations of twins and parents are created with the aid of a translational matrix which facilitates conversion of genotypes to phenotypes automatically. The method of calculation is explained by taking Rh system in Germany as an example. The probability of monozygosity is calculated for all combinations of twin and/or father and/or mother. Effects of parental phenotypes on the efficiency in the diagnosis are analyzed quantitatively. Applicability of this method to other calculations concerning genetics is also discussed.

Blood Group Antigens↗

A computerized mental patient classification system.

This paper presents the detailed logic and flow of a computerized actuarial report system based on the patient's demographic and clinical information routinely collected in a state mental health information system. Probability statements regarding the patient's diagnostic classifications, likelihood of harm to self and others, probable psychotropic drug prescription, likelihood of unauthorized absence, and prediction of length of stay are presented in the report. The multivariate linear discriminant function and linear regression are used in the calculation of the posterior probabilities and the predicted value of length of stay.

Computers↗

A method for the quantification of the decision-making process in a computer-oriented medical world.

The aim of this paper is to suggest an original approach to the decision-making process in a computer-oriented medical record, now in use on an experimental basis, at a major District Hospital in Sesto S. Giovanni, near Milano, in a general medicine department. Two types of algorithms are introduced in order to 'capture' more effectively the different steps of the decisional process on the basis of a differential diagnosis approach. The first refers to the field of symbolic reasoning, close to the area of Artificial Intelligence and uses score variables, while the other can handle qualitative expressions since it follows the fuzzy-set approach. A comparison among the performances offered by such algorithms, the physician's decision and the Bayes Rule is then carried on. Further developments should clarify the problems of parameter sensitivity as regards the successive steps to the final diagnosis. The present implementation is suitable for individual hospital departments and educational purposes.

Decision Making↗

Cell survival probability under ionizing radiation.

The survival probability of a living cell exposed to ionizing radiation in an experimental setup is derived. The survival of a cell depends on the severity of the radiation damage and efficiency of the cellular repair. The formula of the survival probability is expressed as a function of dose, nonlinear rate of lesion induction, nonlinear rate of cellular repair, and a key experimental parameter--the holding time. The result is an extension of the Markovian dose-response model developed by Yang and Swenberg.

Animals↗

Waveguides in medical ultrasonics: an experimental study of mode propagation.

Experimental results of ultrasound of varying frequency (0.8-5.0 MHz) propagating in cold drawn wires of stainless steel and aluminium ranging in diameter from 0.25 to 1.21 mm are in close agreement with theoretical predictions. This agreement is maintained when the coupling medium between the wire and the ultrasound source is a short distance of water. Similar measurements for brass and copper wires are in less close agreement with theory due, probably, to the effect of greater anisotropy.

Aluminum↗

A program for training and feedback about probability estimation for physicians.

Medical decisions are rarely made under conditions of complete certainty. In the past decade there has been a rapid growth of interest in formal methods for optimizing medical decisions under uncertainty. Application of decision-analytic methods requires physicians to make probability estimates about clinical events for which extensive data are not available. This paper describes a computer program to train physicians to be better probability estimators: to make probability estimates that are numerically meaningful for use in formal decision analyses. It is designed to be a stand-alone application requiring about 2 hours of physician time. Use requires an IBM-PC or compatible microcomputer with graphics adaptor and monitor, and 8087 coprocessor.

Computer-Assisted Instruction↗

Is it possible to predict the outcome of peripheral nerve injuries? A probability model based on prospects for regenerating neurites.

The long term functional consequences of peripheral nerve injuries are notoriously unpredictable. We hypothesized that considering the individual regrowth of the elementary components of a nerve (the neurites) rather than the global regeneration of the organ could lead to a better understanding of the mechanisms of nerve repair. Our basic assumptions were that regrowth was random and regrowth of any individual neurite could be defined in terms of its influence on recovery; this influence could be either valid, neutral or invalid. We designed a probability model describing the prospects of regrowth for nerves composed of several types of fibers. Our goal was to propose a general explanation of nerve healing rather than to predict the outcome in individual situations. The results suggested that this model satisfactorily described the events taking place in a healing nerve.

Animals↗