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Radiation and your patient: a guide for medical practitioners.

This didactic text is devoted to the protection of patients against unnecessary exposure to ionising radiation. It is organised in a questions-and-answers format. There are obvious benefits to health from medical uses of radiation, in x-ray diagnostics, interventional radiology, nuclear medicine, and radiotherapy. However, there are well-established risks from high doses of radiation (radiotherapy, interventional radiology), particularly if improperly applied, and possible deleterious effects from small radiation doses (such as those used in diagnostics). Appropriate use of large doses in radiotherapy prevents serious harm, but even low doses carry a risk that cannot be eliminated entirely. Diagnostic use of radiation requires therefore such methodology that would secure high diagnostic gains while minimising the possible harm. For assessment of the risk, a quantitative measure of exposure is a necessary prerequisite. Therefore, dosimetric quantities are explained and defined (absorbed dose, effective dose). Basic facts are presented on mechanisms of action of ionising radiations on living matter. Undesired deleterious effects in man are categorised into two categories. The first one comprises sequelae resulting from massive cell killing (the so-called deterministic effects), requiring a high dose for their manifestation (exceeding the threshold dose). The second category includes those effects originating from mutational changes in the cellular DNA. These may eventually lead to development of radiation-induced cancer and to hereditary changes, transmitted to descendants of exposed individuals after irradiation of their gonads. Data on the magnitude of threshold doses for cell killing effects are presented. On the basis of experimental, clinical, and epidemiological evidence, assessment is also given of the probability with which cancers and hereditary mutations may be induced by doses of various magnitudes, most likely without a threshold dose (below which no effect would obtain). The text provides ample information on opportunities to minimise doses, and therefore the risk from diagnostic uses of radiation. This objective may be reached by avoiding unnecessary (unjustified) examinations, and by optimising the procedures applied both from the standpoint of diagnostic quality and in terms of reduction of the excessive doses to patients. Optimisation of patient protection in radiotherapy must depend on maintaining sufficiently high doses to irradiated tumours, securing a high cure rate, while protecting the healthy tissues to the largest extent possible. Problems related to special protection of the embryo and fetus in the course of diagnostic and therapeutic uses of radiation are presented and practical solutions are recommended. This issue of the Annals of the ICRP also includes a brief report concerning Diagnostic Reference Levels in medical imaging: Review and additional advice.

Adult↗

The effect of various interventions during a typhoid epidemic. Results of a simulation study.

This paper presents an epidemiological model for typhoid fever epidemics or paratyphoid diseases with an enteric course, as well as a deterministic approach for the quantitative representation of this model. The model has been tested against one typhoid and two paratyphoid epidemics which occurred in the Federal Republic of Germany. It was possible to simulate the course of these epidemics with sufficient precision, and to obtain information on the effects of various interventions (e.g. oral vaccination or hygiene measures).

Disease Outbreaks↗

Inverse covariation of spectral density and correlation dimension in cyclic EEG dynamics of the human brain.

The responsiveness or excitability of the central nervous system (CNS) to external or internal stimuli is systematically altered corresponding to transient changes of the EEG background activity, mainly in the alpha range. We hypothesise that a transient alpha power increase is due to an underlying increase in synchronisation or coupling strength between various neuronal elements or cortical networks. Consequently, the 'network' of the CNS may be more ordered and, hence, less complex in the case of high spectral density, and vice versa. The goals of the present paper are (1) to prove the inverse covariation between spectral density and correlation dimension for a set of human EEG data, (2) to falsify the null hypothesis that the observed relationship is a random one, and (3) to propose a neuronal approach which may explain the observed correlations. A sliding computation of the spectral density and correlation dimension [Grassberger P, Procaccia I (1983) Physica D 9:189-208] of mid-occipital EEG recordings derived from eight awake subjects with eyes closed was performed. The similarity between the two time courses was quantified by similarity measures and descriptive correlation coefficients. The temporal pattern of dimensional complexity showed an inverse relationship with simultaneously computed spectral power changes most pronounced in the alpha range. The group means of similarity measures and correlation coefficients were compared with the corresponding means of a sample set established by 20 Gaussian random signals. Statistically significant differences were obtained at the 0.1% level, rejecting the null hypothesis that the observed relationship is a random one. The results support the idea that the dynamics of the EEG signals investigated reflect a chaotic deterministic process with state transitions from 'high-dimensional' to 'low-dimensional' non-linear dynamics, and vice versa. Adequate neuronal models and approaches to interpret the disclosed transients and the inverse covariation between spectral density and dimensional complexity are proposed, giving additional insight into the integrative functioning of the CNS with respect to the strategy of information processing.

Brain↗

Entropy production of diffusion in spatially periodic deterministic systems.

This paper presents an ab initio derivation of the expression given by irreversible thermodynamics for the rate of entropy production for different classes of diffusive processes. The first class is Lorentz gases, where noninteracting particles move on a spatially periodic lattice, and collide elastically with fixed scatterers. The second class is periodic systems, where N particles interact with each other, and one of them is a tracer particle that diffuses among the cells of the lattice. We assume that, in either case, the dynamics of the system are deterministic and hyperbolic, with positive Lyapunov exponents. This work extends methods originally developed for a chaotic two-dimensional model of diffusion, the multi-baker map, to higher-dimensional, continuous-time dynamical systems appropriate for systems with one or more moving particles. Here we express the rate of entropy production in terms of hydrodynamic measures that are determined by the fractal properties of microscopic hydrodynamic modes that describe the slowest decay of the system to an equilibrium state.

Journal Article↗

A Wiener filter approach to the binaural reproduction of stereo sound.

This paper considers authentic binaural reproduction with loudspeakers using cross-talk cancellation. A systematic time domain deconvolution method is presented using both stochastic and deterministic Wiener filters. This method has advantages in that the Wiener filter is inherently causal and stable so that no additional stabilization process, as generally required in the frequency domain methods, is needed. Errors involved in the authentic reproduction are classified into modeling, inverse, and repeatability errors. In addition, the reproduction error is used as the performance measure of a reproduction system. Finally, a series of monaural and binaural reproduction tests were conducted in an anechoic chamber using a PC based reproduction system with a soundcard by changing the length of the inverse filter used. Test results demonstrated that the performance was improved in proportion to the length of the filter used. The reproduction performance error and its test procedure presented here can be used for objectively assessing the performance of a subjective auditory perception test system.

Journal Article↗

Adaptive regularization network based neural modeling paradigm for nonlinear adaptive estimation of cerebral evoked potentials.

In this paper we report an adaptive regularization network (ARN) approach to realizing fast blind separation of cerebral evoked potentials (EPs) from background electroencephalogram (EEG) activity with no need to make any explicit assumption on the statistical (or deterministic) signal model. The ARNs are proposed to construct nonlinear EEG and EP signal models. A novel adaptive regularization training (ART) algorithm is proposed to improve the generalization performance of the ARN. Two adaptive neural modeling methods based on the ARN are developed and their implementation and performance analysis are also presented. The computer experiments using simulated and measured visual evoked potential (VEP) data have shown that the proposed ARN modeling paradigm yields computationally efficient and more accurate VEP signal estimation owing to its intrinsic model-free and nonlinear processing characteristics.

Algorithms↗

Entrances skin dose distribution maps for interventional neuroradiological procedures: a preliminary study.

Dose estimation in interventional neuroradiology can be useful to limit skin radiation injuries. The purpose of this study was to evaluate the role of entrance skin dose (ESD) maps in planning exposure condition optimisation. Thirteen cerebral angiography and five embolisation procedures were monitored, measuring ESD, dose-area product (DAP) and other operational parameters. A transmission ionisation chamber, simultaneously measuring air kerma and DAP, measured dose-related quantities. Data acquisition software collected dosimetric and geometrical data during the interventional procedure and provided a distribution map of ESD on a standard phantom digital image, with maximum value estimation. Values of 88-1710 mGy for maximum skin dose and 16.7-343 Gy cm2 for DAP were found. These data confirm the possibility of deterministic effects during therapeutic interventional neuroradiological procedures like cerebral embolisation. ESD maps are useful to retrospectively study the exposure characteristics of a procedure and plan patient exposure optimisation.

Adult↗

Chaos or noise: difficulties of a distinction

In experiments, the dynamical behavior of systems is reflected in time series. Due to the finiteness of the observational data set, it is not possible to reconstruct the invariant measure up to an arbitrarily fine resolution and an arbitrarily high embedding dimension. These restrictions limit our ability to distinguish between signals generated by different systems, such as regular, chaotic, or stochastic ones, when analyzed from a time series point of view. We propose to classify the signal behavior, without referring to any specific model, as stochastic or deterministic on a certain scale of the resolution epsilon, according to the dependence of the (epsilon,tau) entropy, h(epsilon, tau), and the finite size Lyapunov exponent lambda(epsilon) on epsilon.

Journal Article↗

Analysis of growth of multicellular tumour spheroids by mathematical models.

We wished to determine the applicability of previously proposed deterministic mathematical models to description of growth of multicellular tumour spheroids. The models were placed into three general classes: empirical, functional and structural. From these classes, 17 models were applied systematically to growth curves of multicellular tumour spheroids used as paradigms of prevascular and microregional tumour growth. The spheroid growth curves were determined with uniquely high density of measurements and high precision. The theoretical growth curves obtained from the models were fitted by the weighted least-squares method to the 15 measured growth curves, each corresponding to a different cell line. The classical growth models such as von Bertalanffy, logistic and Gompertz were considered as nested within more general models. Our results demonstrate that most models fitted the data fairly well and that criteria other than statistical had to be used for final selection. The Gompertz, the autostimulation and the simple spheroid models were the most appropriate for spheroid growth in the empirical, functional and structural classes of models, respectively. We also showed that some models (e.g. logistic, von Bertalanffy) were clearly inadequate. Thus, contrary to the widely held belief, the sigmoid character of a three or more parameter growth function is not sufficient for adequate fits.

Cell Division↗

The influence of finite cavities on the sound insulation of double-plate structures.

Lightweight walls are often designed as frameworks of studs with plates on each side--a double-plate structure. The studs constitute boundaries for the cavities, thereby both affecting the sound transmission directly by short-circuiting the plates, and indirectly by disturbing the sound field between the plates. The paper presents a deterministic prediction model for airborne sound insulation including both effects of the studs. A spatial transform technique is used, taking advantage of the periodicity. The acoustic field inside the cavities is expanded by means of cosine-series. The transmission coefficient (angle-dependent and diffuse) and transmission loss are studied. Numerical examples are presented and comparisons with measurement are performed. The result indicates that a reasonably good agreement between theory and measurement can be achieved.

Journal Article↗

Airway branching morphology of mature and immature rabbit lungs.

The scheme of Horsfield et al. for describing the pulmonary airway tree (J Appl Physiol 52: 21-26, 1982) catalogs each airway according to its order and the difference in order of its two daughters (denoted Delta). Although this scheme captures the natural asymmetry in the airway tree, it is still deterministic, because it assumes that all airways of a given order are the same; yet such variability is extremely important in determining the overall behavior of the lungs. We therefore analyzed complete lung lobes from three mature and two immature rabbits and determined the Horsfield order and Delta of every airway down to the terminal bronchioles. We also measured the diameter of each airway. This allowed us to determine the average structure of the rabbit airway tree, the variation about this average, and also how the structures of mature and immature airway trees compare. We found some variation in branching asymmetry and airway diameter at a given order between animals but no evidence of systematic differences in structure between mature and immature lungs. We found evidence of a difference in the branching structure of the peripheral vs. the central part of the airway tree (the break point being around order 20). We also determined the nature of the variation in Delta and diameter as a function of order, which should be valuable for the development of computer models seeking to encapsulate the naturally occurring regional variation in airway geometry in the normal rabbit lung.

Animals↗

Bioeconomic evaluation of embryo transfer in beef production systems: I. Description of a biological model for steer production.

Concepts used to derive a deterministic model for evaluating embryo transfer for commercial steer production taking into consideration genetic merit for growth and mature size, herd feed supply, and recipient maternal environment are discussed. Genetic potential of an embryo is used to derive optimal growth rates that can be sustained by available herd feed per animal per day. Equations are provided for various measures of performance as functions of the feed, genotype of the embryo, and recipient maternal contribution. To assess the value of a particular line of embryos, interactions between genotype and nutrient environment are quantified, so that the benefits of embryos of high genetic merit are evaluated objectively. Product quality and weight are predicted from the model to provide a framework that will allow commercial beef producers to determine marketing strategies likely to result in optimal return.

Animal Feed↗

Force-extension measurements on bacterial flagella: triggering polymorphic transformations.

Bacterial flagella can adopt several different helical shapes in response to varying environmental conditions. A geometric model by Calladine ascribes these discrete shape changes to cooperative transitions between two stable tertiary structures of the constituent protein, flagellin, and predicts an ordered set of 12 helical states called polymorphic forms. Using long polymers of purified flagellin, we demonstrate controlled, reversible transformations between different polymorphic forms. While pulling on a single filament using an optical tweezer, we record the progressive transformation of the filament and also measure the force-extension curve. Both normal and coiled polymorphic forms stretch elastically with a bending stiffness of 3.5 pN x microm(2). At a force threshold of 4-7 pN or 3-5 pN (for normal and coiled forms, respectively), a fraction of the filament suddenly transforms to the next, longer, polymorphic form. This transformation is not deterministic because the force and amount of transformation vary from pull to pull. In addition, the force is highly dependent on stretching rate, suggesting that polymorphic transformation is associated with an activation energy.

Computer Simulation↗

Effects analysis of time-varying or repeated exposures in aquatic ecological risk assessment of agrochemicals.

Exposure to agrochemicals in the aquatic environment often occurs as time-varying or repeated pulses. Time-varying exposures may occur due to runoff events and spray drift associated with precipitation and application events. Hydrologic dilution, dispersion, and degradation also produce pulsed exposures. Standard laboratory toxicity tests using constant exposure concentrations typically do not investigate the toxicity of time-varying or repeated exposures. Detoxification, elimination, and recovery may occur within organisms or populations during the periods between exposures. The difficulty of estimating effects of realistic time-varying exposures from measurements made under constant exposure conditions is often an important source of uncertainty in ecological risk assessment of pesticides. This article discusses the criteria and tools for deciding whether time-varying exposures are relevant in a particular risk assessment, approaches for laboratory toxicity testing with time-varying exposure, modeling approaches for addressing effects oftime-varying exposure, deterministic and probabilistic ecological risk characterization of time-varyingexposures and toxicity, and uncertainty analysis.

Animals↗

Manipulation of the morphology of semiconductor-based nanostructures from core-shell nanoparticles to nanocables: the case of CdSe/SiO(2).

The morphology of CdSe/SiO(2) was manipulated from core-shell-structured nanoparticles to nanocables by using a chemical vapor deposition (CVD) process. The growth of nanocables, with cores no more than 20 nm in diameter, is initiated by the formation of core-shell nanoparticles with SiO(2) as matrix and CdSe clusters dispersed inside. After the subsequent vaporization of the SiO(2) matrix, the follow-up CdSe vapor crystallizes with the remaining CdSe clusters as nuclei to form CdSe nanowires as the furnace was cooled to 1200 degrees C. During the controlled cooling of the furnace, the SiO vapor re-deposits to sheathe the nanowires. The thickness of the shell and the diameter of core were successfully controlled. The photoluminescence measurements show that the CdSe/SiO(2) nanocables have strong visible-light emission bands located at 590 and 688 nm, which are attributed to the defects induced by SiO(2) sheaths nanowires and the quantum confinement effect of the CdSe, respectively. The UV/Vis absorption spectra of the naked CdSe nanowires further validate the above-mentioned quantum confinement effect. The deterministic growth of these nanocables is very important for the design of the nanodevices based on them.

Journal Article↗

Deterministic chaos and the first positive Lyapunov exponent: a nonlinear analysis of the human electroencephalogram during sleep.

Under selected conditions, nonlinear dynamical systems, which can be described by deterministic models, are able to generate so-called deterministic chaos. In this case the dynamics show a sensitive dependence on initial conditions, which means that different states of a system, being arbitrarily close initially, will become macroscopically separated for sufficiently long times. In this sense, the unpredictability of the EEG might be a basic phenomenon of its chaotic character. Recent investigations of the dimensionality of EEG attractors in phase space have led to the assumption that the EEG can be regarded as a deterministic process which should not be mistaken for simple noise. The calculation of dimensionality estimates the degrees of freedom of a signal. Nevertheless, it is difficult to decide from this kind of analysis whether a process is quasiperiodic or chaotic. Therefore, we performed a new analysis by calculating the first positive Lyapunov exponent L1 from sleep EEG data. Lyapunov exponents measure the mean exponential expansion or contraction of a flow in phase space. L1 is zero for periodic as well as quasiperiodic processes, but positive in the case of chaotic processes expressing the sensitive dependence on initial conditions. We calculated L1 for sleep EEG segments of 15 healthy men corresponding to the sleep stages I, II, III, IV, and REM (according to Rechtschaffen and Kales). Our investigations support the assumption that EEG signals are neither quasiperiodic waves nor a simple noise. Moreover, we found statistically significant differences between the values of L1 for different sleep stages.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Evolution of cardiac calcium waves from stochastic calcium sparks.

We present a model that provides a unified framework for studying Ca2+ sparks and Ca2+ waves in cardiac cells. The model is novel in combining 1) use of large currents (approximately 20 pA) through the Ca2+ release units (CRUs) of the sarcoplasmic reticulum (SR); 2) stochastic Ca2+ release (or firing) of CRUs; 3) discrete, asymmetric distribution of CRUs along the longitudinal (separation distance of 2 microm) and transverse (separated by 0.4-0.8 microm) directions of the cell; and 4) anisotropic diffusion of Ca2+ and fluorescent indicator to study the evolution of Ca2+ waves from Ca2+ sparks. The model mimics the important features of Ca2+ sparks and Ca2+ waves in terms of the spontaneous spark rate, the Ca2+ wave velocity, and the pattern of wave propagation. Importantly, these features are reproduced when using experimentally measured values for the CRU Ca2+ sensitivity (approximately 15 microM). Stochastic control of CRU firing is important because it imposes constraints on the Ca2+ sensitivity of the CRU. Even with moderate (approximately 5 microM) Ca2+ sensitivity the very high spontaneous spark rate triggers numerous Ca2+ waves. In contrast, a single Ca2+ wave with arbitrarily large velocity can exist in a deterministic model when the CRU Ca2+ sensitivity is sufficiently high. The combination of low CRU Ca2+ sensitivity (approximately 15 microM), high cytosolic Ca2+ buffering capacity, and the spatial separation of CRUs help control the inherent instability of SR Ca2+ release. This allows Ca2+ waves to form and propagate given a sufficiently large initiation region, but prevents a single spark or a small group of sparks from triggering a wave.

Animals↗

Adhesion mediated by bonds in series.

Cell adhesion in physiological situations and biotechnological applications is often mediated through serial protein/protein linkages. The adhesion strength of cell/substrate contacts through receptor/ligand bonds in series is explored with a simple mathematical model and quantified with an experimental adhesion assay. A deterministic, mass-action model is developed to describe the attachment and detachment of cell/substrate contacts through single and serial bonds. The experimental system is comprised of protein-coated beads, soluble antibody linkers, and an antibody-coated glass surface. Using the Radial-Flow Detachment Assay, the adhesion strengths of bead/substrate contacts through single and serial linkages are measured. Taken together, this work shows that the specific adhesion strength of the cell/substrate contacts comprised of two receptor/ligand bonds in series is less than the specific adhesion strength of the cell/substrate contacts comprised of either of the bonds separately. In addition, the force to rupture contacts comprised of bonds in series varies with the concentration of the solution linker. The model predicts that the locus of linkage fracture location has only a mild dependence on the ratio of relative bond affinities.

Binding Sites↗