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[Bases for the use of information theory in qualitative clinical chemical investigations. Use of information theory in clinical chemical investigations, I].

Using information theory, a model communication channel has been constructed to assess the information gain from the performance of clinical chemical tests, in particular qualitative tests. The construct of the model communication channel is especially clear, and it can be easily adapted to the most varied clinical enquiries. The information theoretical parameters, transinformation and test capacity, are used to characterize the information properties of a clinical chemical test. The calculations necessary for the practical application can (primarily when matrices are used) be performed without difficulty, even by non-mathematicians, using modern table calculators. The procedure is illustrated with many numerical examples, and especially applied to combination of qualitative tests.

Chemistry, Clinical

[Audition and information theory: application to cochlear analysis].

Application of the general theory of information and of communication to auditory function enables the internal ear to be assimilated to a digital-analog converter capable of coding the continuous acoustic signal into discontinuous, impulsional type nervous signals. In this model, the ear selects spatio temporal samples of membranous acoustic forms, discrimination of intensity devolving upon the external ciliated system and that of the height upon the internal ciliated system. It allows simple correlation of apparently paradoxical psycho-acoustic phenomena with objective acoustic or histopathological data.

Cochlea

Emergent information. Towards a unified information theory.

This paper proposes the restoration of information theory by means of a philosophy of evolutionary systems. What this philosophy implies for the conception of information may be called a multi-stage model, comprising both the history and the ordering of information processing by real-world systems. Such a unifying information concept may assist suitable research in the coming field of information science.

Biological Evolution

Quantitative densitometry from the point of view of information theory.

The process of quantitative densitometry is analyzed with methods developed in information theory. It is shown that the steps involved in densitometry, e.g. gel staining, mechanical, optical and electronic processing, as well as all the steps of data processing, can be viewed as communication channels. The factors affecting both the relevant and irrelevant part of the total information passed through these channels are discussed in the consistent frame provided by information theory. This view leads to a unifying context for analyzing the performance of quantitative densitometers.

Densitometry

[Reflexions on the usage of information theory in biology].

For living beings, information is as fundamental as matter or energy. In this paper we show: a) inadequacies of quantitative theories of information, b) how a qualitative analysis leads to a classification of information systems and to a modelling of intercellular communication. From a quantitative point of view, the application in biology of information theories borrowed from communication techniques proved to be disappointing. These theories ignore deliberately the significance of messages, and do not give any definition of information. They refer to quantities, based upon arbitrarily defined probabilistic events. Probability is subjective. The receiver of the message needs to have 'meta-knowledge' of the events. The quantity of information depends on language, coding, and arbitrary definition of disorder. The suggested objectivity is fallacious. In common language, the word 'information' is synonymous with knowledge of order. Following common sense a message (letters, coded signals, etc.) is information just in case it is interpretable, i.e. if it fits to a previously acquired meaning (the words of an available language, etc.). The consequence is that calculation of quantities in the sense of Shannon can be used for transmissions, but it is itself meaningless (has no significance). In linguistics and semantics, information is composed of a 'signifier', a physical medium (letters, coded signals, etc.), and a 'signified' or significance. The nature of information is complex. The laws of linguistics and semantics are valid not only at the human, organismic level, but also at the cellular and molecular level. The physiology of sensations gives us many examples for application of a concept of information An electromagnetic wave of 0.7% give us the sensation of a red colour. Sensations have no physical reality. They are purely subjective. At the cellular level communication operates by means of chemical messengers (first messengers), which generally do not penetrate the plasmic membrane. Specific captors operate as transductors: external factors are converted into secondary messengers (cyclic AMP, Ca ion, etc.). Sometimes, electric signals (like depolarization waves) may also play a part in the intercellular communication. Such processes are characterized by changes in a sequence of different molecules carried by a physical signal. What is transmitted is the meaning of the message (significance) which can be memorized by the cell, providing a possible following use. At the molecular level one can find also the processes of linguistic nature. We know that the significance of a word is changed with changing the order of letters (ADD-->DAD, etc.).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Effects of information conflict and complexity in visual figures on voluntary visual exploration, using structural information theory.

This study was designed to examine the effects of information conflict and complexity on voluntary visual exploration quantitatively. 31 adults viewed each of 16 slides of geometrical figures and places for as long as they wished. The stimuli had two values of information conflict and complexity which had been calculated by means of structural information theory. Free looking times indicated that only when information conflict was low, voluntary visual exploration was positively correlated with complexity. Furthermore, voluntary visual exploration correlated positively with information conflict when complexity was low.

Adult

An analysis of case mix complexity using information theory and diagnostic related grouping.

Case mix complexity measurements are essential to determine health care efficiency and effectiveness. Measures of patient care processes and outcomes must be adjusted for case mix before valid comparisons can be made. Hospital reimbursement, particularly prospective reimbursement, must take into account differences in case mix. In addition, a key variable for hospital classification is case mix. There are, however, no widely accepted easily computed case mix measures. Information theory measures of case mix have been developed but their acceptance has been limited by a lack of verification of their basic assumption that concentration of disease is related to clinical complexity. We discuss the rationale underlying the mathematical computaton of information theory measures and demonstrate a statistically significant relationship between clinical measures of case mix complexity and information theory measures of case mix complexity.

Costs and Cost Analysis

Application of information theory to clinical diagnostic testing. The electrocardiographic stress test.

The inherent imperfection of clinical diagnostic tests introduces uncertainty into their interpretation. The magnitude of diagnostic uncertainty after any test may be quantified by information theory. THe information content of the electrocardiographic ST-segment response to exercise, relative to the diagnosis of angiographic coronary artery disease, was determined using literature-based pooled estimates of the true- and false-positive rates for various magnitudes of ST depression from less than 0.5 mm to greater than or equal to 2.5 mm. This analysis allows three conclusions of clinical relevance. First, the diagnostic information content of exercise-induced ST-segment depression, interpreted by the standard 1.0-mm criterion, averages only 15% of that of coronary angiography. Second, there is a 41% increase in information content when the specific magnitude of ST-segment depression is analyzed, as opposed to the single, categorical 1-mm criterion. Third, the information obtained from ECG stress testing is markedly influenced by the prevalence of disease in the population tested, being low in the asymptomatic and typical angina groups and substantially greater in groups with nonanginal chest pain and atypical angina. The quantitation of information has broad relevance to selection and use of diagnostic tests, because one can analyze objectively the value of different interpretation criteria, compare one test with another and evaluate the cost-effectiveness of both a single test and potential testing combination.

Electrocardiography

Comparison of the predictive abilities of different methods based on information theory: searching for receptor-binding sites.

A comparison of a new method of searching for functionally important sites in proteins and peptide hormones with a previously published method is presented. All methods are based on information theory that holds that rare oligomers contain much information and, thus, are likely to be important for specific functional activity. Twenty-five proteins and peptide hormones with known receptor-binding sites were studied; the new method showed good predictive ability. However, taking into account short-range sequential preferences in protein structures, the predictive ability of methods based on information theory, at least for the receptor-binding site predictions, was not greatly improved.

Algorithms

The need-informational theory of emotions.

As an evolvement of Pavlov ideas on higher nervous (psychic) activity 'the need-informational theory of emotions' was suggested by the author in 1964. According to it an emotion is a function of two major factors: (1) power and quality of actual need (or drive, or motivation) and (2) estimation of probability (possibility) of need satisfaction on the basis of phylo- and ontogenetic experience. In the process of experimental testing of 'the need-informational theory of emotions' the role of different cerebral structures (frontal neocortex, hippocampus, amygdala, hypothalamus) in the genesis of emotional states and in the organization of goal-directed behavior was elucidated. The experimental data showed that these 4 brain structures play the major role in estimation of signals coming from environment and in the choice of subject's reactions. The individual characteristics of the interaction between the 4 brain structures must be taken into consideration in discussing neurophysiological backgrounds of different types of the higher nervous activity (temperaments), parameters of extra-introversion and neurotism (emotionality), the formation of main types of neurosis.

Amygdala

Application of information theory to decision analysis in potentially prostaglandin-responsive neonates.

To define settings in which use of prostaglandin E1 before transfer from a community hospital to a tertiary care center benefits neonates with possible heart disease, information theory was used to predict the probability of a favorable response to prostaglandin therapy from the limited information of clinical variables. Records of 250 patients, newborn to 7 days old, with suspected heart disease were reviewed to assess six clinical variables (cyanosis, respiratory distress, heart murmur, pulse contour, hepatomegaly and prematurity). According to the anatomic and hemodynamic cardiovascular condition, each case was categorized as to whether a favorable response to prostaglandin E1 could be anticipated. Information content of each clinical variable with respect to prostaglandin responsiveness was determined, and patients were classified according to the most informative clinical variable. Stepwise extraction of information proceeded until remaining clinical variables added no significant information. Bayes' rule gave estimates of probability of prostaglandin-responsive defect in final subgroups for use in decision analysis. Cyanosis, murmur, small volume pulses and prematurity gave information about prostaglandin-responsive defects. Decision analysis indicated that frequency of poor outcome is minimized by early prostaglandin treatment of cyanotic term infants with a murmur or poor pulses, regardless of how ill they appear, and by treating any critically ill term newborn who has either cyanosis or poor pulses. Acyanotic patients with normal pulses are best untreated with prostaglandin until after definitive diagnosis is made. Advantage to either course was not seen in some small subgroups. Information theory with decision analysis is a rigorous approach to identify relevant clinical variables and define their roles in critical decisions in pediatric cardiology.

Algorithms

An information theory quality score for reagent sera.

A quality score adapted from information theory is of interest in evaluating HLA typing sera in that it permits the evaluation of a panel of sera detecting a given specificity from the quality characteristics of the sera considered individually. The empirical question of additivity of quality scores is considered using data of the 8th International Histocompatibility Workshop. Additivity is only approximate, which indicates that panels of sera will not be quite as good as would be predicted by summing quality scores of the component sera. Methodological problems regarding estimation of the quality score are considered. The information quality score is related to other indices of serum quality for the special case in which reactions are scored as positive or negative.

Antibody Specificity

Information theory and the analysis of ligand-binding data.

The phenomenological principles of information theory are used in the analysis of ligand-binding phenomena in biological macromolecules. Information maps are constructed to visualize regions of ligand chemical potential with maximum amount of information and to devise suitable experimental strategies therefrom. Extensive simulation studies and analysis of experimental data also point out the properties of information used as a weighting procedure in nonlinear least-squares analyses.

Carbon Monoxide

The use of information theory to analyze genomic changes in neoplasia.

How the cell maintains and uses its heritable information may be a critical factor in neoplasia. For example, neoplastic development is thought to depend upon the interplay between random genomic instability and nonrandom selective forces. Information theory provides a means to analyze these processes. One may quantitate not only the amount and lability of information contained within a segment of genetic code, but also the genotypic heterogeneity and the degree of selection affecting a population of cells. In addition, it is theoretically possible to monitor genetic information as it is processed by cells during replication, transcription, and translation. These parameters could permit a detailed analysis of the evolutionary changes hypothesized to underlie neoplastic development.

Animals

Uncertainty/information as measure of various urographic parameters: an information theory model of diagnosis of renal masses.

A new decision model for differentiating renal masses by urographic criteria has been developed and tested to demonstrate the use of uncertainty/information as a measure. The conditional probabilities used in this model are the relative frequency of occurrence of 15 specific uroradiographic signs in the presence of cyst, tumor, and benign cortical nodule. The decision model was applied to data obtained at the time of initial interpretation of 80 cases of renal mass discovered on urography. The probability of diagnosis was calculated by computer and compared to the radiologist's subjective probability estimate made prospectively at the time of initial interpretation. Information theory was applied to optimize the sequence in which signs were evaluated. The signs likely to maximally reduce the uncertainty of a diagnosis were evaluated first. The utility of this model and the comparative significance of various urographic signs used diagnose renal cysts, tumors, and benign cortical nodules were assessed. This model of renal mass evaluation at urography demonstrates principles of information theory that can be applied to more difficult and complex diagnostic and management problems.

Decision Making

Further developments of protein secondary structure prediction using information theory. New parameters and consideration of residue pairs.

We have re-evaluated the information used in the Garnier-Osguthorpe-Robson (GOR) method of secondary structure prediction with the currently available database. The framework of information theory provides a means to formulate the influence of local sequence upon the conformation of a given residue, in a rigorous manner. However, the existing database does not allow the evaluation of parameters required for an exact treatment of the problem. The validity of the approximations drawn from the theory is examined. It is shown that the first-level approximation, involving single-residue parameters, is only marginally improved by an increase in the database. The second-level approximation, involving pairs of residues, provides a better model. However, in this case the database is not big enough and this method might lead to parameters with deficiencies. Attention is therefore given to overcoming this lack of data. We have determined the significant pairs and the number of dummy observations necessary to obtain the best result for the prediction. This new version of the GOR method increases the accuracy of prediction by 7%, bringing the amount of residues correctly predicted to 63% for three states and 68 proteins, each protein to be predicted being removed from the database and the parameters derived from the other proteins. If the protein to be predicted is kept in the database the accuracy goes up to 69.7%.

Amino Acid Sequence