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Amplitude variations in P300 component due to unpredictable stepwise change of stimulus probability.

The present study investigates whether the amplitude of the P300 in 'normal' subjects adapts to unexpected changes in global stimulus probability. The adaptation level (AL) metrics (in terms of Helson's [1964] theory) was applied to explain the variations in the P300 amplitude. In an oddball paradigm the probability of the deviant tone (target 1000 Hz, 80 dB, 50 ms) occurring randomly in a train of standard ones (non-target 1100 Hz, 80 dB, 50 ms) was changed in a stepwise way from 0.5 to 0.3 and then to 0.1 in 3 blocks without interruption of the stimulus presentation. Two experiments were performed. In the first one the subjects did not receive any prior information about the changes in the stimulus probability, whereas in the second experiment they were aware of such changes. The task always required the subject to silently count the deviants. EEG was recorded monopolarly from Fz, Cz and Pz in a total of 15 subjects. The block averaged P300 increased monotonically with probability, the increase being larger in Expt. II. In contrast to the block averaged P300, the variations in the P300 amplitude following the abrupt change in probability showed a non-linear dependency. On the basis of the AL a simulation of the time course of the P300 variations with probability was performed and a clear similarity between the simulated P300 and the experimental data was found. Some properties of the AL model are discussed.

Acoustic Stimulation

Fixation probability in spatially changing environments.

The fixation probability of a mutant in a subdivided population with spatially varying environments is investigated using a finite island model. This probability is different from that in a panmictic population if selection is intermediate to strong and migration is weak. An approximation is used to compute the fixation probability when migration among subpopulations is very weak. By numerically solving the two-dimensional partial differential equation for the fixation probability in the two subpopulation case, the approximation was shown to give fairly accurate values. With this approximation, we show in the case of two subpopulations that the fixation probability in subdivided populations is greater than that in panmictic populations mostly. The increase is most pronounced when the mutant is selected for in one subpopulation and is selected against in the other subpopulation. Also it is shown that when there are two types of environments, further subdivision of subpopulations does not cause much change of the fixation probability in the no dominance case unless the product of the selection coefficient and the local population size is less than one. With dominance, the effect of subdivision becomes more complex.

Biological Evolution

The prior probability of autosomal linkage.

An expression is derived for the prior probability of linkage between a random trait locus and any one of m random marker loci, and this probability is computed form=1, 10, 20, 30, 50 and 100. A similar expression is derived for two trait loci, and computed for m=1, 10, 20 and 30. When one trait locus and 30 marker loci are being studied, a priori there is over a three-quarter probability that the trait locus should be syntenic with at least one of the markers, and about a one-half probability that there should be a linkage mappable from recombination frequencies. If two traits are studied, then the prior probability that at least one should be syntenic with one of the 30 markers is 0-94, and there is a three-quarter probability that such a linkage should be mappable.

Chromosome Mapping

Clinical assessment of the probability of coronary artery disease: judgmental bias from personal knowledge.

Probability estimates of angiographic coronary artery disease made by experienced, board-certified staff cardiologists were compared with those of cardiologists in training (fellows). In addition, estimates made before coronary angiography were compared with those made several months later based on written clinical summaries of 15 items of objective clinical and test data. Cardiologists were asked to estimate the probabilities of coronary artery disease, multivessel disease, and triple-vessel or left main disease. The study population consisted of 510 consecutive patients without valvular disease referred for the first time for coronary angiography to three hospitals. Both staff and fellows consistently overestimated the pre-angiographic probability of coronary artery disease. The probabilities estimated from patient summaries were always significantly lower than the pre-angiographic assessments. Only staff cardiologists reliably assessed the probabilities of coronary artery disease during the second assessment (p less than 0.05). Thus, estimates of disease probability based on clinical judgment vary according to the source of information, and these estimates are more accurate when physicians have objective data on hand and do not know the identities of the patients.

Coronary Angiography

[The initial clinical probability in the diagnosis of the hospitalized pediatric patient].

OBJECTIVES: 1. To determine the degree of correlation among different physicians concerning their initial diagnosis and 2. identify the degree of correlation between the probability that physicians assing an initial diagnosis and the number of days the patient is hospitalized, laboratory test and X-rays taken of the patient. DESIGN: A comparative questionnaire. STUDY SITE: Pediatric hospitalization Unit of a third level medical care ward of the Mexican Social Security Institute. STUDY UNITS: All new admissions or non-programmed readmitted patients to the hospital during the months of November and December 1990. MAIN MEASUREMENTS: The treating physicians (Staff pediatricians (MB) and third (R3) and second (R2) year residents) were each asked to independently assign a probability (0 to 100) to each of the diagnosis emitted on the day the patient was admitted. When the patient was discharged, the number of days hospitalized as well as the number of laboratory tests and X-rays taken of the patient were added. RESULTS: 106 patients were evaluated, a correlation was gathered between MBs and R3s of 0.79 (P less than 0.001) and among MBs and R2s of 0.83 (P less than 0.001). The correlation between resident physicians was discretely less 0.60 (P less than 0.01). When relating the probability assigned by the physicians and the number of days the patients were hospitalized, associations were observed of 0.31 (P less than 0.05), 0.15 (P less than 0.05) and 0.19 (P = 0.04) for the MB, R3 and R2s respectively. In the case of laboratory test a correlation of 0.38, 0.06 and 0.04 (MB, R3, R2 respectively) was found. None of these correlations were statistically significant. The X-rays showed a significant correlation in cases of the MBs (0.50, P less than 0.05). CONCLUSIONS: The probabilities assigned by the staff physician as well as the resident doctors are closely related and a lesser grade of association is seen when comparing the residents among each other. No tendencies were identified in the correlation of the probability assigned by the residents and the variables analyzed. A consistent relation was seen between the staff physician and high probabilities, longer stays, and greater number of laboratory tests and X-rays.

Adult

An application of probability theory to a group of breath-alcohol and blood-alcohol data.

Many jurisdictions have "per se" driving-while-intoxicated (DWI) status expressed in terms of a blood-alcohol concentration (BAC) standard (in grams per 100 mL or the equivalent). Since breath-alcohol (BrAC) analysis is typically employed to determine BAC, there is often challenge to the use of an assumed 2100:1 conversion ratio. This concern may be relevant in light of considerable data that show a low percentage of cases in which BrAC greater than BAC, and this concern increases when the BrAC is used to predict BAC in the context of "per se" legislation. Probability theory provides a basis for estimating the likelihood of an individual having a BrAC greater than or equal to g/210 L with a corresponding BAC less than 0.10 g/100 mL. Actual field data from the state of Wisconsin (n = 404) were evaluated to determine the probability of this occurrence. The probability for this occurrence involves the multiplication law for independent events. The computed probability from the data was 0.018. The actual number of occurrences where BrAC greater than or equal to 0.10 g/210 L and BAC less than 0.10 g/100 mL was 5, resulting in a probability of 0.012. The concern of having BrAC greater than BAC at the critical "per se" level has a very low probability of occurrence, which thus supports the reasonableness of "per se" DWI legislation based upon a blood-alcohol standard determined by breath-alcohol analysis.

Alcoholic Intoxication

Application of the response probability density function technique to biodynamic models.

A method has been developed, which we call the "response probability density function technique," which has applications in predicting the probability of injury in a wide range of biodynamic situations. The method, which was developed in connection with sonic boom damage prediction, utilized the probability density function of the excitation force and the probability density function of the sensitivity of the material being acted upon. The method is especially simple to use when both these probability density functions are lognormal. Studies thus far have shown that the stresses from sonic booms, as well as the strengths of glass and mortars, are distributed lognormally. Some biodynamic processes also have lognormal distributions and are, therefore, amenable to modeling by this technique. In particular, this paper discusses the application of the response probability density function technique to the analysis of the thoracic response to air blast and the prediction of skull fracture from head impact.

Animals

Radiation risk of tissue late effects, a net consequence of probabilities of various cellular responses.

Late effects from the exposure to low doses of ionizing radiation are hardly or not at all observed in man probably due to the low values of risk coefficients that preclude statistical analyses of data from populations that are exposed to doses less than 0.2 Gy. In order to arrive at an assessment of potential risk from radiation exposure in the low dose range, the microdosimetry approach is essential. In the low dose range, ionizing radiation generates particle tracks, mainly electrons, which are distributed rather heterogenously within the exposed tissue. Taking the individual cell as the elemental unit of life, observations and calculations of cellular responses to being hit by energy deposition events from low LET type are analysed. It emerges that besides the probability of a hit cell to sustain a detrimental effect with the consequence of malignant transformation there are probabilities of various adaptive responses that equip the hit cell with a benefit. On the one hand, an improvement of cellular radical detoxification was observed in mouse bone marrow cells; another adaptive response pertaining to improved DNA repair, was reported for human lymphocytes. The improved radical detoxification in mouse bone marrow cells lasts for a period of 5-10 hours and improved DNA repair in human lymphocytes was seen for some 60 hours following acute irradiation. It is speculated that improved radical detoxification and improved DNA repair may reduce the probability of spontaneous carcinogenesis. Thus it is proposed to weigh the probability of detriment for a hit cell within a multicellular system against the probability of benefit through adaptive responses in other hit cells in the same system per radiation exposure. In doing this, the net effect of low doses of low LET radiation in tissue with individual cells being hit by energy deposition events could be zero or even beneficial. Since there was no simple additivity of equal effects from repeated exposures to equal doses and because of the potential effect of adaptive cell responses on the spontaneous evolution of malignancy in tissue, the extrapolation of risk with absorbed dose reaching down to zero, does not appear to be generally valid.

Cell Survival

Exact computation of pattern probabilities in random sequences generated by Markov chains.

Observed patterns in macromolecular sequences are often considered as words and compared with their probabilities of occurring in random sequences. Calculation of these probabilities, however, often lacks rigour. We have developed an algorithm for exact computation of such probabilities for stochastic sequences that follow a Markov chain model. The method is applicable to the case that a random sequence contains one out of two given patterns P and Q, or both simultaneously. Another application yields the probability function P(x) that a sequence contains pattern P exactly x times. An application to patterns that include wild-card characters yields probabilities for homonucleotide clusters of a given length. We prove the probability of multiple runs of single nucleotides in the SV40 genome to be in accordance with the dinucleotide composition of the sequence, although it is in conflict with mononucleotide composition.

Algorithms

Relation of physicians' predicted probabilities of pneumonia to their utilities for ordering chest x-rays to detect pneumonia.

To investigate the relation between physicians' predicted probabilities of pneumonia and their utilities for ordering chest x-rays to detect pneumonia, the authors studied 52 physicians who ordered chest x-rays of 886 patients presenting to an emergency department with fever or respiratory complaints. Physicians estimated the probability of pneumonia prior to obtaining the results of the chest x-ray. Utilities were assessed by asking physicians to consider a hypothetical patient presenting with acute respiratory symptoms, with unknown chest x-ray status, and to rank on a scale from +50 ("best thing I could do") to -50 ("worst thing I could do") their rating scale utilities for not diagnosing pneumonia and not ordering a chest x-ray when the patient had pneumonia (i.e., missing a pneumonia), and for diagnosing pneumonia and ordering a chest x-ray when the patient did not have pneumonia (i.e., ordering an unnecessary x-ray). The utility for ordering an unnecessary x-ray was negatively correlated with average predicted probability (r = -0.1495, p = 0.29), whereas the utility for missing a pneumonia was positively correlated with average predicted probability (r = 0.2254, p = 0.11), although the correlations were not statistically significant. Relative chagrin, defined as the difference in these utilities, was significantly inversely correlated with average predicted probability (r = -0.2992, p less than 0.035), even after adjusting for the prevalence of pneumonia seen by each physician (partial r = -0.42, p less than 0.0027). It is concluded that physicians who experienced greater regret over missing a pneumonia than over ordering an unnecessary x-ray estimated lower probabilities of pneumonia for patients for whom they ordered x-rays.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost-Benefit Analysis

Worldwide variations in the lifetime probability of reproductive cancer in women: implications of best-case, worst-case, and likely-case assumptions about the effect of oral contraceptive use.

Cancer incidence in countries representative of three patterns of reproductive cancer and age-specific mortality was used to estimate the effect of oral contraceptive use on the lifetime probability of reproductive cancer under three sets of assumptions about the effects of oral contraceptives. Under the set of assumptions considered likely, oral contraceptives were estimated to reduce or increase only slightly the lifetime probability of any reproductive cancer in each setting. Under worst-case assumptions, oral contraceptives were estimated to increase the lifetime probability of reproductive cancer only modestly in settings with low cancer rates and in settings with high rates of breast, ovarian, and endometrial cancer, but it might have a large impact on lifetime probability of reproductive cancer in settings with high cervical cancer rates. Under best-case assumptions, oral contraceptives were estimated to decrease the lifetime probability of reproductive cancer in each setting; this reduction was estimated to be greatest in settings where endometrial and ovarian cancer incidence are high.

Adolescent

Anticipatory HR deceleration as a function of perceived control and probability of aversive loud noise: a deployment of attention account.

Five groups of 10 undergraduate subjects each participated in an experiment to examine the effects of perceived control over, and the probability of occurrence of, noxious (white-noise) stimulation on anticipatory heart rate (HR) deceleration. All groups performed an arithmetic task, the numbers for which were changed on each of the 20 trials, but three groups were defined as active groups since they were instructed that the occurrence of noxious stimulation was contingent upon their performance on the task. The actual probability of occurrence of noxious stimulation (i.e., either 0.9, 0.5 or 0.1) was manipulated between these three groups. A fourth (passive) group (0.5 probability of occurrence) was instructed as to the non-contingent relationship between performance and the aversive white noise. The last group was a control group which only performed the task, and thus both provided an estimate of the rate of return to baseline following the expected HR acceleration to the task and eliminated the need for a within-subject control period to assess HR deceleration. The results indicated that all active and passive groups produced significant HR decelerations, relative to the control group, prior to the noxious stimulus. However, all active groups (regardless of probability levels) displayed significantly greater, and required more trials to maximally develop, anticipatory deceleration than the passive group. In addition, the results for the active groups revealed a direct relationship between the probability of occurrence of noxious stimulation and the magnitude of anticipatory deceleration. It is argued that the results cannot be adequately accommodated by the preparatory-adaptive-response theory. A deployment-of-attention account is suggested since it appears both to account for the obtained pattern of results completely and to generate additional testable predictions for the future.

Adaptation, Psychological

"Upstream" regulation of the release probability in sympathetic nerve varicosities.

The results appear to support the following tentative working hypothesis. (1) Nerve impulse-induced transmitter release from sympathetic nerve varicosities is monoquantal and highly intermittent (probability range: 0-0.03). (2) Nerve impulses invade varicosities as all-or-none, Na+ channel-dependent action potentials; invasion failure may be rare. (3) The release probability is not controlled by properties (amplitude or duration) of the invading action potential or the resulting Ca2+ current, but by the availability of an as yet unidentified permissive factor. (4) The permissive factor is actively transported intra-axonally, probably in association with organelles (LDVs?). (5) The activation and/or transport of the permissive factor are controlled "upstream" of the varicosity; they depend on Ca2+ influx through channels insensitive to nifedipine (hence, not of L-type) but blocked by Cd2+ and apparently opened by slight depolarization of the resting membrane, in this respect behaving more as T- than N-type channels. (6) A high resting K+ efflux "upstream" of the varicosity restricts the availability of the permissive factor; it is the main mechanism maintaining the (economically necessary) low release probability. (7) Prejunctional agonists do not inhibit transmitter secretion by causing a conduction block or by reducing the action potential-induced Ca2+ influx into the varicosity itself, but by depressing the Ca2(+)-dependent activation and/or transport of the permissive factor; they act at least in part via receptors "upstream" of the varicosity. (8) This hypothesis for regulation of the release probability in sympathetic nerves may apply, at least in part, to other neurons as well.

Animals

Statistical mechanical treatment of protein conformation. 6. Elimination of empirical rules for prediction by use of a high-order probability. Correlation between the amino acid sequences and conformations for homologous neurotoxin proteins.

One-dimensional short-range interaction models for specific-sequence copolymers of amino acids have been developed in this series of papers. In this paper, a general method for predicting protein conformation (that is based on a one-dimensional short-range interaction model, and eliminates the need for the empirical rules introduced in papers III and IV) is described. The present method involves the use of conformational (or conformational-sequence) probabilities of higher order than the first- or second-order probabilities used in papers IV and V, i.e., it treats a sequence of any number of residues; it thus alters the predictive methods that involved empirical rules in papers III and IV, and low-order (first- or second-order) probabilities in papers IV and V. The general method is applied here to the prediction of the backbone conformations of proteins, using the three-state model [helical (h), extended (epilson), and other coil (c) states] proposed in the theoretical formulation of paper II. The statistical weights in the three-state model are evaluated from the atomic coordinates of the x-ray structures of 26 proteins. The conformational-sequence probabilities (taken for three consecutive residues for numerical computation in this paper) are calculated for all possible triads (i.e., for all possible combinations of the three states, h, epilson, and c for each residue) for bovine pancreatic trypsin inhibitor and clostridial flavodoxin, in order to select the most probable conformations of these proteins. The predicted results for these proteins are compared to those predicted in paper III and to those observed experimentally. The method is applied further to the prediction of the backbone structures of homologous neurotoxin proteins whose amino acid sequences are known but whose x-ray structures are not. The effects of variation in the amino acid sequence on the conformations of the backbones are discussed from the point of view of the homologies in the amino acid sequences of 19 neurotoxins. Application of the present general predictive method to a four- and a multistate model is also described.

Amino Acid Sequence

Taking attention to task: P300, task response probability, and within-category deviation detection.

Previously, we reported enhanced P3 amplitudes to between-category deviations among high and low probability events. Here, we tested the effects of a within-category difference. Subjects performed a go/no-go button press task as they viewed repeated, randomly-ordered presentations of nine double-digit numbers. Eight numbers fell within a prescribed range (42-49, standards); prior to testing, subjects selected one standard number for later recall. A ninth, out-of-range (91, deviant) number was also included. Subjects were tested under two conditions, in which they responded either to one (low response probability) or to seven (high response probability) standard nonselected numbers, designated as targets. Relatively larger P3s were consistently apparent only when the deviant nontarget was associated with a low probability response to a nontarget. There was a selective effect of nontarget response probability on P3 amplitude to the deviant nontarget. Our results indicate that within-category deviation detection is facilitated by "controlled" attention to the structure of the stimulus field.

Adolescent

Probabilities of transversions and transitions.

The values of the mean relative probabilities of transversions and transitions have been refined on the basis of the data collected by Jukes and found to be equal to 0.34 and 0.66, respectively. Evolutionary factors increase the probability of transversions to 0.44. The relative probabilities of individual substitutions have been determined, and a detailed classification of the nonsense mutations has been given. Such mutations are especially probable in the UGG (Trp) codon. The highest probability of AG, GA transitions correlates with the lowest mean change in the hydrophobic nature of the amino acids coded.

Amino Acids

The attainment of formal operations: a comparison of probability concepts in deaf and hearing adolescents.

In a series of six experiments deaf and hearing adolescents were compared on attainment of formal operations in Piaget's theory as represented by performance on probability problems. Performance of deaf subjects provided a desirable control comparison, since their knowledge of probability concepts was most likely acquired outside school classrooms. The probability problems were usually binary choice situations that required no verbalizations and were designed to illuminate strategies, as well as to indicate conceptual stage. Two experiments, one a long-term training study of over two years' duration, used supplementary preadolescent subject groups. Most of the hearing adolescents and many of the deaf adolescents attained the formal operatory level for probability concepts according to the criteria described by Piaget and Inheldermtheir criteria can be criticized, however, as insufficiently demanding, although they do point up the difficulty of defining the place of computational abilities in formal operationsmresults from several experiments suggested a second and higher level of formal operatory attainment around the ages of 14 to 15. Further theoretical insights were obtained regarding the implicit rules that frequently appeared to guide subjects' choices; a surprising variety of strategies were reported. Analysis of choice tendendies showed consistent avoidance of calculations and selection of the choice with the greatest absolute rather than relative frequency (or area) even when these strategies produced systematic errors. Subjects were generally unable to combine probability information from two different sources. In the long-term training experiment spontaneous improvement was shown by children at formal operatory ages even without training, but not by younger children. Deaf adolescents performed as well as hearing adolescents on easy problems, but they made more errors on several types of more difficult problems; Deaf adolescents were also less consistent than the hearing in use of rules, and in several experiments they showed a two- to three-year performance lag.

Achievement

[Investigation of algorithm for the calculation of probability of paternity likelihood using personal computer program, including the application to parentage testing in the decreased party].

Algorithm for the computerized calculation of probability of paternity likelihood was investigated. The probability is calculated by Essen-Möller's formula as W = X/(X+Y) = 1/(1 + Y/X). The X value is also given as X = Hl, m, n/Kl, m, where kl, m and Hl, m, n are the probabilities of mother-child and mother-child-father combinations, respectively. In this study, four functions as F(PQ) = [1-(P not equal to Q)] x p x q, Z(RS) = (1- (R = S)), K(PQ,RS) = 1/2([(R = P) + (R = Q)].s + [(S = P) + (S = Q)].r).F (PQ)/Z(RS) and H(PQ, RS, TU) = 1/4([(R = P) + (R = Q)] [(S = T) + (S = U)] + [(S = P) + (S = Q)] [(R = T) + (R = U)]) x F(PQ).F(TU)/Z(RS) were created, where PQ, RS and TU were the genotypes of mother, child and the alleged father, P, Q, R, S, T and U were their alleles, and p, q, r, s, t and u were the allele frequencies. The equality or inequality in parenthesis was the relation operator which gave -1 or 0 when the expression was true of false, respectively. Then, three formulae as Y = n sigma k = l F([TU]k), Kl, m = 1 sigma i = l m sigma j = l K ([PQ]i, [RS]j) and Hl, m, n = l sigma i = l m sigma j = l n sigma k = l H([PQ]i, [RS]j, [TU]k) were obtained, where [PQ]i, [RS]j and [TU]k were one of the mother's, one of the child's and one of the putative father's genotypes considered from their phenotypes, respectively. Using these formulae, the probability of paternity likelihood could be calculated in every case. These formulae were programmed in BASIC language using a personal computer. Algorithm for the calculation of the probability in the deceased party was also investigated.

Algorithms