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Dependence on saturation of average minimum resolution in two-dimensional statistical-overlap theory: peak overlap in saturated two-dimensional separations.

A theory is proposed for the dependence on saturation of the average minimum resolution R(*) in point-process statistical-overlap theory for two-dimensional separations. Peak maxima are modelled by clusters of overlapping circles in hexagonal arrangements similar to close-packed layers. Such clusters exist only for specific circle numbers, but equations are derived that facilitate prediction of equivalent cluster properties for any number of circles. A metric is proposed for the average minimum resolution that separates two such clusters into two maxima. From this metric, the average minimum resolution of the two nearest-neighbor single-component peaks (SCPs)--one in each cluster--is calculated. Its value varies with the number of SCPs in both clusters. These resolutions are weighted by the probability that the two clusters contain the postulated numbers of SCPs and summed to give R(*), which decreases with increasing saturation. The dependence of R(*) on saturation is combined with a theory correcting the probability of overlap in a reduced square for boundary effects. The numbers of maxima in simulations of 75, 150, and 300 randomly distributed bi-Gaussians having exponential heights and aspect ratios of 1, 30, and 60 are compared to predictions. Excellent agreement between maxima numbers and theory is found at low and high saturation. Good estimates of the numbers of bi-Gaussians in simulations are calculated by fitting theory to numbers of maxima using least-squares regression. The theory is applied to mimicked GC x GCs of 93 compounds having many correlated retention times, with predictions that agree fairly well with maxima numbers.

Chromatography↗

Epigenesis theory: a mathematical model relating causal concepts of pathogenesis in individuals to disease patterns in populations.

A mathematical modeling approach called epigenesis theory is presented which relates three aspects of pathogenesis to the population distribution of disease. The three aspects of pathogenesis involve how two or more measured variables interact. They are 1) whether the measured variables are related to the same causal action, 2) whether there is only one pathogenic process leading to disease, and 3) whether the measured variables contribute to the same pathogenic process. Epigenesis theory defines the following multivariable relations between two disease causes: 1) "Complementary" causes contribute different causal actions to the sole pathogenic process leading to disease. They have multiplicative relations. 2) "Separate process" causes contribute different causal actions to different pathogenic processes. They have the relations of simple independent action which are slightly less than additive. 3) "Intermediate" causes contribute different causal actions to the same pathogenic process in the presence of additional pathogenic processes where at most one of them may also participate. They have relations somewhere between multiplicative and simple independent actions. 4) "Cooperative-competitive" causes share the same causal action and act within the same pathogenic process. Their relations can change from greater than multiplicative to less than simple independent action at increasing dichotomization points of the measured variables. Epigenesis theory unifies the sufficient-component causes model and the simple independent action model and exceeds either model in the range of observations it can explain. It is most useful given directly causal measured variables and specific disease outcomes, but it will assist in etiologic investigations of nonspecific outcomes in which new disease classifications are proposed. While it is less useful given surveillance-type variables such as age or sex or outcomes resulting from numerous pathogenic processes such as death, it gains utility as more causal variables are entered into an analysis and as more cut points of continuous complementary, independent, or intermediate variables are distinguished.

Adult↗

Decision theoretic steering and genetic algorithm optimization: application to stereotactic radiosurgery treatment planning.

Treatment planning for stereotactic radiosurgery and fractionated radiotherapy is currently a labor intensive, operator-dependent process. Many degrees of freedom exist to make rigorous optimization intractable except by computationally intelligent techniques. The quality of a given plan is determined by an aggregate of clinical objectives, most of which are subject to competing tradeoffs. In this work, we present an autonomous scheme that couples decision theoretic guidance with a genetic algorithm for optimization. Ordinal ranking among a population of viable treatment plans is based on a generalized distance metric, which promotes a decreasing hyperfrontier of the efficient solution set. The solution set is driven toward efficiency by the genetic algorithm, which uses the tournament selection mechanism based on the ordinal ranking. Goals and satisficing conditions can be defined to signal the ultimate and the minimum achievement levels in a given objective. A conventionally challenging case in radiosurgery was used to demonstrate the practical utility and the problem-solving power of the decision theoretic genetic algorithm. Treatment plans with one isocenter and four isocenters were derived under the autonomous scheme and compared to the actual treatment plan manually optimized by the expert planner. Quality assessment based on dose-volume histograms and normal tissue complication probabilities suggested that computational optimization could be driven to offer varying degrees of dosimetric improvement over a human-guided optimization effort. Furthermore, it was possible to achieve a high degree of isodose conformity to the target volume in computational optimization by increasing the degree of freedom in the treatment parameters. The time taken to derive an efficient planning solution was comparable and usually shorter than in the manual planning process, and can be scaled down almost linearly with the number of processors. Overall, the autonomous genetic algorithm scheme was found to be powerful and versatile as a computationally intelligent counterpart to human-guided strategies in treatment optimization for stereotactic radiosurgery and radiotherapy.

Algorithms↗

Applications and extensions of subpopulation theory: a caseworkers guide.

This paper extends the calculation of conditional probabilities from those given by Balding and Nichols to casework situations where a series of possible DNA types are possible. Such situations may occur when a sample is identified containing a mixture of DNA from two or more people or where extra information can be determined about the subpopulation under consideration by analysis of additional samples. Using this approach, the error in the estimated likelihood ratios is expected to reduce as the number of additional individuals typed from the subpopulation increases.

Forensic Medicine↗

Peculiarities of magnetic and spin effects in a biradical/stable radical complex (three-spin system). Theory and comparison with experiment.

The field dependencies of biradical recombination probability in the presence of paramagnetic species with spins S(3) = 1 and S(3) = (1)/(2) have been calculated in the framework of the density matrix formalism. To describe the effect of the "third" spin on the spin evolution in biradical, we have also considered the spin exchange interaction between the added spin and one of the paramagnetic biradical centers. A characteristic feature of the calculated field dependencies is the existence of several extrema with positions and magnitudes depending on the signs and values of the exchange integrals in the system. The method proposed can be used to describe the effect of spin catalysis. It is shown that for the system with the third spin S(3) = 1 spin catalysis manifests itself stronger than in the case of spin S(3) = (1)/(2). The dependence of spin catalysis efficiency on the exchange interaction with the third spin has an extremum with position independent of the value of the spin added.

Journal Article↗

The economics of 'more research is needed'.

BACKGROUND: Results from epidemiology and other health research affect millions of life-years and billions of dollars, and the research directly consumes millions of dollars. Yet we do little to assess the value of research projects for future policy, even amid the ubiquitous assertions that 'more research is necessary' on a given topic. This methodological proposal outlines the arguments for why and how ex ante assessments can inform us about the value of a particular piece of further research on a topic. METHODS: Economics and decision theory concepts-cost-benefit analysis and probability-weighted predictions of outcomes-allow us to calculate the payoff from applied health research based on resulting decisions. Starting with our probability distribution for the parameters of interest, a Monte Carlo simulation generates the distribution of outcomes from a particular new study. Each true value and outcome are associated with a policy decision, and improved decisions are valued to give us the study's contribution as applied research. RESULTS: The analysis demonstrates how to calculate the expected value of further research, for a simplified case, and assess whether it is really warranted. Perhaps more important, it points out what the measure of the value of a further study ought to be. CONCLUSIONS: It is quite possible to improve our technology for assessing the value of particular pieces of further research on a topic. However, this will only happen if the need and possibility are recognized by methodologists and applied researchers.

Cost-Benefit Analysis↗

Children and chess expertise: the role of calibration.

Three studies of calibration are reported. Calibration refers to the accuracy with which one can predict one's own performance. In the first study child chess players, non-chess playing parents, and statistics students were asked to predict chances of winning chess games against hypothetical opponents. These subjective probabilities were compared to the actual probabilities, based on the Elo rating system. Better players' predictions were better calibrated. Confidence and ratings are negatively correlated, indicating that with lower ratings, players re overconfident. Skilled child players' predictions were better calibrated than any of the adults'. In the second study subjects were asked to estimate chances of winning in conjunctive situations, e.g., winning all the rounds in a tournament. Again, better child players were more accurate in their predictions and more accurate than adults. In the third study, child players were asked to predict their chances of winning in a non-chess domain after hearing a hypothetical win/loss history. Higher-rated players' predictions were again better calibrated, even though the domain was outside their expertise. The motivational and cognitive implications of calibration are discussed.

Achievement↗

An analysis of the value of additional diagnostic procedures.

When several diagnostic procedures are performed on a patient, the probability of his having or not having a specific ailment will change as the result of each procedure is known. This paper describes how such a change is readily calculated using Bayes' theorem. Information theory is also used to find the increment in information from each successive test. Numerical estimates are made using data pertinent to lung X-ray examinations. Finally, some implications for diagnostic examinations in general are drawn.

Bayes Theorem↗

Panic attacks during sleep: a hyperventilation-probability model.

Panic attacks during sleep are analysed in terms of a hyperventilation theory of panic disorder. The theory assumes that panic attacks during sleep are a manifestation of severe chronic hyperventilation, a dysfunctional state in which renal compensation has led to a relatively steady state of diminished bicarbonate. Reductions in respiration during deep non-REM sleep lead to respiratory acidosis which triggers hyperventilatory hypocapnea and subsequent panic. A probability model designed to predict when during sleep panic attacks are likely to occur is supported by relevant data from studies of sleep and panic attacks. Implications for treatment are discussed.

Carbon Dioxide↗

Is the theory of planned behavior a useful framework for understanding exercise adherence during phase II cardiac rehabilitation?

PURPOSE: This study evaluated the theory of planned behavior (TPB) as a framework for understanding exercise adherence during phase II cardiac rehabilitation (CR). METHODS: A total of 215 patients completed a baseline questionnaire that included the TPB constructs and past exercise. Exercise adherence was measured via program attendance during phase II CR. RESULTS: Hierarchic regression analyses indicated that attitude, subjective norm, and perceived behavioral control (PBC) explained 30% of the variance in exercise intention, with attitude, subjective norm, and PBC each making significant unique contributions to intention. Furthermore, exercise intention explained 12% of the variance in exercise adherence. Finally, the behavioral, normative, and control beliefs provided novel information concerning why patients in phase II CR hold certain attitudes, subjective norms, PBC, and exercise intentions. CONCLUSION: Results of the present study provide evidence that the TPB is a useful framework for understanding exercise intentions and adherence during phase II CR.

Aged↗

An information theoretic approach for non-rigid image registration using voxel class probabilities.

We propose two information theoretic similarity measures that allow to incorporate tissue class information in non-rigid image registration. The first measure assumes that tissue class probabilities have been assigned to each of the images to be registered by prior segmentation of both of them. One image is then non-rigidly deformed to match the other such that the fuzzy overlap of corresponding voxel object labels becomes similar to the ideal case whereby the tissue probability maps of both images are identical. Image similarity is assessed during registration by the divergence between the ideal and actual joint class probability distributions of both images. A second registration measure is proposed that applies in case a segmentation is available for only one of the images, for instance an atlas image that is to be matched to a study image to guide the segmentation thereof. Intensities in one image are matched to the fuzzy class labels in the other image by minimizing the conditional entropy of the intensities in the first image given the class labels in the second image. We derive analytic expressions for the gradient of each measure with respect to individual voxel displacements to derive a force field that drives the registration process, which is regularized by a viscous fluid model. The performance of the class-based measures is evaluated in the context of non-rigid inter-subject registration and atlas-based segmentation of MR brain images and compared with maximization of mutual information using only intensity information. Our results demonstrate that incorporation of class information in the registration measure significantly improves the overlap between corresponding tissue classes after non-rigid matching. The methods proposed here open new perspectives for integrating segmentation and registration in a single process, whereby the output of one is used to guide the other.

Algorithms↗

An information theory model of hydrophobic interactions.

A molecular model of poorly understood hydrophobic effects is heuristically developed using the methods of information theory. Because primitive hydrophobic effects can be tied to the probability of observing a molecular-sized cavity in the solvent, the probability distribution of the number of solvent centers in a cavity volume is modeled on the basis of the two moments available from the density and radial distribution of oxygen atoms in liquid water. The modeled distribution then yields the probability that no solvent centers are found in the cavity volume. This model is shown to account quantitatively for the central hydrophobic phenomena of cavity formation and association of inert gas solutes. The connection of information theory to statistical thermodynamics provides a basis for clarification of hydrophobic effects. The simplicity and flexibility of the approach suggest that it should permit applications to conformational equilibria of nonpolar solutes and hydrophobic residues in biopolymers.

Journal Article↗

Analysis of symbolic sequences using the Jensen-Shannon divergence.

We study statistical properties of the Jensen-Shannon divergence D, which quantifies the difference between probability distributions, and which has been widely applied to analyses of symbolic sequences. We present three interpretations of D in the framework of statistical physics, information theory, and mathematical statistics, and obtain approximations of the mean, the variance, and the probability distribution of D in random, uncorrelated sequences. We present a segmentation method based on D that is able to segment a nonstationary symbolic sequence into stationary subsequences, and apply this method to DNA sequences, which are known to be nonstationary on a wide range of different length scales.

Computational Biology↗

Assessment of agreement under nonstandard conditions using regression models for mean and variance.

The total deviation index of Lin and Lin et al. is an intuitive approach for the assessment of agreement between two methods of measurement. It assumes that the differences of the paired measurements are a random sample from a normal distribution and works essentially by constructing a probability content tolerance interval for this distribution. We generalize this approach to the case when differences may not have identical distributions -- a common scenario in applications. In particular, we use the regression approach to model the mean and the variance of differences as functions of observed values of the average of the paired measurements, and describe two methods based on asymptotic theory of maximum likelihood estimators for constructing a simultaneous probability content tolerance band. The first method uses bootstrap to approximate the critical point and the second method is an analytical approximation. Simulation shows that the first method works well for sample sizes as small as 30 and the second method is preferable for large sample sizes. We also extend the methodology for the case when the mean function is modeled using penalized splines via a mixed model representation. Two real data applications are presented.

Likelihood Functions↗

Stochastic particle formulation of the vesicle hypothesis. Relevance to short-term phenomena.

Based on the vesicle hypothesis, the modes of elementary quantum-vesicle interactions have been formulated in terms of probabilities of induced and spontaneous interstate quanta transitions and generalized within the framework of the previously developed theory of the double barrier synapse. Among the three allowed states for a quantum, the transition state is a novel formulation for the fraction of immediately available quanta governed by both vesicle and presynaptic membranes. The parameters of the model were determined by fitting solutions to the experimental curves representing effects of single pulse and short train activation on transmitter release at the frog neuromuscular junction. Qualitative differences in particle physics of transmitter release found under low quantal outputs on one hand and normal transmission on the other allowed the formulation of the uncertainty hypothesis and the quantum condition of synaptic homeostasis.

Computer Simulation↗

Two-generation analysis of pollen flow across a landscape. III. Impact of adult population structure.

The rate and distance of instantaneous pollen flow in a population are parameters of considerable current interest for plant population geneticists and conservation biologists. We have recently developed an estimator (phi ft) of differentiation between the inferred pollen clouds that fertilize several females, sampled within a single population. We have shown that there is a simple relation between phi ft and the average pollen dispersal distance (delta) for the case of a population with no geographic structure. Though forest trees usually show considerable pollen flow, assuming an absence of spatially distributed genetic structure is not always wise. Here, we develop analytical theory for the relation between phi ft and delta, for the case where the probability of Identity by Descent (IBD) for two individuals decreases with the physical distance between them. This analytical theory allows us to provide an effective method for estimating pollen dispersal distance in a population with adult genetic structure. Using real examples, we show that estimation errors can be large if genetic structure is not taken into account, so it is wise to evaluate adult genetic structure simultaneously with estimation of phi ft for the pollen clouds. We show that the results are only moderately affected by changes in the decay function, a result of some importance since no completely established theory is available for this function.

Genetics, Population↗

A conceptual framework to study the use of nursing care plans.

Value-expectancy theory proposed by Lewin states that motivation for behaviour is based on the probability that a given action or behaviour will achieve a valued or desired outcome. Becker and Maiman elaborated on this theory and developed a model to study compliance by considering the influence of sociobehavioural determinants in the inter-relationship of motivating and modifying factors which dictate human behaviour. The Becker-Maiman framework was used to determine factors which influence the use of the nursing care plan by staff nurses. From interviews with staff nurses, surveys of nurses attending workshops on NCPs and review of literature a model was developed for use in examining the nursing care planning behaviour of nurses.

Accreditation↗

Cell symbiosis [correction of symbioisis] theory: status and implications for the fossil record.

Recent geological treatises have presented three alternative models of the origins of eukaryotes as if they merited equal treatment. However, modern biological techniques, especially nucleic acid and protein sequencing, have clearly established the validity of the symbiotic theory of the origin of eukaryotic organelles. The serial endosymbiotic theory in its most extreme form states that three classes of eukaryotic cell organelles (mitochondria, plastids and undulipodia) originated as free-living bacteria (aerobic respirers, phototrophic bacteria and spirochetes respectively) in association with hosts that become the nucleocytoplasm (Thermoplasma-like archaebacterial hosts). Molecular biological information, primarily derived from ribosomal RNA nucleotide sequencing studies leads to the conclusion that the symbiotic origin theory for both mitochondria and plastids has been proven. The probability of an ancestral archaebacterial-Thermoplasma-like host for the nucleocytoplasm has been rendered more likely by discoveries by Dennis Searcy and his colleagues and Carl Woese and his colleagues. The most equivocal postulate of the symbiotic theory, the origin of undulipodia (cilia and other organelles of motility that develop from kinetosomes is under investigation now. The status of these postulates, as well as their implications for the fossil record, is briefly summarized here.

Bacteria↗