Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Probability Theory”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 361 records · Page 20Linked to original sources

Emmetropization in the primate eye.

A theory to explain the mechanism of emmetropization of the human eye is reviewed and updated. The theory is probably also valid for the primate eye. It is proposed that the ciliary muscle-choroid layer behaves like a solid sheet of smooth muscle, so that it is able to resist part of the intraocular pressure and to regulate scleral stretch in the growing eye. It is suggested that the autonomic nervous system and stress play a role in the development of ametropia and that interference with the cortical-subcortical control of the ciliary muscle may prevent emmetropization.

Animals↗

Computations of post-inductive dynamics in axolotl heart formation.

This paper reports modelling of heart localization in the axolotl (Ambystoma mexicanum). The region of heart specification in the mesoderm defined by classical induction from the endoderm is larger than the area of final myocardial differentiation. For localizing the area of differentiation within the area of specification, we postulate a reaction-diffusion system that arises within the mesoderm in response to induction from the endoderm. This mechanism generates a spatial pattern for two chemicals, an activator and an inhibitor, corresponding to the area of myocardial differentiation. We postulate a diffusible chemical rescuer, which is absent in the cardiac lethal mutant, and which is a precursor to the reaction-diffusion mechanism. The activator, inhibitor, rescuer, and product of endodermal induction are presented in an enzyme mechanism with rate equations similar to the Gierer-Meinhardt equations. These equations were solved numerically in both one and two spatial dimensions. We have attained quantitative agreement with the experimental data for sizes of tissue regions and for times to heartbeat. Experiments modelled include wild-type heart localization as well as both in vitro and in vivo rescue of cardiac lethal mesoderm with wild-type mesoderm. Based upon the parameters necessary to model heart localization, we make a series of predictions. We predict: a specific profile for the endodermal inducer gradient; the possibility of producing multiple hearts in vivo; and a greater contribution to the heart from the wild-type mesoderm for in vivo transplants with cardiac lethal mesoderm. We make some suggestions as to the possible chemical nature of the substances in the model. We indicate that the inhibitory field and mechanochemical theories are probably not as promising as reaction-diffusion for the mechanism of heart localization.

Ambystoma mexicanum↗

Precentral sulcal complex of the human brain: morphology and statistical probability maps.

The morphology of the precentral sulcus was examined via 3D visualization in 40 structural magnetic resonance images of the human brain to define its common features and their variability. The precentral sulcus is composed of two distinct sulcal configurations: 1) the inferior precentral sulcus (IP), situated caudal to the inferior frontal sulcus, and 2) the superior precentral sulcus (SP), caudal to the superior frontal sulcus. The SP was usually a single connected structure, and only in 24% of cases studied did it consist of two separate folds. The caudal end of the superior frontal sulcus and the SP merge on the surface of the brain. However, a clear separation can be established in 72% of cases by analyzing the morphology of the depth of this region in serial sections. Two or three small sulci can be identified in the area between the SP and the midline: the medial precentral sulcus, the marginal precentral sulcus, and a paramidline sulcus. The IP is composed of three different parts: a dorsal and a ventral branch, both oriented vertically, and a short horizontal extension. The ventral branch forms the caudal border of the inferior frontal gyrus, the dorsal branch forms the caudal border of the ventral portion of the middle frontal gyrus, and the horizontal extension runs in a rostrodorsal direction into the middle frontal gyrus. These three structures are closely related to each other but can, in most cases, be separated in the depth of the inferior precentral sulcal complex.

Adult↗

How useful is the fine-scale mapping of complex trait linkage peaks? Evaluating the impact of additional microsatellite genotyping on the posterior probability of linkage.

The two-stage linkage mapping protocol for complex traits (a primary genome scan with low marker density followed by the high-density genotyping around linkage peaks) is a near-universal practice. The behavior (an increase or a decrease) of the peak upon such fine mapping frequently leads to inferences regarding the veracity of the primary scan finding, namely a true, or a false, positive. We examined by simulation, under the null hypothesis of no linkage and the alternative hypothesis of true linkage, the inferences that can be made regarding the posterior probability of linkage given either a peak increase, or alternatively, a peak decrease, following fine mapping. We considered different models of missing genotype data, fine-mapping LOD score thresholds, and prior probabilities of linkage. Our simulations show that evidence for linkage can increase frequently upon fine mapping under both null and alternative hypotheses, although large increases in LOD scores are more common under the alternative hypothesis. Increased LOD scores accompany an increased posterior probability of linkage, and large LOD score changes and the presence of dominance at the trait locus accentuate this effect. We demonstrate that the greatest changes in the posterior probability of linkage occur when the genotyping data are least complete (and especially when parental genotypes are missing), and the LOD score threshold for fine mapping is relaxed.

Algorithms↗

Modeling of activation data in the BrainMap database: detection of outliers.

We describe a system for meta-analytical modeling of activation foci from functional neuroimaging studies. Our main vehicle is a set of density models in Talairach space capturing the distribution of activation foci in sets of experiments labeled by lobar anatomy. One important use of such density models is identification of novelty, i.e., low probability database events. We rank the novelty of the outliers and investigate the cause for 21 of the most novel, finding several outliers that are entry and transcription errors or infrequent or non-conforming terminology. We briefly discuss the use of atlases for outlier detection.

Brain Mapping↗

Characterizing the conformational ensemble of monomeric polyglutamine.

Studies of synthetic polyglutamine peptides in vitro have established that polyglutamine peptides aggregate via a classic nucleation and growth mechanism. Chen and colleagues [Proc Natl Acad Sci U S A 2002;99:11884-11889] have found that monomeric polyglutamine, which is a disordered statistical coil in solution, is the critical nucleus for aggregation. Therefore, nucleation of beta-sheet-rich aggregates requires an initial disorder to order transition, which is a highly unfavorable thermodynamic reaction. The questions of interest to us are as follows: What are the statistical fluctuations that drive beta-sheet formation in monomeric polyglutamine? How do these fluctuations vary with chain length? And why is this process thermodynamically unfavorable, that is, why is monomeric polyglutamine disordered? To answer these questions we use multiple molecular dynamics simulations to provide quantitative characterization of conformational ensembles for two short polyglutamine peptides. We find that the ensemble for polyglutamine is indeed disordered. However, the disorder is inherently different from that of denatured proteins and the average compactness and magnitude of conformational fluctuations increase with chain length. Most importantly, the effective concentration of sidechain primary amides around backbone units is inherently high and peptide units are solvated either by hydrogen bonds to sidechains or surrounding water molecules. Due to the multiplicity of backbone solvation modes the probability associated with any specific backbone conformation is small, resulting in a conformational entropy bottleneck which makes beta-sheet formation in monomeric polyglutamine thermodynamically unfavorable.

Algorithms↗

Over-ruling a group sequential boundary--a stopping rule versus a guideline.

We evaluate the properties of group sequential procedures where the trial is continued even though the boundary for statistical significance (stopping) to demonstrate effectiveness has been crossed. In this case, one may buy-back the previously spent alpha probability to be re-spent or re-distributed at future looks. We show that such plans using an O'Brien-Fleming-like spending function have a negligible effect on the final type I error probability and on the ultimate power of the study. With a Pocock-like bound, however, there is a small additional loss in power. We also show that this approach can be simplified by using a fixed-sample size Z critical value for future looks after buying-back previously spent alpha, such as using a critical Z value of 1.96 for alpha=0.025. We show that this procedure preserves the type I error probability while incurring a minimal loss in power. In this sense, one still has a stopping boundary rather than simply a guideline. This concept is discussed relative to monitoring procedures for inferiority or futility, and cases where both an upper and lower boundary are employed.

Biometry↗

A probability-based aid for teaching medical students a logical approach to diagnosis.

In this paper we present a method of teaching medical students a logical approach to diagnosis. By using the independent Bayes method, commonly employed in decision aids, students can be made aware of how information on each new symptom affects what is likely in the light of what is known already. This approach is used for the diagnosis of thoracic symptoms in patients with normal chest X-rays and an example is given. Extensions of the system to incorporate information from investigations and error costs are discussed.

Diagnosis↗

Private polymorphisms: how many? How old? How useful for genetic taxonomies?

The data on the distribution and frequencies of private polymorphisms in the tribal populations of Central and South America are used to address the question of the extent to which such data can be used to address questions of phylogenetic history. It is shown that due to the great increases in population number that accompanied agricultural development, most private polymorphisms have arisen since population settlement and tribal differentiation. Conversely, the absence of Amerindian variants of wide distribution confirms the small size of the hemispheric population until relatively recent times. Patterns of recent population decline and recovery that accompanied European contact since 1492 have also had a strong impact on the age distribution of extant variants, eliminating many that were relatively young in 1492. The majority of surviving variants that have achieved polymorphic frequencies in a tribe or group of tribes are from 100 to 400 generations old (2500 to 10,000 years). Such genetic variants thus characterize tribes, or groups of closely related tribes, but do not provide a greater time depth of phylogenetic history.

Alleles↗

Most recent common ancestor probability distributions in gene genealogies under selection.

A computational study is made of the conditional probability distribution for the allelic type of the most recent common ancestor in genealogies of samples of n genes drawn from a population under selection, given the initial sample configuration. Comparisons with the corresponding unconditional cases are presented. Such unconditional distributions differ from samples drawn from the unique stationary distribution of population allelic frequencies, known as Wright's formula, and are quantified. Biallelic haploid and diploid models are considered. A simplified structure for the ancestral selection graph of S. M. Krone and C. Neuhauser (1997, Theor. Popul. Biol. 51, 210-237) is enhanced further, reducing the effective branching rate in the graph. This improves efficiency of such a nonneutral analogue of the coalescent for use with computational likelihood-inference techniques.

Algorithms↗

Evolution of dispersal in a stepping-stone population with overlapping generations.

We use Hamilton's inclusive fitness method to calculate the evolutionarily stable dispersal rate in 1- and 2-dimensional stepping-stone populations. This extends previous results by introducing a positive probability for adults to survive into the next generation and breed again. Relatedness between nearby individuals generally decreases with increasing survival, decreasing competition with kin and favouring greater dispersal rates.

Altruism↗

Modeling oxygen transport: development of methods and current state.

Many investigators have contributed to the quantitative understanding of oxygen transport to tissue. Computers continue to improve in speed and architecture thus allowing more sophisticated modeling approaches to be employed. This paper highlights the development of a unique computational strategy, the B-W-K method, that was developed to handle large simulations on small computers. It has proven to be very effective for the solution of large-scale problems in oxygen transport to tissue.

Animals↗

Coincidence detectors and two-pulse visual temporal integration: new theoretical results and comparison with data.

Exact predictions for two-pulse visual temporal integration data are derived from the Bouman-van der Velden quantum coincidence model for threshold vision. The predictions of the model start with complete summation for superposed pulses, then pass to a transition zone of partial integration, and finally reach the level of probability summation for pulses presented with large interstimulus intervals. From our results we can clearly reject the assumption of constant integration times with the basic model. We thus generalize the coincidence model to allow for variable integration times, derive the corresponding predictions for two-pulse integration data, and compare these predictions to published data currently available. It is shown that detectors of low order of coincidence generally underestimate the actual reduction of threshold intensity (or equivalently the corresponding increase of the detection probability) for two pulses as compared to the simple-pulse performance.

Cybernetics↗

[The basis of diagnostic and therapeutic decisions (author's transl)].

The recent logical and psychological results of the theories of probability, utility and decision are valid also for medicine. Their principles and methods are briefly described. The review deals with the special conditions for their application in medicine. Diagnostic methods are derived from the principles of exclusion and pattern recognition. Concerning treatment the importance of the so called therapeutic index as a quotient of possible benefit and injury is stressed. From these elements decision rules are developed for the usual clinical situations.

Decision Making↗