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PubMed1991

[A control study of some hair trace elements content of schizophrenics before and after treatment].

This is a comparative survey of hair trace elements of 69 schizophrenics matched with normals, the result of which is summarized as follows: It was found that the hair Cu Fe Mg in all patients and Mn in females had significantly lower quantities than normals, in addition to which no significant difference of CU/ZN ratio was found between the patients and the normals and there were no significant differences of hair Cu Fe Mn Zn Mg in schizophrenics before and after chlorpromazine treatment. The hair Fe Mn in recovered group were significantly higher than the improved group, it was probably related to the former had more patients with extrapyramidal symptoms than the later. That was coincident with the hair Fe was increased significantly in the patients with extrapyramidal symptoms of study group after Chlorpromazine treatment. The authors suggest the need for further study on the theory of Parkinson-like Syndrome could probably be related to free-radical formation.

Adolescent↗
PubMed1996

High-resolution random mesh algorithms for creating a probabilistic 3D surface atlas of the human brain.

Striking variations exist, across individuals, in the internal and external geometry of the brain. Such normal variations in the size, orientation, topology, and geometric complexity of cortical and subcortical structures have complicated the problem of quantifying deviations from normal anatomy and of developing standardized neuroanatomical atlases. This paper describes the design, implementation, and results of a technique for creating a three-dimensional (3D) probabilistic surface atlas of the human brain. We have developed, implemented, and tested a new 3D statistical method for assessing structural variations in a data-base of anatomic images. The algorithm enables the internal surface anatomy of new subjects to be analyzed at an extremely local level. The goal was to quantify subtle and distributed patterns of deviation from normal anatomy by automatically generating detailed probability maps of the anatomy of new subjects. Connected systems of parametric meshes were used to model the internal course of the following structures in both hemispheres: the parieto-occipital sulcus, the anterior and posterior rami of the calcarine sulcus, the cingulate and marginal sulci, and the supracallosal sulcus. These sulci penetrate sufficiently deeply into the brain to introduce an obvious topological decomposition of its volume architecture. A family of surface maps was constructed, encoding statistical properties of local anatomical variation within individual sulci. A probability space of random transformations, based on the theory of Gaussian random fields, was developed to reflect the observed variability in stereotaxic space of the connected system of anatomic surfaces. A complete system of probability density functions was computed, yielding confidence limits on surface variation. The ultimate goal of brain mapping is to provide a framework for integrating functional and anatomical data across many subjects and modalities. This task requires precise quantitative knowledge of the variations in geometry and location of intracerebral structures and critical functional interfaces. The surface mapping and probabilistic techniques presented here provide a basis for the generation of anatomical templates and expert diagnostic systems which retain quantitative information on intersubject variations in brain architecture.

Algorithms↗
PubMed1980

A general method for biological inference: illustrated by the estimation of gene nucleotide transition probabilities.

The method of maximum entropy inference developed by Jaynes can be a particularly useful method for obtaining unbiased estimates of biological parameters when the experimental knowledge about a system can be explicitly formulated. Base transition probabilities between genes, though central to evolutionary theory and understanding, present a difficult estimation problem because the ancestral genes are not experimentally accessible. The necessary estimates must therefore be made on the basis of experimental knowledge other than a direct frequency count of base replacements (A leads to C, for example) between contemporary genes. It is shown how maximum entropy inference together with the experimentally observed fact of compositional fidelity in a given gene family can be used to obtain meaningful gene base transition probabilities at each of the three nucleotide positions within codons. Both symmetric and asymmetric transition probabilities are considered. Tables of these probabilities are given for each codon position for the alpha-hemoglobin, beta-hemoglobin, myoglobin, cytochrome c, and the parvalbumin group genes. Tabular values of the average amino acid composition of these five protein families and the average nucleotide composition of their coding genes at varied codon loci are given. It is thus no longer necessary to assume in theories of evolutionary divergence equimolar base ratios A:C:G:U::1:1:1:1 or that each base has an equal chance of mutating to and being fixed as any one of the other three bases.

Amino Acids↗
PubMed2005

Statistical theory for protein ensembles with designed energy landscapes.

Combinatorial protein libraries provide a promising route to investigate the determinants and features of protein folding and to identify novel folding amino acid sequences. A library of sequences based on a pool of different monomer types are screened for folding molecules, consistent with a particular foldability criterion. The number of sequences grows exponentially with the length of the polymer, making both experimental and computational tabulations of sequences infeasible. Herein a statistical theory is extended to specify the properties of sequences having particular values of global energetic quantities that specify their energy landscape. The theory yields the site-specific monomer probabilities. A foldability criterion is derived that characterizes the properties of sequences by quantifying the energetic separation of the target state from low-energy states in the unfolded ensemble and the fluctuations of the energies in the unfolded state ensemble. For a simple lattice model of proteins, excellent agreement is observed between the theory and the results of exact enumeration. The theory may be used to provide a quantitative framework for the design and interpretation of combinatorial experiments.

Models, Statistical↗
PubMed2000

Molecular systematics of the old world monkey tribe papionini: analysis of the total available genetic sequences.

The phylogenetic relationships among the genera of the tribe Papionini are inferred using a taxonomic congruence approach in which gene trees derived for eight unlinked genetic sequence datasets are compared. Population genetics theory predicts that species relationships will be revealed with greater probability when the topology of gene trees from many unlinked loci are found to be congruent. The theory underlying this approach is described. Monophyly of the mangabeys is not supported by any of the gene trees; instead, they are polyphyletic with Cercocebus found to be the sister taxon to Mandrillus in five gene trees (with no conflicting trees), and Lophocebus found to be closely related to Papio and/or Theropithecus in all trees. Theropithecus and Papio are not strongly supported as sister taxa (present in one or two trees only);Lophocebus and Papio are supported as sister taxa in the majority of trees. A close relationship between Mandrillus and Papio is not supported in any of the trees.The relationships among Papio, Lophocebus, and Theropithecus cannot be resolved by congruence, probably due to the short time interval estimated between their divergences. The mtDNA COII sequences are used to estimate divergence dates within the papionins. The internode between the divergences of these species is estimated to be between 290 ka and 370 ka. Lastly, the evolution of morphological features such as long faces, suborbital facial fossae, and terrestrial skeletal adaptations is discussed.

Animals↗
PubMed2005

Optimizing linear optics quantum gates.

In this Letter, the problem of finding optimal success probabilities of linear optics quantum gates is linked to the theory of convex optimization. It is shown that by exploiting this link, upper bounds for the success probability of networks realizing single-mode gates can be derived, which hold in generality for postselected networks of arbitrary size, any number of auxiliary modes, and arbitrary photon numbers. As a corollary, the previously formulated conjecture is proven that the optimal success probability of a nonlinear sign shift without feedforward is 1/4, a gate playing the central role in the scheme of Knill-Laflamme-Milburn for quantum computation. The concept of Lagrange duality is shown to be applicable to provide rigorous proofs for such bounds, although the original problem is a difficult nonconvex problem in infinitely many objective variables. The versatility of this approach is demonstrated.

Journal Article↗
PubMed1994

Singular perturbation theory applied to Markov models for DNA damage caused by ionizing radiation.

The induction of DNA double strand breaks by ionizing radiation, and enzymatic double strand break repair or misrepair, are modeled as continuous time Markov chains. Systems of partial differential equations for appropriate probability generating functions are solved by singular perturbation theory with scaling. The zero-th order singular perturbation result coincides with a model recently suggested in a biological literature. Higher order terms correct for various effects including "overkill". The results are applicable to both sparsely ionizing and densely ionizing radiation.

Animals↗
PubMedDate not supplied

Detection and mapping of abnormal brain structure with a probabilistic atlas of cortical surfaces.

PURPOSE: We have devised, implemented, and tested a technique for creating a comprehensive probabilistic atlas of the human cerebral cortex, based on high-dimensional fluid transformations. The goal of the atlas is to detect and quantify subtle and distributed patterns of deviation from normal cortical anatomy, in a 3D brain image from any given subject. METHOD: Given a 3D MR image of a new subject, a high-resolution surface representation of the cerebral cortex is automatically extracted. The algorithm then calculates a set of high-dimensional volumetric maps, fluidly deforming this surface into structural correspondence with other cortical surfaces, selected one by one from an anatomic image database. The family of volumetric warps so constructed encodes statistical properties of local anatomical variation across the cortical surface. Additional strategies are developed to fluidly deform the sulcal patterns of different subjects into structural correspondence. A probability space of random transformations, based on the theory of anisotropic Gaussian random fields, is then used to encode information on complex variations in gyral and sulcal topography from one individual to another. A complete system of 256(2) probability density functions is computed to reflect the observed variability in stereotaxic space of the points whose correspondences are found by the warping algorithm. Confidence limits in stereotaxic space are determined for cortical surface points in the new subject's brain. RESULTS: Color-coded probability maps are generated, which highlight and quantify regional patterns of deformity in the anatomy of new subjects. These maps indicate locally the probability of each anatomic point being as unusually situated, given the distributions of corresponding points in the scans of normal subjects. 3D MRI volumes are analyzed, from subjects with clinically determined Alzheimer disease and age-matched normal subjects. CONCLUSION: Applications of the random fluid-based probabilistic atlas include the transfer of multisubject 3D functional, vascular, and histologic maps onto a single anatomic template, the mapping of 3D atlases onto the scans of new subjects, and the rapid detection, quantification, and mapping of local shape changes in 3D medical images in disease and during normal or abnormal growth and development.

Aged↗
PubMed1997

Survival probability of drug resistant mutants in malaria parasites.

This study predicts the ultimate probability of survival of a newly arisen drug resistant mutant in a population of malaria parasites, with a view to understanding what conditions favour the evolution of drug resistance. Using branching process theory and a population genetics transmission model, the probabilities of survival of one- and two-locus new mutants are calculated as functions of the degree of drug pressure, the mean and variation in transmission rate, and the degree of natural selection against the mutant. Probability of survival increases approximately linearly with drug pressure, the slope of the line increasing with mean transmission rate. Thus increased drug pressure, especially in combination with high transmission rates, strongly favours the evolution of drug resistance. These conclusions also hold for the case of multiple drug resistance where it is coded for by two unlinked loci: the greater effective recombination breakdown in high transmission areas is counteracted by greater effective selection so that the net effect of higher transmission rates is to favour the evolution of multiple drug resistance. High variability in transmission rate and natural selection against the mutants are unfavourable to mutant survival, though these are relatively weak forces.

Animals↗
PubMedDate not supplied

A shift from significance test to hypothesis test through power analysis in medical research.

Medical research literature until recently, exhibited substantial dominance of the Fisher's significance test approach of statistical inference concentrating more on probability of type I error over Neyman-Pearson's hypothesis test considering both probability of type I and II error. Fisher's approach dichotomises results into significant or not significant results with a P value. The Neyman-Pearson's approach talks of acceptance or rejection of null hypothesis. Based on the same theory these two approaches deal with same objective and conclude in their own way. The advancement in computing techniques and availability of statistical software have resulted in increasing application of power calculations in medical research and thereby reporting the result of significance tests in the light of power of the test also. Significance test approach, when it incorporates power analysis contains the essence of hypothesis test approach. It may be safely argued that rising application of power analysis in medical research may have initiated a shift from Fisher's significance test to Neyman-Pearson's hypothesis test procedure.

Biomedical Research↗
PubMed1998

[Carcinogenesis via microbial infection].

Recent progress in the field of infectious diseases involving carcinogenesis has been striking. Extensive studies of Helicobacter pylori, and hepatitis type B and C virus showed that they are the primary cause of gastric cancer and hepatoma, respectively. Also some parasites such as Opistorchis viverrini and Schistosoma haematobium are also putative causes of cholangiocarcinoma and urinary bladder cancer, respectively. All of them require a chronic infection of more than 15 years. More than 50% of Japanese cancers are thus considered to be caused by chronic infection. The classic theory of carcinogenesis is radiation, chemicals and viral infection. Recent studies in free radical and biochemical research in our infectious diseases show all carcinogenesis involves free radical generation such as superoxide (O2.-), nitric oxide (NO), and their adducts peroxynitrite (ONOO-), H2O2 hydrooxyl radical (.OH), HClO, and NO2Cl as well as alkylperoxy radicals. All these molecular species are capable of modifying nucleic acid and DNA or RNA; furthermore a strand break is frequently observed, and hence potent mutagenicity and a probable cause of cancer. Thus, the unifying theory of carcinogenesis may most likely involve the mechanism of free radicals. This means a paradigm shift is needed in the public health policy for the tactics of cancer prevention.

Animals↗
PubMed1992

A probability nomogram to predict rectal temperature in children.

The relationship between rectal and peripheral-site temperature was investigated to achieve two objectives: 1) to evaluate a prevailing practice of intersite adjustment by use of an invariant temperature difference; and 2) to develop a statistical method for intersite temperature predictions in the individual child, especially for fever as defined by rectal measurement. Rectal, oral, axillary, left abdomen skin, and forehead skin temperatures (degrees F) were measured with an electronic thermometer in 257 children. Objective 1 was not achieved because a simple temperature difference between a peripheral site and the rectal site could not be used to predict rectal temperature reliably. For objective 2, intersite differences met three statistical criteria so that normal distribution theory could be used to derive the probabilities for occurrence of each difference. Accordingly, cumulative probability nomograms were constructed to estimate rectal-site fever from measurements at peripheral sites. This nomogram method produces a clinically reliable prediction of rectal-site fever from temperature measurement at peripheral sites, especially the oral and axillary sites. These predictions offer useful assessments of febrile illness severity when rectal temperature is not available.

Abdomen↗
PubMed1980

H gene theory of inherited autoimmune disease.

Autoimmune disease in inbred mice is probably determined by co-dominant genes associated with both the major and minor histocompatibility loci. It is postulated that the genes involved are histocompatibility-antigen (H) genes themselves, which delete complementary clones in fetal life, in accord with Burnet's theory of clonal selection. Such deletions cause perturbations in the paratope-idiotope network reactions envisaged by Jerne. As well as having negative effects on immune-response capacity, the perturbations have positive effects, because the deletion of clones with specificity for the idiotopes of other clones permists immune responses which would otherwise be absent. Such perturbations can influence the chance of emergence of a forbidden clone by somatic mutations occurring in the V genes of dividing immunocytes and so can provide a genetic predisposition to autoimmune disease.

Animals↗
PubMed2001

Measurements and recovery patterns in a multicenter study of acute spinal cord injury.

STUDY DESIGN: Post hoc, secondary analysis of data from 1992 to 1998 in the trial of Sygen in acute spinal cord injury. OBJECTIVES: Quasi-epidemiologic understanding of measurement tools and of recovery patterns. No drug efficacy results. SUMMARY OF BACKGROUND DATA: Many authors have studied individual scales for measuring the severity of spinal cord injury. METHODS: Emphasis on descriptive, rather than inferential, statistics: consistent with secondary analysis. RESULTS: Of the 760 patients, 43 died within 365 days. The rate was higher for complete injuries (7.1% vs. 3.2%, P = 0.017). Marked recovery at 26 weeks was more frequent in those with better baseline American Spinal Injury Association (ASIA) Impairment Scale (AIS) scores, but was not different for methylprednisolone within versus after 3 hours. Light touch scores improved at each visit, more so in those with higher scores at baseline. Bladder control similarly improved. Motor and sensory scores exhibited departures from assumptions underlying normal-theory statistical techniques: t test and analysis of variance. Furthermore, they were mixtures of differing distributions from different study strata, so that overall conclusions depend on the mixture of patients seen. CONCLUSIONS: The prognosis of these patients with spinal cord injury seen at 28 centers in North America during the mid-1990s appears better than was often assumed earlier. The general patterns are similar across different measurement scales, although there are intriguing differences. The patterns in different strata are different in specifics, and complete injuries do less well. Pooling data from different strata may result in probability distributions that depart from normal-theory assumptions and give misleading results depending on recruitment patterns.

Adolescent↗
PubMedDate not supplied

A sequential diagnostic model for medical questioning.

A medical interview is a very important part of medical treatment since it is conducted when a patient is first admitted to a hospital and treatment is decided afterwards. However, these interviews are not always carried out in sufficient detail because physicians have very heavy work-loads. The development of automated medical questioning equipment which tabulates the answers to questions into a form easily understood by physicians, which enumerates data on doubtful diseases and which indicates pertinent medical examinations may come to the aid of patients and physicians. This paper presents a new diagnostic theory for the design of automated medical questioning equipment. Diagnostic theories can be classified into batch and sequential theories; the authors have investigated the sequential one, because decisions are made using minimal data. The techniques supporting this theory are multi-class recognition systems based on independently designed dual-class recognition systems and Wald's Sequential Probability Ratio Test. To discuss the properties inherent in the present theory, classification of three pattern classes was made. These were normal, hypertension and myocardial infarction classes of patients. The mean error probability of classification was found to be 3.08%.

Diagnosis, Computer-Assisted↗