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PubMed1998

The 'Ideal Homunculus': decoding neural population signals.

Information processing in the nervous system involves the activity of large populations of neurons. It is possible, however, to interpret the activity of relatively small numbers of cells in terms of meaningful aspects of the environment. 'Bayesian inference' provides a systematic and effective method of combining information from multiple cells to accomplish this. It is not a model of a neural mechanism (neither are alternative methods, such as the population vector approach) but a tool for analysing neural signals. It does not require difficult assumptions about the nature of the dimensions underlying cell selectivity, about the distribution and tuning of cell responses or about the way in which information is transmitted and processed. It can be applied to any parameter of neural activity (for example, firing rate or temporal pattern). In this review, we demonstrate the power of Bayesian analysis using examples of visual responses of neurons in primary visual and temporal cortices. We show that interaction between correlation in mean responses to different stimuli (signal) and correlation in response variability within stimuli (noise) can lead to marked improvement of stimulus discrimination using population responses.

Animals↗

PubMed1998

Enzyme-linked immunosorbent assay (ELISA) for detection of anti-Trypanosoma evansi equine antibodies.

The standardization of ELISA for the detection of anti-Trypanosoma evansi antibodies in naturally and experimentally infected horses is described. Bayesian analysis was used to establish the cutoff between positive and negative sera. In order to determine the assessment of the ELISA test, the results obtained were compared with those from an IFA. A relative sensibility of 98.39%, a specificity of 95.12% and a predictive value of 96.83% were determined. The standardized technique was used to evaluate the antibody production against trypanosome in an experimentally infected equine, in which the sera converted 15 days after infection. The test was also used for a study of sera prevalence in a non-random sample from two different populations. A prevalence of 81.7% in workhorse and 57.14% in stable horses was found.

Animals↗

PubMed2001

Comparison of PCR and common clinical tests for the diagnosis of H. pylori in dyspeptic patients.

Helicobacter pylori has been recognized as a major gastric pathogen. The objective of this study was to assess the diagnostic value of common clinical tests to detect H. pylori infection, by comparison with PCR. Serum and gastric biopsy specimens from 106 dyspeptic patients were examined. Serology was performed with Pyloriset Dry test, and biopsies were examined histologically, for rapid urease activity and PCR amplification of an ureA gene segment of H. pylori. PCR primers were specific for H. pylori and required at least 1.47 pg of H. pylori DNA, corresponding to about 800 bacterial cells. According to serology, histology, rapid urease, and PCR, positive results were respectively found in 56%, 86%, 64%, and 85% of dyspeptic patients, primarily with gastritis. Relative to PCR, the sensitivity (and specificity) was 55% (38%) for serology, 86% (13%) for histology, 70% (69%) for urease. When combining histology and urease, Bayesian analysis of data indicated no advantage of using combined methods over rapid urease test alone. Histology should not any longer be considered a gold standard test for Helicobacter pylori. Urea breath test still seems the first option for non invasive diagnostic. If an invasive diagnostic is justified, highly specific and sensitive molecular methods should be used to examine specimens.

Bayes Theorem↗

PubMed1996

Lower diagnostic accuracy of thallium-201 SPECT myocardial perfusion imaging in women: an effect of smaller chamber size.

OBJECTIVES: We attempted to formally compare the diagnostic accuracy of thallium-201 single-photon emission computed tomographic (SPECT) myocardial perfusion imaging in men and women and the effect of chamber size on accuracy. BACKGROUND: The diagnostic accuracy of conventional exercise testing has been shown to be lower in women. Less is known about the relative accuracy of perfusion imaging. Because of smaller body size, women have a smaller heart size than men, a factor that may reduce accuracy. METHODS: We identified 323 patients undergoing thallium-201 SPECT myocardial perfusion imaging who either had < 5% probability of coronary artery disease (CAD) by Bayesian analysis or who underwent cardiac catheterization within 60 days of stress testing. Patients with documented history of infarction, coronary artery bypass grafting, pathologic Q waves on the electrocardiogram, left bundle branch block or nonischemic cardiomyopathy were not included. We performed strict quantitative analysis, and receiver operating characteristic (ROC) curves were generated and the area under the curve was calculated for men and women. A size index was generated from the number of short-axis slices and average radius of each slice, and the group was classified as having a large or a small chamber size. The ROC areas of men and women with a large and a small chamber size were then compared. RESULTS: Diagnostic accuracy was lower in women than in men (ROC are 0.82 vs. 0.93, p < 0.05) despite similar values for peak heart rate and rate-pressure product and similar severity of CAD. There was a greater difference in accuracy between patients with a large versus a small chamber size (ROC area 0.94 vs. 0.73, p < 0.01) despite similar levels of exercise and severity of CAD. When we compared men and women in groups stratified by chamber size, we could not detect a significant difference between ROC area values of men and women (large: 0.94 men, 0.93 women, p = 0.77, power to detect difference in area of 0.15 = 91%; small: 0.79 men, 0.72 women, p = 0.58, power to detect difference in area of 0.15 = 35%). CONCLUSIONS: The diagnostic accuracy of thallium SPECT myocardial perfusion imaging is lower in women than in men. Most of the difference appears to be due to smaller left ventricular chamber size in women, although a small residual gender effect in smaller heart sizes cannot be entirely excluded. It is proposed that the most likely cause for this difference is the relatively greater effect of imaging blurring on smaller hearts.

Aged↗

PubMed2001

Fine-needle aspiration biopsy of the thyroid.

The routine use of thyroid FNAB caused profound changes in the management of thyroid nodules. FNAB allows a prompt identification and treatment of thyroid malignancies and avoids unnecessary surgery in patients with benign lesions, improving quality of life in patients with thyroid nodules. Furthermore, FNAB provides guidance for the type of surgery and reduces costs of care. On average, standard FNAB is nondiagnostic in 25% to 40% of cases, which include inadequate specimens and indeterminate (suspicious) diagnoses. In addition, a small percentage of false-negative diagnoses occur, which are unavoidable and raise concern of a late diagnosis of cancer. To minimize the limitations of FNAB, every center should reach and maintain a high standard of expertise in all of the steps of smear preparation and interpretation. Alternative modes of sampling or sample preparation may result in a reduction of nondiagnostic samples and better accuracy. Every center should set up clinical guidelines tailored to their own FNAB results and including the evaluation of clinical data. More work is needed to increase the accuracy of FNAB in suspicious cases. Toward this goal a variety of molecular markers have been evaluated; although none of them are ideal, some are promising. More studies need to be carried out in larger series to further evaluate the accuracy of these markers in identifying specific cancer histotypes within the group of suspicious lesions. It is hoped that, in the near future, the routine use of a combination of these markers will cost-effectively improve the diagnosis of malignant nodules classified as suspicious on traditional cytology. Statistical methods such as bayesian analysis or neural networks can be advantageously used to integrate different relevant information derived from family and personal history, clinical data, cytologic results, and evaluation of molecular markers.

Biopsy, Needle↗

PubMed1998

Diagnostic value of cytokeratin fragment 19 (CYFRA 21-1) in bronchoalveolar lavage fluid in lung cancer.

The aim of this study was to evaluate the diagnostic value of a new tumour marker, cytokeratin fragment 19 (CYFRA 21-1), in bronchoalveolar lavage fluid (BALF) for the diagnosis of lung cancer. The cross-sectional study included 36 patients with lung cancer, 19 with benign lung diseases and 13 control subjects. In the group with cancer, BAL was performed in the cancer-involved lung and in the opposite lung. Results in BALF were expressed both as absolute concentrations (ng ml-1) and referred to total protein (TP) (ng mg-1 TP), and results in plasma were expressed in ng ml-1. In BALF, there was no significant different between cancer and control groups. Using the 95th percentile of levels obtained in benign lung disease in BALF (specificity 95%) as the cut-off point, the sensitivity of CYFRA 21-1 was 13%. Positive and negative predictive values (PPV and NPV) at different pretest probabilities, and positive and negative gains were obtained applying a Bayesian analysis. Results showed low positive gains for PPV (maximal increase of 22%) and almost none for NPV (negative gains < 5%). In plasma, CYFRA 21-1 provided a sensitivity of 65%. The combination of BALF and plasma tumour marker levels showed a sensitivity of 69%. Therefore, measurement of CYFRA 21-1 in BALF has poor diagnostic value in lung cancer.

Antigens, Neoplasm↗

PubMed2002

Molecular systematics of the Jacks (Perciformes: Carangidae) based on mitochondrial cytochrome b sequences using parsimony, likelihood, and Bayesian approaches.

The Carangidae represent a diverse family of marine fishes that include both ecologically and economically important species. Currently, there are four recognized tribes within the family, but phylogenetic relationships among them based on morphology are not resolved. In addition, the tribe Carangini contains species with a variety of body forms and no study has tried to interpret the evolution of this diversity. We used DNA sequences from the mitochondrial cytochrome b gene to reconstruct the phylogenetic history of 50 species from each of the four tribes of Carangidae and four carangoid outgroup taxa. We found support for the monophyly of three tribes within the Carangidae (Carangini, Naucratini, and Trachinotini); however, monophyly of the fourth tribe (Scomberoidini) remains questionable. A sister group relationship between the Carangini and the Naucratini is well supported. This clade is apparently sister to the Trachinotini plus Scomberoidini but there is uncertain support for this relationship. Additionally, we examined the evolution of body form within the tribe Carangini and determined that each of the predominant clades has a distinct evolutionary trend in body form. We tested three methods of phylogenetic inference, parsimony, maximum-likelihood, and Bayesian inference. Whereas the three analyses produced largely congruent hypotheses, they differed in several important relationships. Maximum-likelihood and Bayesian methods produced hypotheses with higher support values for deep branches. The Bayesian analysis was computationally much faster and yet produced phylogenetic hypotheses that were very similar to those of the maximum-likelihood analysis.

Animals↗

PubMed2003

A phylogeny of the Australian Sphenomorphus group (Scincidae: Squamata) and the phylogenetic placement of the crocodile skinks (Tribolonotus): Bayesian approaches to assessing congruence and obtaining confidence in maximum likelihood inferred relationships.

Australian scincid lizards are a diverse squamate assemblage ( approximately 385 species), divided among three major clades (Egernia, Eugongylus, and Sphenomorphus groups). The Sphenomorphus group is the largest, comprising 61% of the Australian scincid fauna. Phylogenetic relationships within the Australian Sphenomorphus group and the phylogenetic placement of Tribolonotus are inferred using mtDNA (12S and 16S rRNA genes, ND4 protein-coding gene, and associated tRNA genes; 2185bp total). These data were analyzed separately (structural RNA vs protein-coding partitions) and combined using maximum likelihood. Confidence in inferred clades was assessed using non-parametric bootstrapping and Bayesian analysis. Analysis of the combined data strongly supports Sphenomorphus group (as well as the Australian subgroup) monophyly. Notoscincus is strongly placed as the sister taxon of the remaining Australian Sphenomorphus group taxa, with this more exclusive clade being divided into two major groups (one restricted to mesic eastern Australia and the other continent wide). The speciose Australian "Eulamprus" and "Glaphyromorphus" are both polyphyletic. All remaining non-Sphenomorphus group lygosomine skinks strongly form a clade, with Tribolonotus placed as the sister taxon of the Australian Egernia group.

Animals↗

PubMed2002

Remark on utility and error rates of the allopurinol test in detecting mild ornithine transcarbamylase deficiency.

Carriers of X-linked ornithine transcarbamylase deficiency (OTCD) are themselves mildly affected. The allopurinol test is quite sensitive (92.7%) and very specific in detecting these carriers. Consequently, it has also been recommended for the diagnosis of mild OTCD in the general population. However, there is a controversy on its utility since OTCD could not be demonstrated in several patients with positive test results but negative family histories. We show that this controversy is due to an improper use of statistical concepts, i.e., to the postulate of a specificity of "100%," and to the confusion of specificity with type I error rate. Spontaneous orotic aciduria implies a positive allopurinol test and limits the specificity of the test to a maximum of 99.7%. Therefore, according to Bayes' theorem, almost all positive test results in the general population must turn out to be type I errors, due to the minute prevalence (1/32,000) of mild OTCD (i.e., asymptomatic carriers and male patients with inapparent disease). Family history seems to be the only preselective parameter that can sufficiently raise the prevalence in the group to be tested. Bayesian analysis also yields the rate of type II errors (OTCD inspite of a negative test) which is high in closely related at-risk females (22.6% in mothers of male patients) but minimal in the general population. Conclusion. The allopurinol test is useful for the exclusion but not for the diagnosis of inapparent OTCD in sporadic individuals. Test results in possible carriers should be interpreted with caution.

Allopurinol↗

PubMedDate not supplied

The likelihood approach to compare populations: a study on DNA evidence and pitfalls of intuitions.

The paper follows on from earlier work [Taroni F and Aitken CGG. Probabilistic reasoning in the law, Part 1: assessment of probabilities and explanation of the value of DNA evidence. Science & Justice 1998; 38: 165-177]. Different explanations of the value of DNA evidence were presented to students from two schools of forensic science and to members of fifteen laboratories all around the world. The responses were divided into two groups; those which came from a school or laboratory identified as Bayesian and those which came from a school or laboratory identified as non-Bayesian. The paper analyses these responses using a likelihood approach. This approach is more consistent with a Bayesian analysis than one based on a frequentist approach, as was reported by Taroni F and Aitken CGG. [Probabilistic reasoning in the law, Part 1: assessment of probabilities and explanation of the value of DNA evidence] in Science & Justice 1998.

Bayes Theorem↗

PubMed2004

Melanelixia and Melanohalea, two new genera segregated from Melanelia (Parmeliaceae) based on molecular and morphological data.

This paper continues a revision of generic concepts in the parmelioid lichens using molecular data in order to reach a consensus among lichenologists over which segregates proposed over the last two decades should be accepted. Here we employ data from three gene portions to provide a basis for a revised generic concept of the brown parmelioid lichens hitherto classified in Melanelia. The phylogeny was studied using a Bayesian analysis of a combined data set of nuclear ITS, LSU rDNA and mitochondrial SSU rDNA sequences. 173 new sequences were obtained from 38 specimens of 15 Melanelia species, 37 related parmelioid species, and eight non-parmelioid species. The results indicate that Melanelia is not monophyletic but falls into four different clades. The genus Melanelia is restricted here to a small group of saxicolous lichens related to the type species M. stygia, and with bifusiform conidia, while the remaining species, most of which are primarily corticolous and have mainly cylindrical to filiform conidia, belong to two other clades recognised as two new genera: Melanelixia and Melanohalea, to accommodate the M. exasperata and M. glabra groups, respectively. 27 new combinations are made. The epicortex of Melanelixia species have pores or special structures termed here 'fenestrations', while most Melanohalea species are pseudocyphellate. Pleurosticta links to the Melanohalea clade but without strong support, and the phylogenetic position of M. disjuncta and its related species remains uncertain, linking with the Xanthoparmelia (syn. Neofuscelia) clade but also without strong support.

Ascomycota↗

PubMed2005

The beetle gut: a hyperdiverse source of novel yeasts.

We isolated over 650 yeasts over a three year period from the gut of a variety of beetles and characterized them on the basis of LSU rDNA sequences and morphological and metabolic traits. Of these, at least 200 were undescribed taxa, a number equivalent to almost 30% of all currently recognized yeast species. A Bayesian analysis of species discovery rates predicts further sampling of previously sampled habitats could easily produce another 100 species. The sampled habitat is, thereby, estimated to contain well over half as many more species as are currently known worldwide. The beetle gut yeasts occur in 45 independent lineages scattered across the yeast phylogenetic tree, often in clusters. The distribution suggests that the some of the yeasts diversified by a process of horizontal transmission in the habitats and subsequent specialization in association with insect hosts. Evidence of specialization comes from consistent associations over time and broad geographical ranges of certain yeast and beetle species. The discovery of high yeast diversity in a previously unexplored habitat is a first step toward investigating the basis of the interactions and their impact in relation to ecology and evolution.

Animals↗

PubMed2005

New Asian species of the genus Anamika (euagarics, hebelomatoid clade) based on morphology and ribosomal DNA sequences.

Two dark-spored agaric species from Asia are placed in the genus Anamika (Agaricales or euagarics clade). This result is supported by ITS and nLSU-rDNA sequences with strong measures of branch support, in addition to several morphological and ecological similarities. An inclusive ITS study was performed using a mixed model Bayesian analysis that suggests the derived status of Anamika within Hebeloma, thereby rendering Hebeloma a paraphyletic genus. However, the monophyly of Hebeloma cannot be rejected outright given ITS and nLSU-rDNA data. Thus, we propose two new Asian species in Anamika: A. angustilamellata sp. nov. from dipterocarp and fagaceous forests of southwestern China and northern Thailand; and A. lactariolens comb. nov., a Japanese species originally described in the genus Alnicola. A complete description of A. angustilamellata, including illustrations, is provided.

Agaricales↗

PubMed2005

A field comparison of volatile organic compound measurements using passive organic vapor monitors and stainless steel canisters.

Concurrent field measurements of 10 volatile organic compounds (VOCs) were made using passive diffusion-based organic vapor monitors (OVMs) and the U.S. Federal Reference Method, which comprises active monitoring with stainless steel canisters (CANs). Measurements were obtained throughout a range of weather conditions, repeatedly over the course of three seasons, and at three different locations in the Minneapolis/St. Paul metropolitan area. Ambient concentrations of most VOCs as measured by both methods were low compared to those of other large metropolitan areas. For some VOCs a considerable fraction of measurements was below the detection limit of one or both methods. The observed differences between the two methods were similar across measurement sites, seasons, and meteorological variables. A Bayesian analysis with uniform priors on the differences was applied, with accommodation of sometimes heavy censoring (nondetection) in either device. The resulting estimates of bias and standard deviation of the OVM relative to the CAN were computed by tertile of the canister-measured concentration. In general, OVM and CAN measurements were in the best agreement for benzene and other aromatic compounds with hydrocarbon additions (ethylbenzene, toluene, and xylenes). The two methods were not in such good agreement for styrene and halogenated compounds (carbon tetrachloride, p-dichlorobenzene, methylene chloride, and trichloroethylene). OVMs slightly overestimated benzene concentrations and carbon tetrachloride at low concentrations, but in all other cases where significant differences were found, OVMs underestimated relative to canisters. Our study indicates that the two methods are in agreement for some compounds, but not all. We provide data and interpretation on the relative performance of the two VOC measurement methods, which facilitates intercomparisons among studies.

Air Pollutants↗

PubMed2000

RFAC, a program for automated NMR R-factor estimation.

A computer program (RFAC) has been developed, which allows the automated estimation of residual indices (R-factors) for protein NMR structures and gives a reliable measure for the quality of the structures. The R-factor calculation is based on the comparison of experimental and simulated 1H NOESY NMR spectra. The approach comprises an automatic peak picking and a Bayesian analysis of the data, followed by an automated structure based assignment of the NOESY spectra and the calculation of the R-factor. The major difference to previously published R-factor definitions is that we take the non-assigned experimental peaks into account as well. The number and the intensities of the non-assigned signals are an important measure for the quality of an NMR structure. It turns out that for different problems optimally adapted R-factors should be used which are defined in the paper. The program allows to compute a global R-factor, different R-factors for the intra residual NOEs, the inter residual NOEs, sequential NOEs, medium range NOEs and long range NOEs. Furthermore, R-factors can be calculated for various user defined parts of the molecule or it is possible to obtain a residue-by-residue R-factor. Another possibility is to sort the R-factors according to their corresponding distances. The summary of all these different R-factors should allow the user to judge the structure in detail. The new program has been successfully tested on two medium sized proteins, the cold shock protein (TmCsp) from Termotoga maritima and the histidine containing protein (HPr) from Staphylococcus carnosus. A comparison with a previously published R-factor definition shows that our approach is more sensitive to errors in the calculated structure.

Algorithms↗

PubMed1998

Pharmacokinetic-pharmacodynamic modeling of tolmetin antinociceptive effect in the rat using an indirect response model: a population approach.

The relationship between the pharmacokinetics and the antinociceptive effect of tolmetin was characterized by an indirect model using a population approach. Animals received an intra-articular injection of uric acid in the right hindlimb to induce its dysfunction. Once dysfunction was complete, rats received an oral tolmetin dose of 1, 3.2, 10, 31.6, 56.2 or 100 mg/kg and antinociceptive effect and blood tolmetin concentration were simultaneously evaluated. Tolmetin produced a dose-dependent recovery of functionality, which was not directly related to blood concentration. An inhibitory indirect response model was used based on these response patterns and the fact that tolmetin reduced nociception by inhibiting prostaglandin synthesis. Pharmacokinetic (PK) and pharmacodynamic (PD) data were simultaneously fitted using nonlinear mixed effects modeling (NONMEM) to the one-compartment model and indirect response model. The individual time courses of the response were described using Bayesian analysis with population parameters as a priori estimates. There was good agreement between the predicted and observed data. Population analysis yielded a maximal inhibition of the nociceptive response of 76% and an IC50 of 9.22 micrograms/ml. This IC50 is similar to that for tolmetin-induced prostaglandin synthesis inhibition in vitro (3.0 micrograms/ml). The present results demonstrate that mechanism-based PK-PD analysis using a population approach is useful for quantitating individual responses as well as reflecting the actual mechanism of action of a given drug in vivo.

Animals↗

PubMed2000

Discrete duration models combining dynamic and random effects.

Survival data may include two different sources of variation, namely variation over time and variation over units. If both of these variations are present, neglecting one of them can cause serious bias in the estimations. Here we present an approach for discrete duration data that includes both time-varying and unit-specific effects to model these two variations simultaneously. The approach is a combination of a dynamic survival model with dynamic time-varying baseline and covariate effects and a frailty model measuring unobserved heterogeneity with random effects varying independently over units. Estimation is based on posterior modes, i.e., we maximize the joint posterior distribution of the unknown parameters to avoid numerical integration and simulation techniques, that are necessary in a full Bayesian analysis. Estimation of unknown hyperparameters is achieved by an EM-type algorithm. Finally, the proposed method is applied to data of the Veteran's Administration Lung Cancer Trial.

Algorithms↗

PubMed1999

Robust and optimal use of information in stereo vision.

Differences between the left and right eye's views of the world carry information about three-dimensional scene structure and about the position of the eyes in the head. The contemporary Bayesian approach to perception implies that human performance in using this source of eye-position information can be analysed most usefully by comparison with the performance of a statistically optimal observer. Here we argue that the comparison observer should also be statistically robust, and we find that this requirement leads to qualitatively new behaviours. For example, when presented with a class of stereoscopic stimuli containing inconsistent information about eccentricity of gaze, estimates of this gaze parameter recorded from one robust ideal observer bifurcate at a critical value of stimulus inconsistency. We report an experiment in which human observers also show this phenomenon and we use the experimentally determined critical value to estimate the vertical acuity of the visual system. The Bayesian analysis also provides a highly reliable and biologically plausible algorithm that can recover eye positions even before the classic stereo-correspondence problem is solved, that is, before deciding which features in the left and right images are to be matched.

Algorithms↗