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PubMed1983

Patch-clamp studies of slow potential-sensitive potassium channels in longitudinal smooth muscle cells of rabbit jejunum.

1. The patch-clamp technique was used to study single channel currents in membrane patches of longitudinal smooth muscle cells of rabbit jejunum dispersed by collagenase treatment. Recordings were made from both cell-attached and isolated patches.2. The predominant unit currents observed were outward at membrane potentials positive to the potassium equilibrium potential (E(K)) and they were rapidly and reversibly blocked by tetraethylammonium (TEA). Their size varied as E(K) was changed but was not noticeably affected by changing E(Na), E(Cl) or E(Ca); it was little altered in calcium-free EGTA solution. Thus, these currents apparently result mainly, if not exclusively, from the movements of potassium ions through channels insensitive to the calcium ion concentration. The present study describes the properties of these potassium channels.3. The unit conductance varied slightly with potential in most experiments; around zero potential it was about 50 pS. The conductance was dependent upon the potassium, but not the calcium, gradient. Sub levels of conductance of about two-thirds and, less commonly, one-third of the fully conducting channel state were sometimes seen.4. Membrane patches were studied which showed one to about twelve levels of outward current which were presumed to result from the opening of up to twelve channels having the same characteristics. The probability of channel open state varied with membrane potential, increasing in the potential range -40 to +40 mV. Channel openings were rare negative to -40 mV. No inward currents through these potassium channels were observed as openings were not seen at membrane potentials negative to E(K).5. When the probability of channel opening was low, channel openings occurred in bursts which could be separated by several seconds. Analysis of the openings of a single channel revealed that open times and short closed times were exponentially distributed with mean durations of 15-45 ms and about 6 ms at zero potential. In some patches regular cyclical openings of several channels occurred. In other patches openings of individual channels appeared to be independent events as they were reasonably fitted by a binomial distribution.6. Following a step change from negative potentials, where channels were closed, to more positive potentials, channel openings increased during a period of 10 s to reach a steady state. No evidence of inactivation was observed.7. These results suggest the existence of a population of potential-sensitive potassium-selective ion channels in the smooth muscle cell membrane which are closed at the resting membrane potential and which open upon depolarization with slow (seconds) kinetics; these may be involved in the slow potential (wave) activity of this muscle.

Action Potentials↗
PubMed2004

[Statistical models for spatial analysis in parasitology].

The simplest way to study the spatial pattern of a disease is the geographical representation of its cases (or some indicators of them) over a map. Maps based on raw data are generally "wrong" since they do not take into consideration for sampling errors. Indeed, the observed differences between areas (or points in the map) are not directly interpretable, as they derive from the composition of true, structural differences and of the noise deriving from the sampling process. This problem is well known in human epidemiology, and several solutions have been proposed to filter the signal from the noise. These statistical methods are usually referred to as Disease Mapping. In geographical analysis a first goal is to evaluate the statistical significance of the heterogeneity between areas (or points). If the test indicates rejection of the hypothesis of homogeneity the following task is to study the spatial pattern of the disease. The spatial variability of risk is usually decomposed into two terms: a spatially structured (clustering) and a non spatially structured (heterogeneity) one. The heterogeneity term reflects spatial variability due to intrinsic characteristics of the sampling units (e.g. igienic conditions of farms), while the clustering term models the association due to proximity between sampling units, that usually depends on ecological conditions that vary over the study area and that affect in similar way breedings that are close to each other. Hierarchical bayesian models are the main tool to make inference over the clustering and heterogeneity components. The results are based on the marginal posterior distributions of the parameters of the model, that are approximated by Monte Carlo Markov Chain methods. Different models can be defined depending on the terms that are considered, namely a model with only the clustering term, a model with only the heterogeneity term and a model where both are included. Model selection criteria based on a compromise between degree of complexity and goodness of fit are then needed to discriminate among them, because each specification has a different biological meaning. Our aim is to demonstrate that these techniques can be used to study the geographical distribution of a parasite infection. Our analyses are based on data collected in 142 farms of the province of Latina. In each breeding a fixed number of sheeps has been sampled (20) and checked for the presence of C. daubneyi. We have specified a Binomial model for the proportion of infected animals in each breeding. The heterogeneity component is modelled in a standard way, while we have used different prior specifications for the clustering term to show how they affect the results. When we use the usual specification also for clustering, the two models show a completely different spatial pattern of infection, probably because the intrinsic spatial structure of the clustering term tend to bias our inferences. The selection criterion indicates in this case the heterogeneity model as the "best" one. However, if we modify the prior so that a lower degree of spatial interaction is assumed, the clustering model is less complex and its goodness of fit better and it should be preferred.

Animal Husbandry↗
PubMed1988

Approximate interval estimation of the ratio of binomial parameters: a review and corrections for skewness.

Various methods for finding confidence intervals for the ratio of binomial parameters are reviewed and evaluated numerically. It is found that the method based on likelihood scores (Koopman, 1984, Biometrics 40, 513-517; Miettinen and Nurminen, 1985, Statistics in Medicine 4, 213-226) performs best in achieving the nominal confidence coefficient, but it may distribute the tail probabilities quite disparately. Using general theory of Bartlett (1953, Biometrika 40, 306-317; 1955, Biometrika 42, 201-203), we correct this method for asymptotic skewness. Following Gart (1985, Biometrika 72, 673-677), we extend this correction to the case of estimating the common ratio in a series of two-by-two tables. Computing algorithms are given and applied to numerical examples. Parallel methods for the odds ratio and the ratio of Poisson parameters are noted.

Algorithms↗
PubMed2002

Bayesian analysis of overdispersed chromosome aberration data with the negative binomial model.

The usual assumption of a Poisson model for the number of chromosome aberrations in controlled calibration experiments implies variance equal to the mean. However, it is known that chromosome aberration data from experiments involving high linear energy transfer radiations can be overdispersed, i.e. the variance is greater than the mean. Present methods for dealing with overdispersed chromosome data rely on frequentist statistical techniques. In this paper. the problem of overdispersion is considered from a Bayesian standpoint. The Bayes Factor is used to compare Poisson and negative binomial models for two previously published calibration data sets describing the induction of dicentric chromosome aberrations by high doses of neutrons. Posterior densities for the model parameters, which characterise dose response and overdispersion are calculated and graphed. Calibrative densities are derived for unknown neutron doses from hypothetical radiation accident data to deterimine the impact of different model assumptions on dose estimates. The main conclusion is that an initial assumption of a negative binomial model is the conservative approach to chromosome dosimetry for high LET radiations.

Bayes Theorem↗
PubMed2001

A closer look at combining data among a small number of binomial experiments.

In a regulatory environment, the regulators and the regulated may not be able to agree on the use of subjective prior information for a clinical trial. The use of a data-based prior offers a greater possibility for agreement, however, the degree of importance given to the prior data may still be contentious. The use of a hierarchical model to link the prior data and the current trial is shown to provide a relatively objective method for assigning weight to the prior data. Using a series of examples combining two binomial experiments, the effect of a hierarchical model on estimating rates, on the degree to which data is combined and on hypothesis testing is illustrated. In addition, the phenomenon in which combining data reduces the precision is explained. Simpler models based on finite mixtures of beta distributions are shown to work as well as the more computationally intensive, continuous mixtures. Lastly, an example combining three concurrent studies is illustrated. Published in 2001 by John Wiley & Sons, Ltd.

Bayes Theorem↗
PubMed2005

Effect of cryogenic treatment on nickel-titanium endodontic instruments.

AIM: To investigate the effects of cryogenic treatment on nickel-titanium endodontic instruments. The null hypothesis was that cryogenic treatment would result in no changes in composition, microhardness or cutting efficiency of nickel-titanium instruments. METHODOLOGY: Microhardness was measured on 30 nickel-titanium K-files (ISO size 25) using a Vicker's indenter. Elemental composition was measured on two instruments using X-ray spectroscopy. A nickel-titanium bulk specimen was analysed for crystalline phase composition using X-ray diffraction. Half of the specimens to be used for each analysis were subjected to a cryogenic treatment in liquid nitrogen (-196 degrees C) for either 3 s (microhardness specimens) or 10 min (other specimens). Cutting efficiency was assessed by recording operator choice using 80 nickel-titanium rotary instruments (ProFile 20, .06) half of which had been cryogenically treated and had been distributed amongst 14 clinicians. After conditioning by preparing four corresponding canals, each pair of instruments were evaluated for cutting efficiency by a clinician during preparation of one canal system in vitro. A Student's t-test was used to analyse the microhardness data, and a binomial test was used to analyse the observer choice data. Composition data were analysed qualitatively. RESULTS: Cryogenically treated specimens had a significantly higher microhardness than the controls (P < 0.001; beta > 0.999). Observers showed a preference for cryogenically treated instruments (61%), but this was not significant (P = 0.21). Both treated and control specimens were composed of 56% Ni, 44% Ti, 0% N (by weight) with a majority in the austenite phase. CONCLUSIONS: Cryogenic treatment resulted in increased microhardness, but this increase was not detected clinically. There was no measurable change in elemental or crystalline phase composition.

Cold Temperature↗
PubMed2001

Estimation of quantal size and number of functional active zones at the calyx of Held synapse by nonstationary EPSC variance analysis.

At the large excitatory calyx of Held synapse, the quantal size during an evoked EPSC and the number of active zones contributing to transmission are not known. We developed a nonstationary variant of EPSC fluctuation analysis to determine these quantal parameters. AMPA receptor-mediated EPSCs were recorded in slices of young (postnatal 8-10 d) rats after afferent fiber stimulation, delivered in trains to induce synaptic depression. The means and the variances of EPSC amplitudes were calculated across trains for each stimulus number. During 10 Hz trains at 2 mm Ca(2+) concentration ([Ca(2+)]), we found linear EPSC variance-mean relationships, with a slope that was in good agreement with the quantal size obtained from amplitude distributions of spontaneous miniature EPSCs. At high release probability with 10 or 15 mm [Ca(2+)], competitive antagonists were used to partially block EPSCs. Under these conditions, the EPSC variance-mean plots could be fitted with parabolas, giving estimates of quantal size and of the binomial parameter N. With the rapidly dissociating antagonist kynurenic acid, quantal sizes were larger than with a slowly dissociating antagonist, suggesting that the effective glutamate concentration was increased at high release probability. Considering the possibility of multivesicular release and moderate saturation of postsynaptic AMPA receptors, we conclude that the binomial parameter N (637 +/- 117; mean +/- SEM) represents an upper limit estimate of the number of functional active zones. We estimate that during normal synaptic transmission, the probability of vesicle fusion at single active zones is in the range of 0.25-0.4.

Animals↗
PubMed1980

An epidemic chain model.

An epidemic chain model is developed by assuming a beta distribution for the probability of being infected by contact with a given infective from the same household. This model includes, as a particular case, the epidemic chain model corresponding to the stochastic Kermack-McKendrick model and, as a limiting case, the Reed-Frost chain binomial model. The advantages of the more general model are illustrated with an application to household data for the common cold. Finally, it is shown how the coefficient of variation of the duration of the infectious period may be estimated without any direct observations on this duration.

Common Cold↗
PubMed1990

One-parameter item response theory models for psychomotor tests involving repeated, independent attempts.

Three one-parameter item response theory models are given as viable models that describe the observed score probabilities of an examinee who takes a multiple attempts, single-item test of a psychomotor skill. These models include the Binomial Trials Model, the Poisson Counts Model, and the Inverse Binomial Model. The paper presents these models and offers suggestions for their estimation and subsequent use in the assessment of psychomotor behavior.

Bayes Theorem↗
PubMed2001

Cytochrome b phylogeny and the taxonomy of great apes and mammals.

In the Linnaean system of classification, the generic status of a species is part of its binomial name, and it is therefore important that the classification at the level of genus is consistent at least in related groups of organisms. Using maximum-likelihood phylogenetic trees constructed from a large number of complete or nearly complete mammalian cytochrome b sequences, I show that the distributions of intrageneric and intergeneric distances derived from these trees are clearly separated, which allows the limits for a more rational generic classification of mammals to be established. The analysis of genetic distances among hominids in this context provides strong support for the inclusion of humans and chimpanzees in the same genus. It is also of interest to decipher the main reasons for the possible biases in the mammalian classification. I found by correlation analysis that the classification of mammals of large body size tends to be oversplit, whereas that of small mammals has an excess of lumping, which may be a manifestation of the larger difficulty in finding diagnostic characters in the classification of small animals. In addition, and contrary to some previous observations, there is no correlation between body size and rate of cytochrome b evolution in mammals, which excludes the difference in evolutionary rates as the cause of the observed body size taxonomic bias.

Animals↗
PubMed1978

[Behavior of calcemia in breast malignancy. Note I (author's transl)].

The authors report a statistical investigation conducted in 95 patients with mammary carcinoma, designed to show the behavior of calcemia in the course of this malignancy. The data were analyzed statistically by the binomial test, the scatter of values (F test of Snedecor), and the t test of Student. The authors confirmed the existence of a statistically significant alteration of calcemia only in the group of patients with metastasis to bone versus control subjects; conversely there was no significant difference of distribution in the various groups in regard to values beyond those given as normal.

Adult↗
PubMed1994

Statistical models of synaptic transmission evaluated using the expectation-maximization algorithm.

Amplitude fluctuations of evoked synaptic responses can be used to extract information on the probabilities of release at the active sites, and on the amplitudes of the synaptic responses generated by transmission at each active site. The parameters that describe this process must be obtained from an incomplete data set represented by the probability density of the evoked synaptic response. In this paper, the equations required to calculate these parameters using the Expectation-Maximization algorithm and the maximum likelihood criterion have been derived for a variety of statistical models of synaptic transmission. These models are ones where the probabilities associated with the different discrete amplitudes in the evoked responses are a) unconstrained, b) binomial, and c) compound binomial. The discrete amplitudes may be separated by equal (quantal) or unequal amounts, with or without quantal variance. Alternative models have been considered where the variance associated with the discrete amplitudes is sufficiently large such that no quantal amplitudes can be detected. These models involve the sum of a normal distribution (to represent failures) and a unimodal distribution (to represent the evoked responses). The implementation of the algorithm is described in each case, and its accuracy and convergence have been demonstrated.

Algorithms↗
PubMedDate not supplied

[Infection by Toxoplasma gondii in children with infantile cerebral palsy].

An analytic relationship between positivity of the indirect immunofluorescent test (IIFT) for toxoplasmosis and clinical findings in a population of 328 children with cerebral infantile palsy (CIP) was performed. Children were distributed by age in one of four groups: I (0-2 years); II (3-6 years); III (7-12 years) and IV (13-18 years). One control group of 168 children with no PCI clinical findings was included. 125 sera were positive at 1:64 dilutions. The study of the binomial mother-child of 40 cases rendered 26 mothers with significant titer values. The majority of positive mothers to IIFT correlated with the youngest children (Groups I, II and III), mainly with group I (70.0%), which showed the highest titer ranges. Correlation between positive IIFT and clinical features was as high as 100.0%.

Adolescent↗
PubMed2006

Multiscale spatial Monte Carlo simulations: multigriding, computational singular perturbation, and hierarchical stochastic closures.

Monte Carlo (MC) simulation of most spatially distributed systems is plagued by several problems, namely, execution of one process at a time, large separation of time scales of various processes, and large length scales. Recently, a coarse-grained Monte Carlo (CGMC) method was introduced that can capture large length scales at reasonable computational times. An inherent assumption in this CGMC method revolves around a mean-field closure invoked in each coarse cell that is inaccurate for short-ranged interactions. Two new approaches are explored to improve upon this closure. The first employs the local quasichemical approximation, which is applicable to first nearest-neighbor interactions. The second, termed multiscale CGMC method, employs singular perturbation ideas on multiple grids to capture the entire cluster probability distribution function via short microscopic MC simulations on small, fine-grid lattices by taking advantage of the time scale separation of multiple processes. Computational strategies for coupling the fast process at small length scales (fine grid) with the slow processes at large length scales (coarse grid) are discussed. Finally, the binomial tau-leap method is combined with the multiscale CGMC method to execute multiple processes over the entire lattice and provide additional computational acceleration. Numerical simulations demonstrate that in the presence of fast diffusion and slow adsorption and desorption processes the two new approaches provide more accurate solutions in comparison to the previously introduced CGMC method.

Algorithms↗
PubMed2005

[Determinants of smoking and cessation during pregnancy].

UNLABELLED: Smoking during pregnancy is harmful to both foetus and the woman herself. Identification of determinants of the smoking and cessation is important for any intervention efforts. Then the aim is finding these factors and assesment their impact. MATERIALS AND METHODS: 18,177 medical records gathered in 2001-2002 througout nationwide telematic perinatal registry. Binomial and multinomial regression was used. MAIN OBSERVATIONS: 27% of pregnant woman cease smoking at onset of the pregnancy, 36,4% limit or cease smoking during the pregnancy, 36,5% continue smoking withuot alteration. The smoking and cessation during pregrancy is assotiated mainly with sociodemografic and also with heath charakteristics. RESULTS: Distribution of smoking women one year befor pregnancy is two modal with extrema for 18 and 45 years of age. For smoking during pregnancy urban area increases the odd, pathology in pregnancy increases the odd, married status decreases the odd, the odd decrease with increasing level of education. For smoking cessation at onset of pregnancy urban area increases the odd, first baby increases the odd , married status increases the odd, the odds increase with increasing maternal age. Change in odds doesn't depend on pathology of pregnancy and maternal diseases in past. Distribution by age of the percentage of smoking women proves effectiveness of the smoking control in Poland. Crucial for smoking and cessation are socjodemographic factors, in smaller degree heath factors. Pregnancy is favourable time for smoking interventions programs.

Adult↗
PubMed1995

Time-frequency analysis of ECG for late potentials in sudden cardiac death survivors and post-myocardial infarction patients.

Late potentials (LPs) are harbingers of sudden cardiac death (SCD) for certain patient populations, including SCD survivors and patients post myocardial infarction. This retrospective study examined the sensitivity and specificity of time-frequency distributions (TFDs) in detecting late potentials in 90 patients using time-domain signal average ECG criteria as a standard for comparison. Three time-domain criteria were employed: QRS duration > 114 msec; LAS > 30 msec; and RMS40 < 20 microV. Time domain criteria were compared with TFD results derived using the binomial transform. TFDs were considered positive if small magnitude (-30 dB) signals > 40 Hz were present 114 msec after the onset of the QRS complex. Results from the binomial transform are comparable to those from the SAECG method (sensitivity = 92.0-100%, specificity = 78-92%).

Adult↗
PubMed2005

Fecal shedding of Mycobacterium avium subsp. paratuberculosis by dairy cows.

Between 1982 and 2000, fecal samples were obtained from 786 cows that were shedding Mycobacterium avium subsp. paratuberculosis (Map). These cows were resident on 93 Pennsylvania dairies (mean herd size, 64 milk cows) that had no or minimal previous testing for Map. Feces were cultured on four tubes of Herrold's egg yolk medium and the distribution of mean Map colony forming units (CFU) was evaluated. Most cows were light (< 10 CFU/tube, 51.4%) or high (> 50 CFU/tube, 30.8%) fecal shedders with fewer cows in the moderate category (10-50 CFU/tube). Of the 786 cows, 192 (24.4%) had colonies in only one of four tubes. In the multivariable negative binomial model, there were significant associations between mean CFU/tube and prevalence, herd size, and season and an interaction between herd size and season. The linear mixed model of continuous tube counts with a random herd effect yielded similar findings with associations with herd size as a continuous variable, season, and an interaction between categorized prevalence and continuous herd size. Variability in CFU/tube was greatest among cows in the same herd, intermediate for replicate tubes from the same cow, and smallest among cows in different herds. Reduction in the number of replicate tubes from four would have reduced the sensitivity of fecal culture for Map by approximately 6% (for three tubes) to 12% (for two tubes).

Animals↗
PubMed2000

Parametric cure models of relative and cause-specific survival for grouped survival times.

With parametric cure models, we can express survival parameters (e.g. cured fraction, location and scale parameters) as functions of covariates. These models can measure survival from a specific disease process, either by examining deaths due to the cause under study (cause-specific survival), or by comparing all deaths to those in a matched control population (relative survival). We present a binomial maximum likelihood algorithm to be used for actuarial data, where follow-up times are grouped into specific intervals. Our algorithm provides simultaneous maximum likelihood estimates for all the parameters of a cure model and can be used for cause-specific or relative survival analysis with a variety of survival distributions. Current software does not provide the flexibility of this unified approach.

Actuarial Analysis↗