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At least 1,387 records · Page 77Linked to original sources
PubMed2002

Effects of temporal modelling on the statistical uncertainty of spatiotemporal distributions estimated directly from dynamic SPECT projections.

Artefacts can result when reconstructing a dynamic image sequence from inconsistent single photon emission computed tomography (SPECT) projection data acquired by a slowly rotating gantry. The artefacts can lead to biases in kinetic parameters estimated from time-activity curves generated by overlaying volumes of interest on the images. Insufficient sampling and truncation of projections by cone-beam collimators can cause additional artefacts. To overcome these sources of bias in conventional image based dynamic data analysis, we have been investigating the estimation of time-activity curves and kinetic model parameters directly from dynamic SPECT projection data by modelling the spatial and temporal distribution of the radiopharmaceutical throughout the projected field of view. In the present work, we perform Monte Carlo simulations to study the effects of the temporal modelling on the statistical variability of the reconstructed spatiotemporal distributions. The simulations utilize fast methods for fully four-dimensional (4D) direct estimation of spatiotemporal distributions and their statistical uncertainties, using a spatial segmentation and temporal B-splines. The simulation results suggest that there is benefit in modelling higher orders of temporal spline continuity. In addition, the accuracy of the time modelling can be increased substantially without unduly increasing the statistical uncertainty, by using relatively fine initial time sampling to capture rapidly changing activity distributions.

Algorithms↗
PubMedDate not supplied

[Distribution of the cestode Caryophyllaeides fennica (Cestoda: Lytocestidae) in the population of cyprinid fish in the Rybinsk water reservoir].

The distribution of the cestode Caryophyllaeides fennica in populations of the ide, roach, white bream and bream from the Rybinsk reservoir has been analyzed in regard to fish age. The relative abundance of C. fennica in populations of each host species was calculated as product of the helminthes abundance by the fish number in age groups. The highest prevalence and abundance of cestodes was found in the ide. All age classes of this species were infected, with the maximum in fishes of the age 3+ ... 5+. The roach is infected with C. fennica till only 10-year age; brean is infected till the age 4+. In the white bream C. fennica is an occasional parasite. The cestode number among hosts was as follows: bream--68%; roach--26%, ide--5%, white bream--1%. Different approaches to the estimation of the parasite abundance distribution among several host species (in terms of mean prevalence and intensity of the relative abundance of parasites) are discussed.

Aging↗
PubMed2005

Reforming health care: evidence from quantile regressions for counts.

I consider the problem of estimating the effect of a health care reform on the frequency of individual doctor visits when the reform effect is potentially different in different parts of the outcome distribution. Quantile regression is a powerful method for studying such heterogeneous treatment effects. Only recently has this method been extended to situations where the dependent variable is a (non-negative integer) count. An analysis of a 1997 health care reform in Germany shows that lower quantiles, such as the first quartile, fell by substantially larger amounts than what would have been predicted based on Poisson or negative binomial models.

Adult↗
PubMed2002

Determination of cellular strains by combined atomic force microscopy and finite element modeling.

Many organs adapt to their mechanical environment as a result of physiological change or disease. Cells are both the detectors and effectors of this process. Though many studies have been performed in vitro to investigate the mechanisms of detection and adaptation to mechanical strains, the cellular strains remain unknown and results from different stimulation techniques cannot be compared. By combining experimental determination of cell profiles and elasticities by atomic force microscopy with finite element modeling and computational fluid dynamics, we report the cellular strain distributions exerted by common whole-cell straining techniques and from micromanipulation techniques, hence enabling their comparison. Using data from our own analyses and experiments performed by others, we examine the threshold of activation for different signal transduction processes and the strain components that they may detect. We show that modulating cell elasticity, by increasing the F-actin content of the cytoskeleton, or cellular Poisson ratio are good strategies to resist fluid shear or hydrostatic pressure. We report that stray fluid flow in some substrate-stretch systems elicits significant cellular strains. In conclusion, this technique shows promise in furthering our understanding of the interplay among mechanical forces, strain detection, gene expression, and cellular adaptation in physiology and disease.

Actins↗
PubMed2006

The coalescence time of sampled genes in the structured coalescent model.

The aim of this article is to investigate the distribution of the coalescence time (T) for sampled genes in the structured coalescent. We obtain some exact solutions for small samples and approximate distributions for n sampled genes in strong and weak migration. We also conduct computer simulation to evaluate efficiencies of these approximations and show the dependency of the distribution of the coalescence time on the geographical structure and the intensity of migration. In a panmictic population, we prove that the conditional distribution of the coalescence time given the number of segregating sites (S) among sampled genes is given by the weighted mean of the convolution of gamma distributions. We also study the joint distribution of T and S in the structured coalescent model and show some exact solutions.

Analysis of Variance↗
PubMed1995

Reference values for fetal hemoglobin concentration in blood of steel-mill workers.

The concentration of fetal hemoglobin (HbF) in blood of 195 healthy men and 39 women was measured by alkali denaturation method of Singer et al. Arithmetic mean in the group of men was 0.325% whereas in women it was 0.399%. The difference between the means was statistically significant. Frequency histograms showed two unlike subpopulations with wider span of values in women, different standardised skewness and kurtosis. Kolmogorov-Smirnoff test revealed a significant abnormality of both distributions. The data presented may serve for the comparison of HbF values obtained in persons living and working in similar microclimatic conditions.

Adult↗
PubMed1997

Semiparametric regression analysis for recurrent event interval counts.

This paper deals with analysis of data from longitudinal studies where the rate of a recurrent event characterizing morbidity is the primary criterion for treatment evaluation. We consider clinical trials which require patients to visit their clinical center at successive scheduled times as part of follow-up. At each visit, the patient reports the number of events that occurred since the previous visit, or an examination reveals the number of accumulated events, such as skin cancers. The exact occurrence times of the events are unavailable and the actual patient visit times typically vary randomly about the scheduled follow-up times. Each patient's record thus consists of a sequence of clinic visit dates, event counts corresponding to the successive time intervals between clinic visits, and baseline covariates. We propose a semiparametric regression model, extending the fully parametric model of Thall (1988, Biometrics 44, 197-209), to estimate and test for covariate effects on the rate of events over time while also accounting for the possibly time-varying nature of the underlying event rate. Covariate effects enter the model parametrically, while the underlying time-varying event rate is modelled nonparametrically. The method of Severini and Wong (1992, Annals of Statistics 20, 1768-1802) is used to construct asymptotically efficient estimators of the parametric component and to specify their asymptotic distribution. A simulation study and application to a data set are provided.

Biometry↗
PubMed2005

Institutional risk factors for outbreaks of nosocomial gastroenteritis: survival analysis of a cohort of hospital units in South-west England, 2002-2003.

Nosocomial outbreaks of gastroenteritis are a major burden on hospital inpatient services, costing an estimated pound115 million annually to the English National Health Service. We actively followed-up 171 inpatient units from four major acute hospitals and 11 community hospitals in South-west England for one year. Outbreaks of gastroenteritis were ascertained through an active surveillance network using standard clinical definitions. Survival analysis Cox regression models using an outbreak of gastroenteritis as the endpoint were fitted to identify institutional and operational attributes related to increased outbreak rates at the level of the care unit. Greater number of beds in unit [hazard ratio (HR) 1.22 (per 10 additional beds), 95% confidence intervals (CI) 0.96-1.55] was associated with increased hazard, as were geriatric (HR 2.6, 95%CI 1.6-4.3) and general medical (HR 1.7, 95%CI 1.1-2.6) care units. The average length of stay on a unit was inversely associated with outbreak incidence [HR=0.89 (per additional week of stay), 95%CI 0.80-0.99]. Larger care units and those with higher throughput have increased rates of gastroenteritis outbreaks. These results should guide infection control policy and support the design of hospitals with smaller care units.

Caliciviridae Infections↗
PubMed2003

Noise in gene expression as the source of non-genetic individuality in the chemotactic response of Escherichia coli.

A deterministic computer model of the signal transduction pathway mediating bacterial chemotaxis was used to examine the variation in both unstimulated swimming behaviour and adaptation time to stimuli in clonal populations of cells. Copy numbers of proteins in the pathway were computed from a simplified model of transcription and translation that predicts greater-than-Poissonian statistics. Simulated and experimental individuality data could be brought into good agreement on varying the noise strength of the protein copy number distributions. In the simulations, all the proteins in the pathway are involved to a significant degree in the appearance of phenotypic diversity, although there is a modest decrease in influence with increasing copy number.

Adaptation, Biological↗
PubMed2004

Statistical methods for clinical verification of dose-response parameters related to esophageal stricture and AVM obliteration from radiotherapy.

The purpose of this work is to provide some statistical methods for evaluating the predictive strength of radiobiological models and the validity of dose-response parameters for tumour control and normal tissue complications. This is accomplished by associating the expected complication rates, which are calculated using different models, with the clinical follow-up records. These methods are applied to 77 patients who received radiation treatment for head and neck cancer and 85 patients who were treated for arteriovenous malformation (AVM). The three-dimensional dose distribution delivered to esophagus and AVM nidus and the clinical follow-up results were available for each patient. Dose-response parameters derived by a maximum likelihood fitting were used as a reference to evaluate their compatibility with the examined treatment methodologies. The impact of the parameter uncertainties on the dose-response curves is demonstrated. The clinical utilization of the radiobiological parameters is illustrated. The radiobiological models (relative seriality and linear Poisson) and the reference parameters are validated to prove their suitability in reproducing the treatment outcome pattern of the patient material studied (through the probability of finding a worse fit, area under the ROC curve and chi2 test). The analysis was carried out for the upper 5 cm of the esophagus (proximal esophagus) where all the strictures are formed, and the total volume of AVM. The estimated confidence intervals of the dose-response curves appear to have a significant supporting role on their clinical implementation and use.

Angiography↗
PubMed2000

Applying the saddlepoint approximation to bivariate stochastic processes.

The problem of moment closure is central to the study of multitype stochastic population dynamics since equations for moments up to a given order will generally involve higher-order moments. To obtain a Normal approximation, the standard approach is to replace third- and higher-order moments by zero, which may be severely restrictive on the structure of the p.d.f. The purpose of this paper is therefore to extend the univariate truncated saddlepoint procedure to multivariate scenarios. This has several key advantages: no distributional assumptions are required; it works regardless of the moment order deemed appropriate; and, we obtain an algebraic form for the associated p.d.f. irrespective of whether or not we have complete knowledge of the cumulants. The latter is especially important, since no families of distributions currently exist which embrace all cumulants up to any given order. In general the algorithm converges swiftly to the required p.d.f.; analysis of a severe test case illustrates its current operational limit.

Algorithms↗
PubMed1998

Effect of charge interactions on the carboxylate vibrational stretching frequency in c-type cytochromes investigated by continuum electrostatic calculations and FTIR spectroscopy.

The FTIR spectra of the asymmetric carboxylate absorption region of three c-type cytochromes--namely horse heart, yeast and bonito cytochromes c--as well as continuum electrostatic calculations performed on their respective protein matrices, show that these combined methods can target specific protein regions and yield pertinent protein charge information that correlates with the observed spectral data. Deconvolution of the IR carboxylate stretch frequency region (1525-1675 cm-1) in the three cytochromes yield different v(oco)a distributions. In the case of the bonito cytochrome c carboxylates, two v(oco)a populations are clearly distinguishable in the deconvoluted spectra--which is not the case for the more complex v(oco)a deconvolutions of the other two cytochromes. The frequency distributions of the calculated potentials are consistent with the experimental observations and we conclude that the IR carboxylate absorption in proteins can be modified by the electrostatic environment.

Animals↗
PubMed1993

Malaria prevalence amongst Brazilian Indians assessed by a new mathematical model.

An alternative way to estimate the endemic level of malaria amongst Brazilian indians is proposed. This is achieved by estimating the age-related 'force of infection' of malaria (the effective inoculation rate), applying a mathematical model, described elsewhere, to serological data. In addition we present a way to estimate the Basic Reproductive Rate of malaria in the same area. The results have shown a good degree of accuracy in describing the endemic pattern of malaria in the area, and also indicate some relevant aspects of its age distribution related to the design of control strategies.

Adolescent↗
PubMed2000

On the average coefficient of dominance of deleterious spontaneous mutations.

T. Mukai and co-workers in the late 1960s and O. Ohnishi in the 1970s carried out a series of experiments to obtain direct estimates of the average coefficient of dominance (h) of minor viability mutations in Drosophila melanogaster. The results of these experiments, although inconsistent, have been interpreted as indicating slight recessivity of deleterious mutations, with h approximately 0.4. Mukai obtained conflicting results depending on the type of heterozygotes used, some estimates suggesting overdominance and others partial dominance. Ohnishi's estimates, based on the ratio of heterozygous to homozygous viability declines, were more consistent, pointing to the above value. However, we have reanalyzed Ohnishi's data, estimating h by the regression method, and obtained a much smaller estimate of approximately 0.1. This significant difference can be due partly to the different weighting implicit in the estimates, but we suggest that this is not the only explanation. We propose as a plausible hypothesis that a putative nonmutational decline in viability occurring in the first half of Ohnishi's experiment (affecting both homozygotes and heterozygotes) has biased upward the estimates from the ratio, while it would not bias the regression estimates. This hypothesis also explains the very high h approximately 0.7 observed in Ohnishi's high-viability chromosomes. By constructing a model of spontaneous mutations using parameters in the literature, we investigate the above possibility. The results indicate that a model of few mutations with moderately large effects and h approximately 0.2 is able to explain the observed estimates and the distributions of homozygous and heterozygous viabilities. Accounting for an expression of mutations in genotypes with the balancer chromosome Cy does not alter the conclusions qualitatively.

Animals↗
PubMed2000

Predicting time to decompression illness during exercise at altitude, based on formation and growth of bubbles.

For altitude decompressions, we hypothesized that reported onset times of limb decompression illness (DCI) pain symptoms follow a probability distribution related to total bubble volume [V(b.)(t)] as a function of time. Furthermore, we hypothesized that the probability of ever experiencing DCI during a decompression is associated with the cumulative volume of bubbles formed. To test these hypotheses, we first used our previously developed formation-and-growth model (Am J Physiol Regulatory Integrative Comp Physiol 279: R2304-R2316, 2000) to simulate Vb.(t) for 20 decompression profiles in which 334 human subjects performed moderate repetitive skeletal muscle exercise (827 kJ/h) in an altitude chamber. Using survival analysis, we determined that, for a controlled condition of exercise, the fraction of the subject population susceptible to DCI can be approximately expressed as a power function of the formation-and-growth model-predicted cumulative volume of bubbles throughout the altitude exposure. Furthermore, for this fraction, the probability density distribution of DCI onset times is approximately equal to the ratio of the time course of formation-and growth-modeled total bubble volume to the predicted cumulative volume.

Altitude↗
PubMed2005

Estimating the number of plasmids taken up by a eukaryotic cell during transfection and evidence that antisense RNA abolishes gene expression in Physarum polycephalum.

We have estimated the statistical distribution of the number of plasmids taken up by individual Jurkat lymphoma cells during electroporation in the presence of two plasmids, one encoding for yellow (EYFP) the other for cyan (ECFP) fluorescent protein. The plasmid concentration at which most of the cells take up only one plasmid or several molecules was determined by statistical analysis. We found that cells behaved slightly heterogeneous in plasmid uptake and describe how the homogeneity of a cell population can be quantified by Poisson statistics in order to identify experimental conditions that yield homogeneously transfection-competent cell populations. The experimental procedure worked out with Jurkat cells was applied to assay the effectiveness of antisense RNA in knocking down gene expression in Physarum polycephalum. Double transfection of flagellates with vectors encoding EYFP and antisense-EYFP revealed for the first time that gene expression can be suppressed by co-expression of antisense RNA in Physarum. Quantitative analysis revealed that one copy of antisense expressing gene per EYFP gene was sufficient to completely suppress formation of the EYFP protein in Physarum.

Animals↗
PubMed1996

Probability density estimation for the interpretation of neural population codes.

1. Electrophysiological recording data from multiple cells in motor cortex and elsewhere often are interpreted using the population vector method pioneered by Georgopoulos and coworkers. This paper proposes an alternative method for interpreting coding across populations of cells that may succeed under circumstances in which the population vector fails. 2. Population codes are analyzed using probability theory to find the complete conditional probability density of a movement parameter given the firing pattern of a set of cells. 3. The conditional probability density when a single cell fires is proportional to the shape of the cell's tuning curve of firing rate in response to different movement parameters. 4. The conditional density when multiple cells fire is proportional to the product of their tuning curves. 5. Movement parameters can be estimated from the conditional density using statistical maximum likelihood or minimum mean-squared error methods. 6. Simulations show that density estimation correctly finds movement directions for nonuniform distributions of preferred directions and noncosine cell tuning curves, whereas the population vector method fails for these cases. 7. Probability methods thus provide a statistically based alternative to the population vector for interpreting electrophysiological recording data from multiple cells.

Cell Count↗
PubMed2001

Spotting neural spike patterns using an adversary background model.

The detection of a specific stochastic pattern embedded in an unknown background noise is a difficult pattern recognition problem, encountered in many applications such as word spotting in speech. A similar problem emerges when trying to detect a multineural spike pattern in a single electrical recording, embedded in the complex cortical activity of a behaving animal. Solving this problem is crucial for the identification of neuronal code words with specific meaning. The technical difficulty of this detection is due to the lack of a good statistical model for the background activity, which rapidly changes with the recording conditions and activity of the animal. This work introduces the use of an adversary background model. This model assumes that the background "knows" the pattern sought, up to a first-order statistics, and this "knowledge" creates a background composed of all the permutations of our pattern. We show that this background model is tightly connected to the type-based information-theoretic approach. Furthermore, we show that computing the likelihood ratio is actually decomposing the log-likelihood distribution according to types of the empirical counts. We demonstrate the application of this method for detection of the reward patterns in the basal ganglia of behaving monkeys, yielding some unexpected biological results.

Action Potentials↗