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At least 1,459 records · Page 81Linked to original sources
PubMed2007

Statistical modelling of Poisson/log normal data.

In statistical data fitting, self consistency is checked by examining the closeness of the quantity chi(2)/NDF to 1, where chi(2) is the sum of squares of data minus fit divided by standard deviation, and NDF is the number of data minus the number of fit parameters. In order to calculate chi(2) one needs an expression for the standard deviation. In this note several alternative expressions for the standard deviation of data distributed according to a Poisson/log-normal distribution are proposed and evaluated by Monte Carlo simulation. Two preferred alternatives are identified. The use of replicate data to obtain uncertainty is problematic for a small number of replicates. A method to correct this problem is proposed. The log-normal approximation is good for sufficiently positive data. A modification of the log-normal approximation is proposed, which allows it to be used to test the hypothesis that the true value is zero.

Computer Simulation↗
PubMed1993

Analysis of individual positron emission tomography activation maps by detection of high signal-to-noise-ratio pixel clusters.

We present a new method for the analysis of individual brain positron emission tomography (PET) activation maps that looks for activated areas of a certain size rather than pixels with maximum values. High signal-to-noise-ratio pixel clusters (HSC) are identified and their sizes are statistically tested with respect to a Monte-Carlo-derived distribution of cluster sizes in pure noise images. From multiple HSC size tests, a strategy is proposed for control of the overall type I error. The sensitivity and specificity of this method have been assessed using realistic Monte Carlo simulations of brain activation maps. When compared with the gamma 2 statistic of the local maxima distribution, the proposed method showed enhanced sensitivity, particularly for signals of low magnitude and/or large size. Its potential for the individual analysis of PET activation studies is presented in two sets of subjects who underwent two cognitive protocols. Although it can be viewed as an alternative to the classical stereotactic averaging approach, this new method is intended to be a first step toward the analysis of single-subject PET activation studies.

Brain↗
PubMed1995

Modelling patterns of parasite aggregation in natural populations: trichostrongylid nematode-ruminant interactions as a case study.

The characteristically aggregated frequency distribution of macroparasites in their hosts is a key feature of host-parasite population biology. We begin with a brief review of the theoretical literature concerning parasite aggregation. Though this work has illustrated much about both the sources and impact of parasite aggregation, there is still no definite analysis of both these aspects. We then go on to illustrate the use of one approach to this problem--the construction of Moment Closure Equations (MCEs), which can be used to represent both the mean and second moments (variances and covariances) of the distribution of different parasite stages and phenomenological measures of host immunity. We apply these models to one of the best documented interactions involving free-living animal hosts--the interaction between trichostrongylid nematodes and ruminants. The analysis compares patterns of variability in experimental infections of Teladorsagia circumcincta in sheep with the equivalent wildlife situation--the epidemiology of T. circumcincta in a feral population of Soay sheep on St Kilda, Outer Hebrides. We focus on the relationship between mean parasite load and aggregation (inversely measured by the negative binomial parameter, k) for cohorts of hosts. The analysis and empirical data indicate that k tracks the increase and subsequent decline in the mean burden with host age. We discuss this result in terms of the degree of heterogeneity in the impact of host immunity or parasite-induced mortality required to shorten the tail of the parasite distribution (and therefore increase k) in older animals. The model is also used to analyse the relationship between estimated worm and egg counts (since only the latter are often available for wildlife hosts). Finally, we use these results to review directions for future work on the nature and impact of parasite aggregation.

Age Factors↗
PubMed1994

Perception of temporal acoustic patterns by the goldfish (Carassius auratus).

The perception of temporal acoustic patterns was studied in the goldfish using classical respiratory conditioning in combination with a stimulus generalization paradigm. Stimuli consisted of a bandpass filtered pulse repeated in various periodic and aperiodic temporal patterns. In each of 14 experiments, animals received 40 conditioning trials to a given stimulus pattern and were then tested for generalization to eight novel stimuli differing only in temporal pattern. In experiments 1-5, animals were conditioned to a periodic pulse train with a particular interpulse interval (IPI) and then tested to novel periodic pulse trains with various IPIs. Generalization gradients were substantially symmetric and monotonic with repetition rate, suggesting a perceptual continuum in goldfish that is similar to periodicity pitch or roughness in human listeners. Several additional experiments indicated that the perceptual qualities of simple and complex temporal patterns are not primarily determined by spectral structure or pulse rate, but rather are determined by the distribution of IPIs. A model for the central analysis of IPIs was successful in accounting for the results of experiments in which animals were conditioned to simple, periodic stimuli. However, the model failed when animals were conditioned to more complex stimuli having aperiodic temporal patterns. These experiments demonstrate the potential usefulness of the stimulus generalization paradigm for investigating aspects of complex sound source perception in non-human animals.

Acoustic Stimulation↗
PubMed1999

Testing the fit of a quantal model of neurotransmission.

Many studies of synaptic transmission have assumed a parametric model to estimate the mean quantal content and size or the effect upon them of manipulations such as the induction of long-term potentiation. Classical tests of fit usually assume that model parameters have been selected independently of the data. Therefore, their use is problematic after parameters have been estimated. We hypothesized that Monte Carlo (MC) simulations of a quantal model could provide a table of parameter-independent critical values with which to test the fit after parameter estimation, emulating Lilliefors's tests. However, when we tested this hypothesis within a conventional quantal model, the empirical distributions of two conventional goodness-of-fit statistics were affected by the values of the quantal parameters, falsifying the hypothesis. Notably, the tests' critical values increased when the combined variances of the noise and quantal-size distributions were reduced, increasing the distinctness of quantal peaks. Our results support two conclusions. First, tests that use a predetermined critical value to assess the fit of a quantal model after parameter estimation may operate at a differing unknown level of significance for each experiment. Second, a MC test enables a valid assessment of the fit of a quantal model after parameter estimation.

Animals↗
PubMed1997

Variation in labial shoulder geometry of metal ceramic crown preparations: a finite element analysis.

Recent studies have highlighted variations in the geometry of teeth prepared to receive metal ceramic crowns, particularly in the region of the labial shoulder, where shoulder designs have often involved less reduction than is recommended. Using two-dimensional finite element analysis, this study subjected crowns, superimposed upon preparations with clinically common labial margin designs, to loads of 200N in three different directions. The resultant stress distribution within the labial marginal porcelain was examined. Results imply that variations in the marginal preparation geometry of metal ceramic crowns influenced the stress response of the finished crown. Within the limits of this study, a crown constructed a 1.3mm chamfer preparation appeared to have the best response to a simulated load applied to the palatal/incisal surface, at 45 degrees to the long axis.

Crowns↗
PubMed1995

Finite element analysis of stress distribution at the tooth-denture base interface of acrylic resin teeth debonding from the denture base.

Acrylic resin teeth present a problem when they detach unexpectedly from the denture base resin. Detachment is caused by stress concentrations at the tooth/denture base resin interface. In this study, the finite element method was used to examine the stress distribution at this interface when a single static force that resembled incisal bite force was applied. The results indicated that irrespective of the type of acrylic resin teeth used, maximum tensile stresses were found at the palatal aspect of the interface. It is suggested that boxing the tooth in the acrylic resin will help redistribute stress concentrations favorably.

Acrylic Resins↗
PubMed1998

Exponential growth of Escherichia coli B/r during its division cycle is demonstrated by the size distribution in liquid culture.

The Collins and Richmond equation was used to analyze the growth of individual bacterial cells. Birth size was derived from the size of deeply constricted cells in the sample. The analysis was applied to normalized and pooled data from electron micrographs of Escherichia coli showing that cellular length, surface, and volume do not grow linearly as reported before. We present evidence that bacteria grow exponentially during the division cycle, which is consistent with previous proposals. Our results confirm previous incorporation studies that demonstrate basically exponential growth patterns for cell mass during the division cycle.

Bias↗
PubMed1999

Case-control isotonic regression for investigation of elevation in risk around a point source.

Stone's isotonic regression method for analysing count data to estimate disease risk in relation to a point source of environmental pollution is now routinely used. This paper develops the corresponding procedure for case-control data consisting of the locations of individual cases with controls with associated covariate information. In this setting, the generalized likelihood ratio statistic to test the null hypothesis of constant risk against the alternative that risk is a monotone non-increasing function of distance from the point source is intractable. An approximate Monte Carlo test is described, extending an exact test proposed by Bithell for the situation in which there are no covariates. Interval estimates of risk as a function of distance from the point source are constructed by simulation of the sampling distribution of the isotonic regression estimator. The methodology is illustrated by two applications: one to the relative risk of larynx cancers and lung cancers near a now-disused industrial incinerator; the other to the risk of asthma in children in relation to distance of residence from the nearest main road.

Adolescent↗
PubMed2000

Wavelet transforms in estimating scatterer spacing from ultrasound echoes.

Ultrasound echoes from organs such as the liver display resolvable periodicity due to regular scattering centers within tissue. The spacing among such scattering centers has been proposed as a signature to characterize diffuse and focal diseases of the liver. Even though it is highly desirable to be able to estimate an inter-scatterer-spacing (ISS) distribution, current methods can estimate only the mean value of scatterer spacing (MSS) over a tissue length. In this paper, we propose a wavelet transform-based technique that is capable of estimating the location of each scattering center, making it possible to obtain the ISS distribution. We represent liver tissue with a point scatterer model, and show, via computer simulations, that the use of multi-scale information in the wavelet scale-space allows us to estimate the locations of regular scattering centers. We show that both the observation noise and random ultrasound returns from unresolvable tissue microstructure can be removed successfully in the wavelet domain via the properties of the modulus maxima sequence of observation across different scales.

Computer Simulation↗
PubMed1996

Generalization of the variance-covariance method for microdosimetric measurements. I. Basic equations and estimation formulae for constant and time-varying fields.

The variance method of microdosimetric measurements and its extension, the variance-covariance method, permit the determination of an essential parameter of radiation quality, the dose mean event size, y(d). The methods have--among other advantages--the feature that they permit measurements for smaller simulated sites than the conventional single-event technique. It is, therefore, desirable to employ them also for the determination of further moments of the distribution of y. The formulae for the first three moments are here derived both for the case of constant dose rate and of fluctuating dose rates. A second article will use the same mathematical approach to deduce formulae that remain valid even if there are slow changes of the ratio of dose rates in the two detectors for the variance-covariance method. A third article will explore--in terms of microdosimetric data--the applicability of the formulae.

Analysis of Variance↗
PubMedDate not supplied

Triple-goal estimates for disease mapping.

Maps of regional morbidity and mortality rates play an important role in assessing environmental equity. They provide effective tools for identifying areas with potentially elevated risk, determining spatial trend, and formulating and validating aetiological hypotheses about disease. Bayes and empirical Bayes methods produce stable small-area rate estimates that retain geographic and demographic resolution. The beauty of the Bayesian approach lies in its ability to structure complicated models, inferential goals and analyses. Three inferential goals are relevant to disease mapping and risk assessment: (i) computing accurate estimates of disease rates in small geographic areas; (ii) estimating the distribution of disease rates over the region; (iii) ranking the disease rates so that environmental investigation can be prioritized. No single set of estimates can simultaneously optimize these three goals, and Shen and Louis propose a set of estimates that perform well on all three goals. These are optimal for estimating the distribution of rates and for ranking, and maintain a high accuracy in estimating area-specific rates. However, the Shen/Louis method is sensitive to choice of priors. To address this issue we introduce a robustified version of the method based on a smoothed non-parametric estimate of the prior. We evaluate the performance of this method through a simulation study, and illustrate it using a data set of county-specific lung cancer rates in Ohio.

Algorithms↗
PubMed2004

Very diverse CD8 T cell clonotypic responses after virus infections.

We measured CD8 T cell clonotypic diversity to three epitopes recognized in C57BL/6 mice infected with mouse hepatitis virus, strain JHM, or lymphocytic choriomeningitis virus. We isolated epitope-specific T cells with an IFN-gamma capture assay or MHC class I/peptide tetramers and identified different clonotypes by Vbeta chain sequence analysis. In agreement with our previous results, the number of different clonotypes responding to all three epitopes fit a log-series distribution. From these distributions, we estimated that >1000 different clonotypes responded to each immunodominant CD8 T cell epitope; the response to a subdominant CD8 T cell epitope was modestly less diverse. These results suggest that T cell response diversity is greater by 1-2 orders of magnitude than predicted previously.

Animals↗
PubMed1998

Finite element analysis of non-axial versus axial loading of oral implants in the mandible of the dog.

The influence of axial and non-axial occlusal loads on the bone remodelling phenomena around oral implants in an animal experiment is simulated in a finite element analysis. The axial and non-axial loading conditions were introduced by inserting a bilaterally supported fixed partial prosthesis and a cantilever fixed partial prosthesis on two IMZ implants in the mandible of beagle dogs. Earlier quantitative and qualitative histological analyses revealed a statistically significant different remodelling response between both loading conditions. Two-dimensional and three-dimensional models are built to analyse and compare von Mises equivalent stress, maximum principal stress, maximum principal strain and strain energy density distributions, first around a free-standing implant and subsequently around the implants of the two prosthesis designs under the respective resultant in vivo loads. Strong correlations between the calculated stress distributions in the surrounding bone tissue and the remodelling phenomena in the comparative animal model are observed. It is concluded that the highest bone remodelling events coincide with the regions of highest equivalent stress and that the major remodelling differences between axial and non-axial loading are largely determined by the horizontal stress component of the engendered stresses.

Alveolar Process↗
PubMed1999

The modelled benefits of individualizing radiotherapy patients' dose using cellular radiosensitivity assays with inherent variability.

OBJECTIVE: To model the increases in local tumour control that may be achieved, without increasing normal tissue complications, by prescribing a patient's dose based on cellular radiosensitivity measured using an assay possessing inherent variability. METHOD: Patient populations with varying radiosensitivity were simulated, based on measured distributions among cancer patients of the surviving fraction of their fibroblasts given a dose of 2 Gy in vitro (SF2). The dose-response curve for complications in the population was assessed using a formula relating SF2 to normal tissue complication probability (NTCP), by summing the data for the individuals. This curve was similar to clinically-derived dose-response curves. The effect of individualizing the patients' doses was explored, based on individual radiosensitivities measured by SF2, so that every patient had the same low (5%) value of NTCP. RESULTS: It was found that a significant gain (up to around 30%) in tumour control probability (TCP) was predicted for the population when the doses were individualized using a predictive assay result strongly correlated with NTCP. A greater gain in TCP was predicted when each of the individuals were assumed to have a higher sensitivity and the distribution of radiosensitivity in the population was widened to compensate. The gain in TCP was less (around 20%) when considering less-sensitive patients and a narrower distribution of radiosensitivities. The effect of assay variability and other factors that could affect the predictive power of the assay was simulated. Assay variability and an imperfect correlation between in vitro cell survival and tissue complications, rapidly increased the NTCP for the population when treated with individualized doses. However the individualized doses could be reduced so that NTCP declined to an acceptable level, but in this case the TCP for the population also declined. For example, when the assay variability was half the true variability in SF2, the gain in TCP was reduced to around 6%. Also, the predicted gains in population TCP were higher if tumour and normal tissue radiosensitivity were assumed to be correlated. In this case, and in the absence of assay variability, increases in population TCP of about 50% and 30% were predicted, depending on the assumed relative sensitivities of the individual patients compared with that of the population average. For practical application, the division of the patient population simply into three groups of high, average and low radiosensitivity was also examined. The three groups were treated with different doses and the NTCP for the population was kept below 5%. Although the gain in population TCP was less than that predicted with the full individualization, considerable gains of up to 20% were still predicted. This method of dividing the population was more resilient to assay variability and other factors that may affect complications in patients. The modelling suggests that small improvements in TCP (5-10%) may still be achievable even if the correlation between SF2 and late complications is lower at around - 0.4 to - 0.6, as reported in some clinical series. CONCLUSION: Modelling based on measured distributions of fibroblast radiosensitivity shows that improvements in tumour control rates may be achievable through the individualization of radiotherapy dose prescriptions of cancer patients, when assay variability is less than about 50% of the true variability in radiosensitivity, and with greater benefits if tumour and normal tissue radiosensitivity are correlated. Tripartite stratification of the population proved to be less sensitive to assay uncertainty, and can provide most of the benefits of the full individualization.

Algorithms↗
PubMed1996

Switchboard simulation to improve productivity and customer service.

An application of classical industrial engineering/operations research techniques (i.e., multichannel queueing analysis) and detailed workload distribution data. An analytic simulation model developed on a personal computer (PC) is used with interactive analysis to develop switchboard coverage requirements and optimal staffing schedules by time of day and day of week. This represents a tangible example of how classical techniques can be used with newer approaches and a close working relationship between the analyst and line management, to solve a practical problem of optimizing both productivity and customer service quality.

Computer Simulation↗
PubMed1990

Congenital malformations in the Fylde region of Lancashire, England 1957-1973.

This paper uses data collected by a consultant paediatrician to examine variations in the prevalence of neural tube and cardiovascular malformations within the Fylde region of North West England. Results at the district scale indicate contrasts in the geographical distributions of the two classes of malformation and these are then further assessed via a case-control study which standardises for factors such as date of conception, age of mother and parity. The results of this study suggest that there were wards in Blackpool and Fleetwood with unusually high prevalences of neural tube defects. Further research is being undertaken to identify the causes of these concentrations.

Case-Control Studies↗
PubMed2005

Electroosmotic flow analysis of a branched U-turn nanofluidic device.

In this paper, we present the analysis of electroosmotic flow in a branched -turn nanofluidic device, which we developed for detection and sorting of single molecules. The device, where the channel depth is only 150 nm, is designed to optically detect fluorescence from a volume as small as 270 attolitres (al) with a common wide-field fluorescent setup. We use distilled water as the liquid, in which we dilute 110 nm fluorescent beads employed as tracer-particles. Quantitative imaging is used to characterize the pathlines and velocity distribution of the electroosmotic flow in the device. Due to the device's complex geometry, the electroosmotic flow cannot be solved analytically. Therefore we use numerical flow simulation to model our device. Our results show that the deviation between measured and simulated data can be explained by the measured Brownian motion of the tracer-particles, which was not incorporated in the simulation.

Computer Simulation↗