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PubMed2002

PCR detection of Tetramicra brevifilum (Microspora) infection in turbot (Scophthalmus maximus L.) musculature.

This study investigated the spatial distribution of Tetramicra brevifilum spores in the musculature of infected turbot Scophthalmus maximus, with the aim of identifying the most appropriate body locations for diagnostic assays. A PCR protocol optimized for the detection of T. brevifilum spores in turbot muscle is also described. In fish showing low- and moderate-intensity infection, the spatial distribution of spores was best fitted by a negative binomial distribution, indicating a clumped spatial pattern; the negative binomial coefficient k was lower for fish with low-intensity infection, indicating a more markedly clumped pattern in these fish. In fish with high-intensity infection, the spatial distribution of spores was best fitted by the Poisson distribution, indicating a random pattern. In both low- and moderate-intensity infection, spores were present at highest density in the musculature adjoining the dorsal fins. Samples for PCR were therefore obtained from this location. PCR amplification was of the small subunit ribosomal DNA (SSUrDNA), using a pair of species-specific primers that amplify the 1250 bp product. The PCR protocol developed showed better sensitivity than microscopical techniques (detection rate by microscopy 25%, versus 42% by PCR), suggesting that it may be useful for routine screening for Tetramicra brevifilum infection in cultured turbot.

Animals↗
PubMed2000

Random effects modeling of multiple binomial responses using the multivariate binomial logit-normal distribution.

The multivariate binomial logit-normal distribution is a mixture distribution for which, (i) conditional on a set of success probabilities and sample size indices, a vector of counts is independent binomial variates, and (ii) the vector of logits of the parameters has a multivariate normal distribution. We use this distribution to model multivariate binomial-type responses using a vector of random effects. The vector of logits of parameters has a mean that is a linear function of explanatory variables and has an unspecified or partly specified covariance matrix. The model generalizes and provides greater flexibility than the univariate model that uses a normal random effect to account for positive correlations in clustered data. The multivariate model is useful when different elements of the response vector refer to different characteristics, each of which may naturally have its own random effect. It is also useful for repeated binary measurement of a single response when there is a nonexchangeable association structure, such as one often expects with longitudinal data or when negative association exists for at least one pair of responses. We apply the model to an influenza study with repeated responses in which some pairs are negatively associated and to a developmental toxicity study with continuation-ratio logits applied to an ordinal response with clustered observations.

Abnormalities, Drug-Induced↗
PubMed1990

Applicability of presence-absence and sequential sampling for ovitrap surveillance of Aedes (Diptera: Culicidae) in Chiang Mai, northern Thailand.

Applicability of presence or absence sampling for ovitrap surveillance of Aedes aegypti (L.) and Aedes albopictus (Skuse) was examined for data collected in Chiang Mai, northern Thailand. Distribution of eggs per trap was contagious but did not fit the negative binomial distribution with a common k. The relationship between the mean number of eggs per trap and the proportion of positive traps was described using Gerrard & Chiang's model, which does not assume particular distribution patterns. Using this relation, the mean number of eggs per trap with confidence limits can be estimated without egg counts. Potential usefulness of presence or absence sequential sampling for decision making (when to initiate vector control for prevention of dengue hemorrhagic fever) was shown.

Aedes↗
PubMed1996

Chromosome aberrations and rogue cells in lymphocytes of Chernobyl clean-up workers.

A cytogenetic analysis was performed on peripheral blood lymphocytes from 183 Chernobyl clean-up workers and 27 control individuals. Increased frequencies of chromosome aberrations were associated with exposure to radiation at Chernobyl, alcohol abuse and a history of recent influenza infection. However, only approximately 20% of Chernobyl clean-up workers had an increased frequency of dicentric and ring chromosomes. At the same time, an increased frequency of acentric fragments in lymphocytes of clean-up workers was characteristic. The use of multivitamins as dietary supplement significantly decreased the frequency of chromosome aberrations, especially of chromatid breaks. Rogue cells were found in lymphocytes of 28 clean-up workers and 3 control individuals. The appearance of rogue cells was associated with a recent history of acute respiratory disease (presumably caused by adenoviral infection) and, probably, alcohol abuse. Dicentric chromosomes in rogue cells were distributed according to a negative binomial distribution. Occurrence of rogue cells due to a perturbation of cell cycle control and abnormal apoptosis is suggested.

Adult↗
PubMedDate not supplied

Quantal measurement and analysis methods compared for crayfish and Drosophila neuromuscular junctions, and rat hippocampus.

Quantal content of transmission was estimated for three synaptic systems (crayfish and Drosophila neuromuscular junctions, and rat dentate gyrus neurons) with three different methods of measurement: direct counts of released quanta, amplitude measurements of evoked and spontaneous events, and charge measurements of evoked and spontaneous events. At the crayfish neuromuscular junction, comparison of the three methods showed that estimates from charge measurements were closer to estimates from direct counts, since amplitude measurements were more seriously affected by variable latency in evoked release of quantal units. Thus, charge measurements are better for estimating quantal content when direct counts cannot be made, as in crayfish at high frequency of stimulation or in the dentate gyrus neurons. At the Drosophila neuromuscular junction, there is almost no latency variation of quantal release in realistic physiological solutions, and the methods based upon amplitudes and charge give similar results. Distributions of evoked synaptic quantal events obtained by direct counts at the crayfish neuromuscular junction were compared to statistical distributions obtained by best fits. Binomial distributions with uniform or non-uniform probabilities of release generally provided good fits to the observations. From best fit distributions, the quantal parameters n (number of release sites) and p (their probability of release) can be calculated. We used two algorithms to estimate n and p: one allows for non-uniform probability of release and uses a modified chi-square (chi 2) criterion, and the second assumes uniform probability of release and derives parameters from maximum likelihood estimation (MLE). The bootstrap estimate of standard errors is used to determine the accuracy of n and p estimates.

Animals↗
PubMed2006

Bayesian geostatistical prediction of the intensity of infection with Schistosoma mansoni in East Africa.

A Bayesian geostatistical model was developed to predict the intensity of infection with Schistosoma mansoni in East Africa. Epidemiological data from purpose-designed and standardized surveys were available for 31,458 schoolchildren (90% aged between 6 and 16 years) from 459 locations across the region and used in combination with remote sensing environmental data to identify factors associated with spatial variation in infection patterns. The geostatistical model explicitly takes into account the highly aggregated distribution of parasite distributions by fitting a negative binomial distribution to the data and accounts for spatial correlation. Results identify the role of environmental risk factors in explaining geographical heterogeneity in infection intensity and show how these factors can be used to develop a predictive map. Such a map has important implications for schisosomiasis control programmes in the region.

Adolescent↗
PubMed1997

Analysis of overdispersed count data by mixtures of Poisson variables and Poisson processes.

Count data often show overdispersion compared to the Poisson distribution. Overdispersion is typically modeled by a random effect for the mean, based on the gamma distribution, leading to the negative binomial distribution for the count. This paper considers a larger family of mixture distributions, including the inverse Gaussian mixture distribution. It is demonstrated that it gives a significantly better fit for a data set on the frequency of epileptic seizures. The same approach can be used to generate counting processes from Poisson processes, where the rate or the time is random. A random rate corresponds to variation between patients, whereas a random time corresponds to variation within patients.

Anticonvulsants↗
PubMed1996

The shape of the distribution of the number of sexual partners.

Information on the number of sexual partners that people have is necessary for predicting the likely long term course of the AIDS epidemic. More information is required than is provided by simply stating the mean and variance of the number of partners. It is useful to find a family of curves which approximate data on the proportion of people in the various 'number of partners' categories. Two Australian surveys of the sexual behaviour of first year university behavioural science students were analysed. It was found here that log-normal distributions gave good approximations to the distribution of number of partners amongst people who had more than one partner. Gamma and negative binomial distributions gave less satisfactory fits and the truncated normal and Poisson distributions were clearly unable to match the data.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Frequency distribution of Wuchereria bancrofti microfilariae in human populations and its relationships with age and sex.

This paper examines the effects of host age and sex on the frequency distribution of Wuchereria bancrofti infections in the human host. Microfilarial counts from a large data base on the epidemiology of bancroftian filariasis in Pondicherry, South India are analysed. Frequency distributions of microfilarial counts divided by age are successfully described by zero-truncated negative binomial distributions, fitted by maximum likelihood. Parameter estimates from the fits indicate a significant trend of decreasing overdispersion with age in the distributions above age 10; this pattern provides indirect evidence for the operation of density-dependent constraints on microfilarial intensity. The analysis also provides estimates of the proportion of mf-positive individuals who are identified as negative due to sampling errors (around 5% of the total negatives). This allows the construction of corrected mf age-prevalence curves, which indicate that the observed prevalence may underestimate the true figures by between 25% and 100%. The age distribution of mf-negative individuals in the population is discussed in terms of current hypotheses about the interaction between disease and infection.

Adolescent↗
PubMed1994

Monte Carlo methods for exploring sensitivity to distributional assumptions in a Bayesian analysis of a series of 2 x 2 tables.

This paper develops Monte Carlo methods for a Bayesian analysis of a series of 2 x 2 tables under a variety of distributional assumptions. I assume that the data in each table were generated from a pair of binomial distributions and the logarithm of odds of a favourable response follows a bivariate distribution with means that are linear functions of covariates and an arbitrary covariance matrix. I use Gibbs and importance sampling methods to obtain various characteristics of the posterior distribution of the quantities of interest. I apply the method to analyse the data from a population case-control study. Given the size of the population at risk I also derive the posterior distribution of the risk difference defined as the difference in the probabilities of disease development in the exposed and unexposed groups.

Bayes Theorem↗
PubMed1991

Frequency distribution of Brugia malayi microfilariae in human populations.

This study examines the effects of host age and sex on the frequency distribution of Brugia malayi infections in the human host. Microfilarial (mf) counts for a large data base on the epidemiology of brugian filariasis in Shertallai, Kerala, South India are analysed. Frequency distributions of microfilarial counts partitioned by age are successfully described by zero-truncated negative binomial distributions, fitted by maximum likelihood. This analysis provides estimates of the proportion of mf-positive individuals who are identified as negative due to sampling errors, allowing the construction of corrected mf age-prevalence curves, which indicate that the observed prevalence may under-estimate the true figures by between 18 and 47%. There is no evidence from these results for a decrease in the degree of over-dispersion of parasite frequency distributions with host age, such as might be produced by the acquired immunity to infection. This departure from the pattern in bancroftian filariasis (where there is evidence of such decreases in over-dispersion; Das et al. 1990) is discussed in terms of the long history of filariasis control (and consequently low infection prevalence) in Shertallai.

Adolescent↗
PubMed2005

Modeling the dependence between the number of trials and the success probability in binary trials.

A model for binary trials based on a bivariate generalization of the Poisson process for both the number of successes and number of trials with the transition rates dependent on the accumulating numbers of successes and trials is used to reanalyze some recently published data of Zhu, Eickhoff, and Kaiser (2003, Biometrics59, 955-961). This modeling admits alternative distributions for the numbers of trials and the numbers of successes conditional on the number of trials which generalize the Poisson and binomial distributions, without some of the restrictions apparent in the beta-binomial-Poisson mixed modeling of Zhu et al. (2003). Some quite marked differences between the results of this analysis and those described in Zhu et al. (2003) are apparent.

Animals↗
PubMed1999

Use of predictive probabilities in phase II and phase III clinical trials.

Predictive probability is particularly useful in aiding a decision-making process related to drug development. This is especially true for decisions occurring as the result of interim analyses of clinical trials. Examples of clinical trial applications of Bayesian predictive probability and the use of the beta-binomial distribution are described.

Bayes Theorem↗
PubMed2006

Microfilarial distribution of Loa loa in the human host: population dynamics and epidemiological implications.

Severe adverse events (SAEs) following ivermectin treatment may occur in people harbouring high Loa loa microfilarial (mf) densities. In the context of mass ivermectin distribution for onchocerciasis control in Africa, it is crucial to define precisely the geographical distribution of L. loa in relation to that of Onchocerca volvulus and predict the prevalence of heavy infections. To this end, we analysed the distribution of mf loads in 4183 individuals living in 36 villages of central Cameroon. Mf loads were assessed quantitatively by calibrated blood smears, collected prior to ivermectin distribution. We explored the pattern of L. loa mf aggregation by fitting the (zero-truncated) negative binomial distribution and estimating its overdispersion parameter k by maximum likelihood. The value of k varied around 0.3 independently of mf intensity, host age, village and endemicity level. Based on these results, we developed a semi-empirical model to predict the prevalence of heavy L. loa mf loads in a community given its overall mf prevalence. If validated at the continental scale and linked to predictive spatial models of loiasis distribution, this approach would be particularly useful for optimizing the identification of areas at risk of SAEs and providing estimates of populations at risk in localities where L. loa and O. volvulus are co-endemic.

Adolescent↗
PubMed1990

Variability in expression of common fragile sites: in search of a new criterion.

Fragile sites are nonrandom, heritable sites on chromosomes that can be induced to form gaps, breaks, and rearrangements under specific conditions. There is currently no established criterion to define a common fragile site. We applied seven published criteria to our data from three groups of subjects: (1) three pairs of like-sexed twins, (2) four unaffected von Hippel-Lindau (VHL) family members, and (3) six patients affected with VHL disease. Substantial differences were present in the numbers of sites considered positive by these criteria. While some of this variability can be attributed to technical factors, our data illustrate the problems in comparing results from different studies to assess the significance of fragile sites. A recently published criterion is based upon the Poisson distribution. We found this criterion to be flawed in its presentation, and furthermore, the Poisson distribution did not provide an adequate approximation to our data. We propose here an alternative approach based upon the negative binomial distribution.

Binomial Distribution↗
PubMed2005

The performance of mixture models in heterogeneous closed population capture-recapture.

Dorazio and Royle (2003, Biometrics 59, 351-364) investigated the behavior of three mixture models for closed population capture-recapture analysis in the presence of individual heterogeneity of capture probability. Their simulations were from the beta-binomial distribution, with analyses from the beta-binomial, the logit-normal, and the finite mixture (latent class) models. In this response, simulations from many different distributions give a broader picture of the relative value of the beta-binomial and the finite mixture models, and provide some preliminary insights into the situations in which these models are useful.

Animal Identification Systems↗
PubMed1993

The disparity between observed and uniform distributions: a new look at parasite aggregation.

A simple new measure of parasite aggregation is described, the index of discrepancy (D). It quantifies the difference between the observed parasite distribution, and the hypothetical distribution that corresponds to the ideal case where all hosts harbour the same number of parasites. This index, computed for parasite distributions obtained from the literature, is compared to 2 other measures of aggregation, the variance to mean ratio and the parameter k of the negative binomial distribution. Both k and D indicate that aggregation decreases when the prevalence of infection and the mean number of parasites per host increase, while the variance to mean ratio suggests the opposite. Since an increase in prevalence means that parasites exploit a greater proportion of the available hosts and are thus not concentrating in only a few, aggregation should be inversely proportional to prevalence. Unlike k and D, the variance to mean ratio is a host-centered measure that is not very sensitive to the distribution of parasites. The index of discrepancy, on the other hand, is not only much easier to compute than k, but focuses on the difference between an ideal, uniform distribution and the one actually displayed by parasites. Since what it measures is what parasitologists mean by aggregation, the new index appears to be a more adequate measure of aggregation than other measures currently used.

Animals↗
PubMed1996

Global tests for combination drug studies in factorial trials.

To test the hypothesis that there are some studied dose combinations more effective in treating a disease than their respective component doses of two drugs, Hung, Chi and Lipicky proposed two alpha-level tests for normally distributed data. This paper extends the utilities of these tests to the outcome variable that has variance as a function of its mean, such as with a binomially distributed outcome, and to incomplete factorial design settings where some cells are not studied. I explore the impacts of excluding cells from study on the power performances of these tests.

Algorithms↗