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[Incidence of Creutzfeldt-Jakob disease in France, 1992-1995].

BACKGROUND: Recent developments in animal and humans transmissible spongiform encephalopathies have motivated a study on incidence and risk factors of Creutzfeldt-Jakob disease (CJD) in France and 4 other European countries. METHODS: CJD cases were ascertained through a national network including 250 neurological departments or neuropathological laboratories. CJD cases were classified as definite, probable or possible. Overall incidence rate and age-standardized incidence rates by department were computed. Standardized incidence ratios and their 95% confidence intervals were computed for comparing observed and expected number of CJD cases in each department. RESULTS: Between 1992 and 1995, 216 CJD cases were registered (mean incidence rate: 0.87 per million inhabitants). The distribution of CJD cases was heterogeneous (p < 0.007). Nevertheless, the distribution of standardized incidence ratios fitted quite well a Poisson distribution. The observed number of CJD cases was significantly higher than expected in 4 departments and lower in 1 department. CONCLUSION: Incidence of CJD in France is similar to that observed in other European countries. Analysis of distribution of CJD cases by department showed a few significant differences which can be due to random fluctuations.

Adult↗

Analysis of testicular cancer data using a frailty model with familial dependence.

Previously published papers have indicated a fairly strong familial dependence intesticular cancer patients. This is particularly evident in brothers. We have applied a frailty model with familial dependence to family data on brothers of testicular cancer patients from the Norwegian Radium Hospital. The model is a two-level frailty, with variation in susceptibility at both the family and the individual level. Specifically, the frailty variable is assumed to be compound Poisson distributed to allow individuals to be non-susceptible. The underlying Poisson parameter is gamma distributed to model how testicular cancer is distributed among families. This is an extension of a previous compound Poisson frailty model developed for individual testicular cancer data, and an alternative to traditional modelling of survival time family data. The likelihood construction and ascertainment problems are looked at in detail. To avoid ascertainment bias, the likelihood is based on the probability of observing the disease status for each brother in a family, given that at least one brother is ascertained. The estimated relative risk for brothers is 7.4. This paper expands on a previous analysis of the data by using a frailty model, which makes it possible to examine how the cancer is distributed among families. The estimated gamma-shaped parameter is 0.151 (95 per cent confidence interval 0.078-0.294), and this indicates that in order to obtain the high relative risks observed for brothers of testicular cancer patients, the distribution of susceptibility has to be strongly skewed among the families. The vast majority of families have a very low risk and a small proportion have a high risk. In addition, a quantity similar to the relative risk is derived to show that the susceptibility is skewly distributed also if the Poisson parameter is Bernoulli or stable distributed. This indicates that the results are valid also if other distributions are used to model familial dependence in the compound Poisson frailty model.

Genetic Predisposition to Disease↗

A brief history of numbers and statistics with cytometric applications.

A brief history of numbers and statistics traces the development of numbers from prehistory to completion of our current system of numeration with the introduction of the decimal fraction by Viete, Stevin, Burgi, and Galileo at the turn of the 16th century. This was followed by the development of what we now know as probability theory by Pascal, Fermat, and Huygens in the mid-17th century which arose in connection with questions in gambling with dice and can be regarded as the origin of statistics. The three main probability distributions on which statistics depend were introduced and/or formalized between the mid-17th and early 19th centuries: the binomial distribution by Pascal; the normal distribution by de Moivre, Gauss, and Laplace, and the Poisson distribution by Poisson. The formal discipline of statistics commenced with the works of Pearson, Yule, and Gosset at the turn of the 19th century when the first statistical tests were introduced. Elementary descriptions of the statistical tests most likely to be used in conjunction with cytometric data are given and it is shown how these can be applied to the analysis of difficult immunofluorescence distributions when there is overlap between the labeled and unlabeled cell populations.

Cell Count↗

Mean and quasideterministic equivalence for linear stochastic dynamics.

In linear, stochastic dynamics it is shown that the quasideterministic population size is equivalent to the mean population size. The quasideterministic dynamics are defined by the conditional infinitesimal mean of the process. The stochastic component of the dynamics includes both Gaussian and Poisson white noise, with amplitude coefficients proportional to the population size. Generalizations are given for nonautonomous coefficients and for distributed Poisson jump amplitudes. A counter example--an exactly integrable nonlinear jump model--shows that the equivalence result does not hold for nonlinear stochastic dynamics.

Linear Models↗

Poisson and multinomial mixture models for multivariate SIMS image segmentation.

Multivariate statistical methods have been advocated for analysis of spectral images, such as those obtained with imaging time-of-flight secondary ion mass spectrometry (TOF-SIMS). TOF-SIMS images using total secondary ion counts or secondary ion counts at individual masses often fail to reveal all salient chemical patterns on the surface. Multivariate methods simultaneously analyze peak intensities at all masses. We propose multivariate methods based on Poisson and multinomial mixture models to segment SIMS images into chemically homogeneous regions. The Poisson mixture model is derived from the assumption that secondary ion counts at any mass in a chemically homogeneous region vary according to the Poisson distribution. The multinomial model is derived as a standardized Poisson mixture model, which is analogous to standardizing the data by dividing by total secondary ion counts. The methods are adapted for contextual image segmentation, allowing for spatial correlation of neighboring pixels. The methods are applied to 52 mass units of a SIMS image with known chemical components. The spectral profile and relative prevalence for each chemical phase are obtained from estimates of model parameters.

Models, Statistical↗

The clustering of respiratory diseases in early childhood.

BACKGROUND: It has been suggested that early childhood respiratory morbidity is related to asthma and chronic bronchitis in later life. To understand these relations, it is necessary to know how early childhood respiratory diseases are distributed, interrelated, and clustered. This study analyzed the distribution, interrelations, and the clustering of early childhood respiratory morbidity. METHODS: We prospectively collected data of episodes of respiratory illness among 1140 children in the first five years of life, in family practice. To determine if the occurrence of respiratory illness was randomly distributed, we compared the frequency of respiratory illness to random Poisson distribution. We used factor analysis to determine if respiratory illnesses occurred in clusters or patterns according to type of illness. RESULTS: Five percent of subjects never presented a respiratory disease, and 53% presented at least six episodes. The episodes of each illness were not randomly distributed, and most conditions were associated with each other. Factor analysis showed that asthma, acute bronchitis, and pneumonia formed one cluster, and tonsillitis, otitis media, and common cold another cluster. CONCLUSIONS: Early childhood respiratory morbidity is unevenly distributed, but a clear-cut group of children with a much higher rate of more severe respiratory morbidity than other children could not be distinguished. Both upper and lower respiratory tract illnesses show clustering. In research on the long-term prognosis of early childhood respiratory morbidity, this morbidity may best be grouped into the categories identified in this research.

Child, Preschool↗

Spatial interaction between neighbouring counties: cancer mortality data in Valencia Spain.

The statistical analysis of geographical mortality data has usually been approached via regression models that include appropriate covariates. These models assume stochastic independence of mortality counts for neighbouring sites, a questionable assumption that spatial automodels (Besag, 1974, Journal of the Royal Statistical Society, Series B 36, 192-236) make unnecessary. This paper presents the use of the autopoisson distribution in order to detect spatial interaction between neighbouring sites. If this interaction results in being nonsignificant, the auto-Poisson distribution reduces to a usual Poisson regression model, a particular case of generalized linear models (McCullagh and Nelder, 1989, Generalized Linear Models, 2nd edition. London: Chapman and Hall) which can be analyzed with the GLIM package.

Colonic Neoplasms↗

Modelling new enhancing MRI lesion counts in multiple sclerosis.

Magnetic resonance imaging (MRI) has been established as the most relevant paraclinical tool for diagnosing and monitoring multiple sclerosis (MS). In this context, counting the number of new enhancing lesions on monthly MRI scans is widely used as a surrogate marker of MS activity when evaluating the effect of treatments. In this study, we investigated whether parametric models based on mixed Poisson distributions (the Negative Binomial (NB) and the Poisson-Inverse Gaussian (P-IG) distributions) were able to provide adequate fitting of new enhancing lesion counts in MS. We found that the NB model gave good approximations in relapsing-remitting and secondary progressive MS patients not selected for baseline MRI activity, whereas the P-IG distribution modelled better new enhancing lesion counts in relapsing-remitting MS patients selected for baseline activity. This study shows that parametric modelling for MS new enhancing lesion counts is feasible. This approach should provide more targeted tools for the design and the analysis of MRI monitored clinical trials in MS.

Humans↗

Induction of micronuclei by bleomycin in G0 human lymphocytes: I. Dose-response and distribution.

The cytokinesis-block micronucleus assay was used to investigate the induction of chromosomal damage by bleomycin in G0 human lymphocytes. A dose-dependent increase in the frequency of micronuclei was observed in binucleate cells, and the frequency approached 0.5 micronuclei per cell at the highest dosage tested. The distribution of micronuclei among cells was overdispersed, rather than fitting a Poisson distribution. Even at the highest dosage, more than two-thirds of the cells did not contain micronuclei, while some cells were highly damaged, containing more than 4 micronuclei per cell.

Adult↗

Rocuronium and anaphylaxis--a statistical challenge.

Drug induced anaphylaxis is frequently attributed to the use of muscle relaxants during anaesthesia. Recently The Norwegian Medicines Agency recommended that rocuronium bromide (Esmeron) be withdrawn from routine practice due to frequent reports of anaphylaxis. Over a period of two and a half years approximately 150,000 patients received rocuronium as part of their anaesthesia. In this period the Norwegian drug authorities received 29 reports of anaphylaxis or anaphylactoid reactions in patients treated with rocuronium. This is in stark contrast to the situation in other Nordic countries where a total of only seven cases of anaphylaxis in approximately 800,000 patients treated with rocuronium had been recorded by December 2000. This situation highlights the many potential problems of the surveillance of adverse drug reactions: reporting bias may lead to an over-estimate of the risk of one drug compared to another, and the possibility of under-reporting of adverse events (due to a weak reporting culture) further limit the validity of such comparisons. The surveillance of adverse drug reactions also represents a statistical challenge. While adverse event reports may help us to estimate the anaphylaxis rate we need to appreciate the uncertainty of such estimates. Adverse reactions are rare, random, and mostly independent events, resulting from the successive exposure of patients to a low risk intervention. The frequency distribution of adverse events will therefore conform to that of a Poisson process. The resulting Poisson distribution may inform us about the variability of adverse event data. An understanding of these methodological problems and statistical challenges will allow anaesthesiologists to make informed decisions concerning the use of muscle relaxants and other drugs associated with severe adverse reactions.

Adverse Drug Reaction Reporting Systems↗

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↗

[Monitoring microbiological safety of small systems of water distribution. Comparison of two sampling programs in a town in central Italy].

OBJECTIVE: To determine the frequency of sampling in small water distribution systems (<5,000 inhabitants) and compare the results according to different hypotheses in bacteria distribution. DESIGN AND SETTING: We carried out two sampling programs to monitor the water distribution system in a town in Central Italy between July and September 1992; the Poisson distribution assumption implied 4 water samples, the assumption of negative binomial distribution implied 21 samples. Coliform organisms were used as indicators of water safety. The network consisted of two pipe rings and two wells fed by the same water source. The number of summer customers varied considerably from 3,000 to 20,000. RESULTS: The mean density was 2.33 coliforms/100 ml (sd= 5.29) for 21 samples and 3 coliforms/100 ml (sd= 6) for four samples. However the hypothesis of homogeneity was rejected (p-value <0.001) and the probability of II type error with the assumption of heterogeneity was higher with 4 samples (beta= 0.24) than with 21 (beta= 0.05). CONCLUSION: For this small network, determining the samples' size according to heterogeneity hypothesis strengthens the statement that water is drinkable compared with homogeneity assumption.

Binomial Distribution↗

Routine urine drug screening at the first prenatal visit.

OBJECTIVE: The purpose of this study is to determine whether routine urine drug screening at the first prenatal visit will identify and permit early intervention for those at risk for poor outcome. STUDY DESIGN: Comparisons of maternal and neonatal outcomes between 166 randomly chosen patients with positive and 150 randomly chosen patients with negative drug screens identified by the enzyme multiplied immunoassay test were made by unpaired t test, chi 2 test, probit analysis, and tests of independent Poisson distributions. RESULTS: Forty percent of those identified denied drug use. Antepartum (p less than 0.01) and postpartum (p less than 0.05) complications were increased among drug users. Birth weight (p less than 0.001), gestational age (p less than 0.03), and head circumference (p less than 0.05) were decreased among neonates. CONCLUSION: Because of difficulty in identifying illicit substance--using patients, consideration should be given to the implementation of routine urine drug screening at the first prenatal visit in populations with a high rate of illicit substance use.

Chi-Square Distribution↗

[Patterns in the distribution of chromosome aberrations in the cells of hydrobionts under the action of ionizing radiation and environmental chemical mutagens].

In studying the pattern of chromosome aberration distribution among hydrobiont cells in experimental and natural populations, it has been found that the Poisson distribution of chromosomes among cells occurs under the effect of ionizing radiation and under the combined effect of radiation and a chemical mutagen with a higher efficiency of the former. With the comparable efficiencies of both factors and with the effect of a chemical mutagen alone distribution of chromosome aberrations among cells resembles the geometrical one to a greater extent.

Animals↗

Quantitative estimation of chromosome aberration frequency in cancer patients induced by endogenous and exogenous factors.

In patients with skin melanoma and colon cancer, cell distribution by the number of chromosome aberrations cannot be described by Poisson distribution, but corresponds to a bipopulation model combining the Poisson and geometric distributions. In contrast to the control, in patients with malignant tumors, cells with geometric distribution possess the majority of chromosomal aberrations.

Chromosome Aberrations↗

Precision of analysis for waterborne chrysotile asbestos by transmission electron microscopy.

Detailed examinations of water samples were carried out to determine the precision of analysis for chrysotile asbestos by transmission electron microscopy (TEM). Since the frequency distribution of counts fits a Poisson distribution, several statistical inferences were made, including (1) an estimate of precision, and (2) a model for determining the probability of observing chrysotile as a function of its concentration in water and magnitude of area scanned by TEM.

Asbestos↗

The biological activity of hydrogen peroxide. I. Induction of chromosome-type aberrations susceptible to inhibition by scavengers of hydroxyl radicals in human embryonic fibroblasts.

The cytogenetic effect of hydrogen peroxide (H2O2) was investigated in human embryonic fibroblasts. Chromosome-type aberrations were found together with chromatid-type aberrations in metaphase cells harvested 24 h after a single 10-min treatment with 10(-5)-10(-3) M H2O2 in 0.9% NaCl solution. The chromosome-type aberrations were observed to be predominantly dicentrics and deletions. Both types of aberration showed a dose-response relationship to the dose of H2O2 over the range of 10(-5)-1.5 X 10(-4) M H2O2. The intercellular distribution of dicentrics showed a Poisson distribution. Centric and acentric rings and abnormal monocentrics were a minor fraction of the chromosome-type aberrations. The chromatid-type aberrations observed, such as breaks, exchanges and gaps, showed no dose-response relationship. The frequency of isochromatid breaks was higher than that of chromatid breaks and approximately 70% of the isochromatid breaks were found in the centromeric or pericentromeric region. The intercellular distribution of chromatid exchanges showed an over-dispersed distribution. The generation of aberrations by H2O2 was effectively suppressed by catalase and several scavengers of hydroxyl radicals (.OH) such as ethanol, dimethyl sulfoxide (DMSO) and mannitol. This result suggest that .OH plays an essential role in the generation of the chromosome aberrations by H2O2.

Antioxidants↗

Imaging of carrageenan macrocycles and amylose using noncontact atomic force microscopy.

Samples of kappa-carrageenan, iota-carrageenan, and synthetic amylose have been examined by atomic force microscopy (AFM). All samples were spray deposited from aqueous solutions onto freshly cleaved mica, air dried, and imaged in air using noncontact atomic force microscopy (NCAFM). Images of single stranded amylose and carrageenan are presented. At relatively low polymer concentrations in the presence of NaCl iota-carrageenan formed circles that appear to be predominantly head-to-tail associated unimeric duplex (double stranded) structures. At higher iota-carrageenan concentrations the polymer forms circles and aggregates that appear to involve dimeric duplex structure. Direct comparison of synthetic amylose molecular weights determined from NCAFM images with results from solution measurements showed that NCAFM provides an excellent way to measure amylose molecular weight and molecular weight distribution. It is shown that synthetic amylose is single stranded in aqueous solution and that the chain length distribution is broader than the Poisson distribution anticipated from polymerization theory.

Amylose↗