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PubMed2003

Experimental studies on the transmission of Onchocerca volvulus by its vector in the Sanaga valley (Cameroon): Simulium squamosum B. Intake of microfilariae and their migration to the haemocoel of the vector.

As large-scale ivermectin distribution is becoming the mainstay of onchocerciasis control in Africa, the issue of its impact on local transmission is increasing in importance. The vector competence of Simulium squamosum B in the severe focus of the Sanaga valley, Cameroon, was therefore investigated, by feeding 1320 flies on 14 carriers of Onchocerca volvulus microfilariae (mff). The results enabled the relationships between skin microfilarial load, microfilarial intake by the flies, the proportion and mean number of ingested mff that succeed in reaching the fly's haemocoel, and the frequency distribution of the ingested mff to be described, as functions of time post-engorgement (p.e.) and parasite density (while taking account of possible measurement error in the predictor variable). The proportion of flies with haemocoelic mff and the mean number of mff/fly increased up to 3 h p.e. The proportion of flies with ingested mff was non-linearly related to mean intake, via the negative-binomial distribution, with the overdispersion parameter k best described as an increasing (power) function of the mean. Approximately one in every three ingested mff escaped imprisonment by the peritrophic matrix, irrespective of the skin microfilarial load or the intake of mff. The relationship between successful and input mff is nearly linear (indicating proportionality) in S. squamosum B. These results are compared with those from O. volvulus-S. damnosum s.l. combinations in other West African foci.

Adolescent↗
PubMedDate not supplied

Multivariate methods for binary longitudinal data with heterogeneous correlation over time.

Clustered binary data occur frequently in biostatistical work. One particular application is in binary longitudinal data, where several visits are available for the same individual. Several approaches have been proposed for the analysis of clustered binary data. In Rosner, a polychotomous logistic regression model was proposed which is a generalization of the beta-binomial distribution and allows for person- and visit-specific covariates, while controlling for clustering effects. One assumption of this model is that all pairs of visits within an individual are equally correlated, which may be inappropriate if several visits are available over a long follow-up period. In this paper, this approach is extended to allow for heterogeneous correlation over time. The total time period is divided into subintervals and a beta-binomial mixture model is introduced to estimate odds ratios relating outcomes for pairs of visits both within a subinterval as well as in different subintervals. To include covariates, an extension of the polychotomous logistic regression model is proposed, which allows one to estimate effects of person-, subinterval-, and visit-specific covariates, while controlling for clustering using the beta-binomial mixture model. This model is applied to the analysis of respiratory symptom data in children collected over a 14-year period in East Boston, MA, in relation to maternal and child smoking, where the unit is the child and symptom history is divided into early-adolescent and late-adolescent symptom experience.

Humans↗
PubMed1985

The use of historical data for estimating the number of samples required for monitoring drinking water.

Statistical techniques are described for estimating the number of samples required to monitor the quality of drinking water when the dispersion of bacteria in the water can be modeled by the Poisson or the negative binomial distributions. The concept of the operating characteristic (OC) curve of the water distribution system is presented and is used to evaluate the risk of declaring that the bacteriological water quality regulation is met when only a small portion of the water is analyzed. Assuming that the regulation requires that the monthly mean bacterial counts for samples of standard volume are to be less than one per ml, the OC curves are compared for different sample sizes and for different values of the parameters of the negative binomial. The results indicate that the correct specification of the model is very important in evaluating the risk of sampling (i.e. making the wrong decision). Total bacterial counts based on 1-ml samples, from the cities of Nancy and Metz in France, support the use of the negative binomial as a model for the dispersion of bacteria in drinking water. In the few cases where the negative binomial did not fit the data, the lack of fit can be attributed to the greater occurrence of the frequency of finding only one bacterium in the sample than that expected for the negative binomial. The OC curve indicated that the present monitoring strategy for the city of Nancy is adequate for monitoring the water quality if (i) the regulation requires that the monthly mean of total bacterial counts should not exceed one bacterium per ml, and (ii) the probability of accepting that the water quality is meeting the regulation, when the true mean number of bacteria per ml is two, should not be larger than 0.05. On the other hand, the city of Metz data indicated that it is necessary to increase the intensity of sampling both in time and space in order to achieve the same level of adequacy as that of the city of Nancy.

Bacteria↗
PubMed1998

Genetic heterogeneity of benign thyroid lesions. Static and flow cytometry, karyotyping and in situ hybridization analysis.

The present series includes 75 thyroid lesions (38 goiters, 30 adenomas, 3 follicullo-papillary encapsulated carcinomas and 4 normal thyroid) that were studied by static and flow cytometry. Four cases were also analyzed by in situ hybridization (centromeric probes for chromosomes 1 and 17) and 10 cases by G-banding cytogenetics. Results demonstrate a polymorphism and genetic instability in the thyroid tissue that may be related to the spontaneous polyploidization of their cells. The most consistent finding in cytometry was the presence of two clones associated with clinical or histological hyperactivity (46% versus 23% in non-functioning cases; chi2 distribution with a p < 0.05). Chromosomal anomalies were detected in two out of 10 cases: 46, XX, t(5,19) in 87% of cells of a diffuse hyperplastic goiter and 49, XX, +7, +17, +22 in 19% of cells of thyroiditis case. Finally, the in situ hybridization technique showed hidden trisomies of clonal origin in all of the cases studied. Evaluation of clonal trisomies by the in situ hybridization technique using the confidence interval of a binomial distribution is discussed.

Adenoma↗
PubMed1996

The Ames test: the two-fold rule revisited.

Mutagenicity in the Ames assay is evaluated by comparing the number of revertants observed in treated cultures to those in untreated cultures. Often, some form of the '2-fold rule' is employed, whereby a compound is judged mutagenic if a 2-fold or greater increase is seen in a treated culture. In order to understand the underpinnings of this approach, we study some of its statistical properties. We assume that the number of revertants on any plate from a given two-group experiment follows a Poisson distribution and we address the following questions: (1) what is the false-positive error probability of observing at least a doubling of the number of colonies from the control to the treatment group?; (2) if a given mean number of colonies is postulated for a control group, what number of colonies above the observed control mean provides a false-positive rate of 5%? We also present results for question 1 in the case where the number of revertants follows a negative binomial distribution.

False Positive Reactions↗
PubMed1980

[Psychophysics of sweet taste. I. Goals and methods of investigation].

With a view to the solution of problems concerned with the consumer's acceptance of foods in which saccharose had been substituted, a discussion is opened on psychologic and physiologic aspects of the measurability of sensory stimulus-sensation relations. The classic method for measuring taste is the determination of the taste discrimination threshold which is also termed least discernible difference. In the lat years, the discrimination threshold has been determined and calculated mainly as the mean concentration (stimulus) difference resulting from the distribution of the tasters according to their efficiency (probit analysis). In contrast, the new method, which is described in detail, is based on the dependence of the probability of a perception of difference upon the intensity which is linear and represents the initial course of a stimulus-response curve. Differences in efficiency in the group of tasters, which is assumed to be homogeneous, are included in the variance of difference frequencies found. The control of the course of the test by sequential analysis and the binomial weighting of the probabilities obtained allow to perform calculations of the discrimination threshold which are largely free from systematic errors; this discrimination threshold is defined as the concentration difference that engenders the arbitrarily defined alternative probability of Pa = 0.75. To minimize the risk of overrating the measurement result, it is suggested to calculate in addition, on the basis of the binomial distribution, the confidence limits of the discrimination threshold. Furthermore, the constant stimulus method for determining the perception of two stimulus intensities of different sweetening agents is adapted, as to performance and calculation, to the new aspects in discrimination threshold determination.

Consumer Behavior↗
PubMed1995

The distribution of faecal nematode egg counts in Scottish Blackface lambs following natural, predominantly Ostertagia circumcincta infection.

Faecal samples were taken in 2 consecutive years from Scottish Blackface lambs on a commercial farm in central Scotland to examine variation among lambs in the number of nematode eggs in their faeces. Samples were taken at intervals of 4 weeks from 1 to 5 months of age. Lambs were treated with a broad-spectrum anthelmintic at each sample date. Ewes and lambs were naturally infected by grazing pasture contaminated with mixed, predominantly Ostertagia circumcincta, nematode species. The ewes were removed from the lambs when the lambs were three months old. Only 3 of the 6 sets of samples taken prior to removal of the ewes fitted a negative binomial distribution but all sets of samples taken after this did so. The mean and the variance differed with the month and year of sampling. The amount of variation among lambs increased as the lambs grew from 3 to 5 months of age, possibly because of heterogeneity in the rate of development of protective responses. Counts taken in August and September, when the lambs were 4 and 5 months of age, were positively correlated with each other. In contrast, counts taken at 1 or 2 months of age were negatively correlated with counts taken when the lambs were 3-5 months old. Sex, date of birth, sire and dam were all associated with variation in faecal egg counts but the size and significance of their influence was dependent upon the date when faecal samples were taken. Four factors: sire, dam, sex and year accounted for over two-thirds of the variation among older lambs in faecal egg counts.

Animal Husbandry↗
PubMed2002

Regression models for overdispersed jejunal surviving crypts data.

The dose-response model concerns to establish a relationship between a dose and the magnitude of the response produced by the dose. A common complication in the dose-response model for jejunal crypts cell surviving data is overdispersion, where the observed variation exceeds that predicted from the binomial distribution. In this study, two different methods for analyzing jejunal crypts cell survival after regimens of several fractions are contrasted and compared. One method is the logistic regression approach, where the numbers of surviving crypts are predicted by the logistic function of a single dose of radiation. The other one is the transform-both-sides approach, where the arcsine transformation family is applied based on the first-order variance-stabilizing transformation. This family includes the square root, arcsine, and hyperbolic arcsine transformations, which have been used for Poisson, binomial, and negative binomial count data, as special cases. These approaches are applied to a data set from radiobiology. Simulation study indicates that the arcsine transformation family is more efficient than the logistic regression when there exists moderate overdispersion.

Cell Survival↗
PubMed1994

Minisatellite DNA markers in the chicken genome. I. Distribution and abundance of minisatellites in multilocus DNA fingerprints.

This paper reports the detailed characterization of multilocus minisatellite DNA fingerprints in the chicken. Results are presented of DNA fingerprint segregation analyses carried out in three chicken pedigrees, calculating the number of detected loci, testing for Mendelian inheritance, and cosegregation among fingerprint bands. Two pedigrees (families 1 and 2) were analysed using the Jeffreys probes 33.6 and 33.15 only, and one pedigree (family 3) was analysed using 33.6, 33.15, 3' alpha-globin HVR and M13 protein III gene repeat. Mean band transmission frequencies in families 1 and 2 were near to the Mendelian expectation of 0.5 and no mutations were observed. Family 3 showed transmission frequencies slightly exceeding 0.5. Linkage among bands was higher than observed in some other avian species, with each allele represented by a mean of 1.48 HaeIII fragments. Cosegregation of heterozygous parental fragments representing distinguishable loci followed the expected binomial distribution. The number of minisatellites detectable by the four probes was estimated to be 217. The pattern of cosegregation among those minisatellite loci was tested against that expected for different levels of recombination through the use of a simulation model. We conclude that most minisatellites are unlinked and probably widely dispersed in the chicken genome.

Animals↗
PubMed1998

Comparison of four sib-pair linkage methods for analyzing sibships with more than two affecteds: interest of the binomial maximum likelihood approach.

Family samples collected for sib-pair linkage studies usually include some sibships with more than two affecteds (multiplex sibships). Several methods have been proposed to take into account these multiplex sibships, and four of them are discussed in this work. Two methods, which are the most widely used, are based on the number of alleles shared by the sib-pairs constitutive of the multiplex sibship, with the first using the total number of these shared alleles ("all possible pairs" method) and the second considering a weighted number of these alleles (weighted method). The two other approaches considered the sibship as a whole, with in particular a likelihood method based on a binomial distribution of parental alleles among affected offspring. We theoretically show that, in the analysis of sibships with two affecteds, this likelihood method is expected to be more powerful than the classical mean test when a common asymptotic type I error is used. The variation of the sibship informativeness (assessed by the proportion of heterozygous parents) according to the number of affected sibs is investigated under various genetic models. Simulations under the null hypothesis of no linkage indicate that the "all possible pairs" is anticonservative, especially for type I errors < or = 0.001, whereas the weighted method generally provides satisfactory results. The likelihood method shows very consistent results in terms of type I errors, whatever the sample size, and provides power levels similar to those of the other methods. This binomial likelihood approach, which accounts in a natural way for multiplex sibships and provides a simple likelihood-ratio test for linkage involving a single parameter, appears to be a quite interesting alternative to analyze sib-pair studies.

Adult↗
PubMed2000

Description of a new computer wire coding method and its application to evaluate potential control selection bias in the Savitz et al. childhood cancer study.

We developed a new computer wire coding method and then applied it to investigate the suggestion that control selection bias might explain the observed association between wire codes and childhood cancer made in the study conducted by Savitz et al. in the Denver area. The computer wire coding method used a geographic information system approach with data on the local distribution electric system and from tax assessor records. Individual residences were represented as a circle scaled to the ground floor area of the residence and centered on the lot centroid. The wire code of the residence was determined from the distance between the circle and the relevant power line, and from the current carrying capacity of that line. Using this method, wire codes were generated for 238 290 residences built before 1986, the time of the Savitz et al. study, in the Denver metropolitan area. We then attempted to reconstruct the 1985 population of hypothetically eligible control children in the Denver metropolitan area by using 1980 census data. Since data were not available to locate the children in each residence within a census block, uniform, Poisson, and negative binomial distributions were used to randomly assign children to residences. To evaluate the likelihood of the wire code distribution of the controls selected by Savitz et al., 100 random trials were conducted for each distribution, matching two controls to each case. The odds ratios between childhood cancer and very high current configuration (VHCC) wire codes were reduced when the assigned controls were used, suggesting control selection bias may have been present. However, control selection bias is unlikely to account for all the reported association between childhood cancer and wire codes in the Savitz et al. study.

Bias↗
PubMed1994

Sporogonic development of cultured Plasmodium falciparum in six species of laboratory-reared Anopheles mosquitoes.

Sporogonic development of cultured Plasmodium falciparum was compared in six species of Anopheles mosquitoes. A reference species, A. gambiae, was selected as the standard for comparison. Estimates of absolute densities were determined for each lifestage. From these data, four aspects of parasite population dynamics were analyzed quantitatively: 1) successive losses in abundance as parasites developed from gametocyte to ookinete to oocyst stages, 2) oocyst production of sporozoites, 3) correlation between various lifestage parameters, and 4) parasite distribution. Parasite populations in A. gambiae incurred a 316-fold loss in abundance during the transition from macrogametocyte to ookinete stage, a 100-fold loss from ookinete to oocyst stage, yielding a total loss of approximately 31,600-fold (i.e., losses are multiplicative). Comparative susceptibilities in order were A. freeborni >> A. gambiae, A. arabiensis, A. dirus > A. stephensi, A. albimanus. The key transition(s) determining overall susceptibility differed among species. Despite species differences in oocyst densities and infection rates, salivary gland sporozoite production per oocyst (approximately 640) was the same among species. The most consistent association among lifestage parameters was a positive correlation between densities and infection rates of homologous lifestages. A curvilinear relationship between ookinete and oocyst densities in A. gambiae indicated a threshold density was required for ookinete conversion to oocysts (approximately 30 ookinetes per mosquito). The same relationship in A. freeborni was linear, with no distinct threshold. Ookinete and oocyst populations were negative binomially distributed in all species. Indices of heterogeneity in mosquito susceptibility to infection indicated that gene frequencies determining susceptibility fluctuated with time in all species, except A. freeborni where susceptibility remained homogenous throughout the study. This approach provides a framework for identifying mechanisms of susceptibility and evaluating Plasmodium sporogonic development in naturally occurring vector species in nature.

Analysis of Variance↗
PubMed1994

Injection granulomas. Intramuscle or intrafat?

OBJECTIVES: Intramuscular injection is a commonly used route of parenteral drug administration. We studied the fat vs muscle location, the depth of calcified buttock granulomas, and the thickness of subcutaneous fat. Data were assessed with respect to the length of a needle commonly used in intramuscular buttock injections. DESIGN: Three hundred thirty-eight sequential pelvic computed tomographic scans were studied. Subcutaneous fat thickness was measured for each patient at the upper outer quadrant of the buttock. The location and depth of each calcified granuloma were also recorded. SETTING: Tertiary care academic teaching hospital. RESULTS: One hundred sixty-four calcified granulomas were found in 67 patients. One hundred fifty-two of these granulomas were in fat and 12 were in muscle; this was statistically significant using a single-sample binomial distribution (P < .001;95% confidence interval, 0.04 to 0.13). The mean (+/- SD) subcutaneous fat thickness at the upper outer quadrant of the buttock was 5.0 +/- 1.9 cm, with female patients having a mean subcutaneous fat thickness of 5.7 +/- 1.8 cm vs 4.4 +/- 1.7 cm for male patients. CONCLUSIONS: The finding that buttock subcutaneous fat thickness exceeds the length of the most commonly used needle for intramuscular buttock injection (3.8 cm), together with the preponderance of calcified granulomas found in the fat of female patients, suggests that the currently used injection technique may not be therapeutically optimal. We suggest that longer needles be used for intramuscular buttock injections in adults.

Adipose Tissue↗
PubMed1999

Vertical fusional vergence: the key to dissociated vertical deviation.

OBJECTIVES: To test the previous findings of Enright that disparity-induced vertical vergence is mediated primarily by the oblique muscles, and to relate this normal eye movement pattern to the eye movement pattern seen in subjects with dissociated vertical deviation. METHODS: Sixteen normal volunteers underwent 55 measurements of the cycloversion associated with prism-induced vertical vergence using an afterimage apparatus. A Vernier scale measured the direction and magnitude of the torsional shift that occurred with recovery of fusion on removal of a 3- or 4-prism diopter prism. RESULTS: Of the 55 trials, the directions of torsional shift were consistent with the oblique muscles being the primary mediators of vertical fusional vergence in 51 (93%) (P = .03 using a binomial distribution). The mean +/- SD value of torsional shift was 1.15 degrees+/-0.76 degrees in the expected direction. CONCLUSIONS: Vertical fusional vergences in this study were produced primarily by the oblique extraocular muscles. The eye movement patterns of these vertical vergences in normal subjects are qualitatively similar to those seen in recordings of patients with dissociated vertical deviation. Dissociated vertical deviation thus seems to be an exaggeration of a normally occurring eye movement pattern. The cyclovertical component of dissociated vertical deviation may help stabilize the fixing eye by damping vertical nystagmus, while the accompanying hypertropia is an incidental and undesirable side effect.

Adolescent↗
PubMed2001

Chemoreduction for retinoblastoma may prevent intracranial neuroblastic malignancy (trilateral retinoblastoma).

OBJECTIVE: To evaluate whether neoadjuvant intravenous chemotherapy (chemoreduction) for retinoblastoma reduces the risk for associated intracranial neuroblastic tumor (trilateral retinoblastoma). DESIGN: Retrospective consecutive case series. PARTICIPANTS: Two hundred fourteen consecutive children with newly diagnosed retinoblastoma treated at a major ocular oncology center from January 1, 1995, to July 1, 1999. MAIN OUTCOME MEASURE: Development of associated intracranial neuroblastic tumor (trilateral retinoblastoma). RESULTS: During the 54-month study period, 142 patients (66%) received chemoreduction (consisting of vincristine sulfate, etoposide phosphate, and carboplatin therapy) as part of their treatment strategy (chemoreduction group), whereas 72 (34%) were treated with nonchemoreduction methods (nonchemoreduction group). In the chemoreduction group, no associated intracranial neuroblastic tumor developed during the mean 47-month follow-up. Based on a recent meta-analysis of the prevalence of trilateral retinoblastoma, we would have expected the intracranial tumor to develop in 5 to 15 patients with hereditary retinoblastoma. This lack of associated trilateral retinoblastoma in the chemoreduction group was significantly less than expected using binomial distribution (P<.001). In the nonchemoreduction group, associated intracranial tumor (pinealoblastoma) developed in 1 patient, a finding consistent with the expected frequency. CONCLUSION: Chemoreduction protects against the highly fatal associated intracranial neuroblastic tumor (trilateral retinoblastoma). This observation is especially important in children with bilateral or familial retinoblastoma who are at greatest risk for this brain tumor.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Academic and school health issues among children exposed to maternal intimate partner abuse.

OBJECTIVE: To determine the association between children's exposure to maternal intimate partner violence (IPV) and academic problems and school health concerns. DESIGN: The study population consisted of 153 children aged 5 to 16 years who attended public school and whose mothers experienced police- or court-reported IPV. The comparison group consisted of public school peers of the exposed children. Generalized linear modeling using a binomial distribution and log-link function served as the primary method of analysis. SETTING: Urban public school district. MAIN OUTCOME MEASURES: The occurrence of academic problems and type-specific school nurse visits during the 1-year study period. RESULTS: Children whose mothers experienced IPV were more likely to be suspended from school (relative risk [RR], 1.8; 95% confidence interval [CI], 1.2-1.7) and to have had frequent non-suspension-related absences (RR, 1.6; 95% CI, 1.0-2.3) than comparison children after adjusting for relevant confounders. Intimate partner violence-exposed children were more likely to have a school nurse visit for social or emotional complaints (RR, 2.2; 95% CI, 1.3-3.9), a visit that resulted in being sent home from school (RR, 1.6; 95% CI, 1.1-2.3), or a visit that led to referral to the school speech pathologist (RR, 7.5; 95% CI, 1.9-29.6) relative to comparison schoolchildren after adjusting for relevant confounders. CONCLUSIONS: Children's exposure to maternal IPV is significantly associated with the occurrence of academic problems and school health concerns. Describing the increased risk of the academic and health problems exhibited by IPV-exposed children relative to nonexposed children offers the possibility of improving the likelihood that clinicians will identify the woman who experienced abuse and her children, and promote referral to appropriate resources.

Adolescent↗
PubMed1997

Lung involvement in neuroblastoma: incidence and characteristics.

The presence of lung metastases in neuroblastoma often leads to doubt about the diagnosis due to rarity of disease at this site. To determine more precisely the incidence and nature of pulmonary disease in neuroblastoma the data base of the European Neuroblastoma Study Group (ENSG) was examined. Information was obtained about 35/746 stage IV patients (and 1 patient who was registered as having stage II disease) documented to have pulmonary disease at presentation. Of these 5 were registered with pleural effusions, 18 pleural infiltrations, and 13 intrapulmonary lesions. Review of these cases, however, suggested that only 9 patients (1.2%; 95% exact confidence interval 0.42-1.99%, binomial distribution) had disease consistent with secondary neuroblastoma in lung or pleura. There was no correlation with clinical features, age, sex, or other disease sites, and outcome was uniformly poor.

Adolescent↗