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Effects of partial inbreeding on fixation rates and variation of mutant genes.

Diffusion methods were used to investigate the fixation probability, average time until fixation and extinction, and cumulative heterozygosity and genetic variance for single mutant genes in finite populations with partial inbreeding. The critical parameters in the approximation are the coefficient of inbreeding due to nonrandom mating (F) and the effective population size (Ne), which also depends on F and the variance of family size. For large Ns, the fixation probability (u) is u = 2(Ne/N)s (F + h - Fh), where N is the population census, s is the coefficient of selection of the mutant homozygote and h is the coefficient of dominance. For Poisson family size (independent Poisson distributions of selfed and nonselfed offspring with partial selfing, and independent Poisson distributions of male and female numbers with partial sib mating), Ne = N/(1 + F), and the time until fixation is approximately equal to Ne/N times the time to fixation with random mating, but this relation does not hold, however, for other distributions of family size. The cumulative nonadditive variance until fixation or loss for dominant genes is reduced with increasing F while for recessive genes it is increased with intermediate values of F. The average time until extinction of deleterious mutations is reduced by increasing F. This reduction, when expressed as a proportion, is approximately independent of the initial gene frequency as well as the selective disadvantage if this is large.

Animals↗

Impact of demographic distribution and population growth rate on haplotypic diversity linked to a disease gene and their consequences for the estimation of recombination rate: example of a French Canadian population.

A disease gene introduced into a rapidly growing population by a single individual remains in strong linkage disequilibrium with the surrounding molecular markers. Mapping strategies taking advantage of this phenomenon allow increased mapping resolution as compared to pedigree analysis. Demographic models underlying these strategies usually assume the population exponential growth approximated by Poisson distribution of the number of children per individual. Knowing the real demographic distribution in the studied French-Canadian population, we analyzed the validity of the Poisson approximation. We adapted the existing model of the Poisson branching process to the case of a rapidly growing population and to non-Poisson distributions. In consequence, we were able to apply maximum-likelihood methods to estimate the recombination rate under various demographic scenarios. Our analysis shows that the growth rate has a higher impact on the estimation of recombination rate than the shape of the demographic distribution. The choice of the demographic model (Poisson vs. non-Poisson) has little effect on the estimation of the recombination rate but affects the expected distribution of haplotype frequencies. This distribution, however, depends much more on the population growth rate. Finally, we also demonstrate the usefulness of the Luria-Delbrück method, which gives a correct estimation of the recombination rate in a growing population, provided the sampling error is taken into account in the confidence intervals.

Confidence Intervals↗

Bronchoalveolar lavage cellularity. The distribution in normal volunteers.

Bronchoalveolar lavage (BAL) is used to obtain inflammatory cells from the lung. For clinical research, parametric statistics are frequently used to compare cells present in BAL of patients with lung disease with cells present in BAL of normal subjects. To determine if these populations can be compared in this manner we performed BAL on 111 never-smoking, normal volunteers and determined: (1) the mean, median, standard deviation, and range of the cells in BAL; (2) whether the data are normally distributed and satisfy the criteria for use of parametric statistical analysis. The BAL cellularity was expressed as a percentage of total cells, cells per milliliter return, and total cells per lavage. Regardless of the means of expression, no measure of BAL cellularity (total cells, macrophages, lymphocytes, neutrophils, or eosinophils) conformed to the normal (bell-shaped) distribution when tested for goodness of fit with the G statistic (all p < 0.001). The lack of fit to the normal distribution was not substantially altered by either the method of expressing the data (i.e., cells per milliliter, total cells, or percent of cells) or log transformation of the data. The poor fit in all cases resulted from clumping of the data about the mean and large tails. The percent of cells were, therefore, tested for goodness of fit to the Poisson distribution, a distribution of discrete variables. The neutrophil and eosinophil percentages resulted in an excellent fit to the Poisson distribution, but macrophage and lymphocyte percentages did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A comparison of two methods for estimating the effect of a countermeasure in the presence of regression effects.

The report studies the problem of estimating in a non-experimental before-and-after investigation the effect of a countermeasure on the number of traffic accidents at road junctions. The accidents are assumed to occur according to a Poisson process with different intensities at different junctions. The junctions studied in this investigation are assumed to have been selected with the blackspot-technique, i.e. junctions with high numbers of accidents during the before-period have been chosen for the investigation. In the mathematical model this has the consequence that the number of accidents occurring during the before-period at a selected junction has a truncated Poisson distribution. During the after-period the number of accidents has a Poisson distribution (without restrictions), so that the number of accidents on the average decreases between the periods even if the countermeasure has no effect. The magnitude of this regression effect is studied in the report. The observed numbers of accidents during the before and after period are used to estimate the pure effect of the countermeasure both with an intuitive method and with the maximum likelihood method. The characteristics of the two methods of estimation are illustrated with the aid of simulation studies. In general the maximum likelihood method appears preferable, mainly because it produces estimates with higher precision.

Accidents, Traffic↗

LTD induction in adult visual cortex: role of stimulus timing and inhibition.

One Hertz stimulation of afferents for 15 min with constant interstimulus intervals (regular stimulation) can induce long-term depression (LTD) of synaptic strength in the neocortex. However, it is unknown whether natural patterns of low-frequency afferent spike activity induce LTD. Although neurons in the neocortex can fire at overall rates as low as 1 Hz, the intervals between spikes are irregular. This irregular spike activity (and thus, presumably, irregular activation of the synapses of that neuron onto postsynaptic targets) can be approximated by stimulation with Poisson-distributed interstimulus intervals (Poisson stimulation). Therefore, if low-frequency presynaptic spike activity in the intact neocortex is sufficient to induce a generalized LTD of synaptic transmission, then Poisson stimulation, which mimics this spike activity, should induce LTD in slices. We tested this hypothesis by comparing changes in the strength of synapses onto layer 2/3 pyramidal cells induced by regular and Poisson stimulation in slices from adult visual cortex. We find that regular stimulation induces LTD of excitatory synaptic transmission as assessed by field potentials and intracellular postsynaptic potentials (PSPs) with inhibition absent. However, Poisson stimulation does not induce a net LTD of excitatory synaptic transmission. When the PSP contained an inhibitory component, neither Poisson nor regular stimulation induced LTD. We propose that the short bursts of synaptic activity that occur during a Poisson train have potentiating effects that offset the induction of LTD that is favored with regular stimulation. Thus, natural (i.e., irregular) low-frequency activity in the adult neocortex in vivo should not consistently induce LTD.

Action Potentials↗

Multinucleation of cultured canine epithelial and lymphoma cell lines.

The frequency distribution patterns of monuclear and multinuclear giant cells were determined for two canine lymphoma cell lines (DT-5 and 11028), and a normal canine kidney epithelial cell line (DK). The proportion of multinuclear cells in the DK line (1.53%) was approximately twice those of the DT-5 (0.75%) and 11028 (0.73%) cell lines. The observed frequency distributions of cells with single and various numbers of multiple nuclei were compared to Poisson distributions using the chi-square test. For each cell line, the number of cells with three or more nuclei far exceeded the number predicted by the Poisson distribution. Hence, the occurrence of multinuclear cells in these canine cell lines does not follow a random distribution pattern. Possible explanations for the nonrandom accumulation of multinuclear giant cells are discussed.

Animals↗

Frequency distributions of Echinococcus granulosus and other helminths in stray dogs in Tunisia.

The intestinal helminths infecting stray dogs were investigated in the Testour and Bouzid regions of Tunisia. Overall, 21% of the dogs necropsied were found to be infected with Echinococcus granulosus. The prevalence among the animals from Testour (27.0%) was significantly higher than that in the dogs from Bouzid (6.9%). Although the prevalence of this species in the dog populations did give a significant fit to the age-prevalence models reported earlier, the best fit was not consistent with the known biological parameters of the parasite. The frequency distribution of E. granulosus was highly aggregated, with a mean abundance of infection of 538 parasites/host and a mean intensity in infected animals of 2534 parasites/host. Several Taenia species were also found in the dogs, but none of these showed evidence of an aggregated distribution and the frequency distribution of each fitted a Poisson distribution, which is unusual for naturally acquired infections. All the other cestode species and the nematode species encountered had aggregated distributions in the dogs. As there was relatively little correlation between the worm burdens of the different parasite species in the dogs, individual dogs may not be generally susceptible or resistant to intestinal helminths of several species.

Animals↗

Hypothesis testing of time-dependent recurrent events.

This paper examines the problem of hypothesis testing for comparison of time-dependent recurrent events between categorical exposure groups. We compare three methods (a summary chi-square test based on a generalization of the simple Poisson distribution, a chi-square test based on a generalization of the compound Poisson distribution, and a test on risk scores based on individual observed to expected ratios), when the dependent variable may be autocorrelated within an individual, and disease risk may be heterogeneous among subjects. We present a simulation study and an application to a cohort of sickle cell anaemia patients. With autocorrelation or heterogeneous risk present, the simple chi-square test is inappropriate, while the other two methods perform well. An attraction of the risk score method is its relative ease of application.

Anemia, Sickle Cell↗

Relationship of presaccadic activity in frontal eye field and supplementary eye field to saccade initiation in macaque: Poisson spike train analysis.

The purpose of this study was to investigate the temporal relationship between presaccadic neuronal discharges in the frontal eye fields (FEF) and supplementary eye fields (SEF) and the initiation of saccadic eye movements in macaque. We utilized an analytical technique that could reliably identify periods of neuronal modulation in individual spike trains. By comparing the observed activity of neurons with the random Poisson distribution generated from the mean discharge rate during the trial period, the period during which neural activity was significantly elevated with a predetermined confidence level was identified in each spike train. In certain neurons, bursts of action potentials were identified by determining the period in each spike train in which the activation deviated most from the expected Poisson distribution. Using this method, we related these defined periods of modulation to saccade initiation in specific cell types recorded in FEF and SEF. Cells were recorded in SEF while monkeys made saccades to targets presented alone. Cells were recorded in FEF while monkeys made saccades to targets presented alone or with surrounding distractors. There were no significant differences in the time-course of activity of the population of FEF presaccadic movement cells prior to saccades generated to singly presented or distractor-embedded targets. The discharge of presaccadic movement cells in FEF and SEF could be subdivided quantitatively into an early prelude followed by a high-rate burst of activity that occurred at a consistent interval before saccade initiation. The time of burst onset relative to saccade onset in SEF presaccadic movement cells was earlier and more variable than in FEF presaccadic movement cells. The termination of activity of another population of SEF neurons, known as preparatory set cells, was time-locked to saccade initiation. In addition, the cessation of SEF preparatory set cell activity coincided precisely with the beginning of the burst of SEF presaccadic movement cells. This finding raises the possibility that SEF preparatory set cells may be involved in saccade initiation by regulating the activation of SEF presaccadic movement cells. These results demonstrate the utility of the Poisson spike train analysis to relate periods of neuronal modulation to behavior.

Action Potentials↗

Optimal number of beds and occupancy to minimize staffing costs in an obstetrical unit?

PURPOSE: We describe how the science of analyzing patient arrival and discharge data can be used to determine the optimal number of staffed OB beds to minimize labour costs. METHODS: The number of staffed beds represents a balance between having as few staffed beds as possible to care properly for parturients vs having enough capacity to assure available staff for new admissions. The times of admission and discharge of patients from the OB unit can be used to calculate an average census. From this average census, and the properties of the Poisson distribution, the optimal number of staffed beds can be estimated. This calculation requires specification of the risk of having all in-house and on-call staff caring for patients, such that additional staff are unavailable should another parturient arrive. As an example, patient admission and discharge times were obtained for 777 successive patients cared for at an obstetrical unit. The numbers of patients present in the OB unit each two-hour period were calculated and analyzed statistically. PRINCIPAL FINDINGS: There was variation in the average census among hours of the day and days of the week. Poisson distributions fit the data for each of four periods throughout the week. Simply benchmarking the current average occupancy and comparing it to a desired occupancy would have been inadequate as this neglected consideration of the risk of being unable to appropriately care for an additional patient. CONCLUSIONS: The optimal number of beds and occupancy of an OB unit to minimize staffing costs can be determined using straightforward statistical methods.

Anesthesia, Obstetrical↗

HiCPotts: An R/Bioconductor package to identify significant interactions in chromosome conformation capture data and model sources of bias.

MOTIVATION: Chromosome Conformation Capture methods, including Hi-C, micro-C or Capture-C, are used to map chromatin interactions genome-wide. Most of the existing computational methods do not account for sources of bias (such as DNA accessibility, GC content or TE content) in the data. RESULTS: We previously developed ZipHiC, a Bayesian method based on the hidden Markov random field (HMRF) model and the Approximate Bayesian Computation (ABC), that uses zero-inflated Poisson distribution to model the noise, signal and false signal of the data and showed that this approach was able to detect bias from DNA accessibility, GC content and TE content in both Hi-C and micro-C data. Here, we present HiCPotts, another Bayesian method based on the HMRF model and the ABC that uses a zero-inflated Negative Binomial distribution instead to model the noise and signal of the data. We systematically show that HiCPotts reduces false positives and increases recovery of true interactions compared to ZipHiC, but also compared to other methods such as FastHiC, Juicer and HiCExplorer. Most importantly, we provide an R/Bioconductor package that allows modelling the noise, signal and false signal using various distributions such as the zero-inflated Negative Binomial (ZINB) and the zero-inflated Poisson distribution (ZIP). AVAILABILITY AND IMPLEMENTATION: https://bioconductor.org/packages/HiCPotts/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Approximate Bayesian Computation↗

[The number of beds needed for patients with infectious diseases that require hospitalization by law].

PURPOSE: Using a statistical model, a study was conducted on the number of beds that are needed for patients with infectious diseases who are required by law to be hospitalized. METHODS: Based on 1995 data, the incidence of such infectious diseases and the average duration of isolation of these patients in Japan were obtained. Using a Poisson distribution, the probability that the number of patients that exceeds a specific number over an average duration of hospitalization was computed in a finite population. The observation period was then extended to one year and the probability that the number of patients did not exceed a specific number during one year was calculated. RESULTS: In 1995, the annual incidence of infectious diseases requiring isolation by hospitalization was 1.38 per 100,000 population and the average duration of hospital confinement was 13.8 days. The estimated patient numbers calculated based on the probability of less than 0.001 that the number of patients would not exceed a specific number were: 2 for 30,000 population, 3 for 50,000 through 100,000, 5 for 200,000 and 300,000, 5 for 400,000 and 500,000, 6 for 750,000 and 1,000,000, 8 for 2,000,000, and 10 for 3,000,000. CONCLUSION: By using a Poisson distribution, a method was developed for estimating the number of beds that are needed for patients with infectious diseases when hospitalization was mandatory.

Communicable Disease Control↗

[Karyotypic structure of Chinese hamster clone cell populations in prolonged culture].

The Karyotypic structure of some clones and subclones of Chinese hamster cells has been studied (CHO-KI). 60-80% of all the clonal cells demonstrated the identical karyotype (the main structural variant of karyotype - MSVK). The distribution of cells according to the number of chromosomes does not vary within 90 passages of clone cultivation (about 300 cell generations) and 35 passages of subclone cultivation (more than 100 cell generations). In two of three clones the frequencies of cells with MSVK and with additive karyotype variants do not change, while in one clone a long cultivation leads to lowering the frequency of cells with MSVK and to growing the frequency of cells with other karyotype variants. Recloning does not lead to decreasing the karyotypic heterogeneity of clonal populations. The distribution of clonal cells according to the deviation from the modal number of chromosomes is closely related to the Poisson distribution, while the distributions of cells from two clones with the stable karyotypic structure according to the number of greater structural greater deviations from MSVK are related to a degeneration Poisson distribution. Different chromosomes are involved in karyotypic changes in variable proportions, and the frequencies of cells with simultaneous deviations in various chromosome groups are in most instances higher than frequencies expected in the case of independent deviations. The reasons of stability of karyotypic structure in clonal populations is discussed.

Animals↗

[Confidence of 100 per cent sensitivity and specificity].

A new strategy and four new methods are presented to calculate the limits of the confident interval for an estimate of a proportion equal to 1.0 or 0.0. A current formula which includes 1/(2n) for continuity correction leads to a confident interval which does not include the parameter estimate. Thus, it is proposed: 1) The exclusion of the factor 1/(2n) in that formula leads to correct most of its inconsistencies. The new strategy assumes that the upper limit of a confident interval when the estimates is 100%. The lower limit is calculated by assuming that there is a proportion in the population, from where the sample was taken, such as the probability of getting 100% in the sample is equal to the probability of falling into type I error of current statistics (0.05, 0.01, etc). Three methods are proposed with this strategy. 2) A combinatorial solution based in the knowledge of the number of individuals at whom the test can be applied. 3) A solution based on the binomial distribution. 4) A solution based on the Poisson distribution.

Binomial Distribution↗

Simulation study for cloud detection with space lidars by use of analog detection photomultiplier tubes.

Output signal electrons from photomultiplier tubes (PMTs) have neither a Gaussian nor a Poisson distribution because of changes induced by multiplication when the number of input signal photons and dark electrons is fewer than approximately 100. Therefore the assumption of a Gaussian distribution of signal electrons cannot be used in simulations for space lidar observations with PMTs, for which the number of return signal photons is normally small. A theory is introduced for analog detection with PMTs that have Poisson-distributed secondary-electron emission at each dynode stage. The theory is validated by straightforward numerical simulations. It is shown that the multiplication in PMTs is a multiply stochastic Poisson process and that the distribution of output signal electrons can be interpreted basically as Neyman type A. Analysis by the threshold method of cloud detection with a space lidar shows considerable difference between a Gaussian approximation and the exact distribution. The result indicates that the threshold level must be optimized for the exact distribution. Return signals were simulated for a proposed space lidar, and cloud detection with the threshold method was demonstrated.

Journal Article↗

Testing for a change-point in registry data with an example on hypospadias.

The Poisson distribution is often suitable for analysing non-infectious disorders with low prevalence rates. The numbers of babies born with hypospadias in the Liverpool Congenital Malformations Registry during 1960 to 1982 do not fit a Poisson distribution with constant prevalence rates, but a change-point Poisson process does fit. A significance test is described and its power is considered in two simulation studies. A small discrepancy is noted that does not diminish appreciably when Bartlett's correction is applied.

Humans↗

Carbodiimide inactivation of Escherichia coli RNA polymerase promoters on supercoiled simian virus 40 and ColE1 DNAs occurs by a one-hit process at salt concentrations in the physiological range.

A previous study (Hale, P., Woodward, R. W., and Lebowitz, J. (1980) Nature 284, 640-644) showed that Escherichia coli RNA polymerase promoters on superhelical SV40 DNA are highly selective targets for chemical modification by the water-soluble carbodiimide, N-cyclohexyl-N'-beta-(4-methylmorpholinium)ethyl carbodiimide (CMC). To extend the inactivation analysis of supercoiled DNAs, we determined the number and location of RNA polymerase binding sites on the supercoiled and linear forms of ColE1 DNA. We also determined the site distribution of [3H] CMC on the superhelical form. This information, coupled with per cent inhibition of transcription versus CMC-bound curves, allowed a test of the specificity of the CMC inactivation by the Poisson equation. Curves were obtained for supercoiled SV40 DNA modified at 0 and 100 mM NaCl (2 mM NaPi, pH 7.0) and for supercoiled ColE1 DNA modified at 0, 100, and 320 mM NaCl. For supercoiled SV40 DNA, these data, coupled to our knowledge of the number of RNA polymerase binding sites from the study cited above, revealed an excellent fit to a one-hit inactivation by the Poisson equation for DNA modified at 100 mM NaCl. For ColE1 DNA, we obtained an excellent fit to a Poisson distribution when supercoiled DNA was modified at 320 mM NaCl. The Poisson distribution can be applied to [3H] CMC restriction fragment data with equivalent results. These results suggest that promoter sites can be forced into different structural conformations with variable degrees of unpairing.

Affinity Labels↗

Analysis of body-length distribution of Dirofilaria immitis in the cardio-pulmonary blood vessel of naturally infected dogs in Shiga Prefecture, Japan.

Body-length frequencies of Dirofilaria immitis collected from the cardio-pulmonary blood vessel of the dogs were studied in Shiga Prefecture. Japan, in October 1983 and in January and May 1984. The frequencies were not distributed normally because they included the populations of shorter-bodied worms, probably the growing younger worms, whereas the distributions of the body length of worms collected in July 1983 were proved to fit the single normal distribution. From the results of body-length distribution analysis, the worms collected in different seasons were each composed of 1 to 3 groups with different mean body-lengths, standard deviations and composition rates and successive changes were observed in the distribution patterns. According to the analysis of population structures, the infective season was estimated to range from April or May to October or November in 1983 from the respective ages of shorter-bodied worm groups. The annual rates of first infection and re-infection in 1983 determined by the population of shorter-bodied females collected in January were 48% and 93% respectively and the number of newly infecting females per dog ranged from 1 to 27 with a geometric mean of 8.5. The numbers of newly infecting female worms were distributed following the negative binomial and Poisson distributions in newly infected and already infected dogs respectively.

Animals↗