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PubMed1986

The question of the total gene number in Drosophila melanogaster.

A statistical analysis has been carried out on the distribution and allelism of nearly 500 sex-linked, X-ray-induced, cytologically normal and rearranged lethal mutations in Drosophila melanogaster that were obtained by G. Lefevre. The mutations were induced in four different regions of the X chromosome: (1) 1A1-3E8, (2) 6D1-8A5, (3) 9E1-11A7 and (4) 19A1-20F4, which together comprise more than one-third of the entire chromosome.--The analysis shows that the number of alleles found at different loci does not fit a Poisson distribution, even when the proper procedures are taken to accommodate the truncated nature of the data. However, the allele distribution fits a truncated negative binomial distribution quite well, with cytologically normal mutations fitting better than rearrangement mutations. This indicates that genes are not equimutable, as required for the data to fit a Poisson distribution.--Using the negative binomial parameters to estimate the number of genes that did not produce a detectable lethal mutation in our experiment (n0) gave a larger number than that derived from the use of the Poisson parameter. Unfortunately, we cannot estimate the total numbers of nonvital loci, loci with undetectable phenotypes and loci having extremely low mutabilities. In any event, our estimate of the total vital gene number was far short of the total number of bands in the analyzed regions; yet, in several short intervals, we have found more vital genes than bands; in other intervals, fewer. We conclude that the one-band, one-gene hypothesis, in its literal sense, is not true; furthermore, it is difficult to support, even approximately.--The question of the total gene number in Drosophila will, not doubt, eventually be solved by molecular analyses, not by statistical analysis of mutation data or saturation studies.

Alleles↗
PubMed1988

Random oligonucleotide mutagenesis: application to a large protein coding sequence of a major histocompatibility complex class I gene, H-2DP.

We have used random oligonucleotide mutagenesis (or saturation mutagenesis) to create a library of point mutations in the alpha 1 protein domain of a Major Histocompatibility Complex (MHC) molecule. This protein domain is critical for T cell and B cell recognition. We altered the MHC class I H-2DP gene sequence such that synthetic mutant alpha 1 exons (270 bp of coding sequence), which contain mutations identified by sequence analysis, can replace the wild type alpha 1 exon. The synthetic exons were constructed from twelve overlapping oligonucleotides which contained an average of 1.3 random point mutations per intact exon. DNA sequence analysis of mutant alpha 1 exons has shown a point mutant distribution that fits a Poisson distribution, and thus emphasizes the utility of this mutagenesis technique to "scan" a large protein sequence for important mutations. We report our use of saturation mutagenesis to scan an entire exon of the H-2DP gene, a cassette strategy to replace the wild type alpha 1 exon with individual mutant alpha 1 exons, and analysis of mutant molecules expressed on the surface of transfected mouse L cells.

Amino Acid Sequence↗
PubMed1989

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↗
PubMed1992

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↗
PubMed1977

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↗
PubMed1977

Microdosimetry and chromosome aberrations: effects of 230 keV neutrons on Vicia faba chromosomes.

Physical energy deposition events have been related to sub-nuclear cytological events (chromosomal changes) in metaphases sequentially accumulated from the latter part of the cell cycle of Vicia faba. 230 keV neutrons produce about 0.4 recoil protons per late interphase nucleus per rad with the majority of protons traveling 1 to 2 microns from their origin, depositing energy at around 90 keV per micron. The frequency of induced abberrations is basically linear with dose, though varying through consecutive cell sampling periods because of differential induced mitotic delay. Distributions of chromosomal aberrations and total cytological events are overdispersed in relation to the Poisson distribution indicating that some proton recoils produce multiple events. When gaps and aberrations within chromosomes and multiple aberrations between chromosomes, are considered as discrete events, distributions follow Poisson expectations. About 40% of proton recoils result in observable cytological change. The highly energetic proton recoils (approximately 90 keV per micron) which can induce multiple events are the ones most likely to produce effects which result in cell death. The sphere of influence of the proton recoils is probably adequately estimated from their range (approximately 1 to 2 micron) since it seems compatible with the spatial proximity of the initial components of the resultant chromosome aberrations.

Chromosome Aberrations↗
PubMedDate not supplied

Seizure frequency in intractable partial epilepsy: a statistical analysis.

We examined the seizure records of 13 patients (nine men and four women, ages 27-50 years) with intractable partial epilepsy, maintained with steady anti-epileptic drug dosages. Patients recorded daily seizure frequency on calendars. Periods of outpatient observation ranged from 99 to 1,710 days and the number of observed seizures ranged from 18 to over 400, with daily seizure rates of 0.1-4.3 per day. We used the quasi-likelihood regression model to examine the following four departures of the daily seizure counts from a Poisson (random) model: (1) linear increasing or decreasing time trends in expected seizure rates; (2) clustering, where the expected seizure rate on a given day depends on the number of seizures observed on the immediate prior days; (3) monthly cyclicity; and (4) increased variability (overdispersion). Linear time trends were seen in six patients (four increasing and two decreasing), clustering was seen in 10 patients, and a near-monthly cycle appeared in four patients (two of nine men and two of four women). A significant amount of extra variation (overdispersion) relative to a Poisson distribution was observed in all but one of the 13 patients. Departures from a Poisson (random) model appear more common in this population of patients with medically intractable epilepsy than is commonly recognized, and have clinical importance as well as implications for the design of clinical studies.

Adult↗
PubMed1990

Monitoring tsetse fly populations. II. The effect of climate on trap catches of Glossina pallidipes.

In Part I it was shown that the sampling distribution of trap catches of tsetse flies, Glossina pallidipes Austen, at Nguruman, Kenya, using unbaited biconical traps follows a Poisson distribution. In this paper we examine the effect of humidity and temperature on day-to-day and seasonal variations in the trap catches. It is shown that the seasonal variation is significantly correlated with maximum daily temperature, the catches increasing with temperature when the maximum temperature is below 34 degrees C and decreasing with temperature when it is above 34 degrees C. The correlation between trap catches and relative humidity is not as good as the correlation with the maximum temperature, and the two together do not improve the fit to the trap catches. The day-to-day variation is significantly greater than the intrinsic variation due to the stochastic nature of the sampling process and for some traps it is correlated with temperature and humidity. An autoregressive model gives a half-life for the decay of departures from the mean of about 1 day and it is suggested that this indicates the movement of flies in response to animal movement or to climatic factors other than temperature or humidity. After removing the temperature dependent part of the seasonal variation and the autoregressive component of the data, the male and female catches are still significantly correlated.

Animals↗
PubMed1991

Power and detectable risk of seven tests for standardized mortality ratios.

Power and minimum detectable risk are calculated for seven one-sided tests of standardized mortality ratios with Poisson-distributed events. Each test contrasts the number of observed deaths (D) with the number expected (E). Three tests use exact Poisson probabilities: 1) the exact test, which computes a p value as the probability of equaling or exceeding the number of observed events; 2) the optimal randomized exact test which, although not used in practice, serves as a standard for the other statistics; and 3) the exact "mid-p" procedure, which counts only one-half the probability of the observed event. The remaining four tests use normal approximations to the Poisson ("Z statistics"): 4) Z = magnitude of D-E/square root of E; 5) the Z statistic corrected for continuity, Z = (magnitude of D-E)-0.5)/square root of E; 6) a statistic based on a square root transformation, Z = 2(square root of D-square root of E); and 7) a statistic created by Byar, which, when D is greater than E, is Z = square root of 9D[1-1/(9D)-3 square root of D/E]. Power differences among these procedures with one-sided alpha of 0.05, 0.025, and 0.01 are small as long as four or more events are expected. If fewer than four events are expected, the uncorrected Z has unacceptably high type I error. Simple approximations to the power and detectable risk of these tests are evaluated and prove satisfactory. Differences in minimum detectable risk, actual and approximated, are slight for E of 2.0 or more.

Humans↗
PubMed1985

Improved evaluation of binding of ligands to membranes containing several receptor-subtypes.

In order to evaluate accurately affinity characteristics and relative size of populations of receptor-subtypes in one system we analysed three relevant problems encountered in binding assays. Binding to receptors caused a decrease in the free ligand concentration (i.e. "depletion"). The neglect of depletion may lead to significant distortions of the estimates of affinity and size of receptor-subtype population when the concentrations of both receptor and ligand are of similar magnitude. The distortion is particularly marked when the affinity of a competing ligand is higher than the affinity of the radioligand. We present a formula that describes binding inhibition in a system with receptor-subtypes under conditions of depletion. Binding data usually exhibit heteroscedasticity (i.e. heterogeneous variance), which can not be neglected especially in a system with receptor heterogeneity. Assuming a log normal distribution of experimental errors and a Poisson distribution for errors due to radioactivity counting we derived a function for the transformation of binding data. Transformed data show homoscedasticity, as illustrated with experiments on membranes of guinea-pig lung using ICI 118,551 as inhibitor of 3H-(-)-bupranolol binding to beta 1- and beta 2-adrenoceptors. The hypothesis that affinity characteristics of receptor subtypes are independent of the tissue class can not be tested accurately by the use of standard methods because of interferences of errors between experiments. We propose a method to account for differences between experiments. Assuming invariance of affinity characteristics one is able to perform common fits of data from different tissue classes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1992

Exact calculation of probabilities of false positives and false negatives for low background counting.

The purpose of this paper is to demonstrate the derivation and use of exact formulas, and their algorithms, for calculating the probabilities alpha of Type I errors, and beta of Type II errors, for low blank total counts (Poisson-distributed). The calculations are carried out to examine the alpha and beta probabilities at low blank levels of the decision level (DL) and minimum detectable amount (MDA) formulations as adopted in the Health Physics Society Standard, "Performance Criteria for Radiobioassay." These formulations are consistent with those published by L.A. Currie, which have received wide acceptance in defining lower limits of detection (LLD). Although Currie's formulation was derived assuming a normal distribution in net counts, the behavior of the distribution of net counts at low count levels, which is a distribution of the difference between two Poisson variates, is such that the MDA formulation in the standard could be considered acceptable for the purpose of providing one simple formulation of MDA. The derivations in this note can also be useful in other problems involving differences in Poisson variates, such as those in certain population studies.

Background Radiation↗
PubMed1978

Quantal analysis of transmitter release at an inhibitory synapse in the central nervous system of the leech.

The quantal nature of transmitter release has been analysed at central inhibitory synapses in the leech nervous system between an interneurone (HN) and a motoneurone (HE) that regulate the heartbeat. 1. Ganglia were bathed in leech Ringer fluid containing 20 mM-Mg and 1.8 mM-Ca and the membrane of the presynaptic HN interneurone was hyperpolarized by current injection. Under these conditions successive inhibitory potentials in the HE motoneurone, evoked by impulses in the HN interneurone, showed striking fluctuations in amplitude. 2. Assuming a Poisson distribution of the i.p.s.p.s and estimating the number of failures from the amplitude histograms of the observed responses, the mean size of the quantal unit was estimated as 0.25 +/- 0.015 mV (S.E. of mean, n = 26). When m, the mean number of quanta released per trial, was varied by changing the membrane potential of the presynaptic HN cell (Nicholls & Wallace, 1978), the experimentally observed amplitude distributions could be predicted by the Poisson theory. 3. An independent estimate of the unit size was obtained by noise analysis. A long subthreshold depolarizing pulse applied to the presynaptic HN interneurone evoked a sustained hyperpolarization of the HE motoneurone, apparently caused by an increase in the rate of on-going release of quanta by the HN cell terminals. From the mean change in membrane potential and the increase in variance, the size of the unit was calculated as 0.21 +/- 0.039 mV (S.E. of mean, n = 11). For ten pairs of cells an estimate of unit amplitude was made both from the Poisson analysis and the analysis of variance, again with good agreement. For these cells the estimated unit sizes were 0.24 +/- 0.023 mV (S.E. of mean, n = 10) from the failures and 0.21 +/- 0.043 m V (S.E. of mean, n = 10) from the noise. 4. A similar analysis was made of the inhibitory synaptic potentials evoked in one HN interneurone by stimulation of its contralateral homologue. Transmission again appeared to be qualtal; the mean unit amplitude from Poisson analysis was 0.31 +/- 0.022 mV (S.E. of mean, n = 19) and from the noise 0.29 +/- 0.027 mV (S.E. of mean, n = 3). 5. We conclude that transmitter is released from the terminals of the HN interneurone in quantal units that evoke miniature i.p.s.p.s of about 0.25 mV in the post-synaptic cells. Furthermore, modulation of transmission proudced by variation in the presynaptic resting potential and during presynaptic inhibition results from changes in the mean number of quanta released by each impulse.

Animals↗
PubMed1990

Monitoring of genotoxic exposure of humans by the sister chromatid exchange test. Methodology and confounding factors.

During the last decades several in vitro assays for measurement of genotoxic exposure have been developed. Exposure of humans to genotoxic products in their workplaces and the environment may be evaluated by means of the sister chromatid exchange test (SCE), which visualize exchange of DNA material between sister chromatids of a chromosome. This thesis deals with the development of SCE methodology and screening of confounding factors to make the method useful in population monitoring of genotoxic exposure of chemicals in vivo. Human lymphocytes are cultured under standardized conditions. The cells are prepared for chromosome analysis by means of new-developed apparatuses treating 12 samples simultaneously. By this method the preparation is speeded up and breathing of glacial acetic acid is minimized. Slides are prepared and stained. The staining procedure includes irradiation of the slides with long wave UV light. The light source has been optimized with regard to simplicity and spectral distribution to fit the absorption spectrum of the dye bisbenzimid. The irradiation time and dose to produce distinct harlequin stained chromosomes has been found. Population screening demands analysis in microscope of a great number of chromosomes. The working time at microscope is long and improvement of ergonomics and automation to speed up the procedure was obtained by development of a special microscope which projects the picture of SCEs at table level. The scanning table was motorized. These changes gave excellent ergonomic proporties as fixed positions of the eyes and hands were avoided. The system is fast and flexible and may semiautomatically produce karyotypes. By pointing out SCEs the system automatically registers SCE number, cell coordinates, mitosis quality and perform statistics. The statistical model which best describe the distributions of SCE data has been analysed. This was a negative binomial distribution, which is close to the Poisson distribution. The transformation y = (S).5 + (S + 1).5 follows a normal distribution. Variances of the transformation of the sum of SCEs in 30 cells within subjects and between subjects have been calculated, and on that basis the demands to sample size have been calculated. To avoid to make false statements about a connection between an exposure and SCE a detailed knowledge of confounding factors is essential. Of endogenous factors gender, age, race, and heredity have been considered. Of these gender and age contribute to the variation in SCE. Very high SCE level has been found in healthy members of a family and such cases have to be excluded from exposure studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

[Molecular weight distribution of polymeric DNA-products, formed upon the action of matrix enzymes].

Models of processive and distributive DNA synthesis and degradation catalysed by matrix enzymes were investigated. Distribution of polymer products dependent on the reaction model chosen, on the type of the matrix and on the enzyme-matrix initial concentration ratio were determined by methods of numerical modeling. Conditions were found where the scattering of the reaction polymer products was minimal. The homopolymer matrix choice of experimental condition may generate a distribution of product that obeys the Poisson distribution. Numerical investigations of polymerization (hydrolysis) processes showed that for a number of heteropolymer matrixes a distribution may exist with scattering much less than that for homopolymer matrixes. Conditions are found when processive and distributive models give different distributions of the reaction product.

Base Sequence↗
PubMed1990

A statistical method for evaluating suicide clusters and implementing cluster surveillance.

The absence of any standard definition of suicide cluster events hinders understanding of the prevalence of the problem, hinders the development of appropriate public health responses to observed clusters, and ultimately hinders investigation of the mechanisms underlying contagious communication of suicidal behavior. The authors introduce a Poisson mixture model for assessing potential clusters of adolescent suicide, apply that model to the monthly incidence rates of adolescent suicide for one populous US county over the last 11 years, and generate 99% tolerance limits with 95% confidence for the number of suicides which may occur by chance within specific intervals of time in that county. The suicide incidence data showed a remarkable fit to a single Poisson distribution, suggesting it is not unreasonable to consider the cases as randomly-distributed and independent events. The authors conclude that there is no evidence that adolescent suicides occurred in clusters in the place and in the time frame under study, and recommend the Poisson mixture model for ascertaining clusters as well as implementing cluster surveillance.

Adolescent↗
PubMed1992

[Chiasma distribution in the lampbrush chromosomes of the chicken Gallus gallus domesticus: hot spots of recombination and their possible role in proper dysjunction of homologous chromosomes at the first meiotic division].

Chiasma distribution in the lambrush chromosomes of the chicken Gallus gallus domesticus was studied. The data of the authors show that the general pattern of chiasmata in the interstitional region of chromosomes corresponds to the Poisson distribution. However, in the telomeric and subtelomeric regions of all chicken macrochromosomes one can see chiasma as a rule. In the half of 140 microchromosomes from 24 different oocytes, there are also the telomeric chiasmata. On the basis of this observation, it may be predicted that there are hot spots of recombination near or into the telomeric GC-rich heterochromatic bands of chicken chromosomes. We suggest that these hot spots of recombination near the telomeres are a necessary facility for not only macrochromosomes but all microchromosomes as well to have at least one chiasma. The constant presence of at least one chiasma in a bivalent in needed for correct disjunction of homologous chromosomes at the first meiotic division.

Animals↗
PubMed1991

CANEST: a microcomputer program for estimating cancer in a cohort.

Certain diseases and symptoms carry an overrepresentation of cancer. To be able to measure the strength of such an association it is necessary to be able to predict cancer development in the group being observed. A computer program for computers running under the MS DOS operating system has been developed for this purpose. The program is written in the CLIPPER programming language. The estimates are based on incidence and prevalence data from the Swedish Cancer Registry for the years 1958 to 1986. The program also computes confidence intervals based on the Poisson distribution. The results can be printed out or exported to other programs for further analysis.

Cohort Studies↗