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PubMed1993

Mechanoelectrical feedback in cardiac myocytes from stretch-activated ion channels.

Stretch-activated ion channels (SAC's) in cardiac myocytes from neonatal rats were studied in cell-attached patches. Stretch of membrane patches by suction in the recording pipette caused the triggering of action potentials that were recorded as action currents (AC's). The significance of a temporal correlation between SAC open probability and AC's was tested using the Kolmogorov-Smirnov and Poisson distributions. It was shown that the 50-ms epoch immediately preceding the action current had unique kinetics and represented a peak in SAC open probability (p < 0.001). Thus it appears that current from a small number of SAC's injects sufficient charge (0.2 pC during 50 ms) to trigger action potentials in myocytes. These data strengthen the hypothesis that passive mechanical stretch of myocardium can be arrhythmogenic.

Action Potentials↗
PubMed1989

Logistic and Poisson models for infection by multicomponent plant viruses.

A model for the relationship between virus concentration and infectivity of multicomponent plant viruses is based on a combination of logistic and Poisson equations. Two separate equations are derived from the Poisson distribution assuming, (i) that infections occur only when a set of components containing the complete multicomponent genome is established at an infection site, but that any excess of components present does not reduce the probability of infection (no interference postulate); and (ii) that infection can occur only if a set of components containing the full genome reaches an infection site before it can be preempted by an incomplete set (competitive interference postulate). Postulate (i) affects the form of a dilution series without affecting N, the maximum possible number of infections (lesions), and postulate (ii) changes the value of N but not the form of the dilution series. There is a close correlation between the logit slope of a logistic dilution series and the form of the corresponding multiple Poisson dilution series for viruses with 2, 3 or 4 components. Calibrated by Poisson equations, the logit slope may thus suggest whether or not the virus components have invaded independently and infected similar infection sites. The methods of fitting the combined logistic-Poisson model are demonstrated by applying it to data for cowpea chlorotic mottle virus.

Models, Theoretical↗
PubMedDate not supplied

Measurement uncertainty in microbiology.

Testing laboratories wishing to comply with the requirements of ISO/IEC 17025:1999 need to estimate uncertainty of measurement for their quantitative methods. Many microbiological laboratories have had procedures available for monitoring variability in duplicate results generated by laboratory analysts for some time. These procedures, however, do not necessarily include all possible contributions to uncertainty in the calculations. Procedures for estimating microbiological method uncertainty, based on the Poisson distribution, have been published but, at times, the procedures can either underestimate uncertainty or require laboratories to undertake considerable experimental studies and more complex statistical calculations. This paper proposes procedures for estimating uncertainty of measurement in microbiology, whereby routine laboratory quality control data can be analyzed with simple statistical equations. The approaches used in these procedures are also applied to published data and examples, demonstrating that essentially equivalent results can be obtained with these procedures.

Colony Count, Microbial↗
PubMed2004

Improving surveillance for injuries associated with potential motor vehicle safety defects.

OBJECTIVE: To improve surveillance for deaths and injuries associated with potential motor vehicle safety defects. DESIGN: Vehicles in fatal crashes can be studied for indications of potential defects using an "early warning" surveillance statistic previously suggested for screening reports of adverse drug reactions. This statistic is illustrated with time series data for fatal, tire related and fire related crashes. Geographic analyses are used to augment the tire related statistics. RESULTS: A statistical criterion based on the Poisson distribution that tests the likelihood of an expected number of events, given the number of events that actually occurred, is a promising method that can be readily adapted for use in injury surveillance. CONCLUSIONS: Use of the demonstrated techniques could have helped to avert a well known injury surveillance failure. This method is adaptable to aid in the direction of engineering and statistical reviews to prevent deaths and injuries associated with potential motor vehicle safety defects using available databases.

Accidents, Traffic↗
PubMed1994

Statistical characterization of negative control data in the Ames Salmonella/microsome test.

A statistical characterization of negative control data in the Ames Salmonella/microsome reverse mutation test was performed using data obtained at Takeda Analytical Research Laboratories during January 1989 to April 1990. The lot-to-lot variability of bacterial stock cultures and day-to-day variability of experiments were small for Salmonella typhimurium strains TA1535 and TA1537 and Escherichia coli WP2uvrA, but they were larger for S. typhimurium TA100. The number of revertant colonies for all test strains studied here followed Poisson distributions within the same day. The two-fold rule that is an empirical method to evaluate the Ames Salmonella/microsome test results has been widely used in Japan. This two-fold rule was evaluated statistically. The comparison-wise type I error rate was less than 0.05 for TA98, TA100, TA1535, TA1537, and WP2uvrA. Moreover, this rule is particularly conservative for TA100, for which the type I error rate was nearly 0.

Analysis of Variance↗
PubMed2002

The effects of genetic drift in experimental evolution.

Experimental evolution is characterized by exponential or logistic growth and periodic population bottlenecks. The fate of a rare beneficial mutation in these systems is influenced both by the bottleneck effect and by genetic drift. This paper explores the effects of incorporating genetic drift into models of fixation probability in populations with periodic bottlenecks. To model the inherent stochasticity during the growth phase in these populations, we assume a Poisson distribution of offspring. An analytical solution is developed to calculate the fixation probability and a computer simulation is used to verify the results. We find that the fixation rate of a favourable mutant is significantly lower when genetic drift is considered; fixation probability is reduced by over 25% for realistic experimental protocols. Our method is valid for both weak and strong selection; since very large selection coefficients have been reported in the experimental literature, this is an important improvement over previous results.

Biological Evolution↗
PubMed1994

The frequency of apparent acetone in a group of breath alcohol data: statistical treatment and forensic implications.

The potential presence of interfering substances (specifically acetone) is a concern in the forensic reporting of evidential breath alcohol analysis. As a result, manufacturers have designed instruments to monitor its occurrence through various hardware and software features. This paper is a retrospective study where 35,945 duplicate breath samples from BAC Verifier DataMaster instruments are evaluated for the frequency of 'interferant' values > or = 0.010 g per 210 l ethanol equivalent. A total of 264 (0.74%) of the duplicate samples had an interferant value on the first sample only, while 235 (0.66%) had interferant values on the second samples only. A total of 77 (0.21%) of the duplicate samples had in interferant values on both breath samples and only in these cases could the presence of measurable acetone even be considered. The occurrence of interferant results appeared also to be instrument-dependent with 55.7% of the interferant values on the first breath sample occurring on nine (13%) of the instruments displaying such results. The occurrences of interferant values on the first breath sample did not conform to the Poisson distribution (P < 0.0001) for the instrument with the largest number of occurrences, while there was conformance for other instruments evaluated. Finally, approximately 23 cases (0.064%) remained where the presence of acetone is a possible consideration. Several issues are presented that the forensic scientist should consider when attempting to explain an apparent interferant result in an individual case. It should be remembered that measurement results need to be interpreted in their context, and data analysis concerning an instrument's performance should be considered.

Acetone↗
PubMed2001

Variance of protein heterozygosity in different species of mammals with respect to the number of loci studied.

Analysis of published data on protein heterozygosity of 321 species of mammals shows that it varies from 0 up to 22%, an average species being heterozygous at 5% of its protein-coding loci. Many attempts have been made to explain the observed differences in protein heterozygosity, relating its value to various species-, population-, or environment-specific parameters. In this work it is shown that the wide scatter of protein heterozygosity in different species of mammals can be explained by the small numbers of loci studied (usually 20-30). It is shown that with an increasing number of studied loci, the mean of the heterozygosity does not change, while its variance among different species decreases in accordance with a Poisson distribution. The true heterozygosity of the whole protein-coding region of the mammalian genome is thus characterized by a narrow spread around the mean. This means that the true heterozygosity of the protein-coding region is similar in all mammalian species. Its value can be viewed as the threshold level of variability of the protein-coding region of mammals, which characterizes the permissible level of erosion of genetic information of species and is maintained by stabilizing selection in natural ecological niches.

Analysis of Variance↗
PubMed1996

Spatial data aggregation: exploratory analysis of road accidents.

This paper is limited to the "size problem": it empirically and systematically examines to what extent the length of road segment influences the statistical description of accident counts and density. Univariate descriptive statistics are systematically measured for accident count and ratio, using different motorway segment lengths. A classification of the studied aggregation levels is proposed leading to three distinct groups of segments: (1) very small segments (1 hm), where observed accident counts are almost Poisson distributed, (2) large segments (more than 20 hm), where accident counts are almost normally distributed, and (3) medium size segments (3-20 hm), where accident counts have an intermediate empirical distribution. It is suggested that generalizations made at one level of spatial aggregation may not necessarily hold at another level. Conclusions derived at one scale may be invalid at another. The paper shows how important preliminary examination of the data can be, without any sophisticated statistical test. It also shows that one best or unique level of aggregation is not available: it depends upon the objective of the study. Results of any statistical analysis or modelling procedure should be seen as conditional on the scale of the analysis.

Accidents, Traffic↗
PubMed1989

Influenza mortality and excess deaths in the elderly, 1967-82.

This study assessed the influence of influenza on mortality from heart and lung diseases in people over 70 years of age. The data used were obtained from the Dutch Bureau of Statistics. With a regression model, the observed monthly mortality from heart and lung diseases (influenza not included) in people over 70 years is explained with a yearly variable, a monthly variable and the overall monthly number of influenza mortality cases, assuming that monthly mortality has a Poisson distribution. The monthly excess mortality from heart and lung diseases (influenza not included) due to influenza among elderly people (greater than 70 years) is estimated. This study suggests that 1400 deaths per million per year were due to influenza in people over 70 years of age in the study period of 16 years. It can be concluded that one influenza death in the population over 70 years 'generates' almost two deaths diagnosed as heart and lung diseases in the elderly.

Aged↗
PubMed2000

Agricultural work and the risk of Parkinson's disease in Denmark, 1981-1993.

OBJECTIVES: This study examined the possible association between agricultural and horticultural work and the subsequent morbidity of Parkinson's disease. METHODS: Fixed cohorts of 2,273,872 men and women aged 20-59 years on 1 January 1981 and identified in the Central Population Register of Denmark were followed, and all first-time hospitalizations with Parkinson's disease as the principal diagnosis during the 13 years until 31 December 1993 were recorded. Standardized hospitalization ratios (SHR) were calculated using all gainfully employed persons as the standard and by multiplying the ratio by 100. Ninety-five percent confidence intervals (95% CI) were calculated on the assumption of a Poisson distribution. RESULTS: A high risk of Parkinson's disease was found for the men and women in agriculture and horticulture (134 cases, SHR 132, 95% CI 111-156). Statistically significantly high risks were found for farmers (79 cases, SHR 130, 95% CI 103-163) and for all men in agriculture and horticulture (109 cases, SHR 134, 95% CI 109-162). CONCLUSIONS: A consistent pattern of high Parkinson's disease morbidity was found among occupational groups employed in agriculture and horticulture.

Adult↗
PubMed2005

Risk of Wilms' tumour with multicystic kidney disease: a systematic review.

BACKGROUND: Children with multicystic kidney disease (MCKD) are increasingly managed conservatively and are followed up throughout childhood because they are perceived to be at increased risk of developing Wilms' tumour. With this risk still poorly defined and somewhat controversial, the strategy and the duration of follow up do not seem to be based on evidence. METHODS: Systematic review of the literature for all published cohort studies (prospective and retrospective) of children diagnosed to have unilateral MCKD and managed conservatively. EXCLUSION CRITERIA: bilateral MCKD, nephrectomy (not for malignancy) during the follow up period. We estimated for children with MCKD the probability of developing Wilms' tumour during the follow up period, with 95% CI using the Poisson distribution. RESULTS: From 26 reviewed studies, no cases of Wilms' tumour developed in 1041 eligible children. The mean probability of a child with unilateral MCKD to develop Wilms' was therefore nil, with a 97.5% upper CI estimated at 0.0035 (or 3.5 per 1000 children). CONCLUSION: The development of a national or a European registry for children with MCKD would increase the precision of their risk estimate to develop Wilms' tumour. In the meantime, there is no evidence to support any of the different modalities for following up these children by ultrasound, if indeed such a strategy is necessary.

Child↗
PubMed2005

Bayesian proportional hazards model with time-varying regression coefficients: a penalized Poisson regression approach.

One can fruitfully approach survival problems without covariates in an actuarial way. In narrow time bins, the number of people at risk is counted together with the number of events. The relationship between time and probability of an event can then be estimated with a parametric or semi-parametric model. The number of events observed in each bin is described using a Poisson distribution with the log mean specified using a flexible penalized B-splines model with a large number of equidistant knots. Regression on pertinent covariates can easily be performed using the same log-linear model, leading to the classical proportional hazard model. We propose to extend that model by allowing the regression coefficients to vary in a smooth way with time. Penalized B-splines models will be proposed for each of these coefficients. We show how the regression parameters and the penalty weights can be estimated efficiently using Bayesian inference tools based on the Metropolis-adjusted Langevin algorithm.

Bayes Theorem↗
PubMed2000

Hyperacuity and the estimated positional accuracy of a theoretical simple cell.

Receiver operating characteristic (ROC) analysis was used to estimate positional discrimination thresholds for a theoretical simple cell by assuming Poisson distribution of the response, average response strength, and an optimal spatial frequency of 16.0 cyc/deg. These thresholds were compared to the positional difference required to generate a response change of one action potential. This comparison indicated that the inability to alter the response by less than one spike may be limiting positional accuracy. Taking account of this limitation, displacement thresholds were, depending on parameters, estimated to be as small as, or smaller than, the lowest psychophysical thresholds of about 2 sec of arc. This suggests that it may be possible to account for even the lowest human hyperacuity thresholds in terms of single cortical neurons.

Animals↗
PubMed1997

A simple non-linear model in incidence prediction.

A simple model is proposed for incidence prediction. The model is non-linear in parameters but linear in time, following models in environmental cancer epidemiology. Assuming a Poisson distribution for the age and period specific numbers of incident cases approximate confidence and prediction intervals are calculated. The major advantage of this model over current models is that age-specific predictions can be made with greater accuracy. The model also preserves in the period of prediction the age pattern of incidence rates existing in the data. It may be fitted with any package which includes an iteratively reweighted least squares algorithm, for example GLIM. Cancer incidence predictions for the Stockholm-Gotland Oncological Region in Sweden are presented as an example.

Adult↗
PubMed2005

Why high-error-rate random mutagenesis libraries are enriched in functional and improved proteins.

The fraction of proteins that retain wild-type function after mutation has long been observed to decline exponentially as the average number of mutations per gene increases. Recently, several groups have used error-prone polymerase chain reactions (PCR) to generate libraries with 15 to 30 mutations per gene, on average, and have reported that orders of magnitude more proteins retain function than would be expected from the low-mutation-rate trend. Proteins with improved or novel function were isolated disproportionately from these high-error-rate libraries, leading to claims that high mutation rates unlock regions of sequence space that are enriched in positively coupled mutations. Here, we show experimentally that error-prone PCR produces a broader non-Poisson distribution of mutations consistent with a detailed model of PCR. As error rates increase, this distribution leads directly to the observed excesses in functional clones. We then show that while very low mutation rates result in many functional sequences, only a small number are unique. By contrast, very high mutation rates produce mostly unique sequences, but few retain function. Thus an optimal mutation rate exists that balances uniqueness and retention of function. Overall, high-error-rate mutagenesis libraries are enriched in improved sequences because they contain more unique, functional clones. Our findings demonstrate how optimal error-prone PCR mutation rates may be calculated, and indicate that "optimal" rates depend on both the protein and the mutagenesis protocol.

Data Interpretation, Statistical↗
PubMed2000

The index of dispersion of molecular evolution: slow fluctuations.

The most simple neutral model of molecular evolution predicts that the number of substitutions within a lineage in T generations ought to be Poisson distributed. Therefore, the variance in the number of substitutions ought to equal the mean number. The ratio of the variance to the mean number of substitutions is called the index of dispersion, R(T). Assuming infinite sites, no recombination model of the gene, and a haploid, Moran population structure, R(T) is derived for a general stationary model of molecular evolution. R(T) is shown to be affected by fluctuations in parameters only when they occur on a very slow time scale. In order for parameter fluctuations to cause R(T) to deviate significantly from one, the time between parameter changes must be roughly as large, or larger, than the time between substitutions.

Animals↗
PubMed2006

Impact of weather and climate on the incidence of acute coronary syndromes.

BACKGROUND: First investigations of the interactions between weather and the incidence of acute myocardial infarctions date back to 1938. The early observation of a higher incidence of myocardial infarctions in the cold season could be confirmed in very different geographical regions and cohorts. While the influence of seasonal variations on the incidence of myocardial infarctions has been extensively documented, the impact of individual meteorological parameters on the disease has so far not been investigated systematically. Hence the present study intended to assess the impact of the essential variables of weather and climate on the incidence of myocardial infarctions. METHODS: The daily incidence of myocardial infarctions was calculated from a national hospitalization survey. The hourly weather and climate data were provided by the database of the national weather forecast. The epidemiological and meteorological data were correlated by multivariate analysis based on a generalized linear model assuming a log-link-function and a Poisson distribution. RESULTS: High ambient pressure, high pressure gradients, and heavy wind activity were associated with an increase in the incidence of the totally 6560 hospitalizations for myocardial infarction irrespective of the geographical region. Snow- and rainfall had inconsistent effects. Temperature, Foehn, and lightning showed no statistically significant impact. CONCLUSIONS: Ambient pressure, pressure gradient, and wind activity had a statistical impact on the incidence of myocardial infarctions in Switzerland from 1990 to 1994. To establish a cause-and-effect relationship more data are needed on the interaction between the pathophysiological mechanisms of the acute coronary syndrome and weather and climate variables.

Climate↗