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PubMed1982

How long is the wait for an uncommon event?

If the probability of an event is known, the lengths of series until at least 1, 2, ...,r events have taken place in this series are predictable. They have a negative binomial distribution. The use of this distribution is described to predict the lengths of series of patients to be treated with a certain drug until at least 1, 2,...,5 times a patient with for example, the side-effect exanthema will be seen, if an exanthema occurs in 1 out of 100 of these patients. In other examples the events are deaths after an anesthetic, cervical carcinomas in the screening procedure, and significances in statistical tests with alpha = 0.05 as a level of significance.

Anesthesia↗
PubMed1983

The disparity between homologous chromosomes during DNA replication.

When the patterns of replicating chromosome bands of homologous chromosomes within a diploid cell during DNA synthesis phase are compared, the frequency of disparity (i.e. a band present on only one homologue) is less than expected on the basis of chance. This could be taken as implying some "link" between homologues which constrains their programmes of replication to keep in step. This paper develops a model showing that the observed disparities can be accommodated within a framework of homologue independence. Differences between cells in the time of appearance of bands lead in any sample to the summation of an infinitude of binomial distributions and hence to over-dispersion. The model fits observed data for bands replicating in euchromatic and heterochromatic chromosome regions obtained from Syrian hamster fibroblast cells growing in vitro.

Animals↗
PubMed1990

An approach for immunodiagnosis of clinical cases of filariasis.

In this communication an immunodiagnostic approach has been adopted for detection of antigen and antibody in amicrofilaeamic Mf(-) patients by countercurrent immuno electrophoresis (CCIE) and immunodiffusion (ID). Using Setaria cervi and Immune Complex (IC) antigens, out of fifteen clinical cases the number of positive patients in CCIE were twelve and ten respectively. Sixty percent of the Mf(-) cases were positive in antigen detection against both the homologous and heterologous antibody. In ID nine Mf(-) cases gave precipitin bands against S. cervi antigen while with IC antigens ten patients were positive. In similar experiments, it was found that out of fifteen Mf(-) cases nine and eleven patients were positive in antigen detection against microfilaraemic Mf(+) sera and S. cervi antibody respectively. All the Mf(+) cases were positive in both antibody and antigen detection. From the standpoint of immunodiagnosis the data were analysed by two-way analysis of variance study and a newly developed system using Binomial distribution. The sera from the control group were negative in all the immunodiagnostic tests.

Adolescent↗
PubMed1992

A method for the analysis of biological transduction phenomena.

Biological transduction can be defined as the triggering of a cellular response by the binding of molecules of effector substances to specific cellular sites. An example of biological transduction, analyzed in this report, is the triggering of T-cell proliferation by the binding of T-cell growth factor (TCGF) to specific TCGF-binding sites on responsive T-cells. Sigmoidal or S-shaped curves often result when measurements of biological response are plotted as a function of concentration of effector substance. Such curves suggest that effector molecules must bind a critical number of cellular sites, and this critical number of bound complexes must undergo secondary events (cross-linking, association, internalization, second messenger release, etc.) in order to initiate the biological response. The method described here estimates the critical number of cellular sites (R) and the probability of these secondary events (PS/B) as follows: (1) The total number of cellular sites (N) is estimated from binding data, and the probabilities (PB) of effector molecules binding to a site are estimated from response data. (2) The response data are assumed to follow the summed binomial distribution function, which is equated to the incomplete beta function. (3) R and PS/B are estimated by applying nonlinear regression to the incomplete beta function. The T-cell data to which the method was applied gave N = 15,000, R = 5, and PS/B = 7.22 x 10(-4). These results show that the binding of very few TCGF molecules is required for activation of T-cells and that the probability of the secondary events leading to cell proliferation is much smaller than the probability of TCGF binding to T-cells. The method described can be used to analyze any biological transduction experiments where both binding and biological response data are available.

Binding Sites↗
PubMed1995

The population dynamics of communities of parasitic helminths.

This paper considers the dynamics of a host (animal) species that would grow exponentially in the absence of parasitism, and a community of parasite species that may regulate this growth. The model consists of a single differential equation for the host and one for each of the parasite species. This level of simplicity is achieved by assuming that each parasite species has a negative binomial distribution within the host population, with either zero covariance between the species (exploitation competition), or a specified covariance structure (interference competition). Conditions on the model parameters that determine the abundance of the different species are formulated, as are conditions that determine when a parasite species can invade a community and when a species is likely to be squeezed out. The results show that highly aggregated parasite species are more likely to coexist, but are less able to regulate their host population. A negative correlation between the distributions of the parasite species enhances both their ability to coexist and their ability to regulate the host population. The results of this analysis apply more generally to other systems where communities of exploiter species coexist on discretely distributed hosts, for example, insects on plants.

Animals↗
PubMed1986

An assessment of reproductive wastage in sheep.

Reproductive wastage was evaluated by relating ovulation rate to lambs born or raised in range finewool ewes over a ten-year period. The results indicate that reproductive losses are of large magnitude and that these losses are concentrated in the period of ovulation to implantation and in death losses of lambs born. In this study, 33.5% of the potential lamb crop was lost in the early period. Multiple ovulating ewes showed the greatest embryonic loss. The data do not deviate from the binomial distribution, thus suggesting that these losses are largely due to chance. Further work is indicated in the first seventeen days after ovulation to examine losses due to fertilization failure, chromosomal abnormalities, and implantation failure. Abortion or absorption of the fetus was indicated in only 4% of the ewes sampled. An average of 16% of the potential lamb crop was lost from birth to weaning, with 73% of these losses occurring in the first few weeks. Management practices need to be developed to reduce these losses, and these would be expected to vary from one producer to the next depending on conditions. Increasing ovulation rate is one possible method of improving reproductive efficiency, as results of this study indicate that for each unit increase in ovulation rate, there is an increase of 0.52, 0.46, 0.33, and 0.23 in the average number of embryos surviving, lambs born, lambs marked and lambs weaned, respectively.

Journal Article↗
PubMed1979

Statistical tests for recessive lethal-carriers.

This paper presents a statistical method for testing whether a male mouse is a recessive lethal-carrier. The analysis is based on a back-cross experiment in which the male mouse is mated with some of his daughters. The numbers of total implantations and intrauterine deaths in each litter are recorded. It is assumed that, conditional on the number of total implantations, the number of intrauterine deaths follows a binomial distribution. Using computer-simulated experimentation it is shown that the proposed statistical method, which is sensitive to the pattern of intrauterine death rates, is more powerful than a test based only on the total number of implant deaths. The proposed test requires relatively simple calculations and can be used for a wide range of values of total implantations and background implant mortality rates. For computer-simulated experiments, there was no practical difference between the empirical error rate and the nominal error rate.

Animals↗
PubMed1996

Heme-CO binding to tryptophan-containing calmodulin mutants.

The binding of heme-CO to genetically engineered calmodulin containing a single tryptophan residue has been studied. A tryptophan residue was integrated at one of five positions: 26 or 62 of the N-terminal, 81 in the central helix, or 99 or 135 of the C-terminal. As for the wild type, the mutant calmodulins bind four molecules of heme-CO with an average affinity of 1 microM. (i) Homotropic effect. The quenching of the tryptophan fluorescence by energy transfer to the hemes indicates that there is no preference between the N- or C-terminal pockets for heme binding. The quenching is less than expected for a binomial distribution of four sites. This could indicate a lower energy transfer rate due to a specific orientation factor. The weak quenching as a function of the number of hemes bound may also reveal a cooperativity in the heme binding; the data can be simulated assuming two pairs of sites, where each pocket shows a cooperative binding for two hemes. (ii) Heterotropic effect. As observed for the wild type, addition of melittin does not displace the hemes from the mutant calmodulins; the affinity of heme-CO for the calmodulin.melittin complex is higher than that for calmodulin alone. The affinity of heme-CO for native calmodulin is also higher in the presence of trifluoperazine.

Animals↗
PubMed1995

Nail abnormalities in nondermatologic patients: prevalence and possible role as diagnostic aids.

BACKGROUND: Nail changes have traditionally been used as diagnostic aids. Their usefulness in general and predictive value in particular, however, is not known. OBJECTIVE: Our purpose was to survey nail changes and to clarify the potential of nail abnormalities to diagnose nondermatologic diseases. METHODS: The fingernails of 567 patients admitted to general medical and surgical wards were examined. The point prevalence rates were calculated on the basis of a binomial distribution. The results were compared with the diagnosis with logistic regression analysis correcting for age and sex. RESULTS: The most common findings were absence of lunulae (22.9% [19.5% to 26.6%]), white nails or apparent leukonychia (11.8% [9.3% to 14.8%]), and red lunulae (5.1% [3.5% to 7.3%]). The following significant associations were noted: pulmonary disease and clubbing (odds ratio[OR] = 4.1, 95% confidence interval [CI] = 1.7 to 9.5), hematologic disease and brittle nails (OR = 4.6, 95% CI = 1.6 to 13.7), hematologic disease and Terry nails (OR = 8.7, 95% CI = 2.7 to 27.0), gastrointestinal disease and pincer nails (OR = 33.6, 95% CI = 3.7 to 307.3), and gastrointestinal disease and subjective complaints (OR = 2.7, 95% CI = 1.4 to 5.0). CONCLUSION: Several significant associations were identified, suggesting that nail abnormalities can be diagnostic clues in the diagnosis of chronic nondermatologic diseases. An association between pincer nails and gastrointestinal disease has not been previously described.

Adolescent↗
PubMed1994

Simple Bayesian analysis in clinical trials: a tutorial.

In this tutorial paper we give a simple Bayesian analysis of data that arise in clinical trials. We consider the case when there are two treatment groups and the response in each group can be assumed to be binomially distributed. We also assume that prior beliefs about the rate parameter in each group can be adequately expressed by a Beta distribution. Using such a model approximate posterior inferences can then be made about the odds ratio between the two groups. We illustrate this methodology by analyzing a randomized trial to assess the benefits of treating patients with carcinoma of the pelvic region (rectum, bladder, colon, cervix) using high-energy fast neutrons as opposed to conventional megavoltage x-rays (photons). In this trial there was prior information about the relative efficacy of neutron therapy based on the beliefs of 10 clinicians. Some of the deficiencies of this simple approach are high-lighted and other approaches to analysis indicated. The paper facilitates practical consideration of a Bayesian approach without the complexities that a fuller analysis necessitates.

Bayes Theorem↗
PubMed1993

Out-of-hospital resuscitation preferences of emergency health care workers.

The objective of this study was to assess the personal preferences of emergency physicians, nurses, and medical technicians regarding their own potential out-of-hospital resuscitation. An anonymous multiitem survey instrument was used at a statewide emergency medicine educational conference. Emergency personnel who regularly treat out-of-hospital cardiac arrest patients were enlisted to participate. Subjects picked the last intervention that they would wish for themselves in an optimally managed advanced cardiac life support (ACLS)-based resuscitation for ventricular fibrillation. One hundred millimeter visual analog scales were used to measure individual preferences for severe neurological disability or death. Hypothesis testing was by analysis of variance with Newman-Keuls, multiple regression with stepwise variable selection, and the chi 2 and binomial distributions. Of 185 survey instruments, 105 were returned completed by eligible subjects. There was little difference among the three occupational groups (P > .5), although older respondents favored shorter resuscitations (r = -.38; P = .002). Ten subjects did not want cardiopulmonary resuscitation started, and 65% wanted resuscitation stopped before the second dose of epinephrine. Only three subjects chose to undergo the entire ACLS sequence. Eighty-two percent of respondents preferred death to severe neurological disability. Emergency health care professionals have a unique personal awareness of issues surrounding out-of-hospital resuscitation. That a large majority would prefer death to severe disability and few would willingly undergo full resuscitation as currently practiced suggests that prevailing guidelines should be reevaluated.

Adult↗
PubMed1994

Observation unit impact on ED admission for asthma.

The hypothesis that the use of an observation unit (OU) in the emergency department (ED) results in monetary savings by lowering the hospital admission rate for asthma was studied in a retrospective comparative cohort at an urban university county hospital. All acute asthmatic patients seen in the ED during a 22-month period were included. Preobservation patients were seen before the OU opened (n = 834); postobservation patients were treated afterward (n = 390). Postobservation patients in the experimental group meeting standard criteria were admitted to the OU. Fisher's exact test and the binomial distribution were used to analyze proportions of patients admitted. Median charges were compared with the Mann-Whitney test. The difference between groups in hospital admission rate was only 2.7% and was not significant (P = .25). However, 5.3% less patients were admitted directly to the hospital (P = .01), and 6.7% less patients were discharged directly from the ED (P = .005). The OU produced no demonstrable cost savings. The use of an OU for asthmatic patients results in lower initial discharge rates from the ED and does not reduce eventual hospital admission appreciably.

Adolescent↗
PubMed2006

Modeling motor vehicle crashes using Poisson-gamma models: examining the effects of low sample mean values and small sample size on the estimation of the fixed dispersion parameter.

There has been considerable research conducted on the development of statistical models for predicting crashes on highway facilities. Despite numerous advancements made for improving the estimation tools of statistical models, the most common probabilistic structure used for modeling motor vehicle crashes remains the traditional Poisson and Poisson-gamma (or Negative Binomial) distribution; when crash data exhibit over-dispersion, the Poisson-gamma model is usually the model of choice most favored by transportation safety modelers. Crash data collected for safety studies often have the unusual attributes of being characterized by low sample mean values. Studies have shown that the goodness-of-fit of statistical models produced from such datasets can be significantly affected. This issue has been defined as the "low mean problem" (LMP). Despite recent developments on methods to circumvent the LMP and test the goodness-of-fit of models developed using such datasets, no work has so far examined how the LMP affects the fixed dispersion parameter of Poisson-gamma models used for modeling motor vehicle crashes. The dispersion parameter plays an important role in many types of safety studies and should, therefore, be reliably estimated. The primary objective of this research project was to verify whether the LMP affects the estimation of the dispersion parameter and, if it is, to determine the magnitude of the problem. The secondary objective consisted of determining the effects of an unreliably estimated dispersion parameter on common analyses performed in highway safety studies. To accomplish the objectives of the study, a series of Poisson-gamma distributions were simulated using different values describing the mean, the dispersion parameter, and the sample size. Three estimators commonly used by transportation safety modelers for estimating the dispersion parameter of Poisson-gamma models were evaluated: the method of moments, the weighted regression, and the maximum likelihood method. In an attempt to complement the outcome of the simulation study, Poisson-gamma models were fitted to crash data collected in Toronto, Ont. characterized by a low sample mean and small sample size. The study shows that a low sample mean combined with a small sample size can seriously affect the estimation of the dispersion parameter, no matter which estimator is used within the estimation process. The probability the dispersion parameter becomes unreliably estimated increases significantly as the sample mean and sample size decrease. Consequently, the results show that an unreliably estimated dispersion parameter can significantly undermine empirical Bayes (EB) estimates as well as the estimation of confidence intervals for the gamma mean and predicted response. The paper ends with recommendations about minimizing the likelihood of producing Poisson-gamma models with an unreliable dispersion parameter for modeling motor vehicle crashes.

Accidents, Traffic↗
PubMed2005

Selection of control genes for quantitative RT-PCR based on microarray data.

Use of internal reference gene(s) is necessary for adequate quantification of target gene expression by RT-PCR. Herein, we elaborated a strategy of control gene selection based on microarray data and illustrated it by analyzing endomyocardial biopsies with acute cardiac rejection and infection. Using order statistics and binomial distribution we evaluated the probability of finding low-varying genes by chance. For analysis, the microarray data were divided into two sample subsets. Among the first 10% of genes with the lowest standard deviations, we found 14 genes common to both subsets. After normalization using two selected genes, high correlation was observed between expression of target genes evaluated by microarray and RT-PCR, and in independent dataset by RT-PCR (r = 0.9, p < 0.001). In conclusion, we showed a simple and reliable strategy of selection and validation of control genes for RT-PCR from microarray data that can be easily applied for different experimental designs and tissues.

Algorithms↗
PubMed2005

Testing resource value in group-housed animals: an investigation of cage height preference in laying hens.

To avoid unpredictable social effects, animals' behavioural priorities are almost always tested using individuals housed singly, yet many species kept commercially are social animals housed in groups. Our aim was to develop a method of investigating environmental preference in group-housed laying hens, Gallus gallus domesticus, that maximised the external validity of our findings. In a simple test of preference, eight groups of ten hens were given free choice between furnished cages with minimum heights of 38 cm (low) and 45 cm (high). A preference for one cage height over the other would be evident as a shift from a binomial distribution of flock sizes in the two cages. No height preference was found as hens distributed evenly between the two cages more frequently than was expected. This suggests at high stocking densities maximising average inter-individual distance could be a priority over increased cage height. In a second experiment, to investigate the value that hens placed on a change in cage height; a 'cost' in the form of a narrow gap was imposed on movement from a low or high start cage to a high or low target cage, respectively. Cage height did not influence the latency of the first three hens to enter the target cage. However, latencies for subsequent hens were shorter and more hens worked to access a high target cage than a low target cage. We suggest that titrating animals' willingness to tolerate higher stocking densities against access to a resource could be an effective way to compare responses of group-housed animals to resources that are expected to satisfy the same motivational state.

Animal Welfare↗
PubMed2005

Substantial proportions of identical beta-chain T-cell receptor transcripts are present in epithelial ovarian carcinoma tumors.

To determine whether clonally expanded T cells are present in tumor specimens from patients with epithelial ovarian carcinoma (EOC) we amplified by the non-palindromic adaptor PCR (NPA-PCR) or by Vbeta-specific PCR beta-chain T-cell receptor (TCR) transcripts from these tumor specimens. The amplified transcripts were cloned and sequenced. Sequence analysis revealed the presence of substantial proportions of multiple identical copies of beta-chain TCR transcripts, suggesting the presence of clonal expansions of T cells in these patients, which were statistically significant by the binomial distribution in seven of nine patients. Independent amplification in separate experiments of beta-chain TCR transcripts from one patient by either NPA-PCR or by Vbeta-specific PCR, followed by cloning and sequencing, revealed identical clonal expansions irrespectively of the amplification method used. Multiple identical copies of beta-chain TCR transcripts can be derived only by specific antigen-driven proliferation and clonal expansion of the T-cell clones which recognize these antigens. Because of the very large size of the TCR repertoire, the probability of finding by chance multiple identical copies of these transcripts within an independent sample of T cells is negligible. These results demonstrate that T cells infiltrating solid tumor specimens or malignant ascites of patients with EOC contain monoclonal/oligoclonal populations of T cells.

Adult↗
PubMed2005

The relationship between focal seizures and sleep: an analysis of the cyclic alternating pattern.

PURPOSE: The aim of this study was to examine the relationship between focal epileptic seizures and sleep through analysis of the cyclic alternating pattern (CAP). METHODS: We analyzed the recordings of a total of 56 nocturnal partial seizures (13 occurring as isolated events and 43 "in clusters" during a full-night ambulatory polysomnography) in 12 adult patients affected by localization-related focal epilepsy (7 males, 5 females; mean age 35+12.8 years; range 25-71). RESULTS: On exact binomial distribution analysis, seizures were more frequent in CAP than in non-CAP sleep, and in CAP phase A than in CAP phase B (p<0.001). Seizures occurring in clusters were more frequently associated with CAP sleep (p<0.05) than isolated seizures and first seizures of seizure clusters. Increase of CAP rate during the 30-min of sleep period after the occurrence of a seizure was documented in both cluster and isolated seizures. CONCLUSIONS: Our data indicate that an intra-sleep condition of highly fluctuating vigilance constitutes the real substrate for the occurrence of epileptic seizures regardless of the NREM stage in which they occur. The occurrence of partial seizures during sleep appears to induce sleep instability, which may in turn result in the facilitation of clusters of seizures. Together, these data highlight the potential of sleep fragmentation to modulate intra-sleep seizure occurrence.

Adult↗
PubMed2005

Cooperativity in the adsorption of magnetic colloidal particles.

In this paper we investigate the adsorption of magnetic particles onto magnetically patterned substrates. We find that the adsorption process is cooperative, where the probability of adsorption decreases with increasing substrate occupancy (namely, density of adsorbed particles). The effect of cooperativity can be accounted for by a simple modification of the adsorption probability as manifested by the binomial distribution. The negative cooperativity found in the magnetic particle adsorption is not due to direct repulsion between particles, but to screening of the surface's magnetic field by previously adsorbed particles. Thus, the adsorption of magnetic colloids on magnetic substrates is a self-limiting process.

Journal Article↗