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PubMed1984

[Analysis of factors limiting the applications of binomial statistics in studies of mediator secretion at neuromuscular synapses].

Binomial parameters of transmitter secretion were calculated on the basis of synaptic potential analyses at frog sartorius muscle. In some synapses negative values of parameter of the p were found. These negative values often occurred at low concentrations of Ca2+ ions and small amplitude of miniature end plate potentials. The obtained data were interpreted in terms of a model which presupposes the heterogeneity of the quantum transmitter release at different sites. A computer imitation of transmitter secretion showed that the appearance of the negative p parameter values and erroneous n estimations in the experiment are related with the shape of the distribution of quantum transmitter release probability and the amplitude of miniature end plate potentials.

Animals↗
PubMed1998

Nutrient absorption from a fat-enriched diet in young malnourished children: a randomized controlled trial.

A randomized, controlled trial was undertaken to compare nutrient absorption from low fat (22.2% energy as fat) and high fat (48% energy as fat)-containing mixed diets in 39 (26M, 13F) malnourished children aged < 2 y. Subjects of both dietary groups, standard (SDG, n = 18) and experimental (EDG, n = 21), were offered 184.5 ml of feeds/kg body weight/24 h that provided 146 kcal with the low fat diet and 216 kcal with the high fat diet, respectively. The baseline clinical and biochemical parameters and the volume of feeds consumed by the patients in the two groups were comparable. Thus, the subjects in the EDG were ingesting a mean (95% CI) of 50% (23.8%, 76.2%) extra energy than that eaten by the SDG. Coefficients of absorption of energy, nitrogen and carbohydrate were similar in the two dietary groups (p = 0.08-0.98). Median (binomial exact 95% CI) fat absorption among subjects receiving the high fat diet (96.3; 92.9, 98.6) was 7% more than in those consuming the low fat diet (89.3; 86.7, 94.1) (p = 0.01). Subjects of the EDG thus, retained almost 50% additional energy as compared to that by SDG.

Chi-Square Distribution↗
PubMed1992

A geostatistical approach to the analysis of pattern in rare disease.

The incidences of human disease vary from place to place, and some show distinct patterns. Patterns in rare diseases, such as childhood cancer, are not readily discernible, however, and this makes it difficult to relate their distribution to factors in the environment in seeking possible causes of the disease. Provided cases are geographically indexed, data on a disease can be analysed geostatistically. Variograms can be computed to determine the strength and spatial scale of any pattern, and to summarize the variation, and then the risk of developing the disease can be estimated by kriging. This has been done for the incidence rates of childhood cancer from 1980 to 1984 in the West Midlands Health Authority Region of England. A novel modification was made to compute the variogram of the risk from that of the frequencies, taking into account the binomial nature of the data. The incidence of the disease appears patchy. The results show that this patchiness is spatially correlated and not purely random. The risk appears greatest in the rural south west of the Region and in some of the suburbs around the conurbation. This approach using geostatistics seems very promising and will be developed further as more data for this and other diseases become available.

Child↗
PubMed1986

Quantitative description of three modes of activity of fast chloride channels from rat skeletal muscle.

The steady-state kinetic properties of single Cl- channels with fast kinetics active at resting membrane potentials in cultured rat skeletal muscle were studied using the patch-clamp technique. Membrane patches containing single active Cl- channels were often observed, and binomial analysis of the percentage open time in membrane patches containing several Cl- channels indicated that the channels did not occur as obligatory dimers and that they gated independently of one another. Channel activity could be divided into three categories: normal, which included about 99% of the openings and closings; buzz mode, which included about 1% and consisted of bursts of about 50 brief open and shut intervals; and inactivated shut states which included about 0.01% of the shut intervals and lasted for seconds, and occasionally minutes. The method of maximum likelihood was used to determine the number of significant exponential components required to fit the distributions of open and shut intervals during normal activity. Open interval distributions required at least two components, with time constants of 0.52 and 1.5 ms at -40 mV and 7.6 degrees C. Shut interval distributions required at least five exponential components, with time constants of 0.064, 0.72, 1.9, 12.3 and 350 ms. Kinetic reaction schemes were developed for the normal and buzz mode using maximum likelihood techniques to determine the most likely models and rate constants. In developing these models the effects of limited time resolution and missed events were taken into account. Each model tested typically had two or more sets of equally likely rate constants. Incorrect sets of rate constants resulting from the effect of missed events could be eliminated by analysis of the data with different time resolutions. Normal activity could be accounted for by several different seven-state models with two open and five shut states. As different models could be found that gave identical descriptions of the data, the distributions of open and shut intervals were not sufficient to define a unique model. It was established that no other seven-state models would be found that describe the distributions of open and shut intervals during normal activity better than the most likely presented models.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed2001

Clinical trials of multiple sclerosis monitored with enhanced MRI: new sample size calculations based on large data sets.

OBJECTIVE: A new parametric simulation procedure based on the negative binomial (NB) model was used to evaluate the sample sizes needed to achieve optimal statistical powers for parallel groups (with (PGB) and without (PG) a baseline correction scan). It was also used for baseline versus treatment (BVT) design clinical trials in relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS), when using the number of new enhancing lesions seen on monthly MRI of the brain as the measure of outcome. METHODS: MRI data obtained from 120 untreated patients with RRMS selected for the presence of MRI activity at baseline, 66 untreated and unselected patients with RRMS, and 81 untreated and unselected patients with SPMS were fitted using an NB distribution. All these patients were scanned monthly for at least 6 months and were all from the placebo arms of three large scale clinical trials and one natural history study. The statistical powers were calculated for durations of follow up of 3 and 6 months. RESULTS: The frequency of new enhancing lesions in patients with SPMS was lower, but not significantly different, from that seen in unselected patients with RRMS. As expected, enhancement was more frequent in patients with RRMS selected for MRI activity at baseline than in the other two patient groups. As a consequence, the estimated sample sizes needed to detect treatment efficacy in selected patients with RRMS were smaller than those of unselected patients with RRMS and those with SPMS. Baseline correction was also seen to reduce the sample sizes of PG design trials. An increased number of scans reduced the sample sizes needed to perform BVT trials, whereas the gain in power was less evident in PG and PGB trials. CONCLUSION: This study provides reliable estimates of the sample sizes needed to perform MRI monitored clinical trials in the major MS clinical phenotypes, which should be useful for planning future studies.

Adult↗
PubMed2005

Short-term survival after surgery for epiploic foramen entrapment compared with other strangulating diseases of the small intestine in horses.

REASONS FOR PERFORMING STUDY: Epiploic foramen entrapment (EFE) is one of the more common causes of colic in horses, but recent reports suggest a poor prognosis after surgical treatment. HYPOTHESIS: That EFE has a good prognosis compared with other small intestinal strangulating lesions. METHODS: Surgical findings, surgical procedures and short-term outcome were recorded for 157 horses that underwent surgery for strangulating lesions of the small intestine at the University of Illinois from 1994 to 2003. Horses were assigned to 3 groups for comparison; those with EFE, strangulation by lipoma and miscellaneous strangulating lesions. A logistic regression model and Monte Carlo tests of the binomial proportions were used to examine survival rates. The Kruskal-Wallis test was used to determine differences in usage of surgical treatments. Measurements of length and viability indices were analysed using a one-way analysis of variance followed by Tukey's HSD test, and viability scores were analysed using an exact Kruskal-Wallis test. Significance was set at P < 0.05. RESULTS: Horses with EFE were significantly more likely to be discharged (95%) than those with the other conditions (P < 0.05). The proportion of horses with ileal involvement was greater in horses with EFE than in the other 2 groups (P < 0.05), although this did not affect outcome. The distributions of viability grades for EFE and lipoma differed significantly (P < 0.05). CONCLUSIONS: The prognosis for horses that had surgery at this hospital for EFE was better than for those with the other conditions, although the greater proportion of horses with EFE with ileal involvement could influence outcome. Therefore, surgeons must consider ways of improving jejunocaecostomy and determining when bowel is viable, the latter to avoid jejunocaecostomy.

Analysis of Variance↗
PubMed2006

Numerical solutions for patterns statistics on Markov chains.

We propose here a review of the methods available to compute pattern statistics on text generated by a Markov source. Theoretical, but also numerical aspects are detailed for a wide range of techniques (exact, Gaussian, large deviations, binomial and compound Poisson). The SPatt package (Statistics for Pattern, free software available at http://stat.genopole.cnrs.fr/spatt) implementing all these methods is then used to compare all these approaches in terms of computational time and reliability in the most complete pattern statistics benchmark available at the present time.

Algorithms↗
PubMed2006

Population models for threshold-based control of Tetranychus urticae in small-scale Kenyan tomato fields and for evaluating weather and host plant species effects.

The spatial distribution of motile life stages of the two-spotted spider mite Tetranychus urticae Koch in Kenyan small-scale tomato fields was described by Taylor's power law and an enumerative sampling plan was designed for research purposes. The exponential increase of T. urticae populations during three growing seasons permits the development and use of a simple exponential model for the design of a threshold-based chemical control system. For this purpose, a critical threshold of 440 motile mites per sample unit at the end of the growing season (12 weeks after transplanting) was translated into a proportion of 0.83 infested units in sample 3, i.e. five weeks after transplanting. A sequential binomial sampling plan with respect to the proportion of 0.83, five weeks after transplanting, was designed. The exponential model was extended to account for the influence of weather and host plant species. Model development and parameter estimation were based on three data sets (Kenyan tomato fields, Italian and Californian strawberry fields). The model satisfactorily predicted a positive influence on growth rates by (i) changing the host plant from tomato to strawberry, and (ii) temperature, while a negative effect resulted from (iii) rainfall; both (ii) and (iii) are controlled by temperature-rainfall interactions. In contrast, the estimated parameter values did not satisfactorily describe the expected responses at specific temperature and rainfall values. Nevertheless, the model allowed the rating of host plant species in the field. A fourth data set from Swiss apple orchards was used to test the model, and population build-up on the apple host plant appeared to be higher than on tomatoes but lower than on strawberry.

Animals↗
PubMed2005

Within-plant distribution of twospotted spider mites (Acari: Tetranychidae) on impatiens: development of a presence-absence sampling plan.

The twospotted spider mite, Tetranychus urticae Koch, is an important pest of impatiens, a floricultural crop of increasing economic importance in the United States. The large amount of foliage on individual impatiens plants, the small size of mites, and their ability to quickly build high populations make a reliable sampling method essential when developing a pest management program. In our study, we were particularly interested in using spider mite counts as a basis for releasing biological control agents. The within-plant distribution of mites was established in greenhouse experiments and these data were used to identify the sampling unit. Leaves were divided into three zones according to location on the plant: inner, intermediate, and other. On average, 40, 33, and 27% of the leaves belonged to the inner, intermediate, and other leaf zones, respectively. However, because 60% of the mites consistently were found on the intermediate leaves, intermediate leaves were chosen as the sampling unit. These results lead to the development of a presence-absence sampling method for T. urticae by using Taylor coefficients generic for this pest. The accuracy of this method was verified against an independent data set. By determining numerical or binomial sample sizes for consistently estimating twospotted spider mite populations, growers will now be able to determine the number of predatory mites that should be released to control twospotted spider mites on impatiens.

Animals↗
PubMed2006

Trends in incidence rates of oesophagus and gastric cancer in Italy by subsite and histology, 1986-1997.

OBJECTIVE: Population-based studies in Western countries suggest that the incidence of oesophageal adenocarcinoma (OA) and gastric cardia adenocarcinoma (GCA) is increasing, whereas the incidence of distal gastric carcinoma and oesophageal squamous cell carcinoma (OSCC) is declining. This is the first population-based study carried out in a southern European region to evaluate the time trends in incidence rates of oesophageal and gastric tumours according to subsite and histology over the period 1986-1997. METHODS: Cancer cases were drawn from seven registries of the Italian Network of Cancer Registries, which covers approximately 9% of the Italian population (annual average 5 027 944). Time trends in age and sex-standardized incidence rates were reported. Estimated annual percentage changes (EAPC) and related 95% confidence intervals (CI) were estimated by modelling age, sex, subsite and morphology-specific incidence rates through Poisson log-linear regression, and whenever necessary negative-binomial regression. Overall, 25 895 gastric and 2497 oesophageal carcinomas were examined. RESULTS: On the whole, an increasing trend was observed for OA plus GCA. The increase was statistically significant in younger women (<60 years: EAPC 3.7; 95% CI 0.2; 7.3) and in older men (>75 years: EAPC 4.0; 95% CI 1.2; 6.9). Similar trends were also observed in proximal gastric cancer (GCA plus fundus). A decline in the stomach subfundus incidence was observed in both sexes and in each age group. OSCC decreased significantly in men (EAPC-2.6; 95% CI-4.1;-0.9). CONCLUSIONS: It is plausible that the different tendencies in oesophageal and proximal gastric cancer in men and women are attributable to heterogeneous distributions of risk factors by sex or age.

Adenocarcinoma↗
PubMed2003

Alternatives for logistic regression in cross-sectional studies: an empirical comparison of models that directly estimate the prevalence ratio.

BACKGROUND: Cross-sectional studies with binary outcomes analyzed by logistic regression are frequent in the epidemiological literature. However, the odds ratio can importantly overestimate the prevalence ratio, the measure of choice in these studies. Also, controlling for confounding is not equivalent for the two measures. In this paper we explore alternatives for modeling data of such studies with techniques that directly estimate the prevalence ratio. METHODS: We compared Cox regression with constant time at risk, Poisson regression and log-binomial regression against the standard Mantel-Haenszel estimators. Models with robust variance estimators in Cox and Poisson regressions and variance corrected by the scale parameter in Poisson regression were also evaluated. RESULTS: Three outcomes, from a cross-sectional study carried out in Pelotas, Brazil, with different levels of prevalence were explored: weight-for-age deficit (4%), asthma (31%) and mother in a paid job (52%). Unadjusted Cox/Poisson regression and Poisson regression with scale parameter adjusted by deviance performed worst in terms of interval estimates. Poisson regression with scale parameter adjusted by chi2 showed variable performance depending on the outcome prevalence. Cox/Poisson regression with robust variance, and log-binomial regression performed equally well when the model was correctly specified. CONCLUSIONS: Cox or Poisson regression with robust variance and log-binomial regression provide correct estimates and are a better alternative for the analysis of cross-sectional studies with binary outcomes than logistic regression, since the prevalence ratio is more interpretable and easier to communicate to non-specialists than the odds ratio. However, precautions are needed to avoid estimation problems in specific situations.

Cross-Sectional Studies↗
PubMed2003

Modelling and analysing exchangeable binary data with random cluster sizes.

Correlated binary data occur very frequently in cluster sample surveys, dependent repeated cancer screening, teratological experiments, ophthalmologic and otolaryngologic studies, and other clinical trials. The standard methods to analyse these data include the use of beta-binomial models and generalized estimating equations with third and fourth moments specified by 'working matrices'. However, in many applications it is reasonable to assume that the data from the same cluster are exchangeable. When all sampled clusters have equal sizes, Bowman and George introduced maximum likelihood estimates (MLEs) of the population parameters such as the marginal means, moments, and correlations of order two and higher. They also extended their approach to sampled clusters with unequal sizes. It seems that their extension has a gap. This paper points out the source of this gap and shows that estimates introduced by Bowman and George are not the MLEs of the parameters which are used to identify the joint distribution of correlated binary data. We show that the MLEs of the population parameters have no closed form in general and should be calculated by numerical methods. We apply our results and a generalized estimating equation procedure to a data set from a double-blind randomized clinical trial comparing two antibiotics, cefaclor and amoxicillin, used for the treatment of acute otitis media. To see the performance of the MLEs with small or moderate sample sizes, several simulation studies are also conducted.

Amoxicillin↗
PubMed2004

End plate marrow changes in the asymptomatic lumbosacral spine: frequency, distribution and correlation with age and degenerative changes.

PURPOSE: To investigate the frequency and distribution of end plate marrow signal intensity changes in an asymptomatic population and to correlate these findings with patient age and degenerative findings in the spine. MATERIALS AND METHODS: MR imaging studies of the lumbosacral (LS) spine in 59 asymptomatic subjects were retrospectively reviewed by 2 musculoskeletal radiologists to determine the presence and location of fat-like and edema-like marrow signal changes about the end plates of the L1-2 through L5-S1 levels. The presence of degenerative changes in the spine was recorded as was patient age. Descriptive statistics were utilized to determine the frequency and associations of end plate findings and degenerative changes in the spine. Interobserver variability was determined by a kappa score. Binomial probability was used to predict the prevalence of the end plate changes in a similar subject population. The Fisher exact test was performed to determine statistical significance of the relationship of end plate changes with degenerative changes in the spine, superior versus inferior location about the disc and age of the patient population. RESULTS: Focal fat-like signal intensity adjacent to the vertebral end-plate was noted in 15 out of 59 subjects by both readers, and involved 38 and 36 out of 590 end plates by readers 1 and 2, respectively. Focal edema-like signal intensity adjacent to the vertebral end plate was noted in 8 out of 59 subjects by both readers and involved 11 and 10 out of 590 end plates by readers 1 and 2, respectively. Either fat or edema signal intensity occurred most often at the anterior ( p<.05) aspects of the mid-lumbar spine and was seen in an older sub-population of the study ( p<.05). CONCLUSION: End plate marrow signal intensity changes are present in the lumbar spine of some asymptomatic subjects with a characteristic location along the spine and in vertebral end plates.

Adult↗
PubMed2004

Does ambient temperature affect foodborne disease?

BACKGROUND: Foodborne illness is a significant public health issue in most countries, including Australia. We examined the association between temperature and salmonellosis notifications, and compared these associations for 5 Australian cities. METHODS: Log-linear models describing monthly salmonellosis notifications in terms of calendar time and monthly average temperatures were fitted over the period 1991 to 2001 for each city. We used a negative binomial chance model to accommodate overdispersion in the counts. RESULTS: The long-term trend showed an increase in salmonellosis notifications in each of the 5 cities. There was a positive association between monthly salmonellosis notifications and mean monthly temperature of the previous month in every city. Seasonal patterns in salmonellosis notifications were fully explained by changes in temperature. DISCUSSION: The strength of the association, the consistency across 5 cities, and a plausible biologic pathway suggest that higher ambient temperatures are a cause of higher salmonellosis notifications. The lag of 1 month suggests that temperature might be more influential earlier in the production process rather than at the food preparation stage. This knowledge can help to guide policy on food preparation and distribution. It also suggests a basis for an early warning system for increased risk from salmonellosis, and raises yet another possible health problem with global warming.

Australia↗
PubMed2005

Bootstrap tests for overdispersion in a zero-inflated Poisson regression model.

Ridout, Hinde, and Demétrio (2001, Biometrics 57, 219-223) derived a score test for testing a zero-inflated Poisson (ZIP) regression model against zero-inflated negative binomial (ZINB) alternatives. They mentioned that the score test using the normal approximation might underestimate the nominal significance level possibly for small sample cases. To remedy this problem, a parametric bootstrap method is proposed. It is shown that the bootstrap method keeps the significance level close to the nominal one and has greater power uniformly than the existing normal approximation for testing the hypothesis.

Biometry↗
PubMed2000

Spatial distribution and sampling plans for Thrips palmi (Thysanoptera: Thripidae) infesting fall potato in Korea.

The spatial distribution of adult and immature Thrips palmi Karny on fall potato, Solanum tuberosum L., on Cheju Island, Korea, was studied over a 2-yr period by visually inspecting potato leaves. The majority of thrips collected from the leaves were observed in the top one-third of the plant. The within-field spatial patterns of adults and immature thrips were aggregated. The slopes and intercepts of Taylor's power law did not differ among adults and immature thrips. A fixed-precision-level sampling plan was developed using the parameters from Taylor's power law and was tested with resampling simulations using eight independent data sets. Over a wide range of densities, the simulation demonstrated that actual sampling precision (d = SEM/mean) values at d = 0.25 averaged < 0.24 in all cases. A binomial sampling plan for estimating mean density was developed using an empirical model evaluated at tally thresholds (the minimum number of insects present before a leaf is considered infested) of one, three, five, and eight thrips per leaf. Increasing sampling size had little effect on the precision of the estimated mean regardless of tally threshold (T). However, increasing T had a dramatic effect on precision. The best tally threshold for estimating thrips density based on the applicable density ranges and the precision of the model was T = 5. A binomial sampling plan with a tally threshold of five and a fixed sample size of 30 leaves should be an effective replacement for enumerative counts when thrips average < 10 per leaf.

Animals↗
PubMed2006

Serum peptidome patterns that distinguish metastatic thyroid carcinoma from cancer-free controls are unbiased by gender and age.

Serum peptidomics is a special form of functional proteomics. The small number of blood proteins that are the source of most prominent peptides in human serum serve as a substrate pool for commonly occurring and/or cancer-derived proteases. Exoprotease activities in particular, when superimposed on the ex vivo coagulation and complement degradation pathways, contribute to generation of not only cancer-specific but also "cancer type"-specific serum peptides. Following development of a unique, semiautomated serum peptide profiling platform and after completing investigations to eliminate common experimental bias, we have now studied possible effects of gender and age on serum peptidomes of 200 healthy men and women, ages 20-80, and of 60 patients (30 men and 30 women) with metastatic thyroid carcinomas. Extensive MALDI-TOF MS and data analysis suggested negligible contributions of both age and gender to the serum peptidome patterns except that healthy men and women under 35 years, but not older individuals, could be distinguished with approximately 70% accuracy. Considering the more advanced age of most patients, this finding is unlikely to interfere with peptidomics analysis of most cancers. By examining patient samples and age/gender-matched controls followed by variability analysis of either demographic or disease (versus control) groups, we could conclusively rule out demographic bias. An optimized, 12-peptide ion thyroid cancer signature was then developed, enabling classification of an independent validation set with 95% sensitivity and 95% specificity (binomial confidence intervals, 75.1-99.9%). Ten of these peptides had previously been assigned to signature patterns of other solid tumor cancers. One of the two newly discovered peptides was dehydro-Ala(3)-fibrinopeptide A. As we expand this study to include hundreds of thyroid cancer patients, the peptide signature will be adjusted, further validated, and then evaluated in a clinical setting used either independently or in combination with existing markers.

Adult↗
PubMed1986

Probability of quantal transmitter release from nerve terminals: theoretical considerations in the determination of spatial variation.

The release of transmitter occurs in discrete quantal units, such that the number released (m) is equal to the number available (n) times the average probability of release (p). Although a common method of estimating these parameters is to use simple binomial statistics, results may be biased if there is spatial or temporal variation in n and p (vars p, vart n, vart p). The problem arises in the simultaneous analysis of five variables, which is impractical due to the complexity and margin of error involved. The proposed solution is to eliminate two variables (vart n, vart p) by assuming stationarity and to obtain the required information from the first three moments of m. The resulting quadratic equation gives two solutions, p1 and p2. Computer simulation of quantal output as a function of vars p indicates that p1 is the better estimator of p when vars p is small, but that p2 is better when vars p is large. This changeover or "inflection" occurs at points which correspond to the maximum vars p obtainable by unimodal distributions of p (larger vars p being obtained by bimodal distributions). Comparison of the simulated histogram of m with those predicted by p1 and p2 shows that p1 provides the better fit, whether vars p is large or small. This discrepancy indicates that histogram analysis is unable to distinguish the appropriate estimate. The major limitations in the procedure can be met by assuming (1) stationarity (which can be attained and tested experimentally), and (2) normal distribution of p (since vars p is then less than "inflection" point, p1 will always be the correct estimate). The overall findings demonstrate that vars p and unbiased estimates of n and p may be calculated, provided reasonable assumptions are made. This in turn should allow the continued use of quantal parameters for describing transmitter release.

Computer Simulation↗