Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Poisson Distribution”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 397 records · Page 22Linked to original sources
PubMed1995

Trends in colorectal cancer over a half century in Rochester, Minnesota, 1940 to 1989.

Recent reports of increasing incidence, especially in men, led us to update through 1989 an earlier study of colorectal cancer incidence in Rochester that covered the period 1940 through 1979. The combined data reflected cancer trends in the community over half a century. Data resources of the Rochester Epidemiology Project were used to identify new cases of colon and rectal cancer among Rochester residents. Incidence rates were estimated using decennial census data, and 95% confidence intervals were based on the Poisson distribution. The GLIM statistical package was used to evaluate trends over time. Age-adjusted (US white 1970) incidence rates of colorectal cancer for men were 53.7, 61.3, 53.7, 54.2, and 52.5 per 100,000 person-years, respectively, for the decades 1940 to 1949, 1950 to 1959, 1960 to 1969, 1970 to 1979, and 1980 to 1989. Comparable rates for women were 42.7, 49.3, 42.9, 40.7, and 40.9 per 100,000 person-years. No statistically significant changes were seen in the incidence of colon and rectum cancer for men or women. There was no consistent trend in tumor stage at diagnosis and the mean size of the initial lesion did not change with time. The incidence of colorectal cancer has not changed over the past 50 years in this community where case ascertainment has been consistent and complete.

Adult↗
PubMed1997

Measles vaccination and Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré syndrome (GBS) has been associated with several infectious agents, and the possibility that the disorder may be caused by vaccination has been raised. We compared the numbers of cases of GBS observed immediately after mass measles vaccination campaigns with the numbers that would be expected from baseline rates, to assess whether there is a causal relation between measles vaccination and GBS. METHODS: We analysed data on 2296 cases of GBS reported to the Poliomyelitis Eradication Surveillance System of the Pan American Health Organization as cases of suspected poliomyelitis. These cases occurred among 73 million immunised children aged 9 months to 15 years in Argentina, Brazil, Chile, and Colombia, between January, 1990, and December, 1994. These children were targeted for mass measles vaccination campaigns (each lasting 1 month) in 1992 and 1993. The frequency of GBS cases observed during the vaccination campaigns or the next 42 days (the latent period) was compared with that during the rest of the study period, with the assumption of a Poisson distribution. FINDINGS: The average annual incidence of GBS was 0.62 per 100000 children aged 1-14 years. The number of cases that would be expected within any 72-day period would therefore be 92. The average observed number of cases during latent periods after measles vaccination was 97. The probability that 97 or more cases would occur during a period with an expected number of 92 was 0.31. INTERPRETATION: The average annual rates of GBS by age-group for the 5 years analysed were consistent with previous data; thus we are confident that the surveillance system is sufficiently sensitive. There was no statistically significant association between measles vaccination and GBS. If there is any causal relation, the number of GBS cases due to measles vaccination was so small that data from the vaccination of more than 70 million children were not sufficient to detect a rise in the number of observed GBS cases beyond the expected number.

Adolescent↗
PubMed2006

The incidence of stroke after myocardial infarction: a meta-analysis.

PURPOSE: While the risk of stroke after myocardial infarction (MI) is increased compared with the risk among those without MI, the magnitude of this risk remains unclear. Although numerous clinical trials have reported the incidence of stroke following MI, these are among selected populations. We reviewed cohort studies reporting the incidence of stroke after MI to better define the risk of ischemic stroke in an unselected population. METHODS: A computerized literature search (MEDLINE and PubMed) and manual review of reference lists of identified articles were conducted. Population-based studies published from 1978-2004 with at least 100 subjects that reported number or percent of ischemic strokes experienced by MI survivors were identified. Data were extracted using standardized forms, and study quality was assessed by 2 independent reviewers. Ischemic stroke rates were reported as number of events per 1000 MI with 95% confidence intervals (CI) calculated by Poisson distribution. A combined stroke rate was calculated for in-hospital, 30 days, and 1-year post-MI using weights of 1/variance. A random-effects model also was created to estimate in-hospital stroke rate. Variability in study designs and outcome definitions limit synthesis of available data. RESULTS: During hospitalization for the index MI, 11.1 ischemic strokes occurred per 1000 MI compared with 12.2 at 30 days and 21.4 at 1 year. Using a random-effects model, 14.5 strokes occurred per 1000 MI. Positive predictors of stroke after MI included: advanced age, diabetes, hypertension, history of prior stroke, anterior location of index MI, prior MI, atrial fibrillation, heart failure, and nonwhite race. CONCLUSIONS: The public health implications of stroke among MI survivors, as well as the large number of MI survivors, underscore the need to be aware of this devastating complication. Further research is needed to determine the optimal stroke prevention strategies for MI survivors.

Confidence Intervals↗
PubMed2003

Cement, cancers and clusters: an investigation of a claim of a local excess cancer risk related to a cement works.

BACKGROUND: We investigated claims by a campaigning group of a cancer cluster associated with a local cement works. METHODS: To investigate cancer rates in the town we defined the study area as the Census wards matching the geographical area code supplied to the campaigning group. Standard methods were applied to registered cases of cancer for the area for the years 1974-1989 to derive observed and expected numbers. The significance of the relative risk was assessed using the Poisson distribution. By selecting a different denominator population we attempted to reproduce the results of the campaign group. Cancer rates around the cement works were investigated for four cancer types plausibly associated with emissions, using cancer registrations for the years 1985-1994. Cases were mapped to 1981 Census ward boundaries, and the same statistical methods were used, but expected counts were also adjusted for deprivation. Rates were calculated for an inner 2 km zone and outer zone 2-5 km from the works. Relative risk was calculated and the ratio of risks was examined for evidence of increased risk closer to the works. RESULTS: Relative risks were not significantly elevated either in the town or around the cement works itself. We were able to reproduce the likely errors that resulted in the elevated relative risks for five cancer groups claimed by the campaigning group. CONCLUSIONS: We found no evidence of increased incidence of cancer around the cement works. Incorrect handling of cancer registration data can result in spurious cancer clusters and unnecessary public alarm.

Air Pollutants, Occupational↗
PubMedDate not supplied

Red cell selectivity in malaria: a study of multiple-infected erythrocytes.

To characterize red cell susceptibility to invasion in malaria, a selectivity index (SI) was calculated as the ratio of observed number of multiple-infected red cells to that expected from a random process (Poisson distribution). In patients with falciparum malaria (n = 100) SI decreased with increasing parasitaemia (P < 0.001), and correlated inversely with plasma lactate concentrations, chosen prospectively as a measure of disease severity (r = -0.36, P < 0.001). For parasitaemias < 5%, the SI was lower in patients with severe malaria (geometric mean 1.35; 95% confidence interval 1.01-1.80) than in uncomplicated malaria (2.31; 1.89-2.81; P = 0.003), despite similar parasite counts. The geometric mean (range) SI in vivax malaria (n = 20), 7.69 (1.67, 29.75), was significantly greater than that in falciparum malaria at comparable parasitaemias (< or = 2%), 2.44 (0.45, 14.05), P < 0.001, suggesting that about 13% of circulating erythrocytes were susceptible to invasion by Plasmodium vivax. This translates into susceptibility for about 2 weeks after emergence from the bone marrow, if age is the sole determinant of this process. In falciparum malaria selectivity was inversely proportional to severity; lack of selectivity could reflect either a 'favourable' host red cell phenotype, or an indiscriminate parasite population. Both are dangerous for the host.

Animals↗
PubMed1998

[Mortality of men with occupational lead poisoning in Poland].

The cohort method was used in the study. A retrospective observation covered 4.556 males with occupational disease, manifested by lead poisoning, diagnosed during the years 1970-1992. Mortality risk analysis by causes was based on standardized mortality ratios (SMRs) calculated by person-years method. Their statistical significance was assessed by means of the test based on Poisson distribution. The general adult male population was adopted as the reference population. The state of the cohort as of 31 December 1992 was considered. The cohort accessibility was 95.6%. The study revealed increased total mortality among lead poisoned males (670 deaths; SMR = 108; 95% CI: 100-116). Significant excess mortality was observed in diseases of the digestive system (37 deaths; SMR = 148; 95% CI: 104-204), including chronic hepatitis and cirrhosis (19 deaths; SMR = 173; 95% CI: 104-270); malignant neoplasms of respiratory and intrathoracic organs (82 deaths; SMR = 135; 95% CI: 107-168), including malignant neoplasm of larynx (13 deaths; SMR = 213; 95% CI: 113-364). In the subcohort with high exposure, death risk was significantly enhanced in comparison to the general population (153 deaths; SMR = 129; 95% CI: 109-151). In addition, significant excess of malignant neoplasms was observed (43 deaths; SMR = 151; 95% CI: 109-203) including liver (4 deaths; SMR = 419; 95% CI: 114-1073) and respiratory and intrathoracic organs tumors (21 deaths; SMR = 175; 95% CI: 108-268).

Adult↗
PubMed2006

Motor unit number estimation--a Bayesian approach.

All muscle contractions are dependent on the functioning of motor units. In diseases such as amyotrophic lateral sclerosis (ALS), progressive loss of motor units leads to gradual paralysis. A major difficulty in the search for a treatment for these diseases has been the lack of a reliable measure of disease progression. One possible measure would be an estimate of the number of surviving motor units. Despite over 30 years of motor unit number estimation (MUNE), all proposed methods have been met with practical and theoretical objections. Our aim is to develop a method of MUNE that overcomes these objections. We record the compound muscle action potential (CMAP) from a selected muscle in response to a graded electrical stimulation applied to the nerve. As the stimulus increases, the threshold of each motor unit is exceeded, and the size of the CMAP increases until a maximum response is obtained. However, the threshold potential required to excite an axon is not a precise value but fluctuates over a small range leading to probabilistic activation of motor units in response to a given stimulus. When the threshold ranges of motor units overlap, there may be alternation where the number of motor units that fire in response to the stimulus is variable. This means that increments in the value of the CMAP correspond to the firing of different combinations of motor units. At a fixed stimulus, variability in the CMAP, measured as variance, can be used to conduct MUNE using the "statistical" or the "Poisson" method. However, this method relies on the assumptions that the numbers of motor units that are firing probabilistically have the Poisson distribution and that all single motor unit action potentials (MUAP) have a fixed and identical size. These assumptions are not necessarily correct. We propose to develop a Bayesian statistical methodology to analyze electrophysiological data to provide an estimate of motor unit numbers. Our method of MUNE incorporates the variability of the threshold, the variability between and within single MUAPs, and baseline variability. Our model not only gives the most probable number of motor units but also provides information about both the population of units and individual units. We use Markov chain Monte Carlo to obtain information about the characteristics of individual motor units and about the population of motor units and the Bayesian information criterion for MUNE. We test our method of MUNE on three subjects. Our method provides a reproducible estimate for a patient with stable but severe ALS. In a serial study, we demonstrate a decline in the number of motor unit numbers with a patient with rapidly advancing disease. Finally, with our last patient, we show that our method has the capacity to estimate a larger number of motor units.

Action Potentials↗
PubMed2006

Hierarchical Bayesian spatial models for alcohol availability, drug "hot spots" and violent crime.

BACKGROUND: Ecologic studies have shown a relationship between alcohol outlet densities, illicit drug use and violence. The present study examined this relationship in the City of Houston, Texas, using a sample of 439 census tracts. Neighborhood sociostructural covariates, alcohol outlet density, drug crime density and violent crime data were collected for the year 2000, and analyzed using hierarchical Bayesian models. Model selection was accomplished by applying the Deviance Information Criterion. RESULTS: The counts of violent crime in each census tract were modelled as having a conditional Poisson distribution. Four neighbourhood explanatory variables were identified using principal component analysis. The best fitted model was selected as the one considering both unstructured and spatial dependence random effects. The results showed that drug-law violation explained a greater amount of variance in violent crime rates than alcohol outlet densities. The relative risk for drug-law violation was 2.49 and that for alcohol outlet density was 1.16. Of the neighbourhood sociostructural covariates, males of age 15 to 24 showed an effect on violence, with a 16% decrease in relative risk for each increase the size of its standard deviation. Both unstructured heterogeneity random effect and spatial dependence need to be included in the model. CONCLUSION: The analysis presented suggests that activity around illicit drug markets is more strongly associated with violent crime than is alcohol outlet density. Unique among the ecological studies in this field, the present study not only shows the direction and magnitude of impact of neighbourhood sociostructural covariates as well as alcohol and illicit drug activities in a neighbourhood, it also reveals the importance of applying hierarchical Bayesian models in this research field as both spatial dependence and heterogeneity random effects need to be considered simultaneously.

Alcohol Drinking↗
PubMed2006

Properties of correlated neural activity clusters in cat auditory cortex resemble those of neural assemblies.

Spiking activity was recorded from cat auditory cortex using multi-electrode arrays. Cross-correlograms were calculated for spikes recorded on separate microelectrodes. The pair-wise cross-correlation matrix was constructed for the peak values of the correlograms. Hierarchical clustering was performed on the cross-correlation matrix for six stimulus conditions. These were silence, three multi-tone stimulus ensembles with different spectral densities, low-pass amplitude-modulated noise, and Poisson-distributed click trains that each lasted 15 min. The resulting neuron clusters reflect patches in cortex of up to several mm(2) in size that expand and contract in response to different stimuli. Cluster positions and size were very similar for spontaneous activity and multi-tone stimulus-evoked activity but differed between those conditions and the noise and click stimuli. Cluster size was significantly larger in posterior auditory field (PAF) compared with primary auditory cortex (AI), whereas the fraction of common spikes (within a 10-ms window) across all electrode activity participating in a cluster was significantly higher in AI compared with PAF. Clusters crossed area boundaries in <5% of the cases were simultaneous recording were made in AI and PAF. Clusters are therefore similar to but not synonymous with the traditional view of neural assemblies. Common-spike spectrotemporal receptive fields (STRFs) were obtained for common-spike activity and all-spike activity within a cluster. Common-spike STRFs had higher signal-to-noise ratio than all-spike STRFs and showed generally spectral and temporal sharpening. The coincident and noncoincident output of the clusters could potentially act in parallel and may serve different modes of stimulus coding.

Acoustic Stimulation↗
PubMed1996

Cancer incidence on a small island--research opportunities in general practice.

OBJECTIVE: To test the impression of an increased cancer incidence on the island of Pellworm (in the far North of Germany) and to illustrate the feasibility of a general practice-based approach in epidemiological research. DESIGN: Cancer incidence on Pellworm was prospectively registered in the only general practice on the island from 1986 to 1992. Age-standardized rates and expected rates were calculated on the basis of the Saarland cancer registry, the only registry in Germany. Standardized incidence ratios and 95% confidence intervals (CI) for Poisson-distributed events were also calculated. The cancer data were summed up over a seven-year period. SETTING: The only general practice on the island of Pellworm, a North Frisian marshland-island. SUBJECTS: The total practice population between 1986 and 1992 (N = 1172) RESULTS: The crude annual cancer incidence rate for Pellworm was, according to the impression, unexpectedly high: 634/100 000 for men and 502/100 000 for women. After age standardization, however, this increased rate of cancer incidence was even lower than in the Saarland (ratios: 0.86 for men and 0.95 for women). Only the incidence of neoplasms of the lymphatic and haematopoietic tissue in men exceeded the limits of statistical likelihood (ratio: 3.21; 95% CI: 1.17-7.10). CONCLUSION: The impression of an increased rate of cancer on Pellworm could not be validated. The overall incidence rate was even lower than expected. Only the rate of leukaemia/lymphoma (men) was significantly higher. Reasons for this result could not be detected by a descriptive approach. General practice is a suitable place for studies in cancer epidemiology, especially in such ideal circumstances as a clearly limited area and complete and reliable documentation.

Adolescent↗
PubMed2002

A new Poisson and Bayesian-based method to assign risk and causality in patients with suspected hepatic adverse drug reactions: a report of two new cases of ticlopidine-induced hepatotoxicity.

OBJECTIVE: The diagnosis of drug-induced hepatotoxicity is based on circumstantial evidence and is often inaccurate. We have designed a method based on published data to assign causality to suspected cases of drug-induced hepatotoxicity. DESIGN: Forty-seven published cases of ticlopidine-induced hepatotoxicity were identified by a Medline-based literature search. Data regarding abnormal liver function in patients receiving ticlopidine were obtained from the only published placebo-ticlopidine clinical trial (the Canadian American Ticlopidine Study; CATS). Thus, we calculated the maximum number of expected hepatotoxicity cases in patients exposed to ticlopidine and those not exposed to the drug by means of the Poisson distribution. The calculated odds ratio was used as a prior odd for subsequent quantification, using a Bayesian-based approach, of individual ticlopidine-induced hepatotoxicity likelihood. Concretely, the prior odd is modified by several separate likelihood ratios: age; sex; AST level; ALT level; alkaline phosphatase level; total bilirubin level; latent period of adverse reaction appearance; and period of remission of adverse reaction. This methodology was applied to two new cases of suspected ticlopidine-induced hepatotoxicity. RESULTS: The prior probability of ticlopidine-induced hepatotoxicity derived from CATS data is 61.29%. This is in contrast with the 28.83% incidence rate of drug-induced liver alterations in the general population. Alkaline phosphatase levels and total bilirubin levels were six times the normal values among individuals with ticlopidine-induced hepatotoxicity than in the general population. They were the most relevant likelihood ratios of the Bayesian model to establish a high level of causality relationship between a hepatotoxicity event and ticlopidine use. CONCLUSIONS: The proposed method, which links information from clinical trials with the profile of clinical hepatotoxicity of a drug defined from published cases reported after a drug is marketed, can be a useful tool for drug postmarketing surveillance research.

Adult↗
PubMed2003

Deriving reaction-diffusion models in ecology from interacting particle systems.

We use a scaling procedure based on averaging Poisson distributed random variables to derive population level models from local models of interactions between individuals. The procedure is suggested by using the idea of hydrodynamic limits to derive reaction-diffusion models for population interactions from interacting particle systems. The scaling procedure is formal in the sense that we do not address the issue of proving that it converges; instead we focus on methods for computing the results of the scaling or deriving properties of rescaled systems. To that end we treat the scaling procedure as a transform, in analogy with the Laplace or Fourier transform, and derive operational formulas to aid in the computation of rescaled systems or the derivation of their properties. Since the limiting procedure is adapted from work by Durrett and Levin, we refer to the transform as the Durrett-Levin transform. We examine the effects of rescaling in various standard models, including Lotka-Volterra models, Holling type predator-prey models, and ratio-dependent models. The effects of scaling are mostly quantitative in models with smooth interaction terms, but ratio-dependent models are profoundly affected by the scaling. The scaling transforms ratio-dependent terms that are singular at the origin into smooth terms. Removing the singularity at the origin eliminates some of the unique dynamics that can arise in ratio-dependent models.

Animals↗
PubMed1999

Long-term prognosis of cerebral ischemia in young adults. National Research Council Study Group on Stroke in the Young.

BACKGROUND AND PURPOSE: Prognosis of ischemic stroke in young adults is reported as favorable, and transient ischemic attack (TIA) is commonly considered a benign event. We investigated long-term outcome and prognostic predictors of cerebral ischemia in patients under 45 years of age. METHODS: Three hundred thirty-three patients aged 15 to 44 years who suffered from a first-ever TIA or ischemic stroke were prospectively followed up with annual clinical evaluation or complete phone interview. End points were the composite outcome event of stroke, myocardial infarction, and vascular or nonvascular death and death from all causes. The probability of event-free survival was estimated by the Kaplan-Meier method. Univariate and multivariate estimates of hazard ratios were calculated according to the Cox proportional hazards analysis. RESULTS: An average follow-up of 96 months was available in 330 patients (99.1%). Survival was worse in patients with stroke at entry (86.5%) than in those with TIA (97.1%). Mortality in both groups was significantly higher than in the general population (standardized mortality ratio [SMR] 14.5, P<0.0001, Poisson distribution test, and SMR 7.9, P=0.002). The average annual mortality rate was higher during the first (3.94%, 95% CI 1.84 to 6. 04) than in the subsequent years. The average annual incidence rate of new stroke was higher in patients with stroke than in those with TIA at entry, and it declined from 1.56% (95% CI 0.21 to 2.91) during the first year to 0.06% (95% CI 0.04 to 0.08) at the end of the follow-up. Myocardial infarction occurred later, after the first year, with similar rates in patients with stroke and TIA at entry. The average annual rates of new stroke (2.36%), myocardial infarction (1.68%), and death (3.05%) were higher in patients with the mixed atherothrombotic and cardioembolic etiology than in the remaining patients. Male gender, age >35 years, stroke at entry, and cardiac diseases were independent predictors of the composite outcome event at the Cox regression analysis, whereas only stroke at entry and cardiac diseases predicted death from all causes. CONCLUSIONS: Stroke and TIA in young adults have severe prognostic implications, because the mortality risk was highly increased with respect to the general population. Preventive measures are strongly recommended in the presence of any unfavorable prognostic profile.

Adolescent↗
PubMed1992

Relationship between frequency of infectious human immunodeficiency virus type 1-harboring cells and kinetics of viral replication: a simple procedure for quantitation of infectious virus-carrying cells in blood samples.

Statistical analysis of a limiting dilution assay (LDA) showed that the occurrence of infectious human immunodeficiency virus type 1 (HIV-1)-harboring cells in serially diluted samples of peripheral blood mononuclear cells (PBMCs) of HIV-1-seropositive patients fits the model describing a single-hit Poisson distribution. This observation led to the discovery that there is a direct correlation (r = 0.957) between the number of HIV-1-positive cells and the time when viral culture produces 1 ng of the HIV-1 p24 gag protein per ml. Frequency estimates based on this relationship were highly accurate (P less than 0.01) within the first 15 days of viral culture, which consisted of coculture of 10(6) normal PBMCs with the equivalent number of test PBMCs. This approach was less cumbersome than LDA and was sensitive enough to detect a single infectious HIV-1-harboring cell among as many as 320,000 cells. The values obtained for 57 patients agreed well with the data in the literature and showed that the frequencies of infectious cells in PBMCs reflect the advancement in the clinical stage, being 1/38,000, 1/11,000, and 1/7,000 for asymptomatic patients (Centers for Disease Control [CDC] group II/III), patients with AIDS-related complex (CDC group IVa), and patients with AIDS (CDC group IVb/c), respectively. A nearly 10-fold disparity in mean frequencies was observed when these values were correlated with the numbers of CD4-positive cells (1/9,000, 1/1,500, and 1/300, respectively, for asymptomatic patients, patients with AIDS-related complex, and patients with AIDS). The described method provides a simple means of determining infectious HIV-1-positive cells in blood samples.

HIV Infections↗
PubMed2002

Dementia and Alzheimer disease incidence: a prospective cohort study.

CONTEXT: Age-specific incidence rates for dementia and Alzheimer disease (AD) are important for research and clinical practice. Incidence estimates for the United States are few and vary with the population sampled and study design; we present data that will contribute to a consensus of these rates. OBJECTIVES: To provide age-specific incidence estimates for dementia and AD and to estimate the association of sex, educational level, and apolipoprotein E genotype with onset. DESIGN: Prospective cohort study; begun in 1994 with follow-up interviews every 2 years. SETTING: Members of community-based, large health maintenance organization with demographics consistent with the surrounding base population; diagnostic evaluation by university-based study clinicians. SUBJECTS: Random sample of subjects aged 65 years or older from the base population; dementia free, nonnursing home residents. Of 5422 who were eligible, 2581 were enrolled, and 2356 had at least 1 follow-up evaluation (10 591 person-years of observation). MAIN OUTCOME MEASURE: Dementia and Alzheimer disease diagnoses were based on standard criteria. Age-specific incidence rates were calculated using a person-years approach with Poisson distribution confidence intervals. Cox proportional hazards model analysis was used to examine other factors. RESULTS: Two hundred fifteen cases of dementia and 151 cases of AD were diagnosed. Incidence rates for dementia and AD increase across the 5-year age groups; AD rates rise from 2.8 per 1000 person-years (age group, 65-69 years) to 56.1 per 1000 person-years in the older than 90-year age group. The rates nearly triple from the 75-to-79-year and 80-to-84-year age groups, but the relative increase is much less thereafter. Sex was not associated with AD onset. Educational level (>15 years vs <12 years) was associated with a decreased risk of AD; however, the association was also dependent on the baseline cognitive screening test score. CONCLUSIONS: Our dementia and AD incidence rates are consistent with recent US and European cohort studies, providing clinicians and researchers new information concerning the reproducibility of incidence estimates across settings. Increased risk was associated with age and the apolipoprotein E genotype; also with a low baseline cognitive screening test score. Educational level was inversely associated with the risk of dementia and positively associated with the baseline cognitive test score; thus, detection of AD by the screening test could also be influenced by educational level.

Age Factors↗
PubMed1999

Testing the classification of static gamma axons using different patterns of random stimulation.

The possibility of using randomly generated stimulus intervals (with a Poisson distribution) to identify the type(s) of intrafusal fiber activated by the stimulation of single static gamma axons was tested in Peroneus tertius muscle spindles of anesthetized cats. Three patterns of random stimulation with different values of mean intervals [20 +/- 4. 47, 30 +/- 8.94, and 40 +/- 8.94 (SD) ms] were used. Single static gamma axons activating, in single spindles, either the bag2 fiber alone or the chain fibers alone or both types of intrafusal fiber were prepared. Responses of spindle primary endings elicited by the stimulation of gamma axons were recorded from Ia fibers in cut dorsal root filaments. Cross-correlograms between stimuli and spikes of the primary ending responses, autocorrelograms, interval histograms of responses, and stimulations were built. The characteristics of cross-correlograms were found to be related not only to the type of intrafusal muscle fibers activated but also to the parameters of the stimulation. Moreover some cross-correlograms with similar characteristics were produced by the activation of different intrafusal muscle fibers. It also was observed that, whatever the type of intrafusal muscle fiber activated, cross-correlograms could exhibit oscillations after an initial peak, provided the extent in frequency of the primary ending response was small; these oscillations arise in part from the autocorrelation of the primary ending responses. Therefore, cross-correlograms obtained during random stimulation of static gamma axons cannot be used for unequivocally identifying the type(s) of intrafusal muscle fiber these axons supply.

Algorithms↗
PubMed2003

Trends in U.S. pleural mesothelioma incidence rates following simian virus 40 contamination of early poliovirus vaccines.

BACKGROUND: Poliovirus vaccines that were used during the late 1950s and early 1960s were contaminated with simian virus 40 (SV40), a monkey virus that is tumorigenic in rodents. SV40 DNA sequences have been detected in some human cancers, especially pleural mesotheliomas, although results are conflicting. We examined the relationship between SV40-contaminated poliovirus vaccine exposure and subsequent rates of pleural mesothelioma in the United States. METHODS: We used data from the Surveillance, Epidemiology, and End Results Program to estimate age- and sex-specific pleural mesothelioma incidence rates per 10(5) person-years (py) from 1975 through 1997 and the Poisson distribution to determine 95% confidence intervals (CIs) for each rate. The prevalence, by birth cohort, of poliovirus vaccine exposure during the period of widespread SV40 contamination was determined from published survey data. Trends in mesothelioma incidence rates were assessed by examining age- and sex-specific rates over calendar periods and with the use of the age-period-cohort model. Trends in mesothelioma incidence were then compared with trends in prevalence of exposure. All statistical tests were two-sided. RESULTS: The age-standardized pleural mesothelioma incidence rate for 1975 through 1997 was 1.29/10(5) py (95% CI = 1.24/10(5) to 1.34/10(5) py) in males and 0.21/10(5) py (95% CI = 0.20/10(5) to 0.23/10(5) py) in females. The rate in males increased from 0.79/10(5) py (95% CI = 0.62/10(5) to 1.0/10(5) py) in 1975 to a peak of 1.69/10(5) py (95% CI = 1.46/10(5) to 1.95/10(5) py) in 1992. Incidence rates increased the most among males who were 75 years of age or older, the age group least likely to have been immunized against poliovirus. Incidence rates among males in the age groups most heavily exposed to SV40-contaminated poliovirus vaccine remained stable or decreased from 1975 through 1997. Similar age-specific trends were observed among females. The age-period-cohort models for men and women also indicated that the trends in pleural mesothelioma incidence were not related to trends in exposure to SV40-contaminated poliovirus vaccine. CONCLUSIONS: Age-specific trends in U.S. pleural mesothelioma incidence rates are not consistent with an effect of exposure to SV40-contaminated poliovirus vaccine. Nonetheless, given reports of the detection of SV40 genomic DNA sequences in human mesotheliomas, monitoring of vaccine-exposed cohorts should continue.

Adolescent↗
PubMed2003

Evaluation of mixture modeling with count data using NONMEM.

Mixture modeling within the context of pharmacokinetic (PK)/pharmacodynamic (PD) mixed effects modeling is a useful tool to explore a population for the presence of two or more subpopulations, not explained by evaluated covariates. At present, statistical tests for the existence of mixed populations have not been developed. Therefore, a simulation study was undertaken to evaluate mixture modeling with NONMEM and explore the following questions. First, what is the probability of concluding that a mixed population exists when there truly is not a mixture (false positive significance level)? Second, what is the probability of concluding that a mixed population (two subpopulations) exists when there is truly a mixed population (power), and how well can the mixture be estimated, both in terms of the population parameters and the individual subjects classification. Seizure count data were simulated using a Poisson distribution such that each subject's count could decrease from its baseline value, as a function of dose via an Emax model. The dosing design for the simulation was based on a trial with the investigational anti-epileptic drug pregabalin. Four hundred and forty seven subjects received pregabalin as add on therapy for partial seizures, each with a baseline seizure count and up to three subsequent seizure counts. For the mixtures, the two subpopulations were simulated to differ in their Emax values and relative proportions. One subpopulation always had its Emax set to unity (Emax hi), allowing the count to approach zero with increasing dose. The other subpopulation was allowed to vary in its Emax value (Emax lo = 0.75, 0.5, 0.25, and 0) and in its relative proportion (pr) of the population (pr = 0.05, 0.10, 0.25, and 0.50) giving a total of 4.4 = 16 different mixtures explored. Three hundred data sets were simulated for each scenario and estimations performed using NONMEM. Metrics used information about the parameter estimates, their standard errors (SE), the difference between minimum objective function (MOF) values for mixture and non-mixture models (MOF (delta)), the proportion of subjects classified correctly, and the estimated conditional probabilities of a subject being simulated as having Emax lo (Emax hi) given that they were estimated as having Emax lo (Emax hi) and being estimated as having Emax lo (Emax hi) given that they were simulated as having Emax lo (Emax hi). The false positive significance level was approximately 0.04 (using all 300 runs) or 0.078 (using only those runs with a successful covariance step), when there was no mixture. When simulating mixed data and for those characterizations with successful estimation and covariance steps, the median (range) percentage of 95% confidence intervals containing the true values for the parameters defining the mixture were 94% (89-96%), 89.5% (58-96%), and 95% (92-97%) for pr, Emax lo, and Emax hi, respectively. The median value of the estimated parameters pr, Emax lo (excluding the case when Emax lo was simulated to equal 0) and Emax hi within a scenario were within +/- 28% of the true values. The median proportion of subjects classified correctly ranged from 0.59 to 0.96. In conclusion, when no mixture was present the false positive probability was less than 0.078 and when mixtures were present they were characterized with varying degrees of success, depending on the nature of the mixture. When the difference between subpopulations was greater (as Emax lo approached zero or pr approached 0.5) the mixtures became easier to characterize.

Computer Simulation↗