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PubMed1999

Stillbirths among offspring of male radiation workers at Sellafield nuclear reprocessing plant.

BACKGROUND: Ionising radiation is a known mutagen, but few studies have examined transgenerational effects of paternal exposure in human beings. The workforce at the Sellafield nuclear reprocessing plant in the county of Cumbria, UK, is the most highly exposed workforce in western Europe and North America. This study, which is part of a larger programme of work investigating the health of the children of the Sellafield workforce, set out to find whether there was evidence of an association between stillbirth risk and paternal exposure to ionising radiation. METHODS: We collected details from birth registration documents for all singleton 248,097 livebirths and 3715 stillbirths in the county of Cumbria 1950-89. Within this cohort the 130 stillbirths and 9078 livebirths to partners of male radiation workers employed at Sellafield were identified. Logistic regression was used to analyse the relation between stillbirth risk and father's preconceptional radiation exposure, with adjustment for social class, year of birth, father's age, and birth order. FINDINGS: A significant positive association was found between the risk of a baby being stillborn and the father's total exposure to external ionising radiation before conception (adjusted odds ratio per 100 mSv 1.24 [95% CI 1.04-1.45], p=0.009). The risk was higher for stillbirths with congenital anomaly and was highest for the nine stillbirths with neural-tube defects. The statistical models predicted that, were the association to be interpreted as causal, between 0 and 31.9 of the 130 stillbirths to the workforce may be attributable to father's radiation exposure. INTERPRETATION: The findings of an increased risk of stillbirth with increasing paternal occupational exposure to external radiation are qualitatively consistent with those from animal models, though the risk estimate is higher. Although we cannot exclude the possibility of an unmeasured risk factor for stillbirth, confounded with paternal preconceptional irradiation, extensive checks confirmed that the statistical models were a good fit to the data and there was not statistical evidence of unmeasured factors.

Adult↗

PubMed1995

Presentation of comparative audit data.

The Royal College of Surgeons of England organizes a voluntary comparative audit service for its general surgical fellows. To date, the information from the audit has been presented purely descriptively, which does not take account of statistical variability and the effects of differences in case mix between the participants. A new approach to the presentation of these data, based on statistical modelling of the effects of case mix, is presented. The approach is illustrated in an application based on data relating to 136203 admissions reported by 110 surgeons. The result of adjusting for case mix is a substantial change in the relative performance of the participating surgeons, which demonstrates the folly of attempting to compare surgical performance on the basis of a measure as crude as the unadjusted mortality rate. Further development of the statistical modelling is required, but this new statistical approach appears to enhance greatly the credibility of the audit data, by quantifying its strengths and limitations.

Age Distribution↗

PubMed1989

A model for prediction of endometrial cancer.

An epidemiological statistical model was designed to identify women at low and high risk of developing endometrial cancer (EC). The model was based on a number of easily identified clinical factors such as hirsutism, parity, diabetes mellitus, body mass index (BMI) and smoking. A retrospectively collected series of 77 women aged 31 to 45 years with EC and a prospectively collected series of 122 women aged 43 to 70 years with EC were compared with 1409 controls. The participation frequencies in the two case materials were 83 and 87%, respectively. The series were examined by means of a questionnaire. In a stepwise multiple logistic regression analysis of the entire series the following variables were found to be significant; hirsutism, parity, BMI, diabetes mellitus and smoking.

Adult↗

PubMed1997

A dynamic frailty model for multivariate survival data.

We consider the statistical modeling of data consisting of many study subjects with serially correlated multivariate survival responses. The (ordinary) frailty model handles the serial correlation in such data by introducing an unobserved multiplicative random effect term, called the frailty, in the hazard function. The frailties are often assumed to be identical for the survival times from the same unit. We have generalized the frailty model by allowing the frailties to vary stochastically with the indices. We have proposed a simple scheme to update the dynamic frailties. This approach assumes that the random effects are gamma distributed. At each occurrence, the two gamma parameters are updated according to the past information. In terms of their marginal distributions, the dynamic frailties form a multiplicative random walk. This approach results in a tractable likelihood. The small sample behavior of the MLE is studied via a simulation experiment. The model is then illustrated with a data set from an animal carcinogenesis experiment.

Biometry↗

PubMed2001

When parents are given greater access to health information, does it affect pediatric utilization?

OBJECTIVE: Most studies assessing the effects of consumer health information on medical utilization have used randomized controlled clinical trials with the chronically ill. In this paper, we analyze the effect of the Healthwise Communities Project, a natural experiment that provided free self-care resources, on reported pediatric utilization. RESEARCH DESIGN: Random household surveys were collected before and after the intervention in Boise, Idaho and in two control communities. SUBJECTS: A total of 5,909 surveys were completed, representing an overall response rate of 54%. Of these, 1,812 respondents were between 18 and 55 years of age and had children under 18 years of age living in the home. All analyses were restricted to these 1,812 persons. MEASURES: Parents were asked how many times their children visited a physician in the last year. Responses were gathered with a categorical response scale, which was then transformed into a continuous variable (number of pediatric visits). RESULTS: The intervention was associated with a decrease in reported pediatric utilization rates. The decrease in visits ranged from -0.72 to -0.66 (P approximately 0.05), depending on the statistical model used. Further analyses of 423 families followed over time found a more modest decrease (-0.19) that was not statistically significant. CONCLUSIONS: This study found that increasing access to self-care books, telephone advice nurses, and Internet-based health information is associated with decreases in reported pediatric utilization. However, the significance of the results was sensitive to the statistical model. More research is needed to understand the average and marginal costs of providing health information to consumers.

Adult↗

PubMed2000

Regression analysis of time trends in perinatal mortality in Germany 1980-1993.

Numerous investigations have been carried out on the possible impact of the Chernobyl accident on the prevalence of anomalies at birth and on perinatal mortality. In many cases the studies were aimed at the detection of differences of pregnancy outcome measurements between regions or time periods. Most authors conclude that there is no evidence of a detrimental physical effect on congenital anomalies or other outcomes of pregnancy following the accident. In this paper, we report on statistical analyses of time trends of perinatal mortality in Germany. Our main intention is to investigate whether perinatal mortality, as reflected in official records, was increased in 1987 as a possible effect of the Chernobyl accident. We show that, in Germany as a whole, there was a significantly elevated perinatal mortality proportion in 1987 as compared to the trend function. The increase is 4.8% (p = 0.0046) of the expected perinatal death proportion for 1987. Even more pronounced levels of 8.2% (p = 0. 0458) and 8.5% (p = 0.0702) may be found in the higher contaminated areas of the former German Democratic Republic (GDR), including West Berlin, and of Bavaria, respectively. To investigate the impact of statistical models on results, we applied three standard regression techniques. The observed significant increase in 1987 is independent of the statistical model used. Stillbirth proportions show essentially the same behavior as perinatal death proportions, but the results for all of Germany are nonsignificant due to the smaller numbers involved. Analysis of the association of stillbirth proportions with the (137)Cs deposition on a district level in Bavaria discloses a significant relationship. Our results are in contrast to those of many analyses of the health consequences of the Chernobyl accident and contradict the present radiobiologic knowledge. As we are dealing with highly aggregated data, other causes or artifacts may explain the observed effects. Hence, the findings should be interpreted with caution, and further independent evidence should be sought.

Female↗

PubMed2000

In vivo transgenic mutation assays.

Transgenic rodent gene mutation models provide quick and statistically reliable assays for mutations in the DNA from any tissue. For regulatory applications, assays should be based on neutral genes, be generally available in several laboratories, and be readily transferable. Five or fewer repeated treatments are inadequate to conclude that a compound is negative but more than 90 daily treatments may risk complications. A sampling time of 35 days is suitable for most tissues and chemicals, while shorter sampling times might be appropriate for highly proliferative tissues. For phage-based assays, 5 to 10 animals per group should be analyzed, assuming a spontaneous mutant frequency (MF) of approximately 3 x 10(-5) mutants/locus and 125,000-300,000 plaque or colony forming units (PFU or CFU) per tissue. Data should be generated for two dose groups but three should be treated, at the maximum tolerated dose (MTD), two-thirds the MTD, and one-third the MTD. Concurrent positive control animals are only necessary during validation, but positive control DNA must be included in each plating. Tissues should be processed and analyzed in a block design and the total number of PFUs or CFUs and the MF for each tissue and animal reported. Sequencing data would not normally be required but might provide useful additional information in specific circumstances. Statistical tests used should consider the animal as the experimental unit. Nonparametric statistical tests are recommended. A positive result is a statistically significant dose-response and/or statistically significant increase in any dose group compared to concurrent negative controls using an appropriate statistical model. A negative result is statistically nonsignificant with all mean MF within two standard deviations of the control.

Animals↗

PubMed1988

Statistical inference for infectious diseases. Risk-specific household and community transmission parameters.

A statistical model is presented for the analysis of infectious disease data from family studies in the community. The model partitions the sources of infection into those from within the household and those from the community at large. The parameters reflecting these sources of infection are estimated as functions of the risk factors. This new model is used to overcome problems associated with the lack of independence of observations in infectious disease data and negative confounding due to the association of unmeasured exposures and immunity. An example of how this new statistical model is used to provide a clearer and less confounded description of risk factor effects is presented for data from influenza A(H3N2) epidemic seasons in the Tecumseh Respiratory Illness Study. The risk factors examined are age and pre-epidemic season antibody level as measured by the hemagglutination-inhibition test, while the outcome is the infection rate. A standard analysis of the data indicates that the efficacy of protective antibodies is 70% in children and only 47% in adults. However, such an efficacy measurement is negatively confounded by past exposure which is age dependent. By means of the model, the true, unconfounded, efficacy of protective antibodies is shown to be 90% in both adults and children.

Adolescent↗

PubMed2007

MODEL-molecular descriptor lab: a web-based server for computing structural and physicochemical features of compounds.

Molecular descriptors represent structural and physicochemical features of compounds. They have been extensively used for developing statistical models, such as quantitative structure activity relationship (QSAR) and artificial neural networks (NN), for computer prediction of the pharmacodynamic, pharmacokinetic, or toxicological properties of compounds from their structure. While computer programs have been developed for computing molecular descriptors, there is a lack of a freely accessible one. We have developed a web-based server, MODEL (Molecular Descriptor Lab), for computing a comprehensive set of 3,778 molecular descriptors, which is significantly more than the approximately 1,600 molecular descriptors computed by other software. Our computational algorithms have been extensively tested and the computed molecular descriptors have been used in a number of published works of statistical models for predicting variety of pharmacodynamic, pharmacokinetic, and toxicological properties of compounds. Several testing studies on the computed molecular descriptors are discussed. MODEL is accessible at http://jing.cz3.nus.edu.sg/cgi-bin/model/model.cgi free of charge for academic use.

Amino Acids↗

PubMed1999

Femoral strength is better predicted by finite element models than QCT and DXA.

Clinicians and patients would benefit if accurate methods of predicting and monitoring bone strength in-vivo were available. A group of 51 human femurs (age range 21-93; 23 females, 28 males) were evaluated for bone density and geometry using quantitative computed tomography (QCT) and dual energy X-ray absorptiometry (DXA). Regional bone density and dimensions obtained from QCT and DXA were used to develop statistical models to predict femoral strength ex vivo. The QCT data also formed the basis of a three-dimensional finite element (FE) models to predict structural stiffness. The femurs were separated into two groups; a model training set (n = 25) was used to develop statistical models to predict ultimate load, and a test set (n = 26) was used to validate these models. The main goal of this study was to test the ability of DXA, QCT and FE techniques to predict fracture load non-invasively, in a simple load configuration which produces predominantly femoral neck fractures. The load configuration simulated the single stance phase portion of normal gait; in 87% of the specimens, clinical appearing sub-capital fractures were produced. The training/test study design provided a tool to validate that the predictive models were reliable when used on specimens with "unknown" strength characteristics. The FE method explained at least 20% more of the variance in strength than the DXA models. Planned refinements of the FE technique are expected to further improve these results. Three-dimensional FE models are a promising method for predicting fracture load, and may be useful in monitoring strength changes in vivo.

Absorptiometry, Photon↗

PubMed1997

The influence of day of life in predicting the inpatient costs for providing care to very low birth weight infants.

The purpose of this study was to test, refine, and extend a statistical model that adjusts neonatal intensive care costs for a very low birth weight infant's day of life and birth weight category. Subjects were 62 infants with birth weights below 1,501 g who were born and cared for in a university hospital until discharged home alive. Subjects were stratified into 250-g birth weight categories. Clinical and actual daily room and ancillary-resource costs for each day of care of each infant were tabulated. Data were analyzed by using a nonlinear regression procedure specifying two separate for modeling. The modeling was performed with data sets that both included and excluded room costs. The former set of data were used for generating a model applicable for comparing interhospital performances and the latter for comparing interphysician performances. The results confirm the existence of a strong statistical relationship between an infant's day of life and both total hospital costs and the isolated costs for ancillary-resource alone (P < 0.0001). A refined series of statistical models have been generated that are applicable to the assessment of either interhospital or interphysician costs associated with providing inpatient care to very low birth weight infants.

Hospital Costs↗

PubMed1999

Theoretical and empirical review of multinomial process tree modeling.

We review a current and popular class of cognitive models called multinomial processing tree (MPT) models. MPT models are simple, substantively motivated statistical models that can be applied to categorical data. They are useful as data-analysis tools for measuring underlying or latent cognitive capacities and as simple models for representing and testing competing psychological theories. We formally describe the cognitive structure and parametric properties of the class of MPT models and provide an inferential statistical analysis for the entire class. Following this, we provide a comprehensive review of over 80 applications of MPT models to a variety of substantive areas in cognitive psychology, including various types of human memory, visual and auditory perception, and logical reasoning. We then address a number of theoretical issues relevant to the creation and evaluation of MPT models, including model development, model validity, discrete-state assumptions, statistical issues, and the relation between MPT models and other mathematical models. In the conclusion, we consider the current role of MPT models in psychological research and possible future directions.

Association↗

PubMed1999

Modelling MRI enhancing lesion counts in multiple sclerosis using a negative binomial model: implications for clinical trials.

In multiple sclerosis (MS) the number of new enhancing lesions seen on monthly magnetic resonance imaging (MRI) scans is the most widely used response variable in MRI-monitored studies of experimental treatments. However, no statistical model has been proposed to describe the distribution of the number of such lesions across MS patients. This article briefly summarizes the statistical models for counted data. The negative binomial (NB) model is proposed to fit the number of new enhancing lesions counted in a set of 56 untreated MS patients followed for 9 months. It is shown that the large variability present in this data set is better addressed by the NB model (residual deviance=66.6, 54 degrees of freedom) than by the Poisson model (residual deviance=1830.1, 55 degrees of freedom). Applications of the parametrization of lesion counts are discussed, and an example related to computer simulations for the sample size estimation is presented.

Adolescent↗

PubMed1982

About the importance of account of some microcirculation parameters dispersion in modelling oxygen transport.

During the recent years various investigators have developed the technique of kryophotometric measurements of oxyhemoglobin saturation with oxygen (psi) in small vessels. In this paper, on the basis of the statistical model of the organ developed by the authors, a theoretical relationship is established between the distributions of measured in various groups of experiments in the capillaries and the distributions of psi in the arterioles and venules. It is shown that for the description of the distribution of psi in a separate multicapillary unit, lying between the arteriole and the venule, it is possible to introduce a special distribution function. In some cases this function may be determined analytically. Statistical distributions of other microcirculation parameters may be included into the statistical model of the organ using the similar procedure described in this paper for the parameters psi a' psi v- arteriolar and venular psi.

Humans↗

PubMed1999

Dose-rate effects of ethylene oxide exposure on developmental toxicity.

In risk assessment, evaluating a health effect at a duration of exposure that is untested involves assuming that equivalent multiples of concentration (C) and duration (T) of exposure have the same effect. The limitations of this approach (attributed to F. Haber, Zur Geschichte des Gaskrieges [On the history of gas warfare], in Funf Vortrage aus den Jahren 1920-1923 [Five lectures from the years 1920-1923], 1924, Springer, Berlin, pp. 76-92), have been noted in several studies. The study presented in this paper was designed to specifically look at dose-rate (C x T) effects, and it forms an ideal case study to implement statistical models and to examine the statistical issues in risk assessment. Pregnant female C57BL/6J mice were exposed, on gestational day 7, to ethylene oxide (EtO) via inhalation for 1.5, 3, or 6 h at exposures that result in C x T multiples of 2100 or 2700 ppm-h. EtO was selected because of its short half-life, documented developmental toxicity, and relevance to exposures that occur in occupational settings. Concurrent experiments were run with animals exposed to air for similar periods. Statistical analysis using models developed to assess dose-rate effects revealed significant effects with respect to fetal death and resorptions, malformations, crown-to-rump length, and fetal weight. Animals exposed to short, high exposures of EtO on day 7 of gestation were found to have more adverse effects than animals exposed to the same C x T multiple but at longer, lower exposures. The implication for risk assessment is that applying Haber's Law could potentially lead to an underestimation of risk at a shorter duration of exposure and an overestimation of risk at a longer duration of exposure. Further research, toxicological and statistical, are required to understand the mechanism of the dose-rate effects, and how to incorporate the mechanistic information into the risk assessment decision process.

Administration, Inhalation↗

PubMed1997

Estimating test-retest reliability in functional MR imaging. I: Statistical methodology.

A common problem in the analysis of functional magnetic resonance imaging (fMRI) data is quantifying the statistical reliability of an estimated activation map. While visual comparison of the classified active regions across replications of an experiment can sometimes by informative, it is typically difficult to draw firm conclusions by inspection; noise and complex patterns in the estimated map make it easy to be misled. Here, several statistical models, of increasing complexity, are developed, under which "test-retest" reliability can be meaningfully defined and quantified. The method yields global measures of reliability that apply uniformly to a specified set of brain voxels. The estimates of these reliability measures and their associated uncertainties under these models can be used to compare statistical methods, to set thresholds for detecting activation, and to optimize the number of images that need to be acquired during an experiment.

Brain↗

PubMed1994

RNA modeling using Gibbs sampling and stochastic context free grammars.

A new method of discovering the common secondary structure of a family of homologous RNA sequences using Gibbs sampling and stochastic context-free grammars is proposed. Given an unaligned set of sequences, a Gibbs sampling step simultaneously estimates the secondary structure of each sequence and a set of statistical parameters describing the common secondary structure of the set as a whole. These parameters describe a statistical model of the family. After the Gibbs sampling has produced a crude statistical model for the family, this model is translated into a stochastic context-free grammar, which is then refined by an Expectation Maximization (EM) procedure to produce a more complete model. A prototype implementation of the method is tested on tRNA, pieces of 16S rRNA and on U5 snRNA with good results.

Animals↗

PubMed1998

Biodiversity of parasites in a freshwater environment with respect to pollution: metazoan parasites of chub (Leuciscus cephalus L.) as a model for statistical evaluation.

This paper represents an attempt to evaluate the environmental indicative potential of the biodiversity of monogenean parasites using hierarchically structured species-abundance data. A logical set of statistical methods integrating standard diversity indices, a novel approach to quantitative analysis of cumulative species-abundance curves and species-abundance models was applied for this purpose. Applicability of biodiversity measures was demonstrated using experimental data from a 1-year study on the ecology of metazoan parasites of chub (Leuciscus cephalus) in one polluted and one control site in the Morava river, Czech Republic. Analyses at the component community level revealed a significant decrease in the number of parasite species with a more equal distribution of their abundances in the polluted site compared with the control site. In order to reach a better understanding of the changes, diversity of Monogenea as a dominant part of the community was further examined within categories of species created according to: (1) specificity of infection (specialists and generalists), (2) monogenean genera (Dactylogyrus, Gyrodactylus and Paradiplozoon) and (3) inhabited guilds (skin + fins, gills). Assemblages of specialists in the polluted site exhibited a significantly reduced species richness and unequal distribution of abundances. The opposite pattern was observed in the case of generalists. The influence of pollution was also reflected by the distribution of species abundances within communities of Dactylogyrus and Paradiplozoon, while no significant shift was identified in the genus Gyrodactylus.

Animals↗