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PubMed2003

What difference does it make? Implications of the size of the difference between the means of two groups.

This study employed a model with two normal distributions of scores to study group differences and similarities as a function of the distance between group means. The mean of one distribution was systematically moved further and further away from the mean of the other. A table was developed of associated measures of group overlap and separation, e.g., r, eta, percent correct classification, percentage of overlap, for several levels of d' (difference between means expressed in standard deviation units). The implications of various d' values for the selection of extreme groups, e.g., top 1% of scorers, were discussed. It was noted that even small differences between means could result in an extremely disproportionate inclusion of members from the two original groups in a high-scoring subgroup.

Adult↗
PubMed2003

Robustness of inference on measured covariates to misspecification of genetic random effects in family studies.

Family studies to identify disease-related genes frequently collect only families with multiple cases. It is often desirable to determine if risk factors that are known to influence disease risk in the general population also play a role in the study families. If so, these factors should be incorporated into the genetic analysis to control for confounding. Pfeiffer et al. [2001 Biometrika 88: 933-948] proposed a variance components or random effects model to account for common familial effects and for different genetic correlations among family members. After adjusting for ascertainment, they found maximum likelihood estimates of the measured exposure effects. Although it is appealing that this model accounts for genetic correlations as well as for the ascertainment of families, in order to perform an analysis one needs to specify the distribution of random genetic effects. The current work investigates the robustness of the proposed model with respect to various misspecifications of genetic random effects in simulations. When the true underlying genetic mechanism is polygenic with a small dominant component, or Mendelian with low allele frequency and penetrance, the effects of misspecification on the estimation of fixed effects in the model are negligible. The model is applied to data from a family study on nasopharyngeal carcinoma in Taiwan.

Analysis of Variance↗
PubMed2007

A score test for overdispersion in zero-inflated poisson mixed regression model.

Count data with extra zeros are common in many medical applications. The zero-inflated Poisson (ZIP) regression model is useful to analyse such data. For hierarchical or correlated count data where the observations are either clustered or represent repeated outcomes from individual subjects, a class of ZIP mixed regression models may be appropriate. However, the ZIP parameter estimates can be severely biased if the non-zero counts are overdispersed in relation to the Poisson distribution. In this paper, a score test is proposed for testing the ZIP mixed regression model against the zero-inflated negative binomial alternative. Sampling distribution and power of the test statistic are evaluated by simulation studies. The results show that the test statistic performs satisfactorily under a wide range of conditions. The test procedure is applied to pancreas disorder length of stay that comprised mainly same-day separations and simultaneous prolonged hospitalizations.

Adult↗
PubMed1991

Fitting mixture distributions to phenylthiocarbamide (PTC) sensitivity.

A technique for fitting mixture distributions to phenylthiocarbamide (PTC) sensitivity is described. Under the assumptions of Hardy-Weinberg equilibrium, a mixture of three normal components is postulated for the observed distribution, with the mixing parameters corresponding to the proportions of the three genotypes associated with two alleles A and a acting at a single locus. The corresponding genotypes AA, Aa, and aa are then considered to have separate means and variances. This paper is concerned with estimating the parameters of the model, and their standard errors, by using an application of the EM algorithm. This technique also caters for the fact that the sensitivity measurements are only known to lie between the endpoints of certain intervals and that the exact measurement of the attribute is not possible.

Algorithms↗
PubMed2000

Inferring infection processes of a parasitic nematode using population genetics.

The distribution of genetic differentiation in a population of the parasitic nematode Strongyloides ratti divided between rat hosts was determined. We applied population genetic theory to these data to determine the source of new infections. We estimate the rate at which a rat acquires a new infection from (a) the existing subpopulation of parasites within that rat ('self-reinfection') versus (b) the wider environment ('immigration'). We find that the observed levels of genetic diversity and differentiation in the study population are consistent with low to moderate rates of self-reinfection and inconsistent with high rates of self-reinfection.

Animals↗
PubMed2006

Generalized additive modeling with implicit variable selection by likelihood-based boosting.

The use of generalized additive models in statistical data analysis suffers from the restriction to few explanatory variables and the problems of selection of smoothing parameters. Generalized additive model boosting circumvents these problems by means of stagewise fitting of weak learners. A fitting procedure is derived which works for all simple exponential family distributions, including binomial, Poisson, and normal response variables. The procedure combines the selection of variables and the determination of the appropriate amount of smoothing. Penalized regression splines and the newly introduced penalized stumps are considered as weak learners. Estimates of standard deviations and stopping criteria, which are notorious problems in iterative procedures, are based on an approximate hat matrix. The method is shown to be a strong competitor to common procedures for the fitting of generalized additive models. In particular, in high-dimensional settings with many nuisance predictor variables it performs very well.

Biometry↗
PubMed1997

[The HLA phenotype and duodenal ulcers in patients following kidney transplantation].

The authors have performed an investigation of the association between ulcer disease of the duodenum and bleedings from the ulcers in 204 patients after transplantations of the kidney with the antigen of HLA system histocompatibility. Duodenal ulcers were found in 25 patients (12.9%), in 11 of them the ulcers were complicated by bleedings which was 5.4% of the total number of the patients with the transplanted kidney. The evaluation of the HLA antigen distribution has revealed an association of duodenal ulcers with A2 and B13 antigens which took place significantly more often than in a group of practically healthy people (RR = 1.85 and 1.9 correspondingly). In patients with the transplanted kidney and following ulcerous bleedings this association was more obvious (RR = 2.32 and 3.74 correspondingly). According to the calculated etiological fraction 40% of the patients can be supposed to have the etiological association of the disease with A2 antigen and 20% of the patients with B13 antigen. A typical feature was the presence of possible "protective" A9 antigen which was found in the group under study two times more seldom than in the control group (RR = 0.25). A comparison of the distribution of HLA antigens in the patients in whom there developed bleeding duodenal ulcers with those who had no such complications has also established the association of the disease with HLA A2 and B13 antigens. The probable "protective" A9 antigen was also found. Since the kidney transplantation is preceded by determination of the recipient's HLA phenotype, these data can be used as prognostic criteria as well as the indications to performing preventive antiulcerous therapy in patients with high risk of the development of ulcerous lesions of the gastrointestinal tract.

Adult↗
PubMed1999

On the utility of the Dirichlet distribution for meta-analysis of clinical studies.

Recently, there has been an increasing interest in combining efficacy (or safety) results from several clinical trials to draw an overall conclusion about the efficacy (or safety) of new investigational drugs. In a two-armed clinical trial, these efficacy outcomes are often expressed in terms of the two treatment effect means or the proportions of treatment success. For several clinical trials, efficacy assessment could be based on different types of clinical outcomes. These outcomes might be both categorical and noncategorical. Therefore, it is desirable to have a statistical model that is flexible enough for combining clinical trial data of both outcomes across several trials or studies. We discuss a simple statistical model with a potential for such flexibility. We illustrate the use of the model by providing a couple of numerical examples on the meta-analyses of efficacy data from prospective clinical trials/studies.

Bayes Theorem↗
PubMed1995

Computer model of the maintenance and selection of genetic heterogeneity in polygamous helminths.

A stochastic simulation model of the transmission and maintenance of genetic heterogeneity in the absence and presence of external selection pressures is presented for polygamous intestinal helminths such as Ascaris. The model assumes that the density distribution of the adult parasites is highly aggregated and that density-dependent effects on fecundity are important. The model gives rise to stable infection rates in the host. Where the parasite population contains genetic heterogeneity, with the exception of stochastic fluctuations which models genetic drift, the ratio of the different alleles remained constant over extended periods of time. This result contrasts with that of an earlier analytical model (Anderson, R.M., May, M.R. & Gutpa S. (1989) Parasitology 99, S59-S79), in which uneven mating probabilities for the different combinations of worm possible in a host was postulated to inevitably lead to fixation of the most abundant allele. New results suggest that in spite of the restricted choice of mating available to a worm in the confines of a host, selection pressure always leads to enrichment of the parasites carrying resistant alleles.

Animals↗
PubMed1994

Smell acuity for acetone and its relationship to taste ability to phenylthiocarbamide in a Nigerian population.

Acetone smell sensitivity and phenylthiocarbamide taste sensitivity thresholds have been measured simultaneously for 970 Nigerians (542 males and 428 females) using modified sorting techniques. The distribution was bimodal in both cases and the frequency of subjects with high smell acuity for acetone was 9.6% while that of non-tasters was 12.60% with a gene frequency, as computed by maximum likelihood methods, of 0.355 +/- 0.015. Females showed a higher frequency for smell sensitivity to acetone but a slightly lower frequency of non-tasters compared to males. Acetone smell sensitivity and PTC with high smell acuity for acetone were tasters while 30.28% of subjects least sensitive taste ability decreased with age in the overall population. All the subjects least sensitive to acetone were non-tasters, a significantly higher proportion than in the overall population. The correlation between acetone smell acuity and phenylthiocarbamide taste ability demonstrates a strong allelic association. All the 94 individuals with high smell acuity for Acetone were tasters for phenylthiocarbamide.

Acetone↗
PubMed2006

Numerical study of the effects of inferior and superior vocal fold surface angles on vocal fold pressure distributions.

Vocal fold geometry plays an important role in human phonation. A wide range of inferior and superior vocal fold surface angles has been shown to be present during phonation [Nanayakkara, Master's thesis, Bowling Green State University, Bowling Green, OH (2005)]. This study explored how these angles affect pressure distributions on the vocal folds, and thus how they may affect phonation. The computational code FLUENT was used to obtain pressure distributions for laminar, incompressible flow. Eighteen inferior vocal fold surface angles and nineteen superior vocal fold surface angles were selected for three specific glottal angles, uniform 0 degrees, convergent 10 degrees, and divergent 10 degrees. Minimal glottal diameter (0.01 cm), transglottal pressure (8 cm H2O), and glottal entrance radius (0.15 cm) were held constant, and the glottal exit radius was constant for each glottal angle. Results suggest that the vocal fold surface pressures are independent of the inferior and superior vocal fold surface angles realistic for human phonation. These results suggest that, in contrast to the important effects of glottal entrance and exit radii, minimal diameter, and angle on intraglottal pressures, the inferior and superior vocal fold surface angles (excluding possible interactive effects with the false vocal folds) do not have an influence on the intraglottal pressures.

Binomial Distribution↗
PubMed1995

Recruitment-driven, spatially discontinuous communities: a null model for transferred patterns in target communities of intestinal helminths.

Populations and therefore communities of intestinal helminths of vertebrates are fueled by recruitment of new individuals from outside the host. The source of new individuals is often an intermediate host that harbors several infective propagules of 1 or more species. Hence these source communities are transmitted in packets of infective propagules to target communities in definitive hosts. Packets not only provide recruits to target communities, but, because a packet of propagules possesses its own structure, it may also transmit structure to the target community. We use this system to examine the contribution that structure in the source pool of propagules makes to the structure of recruitment-driven target populations and communities. By treating the dynamics of such target populations and communities as immigration-death processes, we conclude: (1) Unlike a birth-driven population a recruitment-driven target population will grow to an asymptotic limit even in the absence of density-dependent processes or reaching carrying capacity; (2) the frequency distribution of the number of recruits entering target populations will determine the frequency distribution of adults in target populations; (3) interspecific associations among species in the source community will be transmitted to target communities, but the magnitude of the transmitted associations will depend upon the relative survival rates of the species; and (4) for associations of equal magnitude in a source community, the magnitude of a transferred negative association will be less than the magnitude of a positive association in a target community. Two examples of source communities in salt marsh crabs reveal that source infracommunities exist with the hypothesized structure. Further, the source helminth communities display a greater number of positive than negative interspecific associations. The inequity in transfer and the existence of a greater proportion of positive associations in source communities may explain the widespread occurrence of excess positive associations that has been noted in recruitment-driven communities.

Animals↗
PubMedDate not supplied

Counting statistics.

The low radiation dose rates used in nuclear medicine necessitate image formation and measurements that are severely count limited. This limitation may mask our ability to perceive contrast in an image or may affect our confidence in quantitative functional measurements. The randomness of the signal can be described by using the Poisson probability distribution with its associated mean and variance. The validity of a measurement and uncertainties in a result can be determined by examining the count statistics. If multiple measurements are used to derive a result, confidence levels can be determined by examination of the propagation of errors. The statistical properties of the detected signal can also be evaluated to determine if the equipment is functioning properly. For example, the chi2 test can be used to determine if there is too much or too little variability in count samples. Finally, image formation with limited numbers of photons results in noisy images that may be difficult to interpret. An understanding of the trade-offs between contrast, noise, and object size is required to set proper image acquisition parameters and thereby ensure that the information required to make a diagnosis is contained in the final image.

Algorithms↗
PubMed1993

Data on the CGG repeat at the fragile X site in the non-retarded Japanese population and family suggest the presence of a subgroup of normal alleles predisposing to mutate.

The fragile X mutation is the result of amplification in the repeat number of p(CGG)n in FMR-1; alleles with more than 52 repeats have been shown to be so unstable as to mutate in the repeat number in almost every transmission. To improve our understanding of mutations in normal alleles of FMR-1, the following studies were carried out in the Japanese population: a study on length variation in the repeat to determine the allele distribution of the repeat length in a non-retarded population, family studies to observe new mutations in normal allele, and haplotype analyses with microsatellite markers flanking the repeat to confirm estimated mutation rates and founder chromosomes in the fragile X syndrome. Analysis of the p(CGG)n in 370 unrelated males detected 24 distinct alleles with repeats of 18-44. A comparison with previously reported data suggests the presence of racial/ethnic differences in the allele distribution. No premutation allele was found in 824 unrelated X chromosomes examined by the polymerase chain reaction and Southern blot analysis. Family studies detected one new mutation in a total of 303 meioses. However, the mutation rate was not in accordance with the expected or observed heterozygosities in the population or with linkage disequilibrium observed between the repeat numbers and the haplotypes of the markers flanking the CGG. The haplotype in the chromosome in which the new mutation was found was the same as that frequently found in the Japanese fragile X chromosomes, and the variance in the CGG repeat number was wider in chromosomes with the haplotypes frequently found in the fragile X chromosome than in those with the other haplotypes. These observations suggest that a subgroup is present in normal alleles and that this subgroup is more liable to mutate than others.

Alleles↗
PubMed1990

[An analysis of industrial accidents in the working field with a particular emphasis on repeated accidents].

The present study is based on an analysis of routinely submitted reports of occupational accidents experienced by the workers of industrial enterprises under the jurisdiction of Kagoshima Labor Standard Office during a 5-year period 1983 to 1987. Officially notified injuries serious enough to keep employees away from their job for work at least 4 days were utilized in this study. Data was classified so as to give an observed frequency distribution for workers having any specified number of accidents. Also, the accident rate which is an indicator of the risk of accident was compared among different occupations, between age groups and between the sexes. Results obtained are as follows; 1) For the combined total of 6,324 accident cases for 8 types of occupation (Construction, Transportation, Mining & Quarrying, Forestry, Food manufacture, Lumber & Woodcraft, Manufacturing industry and Other business), the number of those who had at least one accident was 6,098, of which 5,837 were injured only once, 208 twice, 21 three times and 2 four times. When occupation type was fixed, however, the number of workers having one, two, three and four times of accidents were 5,895, 182, 19 and 2, respectively. This suggests that some workers are likely to have experienced repeated accidents in more than one type of occupation.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Occupational↗
PubMedDate not supplied

Classifying binormal diagnostic tests using separation-asymmetry diagrams with constant-performance curves.

A method is proposed for classifying diagnostic tests that have underlying binormal distributions. The method involves using the parameters that characterize these distributions as axes of a two-dimensional graph called a separation-asymmetry (S-A) diagram. Each point on an S-A diagram corresponds to a possible diagnostic test. The diagram also has superimposed on it any of three possible families of curves of constant performance: curves of constant area under the ROC graph (iso-AUR), curves of constant overlap area (iso-OA), and curves of constant maximum information (iso-MaxInfo). Thus, the performance of any test can be determined immediately by identifying the iso-performance curve of the desired type that passes through the corresponding point of the S-A diagram. The concept of "eccentric" diagnostic tests is defined and incorporated into the S-A diagrams. The classification scheme is applied to 28 diagnostic tests. Excellent agreement is found in the ranking between the iso-OA and iso-MaxInfo measures of performance, but the iso-AUR produces markedly different results. Only three of the 28 tests were found to be eccentric. Several other interesting patterns emerged.

Bias↗
PubMed2004

Assessment of families for excess risk of lymphedema of the leg in a lymphatic filariasis-endemic area.

The influence of host genes on the distribution of lymphedema due to lymphatic filariasis is unknown. To assess this, pedigree and disease information were collected from lymphedema patients in a lymphatic filariasis-endemic area. These patients were female, with an average age of approximately 40 years, who were enrolled between June 1995 and July 1999 in a lymphedema treatment clinic, and from the rural Haitian community served by the clinic. Interviews were conducted between September 1998 and December 1999. Families with multiple lymphedema cases were of similar size, with an average of 15 members, as those families with only a single lymphedema case. We determined whether families observed to have multiple lymphedema cases had a higher prevalence of lymphedema than expected when stratified population estimates and family size were considered. Lymphedema of the leg was excessive in 15 of 43 families with multiple lymphedema cases. The number of families demonstrating excess disease was significantly different than was expected based on population estimates of lymphedema prevalence (P = 0.026). Families with multiple cases of lymphedema were not significantly larger in family size than families with a single lymphedema cases. Twelve of the 15 families had a male with lymphedema, which influenced the interpretation of the results. The significance of these results is discussed.

Adult↗
PubMed2001

Obesity and body mass index in Spain: the 'single population' theory revisited.

OBJECTIVE: The 'single population' theory suggests that the distribution of body mass index (BMI) moves up and down as a whole. We test directly whether this theory is valid among the adult population within one country over time, by examining the association between median BMI and the prevalence of obesity in the adult population of Spain's 17 regions between 1987 and 1993. DESIGN AND SETTING: Ecological study using data from two national health surveys. SUBJECTS AND INTERVENTIONS: Self-reported weight and height for persons aged 20-64 y were drawn from representative Spanish-population samples from two similar National Health Surveys carried out in 1987 (n = 20 705) and 1993 (n = 15 490). MAIN OUTCOME MEASURES: Correlation and linear regression between the difference in median BMI and the difference in the prevalence of obesity (BMI > or = 30 kg/m(2)) between 1987 and 1993. RESULTS: Between 1987 and 1993 the change in median BMI was in general strongly correlated with the change in the prevalence of obesity (r = 0.85; P < 0.001). The correlation is greater in women, persons over 45 y, and those with lower educational levels. Between 1987 and 1993 each unit of increase in median BMI is associated with an absolute increase of 5.1% (95% CI 3.3-6.8%) in the prevalence of obesity. CONCLUSIONS: The single population hypothesis holds true among the adult population within a whole country over time. This could be useful for monitoring and understanding the prevalence of obesity within a population.

Adult↗