Item analysis for the written test of Taiwanese board certification examination in anaesthesiology using the Rasch model.

BACKGROUND: On the written test of board certification examination for anaesthesiology, the probability of a question being answered correctly is subject to two main factors, item difficulty and examinee ability. Thus, item analysis can provide insight into the appropriateness of a particular test, given the ability of examinees. METHODS: Study subjects were 36 Taiwanese examinees tested with 100 questions related to anaesthesiology. We used the Rasch model to perform item analysis of questions answered by each examinee to assess the effects of question difficulty and examinee ability using a common logit scale. Additionally, we evaluated test reliability and virtual failure rates under different criteria. RESULTS: The mean examinee ability was higher than the mean item difficulty in this written test by 1.28 (sd=0.57) logit units, which means that the examinees, on average, were able to correctly answer 78% of items. The difficulty of items decreased from 4.25 to -2.43 on the logit scale, corresponding to the probability of having a correct answer from 5% to 98%. There were 60 items with difficulty lower than the least able examinee and seven difficult items beyond the most able one. The agreement of item difficulty between test developers and our Rasch model was poor (weighted kappa=0.23). CONCLUSIONS: We demonstrated how to assess the construct validity and reliability of the written examination in order to provide useful information for future board certification examinations. The study was approved by the institutional review board with the following trial registered number: VGHIRB No. 97-08-14A.

The effect of metabolic risk factors on the natural course of gastro-oesophageal reflux disease.

BACKGROUND AND AIMS: The effect of metabolic risk factors on the natural course of gastro-oesophageal reflux disease (GORD), which remains elusive, was quantified. METHODS: The population included 3669 subjects undergoing repeated upper endoscopy. Data were analysed using a three-state Markov model to estimate transition rates (according to the Los Angeles classification) regarding the natural course of the disease. Individual risk score together with the kinetic curve was derived by identifying significant factors responsible for the net force between progression and regression. RESULTS: During three consecutive study periods, 12.2, 14.9 and 17.9% of subjects, respectively, progressed from non-erosive to erosive disease, whereas 42.5, 37.3 and 34.6%, respectively, regressed to the non-erosive stage. The annual transition rate from non-erosive to class A-B disease was 0.151 per person year (95% CI 0.136 to 0.165) and from class A-B to C-D was 0.079 per person year (95% CI 0.063 to 0.094). The regression rate from class A-B to non-erosive disease was 0.481 per person year (95% CI 0.425 to 0.536). Class C-D, however, appeared to be an absorbing state when not properly treated. Being male (relative risk (RR) 4.31; 95% CI 3.22 to 5.75), smoking (RR 1.20; 95% CI 1.03 to 1.39) or having metabolic syndrome (RR 1.75; 95% CI 1.29 to 2.38) independently increased the likelihood of progressing from a non-erosive to an erosive stage of disease and/or lowered the likelihood of disease regression. The short-term use of acid suppressants (RR 0.54; 95% CI 0.39 to 0.75) raised the likelihood of regression from erosive to non-erosive disease. CONCLUSIONS: Intraoesophageal damage is a dynamic and migratory process in which the metabolic syndrome is associated with accelerated progression to or attenuated regression from erosive states. These findings have important implications for the design of effective prevention and screening strategies.

Robust quantitative trait association tests in the parent-offspring triad design: conditional likelihood-based approaches.

Association studies, based on either population data or familial data, have been widely applied to mapping of genes underlying complex diseases. In family-based association studies, using case-parent triad families, the popularly used transmission/disequilibrium test (TDT) was proposed for avoidance of spurious association results caused by other confounders such as population stratification. Originally, the TDT was developed for analysis of binary disease data. Extending it to allow for quantitative trait analysis of complex diseases and for robust analysis of binary diseases against the uncertainty of mode of inheritance has been thoroughly discussed. Nevertheless, studies on robust analysis of quantitative traits for complex diseases received relatively less attention. In this paper, we use parent-offspring triad families to demonstrate the feasibility of establishment of the robust candidate-gene association tests for quantitative traits. We first introduce the score statistics from the conditional likelihoods based on parent-offspring triad data under various genetic models. By applying two existing robust procedures we then construct the robust association tests for analysis of quantitative traits. Simulations are conducted to evaluate empirical type I error rates and powers of the proposed robust tests. The results show that these robust association tests do exhibit robustness against the effect of misspecification of the underlying genetic model on testing powers.

A confirmation analysis method for identification of chromosomal fragile sites.

Fragile sites are chromosome bands that do not manifest a presumed breakage pattern. Identification of fragile sites is a way to investigate the mechanism of carcinogenesis because the fragility at a specific chromosome position may be the causation of an associated cancer. A problem in the identification of fragile sites is the high false positive rate arising from simultaneously carrying out a large number of significance tests. To control it, we propose to find a reference study to confirm the identification result of an objective study. We utilize the Bayesian concept for linking two studies. Basically, our method demonstrates a conservative way to take account of the prior information of a binomial parameter. The derived estimate of breakage probability can be interpreted as a resampling weighted sample-pooling method. It is applied to confirm the identification of fragile sites for a data set of neuroblastoma patients.

The significance of body weight change in non-Hodgkins lymphoma.

BACKGROUND: The purpose of this study was to evaluate the effect of weight changes after completion of chemotherapy on the prognosis and survival of patients with intermediate and high grade non-Hodgkin's lymphoma. MATERIALS AND METHODS: A retrospective analysis of data on patients from the TCOG T1488 protocol, a phase II study using CHOP in the treatment of intermediate and high grade lymphoma. From September, 1988 to December 1994, 138 adult patients had complete weight data for analysis. Weight gain in lymphoma patients after therapy significantly correlated with improved survival (Logrank test p = .0031). In patients with initial B symptoms, weight gain after therapy correlated with survival (Logrank test p = .0039), female patients (odds ratio = 6.2) were less likely to gain weight on treatment. CONCLUSION: Weight gain after chemotherapy for lymphoma is a significant positive prognostic factor for survival.

Chromosomal study in lymphocytes from subjects living or working in buildings constructed with radioactively contaminated rebar.

It has recently been found that many buildings in Taiwan were constructed with radioactively contaminated rebar, which raised great concern among the residents as well as governmental officials. In order to investigate the possible cytogenetic damage to the residents of contaminated buildings, a G-banding method was carried out on the lymphocytes of 30 radiation-exposed individuals from four families and one office building, as well as 15 control individuals from laboratory personnel. The estimated cumulative radiation doses for the exposed people range from 19.63 to 280.50 mSv. Altogether, 13 females and 17 males belonging to the radiation-exposed group, and 7 females and 8 males in the control group, were included in this study. With the exception of one sample, at least 500 metaphase spreads were scored and analyzed for each individual. All the recognizable structural aberrations of chromosomes or chromatids were recorded and statistically analyzed. Comparison of either percentage of cells with chromosome aberrations or number of aberrated chromosomes per 100 cells between the radiation-exposed and the control groups manifested insignificant differences (p = 0.1145 and 0.0766, respectively). In addition, the chromosomal regions close to the centromere were found to break more frequently than elsewhere in the genome.

Human leukocyte antigens in inhabitants of Taiwan.

Human leukocyte antigens (HLA) were investigated in 200 healthy Taiwan inhabitants of Taiwanese (46 persons), Hakka (36), Tai-Ya Tribe (28) Pu-Long Tribe (30) Pai-Wan Tribe (30) and Lu-kai (30) descent. In those of Taiwanese and Hakka descent, HLA-A11 and A2 were the two most frequently seen human leukocyte antigens. HLA-A11 was seen in 69.6% in those of Taiwanese descent and 61.1% in those of Hakka descent. HLA-A2 was seen in 50.0% of the Taiwanese and 44.4% of the Hakka. For the B loci, B40 (Taiwanese, 43.5%; Hakka, 44.4%), Bw46 (Taiwanese, 28.3%; Hakka, 19.4%) and B13 (Taiwanese, 15.2%; Hakka, 30.6%) were the most common antigens. For the C loci, Cw3 (Taiwanese, 57.1%; Hakka 64.9%), Cw1 (Taiwanese, 28.6%; Hakka, 35.1%) and Cw7 (Taiwanese, 40.5%; Hakka, 29.9%) were commonly seen antigens. The most commonly detected antigens for the DR loci were: DR2 (Taiwanese, 45.1%; Hakka, 56.8%) and DR4 (Taiwanese, 37.3%; Hakka, 32.4%). These results disclose that no major human leukocyte antigenic differences exist between the two aforementioned groups in this study. In addition, there are no major differences in Taiwanese and Hakka descent, and those of south and north mainland Chinese descent. All bear some antigenic similarities. However, for aborigines, the original inhabitants of Taiwan, the HLA antigens are significantly different from the Han Chinese as a whole. Characteristic features are seen in A24, Bw60, DRw6 and DRw8. In the meantime, a high frequency of common antigens are shared among the tribes and consequently a large number of blank alleles are seen in the aborigines. This reflects the homozygosity effect which is often seen in an isolated society.

Polymorphisms of the apolipoprotein B 3' variable number of tandem repeats region associated with coronary artery disease in Taiwanese.

We studied the allelic frequency of the variable number of tandem repeats region 3' of the apolipoprotein B gene (apoB 3' VNTR) and its impact on coronary artery disease (CAD) in 150 patients with CAD and 153 normal controls in a Taiwan population. apoB 3' VNTR alleles were classified according to the number of repeats of a 15-bp hypervariable elements (HVE), the sequence of which was determined using the polymerase chain reaction and direct sequencing. Thirteen alleles comprising from 26 to 54 HVEs were identified. The CAD patients had greater heterozygosity (0.58 vs 0.42) and a higher frequency of long (> 36-HVE) apoB 3' VNTR alleles than the controls (18.7% vs 10.8%, p < 0.01). CAD patients with two HVE-36 alleles and no HVE-32 alleles (the two most common forms) had significantly higher concentrations of LDL-cholesterol, apolipoprotein B, and triglycerides, and significantly lower values of HDL-cholesterol and apolipoprotein AI than the control group (p < 0.01 for all comparisons). The length of the apoB 3' VNTR was not correlated with the plasma concentrations of any of the lipids. We conclude that long apoB 3' VNTR alleles occur more frequently in CAD patients, but that apoB 3'VNTR genotypic variation has little impact on the risk of dyslipidemia in Taiwanese.

A robust linkage analysis method using combined allele sharing and transmission disequilibrium information from case-parent tetrad families.

There are two types of linkage information, the allele sharing information and transmission disequilibrium information, that can be extracted from case-parent tetrad families for deriving statistics for test of linkage. By extracting allele sharing information the mean test can be derived. By extracting transmission disequilibrium information the transmission/disequilibrium test (TDT) can be derived. The power performances of the two tests are different with respect to the extent of linkage disequilibrium. The TDT is more powerful than the mean test when the extent of linkage disequilibrium is moderate to strong, but the mean test has better power performance than the TDT when linkage disequilibrium is weak. Some previous studies have proposed several post-combination analysis methods, which combine the two tests after they are derived using the two types of linkage information respectively, to yield robust test statistics against the interference of linkage disequilibrium. Instead of adopting the post-combination approach, in this paper we investigate the approach of using the pre-combination idea to yield robust statistics for test of linkage. The pre-combination methods combine the two types of linkage information first, and then use the combined information to construct robust test statistics. Simulation studies are conducted to compare the power performances of the proposed pre-combination tests with those of the existing post-combination methods.

Analysis of linkage with disease-marker association.

This paper proposes a method to deal with linkage analysis under the existence of association between a disease and a marker locus. We specially consider the disease as a quantitative trait. At first, we propose a so-called "a minimum sum of square errors approach" to classify individuals in a family genetically, then use the classification results to detect linkage with association by the developed method.

Pseudo-random mating systems for 3-allele loci.

A random mating population attains equilibrium by the Hardy-Weinberg law. By demonstrating some simple examples for 2-allele loci, Li (1988) showed that a nonrandom mating population of certain mating patterns may also attain equilibrium. He called such a type of population a pseudo-random mating population. Tai (1990), then, gave a generalized representation of these pseudo-random mating systems. In this paper the clear patterns of pseudo-random mating behavior for a 3-allele locus are derived. Both autosomal and sex-linked systems are discussed. The study of these mating patterns provides a way to understand the complicated mating system of a population, which usually is only with difficulty realized through sampled individuals from that population.

Self-contained subsets method for estimation of gene frequencies of truncated genetic data.

The self-contained subsets method subdivides a genetic data set into a number of subsets from which estimates are computed. The advantage of such a method is that when a subset is suspected of containing unreliable data then discarding that subset will not invalidate the remaining subsets for estimation. Thus, the complicated computation required to deal with truncated data can be avoided. In this paper, using estimation of gene frequencies as an example for one subset case, the marginal distribution of a subset total is derived and then, using this distribution, the variance of the frequency estimate of a gene frequency from the subdivision method is calculated. The subdivision method is also applied to impute the number of people of a truncated group. Finally, more complex cases where there are multiple subsets available for estimation are discussed. Results are compared to those of previous studies.

Linkage disequilibrium and linkage information from one-child families.

In linkage analysis a single-child family is usually considered to be completely uninformative. This article shows that such a family can provide information on linkage disequilibrium, even if it provides no information on linkage equilibrium. A transition matrix consisting of the recombination fraction and the phase proportion is proposed to study the genetic transmission from a pair of parents to their single child. The information about linkage for a single-child family is shown to be confounded by the phase proportion. This explains why such a family used to be considered uninformative under the assumption of linkage equilibrium. By reparametrizing the recombination fraction and the phase proportion into one parameter, it is demonstrated that extracting information on linkage disequilibrium is feasible. The study of power of the testing method proposed here is carried out by simulation.

Asymptotic distribution of the lod score for familial data.

Using a linkage model with mixed parental mating types between a trait locus and a marker locus the asymptotic null distribution of the statistic U = 2ln(10)Z(theta) was stimulated and compared to the chi square type distribution function 1/2 + 1/2 Pr [chi 2(1) less than mu]. The stimulation results show that the chi square approximation fits the asymptotic null distribution well when both loci are predominated by either one of the two alleles at their loci, respectively, or the linkage phase tends to disequilibrium.

A non-excluded set method for the calculation of paternity probability.

Forensic judgment of paternity depends on genetic and nongenetic evidence. Sometimes genetic marker tests can provide clear evidence to exclude a falsely accused man, but they do not always succeed. On the other hand, if the accusation is true, the alleged father will not ever be excluded by genetic marker tests. When a nonexclusion case occurs after one or more marker tests, a report of paternity probability is required in the court. The current methods for calculating the paternity probability are the "paternity index method" and the "nonexclusion method." A number of recent articles have openly debated the fallacies, validity and utility of both methods. This paper briefly reviews the two methods and proposes a non-excluded set method along with examples for illustrating the various patterns of paternity probabilities of the three methods.

Effects of implicit parameters in segregation analysis.

In human genetic analysis, data are collected through the so-called 'ascertainment procedure'. Statistically this sampling scheme can be thought of as a multistage sampling method. At the first stage, one or several probands are ascertained. At the subsequent stages, a sequential sampling scheme is applied. Sampling in such a way is virtually a nonrandom procedure, which, in most cases, causes biased estimation which may be intractable. This paper focuses on the underlying causes of the intractability problem of ascertained genetic data. Three types of parameters, i.e. target, design and nuisance parameters, are defined as the essences to formulate the true likelihood of a set of data. These parameters are also classified into explicit or implicit parameters depending on whether they can be expressed explicity in the likelihood function. For ascertained genetic data, a sequential scheme is regarded as an implicit design parameter, and a true pedigree structure as an implicit nuisance parameter. The intractability problem is attributed to loss of information of any implicit parameter in likelihood formulation. Several approaches to build a likelihood for estimation of the segregation ratio when only an observed pedigree structure is available are proposed.

Bias correction for segregation ratio estimation in human genetics.

Segregation ratio estimation has long been important in human genetics. A simple truncated binomial model is considered that assumes complete ascertainment and a deterministic genotype-phenotype relationship. A simple but intuitively appealing estimator of the segregation ratio, previously proposed, is shown to have a negative bias. It is also shown that the bias of this estimator can be largely reduced via a randomization device, resulting in a new estimator that has the same large-sample behavior but with a negligible bias (decaying at a geometric rate). Numerical results are given to show the small-sample performance of this new estimator. An extension to incomplete ascertainment is also considered.

Identifying chromosomal fragile sites from a hierarchical-clustering point of view.

Identification of fragile sites is a way to investigate the genetic abnormalities that are the hallmark of cancer and play an important role in carcinogenesis. Manifestation of nonrandom breakage at a chromosome band is an essential criterion for determination of the fragility of the band. In this article, a new detection procedure is proposed. This new procedure takes the relationship of one site with the others into consideration and can be applied to tests of the randomness of breakpoints under either the proportional probability model (PPM) or the equiprobability model (EPM). The procedure can form a grouping structure that classifies all sites into several clusters. It is applied to identification of fragile sites for a real data set for Chinese patients with colorectal carcinoma for illustration of the proposed method.

Effect of hyperbaric oxygen on GABA transport in rat brain synaptosomes.

Initial velocities of uptake of GABA have been measured in rat brain synaptosomes from animals which had been exposed to oxygen at high pressure (OHP) and compared to similar measurements in normobaric controls. For hypothalamus, no changes in GABA uptake occurred subsequent to exposure to OHP. For cortical synaptosomes, however, exposure to OHP resulted in a decreased velocity of GABA uptake at all combinations of [Na] and [GABA] used. The OHP data were found to fit the same transport model as found previously for control data. Thus, OHP exposure did not alter the basic mechanism by which sodium and GABA interact with the carrier in the process of transport. However, the constants which quantitate the model were changed by OHP exposure. As a consequence, the several kinetic parameters which are calculated from the model change in the OHP animals. These kinetic parameters are compared to similar calculations for both normobaric control animals and normobaric aged animals. Although the effects of OHP do not precisely parallel the effects of aging, the alterations in kinetic parameters are in several ways similar in the aged and OHP animals.

Testing the nonrandomness of chromosomal breakpoints using highest observed breakages.

To determine whether a chromosomal band is a fragile site rather than a spontaneous breakpoint, an essential step is to test the nonrandomness of breakage at the region. In this paper, the nonapplicability of the testing procedure introduced by Bohm et al. is discussed, and a new detection procedure is proposed. This new procedure considers the relations of one site with the others, and can be applied to tests of the nonrandomness of breakpoints under either the proportional probability model, or the equiprobability model. A data set for Chinese patients with colorectal carcinoma is analyzed as an illustration of the proposed method.