bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Item-Specific Instructional Information in Achievement Modeling
Authors: Muthén Bengt O.
Published: January 2006

The problem of detecting instructional sensitivity (“item basis”) in test items is considered. An illustration is given which shows that for tests with many biased items, traditional item bias detection schemes give a very poor assessment of bias. A new method is proposed instead. This method extends item response theory (IRT) by including item-specific auxiliary measurement information related to opportunity-to-learn. Item-specific variation in measurement relations across students with varying opportunity-to-learn is allowed for.
Inferential Theory for Partially Disattenuated Correlation Coefficients
Authors: Hakstian A. Ralph , Schroeder Marsha L. , Rogers W. Todd
Published: January 2006

Four measurement designs are presented for use with correlation coefficients corrected, in one variable, for attenuation due to unreliability—coefficients that we term partially disattenuated correlation coefficients. Asymptotic expressions are derived for the variances and covariances of the estimates accompanying each design. Empirical simulation results that bear on the preceding mathematical developments are then presented. In addition to providing insights into the distributions of the estimates, the empirical results demonstrate satisfactory Type I error control for typical inferential applications. Power is shown to be equal to or greater than that of corresponding product-moment correlations in three of the four designs. Implications for practice are discussed.
Weighted Likelihood Estimation of Ability in Item Response Theory
Authors: Warm Thomas A.
Published: January 2006

Applications of item response theory, which depend upon its parameter invariance property, require that parameter estimates be unbiased. A new method, weighted likelihood estimation (WLE), is derived, and proved to be less biased than maximum likelihood estimation (MLE) with the same asymptotic variance and normal distribution. WLE removes the first order bias term from MLE. Two Monte Carlo studies compare WLE with MLE and Bayesian modal estimation (BME) of ability in conventional tests and tailored tests, assuming the item parameters are known constants. The Monte Carlo studies favor WLE over MLE and BME on several criteria over a wide range of the ability scale.
A Stochastic Growth Model Applied to Repeated Tests of Academic Knowledge
Authors: Albers W. , Does R. J. M. M. , Imbos Tj. , Janssen M. P. E.
Published: January 2006

In the course of the medical program at the University of Limburg, students complete a total of 24 progress tests, consisting of items drawn from a constant itembank. A model is presented for the growth of knowledge reflected by these results. The Rasch model is used as a starting point, but both ability and difficulty parameters are taken to be random, and moreover the logistic distribution is replaced by the normal. Both individual and group abilities are estimated and explained through simple linear regression. Application to real data shows that the model fits very well.
A Comparison of Three Simple Test Theory Models
Authors: Ramsay J. O.
Published: January 2006

In very simple test theory models such as the Rasch model, a single parameter is used to represent the ability of any examinee or the difficulty of any item. Simple models such as these provide very important points of departure for more detailed modeling when a substantial amount of data are available, and are themselves of real practical value for small or even medium samples. They can also serve a normative role in test design.

As an alternative to the Rasch model, or the Rasch model with a correction for guessing, a simple model is introduced which characterizes strength of response in terms of the ratio of ability and difficulty parameters rather than their difference. This model provides a natural account of guessing, and has other useful things to contribute as well. It also offers an alternative to the Rasch model with the usual correction for guessing. The three models are compared in terms of statistical properties and fits to actual data. The goal of the paper is to widen the range of “minimal” models available to test analysts.
Tail-Measurability in Monotone Latent Variable Models
Authors: Ellis Jules L. , Junker Brian W.
Published: January 2006

We consider latent variable models for an infinite sequence (or universe) of manifest (observable) variables that may be discrete, continuous or some combination of these. The main theorem is a general characterization by empirical conditions of when it is possible to construct latent variable models that satisfy unidimensionality, monotonicity, conditional independence, and tail-measurability. Tail-measurability means that the latent variable can be estimated consistently from the sequence of manifest variables even though an arbitrary finite subsequence has been removed. The characterizing, necessary and sufficient, conditions that the manifest variables must satisfy for these models are conditional association and vanishing conditional dependence (as one conditions upon successively more other manifest variables). Our main theorem considerably generalizes and sharpens earlier results of Ellis and van den Wollenberg (1993), Holland and Rosenbaum (1986), and Junker (1993). It is also related to the work of Stout (1990).

The main theorem is preceded by many results for latent variable models in general—not necessarily unidimensional and monotone. They pertain to the uniqueness of latent variables and are connected with the conditional independence theorem of Suppes and Zanotti (1981). We discuss new definitions of the concepts of “true-score” and “subpopulation,” which generalize these notions from the “stochastic subject,” “random sampling,” and “domain sampling” formulations of latent variable models (e.g., Holland, 1990; Lord & Novick, 1968). These definitions do not require the a priori specification of a latent variable model.
Techniques for Rotating Two or More Loading Matrices to Optimal Agreement and Simple Structure: A Comparison and Some Technical Details
Authors: Kiers Henk A. L.
Published: January 2006

Matrices of factor loadings are often rotated to simple structure. When more than one loading matrix is available for the same variables, the loading matrices can be compared after rotating them all (separately) to simple structure. An alternative procedure is to rotate them to optimal agreement, and then compare them. In the present paper techniques are described that combine these two procedures. Specifically, five techniques that combine the ideals of rotation to optimal agreement and rotation to simple structure are compared on the basis of contrived and empirical data. For the contrived data, it is assessed to what extent the rotations recover the underlying common structure. For both the contrived and the empirical data it is studied to what extent the techniques give well matching rotated matrices, to what extent these have a simple structure, and to what extent the most prominent parts of the different loading matrices agree. It was found that the simple procedure of combining a Generalized Procrustes Analysis (GPA) with Varimax on the mean of the matched loading matrices performs very well on all criteria, and, for most purposes, offers an attractive compromise of rotation to agreement and simple structure. In addition to this comparison, some technical improvements are proposed for Bloxom's rotation to simple structure and maximum similarity.
Correspondence Analysis and Optimal Structural Representations
Authors: Hubert Lawrence , Arabie Phipps
Published: January 2006

Many well-known measures for the comparison of distinct partitions of the same set of n objects are based on the structure of class overlap presented in the form of a contingency table (e.g., Pearson's chi-square statistic, Rand's measure, or Goodman-Kruskal's τb), but they all can be rephrased through the use of a simple cross-product index defined between the corresponding entries from two n ×n proximity matrices that provide particular a priori (numerical) codings of the within- and between-class relationships for each of the partitions. We consider the task of optimally constructing the proximity matrices characterizing the partitions (under suitable restriction) so as to maximize the cross-product measure, or equivalently, the Pearson correlation between their entries. The major result presented states that within the broad classes of matrices that are either symmetric, skew-symmetric, or completely arbitrary, optimal representations are already derivable from what is given by a simple one-dimensional correspondence analysis solution. Besides severely limiting the type of structures that might be of interest to consider for representing the proximity matrices, this result also implies that correspondence analysis beyond one dimension must always be justified from logical bases other than the optimization of a single correlational relationship between the matrices representing the two partitions.
A Subset Selection Technique for Scoring Items on a Multiple Choice Test
Authors: Gibbons Jean D. , Olkin Ingram , Sobel Milton
Published: January 2006

On a multiple-choice test in which each item has k alternative responses, the test taker is permitted to choose any subset which he believes contains the one correct answer. A scoring system is devised that depends on the size of the subset and on whether or not the correct answer is eliminated. The mean and variance of the score per item are obtained. Methods are derived for determining the total number of items that should be included on the test so that the average score on all items can be regarded as a good measure of the subject's knowledge. Efficiency comparisons between conventional and the subset selection scoring procedures are made. The analogous problem of r > 1 correct answers for each item (with r fixed and known) is also considered.
Tests of Homogeneity of Independent Correlation Coefficients
Authors: Kraemer Helena Chmura
Published: January 2006

It is demonstrated that tests of homogeneity of independent correlation coefficients based on the simple forms of the normal and t approximations to the distribution of the correlation coefficients are comparable in terms of robustness, size and power.
Application of Optimal Sign-Vectors to Reliability and Cluster Analysis
Authors: Woodward J. Arthur , Bentler P. M.
Published: January 2006

Expressions involving optimal sign vectors are derived so as to yield two new applications. First, coefficient alpha for the sign-weighted composite is maximized in analogy to Lord's scale-independent solution with differential weights. Second, optimal sign vectors are used to define two groups of objects that are maximally distinct in terms of a function of the squared euclidean distances between groups. An efficient computing algorithm is described along with several examples.
On Local Influence Analysis of Full Information Item Factor Models
Authors: Lee Sik-Yum , Xu Liang
Published: January 2006

The full information item factor (FIIF) model is very useful for analyzing relations of dichotomous variables. In this article, we present a feasible procedure to assess local influence of minor perturbations for identifying influence aspects of the FIIF model. The development is based on a Q-displacement function which is closely related with the Monte Carlo EM algorithm in the ML estimation. In the E-step of this algorithm, the conditional expectations are approximated by sample means of observations simulated by the Gibbs sampler from the appropriate conditional distributions. It turns out that these observations can be utilized for computing the building blocks of the proposed diagnostic measures. The diagnoses are based on the conformal normal curvature that can be computed easily. A number of interesting perturbation schemes are considered. The methodology is illustrated with two real examples.
Markov Chain Estimation for Test Theory Without An Answer Key
Authors: Karabatsos George , Batchelder William H.
Published: January 2006

This study develops Markov Chain Monte Carlo (MCMC) estimation theory for the General Condorcet Model (GCM), an item response model for dichotomous response data which does not presume the analyst knows the correct answers to the test a priori (answer key). In addition to the answer key, respondent ability, guessing bias, and difficulty parameters are estimated. With respect to data-fit, the study compares between the possible GCM formulations, using MCMC-based methods for model assessment and model selection. Real data applications and a simulation study show that the GCM can accurately reconstruct the answer key from a small number of respondents.
The Dutch Identity: A New Tool for the Study of Item Response Models
Authors: Holland Paul W.
Published: January 2006

The Dutch Identity is a useful way to reexpress the basic equations of item response models that relate the manifest probabilities to the item response functions (IRFs) and the latent trait distribution. The identity may be exploited in several ways. For example: (a) to suggest how item response models behave for large numbers of items—they are approximate submodels of second-order loglinear models for 2J tables; (b) to suggest new ways to assess the dimensionality of the latent trait—principle components analysis of matrices composed of second-order interactions from loglinear models; (c) to give insight into the structure of latent class models; and (d) to illuminate the problem of identifying the IRFs and the latent trait distribution from sample data.
Posterior Probabilities for a Consensus Ordering
Authors: Fligner Michael A. , Verducci Joseph S.
Published: January 2006

In the situation where subjects independently rank order a fixed set of items, the idea of a consensus ordering of the items is defined and employed as a parameter in a class of probability models for rankings. In the context of such models, which generalize those of Mallows, posterior probabilities may be easily formed about the population consensus ordering. An example of rankings obtained by the Graduate Record Examination Board is presented to demonstrate the adequacy of these generalized Mallows' models for describing actual data sets of rankings and to illustrate convenient summaries of the posterior probabilities for the consensus ordering.
A Note on the Unbiased Estimation of the Intraclass Correlation
Authors: Donoghue John R. , Collins Linda M.
Published: January 2006

The intraclass correlation, ρ, is a parameter featured in much psychological research. Two commonly used estimators of ρ, the maximum likelihood and least squares estimators, are known to be negatively biased. Olkin and Pratt (1958) derived the minimum variance unbiased estimator of the intraclass correlation, but use of this estimator has apparently been impeded by the lack of a closed form solution. This note briefly reviews the unbiased estimator and gives a FORTRAN 77 subroutine to calculate it.
Specifying Optimum Examinees for Item Parameter Estimation in Item Response Theory
Authors: Stocking Martha L.
Published: January 2006

Information functions are used to find the optimum ability levels and maximum contributions to information for estimating item parameters in three commonly used logistic item response models. For the three and two parameter logistic models, examinees who contribute maximally to the estimation of item difficulty contribute little to the estimation of item discrimination. This suggests that in applications that depend heavily upon the veracity of individual item parameter estimates (e.g. adaptive testing or text construction), better item calibration results may be obtained (for fixed sample sizes) from examinee calibration samples in which ability is widely dispersed.
The Problem of Local Optimality with OSMOD
Authors: Otsu Tatsuo , Saito Takayuki
Published: January 2006

The possibility of obtaining locally optimal solutions with categorical data is pointed out for the original version of OSMOD development by Saito and Otsu. A revision of the initialization strategy in OSMOD is suggested, and its effectiveness in diminishing this possibility is demonstrated.
Matfit: A Fortran Subroutine for Comparing Two Matrices in a Subspace
Authors: Ramsay J. O.
Published: January 2006

Given two matrices, A and B, each with n rows, and with p and q columns, respectively, a very common goal is the comparison of these matrices in a subspace of dimension s, 1 ≤ s ≤ min p, q. That is, assuming linear mappings of A and B into the subspace, the comparison involves the choice of two transformation matrices L and M of dimensions p by s and q by s, respectively, and the subsequent comparisons of the images AL and BM in some fashion.
A Bayesian Estimation of Factor Score in Confirmatory Factor Model with Polytomous, Censored or Truncated Data
Authors: Shi Jian-Qing , Lee Sik-Yum
Published: January 2006

The posterior analysis in estimating factor score in a confirmatory factor analysis model with polytomous, censored or truncated data is investigated in this paper. For the above three types of data, posterior distributions of the factor score are studied, and the estimators of the factor score are obtained to be the location parameters of the posterior distributions. The accuracy of Bayesian estimates is studied via simulation studies.
The Knowledge Content of Statistical Data
Authors: Preuss Lucien , Vorkauf Helmut
Published: January 2006

An information-theoretic framework is used to analyze the knowledge content in multivariate cross classified data. Several related measures based directly on the information concept are proposed: the knowledge content (S) of a cross classification, its terseness (Zeta), and the separability (GammaX) of one variable, given all others. Exemplary applications are presented which illustrate the solutions obtained where classical analysis is unsatisfactory, such as optimal grouping, the analysis of very skew tables, or the interpretation of well-known paradoxes. Further, the separability suggests a solution for the classic problem of inductive inference which is independent of sample size.
Oblique Factors and Components with Independent Clusters
Authors: Ogasawara Haruhiko
Published: January 2006

Relationships between the results of factor analysis and component analysis are derived when oblique factors have independent clusters with equal variances of unique factors. The factor loadings are analytically shown to be smaller than the corresponding component loadings while the factor correlations are shown to be greater than the corresponding component correlations. The condition for the inequality of the factor/component contributions is derived in the case with different variances for unique factors. Further, the asymptotic standard errors of parameter estimates are obtained for a simplified model with the assumption of multivariate normality, which shows that the component loading estimate is more stable than the corresponding factor loading estimate.
A Generalized Method of Image Analysis from an Intercorrelation Matrix which may be Singular
Authors: Yanai Haruo , Mukherjee Bishwa Nath
Published: January 2006

Following the works of Guttman (1953) and Kaiser (1976), we show that the image and anti-image covariance matrices can be derived from a singular correlation matrix, by making use of the orthogonal projector and a weaker generalized inverse matrix.
A Nonparametric Approach for Assessing Latent Trait Unidimensionality
Authors: Stout William
Published: January 2006

Assuming a nonparametric family of item response theory models, a theory-based procedure for testing the hypothesis of unidimensionality of the latent space is proposed. The asymptotic distribution of the test statistic is derived assuming unidimensionality, thereby establishing an asymptotically valid statistical test of the unidimensionality of the latent trait. Based upon a new notion of dimensionality, the test is shown to have asymptotic power 1. A 6300 trial Monte Carlo study using published item parameter estimates of widely used standardized tests indicates conservative adherence to the nominal level of significance and statistical power averaging 81 out of 100 rejections for examinee sample sizes and psychological test lengths often incurred in practice.
A General Model for Two-Level Data with Responses Missing at Random
Authors: McDonald Roderick P.
Published: January 2006

A general model for two-level multivariate data, with responses possibly missing at random, is described. The model combines regressions on fixed explanatory variables with structured residual covariance matrices. The likelihood function is reduced to a form enabling computational methods for estimating the model to be devised.
Ability Estimation for Conventional Tests
Authors: Kim Jwa K. , Nicewander W. Alan
Published: January 2006

Five different ability estimators—maximum likelihood [MLE (θ)], weighted likelihood [WLE (θ)], Bayesian modal [BME (θ)], expected a posteriori [EAP (θ)] and the standardized number-right score [Z (θ)]—were used as scores for conventional, multiple-choice tests. The bias, standard error and reliability of the five ability estimators were evaluated using Monte Carlo estimates of the unknown conditional means and variances of the estimators. The results indicated that ability estimates based on BME (θ), EAP (θ) or WLE (θ) were reasonably unbiased for the range of abilities corresponding to the difficulty of a test, and that their standard errors were relatively small. Also, they were as reliable as the old standby—the number-right score.
A Variable-Selection Heuristic for K-means Clustering
Authors: Brusco Michael J. , Cradit J. Dennis
Published: January 2006

One of the most vexing problems in cluster analysis is the selection and/or weighting of variables in order to include those that truly define cluster structure, while eliminating those that might mask such structure. This paper presents a variable-selection heuristic for nonhierarchical (K-means) cluster analysis based on the adjusted Rand index for measuring cluster recovery. The heuristic was subjected to Monte Carlo testing across more than 2200 datasets with known cluster structure. The results indicate the heuristic is extremely effective at eliminating masking variables. A cluster analysis of real-world financial services data revealed that using the variable-selection heuristic prior to the K-means algorithm resulted in greater cluster stability.
Loglinear Multidimensional IRT Models for Polytomously Scored Items
Authors: Kelderman Henk , Rijkes Carl P. M.
Published: January 2006

A loglinear IRT model is proposed that relates polytomously scored item responses to a multidimensional latent space. The analyst may specify a response function for each response, indicating which latent abilities are necessary to arrive at that response. Each item may have a different number of response categories, so that free response items are more easily analyzed. Conditional maximum likelihood estimates are derived and the models may be tested generally or against alternative loglinear IRT models.
Modeling Item Responses When Different Subjects Employ Different Solution Strategies
Authors: Mislevy Robert J. , Verhelst Norman
Published: January 2006

A model is presented for item responses when different subjects employ different strategies, but only responses, not choice of strategy, can be observed. Using substantive theory to differentiate the likelihoods of response vectors under a fixed set of strategies, we model response probabilities in terms of item parameters for each strategy, proportions of subjects employing each strategy, and distributions of subject proficiency within strategies. The probabilities that an individual subject employed the various strategies can then be obtained, along with a conditional estimate of proficiency under each. A conceptual example discusses response strategies for spatial rotation tasks, and a numerican example resolves a population of subjects into subpopulations of valid responders and random guessers.
On the Large Sample Distributions of Modified Sample Biserial Correlation Coefficients
Authors: Bedrick Edward J.
Published: January 2006

The asymptotic distributions of Brogden's and Lord's modified sample biserial correlation coefficients are derived. The asymptotic variances of these estimators are evaluated for bivariate normal populations and compared to the asymptotic variance of the maximum likelihood estimator.
The Direct Product Model for the Mtmm Matrix Parameterized as a Second Order Factor Analysis Model
Authors: Wothke Werner , Browne Michael W.
Published: January 2006

The composite direct product model for the multitrait-multimethod matrix is reparameterized as a second-order factor analysis model. This facilitates the use of widely available computer programs such as LISREL and LISCOMP for fitting the model.
Some Properties of Estimated Scale Invariant Covariance Structures
Authors: Dijkstra T. K.
Published: January 2006

Scale invariance is a property shared by many covariance structure models employed in practice. An example is provided by the well-known LISREL model subject only to classical normalizations and zero constraints on the parameters. It is shown that scale invariance implies that the estimated covariance matrix must satisfy certain equations, and the nature of these equations depends on the fitting function used. In this context, the paper considers two classes of fitting functions: weighted least squares and the class of functions proposed by Swain.
Multivariate Thurstonian Models
Authors: Böckenholt Ulf
Published: January 2006

The recent development of probabilistic Thurstonian choice models for analyzing preference data has been motivated by the need to describe both inter- and intra-individual difference, the multidimensional nature of choice objects, and the effects of similarity and comparability among choice objects. A common feature of these models is that they focus on a single preference judgment. It is customary, however, to ask subjects not only for an overall preference judgment but also for additional paired comparison responses regarding specific attributes. This paper proposes a generalization of Thurstonian probabilistic choice models for analyzing both multiple preference responses and their relationships. The approach is illustrated by modeling data from two multivariate preference experiments.
Reliability as a Function of the Number of Item Options Derived from the “Knowledge or Random Guessing” Model
Authors: MacCann Robert G.
Published: January 2006

For (0, 1) scored multiple-choice tests, a formula giving test reliability as a function of the number of item options is derived, assuming the “knowledge or random guessing model,” the parallelism of the new and old tests (apart from the guessing probability), and the assumptions of classical test theory. It is shown that the formula is a more general case of an equation by Lord, and reduces to Lord's equation if the items are effectively parallel. Further, the formula is shown to be closely related to another formula derived from Lord's randomly parallel tests model.
Generalized Multilevel Structural Equation Modeling
Authors: Rabe-Hesketh Sophia , Skrondal Anders , Pickles Andrew
Published: January 2006

A unifying framework for generalized multilevel structural equation modeling is introduced. The models in the framework, called generalized linear latent and mixed models (GLLAMM), combine features of generalized linear mixed models (GLMM) and structural equation models (SEM) and consist of a response model and a structural model for the latent variables. The response model generalizes GLMMs to incorporate factor structures in addition to random intercepts and coefficients. As in GLMMs, the data can have an arbitrary number of levels and can be highly unbalanced with different numbers of lower-level units in the higher-level units and missing data. A wide range of response processes can be modeled including ordered and unordered categorical responses, counts, and responses of mixed types. The structural model is similar to the structural part of a SEM except that it may include latent and observed variables varying at different levels. For example, unit-level latent variables (factors or random coefficients) can be regressed on cluster-level latent variables. Special cases of this framework are explored and data from the British Social Attitudes Survey are used for illustration. Maximum likelihood estimation and empirical Bayes latent score prediction within the GLLAMM framework can be performed using adaptive quadrature in gllamm, a freely available program running in Stata.
Seeing the Fisher Z-transformation
Authors: Bond Charles F. , Richardson Ken
Published: January 2006

Since 1915, statisticians have been applying Fisher's Z-transformation to Pearson product-moment correlation coefficients. We offer new geometric interpretations of this transformation.
Remarks on “Equivalent Linear Logistic Test Models” by Bechger, Verstralen, and Verhelst (2002)
Authors: Fischer Gerhard H.
Published: January 2006

This paper discusses a new form of specifying and normalizing a Linear Logistic Test Model (LLTM) as suggested by Bechger, Verstralen, and Verhelst (Psychometrika, 2002). It is shown that there are infinitely many ways to specify the same normalization. Moreover, the relationship between some of their results and equivalent previous results in the literature is clarified, and it is shown that the goals of estimating and testing a single element of the weight matrix, for which they propose new methods, can be reached by means of simple, well-known tools already implemented in published LLTM software.
False‐positive results in neonatal screening for cystic fibrosis based on a three‐stage protocol (IRT/DNA/IRT): Should we adjust IRT cut‐off to ethnic origin?
Authors: Cheillan D. , Vercherat M. , Chevalier‐Porst F. , Charcosset M. , Rolland M. O. , Dorche C.
Published: January 2006

Since 1979, newborn screening for cystic fibrosis (CF) has been possible by measuring immunoreactive tryspinogen (IRT) in blood spots. In France, a programme based on a three‐stage strategy (IRT/DNA/IRT) started in 2002. In the Rhône‐Alpes area, the positive screening rate (i.e. the proportion of samples sent for genotyping) observed after the first IRT measurement was higher than the expected rate (0.65% versus 0.50%), without a greater CF incidence. We hypothesized that the IRT reference range could differ according to the ethnic origin of the newborns. 35 141 newborns were studied and divided into two groups: European ethnic group 26 324 (75%) and North African ethnic group 8817 (25%). 243 positive newborns were identified: 146 (60%) in the European ethnic group and 97 (40%) in the North African ethnic group. Three CF patients and 11 unaffected heterozygotes were found in the European group, but no mutations were found in the North African group. Mean IRT values and the percentage of IRT values over the cut‐off were significantly higher in the North African group than in the European group (mean IRT = 21.17 μg/L and 19.74 μg/L, p < 0.0001; %IRT > cut‐off = 1.1% and 0.5%, respectively). For the positive screened newborns, term and IRT mean were comparable, whereas birth weight was higher in the North African ethnic group. These results lead us to conclude that (i) newborns from families of North African origin have higher IRT values and (ii) most of the positive screened newborns in this population could be considered as ‘false positives’. These conclusions could explain, in part, the large variations seen in the positive screening rate in the French CF neonatal screening and raise the question whether it is relevant to adapt cut‐off to ethnic origin of the newborns.
Identification of a common novel mutation in Saudi patients with argininosuccinic aciduria
Authors: Al‐Sayed M. , AlAhmed S. , Alsmadi O. , Khalil H. , Rashed M. S. , Imtiaz F. , Meyer B. F.
Published: January 2006

We have identified a common novel mutation (Q354X) in the argininosuccinate lyase (ASL) gene in Saudi patients with argininosuccinic aciduria (ASAuria; McKusick 207900). The two index patients were siblings, had a neonatal onset of the disease and were diagnosed based on the clinical presentation and confirmed by analysis of their dried blood spots (DBS) by tandem mass spectrometry (MS/MS). The ASL gene was then analysed by direct sequencing. A further 28 patients with a confirmed diagnosis of ASAuria based on MS/MS of their DBS were tested by sequencing for the presence of the Q354X mutation. This mutation was found in 14 out of the 28 patients (50%) tested. Our work indicates that the Q354X allele is common, may account for 50% of the abnormal ASL genes in the Saudi population, and is likely to be associated with the neonatal form of the disease. We recommend that all patients diagnosed with ASAuria in Saudi Arabia or of Arab origin be tested for this mutation and for Q116X, which has been described previously. In addition, further analysis is needed to identify other underlying disease mutations for ASAuria in the Saudi population.
Search for mutations in SLC1A5 (19q13) in cystinuria patients
Authors: Brauers E. , Vester U. , Zerres K. , Eggermann T.
Published: January 2006

To elucidate whether SLC1A5 is involved in the aetiology of cystinuria, we screened two non‐type I cystinuria families without detectable mutations inSLC7A9 (and SLC3A1) but compatible with linkage to 19q13 for genomic variants in SLC1A5. Despite evidence for an involvement of SLC1A5 in the aetiology of cystinuria, we could not identify any mutation in this gene in the two families. With SLC1A5, a further candidate gene for cystinuria can be excluded as being involved in the pathogenesis of this disease in these two families. Of course, there remains the possibility that other genes are involved in cystinuria; further molecular studies will clarify the complex nature of this disorder.
Genetic variants of transferrin in the diagnosis of protein hypoglycosylation
Authors: Albahri Z. , Marklová E. , Vaníček H. , Minxová L. , Dédek P. , Skálová S.
Published: January 2006

Human transferrin (Tf) shows genetic polymorphisms, which may interfere in the screening of congenital disorders of glycosylation (CDG). Isoelectric focusing followed by direct immunofixation was used for Tf analysis in controls and several groups of patients. Equivocal results in one case have been recognized as a rare Tf CD variant. A higher incidence of some genetic variants has been reported in connection with certain diseases; of the seven Tf phenotypes detected in our set of samples, an apparently higher frequency of Tf C1C2 variant found in some groups of patients was not significant.
Kinetic characterization of human hydroxyacid–oxoacid transhydrogenase: Relevance toD‐2‐hydroxyglutaric and γ‐hydroxybutyric acidurias
Authors: Struys E. A. , Verhoeven N. M. , Ten Brink H. J. , Wickenhagen W. V. , Gibson K. M. , Jakobs C.
Published: January 2006

We investigated the presence of hydroxyacid–oxoacid transhydrogenase (HOT), which catalyses the cofactor‐independent conversion of γ‐hydroxybutyrate (GHB) to succinic semialdehyde coupled to reduction of 2‐ketoglutarate (2‐KG) to D‐2‐hydroxyglutarate (D‐2‐HG), in human liver extracts employing [2H6]GHB and 2‐KG as substrates. We measured incorporation of 2H in D‐[2H]2‐HG using GC‐MS analyses, providing evidence for HOT activity in humans. Kinetic characterization of HOT was undertaken in forward and reverse directions. We employed [2H6]GHB and [2H4]2‐KG as cosubstrates in order to develop a HOT activity assay in cultured human fibroblasts derived from patients with D‐2‐hydroxyglutaric aciduria. HOT activity was quantified in this system by the measurement of D‐[2H5]2‐HG production. Fibroblasts derived from patients with D‐2‐hydroxyglutaric aciduria showed normal HOT activities. Our results provide the first demonstration and preliminary kinetic characterization of HOT activity in human tissues.
Increased HVA detected on organic acid analysis in a patient with Costello syndrome
Authors: Bowron A. , Scott J. G. , Brewer C. , Weir P.
Published: January 2006

Urine organic acid analysis is routinely performed to investigate inborn errors of metbolism; however, interpretation can be difficult owing to the detection of compounds derived from other disease states or from nonpathological causes. We describe the finding of elevated homovanillc acid (HVA) on urine organic acid analysis which was not associated with medication or a neuroendocrine tumour but with Costello syndrome.
First‐trimester enzymatic and molecular prenatal diagnosis of mevalonic aciduria
Authors: Rolland M. O. , Cuisset L. , Le Bozec J. , Guffon N. , VianeySaban C.
Published: January 2006

Prenatal diagnosis was offered to a family at risk of mevalonic aciduria. A chorionic villus sample was obtained and both mevalonate kinase activity and mutation analysis were done. An affected fetus was diagnosed.
Effect of copper and diethyldithiocarbamate combination therapy on the macular mouse, an animal model of Menkes disease
Authors: Kodama H. , Sato E. , Gu Y.‐H. , Shiga K. , Fujisawa C. , Kozuma T.
Published: January 2006

Menkes disease (MD) is a neurodegenerative disorder characterized by a copper deficiency in the brain. It is caused by the defective intestinal absorption of copper resulting from a deficiency of a copper‐transporting ATPase, ATP7A. This gives rise to an accumulation of copper in the intestine. The copper deficiency in the brain of MD patients cannot be improved by copper injections, because the administered copper accumulates at the blood–brain barrier and is not transported across to the neurons. To resolve this problem, we investigated the effect of a combination therapy of copper and sodium diethyldithiocarbamate (DEDTC), a lypophilic chelator, in an animal model of MD, the macular mouse. Four‐week‐old macular mice treated with 50 μg of CuCl2 on the 7th day after birth were used. Experimental mice were given a subcutaneous injection of CuCl2 (4 μg) and an intraperitoneal injection of DEDTC (0.2 mg/g body weight) twice a week for 4 weeks and then sacrificed. Copper concentrations and cytochrome‐c oxidase activity in the brains of treated mice were higher than those of control macular mice, which received only copper or saline. The ratios of brain noradrenaline to dopamine and of adrenaline to dopamine were also increased by the treatment, suggesting that the activity of dopamine β‐hydroxylase, a copper‐dependent enzyme, was improved by the treatment. Liver and renal function tests showed no abnormalities in the treated mice, although copper concentrations in the kidneys of treated mice were higher than those of control macular mice. These results suggest that DEDTC facilitates the passage of copper across the blood–brain barrier and that the combination therapy of copper and DEDTC may be an effective treatment for the neurological disturbances suffered by patients with MD.
Predicting the phenylalanine blood concentration from urine analyses. An approach to noninvasive monitoring of patients with phenylketonuria
Authors: Langenbeck U. , Baum F. , Mench‐Hoinowski A. , Luthe H. , Behbehani A. W.
Published: January 2006

The need for regular blood‐drawing in the management of chronic metabolic disorders may negatively influence the compliance of patients and their parents; noninvasive analytical procedures could well alleviate this burden. Using data obtained in six adult probands with phenylketonuria, we evaluate the feasibility of noninvasive prediction of phenylalanine blood concentrations from analysis of phenylalanine and creatinine in urine. Cross‐validated regression equations correct for the significant inter‐individual variation of phenylalanine fractional excretion rates. With sensitive and specific enzymatic assays for phenylalanine and creatinine, the accuracy of this noninvasive procedure may also become clinically satisfactory for the purpose of self‐monitoring.
Mutation detection in four candidate genes (OXA1L, MRS2L, YME1L and MIPEP) for combined deficiencies in the oxidative phosphorylation system
Authors: Coenen M. J. H. , Smeitink J. A. M. , Smeets R. , Trijbels F. J. M. , van den Heuvel L. P.
Published: January 2006

Mitochondria are the main energy‐producing organelles of the cell. Five complexes embedded in the mitochondrial inner membrane, together constituting the oxidative phosphorylation (OXPHOS) system, comprise the final steps in cellular energy production. Many patients with a mitochondrial defect suffer from a so‐called combined deficiency, meaning that the enzymatic activities of two or more complexes of the OXPHOS system are decreased. Numerous mutations have been described in nuclear genes that are involved in the functioning of a single complex of the OXPHOS system. However, little attention has been paid to patients with a deficiency of more than one complex of this particular system. In this study we have investigated four nuclear genes (OXA1L, MRS2L, YME1L and MIPEP) that might be involved in the pathology of combined enzymatic deficiencies of the OXPHOS system. Based on the results of yeast knockouts of these four proteins, we have sequenced the open reading frame of OXA1L in eight patients with an enzymatic deficiency of complexes I and IV. MRS2L, YME1L and MIPEP have been sequenced in three patients with a combined defect of complexes III and IV. No mutations were detected in these patients, showing that at least in these patients the OXPHOS system deficiency cannot be explained by a mutation in these four genes.
Pulmonary hypertension—A new manifestation of mitochondrial disease
Authors: Barclay A. R. , Sholler G. , Christodolou J. , Shun A. , Arbuckle S. , Dorney S. , Stormon M. O.
Published: January 2006

Mitochondrial respiratory chain (RC) abnormalities in children can present as multiorgan disease, including liver failure, usually within the first year of life. Cardiorespiratory complications have previously been described in association with RC defects; however, to our knowledge no cases of pulmonary hypertension have been described. We discuss two patients with proven mitochondrial RC liver disease who developed severe pulmonary hypertension, one subsequent to cadaveric orthotopic liver transplantation, the second in the neonatal period. It is our contention that pulmonary hypertension should now be included as another potential manifestation of paediatric mitochondrial disease.
Isolation and identification of some major peptides in the ethanol-soluble fraction of the pH 4·6-soluble extract from Manchego cheese
Authors: Poveda Justa M , Cabezas Lourdes , Geary Sinéad , McSweeney Paul LH
Published: January 2006

Proteolysis is one of the major biochemical events which takes place during cheese ripening and its degradation products, amino acids and peptides, have a considerable influence on the sensory characteristics of cheese (Urbach, 1993). Primary proteolysis leads to the formation of large water-insoluble peptides and smaller water-soluble peptides. Several peptides from bovine milk cheeses have been isolated and identified, particularly from Cheddar cheese (e.g., McSweeney et al. 1994; Singh et al. 1994, 1995, 1997; Gouldsworthy et al. 1996; Fernández et al. 1998). However, there are few data available on the identification of peptides from ewes’ milk cheeses, although Michaelidou et al. (1998) identified some major peptides in the water-soluble fraction of Feta cheese (ewe's milk cheese).
Long‐term stratospheric carbon tetrafluoride (CF4) increase inferred from 1985–2004 infrared space‐based solar occultation measurements
Authors: Rinsland C. P. , Mahieu E. , Zander R. , Nassar R. , Bernath P. , Boone C. , Chiou L. S.
Published: January 2006

The long‐term stratospheric carbon tetrafluoride (CF4) increase has been determined from infrared high spectral resolution solar occultation Fourier transform spectrometer measurements between 3 and 50 hPa (∼20 to 40 km altitude) and latitudes from 50°N to 50°S during 1985, 1992, 1993, 1994, and 2004. The 1985 to 1994 measurements were recorded from the ATMOS (Atmospheric Trace MOlecule Spectroscopy) instrument at 0.01 cm−1 resolution and in 2004 by the Atmospheric Chemistry Experiment (ACE) instrument at 0.02 cm−1 resolution. Stratospheric volume mixing ratios, inferred from a polynomial fit to averages from the time periods considered here, increased from 49.37 ± 2.60 pptv (10−12 per unit volume) in 1985 to 58.38 ± 4.14 pptv in 1992, 60.46 ± 2.97 pptv in 1993, 60.11 ± 3.60 pptv in 1994 and to 70.45 ± 3.40 pptv in 2004. The stratospheric CF4 mixing ratio has continued to increase but at a slower rate than in previous years, for example, (1.14 ± 0.68)% yr−1 in 2004 as compared to (2.77 ± 0.47)% yr−1 in 1985, 1 sigma. Correlations of CF4 with N2O taking into account the increase of N2O with time also show the increase in the stratospheric CF4 burden over the two decade measurement time span. Our space‐based measurements show that the slowdown in the rate of CF4 accumulation previously reported from surface measurements through 1997 has propagated to the stratosphere and is continuing.
Coseismic versus interseismic ground deformations, fault rupture inversion and segmentation revealed by 2003 Mw 6.8 Chengkung earthquake in eastern Taiwan
Authors: Wu Y. M. , Chen Y. G. , Shin T. C. , Kuochen H. , Hou C. S. , Hu J. C. , Chang C. H. , Wu C. F. , Teng T. L.
Published: January 2006

The 2003 Chengkung earthquake (Mw 6.8) provided diagnostic evidence for a source model showing the deformation process of the seismogenic Chihshang fault in eastern Taiwan. The aftershocks show a fault‐bend at a depth of 18 km. Coseismic ground displacements recorded by strong‐motion records allow us to deduce instant rupturing of this event. Our resulting model shows a fault length of ∼33 km and dip‐slip dominant rupture on fault‐plane deeper than 18 km. Estimated coseismic displacements constrain two fault planes: one at 5–18 km depth dipping 60°E and 18–36 km depth dipping 45°E. The uppermost fault‐plane of the Chihshang Fault (0–5 km) did not break immediately after the main shock; however, it may have a major role in after‐slip and even interseismic ground deformation. The Taiyuan basin developed in the hanging wall is a geomorphic feature consistent with and adequately explained by coseismic ground displacements.
A physical mechanism for North Atlantic SST influence on the Indian summer monsoon
Authors: Goswami B. N. , Madhusoodanan M. S. , Neema C. P. , Sengupta D.
Published: January 2006

A link between the Atlantic Multidecadal Oscillation (AMO) and multidecadal variability of the Indian summer monsoon rainfall is unraveled and a long sought physical mechanism linking Atlantic climate and monsoon has been identified. The AMO produces persistent weakening (strengthening) of the meridional gradient of tropospheric temperature (TT) by setting up negative (positive) TT anomaly over Eurasia during northern late summer/autumn resulting in early (late) withdrawal of the south west monsoon and persistent decrease (increase) of seasonal monsoon rainfall. On inter–annual time scales, strong North Atlantic Oscillation (NAO) or North Annular mode (NAM) influences the monsoon by producing similar TT anomaly over Eurasia. The AMO achieves the interdecadal modulation of the monsoon by modulating the frequency of occurrence of strong NAO/NAM events. This mechanism also provides a basis for explaining the observed teleconnection between North Atlantic temperature and the Asian monsoon in paleoclimatic proxies.