bluuebunny/crossref_metadata_2025 huggingface dataset:
Failure Mode Identification through Clustering Analysis
Authors: Arunajadai Srikesh G. , Uder Scott J. , Stone Robert B. , Tumer Irem Y.
Published: July 2004

Research has shown that nearly 80% of the costs and problems associated with product design are created during product development, and cost and quality are essentially designed into products during the conceptual design stage. Failure identification procedures (such as failure modes and effects analysis (FMEA), failure modes, effects and criticality analysis (FMECA) and fault tree analysis (FTA)) and design of experiments are currently being used for both quality control and for the detection of potential failure modes during the design stage or post‐product launch. Although all of these methods have their own advantages, they do not provide the designer with an indication of the predominant failures that should receive considerable attention while the product is being designed. The work presented here proposes a statistical clustering procedure to identify potential failures in the conceptual design stage. A functional approach, which hypothesizes that similarities exist between different failure modes based on the functionality of the product/component, is employed to identify failure modes. The various steps of the methodology are illustrated using a hypothetical design example. Copyright © 2004 John Wiley & Sons, Ltd.
Synthetic Approaches Towards Quinazolines, Quinazolinones and Quinazolinediones on Solid Phase
Authors: Vögtle Markus M. , Marzinzik Andreas L.
Published: July 2004

Quinazolines are a pharmacologically very attractive class of compounds and have shown activity in various assays. Several successfully launched drugs are based on this scaffold. As a consequence, a more intensive exploitation in drug discovery by solid‐phase syntheses of quinazoline libraries has been initiated. A diverse array of combinatorial quinazoline syntheses have been published and an increasing effort is to be expected in the near future to provide more efficient solid phase approaches towards quinazolines, quinazolinones and quinazolinediones. This review summarizes the literature published until January 2004 describing methods for synthesis and modification of these compounds on solid phase.
Classical QSAR Modeling of CCR5 Receptor Binding Affinity of Substituted Benzylpyrazoles
Authors: Leonard J. Thomas , Roy Kunal
Published: July 2004

CCR5 receptor binding affinity of a series of substituted benzylpyrazole derivatives was subjected to QSAR study using Fujita‐Ban type analysis and a mixed approach based on Hansch and Fujita‐Ban analyses. Apart from appropriate indicator variables encoding different group contributions, different physicochemical variables like hydrophobicity (π), electronic (Hammett σ) and steric (molar refractivity, STERIMOL values) parameters of phenyl ring substituents of the benzyl moiety of the compounds were used as predictor variables. Additionally, Wang‐Ford charges of the common atoms of the compounds calculated from molecular electrostatic potential surface of AM1 optimized geometries of the compounds and various topological parameters were used as additional descriptors. The variables for the multiple regression analyses were selected based on principal component factor analysis and generated equations were statistically validated using leave‐one‐out technique and predicting the binding affinities of test set compounds. The analysis explores the substitutional requirements of the phenyl nucleus of the benzylpyrazole moiety of the compounds for effective binding with CCR5 receptor.
Quantitative Structure–Micellization Relationship Study of Gemini Surfactants Using Genetic‐PLS and Genetic‐MLR
Authors: Absalan G. , Hemmateenejad B. , Soleimani M. , Akhond M. , Miri R.
Published: July 2004

A Quantitative structure‐property relationship analysis had been applied to a set of gemini surfactants which were of special interest because of their roles in environmental samples. Modeling of the critical micelle concentrations (CMC) of 94 gemini surfactants as a function of their theoretically‐derived descriptors (i.e. topological indices) was established by means of multiple linear regression (MLR) and partial least squares (PLS) regression methods. The genetic algorithm was used to find a set of descriptors that resulted in the best‐fitted models. The results showed that both MLR (with 9 selected descriptors) and PLS (with 20 selected descriptors) methods could model the relationship between CMC of gemini surfactants and their topological descriptors perfectly. However, better results obtained by PLS regression. The stability and validity of models were tested by cross‐validation technique and by prediction of the response values for the prediction set. The average relative error of prediction for the best MLR and PLS models, was equal to 2.94 and 0.36, respectively. Also, the respective squares of correlation coefficients of these models were 0.979 and 0.985.
Quantitative Structure‐Activity Relationships of Streptococcus pneumoniae MurD Transition State Analogue Inhibitors
Authors: Kotnik Miha , Oblak Marko , Humljan Jan , Gobec Stanislav , Urleb Uros , Solmajer Tom
Published: July 2004

Quantitative structure‐activity relationship (QSAR) studies on a set of Streptococcus pneumoniae MurD transition‐state inhibitors were performed, using a comprehensive set of molecular descriptors calculated by CODESSA software. Multiple and best multiple linear regressions were applied to generate models for predicting their inhibitory activity. The results (the best model had r2 = 0.8818, s2 = 0.0749, F = 87.04 and r$\rm{ {_{cv}^{2}}}$=0.8488) demonstrate the importance of hydrogen bonding and that a matching conformation of ligands for interaction with the enzyme active site is required.
Impact of neglecting p‐type spin–orbit coupling during electronic structure calculations on solids
Authors: Boettger Jonathan C.
Published: July 2004

Fully relativistic density functional theory electronic structure calculations for crystalline solids have become nearly commonplace. It has been demonstrated, however, that two of the more common methods used for such calculations produce spin–orbit coupling energies for p‐type orbitals that are numerically unstable. The source of the instability and methods for its mitigation are discussed here. In particular, a stabilization strategy suggested by Söderlind, the complete neglect of p‐type spin–orbit coupling, is tested for a prototypical p‐bonded metal, Pb, using the linear combinations of Gaussian‐type orbitals–fitting function method. The zero‐pressure lattice constant and bulk modulus are both insensitive to the p‐type spin–orbit coupling. The density of states and the fcc‐bcc structural energy difference, however, are shown to be significantly affected by p‐type spin–orbit coupling. The complete neglect of p‐type spin–orbit coupling approximation should not be used to determine structural phase transition pressures for materials in which the bonding has a strong p character. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Spectroscopic constants of H2 using Monte Carlo methods
Authors: Alexander S. A. , Coldwell R. L.
Published: July 2004

We have computed the spectroscopic constants we, wexe, αe, and Be of the ground state of H2 using two methods. In the first method, a highly accurate potential energy surface was generated using explicitly correlated wave functions and variational Monte Carlo techniques. We calculated the vibrational‐rotational energies from this surface and then obtained the spectroscopic constants by fitting these energies to a simple equation. In the second method, the spectroscopic constants were determined from local derivatives of the energy with respect to the internuclear distance. These derivatives have also been calculated using variational Monte Carlo techniques. For this system we find that the first method yields spectroscopic constants that are in excellent agreement with experiment. We also find that the second method, although slightly less accurate, is extremely well suited to Monte Carlo calculations. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Wave‐function‐based ab initio correlation treatment for the buckminsterfullerene C60
Authors: Paulus Beate
Published: July 2004

First‐principle calculations for large extended systems such as the buckminsterfullerene C60 are mainly performed within density functional theory. They yield reasonable agreement with experiment, but wave‐function‐based correlations methods are preferable to obtain better insight into the correlation properties. Starting from a Hartree–Fock calculation for the solid, an incremental scheme relying on localized orbitals is developed for the correlation energy of C60. This many‐body expansion converges well with distance of localized bonds involved in the correlation methods and with order of increments. A detailed knowledge of the influence of the correlation effects on the binding and the bond alternation is achieved. Comparison with diamond, graphite, and polyacetylene is made. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
New methods for old Coulomb few‐body problems
Authors: Harris Frank E. , Frolov Alexei M. , Smith Vedene H.
Published: July 2004

Coulomb problems involving three or four particles can advantageously be described using wavefunctions that explicitly involve all the interparticle distances. In what is known as the Hylleraas method, a set of Slater‐type orbitals for the electrons of an atom is augmented by linear (or in some cases higher powers) of the interelectron separation(s). An alternative approach, of particular value when all the particles have comparable masses, is to use a wavefunction containing exponentials in all the interparticle distances. This “exponential ansatz” is straightforward to implement when there are three particles but has only recently been implemented for four‐body systems. Integral evaluation is reviewed for both the exponential ansatz and the Hylleraas method, the treatment of general angular symmetry is discussed, and kinetic‐energy matrix elements are examined and related to simpler integrals. Some illustrative results for the positronium molecule (e+e−e+e−) are included. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Deductive molecular mechanics of sp3 nitrogen atom and its application to analysis of a QM/MM interface
Authors: Tchougréeff A. L. , Tokmachev A. M.
Published: July 2004

The antisymmetrized product of strictly localized geminals (APSLG) wave function is used to construct a mechanistic picture for the sp3 nitrogen atom. We previously showed 18 that the classical force fields for the sp3 carbon atom can be sequentially derived from the APSLG‐MINDO/3 method. Here we try to extend this approach. Special attention is given to the hybridization pattern for the nitrogen atom. Interpolation formulae for the inversion potential are obtained and the role of different physical contributions to the local geometry structure around nitrogen is elucidated. The results obtained are applied to construction of the junction in QM/MM hybrid procedures when a lone pair is assigned to the QM subsystem while three covalent bonds are considered to be a part of the MM subsystem. Changes in the hybridization due to QM/MM boundary are considered as a source of modification of the QM lone‐pair characteristic as well as of that of the MM force fields. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Formulation and numerical approach to molecular systems by the Green function method without Born–Oppenheimer approximation II: Nucleus–electron correlation
Authors: Ito T. , Yoshimoto T. , Ohta Y. , Kawabe H. , Nagao H. , Nishikawa K.
Published: July 2004

We present a nucleus–electron gas model to estimate the nucleus–electron correlation energy. The expression of the effective interaction between nucleus and electron in the framework of the random‐phase approximation is derived. We find that the attractive interaction between nucleus and electron can be shielded. The expression of the perturbation energy within the ladder approximation is also derived by some simplicities. We present a numerical procedure to calculate the correlation energy and the correlation potential between nucleus and electron and estimate the nucleus–electron correlation potential. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Application of spectral intensities through a model potential approach to the prediction of photodissociation rate constants of CFC molecules in the ionosphere
Authors: Martín I. , Mayor E. , Velasco A. M.
Published: July 2004

Absorption of high‐frequency radiation by chlorofluorocarbon (CFC) compounds in the ionosphere leads to their photoionization and photodissociation. Rydberg states are known to play an essential role in the initiation of photochemical processes. The photoabsorption intensities in both bound and continuous spectral regions, through all the allowed Rydberg channels, of two Freon molecules, have been first calculated. Then, through the use of the intensity data, photolysis rate constants corresponding to dissociation pathways in zones E and D of the ionosphere have been determined. An extension of the molecular quantum defect orbital approach has been used to supply these rate constants for the first time. Neither previous measurements nor theoretical calculations on these properties have, to our knowledge, been reported. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Balancing economic considerations and the rights of indigenous people. The Mapuche people of Chile
Authors: Newbold Jane
Published: July 2004

Natural resources, principally minerals, agriculture and forestry, underpin the economic achievements of Chile. As a consequence of this, successive governments have had to develop policies that encourage growth while protecting the country's resources, heritage and biodiversity. A major challenge has been to redress historical injustices perpetrated against indigenous people plus resolving present day conflicts between these people and encroaching industries, particularly from the forestry and energy sectors. A balance is needed between the price paid for economic advancement and the destruction of indigenous people's cultural heritage. Conflicting government legislation has complicated the situation. Copyright © 2004 John Wiley & Sons, Ltd and ERP Environment.
X‐ray photoelectron microscopic imaging of the chemical bonding state of Si in a rock sample
Authors: Seyama H. , Wang D. , Soma M.
Published: July 2004

A microscopic surface analytical technique is desirable for detailed studies of environmental and geochemical surface processes because most of the relevant solid components from natural sources are heterogeneous and have intricate microstructures. Recent advances in XPS instrumentation have allowed chemical mapping of surfaces. This paper demonstrates the imaging of the chemical bonding state of Si in a rock sample (granodiorite) by X‐ray photoelectron microscopy. An Si 2p photoelectron image of the granodiorite was acquired from the boundary between the quartz and biotite phases, and the image was deconvoluted into quartz and biotite components on the basis of the difference (chemical shift) between the Si 2p binding energies of the two minerals. The two phases were clearly distinguishable in the chemical‐bonding‐state images for Si. Copyright © 2004 John Wiley & Sons, Ltd.
In situ UV–visible and IR absorption study of the aggregation of silver colloidal particles via chemisorption of octadecanethiol
Authors: Wadayama T. , Yano H. , Sasaki Y. , Takahashi J. , Hatta A.
Published: July 2004

Aggregation of silver colloidal particles in the hydrosol via chemisorption of octadecanethiol (ODT) molecules was investigated based on in situ UV–visible transmission and infrared attenuated total reflection (ATR) measurements. As‐prepared silver hydrosol exhibits a single absorption peak at 395 nm because of the plasma resonance of the metal particles. Upon addition of ODT‐dissolved ethanol to the hydrosol, the resonance band red‐shifts and broadens, the detailed features of which depend on the ODT concentration and elapsed time. Both the red‐shift and the broadening are attributed to particle aggregation in the solution via ODT chemisorption. Aggregation on a germanium prism surface by the addition of ODT‐dissolved ethanol to the hydrosol was investigated using infrared ATR spectroscopy. At moderate ODT concentrations, intense aggregation via ODT chemisorption occurs strongly on the prism surface, allowing observation of ODT absorption bands. Angle‐dependent infrared ATR measurements for the ethanol and ODT molecules at the prism/solution interface clearly show that aggregation on the prism surface proceeds via the exclusion of ethanol. Copyright © 2004 John Wiley & Sons, Ltd.
XPS analysis with external bias: a simple method for probing differential charging
Authors: Ertas Gulay , Suzer Sefik
Published: July 2004

The XPS spectra of thermally grown oxide layers on Si, Al, W and Hf substrates have been recorded while the samples were subjected to external d.c. voltage bias. The bias induces additional shifts in the measured binding energy differences between the XPS peaks of the oxide and that of the metal substrate in Si and Al (as probed both in the 2p and the KLL Auger regions), but not in W and Hf (as probed in the 4f region). These bias induced shifts are attributed to differential charging between the oxide layer and the substrate, which in turn is postulated to be related to the capacitance and inversely to the dielectric constant of the oxide layer. Accordingly, silicon dioxide with the smallest dielectric constant undergoes the largest differential charging, aluminium oxide is in the middle and no appreciable charging can be induced in the high‐k tungsten and hafnium oxides, all of which are ∼6 nm thick. Copyright © 2004 John Wiley & Sons, Ltd.
XPS and AES characterization of hydrolysed γ‐mercaptopropyltrimethoxysilane deposited on Al, Zn and Al–43.4Zn–1.6Si alloy‐coated steel
Authors: Bexell Ulf , Grehk Mikael , Olsson Mikael , Gelius Ulrik
Published: July 2004

In this paper Al, Zn and Al–43.4Zn–1.6Si (AlZn) alloy‐coated steel have been treated with the organofunctional silane γ‐mercaptopropyltrimethoxysilane (γ‐MPS). The influence of different metal substrates on the structure and composition of the silane films was investigated with XPS and AES. The films were obtained by dipping the substrates in the silane solution followed by a blow‐dry procedure in nitrogen gas.

The results show that the surface concentration of the deposited silane is independent of the metal substrate and that the thickness of the silane film is non‐uniform. The AES measurements indicate that the silane film covers the entire substrate surface and XPS analysis of the silane‐treated substrate surfaces at different take‐off angles indicates that the γ‐MPS molecule is randomly orientated. Also, the results show that the silane is well hydrolysed under the solution conditions used. Finally, in the zinc‐containing silane‐metal systems, i.e. the silane‐treated AlZn and Zn substrates, the results indicate that the γ‐MPS molecules can bond to the substrate surfaces via the thiol group of the molecule. Copyright © 2004 John Wiley & Sons, Ltd.
In situ XPS and SIMS analysis of O2+ beam‐induced silicon oxidation
Authors: Tan S. K. , Yeo K. L. , Wee A. T. S.
Published: July 2004

The chemical composition variation of silicon under 4 keV O2+ ion beam bombardment at different incident angles was studied by in situ small‐area XPS. The changes in secondary ion profile (30Si+, 44SiO+, 56Si2+, 60SiO2+) during oxygen ion beam bombardment also have been monitored. We present a direct correlation of the changes in secondary ion depth profile with surface composition during sputtering. Evolution of the secondary ion profile obtained from SIMS shows similar trends with variation of oxygen concentration in the crater surface measured by XPS. It is shown that when the oxygen ion beam incidence angle is < 40° silicon dioxide is the dominant species on the crater surface and the matrix ion species ratio (MISR) value for 44SiO+/56Si2+ is higher than for 30Si+/56Si2+. For incidence angles of >40°, the formation of sub‐oxide is favoured and thus the MISR value for 44SiO+/56Si2+ is lower than for 30Si+/56Si2. At 40° bombardment there are similar amounts of SiO2 and sub‐oxides present on the crater surface and the MISR values for 44SiO+/56Si2+ and 30Si+/56Si2+ are also similar. Copyright © 2004 John Wiley & Sons, Ltd.
Quantitative analyses of impurities in ZnO
Authors: Sakaguchi Isao , Hishita Syunichi
Published: July 2004

Problems on the quantitative analyses of impurities in secondary ion mass spectrometry (SIMS) were revealed by analysing standard samples. One problem is the interference confirmed when 27Al16O, 63Cu and 67Zn16O negative ions were measured, which can be avoided by measuring a high‐resolution mass spectrum. Another problem is that light elements such as hydrogen can be measured accurately only after using a cooling system to reduce the background intensity. These remedies were applied in the quantitative analysis of single‐crystal ZnO grown by hydrothermal and vapour transport techniques. Copyright © 2004 John Wiley & Sons, Ltd.
Summary of ISO/TC 201 Technical Report: ISO/TR 19319: 2003—Surface chemical analysis—Auger electron spectroscopy and x‐ray photoelectron spectroscopy—Determination of lateral resolution, analysis area and sample area viewed by the analyser
Authors: Powell C. J.
Published: July 2004

ISO Technical Report 19319:2003 contains information on the determination of lateral resolution, analysis area and sample area viewed by the analyser in surface analyses by Auger electron spectroscopy and x‐ray photoelectron spectroscopy. This article provides a brief summary of this information. Copyright © 2004 John Wiley & Sons, Ltd.
Mechanical properties of the Ni filler metal layer in Si3N4 joints measured by nanoindentation
Authors: Miranzo P. , Osendi M. I. , Vergara I.
Published: July 2004

Nanoindentation experiments were done on Si3N4/Ni/Si3N4 specimens bonded at different temperatures. Tests were carried out in both the ceramic adherent and the metal filler. Results from nanoindentation experiments done across the interlayer verify that a solution of Si atoms in the Ni interlayer did not modify the mechanical properties of the metal (elastic modulus and hardness). The increase in bonding temperature produced an increase in hardness in the metal interlayer but did not affect its elastic modulus. This hardening of the Ni interlayer was related to the decrease in the shear strength of these joints. Copyright © 2004 John Wiley & Sons, Ltd.
X‐ray microanalysis in STEM of short‐term physicochemical reactions at bioactive glass particle/biological fluid interface. Determination of O/Si atomic ratios
Authors: Banchet V. , Jallot E. , Michel J. , Wortham L. , Laurent‐Maquin D. , Balossier G.
Published: July 2004

Short‐term physicochemical reactions at the interface between bioactive glass particles and biological fluids are studied and we focus our attention on the measurements of O/Si atomic ratio. The studied bioactive glass is in the SiO2Na2OCaOP2O5K2OAl2O3MgO system. The elemental analysis is performed at the submicrometre scale by scanning transmission electron microscopy associated with energy‐dispersive x‐ray spectroscopy (EDXS) and electron energy‐loss spectroscopy (EELS). We previously developed an EDXS quantification method based on the ratio method and taking into account local absorption corrections. In this way, we use EELS data to determine, by an iterative process, the local mass thickness, which is an essential parameter for correcting absorption in EDXS spectra. After different immersion times of bioactive glass particles in a simulated biological solution, results show the formation of different surface layers at the bioactive glass periphery. Before 1 day of immersion, we observe the presence of an already shown (Si,O,Al)‐rich layer at the periphery. In this paper, we demonstrate that a thin ‘electron dense’ (Si,O)‐layer is formed on top of the (Si,O,Al)‐layer. In this (Si,O)‐layer, depleted in aluminium, we point out an increase of oxygen weight concentration that can be interpreted by the presence of Si(OH)4 groups, which permit the formation of a (Ca,P)‐layer. Aluminium plays a role in the glass solubility and may inhibit apatite nucleation. After the beginning of the (Ca,P)‐layer formation, the size of the ‘electron dense’ (Si,O)‐layer decreases and tends to disappear. After 2 days of immersion, the (Ca,P)‐layer grows in thickness and leads to apatite precipitation. Copyright © 2004 John Wiley & Sons, Ltd.
A sample size computation method for non‐linear mixed effects models with applications to pharmacokinetics models
Authors: Kang Dongwoo , Schwartz Janice B. , Verotta Davide
Published: July 2004

We propose a simple method to compute sample size for an arbitrary test hypothesis in population pharmacokinetics (PK) studies analysed with non‐linear mixed effects models. Sample size procedures exist for linear mixed effects model, and have been recently extended by Rochon using the generalized estimating equation of Liang and Zeger. Thus, full model based inference in sample size computation has been possible. The method we propose extends the approach using a first‐order linearization of the non‐linear mixed effects model and use of the Wald χ2 test statistic. The proposed method is general. It allows an arbitrary non‐linear model as well as arbitrary distribution of random effects characterizing both inter‐ and intra‐individual variability of the mixed effects model. To illustrate possible uses of the method we present tables of minimum sample sizes, in particular, with an illustration of the effect of sampling design on sample size. We demonstrate how (D‐) optimal or frequent sampling requires fewer subjects in comparison to a sparse sampling design. We also present results from Monte Carlo simulations showing that the computed sample size can produce the desired power. The proposed method greatly reduces computing times compared with simulation‐based methods of estimating sample sizes for population PK studies. Copyright © 2004 John Wiley & Sons, Ltd.
A new approach to modelling interactions between treatment and continuous covariates in clinical trials by using fractional polynomials
Authors: Royston Patrick , Sauerbrei Willi
Published: July 2004

We consider modelling interaction between a categoric covariateTand a continuous covariateZin a regression model. HereTrepresents the two treatment arms in a parallel‐group clinical trial andZis a prognostic factor which may influence response to treatment (known as a predictive factor). Generalization to more than two treatments is straightforward. The usual approach to analysis is to categorizeZinto groups according to cutpoint(s) and to analyse the interaction in a model with main effects and multiplicative terms. The cutpoint approach raises several well‐known and difficult issues for the analyst. We propose an alternative approach based on fractional polynomial (FP) modelling ofZin all patients and at each level ofT. Other prognostic variables can also be incorporated by first constructing a multivariable adjustment model which may contain binary covariates and FP transformations of continuous covariates other thanZ. The main step involves FP modelling ofZand testing equality of regression coefficients between treatment groups in an interaction model adjusted for other covariates. Extensive experience suggests that a two‐term fractional polynomial (FP2) function may describe the effect of a prognostic factor on a survival outcome quite well. In a controlled trial, this FP2 function describes the prognostic effect averaged over the treatment groups. We refit this function in each treatment group to see if there are substantial differences between groups. Allowing different parameter values for the chosen FP2 function is flexible enough to detect such differences. Within the same algorithm we can also deal with the conceptually different cases of a predefined hypothesis of interaction or searching for interactions. We demonstrate the ability of the approach to detect and display treatment/covariate interactions in two examples from controlled trials in cancer. Copyright © 2004 John Wiley & Sons, Ltd.
Quantile estimation following non‐parametric phase I clinical trials with ordinal response
Authors: Paul Ranjan K. , Rosenberger William F. , Flournoy Nancy
Published: July 2004

A non‐parametric multi‐dimensional isotonic regression estimator is developed for use in estimating a set of target quantiles from an ordinal toxicity scale. We compare this estimator to the standard parametric maximum likelihood estimator from a proportional odds model for extremely small data sets. A motivating example is from phase I oncology clinical trials, where various non‐parametric designs have been proposed that lead to very small data sets, often with ordinal toxicity response data. Our comparison of estimators is performed in conjunction with three of these non‐parametric sequential designs for ordinal response data, two from the literature and a new design based on a random walk rule. We also compare with a non‐parametric design for binary response trials, by keeping track of ordinal data for estimation purposes, but dichotomizing the data in the design phase. We find that a multidimensional isotonic regression‐based estimator far exceeds the others in terms of accuracy and efficiency. A rule by Simon et al. (J. Natl. Cancer Inst. 1997; 89:1138–1147) yields particularly efficient estimators, more so than the random walk rule, but has higher numbers of dose‐limiting toxicity. A small data set from a leukemia clinical trial is analysed using our multidimensional isotonic regression‐based estimator. Copyright © 2004 John Wiley & Sons, Ltd.
A measurement error model with a Poisson distributed surrogate
Authors: Li Liang , Palta Mari , Shao Jun
Published: July 2004

We study a linear model in which one of the covariates is measured with error. The surrogate for this covariate is the event count in unit time. We model the event count by a Poisson distribution, the rate of which is the unobserved true covariate. We show that ignoring the measurement error leads to inconsistent estimators of the regression coefficients and propose a set of unbiased estimating equations to correct the bias. The method is computationally simple and does not require using supplemental data as is often the case in other measurement error analyses. No distributional assumption is made for the unobserved covariate. The proposed method is illustrated with an example from the Wisconsin Sleep Cohort Study. Copyright © 2004 John Wiley & Sons, Ltd.
A simple significance test for quantile regression
Authors: Redden David T. , Fernández José R. , Allison David B.
Published: July 2004

Where OLS regression seeks to model the mean of a random variable as a function of observed variables, quantile regression seeks to model the quantiles of a random variable as functions of observed variables. Tests for the dependence of the quantiles of a random variable upon observed variables have only been developed through the use of computer resampling or based on asymptotic approximations resting on distributional assumptions. We propose an exceedingly simple but heretofore undocumented likelihood ratio test within a logistic regression framework to test the dependence of a quantile of a random variable upon observed variables. Simulated data sets are used to illustrate the rationale, ease, and utility of the hypothesis test. Simulations have been performed over a variety of situations to estimate the type I error rates and statistical power of the procedure. Results from this procedure are compared to (1) previously proposed asymptotic tests for quantile regression and (2) bootstrap techniques commonly used for quantile regression inference. Results show that this less computationally intense method has appropriate type I error control, which is not true for all competing procedures, comparable power to both previously proposed asymptotic tests and bootstrap techniques, and greater computational ease. We illustrate the approach using data from 779 adolescent boys age 12–18 from the Third National Health and Nutrition Examination Survey (NHANES III) to test hypotheses regarding age, ethnicity, and their interaction upon quantiles of waist circumference. Copyright © 2004 John Wiley & Sons, Ltd.
A general statistical principle for changing a design any time during the course of a trial
Authors: Müller Hans‐Helge , Schäfer Helmut
Published: July 2004

A general method is presented that allows the researcher to change statistical design elements such as the residual sample size during the course of an experiment, to include an interim analysis for early stopping when no formal rule for early stopping was foreseen, to increase or reduce the number of planned interim analyses, to change time points and the type I error spending function for the further design of interim analyses, or to change the test statistic, the outcome measure, etc. At the time of a pre‐planned interim analysis for early stopping or at any time of an interim look without spending part of the type I error level the method offers the option to completely redesign the remaining part of the trial, without affecting the type I error level. The method is described in the usual Brownian motion model and extended to the general context of statistical decision functions. It is based on the conditional rejection probability of a decision variable. Copyright © 2004 John Wiley & Sons, Ltd.
Revitalizing modifiability of legacy assets
Authors: Veerman Niels
Published: July 2004

The modifiability of Cobol legacy code is discussed and an approach is proposed to improve the modifiability using automatic restructuring transformations. An algorithm is presented that enables the application of these transformations to large industrial Cobol systems. The transformations were adapted to a system of 80 000 lines of code by extending them with new transformations and transformation patterns. The resulting source code is analysed and discussed. Two case studies (over 5 million lines of code in total) with real‐life Cobol programs show the large‐scale application of the transformations. Copyright © 2004 John Wiley & Sons, Ltd.
An assessment strategy for identifying legacy system evolution requirements in eBusiness context
Authors: Aversano Lerina , Tortorella Maria
Published: July 2004

The enactment of e Business processes requires the effective usage of the existing legacy applications in the e Business initiatives. Technical issues are not enough to drive the evolution of the existing legacy applications, but problems concerning the perspectives, strategies, and business of the enterprises have to be considered. In particular, there is a strict relationship between the evolution of the legacy systems and the evolution of the e Business processes.

This paper proposes a strategy to extract the requirements for a legacy system evolution from the requirements of the e Business evolution. The proposed strategy aims at characterizing the software system within the whole environment in which its evolution will be performed. It provides a useful set of attributes addressing technical, process, and organizational issues. Moreover, a set of assessment activities is proposed affecting the order in which the attributes are assessed. Copyright © 2004 John Wiley & Sons, Ltd.
A debugging strategy based on the requirements of testing
Authors: Chaim Marcos L. , Maldonado José C. , Jino Mario
Published: July 2004

Testing and debugging activities consume a significant amount of the software development and maintenance budget. To reduce this cost, the use of testing information for debugging purposes has been advocated. In general, heuristics are used to select structural testing requirements (nodes, branches and definition–use associations) more closely related to the manifestation of a failure, which are then mapped into a piece of code. The intuition is that the selected piece of code is likely to contain the fault. However, this approach has its drawbacks. Heuristics that select a manageable piece of code are less likely to hit the fault and the piece of code itself does not provide enough guidance for program understanding—a major factor in program debugging. These problems occur because this approach relies only on static information—a fragment of code. We introduce a strategy for fault localization that addresses these problems. The strategy—called the debugging strategy based on the requirements of testing (DRT)—is based on the investigation of indications (or hints) provided at run‐time by data‐flow testing requirements (definition–use associations). Our claim is that the selected definition–use associations may fail to hit the fault site, but still provide information useful for fault localization. The strategy's novelty and attractiveness are threefold: (i) the focus on dynamic information related to testing data; (ii) implementation in state‐of‐the‐practice symbolic debuggers with a low overhead; and (iii) the use of algorithms which consume constant memory and are linear on the number of branches in the program. A case study shows that our claim is valid (for the subject program) and a prototype tool implements the strategy. Copyright © 2004 John Wiley & Sons, Ltd.
Problems within front‐end support
Authors: Kajko‐Mattsson Mira
Published: July 2004

Within corrective maintenance, the front‐end support mainly assists the customer‐ and back‐end maintenance organizations in the communication of corrective maintenance demands. This implies receiving problem reports from customers, transferring them on to the back‐end maintenance organization/vendor, and delivering problem solutions from the back‐end maintenance organization/vendor to the customers. In this paper, we identify problems as experienced within 37 front‐end support organizations in Sweden. Our results show a great variety of problems within the organizations studied. The dominating problems are the complexity of applications, customer knowledge, and complexity of support organizations. Copyright © 2004 John Wiley & Sons, Ltd.
Quantitative three‐dimensional power Doppler ultrasound predicts the outcome of placental chorioangioma
Authors: Shih J. C. , Ko T. L. , Lin M. C. , Shyu M. K. , Lee C. N. , Hsieh F. J.
Published: July 2004

The relationship of large and vascularized chorioangiomas to adverse pregnancy outcome is well recognized. We present a patient with a large placental tumor and signs of impending fetal cardiac failure. The angioarchitecture of the tumor depicted by three‐dimensional (3D) power Doppler ultrasound enabled us to accurately diagnose a placental chorioangioma. During the follow‐up period, quantitative flow data obtained using 3D power Doppler indicated altered hemodynamics in the tumor and concomitant improvement in the condition of the fetus, enabling us to manage the mother conservatively. Spontaneous delivery occurred at 38 weeks without any complications. This report demonstrates the potential value of 3D power Doppler in prenatal diagnosis and monitoring of pregnancies complicated by large, vascularized chorioangioma. Copyright © 2004 ISUOG. Published by John Wiley & Sons, Ltd.
Prevalence of neurological damage in monochorionic twins with selective intrauterine growth restriction and intermittent absent or reversed end‐diastolic umbilical artery flow
Authors: Gratacós E. , Carreras E. , Becker J. , Lewi L. , Enríquez G. , Perapoch J. , Higueras T. , Cabero L. , Deprest J.
Published: July 2004

Objective

To assess the incidence of parenchymal lesions on early and late neonatal brain scans and its association with the presence or absence of intermittent absent or reversed end‐diastolic umbilical artery flow velocity (A/REDV) in monochorionic twins complicated by selective intrauterine growth restriction (IUGR), as compared to dichorionic twins and monochorionic twins without selective IUGR.

Methods

This was a prospective cohort study involving 42 monochorionic twins diagnosed with selective IUGR and managed expectantly. The presence or absence of intermittent A/REDV was recorded in all cases. This study group was compared to dichorionic twins (n = 29) and monochorionic twins without selective IUGR (n = 32) delivered at 26–34 weeks during the study period. All infants underwent an early neonatal brain scan (at or before the fourth day of postnatal life) and at least one follow‐up scan during the first 28 days of postnatal life. Perinatal outcome and the incidence of neurological damage were compared between the study groups.

Results

The incidence of intrauterine fetal death (IUD) and periventricular leukomalacia was significantly increased in monochorionic twins complicated with selective IUGR, as compared with the other study groups. Intermittent A/REDV was observed in 22/42 (52.4%) twin pairs, and was always present in the growth‐restricted twin. The incidence of IUD (overall 9/44 (20.5%) vs. 0/40, P < 0.001; smaller twin 6/22 (27.3%) vs. 0/20, P < 0.05) and parenchymal brain damage (overall 7/35 (20.0%) vs. 2/40 (5.0%), P = 0.07; larger twin 7/19 (36.8%) vs. 1/20 (5.0%), P < 0.05) was significantly higher in pregnancies with intermittent A/REDV than in those without intermittent A/REDV. Brain damage usually occurred in the larger twin, irrespective of whether the smaller twin was liveborn or not.

Conclusions

The presence of intermittent A/REDV in monochorionic twins with selective IUGR identifies a subgroup with an elevated risk of intrauterine demise of the smaller twin and neurological damage in the larger twin; this latter finding is not restricted to cases with IUD of the cotwin. Copyright © 2004 ISUOG. Published by John Wiley & Sons, Ltd.
Fetal lung dysplasia: clinical outcome based on a new classification system
Authors: Achiron R. , Zalel Y. , Lipitz S. , Hegesh J. , Mazkereth R. , Kuint J. , Jacobson J. , Yagel S.
Published: July 2004

Objective

To evaluate the clinical application of a new classification system of fetal lung anomalies.

Methods

Forty fetal diagnoses of lung lesions were analyzed according to our proposed classification system in which each lung component is considered using two‐dimensional ultrasound and color and power Doppler technology. Medical files, natural history and neonatal follow‐up were recorded.

Results

Type I dysplasia: Four cases of agenesis of the lung were diagnosed, three with right lung agenesis and one with left lung agenesis. Three of the four patients elected to undergo termination of pregnancy (TOP). The surviving fetus was diagnosed with scimitar syndrome and postnatal embolization of the aberrant vessel was performed. Type II dysplasia: One case of normal lung with abnormal systemic feeding artery was diagnosed with normal neonatal outcome. Type III dysplasia: Abnormal lung with abnormal vascularity was found in 14 cases, presenting in most cases as echogenic lung masses. Seven were supradiaphragmatic, six subdiaphragmatic and one case was of undetermined position. All 14 fetuses showed an aberrant systemic artery emerging from the aorta. Abnormal venous drainage could be identified in only five (36%) of the fetuses: three had prominent azygos vein, one showed drainage to the inferior vena cava and one had multiple intrapulmonary veins forming a huge arteriovenous (A‐V) shunt. Two cases in this group underwent TOP, the case with A‐V shunt following development of hydrops, and one on maternal request. The remaining 12 fetuses (86%) survived and were alive and well at the time of writing; only one of them needed immediate postnatal embolization of the bilateral aberrant feeding arteries. Type IV dysplasia: Abnormal lung with no vascular abnormality was diagnosed in 20 fetuses. In this group there was one case of intrauterine fetal death, two patients underwent TOP, one complicated with hydrops and one on maternal request. The survival rate in this group was 85%. Only two cases needed immediate surgical repair. Type V miscellaneous dysplasia: One fetus demonstrated echogenic lung with split notochord syndrome and survived.

Conclusions

Congenital bronchopulmonary and related vascular anomalies can be categorized using the new classification system. This new approach enabled prenatal evaluation of each lung component and facilitated cogent management of the fetus with congenital lung dysplasia. Copyright © 2004 ISUOG. Published by John Wiley & Sons, Ltd.
Prenatal diagnosis of fetal skeletal dysplasias by combining two‐dimensional and three‐dimensional ultrasound and intrauterine three‐dimensional helical computer tomography
Authors: Ruano R. , Molho M. , Roume J. , Ville Y.
Published: July 2004

Objective

To evaluate the contribution of new imaging techniques in the prenatal diagnosis of skeletal dysplasia.

Methods

Between May and October 2003, a prospective study was conducted in a single referral center. Three‐dimensional ultrasound (3D‐US) and three‐dimensional helical computer tomography (3D‐HCT) were performed after two‐dimensional ultrasound (2D‐US) in six cases of skeletal dysplasia. Diagnostic accuracy and detailed findings with each of the three techniques were compared with postnatal radiological findings.

Results

There were three cases of achondroplasia, two cases of osteogenesis imperfecta type II and one case of chondrodysplasia punctata. Termination of pregnancy was performed in five cases and one fetus with osteogenesis imperfecta type II was delivered at term by Cesarean section. 2D‐US made the correct diagnosis in four cases. 3D‐US and 3D‐HCT achieved an accurate diagnosis in all six cases. 3D‐HCT and 3D‐US identified significantly more abnormalities than did 2D‐US (3D‐HCT: 94.3% (33/35); 3D‐US: 77.1% (27/35); 2D‐US: 51.4% (18/35); P < 0.01). The diagnosis was made between 27 and 36 weeks' gestation in all cases. The advantage of 3D‐HCT over 3D‐US was the possibility of imaging the entire fetus.

Conclusion

3D‐US and 3D‐HCT seem to be useful complementary methods to 2D‐US, and may improve accuracy of the prenatal diagnosis of skeletal disorders. These new imaging technologies may have a role in the prenatal multidisciplinary approach to the diagnosis of skeletal dysplasias. Copyright © 2004 ISUOG. Published by John Wiley & Sons, Ltd.