bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrospray ionisation mass spectrometric study of degradation products of quercetin, quercetin‐3‐glucoside and quercetin‐3‐rhamnoglucoside, produced by in vitro fermentation with human faecal flora
Authors: Justesen Ulla , Arrigoni Eva
Published: August 2002

Eight phenolic compounds, obtained by in vitro fermentation of quercetin, quercetin‐3‐glucoside and quercetin‐3‐rhamnoglucoside were analysed by electrospray ionisation mass spectrometry (ESI‐MS). Low‐energy collision‐induced dissociation tandem mass spectrometry (CID‐MS/MS) was performed on the [M − H]− precursor ions to obtain specific fragmentation. Typical fragmentation of the phenolic acids was loss of 44 (CO2) and 18 (H2O) u. Production of m/z 108 by loss of neutral radicals, e.g. HCO2, CH3 or HCO, was also favoured. Structures of the compounds, numbered 1–8, were suggested based on the fragmentation patterns. Copyright © 2001 John Wiley & Sons, Ltd.
Direct analysis of pharmaceutical compounds in human plasma with chromatographic resolution using an alkyl‐bonded silica rod column
Authors: Plumb Robert , Dear Gordon , Mallett David , Ayrton John
Published: August 2002

Monolithic columns have been successfully used with steep gradient and high flow rates for the direct analysis of a candidate pharmaceutical compound in human plasma. The monolithic columns showed excellent robustness with nearly 300 20‐µL injections of plasma (diluted 1:1 with water) being made onto one column without significant deterioration in performance. The system gave excellent sensitivity with a limit of quantification of 5 ng/mL being achieved. Unlike previous methods of direct analysis the monolithic columns showed excellent resolution even after nearly 300 plasma injections. The column performance was measured before and after the analysis of the plasma samples. Copyright © 2001 John Wiley & Sons, Ltd.
Determination of drug concentrations in plasma by a highly automated, generic and flexible protein precipitation and liquid chromatography/tandem mass spectrometry method applicable to the drug discovery environment
Authors: O'Connor Desmond , Clarke Dawn E. , Morrison Denise , Watt Alan P.
Published: August 2002

This report presents a highly automated procedure for the determination of drug concentrations in plasma samples. The method is generic, in that it has been applied without adaptation to many different drug candidate molecules, but is also flexible, in that variations in the nature and number of samples to be analyzed can be readily accommodated. The method includes preparation of dilutions of analyte stock solutions, spiking these into control plasma to generate analytical standards, and preparation of samples suitable for analysis by high‐performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) by precipitation of plasma proteins with acetonitrile, centrifugation, and dilution of the supernatants with HPLC buffer. All of these steps, apart from centrifugation, are performed without manual intervention on an automated liquid‐handling workstation using 96‐well plates. Analysis is by HPLC/MS/MS, using a generic HPLC gradient. Commercially available software was used for optimization of parameters for analysis by HPLC/MS/MS, integration of chromatographic peaks, and quantification of drug concentrations. The use of this methodology in our laboratory has greatly facilitated the analysis of small sample sets for a large number of analytes, a situation regularly encountered in an early drug discovery environment. Copyright © 2002 John Wiley & Sons, Ltd.
Molecular epidemiology of respiratory syncytial virus
Authors: Cane Patricia A.
Published: August 2002

Human respiratory syncytial virus (RSV) is the major cause of lower respiratory tract disease in infants. It is unusual in that it causes repeated infections throughout life. Despite considerable efforts there is as yet no satisfactory vaccine available. This paper reviews the molecular epidemiology of the RSV and describes the complex genotypic structure of RSV epidemics. The evolution of the virus is discussed, with particular reference to the antigenic and genetic variability of the attachment glycoprotein. Copyright © 2001 John Wiley & Sons, Ltd.
LPV controller design for the nonlinear RTAC system
Authors: Park PooGyeon , Choi Doo Jin
Published: August 2002

This paper proposes three kinds of state‐feedback controllers for the nonlinear rotational and translational actuator (RTAC) benchmark problem. Interpolating a nonlinear system into an LPV system associated with time‐varying and state‐dependent weighting functions allows one to apply various linear system theories and techniques for analysing and synthesizing nonlinear systems, and thus to generate LMI criteria to supply various stabilizers and guaranteed cost controllers. This approach is more flexible for this benchmark problem than existing approaches in the literature because the other controllers excessively depend on the structure of the nonlinear system. Simulation results show the performance of the resulting controllers. Copyright © 2001 John Wiley & Sons, Ltd.
Some nonlinear optimal control problems with closed‐form solutions
Authors: Margaliot Michael , Langholz Gideon
Published: August 2002

Optimal controllers guarantee many desirable properties including stability and robustness of the closed‐loop system. Unfortunately, the design of optimal controllers is generally very difficult because it requires solving an associated Hamilton–Jacobi–Bellman equation. In this paper we develop a new approach that allows the formulation of some nonlinear optimal control problems whose solution can be stated explicitly as a state‐feedback controller. The approach is based on using Young's inequality to derive explicit conditions by which the solution of the associated Hamilton–Jacobi–Bellman equation is simplified. This allows us to formulate large families of nonlinear optimal control problems with closed‐form solutions. We demonstrate this by developing optimal controllers for a Lotka–Volterra system. Copyright © 2001 John Wiley & Sons, Ltd.
Missile autopilot design via a multi‐channel LFT/LPV control method
Authors: Pellanda Paulo C. , Apkarian Pierre , Tuan Hoang Duong
Published: August 2002

In this paper, the missile pitch‐axis autopilot design is revisited using a new and recently available linear parameter‐varying (LPV) control technique. The missile plant model is characterized by a linear fractional transformation (LFT) representation. The synthesis task is conducted by exploiting new capabilities of the LPV method: firstly, a set ofH2/H∞criteria defined channel‐wise is considered; secondly, different Lyapunov and scaling variables are used for each channel/specification which is known to reduce conserva tism; and finally, the controller gain‐scheduling function is constructed as affine matrix‐valued function in the polytopic co‐ordinates of the scheduled parameter. All these features are examined and evaluated in turn for the missile control problem. The method is shown to provide additional flexibility to tradeoff conflicting and demanding performance and robustness specifications for the missile while preserving the practical advantage of previous single‐objective LPV methods. Finally, the method is shown to perform very satisfactorily for the missile autopilot design over a wide range of operating conditions. Copyright © 2001 John Wiley & Sons, Ltd.
Interactive force control of an operator–mobile manipulator coordination system
Authors: Chung Jae H.
Published: August 2002

In this article, a new type of coordination control called interactive force control is developed for an operator–mobile manipulator coordination system (OMMCS) based on a base force/torque sensor. In the interactive force control scheme, a robust force control of the manipulator and impedance control of the mobile platform are integrated to achieve smooth interaction between the operator, the manipulator, and the mobile platform. In simulation, the developed methods are compared for control performance in tracking and force regulation. Simulation results show the promise of the developed control scheme, which utilizes robust force control based on a base force/torque sensor. © 2002 Wiley Periodicals, Inc.
Spherically actuated platform manipulator
Authors: Williams Robert L. , Poling Dana B.
Published: August 2002

This article presents the inverse and forward pose and rate kinematics solutions for a novel 6‐DOF platform manipulator, actuated by two base‐mounted spherical actuators. The moving platform is connected to the fixed base by two identical spherical‐prismatic‐universal serial chain legs. The S‐joint is active, and the remaining two joints in each chain are passive. An analytical solution is presented for the inverse pose problems, a semi‐analytical solution is presented for the rate problems, and the numerical Newton–Raphson technique is employed to solve the forward pose problem. Unfortunately, the passive joint variables cannot be ignored in the kinematics solutions as they can for the Gough–Stewart platform. Examples are presented and hardware has been built, using two Rosheim Omni‐Wrists on loan from NASA as the spherical actuators. © 2001 John Wiley & Sons, Inc.
A performance criterion for the depth estimation with application to robot visual servo control
Authors: Fang Chang‐Jia , Lin Shir‐Kuan
Published: August 2002

This article deals with the depth observability problem of a robot visual system with a moving camera. In the visual system, the unknown depth of a feature point is estimated from the input of the camera velocity and the output of the image of the feature point. Although it is well known that the linear velocity of the camera must satisfy some constraints for successful depth estimation, this proposes a criterion to measure the performance of the depth estimation, which is a heuristic extension from an estimation result of a linear system. This performance criterion depends on both the image position and the linear velocity of the camera. Some simulation and experiment examples demonstrate and verify the proposed performance criterion. Furthermore, this criterion is used to develop a new visual servo control scheme that has good performance in both the depth estimation and the visual control. This control scheme is also verified by a simulation example. © 2001 John Wiley & Sons, Inc.
Analytic determination of workspace and singularities in a parallel pointing system
Authors: Di Gregorio Raffaele
Published: August 2002

This paper studies a parallel pointing system, named U‐2PUS, used in biomechanic and aerospace
applications. In the literature, U‐2PUS position analysis has already been solved in closed form, whereas
simple and efficient tools to address workspace determination and singularity locations are still lacking. In this
paper, the analytic expression of the U‐2PUS workspace is derived, and a bidimensional representation of
the workspace is proposed. The U‐2PUS mobility analysis is addressed, and a singularity locus analytic
expression, explicitly containing the manipulator geometric parameters and the end‐effector orientation
parameters, is derived. Moreover, it is shown that the U‐2PUS singularity locus can be represented by
curves (singularity curves) on a Cartesian plane having the U‐2PUS generalized coordinates on the
coordinate axes. Finally, the presented singularity conditions are geometrically interpreted. © 2002 John
Wiley & Sons, Inc.
Identifying the natural flow regime and the relationship with riparian vegetation for two contrasting western Australian rivers
Authors: Pettit N.E. , Froend R.H. , Davies P.M.
Published: August 2002

The natural flow regime and the relationship between flows and riparian vegetation are described for sites on both the Blackwood River in south‐western Australia and the Ord River in north‐western Australia. Analysis of long‐term flow data showed the historic mean monthly river discharge for the Blackwood River is strongly seasonal and highly predictable with generally low variability each month. The Ord River showed a strong seasonality of flows with about 92% of the (total) yearly flow occurring between December and March. Flow variability was very high (e.g. coefficient of variation >100% for all months) but highly predictable, with this mostly attributed to low but constant dry‐season flows. Water depth, duration of flood events and the number of flood events per year show a significant correlation with aspects of the riparian vegetation within experimental vegetation plots. Results highlight the strong relationship between floristics, life form structure and population dynamics with stream hydrology. On the Blackwood River, species richness and cover of shrubs reduced with increased duration and frequency of flooding, while cover of exotic species and annual herbs increased with increased flooding. Germination of tree seedlings was not influenced by flood regime but size class of tree species increased with flooding frequency. On the Ord River, species richness was not influenced by flooding regime. However, cover of perennial grasses increased with flooding frequency whilst cover of shrubs decreased. There was no relationship between flooding and seedling establishment whilst tree size class decreased with increased flooding. The methods described here can be used to compare the response of different components of the riparian vegetation to different fluvial regimes (e.g. because of impoundment and abstraction). This technique can be expanded for the management of riparian zones and planning rehabilitation programmes. It may also be useful for improving the ecological knowledge base for setting environmental flows in regulated systems. Copyright © 2001 John Wiley & Sons, Ltd.
Stochastic optimization of LMS resource assignments
Authors: Jahn Axel
Published: August 2002

This paper presents stochastic optimization methods for frequency assignments in land mobile satellite systems. Genetic algorithms and simulated annealing can be used for channel assignment in satellite multibeam antennas. The principles of stochastic optimization is described, the performance of the assignment is evaluated as fitness or cost criteria based on the co‐channel interference. Several operators for selection, mutation and crossover are investigated. Finally, results show the applicability and power of the algorithms. The results are compared against regular reuse patterns for satellite antennas with equal beamwidth and equal cell area. Copyright © 2001 John Wiley & Sons, Ltd.
“Mapping to know”: The effects of representational guidance and reflective assessment on scientific inquiry
Authors: Toth Eva Erdosne , Suthers Daniel D. , Lesgold Alan M.
Published: August 2002

This study documents an instructional methodology to teach a fundamental reasoning skill during scientific inquiry: the evaluation of empirical evidence against multiple hypotheses. Using the “design experiment” approach, with iterative cycles we developed an instructional framework that lends itself to authentic scientific inquiry by providing a nontraditional approach to three aspects of learning: the activities students are engaged in during scientific inquiry, the tools students use while constructing knowledge, and the assessment of learning outcomes. The present article focuses on the contribution of two components of this instructional framework: the effect of technology‐based knowledge‐representation tools and the effect of reflective assessment on learning to act and think scientifically. The technological tools of the framework allowed students to represent their developing knowledge of natural phenomena with either graphical mapping or with word‐processed prose. The reflective assessment we used was a form of inquiry rubrics that provided clear expectations for optimal progress throughout the entire process of inquiry by indicating specific assessment criteria for the various components of scientific inquiry. The results indicated that in real‐life‐like classroom investigations designed to teach students how to evaluate data in relation to theories, the use of evidence mapping is superior to prose writing. Furthermore, this superior effect of evidence mapping was greatly enhanced by the use of reflective assessment throughout the inquiry process. Modes of representational guidance explain both the superior effect of evidence mapping as well as the discrepancy between the effects of explicit reflection on evidence mapping compared to prose writing. These results have fundamental implications for the development of cognitively‐based classroom learning environments and for the design of further research on learning. © 2002 Wiley Periodicals, Inc. Sci Ed 86:264–286, 2002; DOI 10.1002/sce.10004
Considering the nature of scientific problems when designing science curricula
Authors: Stewart James , Rudolph John L.
Published: August 2002

A recurring theme of science education reform has been the creation of classroom opportunities that allow students to develop insights into the professional practice of scientists. The posing and solving of problems of a variety of types, a process central to scientific practice, provides a useful framework for structuring such opportunities for students. Most problems that students encounter can be characterized as model–data fit problems, in which solvers fit available data to an appropriate explanatory model. Although these problems are important, we argue that it is essential to expand the range of problems students encounter to include those that require solvers to confront the conceptual coherence of their explanatory models and to examine the relationship of those models to other scientific models, methodological norms, and common worldviews. In this article, we describe the nature and existence of both model–data fit and conceptual problems in science and then examine two curricular projects, one in genetics and one in evolutionary biology, that attempt to integrate these problems into classroom instruction. © 2001 John Wiley & Sons, Inc. Sci Ed 85:207–222, 2001.
Precise subpixel estimation on area‐based matching
Authors: Shimizu Masao , Okutomi Masatoshi
Published: August 2002

Area‐based matching is a common procedure in various fields such as image‐based measurements, stereo image processing, and fluidics. Subpixel estimation using parabola fitting over three points with their similarity measures is also a common method to increase the resolution of matching. However, few investigations or studies concerning the characteristics of this estimation have been reported. In this paper, we have analyzed the subpixel estimation error by using an approximate image function and three kinds of similarity measures for matching. The results illustrate some inherently problematic phenomena such as so‐called “pixel‐locking.” In addition, we propose a new algorithm to greatly reduce subpixel estimation error. This method is independent of the similarity measure and quite simple to implement. The advantage of our novel method is confirmed through experiments using three different types of images. © 2002 Wiley Periodicals, Inc. Syst Comp Jpn, 33(7): 1–10, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.10098
Study on Reduction Methods of Moiré Noise in Image Acquisition of Periodic Gray‐Scale Pattern
Authors: Mochizuki Jun , Asano Toshio
Published: August 2002

Creating valid digital images for display surfaces is vital for the quantification of display quality (defects, spots) for display devices. However, when imaging a spatially discrete display surface using individual acquisition elements, an acquisition moiré appears in the acquisition image. In this paper the authors quantify the display acquisition image, then clarify how to find the acquisition moiré from the dimensions of the display system and acquisition target using computations. Based on these results, the authors formulate a method for determining a pixel shift which inverts the moiré phase in a pixel‐shifted image. They then propose a method to compute the average in pixel units of gradations between a reference image and a pixel‐shifted image given by a reference image and a pixel‐shifted image created using the above method. Finally, they verify the effects of reducing the acquisition moiré using simulations. © 2001 Scripta Technica, Syst Comp Jpn, 33(1): 27–37, 2002
Implications of Brain Lateralization for Intensive Short‐Term Dynamic Psychotherapy
Authors: Gaillard J.‐M.
Published: August 2002

The possible implications of brain lateralization in the mode of action of the method developed by Davanloo for intensive short‐term psychotherapy are discussed. The two hemispheres appear to treat differently sensory information, and to play an asymmetric role in the control of behavior. The left hemisphere, which houses the mechanisms of language production, is dominant in this respect, but interhemispheric cooperation is probably a prerequisite for a normal course of behavior. It is proposed that interhemispheric dysharmony is a factor to be considered in the physiopathology of human neuroses and that the work of psychotherapy would be to correct such dysharmony.
Resistance and Transference in Intensive Short‐Term Dynamic Psychotherapy (IS‐TDP) and Classical Psychoanalysis—Similarities and Differences—Part II
Authors: Davis David M.
Published: August 2002

Part I of this article discussed the concepts of resistance and transference in classical psychoanalysis and in Intensive Short‐Term Dynamic Psychotherapy (IS‐TDP). The psychotherapeutic setting and the technical interventions utilized by the two therapies, to work with resistance and transference, differ dramatically. This present article, via edited excerpts from an IS‐TDP trial therapy evaluation, discusses the similarities and differences between classical psychoanalysis and IS‐TDP, regarding the technical approaches to the management of resistance and transference. Copyright © 1990 John Wiley & Sons, Ltd.
Beyond Interpretation: Initial Evaluation and Technique in Short‐Term Dynamic Psychotherapy. Part II.
Authors: Malan David
Published: August 2002

This is the second part of a two‐part article, the first part of which appears in this issue of the journal. The article considers the basic problems of Short‐term Dynamic Psychotherapy, namely (1) how to develop techniques that maximize success, and (2) how to recognize suitable patients. In addition, there is a deep theoretical problem: why is it that purely interpretative therapy, even when intense dynamic interaction occurs, only a relatively small proportion of patients experience resolution of their neurosis? Davanloo has developed a technique which leads to solutions to all these problems. The technique is illustrated by an initial evaluation, begun in Part I and completed in the present Part. The article ends with a discussion of the practical and theoretical consequences of this work. Copyright © 1986 John Wiley & Sons, Ltd.
Handling Resistance in Depressed Patients
Authors: Zois C.
Published: August 2002

The present article describes the specific problems of handling resistance when treating depressed patients with Davanloo's technique. These include: (1) the need to bring patients to the actual experience of the ways in which they use regressive mechanisms to defend themselves against transference feelings, (2) the need to take particular care to make patients consciously aware of their mechanisms, and (3) the need to assess very carefully the quality of the depression and the danger of suicide. These issues are illustrated with a clinical example. Copyright © 1986 John Wiley & Sons, Ltd.
Elastic electron backscattering from overlayer/substrate systems
Authors: Jablonski A. , Zemek J. , Jiricek P.
Published: August 2002

Elastic electron backscattering probability for Au overlayers deposited on Ni were determined experimentally in the energy range 200–1000 eV. These measurements were accompanied by characterization of the overlayer structure and the mean overlayer thickness. The elastic backscattering probabilities also were derived from extensive Monte Carlo simulations of the electron transport in overlayer/substrate systems. Two overlayer structures were considered in these calculations: a uniform Au layer, and isolated Au islands located on the uncovered substrate. Analysis of the shape of Au 4d spectra with QUASES‐Tougaard software indicated that the latter structure is more probable. It has been found that the experimental elastic backscattering probabilities compare better with the theoretical probabilities calculated for the island structure. The possibility of characterization of the overlayer thickness and structure from the elastic backscattering probabilities has been discussed. Copyright © 2001 John Wiley & Sons, Ltd.
Prediction of enthalpy and entropy of grain boundary segregation
Authors: Lejček P. , Hofmann S.
Published: August 2002

The fundamental methods for the prediction of segregation enthalpy and entropy of any element at any grain boundary are outlined, based on grain boundary segregation diagrams and a linear dependence between segregation entropy and enthalpy. The capability of these methods is evaluated by comparison of the predicted interfacial composition of α‐iron‐based binary systems with Si, Al, P, Sn, S, Sb, Ni, Mo, C and B with recently measured experimental data for the same systems. Copyright © 2002 John Wiley & Sons, Ltd.
Analytical TEM study on the dispersion of Au nanoparticles in Au/TiO2 catalyst prepared under various temperatures
Authors: Akita Tomoki , Lu Ping , Ichikawa Satoshi , Tanaka Koji , Haruta Masatake
Published: August 2002

Transmission electron microscopy (TEM) observations were made for Au/TiO2 catalysts prepared by calcination in air at different temperatures from room temperature to 873 K in order to study the growth process of Au particles over the surface of TiO2. Many Au clusters with diameters of ∼1 nm were observed on the TiO2 surface when Au(OH)3/TiO2 precursor prepared by the deposition precipitation method was calcined at temperatures below 473 K. They grew to form larger particles being trapped at the interface between TiO2 particles at temperatures above 573 K. The growth of Au particles became markedly rapid above 673 K. The growth process of Au particles during calcination was discussed based on the size distribution of Au particles and the Arrhenius plots of the mean diameter of Au particles against calcination temperature. Both TEM and electron energy‐loss spectroscopy measurements based on a scanning transmission electron microscope revealed that the Au clusters were preferentially deposited with high density on specific TiO2 particles that have the rutile structure. Copyright © 2001 John Wiley & Sons, Ltd.
Regression models for allele sharing: analysis of accumulating data in affected sib pair studies
Authors: Bull Shelley B. , Greenwood Celia M.T. , Mirea Lucia , Morgan Kenneth
Published: August 2002

Advances in human genome mapping have led to the identification of large numbers of genetic markers that allow systematic searches for multiple disease susceptibility genes for complex traits. A common design involves the recruitment of families with at least two children affected with the disease of interest. The objective is to find chromosomal regions that harbour susceptibility genes for the disease. The affected children, their parents if available, and sometimes other, unaffected, siblings are genotyped using sets of microsatellite DNA markers representing chromosomal sites distributed across the genome. Each marker can occur in several different variants known as alleles, and a pair of alleles constitutes the marker genotype. Each child randomly inherits one of their mother's two alleles and one of their father's two alleles. If a marker is close to a disease susceptibility gene, then affected siblings are expected to have more sharing of the same maternal and/or paternal marker alleles. Statistical methods are used to estimate the distribution of allele sharing in each affected sib pair (ASP) using the set of markers typed across each chromosome, and to test for the presence of excess sharing in the families as a group at each point across the genome. Regression models that allow the allele sharing proportions to depend on characteristics of the family such as diagnostic subtype or ethnic background have been developed to address the heterogeneity that is characteristic of complex disease, but these have not yet been widely applied. In this paper, we apply regression modelling to investigate variation associated with family‐level covariates and with the order in which families are recruited and genotyped. We also discuss how some of the concepts of group sequential analysis apply to accumulating data from genome scans of complex disease. Copyright © 2002 John Wiley & Sons, Ltd.
Advanced methods in meta‐analysis: multivariate approach and meta‐regression
Authors: van Houwelingen Hans C. , Arends Lidia R. , Stijnen Theo
Published: August 2002

This tutorial on advanced statistical methods for meta‐analysis can be seen as a sequel to the recent Tutorial in Biostatistics on meta‐analysis by Normand, which focused on elementary methods. Within the framework of the general linear mixed model using approximate likelihood, we discuss methods to analyse univariate as well as bivariate treatment effects in meta‐analyses as well as meta‐regression methods. Several extensions of the models are discussed, like exact likelihood, non‐normal mixtures and multiple endpoints. We end with a discussion about the use of Bayesian methods in meta‐analysis. All methods are illustrated by a meta‐analysis concerning the efficacy of BCG vaccine against tuberculosis. All analyses that use approximate likelihood can be carried out by standard software. We demonstrate how the models can be fitted using SAS Proc Mixed. Copyright © 2002 John Wiley & Sons, Ltd.
Improved approximate confidence intervals for the mean of a log‐normal random variable
Authors: Taylor Douglas J. , Kupper Lawrence L. , Muller Keith E.
Published: August 2002

Data analysts often compute approximate 100(1‐α) per cent confidence intervals for the mean of a log‐normal random variable due to the computational effort required for exact intervals. We evaluate two simple approximations and demonstrate that the probabilities with which the intervals fail to capture the population mean (that is, the coverage error) can range from well above the desired level, α, to very near zero in small to moderate sample sizes (n⩽100). The performance of a more sophisticated approximation, implemented via numerical integration or bootstrap sampling, is noticeably improved, but also suffers from coverage errors that are too large when n⩽25. A new procedure is developed which outperforms existing approximations. Computing these improved intervals requires the integration of standard distribution functions. The calculations are straightforward, however, and lead to satisfactory coverage errors for n as small as 5. A related method that avoids the integration step generally outperforms existing simple approximations for n⩽100, while maintaining the coverage error at or below α. Programs to implement the new procedures are provided in an Appendix. Copyright © 2002 John Wiley & Sons, Ltd.
Towards a curriculum for the consultant biostatistician: identification of central disciplines
Authors: Tobi Hilde , Joop Kuik D. , Dick Bezemer P. , Ket Paul
Published: August 2002

The variation in the background of biostatistical consultants is huge. This varying background in formal education complicates communication. It may obscure clients' expectations as well as any discussion on qualifications and registration. To tackle these disadvantages as well as to facilitate the training of a new colleague, we need to find common ground. The aim of this paper is to identify the central disciplines which constitute the foundation of biostatistical consultancy. Any task‐aimed curriculum should be based on these disciplines. Curriculum design theory was used to guarantee a logical and rational process. The result is the identification of a sextet of disciplines: applied statistics; methodology; epidemiology; communication; computational science, and personal effectiveness. Copyright © 2001 John Wiley & Sons, Ltd.
Small‐sample adjustments in using the sandwich variance estimator in generalized estimating equations
Authors: Pan Wei , Wall Melanie M.
Published: August 2002

The generalized estimating equation (GEE) approach is widely used in regression analyses with correlated response data. Under mild conditions, the resulting regression coefficient estimator is consistent and asymptotically normal with its variance being consistently estimated by the so‐called sandwich estimator. Statistical inference is thus accomplished by using the asymptotic Wald chi‐squared test. However, it has been noted in the literature that for small samples the sandwich estimator may not perform well and may lead to much inflated type I errors for the Wald chi‐squared test. Here we propose using an approximate t‐ or F‐test that takes account of the variability of the sandwich estimator. The level of type I error of the proposed t‐ or F‐test is guaranteed to be no larger than that of the Wald chi‐squared test. The satisfactory performance of the proposed new tests is confirmed in a simulation study. Our proposal also has some advantages when compared with other new approaches based on direct modifications of the sandwich estimator, including the one that corrects the downward bias of the sandwich estimator. In addition to hypothesis testing, our result has a clear implication on constructing Wald‐type confidence intervals or regions. Copyright © 2002 John Wiley & Sons, Ltd.
Statistical models appropriate for designs often used in group‐randomized trials
Authors: Murray David M.
Published: August 2002

Group‐randomized trials are characterised by the allocation of identifiable groups rather than individuals to study conditions; members within those groups are then observed to assess the effect of the intervention. It is convenient to categorize the designs employed in group‐randomized trials along two dimensions, each with two levels. The first distinguishes between designs having just one or two time intervals and those having three or more intervals. The second distinguishes between nested cohort and nested cross‐sectional designs. Following a brief review of the design and analytic issues common to group‐randomized trials, and their general solutions, this paper presents the adaptations of the mixed‐model analysis of covariance and random coefficients models that are required for the four combinations that result from this categorization scheme. The assumptions, strengths and weaknesses of each model are discussed. Copyright © 2001 John Wiley & Sons, Ltd.
Hidden Markov models for the onset and progression of bronchiolitis obliterans syndrome in lung transplant recipients
Authors: Jackson Christopher H. , Sharples Linda D.
Published: August 2002

Chronic rejection in lung transplant recipients is monitored by repeated measurement of forced expiratory volume in one second (FEV1). This marker is measured at irregular intervals and is also affected by covariates and short‐term fluctuation. This paper describes the use of hidden Markov models for the underlying staged functional decline. Maximum likelihood methods are used to simultaneously estimate disease progression rates and the effects of mismeasurement and covariates. Copyright © 2002 John Wiley & Sons, Ltd.
Covariance models for nested repeated measures data: analysis of ovarian steroid secretion data
Authors: Park Taesung , Lee Young Jack
Published: August 2002

We consider several covariance models for analysing repeated measures data from a study of ovarian steroid secretion in reproductive‐aged women. Urinary oestradiol and serum oestrogen were repeatedly observed over three or four menstrual periods, each period separated by one year. For each menstrual period, daily first morning urine specimens were collected 8 to 18 times, and serum specimens 2 to 5 times. Thus, measurements were repeatedly observed over menstrual cycle days within menstrual periods. Owing to missing observations, the number of observations differed from subject to subject. In this study, there were two repeat factors: menstrual cycle day and menstrual period. The first repeat factor, cycle day, is nested within the second repeat factor, menstrual period. In analysing these nested repeated measures data, the correlation structure should be modelled that will account for both repeat factors. We present several covariance models for defining appropriate covariance structures for these data. Published in 2002 by John Wiley & Sons, Ltd.
Prospective prediction in the presence of missing data
Authors: Marshall Guillermo , Warner Bradley , MaWhinney Samantha , Hammermeister Karl
Published: August 2002

A variety of methods and algorithms are available for estimating parameters in the class of a generalized linear model in the presence of missing values. However, there is little information on how this already built model can be used for prediction in new observations with missing data in the covariates. Dropping the observations with missing values is a widespread practice with serious statistical and non‐statistical implications. One solution is to fit separate regression models, or submodels, to each pattern of missing covariates. In practice, for any iterative regression method, this approach is computationally intensive. We propose a simple methodology to predict outcomes for individuals with incomplete information based on the estimated coefficients and covariance from the already built model. This method does not require revisiting the original data set used to build the original model and works by generating a first‐order approximation of any submodel coefficient estimates. This is achieved by using the SWEEP operator on an augmented covariance matrix obtained from the original model. We refer to this approach as theone‐step sweep(OSS) method. The methodology is demonstrated using data from the Department of Veterans Affairs Continuous Improvement in Cardiac Surgery Program (CICSP). These data contain 30 day mortality, the outcome of interest, and risk information for over 14000 patients who underwent coronary artery bypass grafting (CABG) surgery over a four‐yearperiod. Using complete data from the first 3.5 years of this study period, a logistic regression model was built. This model was then used to predict mortality for patients undergoing CABG in the most recent 6‐months. In order to evaluate the performance of the OSS method we randomly generated observations with missing covariates in the 6‐month prediction database. We use this simulation to demonstrate that the computationally efficient OSS substantially reduces the error in risk‐adjusted mortality created when cases with incomplete information are eliminated. Lastly, we derive the relationship between the OSS method and data imputation. Copyright © 2002 John Wiley & Sons, Ltd.
Non‐linear hierarchical models for monitoring compliance
Authors: Pauler Donna K. , Laird Nan M.
Published: August 2002

As biomarkers transformable by specific drug agents increasingly become available, so their usefulness also increases for monitoring compliance in clinical and prevention trials, and for subsequent monitoring in the general population if a treatment is found successful. Marker levels measured over the course of a treatment yield a longitudinal trajectory that is typically non‐linear, with varying velocities during the phase‐in and steady‐state periods of treatment, followed by decays back to normal in the presence of non‐compliance. There is often considerable between‐individual variability both in the mean parameters of the trajectory and the variability over time. An example is the biomarker mean corpuscular volume (MCV), which increases by 20 per cent from the drug zidovudine (AZT), and has been used to monitor compliance to AZT. Using MCV data from a previous AIDS clinical trial as an example, we describe a non‐linear hierarchical growth model suitable for biomarkers that exhibit sigmoidal and/or asymptotic growth behaviour and show how such models can be supplemented with a change‐point to identify potential times of non‐compliance. We perform a fully Bayesian analysis to obtain a variety of posterior summaries for the behaviour of the longitudinal trajectory and the times of non‐compliance, and describe how to obtain predictions of non‐compliance for new individuals. Copyright © 2002 John Wiley & Sons, Ltd.
Beyond local search: boundary‐spanning, exploration, and impact in the optical disk industry
Authors: Rosenkopf Lori , Nerkar Atul
Published: August 2002

Recognition of the firm's tendency toward local search has given rise to concepts celebrating exploration that overcomes this tendency. To move beyond local search requires that exploration span some boundary, be it organizational or technological. While several studies have encouraged boundary‐spanning exploration, few have considered both types of boundaries systematically. In doing so, we create a typology of exploration behaviors: local exploration spans neither boundary, external boundary‐spanning exploration spans the firm boundary only, internal boundary‐spanning exploration spans the technological boundary only, and radical exploration spans both boundaries. Using this typology, we analyze the impact of knowledge generated by these different types of exploration on subsequent technological evolution.

In our study of patenting activity in optical disk technology, we find that exploration that does not span organizational boundaries consistently generates lower impact on subsequent technological evolution. In addition, we find that the impact of exploration on subsequent technological evolution within the optical disk domain is highest when the exploration spans organizational boundaries but not technological boundaries. At the same time, we find that the impact of exploration on subsequent technological development beyond the optical disk domain is greatest when exploration spans both organizational and technological boundaries. Copyright © 2001 John Wiley & Sons, Ltd.
When will boards influence strategy? inclination × power = strategic change
Authors: Golden Brian R. , Zajac Edward J.
Published: August 2002

While boards of directors are usually recognized as having the potential to affect strategic change in organizations, there is considerable debate as to whether such potential is typically realized. We seek to reconcile the debate on whether boards are typically passive vs. active players in the strategy realm by developing a model that specifies when boards are likely to influence organizational strategy and whether such an influence is likely to impel vs. impede change. Specifically, we develop arguments as to when certain demographic and processual features of boards imply a greater inclination for strategic change, when these features imply a greater preference for the status quo, and how differences in such inclinations will influence strategic change. We then also propose that a board's inclination for strategic change interacts with a board's power to affect change, generating a multiplicative effect on strategic change. These ideas are tested using survey and archival data from a national sample of over 3000 hospitals. The supportive findings suggest that strategic change is significantly affected by board demography and board processes, and that these governance effects manifest themselves most strongly in situations where boards are more powerful. We discuss these findings in terms of their relevance for theories of demography, agency, and power. Copyright © 2001 John Wiley & Sons, Ltd.
The adoption of agency business activity, product innovation, and performance in Chinese technology ventures
Authors: Li Haiyang , Atuahene‐Gima Kwaku
Published: August 2002

This study examines the roles of firm characteristics and environmental factors in the formation of interfirm alliances. Specifically, we examine the dual role of these groups of factors as inducements and opportunities for Chinese high‐technology new ventures (HTNVs) in their adoption of agency business activity, a downstream type of alliance involving marketing and distribution of the products of foreign firms. Results suggest that both internal and external factors are related to the adoption of agency business activity but the inducement and opportunity value of environmental uncertainty may be dampened by institutional support provided to HTNVs. Further, we find that successful agency business activity is positively related to new venture performance but negatively related to its product innovation efforts. Theoretical and managerial implications are discussed. Copyright © 2002 John Wiley & Sons, Ltd.
An empirical investigation of firm public and private knowledge
Authors: Matusik Sharon F.
Published: August 2002

Many studies examine firm private knowledge, but purport to be generalizable to the totality of firm knowledge, both public and private. This study demonstrates that public and private firm knowledge are empirically separable constructs that have significant and yet different influences on innovative outcomes. The example of product development effectiveness within this study shows that both public and private knowledge are significantly related to product development quality; however, public knowledge is negatively related to quality lapses while private knowledge is positively related to quality lapses. Copyright © 2002 John Wiley & Sons, Ltd.
JAC—Access right based encapsulation for Java
Authors: Kniesel Günter , Theisen Dirk
Published: August 2002

Unwanted effects of aliasing cause encapsulation problems in object‐oriented programming. Nevertheless, aliasing is part of common and efficient programming techniques for expressing sharing of objects and as such its general restriction is not an option in practice. This paper proposes an approach that allows full referential object sharing but adds transitive access control to object references to limit the effects of aliasing. The approach relies on well‐known properties of object‐oriented type systems but exploits them in a novel way to support an access‐right‐based model of encapsulation. It is presented as an extension of Java, called JAC (Java with Access Control). Copyright © 2001 John Wiley & Sons, Ltd.
An architecture for extensible middleware platforms
Authors: Bruneton Eric , Riveill Michel
Published: August 2002

This article presents a middleware platformarchitecturewhose goals, motivated by the needs of a real‐world application, are the following: separation of functional and non‐functional code in applications, composition of non‐functional properties, and modularity and extensibility of the middleware platform itself. This architecture is inspired by the Enterprise Java Beans platform, and uses a new object composition model to separate and compose the non‐functional properties. In order to evaluate this architecture, we have implemented the JavaPod platform which we have used to implement a prototype of the application that motivated our goals. The results of these experiments show that our goals can indeed be achieved with our architecture. Copyright © 2001 John Wiley & Sons, Ltd.
Software process matrix: a small company SPI model
Authors: Richardson Ita
Published: August 2002

Because small company structure is very different to that of large organizations, models which help them to improve their software process must be created with this in mind. The author of this paper has developed and verified such a model, based on quality function deployment, the software process matrix. A summary of its development and verification is presented. Subsequently, the matrix was validated in two small software development companies during a longitudinal study and the paper discusses an analysis of some of the processes which changed as a result of its implementation—organization, customer management and project management. This provides some insight into the software process of the companies, both prior to and at the end of the research period. Generalization and validity to other companies, large and small, is considered. Copyright © 2001 John Wiley & Sons, Ltd.