bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential stable isotope labeling of peptides for quantitation and de novo sequence derivation
Authors: Goodlett David R. , Keller Andrew , Watts Julian D. , Newitt Richard , Yi Eugene C. , Purvine Samuel , Eng Jimmy K. , Haller Priska von , Aebersold Ruedi , Kolker Eugene
Published: August 2002

We have demonstrated the use of per‐methyl esterification of peptides for relative quantification of proteins between two mixtures of proteins and automated de novo sequence derivation on the same dataset. Protein mixtures for comparison were digested to peptides and resultant peptides methylated using either d0‐ or d3‐methanol. Methyl esterification of peptides converted carboxylic acids, such as are present on the side chains of aspartic and glutamic acid as well as the carboxyl terminus, to their corresponding methyl esters. The separate d0‐ and d3‐methylated peptide mixtures were combined and the mixture subjected to microcapillary high performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). Parent proteins of methylated peptides were identified by correlative database searching of peptide tandem mass spectra. Ratios of proteins in the two original mixtures could be calculated by normalization of the area under the curve for identical charge states of d0‐ to d3‐methylated peptides. An algorithm was developed that derived, without intervention, peptide sequence de novo by comparison of tandem mass spectra of d0‐ and d3‐peptide methyl esters. Copyright © 2001 John Wiley & Sons, Ltd.
Strategies for determination of insulin with tandem electrospray mass spectrometry: implications for other analyte proteins?
Authors: Fierens Colette , Stöckl Dietmar , Thienpont Linda M. , De Leenheer André P.
Published: August 2002

Using human insulin (MW 5808 Da) as a model compound, the possible strategies towards optimization of sensitivity and selectivity of measurement by electrospray ionization with a standard triple quadrupole mass spectrometer were investigated. For measurement in selected ion‐monitoring (SIM) mode, these strategies involved systematic variation of instrumental parameters and spray pH. In this investigation four different operating modes were used corresponding to positive/negative ionization modes with acidic/basic sprays and pH reversed (hereafter termed ‘wrong‐way‐round’ operation); the cone voltage was optimized for each mode of operation. When collision‐activated dissociation (CAD) is employed, two additional operation modes are possible: namely, low collision energies (10–35 eV, CAD‐l) for the generation of sequence‐specific fragments and high collision energies (>80 eV, CAD‐h) for the generation of nonspecific fragments. Overall, this results in twelve different modes of operation.

Loop‐injection of aqueous insulin standards were run for each of the twelve operating modes and measurements made for five different charge states (n = 2–6) observable with our instrument that has an upper mass limit of m/z 4000. The signal/noise (S/N) ratio was optimized for each charge state, resulting in 60 measurements. The best S/N ratios (20 000) were achieved under positive SIM conditions with charge state 6 (m/z 969) and under ‘wrong‐way‐round’ negative SIM conditions with charge state 3 (m/z 1935). Lower S/N ratios were observed under positive CAD‐h conditions with charge state 5 (m/z 1163, S/N 15 000) and positive CAD‐l conditions with charge state 6 (m/z 969, S/N 10 000). All other operating modes gave maximum S/N ratios of 4000.

For measurement of insulin standards, the results obtained show SIM to give the best S/N ratio. However, for samples in complex matrices, our general experience suggests CAD to be the preferable operating mode. Consequently, for the development of a quantitative method for proteins in general, it might be advocated that all of the twelve operating modes and all relevant charge states be investigated to find the optimum S/N ratio. Copyright © 2001 John Wiley & Sons, Ltd.
Analysis of fatty acids by graphite plate laser desorption/ionization time‐of‐flight mass spectrometry
Authors: Park Kyung‐Ho , Kim Hie‐Joon
Published: August 2002

Fatty acids obtained from triglycerides (trioelin, tripalmitin), foods (milk, corn oil), and phospholipids (phosphotidylcholine, phosphotidylserine, phosphatidic acid) upon alkaline hydrolysis were observed directly without derivatization by graphite plate laser desorption/ionization time‐of‐flight mass spectrometry (GPLDI‐TOFMS). Mass‐to‐charge ratios predicted for sodium adducts of expected fatty acids (e.g. palmitic, oleic, linoleic and arachidonic acids) were observed without interference. Although at present no quantitation is possible, the graphite plate method enables a simple and rapid qualitative analysis of fatty acids. Copyright © 2001 John Wiley & Sons, Ltd.
High‐speed gradient parallel liquid chromatography/tandem mass spectrometry with fully automated sample preparation for bioanalysis: 30 seconds per sample from plasma
Authors: Deng Yuzhong , Wu Jing‐Tao , Lloyd Thomas L. , Chi Cecilia L. , Olah Timothy V. , Unger Steve E.
Published: August 2002

In this work, a high‐throughput and high‐performance bioanalytical system is described that is capable of extracting and analyzing 1152 plasma samples within 10 hours. A Zymark™ track robot system interfaced with a Tecan Genesis™ liquid handler was used for simultaneous solid‐phase extraction of four 96‐well plates in a fully automated fashion. The extracted plasma samples were injected onto four parallel monolithic columns for separation via a four‐injector autosampler. The use of monolithic columns allowed for fast and well‐resolved separations at a considerably higher flow rate without generating significant column backpressure. This resulted in a total chromatographic run cycle time of 2 min on each 4.6 × 100 mm column using gradient elution. The effluent from the four columns was directed to a triple quadrupole mass spectrometer equipped with an indexed four‐probe electrospray ionization source (Micromass MUX™ interface). Hence, sample extraction, separation, and detection were all performed in a four‐channel parallel format that resulted in an overall throughput of about 30 s per sample from plasma. The performance of this system was evaluated by extracting and by analyzing twelve 96‐well plates (1152) of human plasma samples spiked with oxazepam at different concentrations. The relative standard deviation (RSD) of analyte sensitivity (slope of calibration curve) across the four channels and across the 12 plates was 5.2 and 6.8%, respectively. An average extraction recovery of 77.6% with a RSD of 7.7% and an average matrix effect of 0.95 with a RSD of 5.2% were achieved using these generic extraction and separation conditions. The good separation efficiency provided by this system allowed for rapid method development of an assay quantifying the drug candidate and its close structural analog metabolite. The method was cross‐validated with a conventional liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay. Copyright © 2002 John Wiley & Sons, Ltd.
Interactions of Natural Colloidal Material and Phenanthrene in the Aquatic Environment
Authors: Tulve Nicolle S. , Young Thomas C.
Published: August 2002

Resuspension of contaminated aquatic sediments by natural and anthropogenic activities (i.e., dredging, boat activities, fish, wildlife, storms, runoff) increases the flux of natural colloidal material and colloidally bound contaminants into the overlying water column. Colloidal material extracted from lower Fox River sediments was analyzed for various physical and chemical characteristics and subjected to batch aggregation studies under controlled conditions of pH (∼3–8) and colloid concentrations (5 and 9 mg L−1 as TOC equivalents) in the presence of dissolved phenanthrene in solution. Under water chemistry conditions where pH and K+ concentration are typical of most natural waters (10−2 M K+ and pH∼8), the presence of phenanthrene in solution (average [phen] = 0.2–0.4 mg/L) prevents particle aggregation and decreases the settling rate of these particles. Ultimately, this increases the total concentration of colloidally bound contaminants in the water column. Dredging is the most popular remediation technique for removing contaminated sediments from the aquatic environment. However, this laboratory study suggests that for typical waters, dredging may potentially elevate the concentrations of contaminants found in the water column. © 2001 John Wiley & Sons, Inc.
Long‐Term Contaminant Trends at the Picillo Farm Superfund Site in Rhode Island
Authors: Boving Thomas B. , Blue Julie
Published: August 2002

Environmental disasters, such as the infamous Love Canal site or the Valley of Drums, have taken many years
and consumed billions of dollars to investigate and remediate. In consequence, a large amount of geologic and
hydrologic information has been gathered over the past few decades. Because of the difficulties involved with
compiling this information, scientists and professionals rarely use the data to investigate the unique
long‐term databases. This article presents for the first time the compilation of chemical fate and
transport data from the Picillo Farm Superfund site in Rhode Island. The data cover a quarter of a century worth
of geologic, hydrogeologic, and geochemical information and indicate significant changes in the contaminant
inventory and the center of mass contaminant location over time. Many of these changes would have been missed if
a data set of shorter duration were evaluated. Thus, compiling and evaluating data collected over many years can
be extremely valuable in understanding the fate and transport of contaminants and determining the effectiveness
of remediation. © 2002 Wiley Periodicals, Inc.
Treatment of Highly Contaminated Groundwater: A SITE Demonstration Project
Authors: Sullivan Daniel , Merdinger Michael , Kosco William , Ray Asim B.
Published: August 2002

From September through November 1994, the U.S. Environmental Protection Agency (EPA) conducted a
field demonstration of the remediation of highly contaminated groundwater at the Nascolite Superfund site
located in Millville, New Jersey. Besides high concentrations of the major contaminant, methyl methacrylate
(MMA), the groundwater also contained small amounts of volatile and semivolatile organic compounds.
ZenoGem® technology, an integrated bioreactor and ultrafiltration membrane system, was employed for this
demonstration project. Approximately 30,000 gallons of groundwater containing MMA in concentrations of 567 to
9,500 milligrams per liter (mg/L) and chemical oxygen demand (COD) values ranging from
1,490 to 19,600 mg/L was treated. The demonstration focused on the system's ability to remove MMA and
reduce COD from the groundwater. Results of the three‐month demonstration showed that average MMA and COD
removal efficiencies were greater than 99.9 and 86.9, respectively. The total cost of treatment, depending on
the duration of the project, is estimated to vary from $0.22 to $0.55 (in 1994 dollars)
per gallon of groundwater treated. © 2001 John Wiley & Sons.
Brownfields Update: The Reform of the Brownfields Economic Redevelopment Initiative
Authors: Green Keith E. , Bonner Colleen E.
Published: August 2002

This journal first reported on the U.S. EPA's Brownfields Initiative in the summer 1995 edition of
Remediation. At that time, the initiative was only about 15 months old, most of the state
programs were in proposal stages, and little federal legislation addressing brownfields had been proposed.
Today, brownfields has become such a common term that almost every environmental professional is familiar with
it. The EPA has placed extremely high priority on the Brownfields Initiative and it has become a politically hot
issue. This article provides an update on the current status of EPA's Brownfields program and also
discusses recent legislation proposed by Congress to promote brownfields redevelopment. © 2001 John Wiley
& Sons, Inc.
Hepatitis B and hepatitis C co‐infection in patients with HIV
Authors: Herrero Martínez E.
Published: August 2002

An Erratum has been published for this article in Reviews in Medical Virology 11 (5) 2001, 343

HAART has increased the life expectancy of patients with HIV. However, as their life expectancy increases, it becomes increasingly important to focus on the management of concurrent illnesses such as chronic HBV and HCV infections which have the potential to increase mid to long term morbidity and mortality. Shared epidemiological risks have resulted in the HIV infected population having a higher incidence of both HBV and HCV than those uninfected with HIV. Co‐infection with HIV modifies the natural history of HBV infection, increasing the rate of viral replication, risk of carriage and chronic hepatitis but without increasing liver necroinflammatory processes. In chronic HCV infection, the presence of HIV enhances the risk of severe liver disease. There is no evidence as yet that HBV directly impacts on HIV disease progression but HCV infection increases the risk of death or an AIDS defining illness and impairs CD4+ T cell recovery during antiretroviral therapy. Treatment of either hepatitis virus is complex because of pharmacokinetic interactions with components of HAART regimens. Copyright © 2001 John Wiley & Sons, Ltd.
Molecular techniques should now replace cell culture in diagnostic virology laboratories
Authors: Carman Bill
Published: August 2002

Cell cultures have been important historically for the development of virology. However, I will argue that they are no longer essential for a diagnostic laboratory and should be replaced with nucleic acid detection methods. This change of technology should be cost‐neutral once the full costs to the laboratory of cell cultures, including staff time, are calculated. Molecular methods are more sensitive than cell cultures and provide answers much more rapidly, especially for negative samples. Since negative results are frequently as important to our clinical colleagues as positive results, we should change now to routine diagnostic services based upon nucleic acid detection. Copyright © 2001 John Wiley & Sons, Ltd.
Convergence properties of functional estimates for discrete distributions
Authors: Antos András , Kontoyiannis Ioannis
Published: August 2002

Suppose P is an arbitrary discrete distribution on acountable alphabet 𝒳. Given an i.i.d. sample (X1,…,Xn) drawnfrom P, we consider the problem of estimating the entropy H(P) or some other functional F=F(P) of the unknown distribution P. We show that, for additive functionals satisfying mild conditions (including the cases of the mean, the entropy, and mutual information), the plug‐in estimates of F are universally consistent. We also prove that, without further assumptions, no rate‐of‐convergence results can be obtained for any sequence of estimators. In the case of entropy estimation, under a variety of different assumptions, we get rate‐of‐convergence results for the plug‐in estimate and for a nonparametric estimator based on match‐lengths. The behavior of the variance and the expected error of the plug‐in estimate is shown to be in sharp contrast to the finite‐alphabet case. A number of other important examples of functionals are also treated in some detail. © 2001 John Wiley & Sons, Inc. Random Struct. Alg., 19: 163–193, 2001
Blind equalization of quadrature partial response‐trellis coded modulated signals in Rician fading
Authors: Cirpan Hakan A. , Ucan Osman N.
Published: August 2002

In this paper, a blind maximum‐likelihood channel estimation algorithm is developed for quadrature partial response‐trellis coded modulated (QPR‐TCM) signals propagating through a Rician fading environment. A hidden Markov model (HMM) formulation of the problem is introduced and the Baum–Welch parameter estimation algorithm is modified to provide a computationally efficient solution to the resulting optimization problem. Performance analysis of the proposed method is carried out through the evaluation of bit‐error probability upper bound for Rician fading channels. Also, some illustrative simulations are presented. Copyright © 2001 John Wiley & Sons, Ltd.
To appreciate variation between scientists: A perspective for seeing science's vitality
Authors: Wong E. David
Published: August 2002

At the heart of theoretical and practical ideas about science education is an image of scientific work. This image draws attention to particular features of scientific work, which then guides scholarship and pedagogy in science education. In the field of science education, much discussion in this vein focuses on the question, “What is the nature of science?” Most images of science found in education, psychology, and philosophy emerge from conceptual and methodological perspectives that emphasize norms, conventions, and broad trends. Some groups are motivated to distinguish science from other activities while some groups work in the opposite direction and blur the lines between science and others ways of knowing. Underlying both perspectives is an implicit focus on general qualities common to groups or subgroups (e.g. believing that ideas are subject to change, explanations demand evidence, science is a complex social activities, etc.). I propose that the vital qualities of science are best illuminated by just the opposite process: by appreciating the uncommon, rather than common, features. By attending to individual variation, we are more likely to understand what makes science a creative, motivating, and deeply personal enterprise. In addition, appreciating these variations reveals judgment, creativity, adaptation—the hallmark of scientific work. Implications of this perspective for science education are discussed. © 2002 Wiley Periodicals, Inc. Sci Ed 86:386–400, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/sce.10023
A partial matching method for a fully automated directory assistance system using touch‐tone telephones as input devices
Authors: Oku Masahiro , Nagai Ryoji , Noda Ryousuke , Hayashi Tomosada , Higashida Masanobu
Published: August 2002

We have been developing a fully automated Japanese directory assistance system using touch‐tone telephones as input devices. This system is characterized by a newly developed input interface, called the degenerated keyword input method, which reduces the user's input workload. This input method associates one push on a button with one character of kana (Japanese syllabary). Since each touch‐tone button on a telephone can represent several different kana characters, using a touch‐tone numeral string as the search keyword inevitably leaves some ambiguity. This paper proposes a partial matching method, which is especially suitable for the fully automated Japanese directory assistance system. This method eliminates ambiguity in the degenerated keyword inputs and allows fast and highly accurate database searching. The method features the following. (1) It focuses on the PAT‐tree in the field of full‐text searching, and derives modified semi‐infinite strings (sistrings) at a word level, rather than at a character level, in the PAT‐tree for each record. (2) Word boundaries are marked in the index records, and only those candidates whose word boundary position coincides with the last character of the search keyword are selected as retrieval results. This use of word boundaries reduces retrieval noise. This paper also describes the results of evaluation experiments conducted to validate the proposed method. © 2002 Wiley Periodicals, Inc. Syst Comp Jpn, 33(6): 19–31, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.1129
Recognition of abdominal organs using 3D mathematical morphology
Authors: Fujimoto Hideyuki , Gu Lixu , Kaneko Toyohisa
Published: August 2002

This paper describes a method for recognizing abdominal organs in a computed tomography image primarily based on mathematical morphology. We first identify the coordinate origin and the scale in the abdominal region and then set up four regions for recognition. The recognition process consists of two steps: segmentation and identification. For the segmentation step we employ a differential top‐hat (DTT) operation. For the identification step, we first identify the vertebra that the lowest rib meets. The gravity center of this vertebra is used to set the coordinate origin. In three regions, we separate organs based on threshold values, while in a region containing the liver and stomach we use RE (Recursive Erosion) and GI (Geodesic Influence) in order to separate touched organs. The separated organs are identified or labeled based on the size and position. This method is judged to be effective since we were able to obtain a recognition or labeling rate of approximately 91%. © 2002 Wiley Periodicals, Inc. Syst Comp Jpn, 33(8): 75–83, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.1148
Towards sustainable urban water resource management: a case study in Tianjin, China
Authors: Bai Xuemei , Imura Hidefumi
Published: August 2002

Sustainable water resource management has become a critical issue for the development of cities that suffer scarce water resources. Tianjin City, located in China's Huaihe basin, one of the most polluted and water‐scarce river basins in the country, is a typical example in which water is posing a major constraint to the development. This paper examines the current status of the use of water resources, and the current practices and policy measures taken for water resource management in Tianjin, with a view to drawing lessons through an evaluation of these measures. The study illustrates the role of cities and their complex interaction with their peripheries for the allocation of scarce water resources, and it suggests that a systems approach should be adopted in order to analyse and understand the complexity of the entire picture. Based on this review and evaluation of Tianjin's experience, the authors propose a framework for sustainable water resource management in cities, emphasizing the importance of taking full consideration of resource/environmental capacity and an integrated systems approach for problem solving. Copyright © 2001 John Wiley & Sons, Ltd. and ERP Environment
A distributed computing approach to system dynamics
Authors: Duggan Jim
Published: August 2002

This article describes ongoing research into the application of distributed computing technologies to system dynamics. To date, a distributed modelling environment has been constructed. This is designed to support geographically dispersed decision makers—for example, participants in a virtual organisation who may wish to examine scenarios for their interconnected value chain. The implementation is based on distributed object technology and is tested using a negative feedback model of a business supply chain. Copyright © 2002 John Wiley & Sons, Ltd.
Oxidation studies of Au‐Al alloys using x‐ray photoelectron spectroscopy (XPS) and x‐ray absorption near‐edge structure (XANES)
Authors: Piao H. , McIntyre N. S.
Published: August 2002

The oxidation of thin‐film Au‐ Al alloy, as well as pure Al, has been studied using XPS across a wide range of water vapour and air exposures (0.1 L to 1 × 1014 L). The alloys and the pure Al all undergo a similar set of oxide growth kinetics. In addition to the three stages of early growth kinetics identified for Al in previous studies, a fourth stage is identified at air exposure doses of >109 L. During this stage, the average composition of the film changes from Al2O3 to Al2O3·H2O. The Al 2p lineshapes for the oxides grown on pure Al and Au‐Al alloy are different; the origins of this appear to result, in part, from a change in the Fermi level as the oxide thickens. The Al L2,3 X‐ray absorption near‐edge structure (XANES) furthermore provides a complementary probe of the different oxide structures on alloy and Al metal. Thus, their chemical characteristics are affected also by the presence of the gold. This difference in oxide structure is detected at the interface and not through the oxide generally. Copyright © 2001 John Wiley & Sons, Ltd.
Effects of temperature and Ar+ ion bombardment on the initial oxidation stages of polycrystalline aluminium with water vapour
Authors: Do T. , McIntyre N. S.
Published: August 2002

The initial stages of oxide formation following the interaction of water vapour with polycrystalline aluminium surfaces have been studied using x‐ray photoelectron spectroscopy (XPS) and Auger electron spectroscopy (AES). Attenuation of the electron signal from the metallic substrate has been used to follow the oxidation kinetics of aluminium as a function of energy and dose of Ar+ ion bombardment and temperature. The effects of energy and doses of Ar+ ion bombardment on oxidation kinetics have been examined in the energy range 1–5 keV and ion dose ranging from 1.3 × 1016 to 3.8 × 1017 ions cm−2. Although the increase in energy of Ar+ ion bombardment slightly modified the oxidation kinetics, the effects of ion dose on oxidation kinetics are shown to be more complex. There is a threshold dose of Ar+ ions above which the surface activity becomes significantly reduced; this is ascribed to cluster formation blocking the surface diffusion pathway in the near‐surface region. The oxidation kinetics of aluminium also have been studied in a range of temperature from room temperature up to 573 K. As the temperature increases, the oxidation rate of aluminium decreases due to a decrease in the sticking probability of water molecules on the aluminium surfaces. The observed temperature dependence of the oxidation kinetics is likely to be due to a precursor mechanism of water desorption. Copyright © 2001 John Wiley & Sons, Ltd.
Auger depth profiling of heat‐treated Au/Ni thin films
Authors: Abdul‐Lettif Ahmed M.
Published: August 2002

Gold/nickel thin films heat treated in the temperature range 200–500°C, have been analysed for composition–depth profiles using Auger electron spectroscopy in combination with simultaneous Ar+ ion sputtering. The present investigation indicates that pronounced nickel diffusion through the gold layer takes place due to annealing at 500°C for 5 min, whereas a noticeable nickel diffusion through the gold layer needs 3 h of annealing at 200°C. The measured concentration profiles suggest diffusion mechanisms involving infinitely fast grain boundary diffusion coupled with defect‐enhanced diffusion into the grains. Copyright © 2002 John Wiley & Sons, Ltd.
ToF‐SIMS studies of carbon‐fibre composite fracture surfaces and the development of controlled Mode in situ fracture
Authors: Prickett A. C. , Smith P. A. , Watts J. F.
Published: August 2002

The application of mechanical test methods and time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) to characterize the intralaminar failure of unidirectional carbon‐fibre‐reinforced polymer (CFRP) composites under different modes of loading is discussed. The development of a fracture stage that is able to generate fracture surfaces in situ within the spectrometer under a pure mode I tensile loading and a predominantly mode II shear loading is documented. The preparation of microtomed sections is shown to be a convenient and reliable method for the production of samples of heavily cross‐linked materials, such as matrix materials for CFRP composites, particularly for analysis in older ToF‐SIMS systems because of the reduced sample charging effects. Spectra from the bulk matrix material are compared with those from composite fracture surfaces. It is shown that the mechanism of failure in both of the composite loading situations is matrix dominated. Copyright © 2001 John Wiley & Sons, Ltd.
Synthesis of 6‐(1′‐pyrrolyl)‐n‐hexyltrichlorosilane and 6‐(1′‐pyrrolyl)‐n‐hexyltrimethoxysilane: XPS characterization of their monolayers self‐assembled on polycrystalline titanium surfaces
Authors: Cossement D. , Pierard C. , Delhalle J. , Pireaux J.‐J. , Hevesi L. , Mekhalif Z.
Published: August 2002

In this work are reported the synthesis of 6‐(1′‐pyrrolyl)‐n‐hexyltrichlorosilane (PyHTCS) and 6‐(1′‐pyrrolyl)‐n‐hexyltrimethoxysilane (PyHTMS) and the XPS characterization of polycrystalline titanium surfaces modified with these two molecules (10−3 M in toluene). PyHTCS forms densely packed monolayers after 15 min of reaction, whereas PyHTMS chemisorbs poorly, even after 2 h of reaction. Copyright © 2001 John Wiley & Sons, Ltd.
Tapping mode and phase imaging of biaxially oriented polyester films
Authors: Beake Ben D. , Leggett Graham J. , Shipway Philip H.
Published: August 2002

The surface morphology and mechanical properties of biaxially drawn poly(ethylene terephthalate) film surfaces have been investigated with tapping mode scanning force microscopy. Imaging with high tapping forces caused tip‐induced wear of the polymer surface. The damage was avoided by tapping at lower force. It is then possible to utilize phase detection imaging to provide ready access to surface properties such as stiffness and adhesion. Phase imaging has revealed a wealth of detailed surface structure information not seen in previous studies of heterogeneous polyester film materials. Not only are the different components of heterogeneous materials resolved with remarkable clarity, but detailed information is also provided on the phase morphology of individual components and on homogeneous polyester film materials. Copyright © 2001 John Wiley & Sons, Ltd.
Selection effects in randomized trials with count data
Authors: Cook Richard J. , Wei Wei
Published: August 2002

Selection criteria are specified in clinical trials to define the study population from which the sample will be obtained. It is common for one of these criteria to be based on historical or baseline measurements of the clinical sign or symptom that will serve as the response variable in the trial. The effect of such selection criteria has been studied extensively for normally distributed responses, but less is known about the situation in which the response is a count or a possibly recurrent event. In this paper we examine the bias and relative efficiency of some common methods of analysis for count data in the presence of selection criteria. The investigation is carried out using asymptotic theory pertaining to misspecified models and by simulation. Applications involving data from an epilepsy trial and a study of transient myocardial ischaemia illustrate the effect of ignoring the selection mechanism. Copyright © 2002 John Wiley & Sons, Ltd.
Non‐parametric confidence interval estimation for competing risks analysis: application to contraceptive data
Authors: Choudhury Jahar B.
Published: August 2002

Non‐parametric maximum likelihood estimation of the cause specific failure probability, and of its standard error, in the presence of competing risks is discussed with reference to some contraceptive use dynamics data from Bangladesh. The cause specific incidence function provides an intuitively appealing summary curve for failure rates and probabilities, such as probabilities of discontinuation of different kinds of contraception, based on right‐censored data of the particular event. Dinse and Larson's formula can be utilized to calculate the standard error of the cause specific probability for the failure type of interest, and to construct pointwise confidence intervals. The accuracy of these intervals, as well as those based on the log(‐log) transformation and the arcsine transformation, are compared by simulations. We find that Dinse and Larson's formula, used in conjuction with a log(‐log) transform, yields reliable standard error estimates and accurate coverage in samples of small and large size, and can be recommended for use in this situation. Copyright © 2002 John Wiley & Sons, Ltd.
Baseline information in structural failure time estimators for the effect of observed treatment compliance
Authors: Loeys T. , Goetghebeur E.
Published: August 2002

Structural accelerated failure time models allow expression of the effect of treatment actually received in placebo‐controlled randomized trials with non‐compliance. Without further assumptions, the structural parameter is typically estimated via a series of auxiliary logrank tests, searching for the structural parameter that back‐transforms treated survival times to latent treatment‐free survival times which are equally distributed between randomized arms. In this paper we investigate to what extent score tests involving baseline covariates provide more powerful auxiliary tests and lead to more precise estimates of the structural parameter without compromising the α‐level. We propose a set of estimating equations which combines score components for covariate effects based on the control arm only, with a log‐likelihood score for treatment effect based on both arms. Analytic results for exponential models as well as simulation studies for the semi‐parametric approach indicate that in many practical situations this incorporation of baseline covariates leads to more precise estimators of the structural effect. Relative efficiency is shown to depend on the selective nature of compliance. In a leukaemia trial we find the length of the 95 per cent confidence interval for the structural parameter is reduced to two‐thirds of the original length by incorporating baseline covariates in this way. Copyright © 2002 John Wiley & Sons, Ltd.
Enhancing the value delivered by the statistician throughout drug discovery and development: putting statistical science into regulated pharmaceutical innovation
Authors: Enas Gregory G. , Andersen John S.
Published: August 2002

With the dawn of the 21st century, the pharmaceutical industry faces a dramatically different constellation of business and scientific predictors of success than those of just a few years ago. Significant advances in science at the genetic, molecular and cellular levels, combined with progress demonstrated around the globe with drug regulations, have increased business and competitive opportunities. This has occurred in search of better and cheaper medicines that reach patients with unmet medical needs as quickly as possible. Herein lie new opportunities for those who can help business and regulatory leaders make good decisions about drug development and market authorization as quickly and efficiently as possible in the presence of uncertainty. The statistician is uniquely trained and qualified to render such value. We show how the statistician can contribute to the process of drug innovation from the very early stages of drug discovery until patients, payers and regulators are satisfied. Indeed, the very nature of regulated innovation demands that efficient and effective processes are implemented which yield the right information for good decision making. The statistician can take the lead in setting a strategy that directs such processes in the direction of greatest value. This demands skills that enable one to identify important sources of variability and uncertainty and then leverage those skills to make decisions. If such decisions call for more information, then the statistician can render experimental designs which generate the right information needed to make the decision in an efficient, timely manner. To add value to the enterprise, statisticians will have to become more intimately associated with business and regulatory decisions by building on their traditional roles (for example, numerical analyst, tactician) and unique skill sets (for example, analysis, computation, logical thought and work process, precision, accuracy). Business and regulatory savvy, coupled with excellent communication and interpersonal skills, will allow statisticians to help create the knowledge needed to drive success in the future. Copyright © 2001 John Wiley & Sons, Ltd.
Estimation of gender bias in clinical trials
Authors: Meinert Curtis L. , Gilpin Adele Kaplan
Published: August 2002

The perception is that the clinical trials enterprise has been biased in favour of males by devoting a disproportionate effort to males and to the diseases and conditions afflicting them – a perception reinforced by a few high profile male‐only heart trials undertaken in the 1970s and 1980s. The perception was sufficient to cause the U.S.A. Congress to enact legislation to require that a clinical trial ‘is designed and carried out in a manner sufficient to provide for a valid analysis of whether the variables being studied in the trial affect women … differently than other subjects in the trial’. Observed effort differentials are based on counts of single‐gender trials indexed in MEDLINE and published in U.S. journals. Differentials are compared to those expected using male–female differentials in mortality and years of potential life loss due to mortality before age 65 to estimate effort bias. The ratios of female‐only to male‐only published trials were 0.53, 0.89 and 0.95 for the decades of 1966–1975, 1976–1985 and 1986–1995, respectively. The expected ratios, if single‐gender trials were done in proportion to female–male mortality differentials, would be 0.57, 0.56 and 0.57, respectively. The differences in observed versus expected female to male ratios correspond to a slight excess of male‐only trials in the decade of 1966–1975 and to sizeable excesses in female‐only trials in the decades of 1976–1985 and 1986–1995. The results do not support the perception that women have been understudied relative to males in clinical trials. Most differentials favour females, whether based on mortality or years of potential life loss due to mortality before age 65 years. Copyright © 2001 John Wiley & Sons, Ltd.
Predicting analysis times in randomized clinical trials
Authors: Bagiella Emilia , Heitjan Daniel F.
Published: August 2002

Randomized clinical trial designs commonly include one or more planned interim analyses. At these times an external monitoring committee reviews the accumulated data and determines whether it is scientifically and ethically appropriate for the study to continue. With failure‐time endpoints, it is common to schedule analyses at the times of occurrence of specified landmark events, such as the 50th event, the 100th event, and so on. Because interim analyses can impose considerable logistical burdens, it is worthwhile predicting their timing as accurately as possible. We describe two model‐based methods for making such predictions during the course of a trial. First, we obtain a point prediction by extra‐polating the cumulative mortality into the future and selecting the date when the expected number of deaths is equal to the landmark number. Second, we use a Bayesian simulation scheme to generate a predictive distribution of milestone times; prediction intervals are quantiles of this distribution. We illustrate our method with an analysis of data from a trial of immunotherapy in the treatment of chronic granulomatous disease. Copyright © 2001 John Wiley & Sons, Ltd.
Evaluating inter‐hospital variability in mortality rates over time, allowing for time‐varying effects
Authors: Galai Noya , Simchen Elisheva , Braun Dalit , Mandel Micha , Zitser‐Gurevich Yana
Published: August 2002

In outcome studies, quality of care in various institutions is typically assessed by comparing observed to expected outcome rates, after adjusting for patients' case‐mix factors in logistic regression models. However, differences in patterns of outcome rates over time, especially when there is a distinction between the determinants affecting early and later events, are rarely studied. We use six‐month mortality after coronary artery bypass graft operation (CABG) as an example. We present a statistically valid approach to estimate expected survival curves for different subgroups, based on a Cox survival model with time‐varying effects. Bootstrap confidence intervals around the expected survival curves are constructed. This approach is applied for examining the pattern of deviation of high‐mortality hospitals after CABG. Implications for quality assessment in comparative outcome studies are discussed. Copyright © 2002 John Wiley & Sons, Ltd.
A model for foetal growth and diagnosis of intrauterine growth restriction
Authors: Hooper Peter M. , Mayes Damon C. , Demianczuk Nestor N.
Published: August 2002

A model for foetal growth is developed and used to construct tools for diagnosis of intrauterine growth restriction. Foetal weight estimates are first transformed to normally distributed z‐scores. The covariance structure over gestational ages is then estimated using a novel regression model. The diagnostic tools include individual growth curves with error bounds, probabilities to assess whether a foetus is small for its gestational age, and residual scores to determine whether current growth rates are unusual. The methods were developed sing data from 13593 ultrasound examinations involving 7888 oetal subjects. The model shows that median foetal growth elocity increases up to a gestational age of 35 weeks and then ecreases during the final weeks of pregnancy. When growth is xpressed as change in log weight, or equivalently as change oportional to current weight, the model reveals a constant celeration as gestational age increases from 14 to 42 weeks. Copyright © 2002 John Wiley & Sons, Ltd.
Bias adjustment in analysing longitudinal data with informative missingness
Authors: Park Soomin , Palta Mari , Shao Jun , Shen Lei
Published: August 2002

The recent biostatistical literature contains a number of methods for handling the bias caused by ‘informative censoring’, which refers to drop‐out from a longitudinal study after a number of visits scheduled at predetermined intervals. The same or related methods can be extended to situations where the missing pattern is intermittent. The pattern of missingness is often assumed to be related to the outcome through random effects which represent unmeasured individual characteristics such as health awareness. To date there is only limited experience with applying the methods for informative censoring in practice, mostly because of complicated modelling and difficult computations. In this paper, we propose an estimation method based on grouping the data. The proposed estimator is asymptotically unbiased in various situations under informative missingness. Several existing methods are reviewed and compared in simulation studies. We apply the methods to data from the Wisconsin Diabetes Registry Project, a longitudinal study tracking glycaemic control and acute and chronic complications from the diagnosis of type I diabetes. Copyright © 2002 John Wiley & Sons, Ltd.
Ecological investigation of firm effects in horizontal mergers
Authors: Lubatkin Michael , Schulze William S. , Mainkar Avinash , Cotterill Ronald W.
Published: August 2002

Using an ecological lens, we extend strategic management and industrial organization theory to investigate the performance effects of horizontal mergers. We theorize that firms differ in their ability to benefit from horizontal mergers; that the products involved in the merger differ in their ability to attain and sustain any increase in performance above their premerger level; and that resource niches in which each product competes differ in terms of competitive constraints. We then test these predictions using longitudinal data specified at the product–market level, a unit of analysis that is less influenced by aggregation bias than are industry, firm, and even line‐of‐business level data. Our findings demonstrate how organizational ecology, when coupled with strategic management and industrial organization economic theories, can enrich our understanding of horizontal mergers. Copyright © 2001 John Wiley & Sons, Ltd.
Corporate boards and outside stakeholders as determinants of environmental litigation
Authors: Kassinis George , Vafeas Nikos
Published: August 2002

Each year, hundreds of firms are prosecuted for violating environmental laws and hundreds of millions of dollars in penalties are assessed. At the same time, a much larger number of firms escape the various costs associated with litigation by adhering to the provisions of the same laws and regulations. It is not a priori apparent why this dichotomy exists. In this paper we draw on corporate governance and stakeholder theories to empirically investigate environmental lawsuits. Specifically, we compare the pre‐lawsuit profile of 209 violators to a sample of matched control firms between 1994 and 1998. We find that the likelihood of becoming a lawsuit defendant increases with board size, with the fraction of directors in industrial firms, and with the fraction of inside ownership, and decreases with the number of directorships held by outside directors. These findings are robust to alternative dependent variable specifications. Together, our results suggest that managers, researchers, and policy‐makers need to direct their attention to the corporate board as the core decision‐making unit forming corporate environmental policies. Copyright © 2002 John Wiley & Sons, Ltd.
A case study in repeated maintenance
Authors: Wang Shuanglin , Schach Stephen R. , Heller Gillian Z.
Published: August 2002

RTP is a widely used commercial real‐time product that has been maintained over a period of 13 years. We have analyzed multiple versions of RTP, which is written in C and Assembler. We measured increases in dependencies within the code between successive versions and performed statistical analyses on the data. There was no significant difference between the maintenance of Assembler files and C files. Also, there was no significant difference between the versions written by the original developers and those written by maintenance programmers not involved in the original development. The differences between individual programmers were very highly significant. Our interpretation of these results is that the skill of the individual programmer is an important factor in ensuring that a software product remains maintainable over its lifetime and that software engineering education and training are therefore of major importance. Copyright © 2001 John Wiley & Sons, Ltd.
Comments on ‘A cohesion measure for object‐oriented classes’ by Heung Seok Chae, Yong Rae Kwon and Doo Hwan Bae (Softw. Pract. Exper. 2000; 30:1405–1431)
Authors: Xu Baowen , Zhou Yuming
Published: August 2002

Although H. S. Chae's class cohesion measure considers not only the number of interactions, but also the patterns of the interactions among the constitute members of a class (which overcomes the limitations of previous class cohesion measures) it, however, only partly considers the patterns of interactions, and might cause the measuring results to be inconsistent with intuition in some cases. This paper discusses the demerits and proposes constructive amendments to Chae's cohesion measure. Copyright © 2001 John Wiley & Sons, Ltd.
Response to ‘Comments on: A cohesion measure for object‐oriented classes’
Authors: Chae Heung‐Seok , Kwon Yong‐Rae , Bae Doo‐Hwan
Published: August 2002

Indicating that CBMC does not satisfy the monotonic property in terms of the number of interactions, Xu and Zhou proposed an augmented definition of CBMC by adopting cut set instead of glue methods. The augmented CBMC clearly satisfies the monotonic property. However, CBMC is designed to overcome the problem with respect to the number of interactions and, therefore, focuses on the interaction pattern, especially, member connectivity. Consequently, it does not make sense to mention the monotonic property of CBMC with respect to interaction number. Moreover, the notion of glue methods allows several interpretations on the design quality of a class. However, that meaningful interpretation is not possible for the augmented definition due to the removal of the notion of glue methods. Copyright © 2001 John Wiley & Sons, Ltd.