bluuebunny/crossref_metadata_2025 huggingface dataset:
An Alternative Technique For Nasal Biopsy
Authors: Thornton M. A. , Walshe P. , Costello R.W , McConn‐Walsh R. , Walsh M.A.
Published: May 2004

Objectives/Hypothesis: The objective was to investigate the effectiveness of co‐phenylcaine as a topical anesthetic agent for nasal mucosal biopsy.

Study Design: A prospective study.

Methods: Nasal mucosal biopsy specimens were taken from a site just anterior to the inferior turbinate following topical anesthesia with co‐phenylcaine. All volunteers graded pain according to standard visual analogue scale (0–10) (VAS) scoring, and all were followed up after 24 hours for any epistaxis.

Results: Ninety nasal biopsy specimens were removed from 41 patients in all. Eight‐two percent did not report any discomfort following this procedure (VAS score, 0). Ten patients reported mild discomfort (VAS scores ranging between, 1and3) and only six reported pain (VAS scores ranging from 5 to7). However, five of these patients agreed to further biopsy and documented no discomfort during the repeat procedure. Only one patient required immediate intervention for hemorrhage after the procedure. In cases in which bleeding occurred (seven patients) it was documented within the first 6 hours, was minimal in content, and was controlled with local pressure. No systemic side effects were experienced.

Conclusion: Co‐phenylcaine is a suitable topical anesthetic agent for nasal mucosal biopsy. Removal of nasal tissue from a site anterior to the inferior turbinate can be performed under direct vision and provides sufficient tissue for histological assessment.
Functional Significance of Peripheral Head‐Shaking Nystagmus
Authors: Pérez Paz , Llorente José Luis , Gómez Justo R. , Campo Alfredo del , López Aurora , Suárez Carlos
Published: May 2004

Objectives/Hypothesis: The objective was to determine the characteristics of horizontal head‐shaking nystagmus of peripheral origin and its relationship to vestibular dysfunction.

Study Design: Retrospective case series.

Methods: Eighty‐three patients met the inclusion criteria of having peripheral and unilateral vestibular disease. Patients were tested with video nystagmography. Head‐shaking nystagmus was performed in the horizontal plane during 30 cycles at a frequency of approximately 3 Hz. Head‐shaking nystagmus was classified as monophasic or biphasic and, based on the pathological ear, as ipsilateral or contralateral related to nystagmus fast phases. The two‐tailed t test, ANOVA, Mann‐Whitney and χ2 tests, and lineal and polynomial regression tests were used for statistical analysis.

Results: Twenty‐three patients showed a positive head‐shaking nystagmus. All cases of head‐shaking nystagmus observed were horizontal. There were four biphasic and 19 monophasic cases of head‐shaking nystagmus. First phases of biphasic head‐shaking nystagmus beat toward the normal ear. Eleven of the monophasic cases of head‐shaking nystagmus were ipsilateral, and nine were contralateral. There was a statistically significant correlation between caloric weakness and head‐shaking nystagmus. Ipsilateral head‐shaking nystagmus corresponded to lower caloric asymmetries, and contralateral and biphasic head‐shaking nystagmus corresponded to greater caloric weakness (P < .001). As the caloric asymmetry increased, the maximal slow‐phase eye velocity of head‐shaking nystagmus was greater (P = .01) and its duration shortened (P = .008). Ipsilateral responses could be distinguished from contralateral responses based on their latency (P = .03), maximal slow‐phase eye velocity (P < .05), and duration (P = .02). The frequency of head‐shaking nystagmus was significantly higher among older patients. There was no correlation between head‐shaking nystagmus and clinical patterns.

Conclusion: Head‐shaking nystagmus of peripheral vestibular origin is a response both qualitatively and quantitatively associated with the degree of the vestibular loss.
Incidence of Unexpected Malignancies in Routine Tonsillectomy Specimens in Children
Authors: Garavello Werner , Romagnoli Marco , Sordo Lorenza , Spreafico Roberto , Gaini Renato Maria
Published: May 2004

Objectives: Controversy continues to exist regarding the necessity to routinely send for histologic examination those specimens obtained after tonsillectomy with or without adenoidectomy in children. Otolaryngologists fear missing an unsuspected diagnosis, such as a tonsil malignancy. However, given the rare incidence of this event, the cost‐effectiveness ratio of routine microscopic analysis is questionable. The purpose of this study was to assess the incidence of clinically relevant unexpected diagnosis among children who underwent tonsillectomy with or without adenoidectomy in our units and to review current available series on this topic.

Study Design: Retrospective study and review.

Methods: All patients aged less than 16 years who underwent routine tonsillectomy (with or without adenoidectomy) at San Gerardo Hospital, Monza, Italy from January 1994 to June 2002 were reviewed. Histologic examination is routinely performed in our units. Patients were excluded if the primary indication for surgery was to rule out a tonsil malignancy.

Results: One thousand one hundred twenty‐three (1,123) patients were recruited. Two cases of non‐Hodgkin's lymphoma were detected, corresponding to a rate of 0.18% (95% confidence interval [CI] 0.07–0.56). Three previously published series were identified. The reported incidences of unexpected clinically relevant diagnoses varied between 0.0% and 0.05%.

Conclusions: The results of our study highlight that the incidence of unexpected clinically relevant diseases of the tonsil in pediatric patients is low, albeit not extremely rare. This finding could be used to perform a cost‐effectiveness analysis.
Modified Translabyrinthine Approach and Hearing Preservation
Authors: Magliulo Giuseppe , Parrotto Donato , Stasolla Alessandro , Marini Mario
Published: May 2004

Objectives/Hypothesis: In 1991, the translabyrinthine approach was modified by sealing the vestibule with bone wax, which allowed preservation of the hearing function in one patient. The present study aimed specifically at evaluating the effectiveness of the modified translabyrinthine approach in preserving hearing function in a group of patients with vestibular schwannoma that involved the internal auditory canal.

Study Design: Prospective study.

Methods: The series consisted of 12 patients with vestibular schwannoma (average age, 49.7 y). The schwannoma was smaller than 2 cm in all patients who had surgery. The patients accepted for the study were required to have preserved hearing function.

Results: None of the patients has shown signs of persistence or tumoral relapse on postoperative magnetic resonance imaging. Immediately after surgery, the entire group had excellent facial functionality. Six patients had maintained their hearing function (four in Class 1 and two in Class 2 according to the Gardner‐Robertson scale) at the last follow‐up after surgery. A patient during follow‐up noted fluctuating hearing contemporarily with a tinnitus in the ear that had maintained its hearing, which was attributable to an endolymphatic hydrops. Three of the six patients with preserved hearing complained of persistent tinnitus. None of the patients had any of the complications or consequences of cerebellopontine surgery.

Conclusion: In our patients, Class 1 or 2 hearing was preserved in 50% of the patients, with no persistence or tumoral relapse. The follow‐up has obviously been short, but the first results are encouraging and deserve to be studied further in a more comprehensive survey.
Uncovering the Arundel Library at the Royal Society: changing meanings of science and the fate of the Norfolk donation
Authors: Peck L. V.
Published: May 2004

Thomas Howard, Earl of Arundel, was the most important collector in early 17th Century Britain. Much attention has been paid to his collections of painting and sculpture, his patronage of painters such as Rubens and Van Dyck and architects such as Inigo Jones, and his search through Greece and Turkey for antiquities. Little, however, has been written on the Arundel Library, which was equally famous. The cause is not hard to find: the library has been dispersed whereas the marbles and antiquities have found a home at Oxford, the manuscripts at the British Library and the College of Arms, and the paintings and sculpture remain identifiable whether at Arundel Castle or in British, continental or American museums. Yet the Arundel Library is of great significance: to the history of book–collecting by the great bibliophiles Willibald Pirckheimer and Arundel himself; to the study of the reading practices and libraries of members of the Howard family, possibly including Henry Howard, Earl of Surrey, and, certainly, his son, Henry Howard, Earl of Northampton; and, more generally, to the history of the book in the Renaissance and early modern Europe and the concomitant study of communities of readers.
Address of the President, Sir Aaron Klug, O.M., P.R.S., given at the Anniversary Meeting on 1 December 1997
Authors: Klug A.
Published: May 2004

Last year I devoted a good part of my address to matters of science policy and the role of the Royal Society in science advice. Over the last 15 years the Society has been increasingly drawn into this role, so that now it is a major part of our activities. This has been inescapable. The Society, as the premier society for science in this country, must expect to bear the responsibility for speaking for science to the public and to the government, not only for its relevance to national issues, but also to global issues.
Searching for people on Web search engines
Authors: Spink Amanda , Jansen Bernard J. , Pedersen Jan
Published: May 2004

The Web is a communication and information technology that is often used for the distribution and retrieval of personal information. Many people and organizations mount Web sites containing large amounts of information on individuals, particularly about celebrities. However, limited studies have examined how people search for information on other people, using personal names, via Web search engines. Explores the nature of personal name searching on Web search engines. The specific research questions addressed in the study are: “Do personal names form a major part of queries to Web search engines?”; “What are the characteristics of personal name Web searching?”; and “How effective is personal name Web searching?”. Random samples of queries from two Web search engines were analyzed. The findings show that: personal name searching is a common but not a major part of Web searching with few people seeking information on celebrities via Web search engines; few personal name queries include double quotations or additional identifying terms; and name searches on Alta Vista included more advanced search features relative to those on AlltheWeb.com. Discusses the implications of the findings for Web searching and search engines, and further research.
Is library anxiety important?
Authors: Jiao Qun G. , Onwuegbuzie Anthony J.
Published: May 2004

The prevalence of library anxiety among college students has been acknowledged by librarians and educators for over a decade. However, there are still people who question whether library anxiety is a real phenomenon. The importance of library anxiety among graduate students is particularly challenged. This study examined the relationship between library anxiety and trait anxiety of 115 graduate students in the United States. Findings revealed that trait anxiety was not significantly related to any of the five dimensions of library anxiety, suggesting that library anxiety is a unique, independent phenomenon. Therefore, library anxiety should be taken seriously. An action‐research approach to addressing library anxiety was recommended.
IBM: Decline or Resurrection?
Authors: Lloyd Bruce , Heller Robert
Published: May 2004

Robert Heller, author of The Fate of IBM, in discussion with Bruce Lloyd
(Head of Strategic and International Management, South Bank University).
Heller argues that at the core of IBM′s problem was a gap between its
management perceptions, driven by its historic success, and the reality
of the marketplace as seen by its customers. Until this gap was
recognized it was not possible for the need for radical change to be
accepted. The extent to which these challenges are inevitable is to
ensure that appropriate performance indicators are used, as these are
critical mechanisms for generating the required changes in culture
within the organization. It is also necessary to combine the effective
management of these performance indicators with effective learning
processes that focus on the future, rather than indulging in reflecting
on past glories and managing history.
The Strategic Leadership Star:
Authors: Nicholls John
Published: May 2004

Describes the Strategic Leadership Star, which provides a logical
framework which unifies the myriad of tools and techniques that are
proliferating under the TQM “umbrella”, change‐management practice and
modern strategic thinking. The central focus of all of these is superior
performance in the creation of “value to the customer”. Consequently,
customer value lies at the heart of the star. The first three points of
the star – “define your purpose”, “face the customer” and “focus on
essentials” ‐cover tools and techniques related to strategy formulation.
These include vision, intent, mission, process streams, core competences
and capabilities. The final two points ‐“create a challenge” and “trigger
enthusiasm” – relate to strategy implementation. They lead back to the
first point, fulfilment of the fundamental purpose, through such things
as: stretch, creative tension, benchmarking, systems thinking and
transforming leadership. Thus, the Strategic Leadership Star looks at
strategy making from a leadership perspective. Strategic leadership
requires equal attention to both path‐finding and culture‐building. This
means that, in performing the strategic leadership role, strategy
formulation and strategy implementation are no longer sequential and
separate but are subsumed in the complementary leadership activities of
strategic leadership. By following the star – i.e. using it as a daily
guide to behaviour – the management of an organization would
simultaneously be performing their strategic leadership role and
ensuring its strategic success.
Idea processing support systems
Authors: Proctor Tony
Published: May 2004

The article explores the concept of idea processing support systems noting their relevance and usefulness in management decision. A review of some of the pertinent software is offered along with an account of the development of an integrated idea processing support system called the creative decision support system. The latter takes the user through a seven stage process towards solving problems and includes graphic and audio triggers to creative thinking. Additionally there are databases for analogies, change of perspective and potential problem analysis. The package also has a drop and drag facility which allows the execution of external programs and text documents within the package.
No such thing as … the language of business: colourless green ideas sleep furiously
Authors: Rowe Jim
Published: May 2004

It is often said, in business and business schools, that accounting is the language of business. This paper attempts to deconstruct this nostrum by demonstrating the possibility of a language of business existing and why accounting is not it. The paper will briefly discuss the technical ability of accounting to behave as a communication medium and finally suggest that other functions may have a stronger claim.
Crafting corporate meaning
Authors: Karathanos Patricia
Published: May 2004

This article examines how meaning comes about through the symbolic interactions of organizational members. The article also explores the power dimension of creating and sustaining corporate meaning and proposes that leaders are well‐positioned to influence shared organizational meaning (culture). Specific attention is given to symbolic devices which corporate leaders can use to both craft and sustain meaning structures. Communicative implications for leaders who desire to craft corporate meaning are provided. Suggestions for research contributing to the verification and critical examination of shared corporate meaning are put forward.
World Wide Web technologies in CWRU libraries
Authors: Murray Peter
Published: May 2004

In this paper we focus on the development of World Wide Web technologies in our university libraries. We first outline a task force set up to design library services and to share techniques and resources across department boundaries. Next is a description of the first main project of the task force: the design of the Web interface into the library catalog, including a description of the final outcome and the design criteria used. Third, a description of the Master List of Databases project, an effort to centralize the list of all CWRU‐available indexes and full‐text resources. Following the database list project is a discussion of the evolution of our OPAC station software from a custom‐written DOS application to a Web‐based menu system. Finally, a description of the problem of remote access to library resources and an outline of two possible solutions: authenticating proxy servers and the Layer 2 Tunneling Protocol.
Information and technology transfer in Brazil: evolution and perspectives
Authors: Matilde Kronka Dias Maria , Vergueiro Waldomiro
Published: May 2004

Presents the evolution of the scientific and technological information infrastructure in Brazil, considering information as an input in the organization’s chain of values. Discusses the problem of information services for science and technology, as well as the offer and use of technological information in Brazil. Analyses the perspectives for information management in the technological transference process.
CD publishing and its scenario in India
Authors: Subba Rao Siriginidi
Published: May 2004

Highlights the features of CD‐ROM as a choice medium for information storage and dissemination, factors favouring CD publishing, and its areas of application. Describes how the newly arrived CD recordable drive changed the idea of desktop CD making, its working and limitations while mentioning the organizations that use CD‐Rs. Discusses the scenario of a CD‐ROM industry in India while listing a few Indian CD products. Concludes that CD‐ROM is the most sought‐after medium for commercial publishers and corporate communication and that, in India, the introduction of compulsory computer education in schools would augur well for the CD‐ROM market.
Cybernetics, the conscience of science Studies of interactions between physical and sociopolitical feedbacks and the theory behind them
Authors: Musès C.
Published: May 2004

Cybernetics is considered in its fundamental aspect of a unique master science embracing the concepts of the causation and precipitation of consequences, and hence entraining values and history. In this context a deeper approach to feedback and socio‐political realities becomes possible and is developed, in which practical problems are squarely addressed.
Collection management in the electronic environment
Authors: Singh S.P.
Published: May 2004

Describes briefly the impact of Information Technology on collection management in libraries and also on the librarian's role. Discusses the factors affecting collection management in libraries and emphasizes the need for change in collection management policy. Provides information about the availability of various electronic formats such as online sources, CD‐ROMs, Internet sources and Web sites along with criteria to evaluate them. Discusses the usefulness of subject gateways and compares pricing structures of different e‐sources.
Buyer‐seller relationships: how libraries can make the system work
Authors: Holt Glen E.
Published: May 2004

While there is always the potential for dissatisfaction in any buyer‐seller relationship, some libraries have been more successful than others in negotiating with vendors. Even though there is no one strategy that will work for all situations, five approaches seem to have proven themselves. By employing them, vendor negotiations will be far more successful than not, and major dissatisfaction can be avoided.
Electronic journals redux
Authors: Maxymuk John
Published: May 2004

When academic journals in electronic format were introduced, librarians eagerly anticipated a drop in wildly escalating journal prices. After all, publishers incur no paper costs, no mailing costs, and no significant additional production costs in distributing an electronic equivalent to their paper journals. However, to date, the crisis in rising serial costs has not been alleviated by the availability of electronic journals. Seven years after his first column discussing libraries' struggles with serial prices, the author revisits the topic of electronic journals and summarizes what we have learned about using journals in this format.
Using the philosophy of mobile agent technology for e‐service in the field of reverse engineering applications
Authors: Yingjie Zhang , Liling Ge
Published: May 2004

Reverse engineering methodology paves an efficient way for simulating and manufacturing existing objects with complex shapes, and a range of applications also has shown this approach to be feasible and efficient. However, in many applications, a lot of sub‐tasks in reverse engineering are usually not done in the same place, they need to be done cooperatively over the Internet or Intranet. So, this paper is concerned with developing a novel e‐service platform for remote service in reverse engineering applications based on mobile agent technology, and some correlative enabling technologies such as data compression, security considerations, agent models and so on. The framework was programmed using the Java Sevlets and Java Beans component models, and data transferring and processing were implemented based on the dispatch/retract mechanisms of mobile agents. The mobile agent is developed with IBM's Aglets Workbench, and the feasibility of the proposed method has been verified by a case.
An experimental study of surface quality and dimensional accuracy for selective inhibition of sintering
Authors: Asiabanpour Bahram , Palmer Kurt , Khoshnevis Behrokh
Published: May 2004

Selective inhibition of sintering (SIS) is a new rapid prototyping method that builds parts in a layer‐by‐layer fabrication basis. SIS works by joining powder particles through sintering in the part's body, and by sintering inhibition of some selected powder areas. In this research, statistical tools were applied to improve some important properties of the parts fabricated by the SIS process. An investigation of surface quality and dimensional accuracy was conducted using response surface methodology and through analysis of the experimental results, the impact of the factors on them was modeled. After developing a desirability function model, process operating conditions for maximum desirability are identified. Finally, the desirability model is validated.
A rapid design and manufacturing system for product development applications
Authors: Guangchun Wang , Huiping Li , Yanjin Guan , Guoqun Zhao
Published: May 2004

In recent years, rapid prototyping (RP) and rapid tooling (RT) technologies have been implemented in many aspects of industry, especially in the area of new product development. Based on RP and RT technologies, the paper proposes a rapid design and manufacturing system of the product. There are two ways to develop a new product in this system. One is beginning with a design concept, and another is from a sample as a reference. The reverse engineering technology, transmission processing software or modules of the input data, structure analysis and optimization means and manufacturing process analysis tools were integrated in the system. Some examples show that the integrated system not only can reduce the number of design iterations but also improve the efficiency and reliability of the product design.
RP in medicine: a case study in cranial reconstructive surgery
Authors: Gopakumar Sunil
Published: May 2004

During the repair of compound skull fractures or penetrating wounds to the brain, removal of significant portions of the skull may be required. Conventional prefabricated alloplastic implants require the use of complicated procedures during surgery, which can endanger a patient. Since prior rehearsals of the surgery are next to impossible, the surgery is usually complicated and lengthy. This paper aims to outline the importance of rapid prototyping (RP) in medicine, and also it details the use of RP for a cranioplastic surgery that was conducted in the South East Asian region. RP offers an easier way to design customized implants and manufacture them within a very short period. Rapid Prototyping can be used as an effective tool to generate complex 3D medical models from computed tomographic (CT) images. The models can be used for didactic purposes, as it helps the surgeons plan and rehearse the surgery well in advance. The RP prototype was used to successfully complete a cranioplastic surgery and realize the desired results. The operation time was also significantly reduced.
Hype and reality in performance management
Authors: Barrett Richard
Published: May 2004

Although few organizations would claim to have sophisticated and well integrated performance management programs up and running, during the last two years the concept of performance management has undergone a major transition. Up until the late 1990s, performance management as a concept was being nurtured in business schools and was predominantly concerned with the balanced scorecard. Other than for a few best of breed vendors, it was not something that the software industry got too involved with, as implementing wall‐to‐wall ERP and CRM solutions was far more lucrative. However, things have changed. Performance management has leapt out of its pram and started to scream around the nursery. Just like any toddler, it is making a lot of noise and at times can be very difficult to comprehend. Exactly how, when and in what order events happened is difficult to pin down, but its transformation is certainly manifest. This article discusses the rapid evolution of performance management; the competitive and regulatory pressures that are providing momentum to performance management and concludes by examining how companies are merging individual performance management methodologies into integrated solutions.
Why the property and casualty insurance industry needs a new performance measure
Authors: Calandro Joseph , Lane Scott
Published: May 2004

The property and casualty insurance industry has historically focused on the underwriting ratio as the primary measure of operating performance. Many dramatic changes have occurred in this industry and its operating environment over the past 30 years. These changes have dramatically decreased opportunities for underwriting profits, forcing the industry to rely more on investment returns and careful reinsurance. An alternative performance measurement system, the insurance performance measure (IPM), is presented and illustrated. The IPM integrates these other areas of operating activity into a more comprehensive measure of profitability.
Comprehensive Approach to Strategic Management:
Authors: Richardson Bill
Published: May 2004

Attempts to provide clarification over the definition of strategic management. Identifies and discusses a number of interrelated components which collectively create a configuration or domain for strategic management.
Simulated Likelihood Methods for Complex Double‐Platform Line Transect Surveys
Authors: Schweder Tore , Skaug Hans J. , Langaas Mette , Dimakos Xeni K.
Published: May 2004

Summary.The conventional line transect approach of estimating effective search width from the perpendicular distance distribution is inappropriate in certain types of surveys, e.g., when an unknown fraction of the animals on the track line is detected, the animals can be observed only at discrete points in time, there are errors in positional measurements, and covariate heterogeneity exists in detectability. For such situations a hazard probability framework for independent observer surveys is developed. The likelihood of the data, including observed positions of both initial and subsequent observations of animals, is established under the assumption of no measurement errors. To account for measurement errors and possibly other complexities, this likelihood is modified by a function estimated from extensive simulations. This general method of simulated likelihood is explained and the methodology applied to data from a double‐platform survey of minke whales in the northeastern Atlantic in 1995.
Marginally Specified Logistic‐Normal Models for Longitudinal Binary Data
Authors: Heagerty Patrick J.
Published: May 2004

Summary.Likelihood‐based inference for longitudinal binary data can be obtained using a generalized linear mixed model (Breslow, N. and Clayton, D. G., 1993,Journal of the American Statistical Association88, 9–25; Wolfinger, R. and O'Connell, M., 1993,Journal of Statistical Computation and Simulation48, 233–243), given the recent improvements in computational approaches. Alternatively, Fitzmaurice and Laird (1993,Biometrika80, 141–151), Molenberghs and Lesaffre (1994,Journal of the American Statistical Association89, 633–644), and Heagerty and Zeger (1996,Journal of the American Statistical Association91, 1024–1036) have developed a likelihood‐based inference that adopts a marginal mean regression parameter and completes full specification of the joint multivariate distribution through either canonical and/or marginal higher moment assumptions. Each of these marginal approaches is computationally intense and currently limited to small cluster sizes. In this manuscript, an alternative parameterization of the logistic‐normal random effects model is adopted, and both likelihood and estimating equation approaches to parameter estimation are studied. A key feature of the proposed approach is that marginal regression parameters are adopted that still permit individual‐level predictions or contrasts. An example is presented where scientific interest is in both the mean response and the covariance among repeated measurements.
Approximate Standard Errors in Semiparametric Models
Authors: Durban Maria , Hackett Christine A. , Currie I. D.
Published: May 2004

Summary.SUMMARY. We consider semiparametric models with p regressor terms and q smooth terms. We obtain an explicit expression for the estimate of the regression coefficients given by the back‐fitting algorithm. The calculation of the standard errors of these estimates based on this expression is a considerable computational exercise. We present an alternative, approximate method of calculation that is less demanding. With smoothing splines, the method is exact, while with loess, it gives good estimates of standard errors. We assess the adequacy of our approximation and of another approximation with the help of two examples.
Bayesian Inference for Small‐Sample Capture‐Recapture Data
Authors: Chavez‐Demoulin V.
Published: May 2004

Summary.We consider data on the survival of a population ofCephalorhynchus hectori, Hector's dolphins, in a marine area of New Zealand. To estimate survival probabilities of animal populations, a multiple capture‐recapture sampling scheme can be used. In this paper, we propose a practical methodology to derive approximations to posterior distributions based on Laplace methods. We show how to calculate Bayes estimates and credible intervals in this setting.
Treatment Comparisons Based on Two‐Dimensional Safety and Efficacy Alternatives in Oncology Trials
Authors: Thall Peter F. , Chengt Su‐Chun
Published: May 2004

Summary. In addition to their desired anticancer effects, most cancer treatments may also cause transient toxicity, permanent organ damage, or death. A critical question in comparing an experimental treatment to a standard is haw much increase in an adverse event rate is an acceptable trade‐off for achieving a targeted improvement in efficacy, or vice versa. We consider settings where one may characterize patient outcome as a bivariate (efficacy, safety) variable and quantify treatment effect as a corresponding two‐dimensional parameter. A set of target parameters, each representing a clinically meaningful improvement over the standard, are elicited from the physician. Each target is a two‐dimensional generalization of the usual one‐dimensional shift parameter. We define the alternative hypothesis in the two‐dimensional effect space as the convex hull of the sets of parameters that are at least as desirable as each target point. The rejection region is obtained by shifting the alternative toward (0,0) to achieve a given type I error, with sample size computed to achieve a given power at the targets. The method is illustrated by application to two cancer chemotherapy trials.
A Simple Permutation‐Type Method for Testing Circular Uniformity with Correlated Angular Measurements
Authors: Follmann Dean A. , Proschan Michael A.
Published: May 2004

Summary.A simple method is provided for testing uniformity on the circle that allows dependence among repeated angular measurements on the same subject. Our null hypothesis is that the distribution of repeated angles is unaffected by rotation. This null can be evaluated with any test of uniformity by using a null reference distribution obtained by simulation, where each subject's vector of angles is rotated by a random amount. A new weighted version of the univariate Rayleigh test of circular uniformity is proposed.
Estimating Equations for a Latent Transit ion Model with Multiple Discrete Indicators
Authors: Reboussin Beth A. , Liang Kung‐Yee , Reboussin David M.
Published: May 2004

Summary.This paper proposes a two‐part model for studying transitions between health states over time when multiple, discrete health indicators are available. The includes a measurement model positing underlying latent health states and a transition model between latent health states over time. Full maximum likelihood estimation procedures are computationally complex in this latent variable framework, making only a limited class of models feasible and estimation of standard errors problematic. For this reason, an estimating equations analogue of the pseudo‐likelihood method for the parameters of interest, namely the transition model parameters, is considered. The finite sample properties of the proposed procedure are investigated through a simulation study and the importance of choosing strong indicators of the latent variable is demonstrated. The applicability of the methodology is illustrated with health survey data measuring disability in the elderly from the Longitudinal Study of Aging.
Dual Screening
Authors: Johnson Wesley O. , Pearson Larry M.
Published: May 2004

Summary.We discuss the problem of screening a general population for characteristics such as HIV or drug use. Our main approach is Bayesian, which allows for the incorporation of prior information about parameters. In the particular problem we consider, there is currently no information in the data for estimating the sensitivity of the screening test, and consequently, the prevalence of the characteristic among screened negatives cannot be estimated from the collected data alone. Our inferences are straightforward to obtain using Gibbs sampling techniques, and they are valid for large or small samples and for arbitrary prevalence or accuracy of screening tests. We also develop the maximum‐likelihood approach using the EM algorithm.
A Penalized Likelihood Approach for a Progressive Three‐State Model with Censored and Truncated Data: Application to AIDS
Authors: Joly Pierre , Commenges Daniel
Published: May 2004

Summary.We consider the estimation of the intensity and survival functions for a continuous time progressive three‐state semi‐Markov model with intermittently observed data. The estimator of the intensity function is defined nonparametrically as the maximum of a penalized likelihood. We thus obtain smooth estimates of the intensity and survival functions. This approach can accommodate complex observation schemes such as truncation and interval censoring. The method is illustrated with a study of hemophiliacs infected by HIV. The intensity functions and the cumulative distribution functions for the time to infection and for the time to AIDS are estimated. Covariates can easily be incorporated into the model.
Standard Errors of Heritabilities for Forage Breeding Nurseries
Authors: Real Daniel , Gordon Ian L.
Published: May 2004

Summary. Estimators for standard errors of heritability for two typical and complex forage breeding models are illustrated with estimates of variance and covariance components from least‐squares and restricted maximum likelihood methods. The first experiment (Model 1) is a factorial design (two grazing management factors) with two layers of split plots (populations and grazing periods) and with plants within populations nested beneath the first split. The second model is for a sites pooling of randomized complete block experiments, with plants nested inside plots and with a split in time. One definition of heritability was applied to the plant habit character for both models in a red clover germplasm. Heritability estimates were statistically the same for the two methods for both models.
A Mixed Model for Two‐State Markov Processes Under Panel Observation
Authors: Cook Richard J.
Published: May 2004

Summary. Many chronic medical conditions can be meaningfully characterized in terms of a two‐state stochastic process. Here we consider the problem in which subjects make transitions among two such states in continuous time but are only observed at discrete, irregularly spaced time points that are possibly unique to each subject. Data arising from such an observation scheme are called panel data, and methods for related analyses are typically based on Markov assumptions. The purpose of this article is to present a conditionally Markov model that accommodates subject‐to‐subject variation in the model parameters by the introduction of random effects. We focus on a particular random effects formulation that generates a closed‐form expression for the marginal likelihood. The methodology is illustrated by application to a data set from a parasitic field infection survey.
Exact Inference for Growth Curves with Intraclass Correlation Structure*
Authors: Weerahandi Samaradasa , Berger Vance W.
Published: May 2004

Summary. We consider repeated observations taken over time for each of several subjects. For example, one might consider the growth curve of a cohort of babies over time. We assume a simple linear growth curve model. Exact results based on sufficient statistics (exact tests of the null hypothesis that a coefficient is zero, or exact confidence intervals for coefficients) are not available to make inference on regression coefficients when an intraclass correlation structure is assumed. This paper will demonstrate that such exact inference is possible using generalized inference.
Optimal Designs When the Variance Is A Function of the Mean
Authors: Dette Holger , Wong Weng Kee
Published: May 2004

Summary.We develop locallyD‐optimal designs for nonlinear models when the variance of the response is a function of its mean. Using the two‐parameter Michaelis–Menten model as an example, we show that the optimal design depends on both the type of heteroscedasticity and the magnitude of the variation. In addition, our results suggest that the homoscedasticD‐optimal design has high efficiency under a broad class of heteroscedastic patterns and that it is fairly insensitive to nominal values of the parameters.
Prediction Using Partly Conditional Time‐Varying Coefficients Regression Models
Authors: Pepe Margaret Sullivan , Heagerty Patrick , Whitaker Robert
Published: May 2004

Summary.Data collected longitudinally in time provide the opportunity to develop predictive models of future observations given current data for an individual. Such models may be of particular value in defining individuals at high risk and thereby in suggesting subgroups for targeting of prevention intervention research efforts. In this paper, we propose a method for estimating predictive functions. The method uses an extension of the marginal regression analysis methods of Liang and Zeger (1986,Biometrika73, 13–22) and is implemented using simple estimating equations. A key feature of the models is that regression coefficients are modelled as smooth functions of the times both at and for prediction. Data from a study of obesity in childhood and early adulthood is used to demonstrate the methodology. Criteria for defining individuals to be at high risk can be defined on the basis of estimated predictive functions. We suggest methods for evaluating the diagnostic accuracy (sensitivity and specificity) of such rules using cross‐validation. The method holds promise as a robust and technically easy way of evaluating information about future prognosis that may be gleaned from a patient's current and past clinical status.
Minimally Selected P and Other Tests for A Single Abrupt Changepoint in A Binary Sequence
Authors: Halpern Aaron L.
Published: May 2004

Summary. A novel changepoint statistic based on the minimum value, over possible changepoint locations, of Fisher's Exact Test, is introduced. Specific points in the exact distribution of the minimally selected Fisher's value may be rapidly calculated as a lattice‐path counting problem via known recurrence methods. The test is compared to the Kolmogorov‐Smirnov two‐sample test, the maximally selected chi‐square, and a likelihood ratio test. The tests are applied to assessing recombination in genetic sequences of HIV.
Multitype Spatial Point Patterns with Hierarchical Interactions
Authors: HöUgmander Harri , SäUrkkä Aila
Published: May 2004

Summary.Multitype spatial point patterns with hierarchical interactions are considered. Here hierarchical interaction means directionality: points on a higher level of hierarchy affect the locations of points on the lower levels, but not vice versa. Such relations are common, for example, in ecological communities. Interacting point patterns are often modeled by Gibbs processes with pairwise interactions. However, these models are inherently symmetric, and the hierarchy can be acknowledged only when interpreting the results. We suggest the following in allowing the inclusion of the hierarchical structure in the model. Instead of regarding the pattern as a realization of a stationary multivariate point process, we build the pattern one type at a time according to the order of the hierarchy by using nonstationary univariate processes. As interactions connected to points x on a certain level are considered, the effect of the higher levels is interpreted as heterogeneity of the pattern x, and the points on the lower levels are neglected because of the hierarchical structure.
Estimating Regression Parameters and Degree of Dependence for Multivariate Failure Time Data
Authors: Mahé Cédric , Chevret Sylvie
Published: May 2004

Summary.Multivariate failure time data are frequently encountered in longitudinal studies when subjects may experience several events or when there is a grouping of individuals into a cluster. To take into account the dependence of the failure times within the unit (the individual or the cluster) as well as censoring, two multivariate generalizations of the Cox proportional hazards model are commonly used. The marginal hazard model is used when the purpose is to estimate mean regression parameters, while the frailty model is retained when the purpose is to assess the degree of dependence within the unit. We propose a new approach based on the combination of the two aforementioned models to estimate both these quantities. This two‐step estimation procedure is quicker and more simple to implement than the EM algorithm used in frailty models estimation. Simulation results are provided to illustrate robustness, consistency, and large‐sample properties of estimators. Finally, this method is exemplified on a diabetic retinopathy study in order to assess the effect of photocoagulation in delaying the onset of blindness as well as the dependence between the two eyes blindness times of a patient.
Efficient Estimation of the Distribution of Quality‐Adjusted Survival Time
Authors: Zhao Hongwei , Tsiatis Anastasios A.
Published: May 2004

Summary. Quality of life is an important aspect in evaluation of clinical trials of chronic diseases, such as cancer and AIDS. Quality‐adjusted survival analysis is a method that combines both the quantity and quality of a patient's life into one single measure. In this paper, we discuss the efficiency of weighted estimators for the distribution of quality‐adjusted survival time. Using the general representation theorem for missing data processes, we are able to derive an estimator that is more efficient than the one proposed in Zhao and Tsiatis (1997, Biometrika84, 339–348). Simulation experiments are conducted to assess the small sample properties of this estimator and to compare it with the semiparametric efficiency bound. The value of this estimator is demonstrated from an application of the method to a data set obtained from a breast cancer clinical trial.
Ascertainment Bias in Rate Ratio Estimation from Case‐Sibling Control Studies of Variable Age‐At‐Onset Diseases
Authors: Langholz Bryan , Ziogas Argyrios , Thomas Duncan C. , Faucett Cheryl , Huberman Mark , Goldstein Larry
Published: May 2004

Summary.Motivated by a Finnish case‐control study of early onset diabetes in which diabetic children are matched to sibling controls, we investigate ascertainment bias of the usual rate ratio estimator from case‐control data under simplex complete ascertainment of families during a fixed interval of time. Analytic results indicate that the assumptions necessary for valid estimation are that the disease is rare and the factors under study are exchangeable–essentially that the covariate distribution does not depend on calendar time or birth order. Further, we found that the rare disease assumption could be dropped by restricting to cases that were diagnosed during the enrollment period of the study or including all cases but eliminating the proband as a control for non‐enrollment‐period cases. An important consequence of this work is that standard family‐based case‐control studies are subject to ascertainment bias if exchangeability of the covariates under investigation does not hold.
Bayesian Inference for Prevalence in Longitudinal Two‐Phase Studies
Authors: Erkanli Alaattin , Soyer Refik , Costello Elizabeth J.
Published: May 2004

Summary.We consider Bayesian inference and model selection for prevalence estimation using a longitudinal two‐phase design in which subjects initially receive a low‐cost screening test followed by an expensive diagnostic test conducted on several occasions. The change in the subject's diagnostic probability over time is described using four mixed‐effects probit models in which the subject‐specific effects are captured by latent variables. The computations are performed using Markov chain Monte Carlo methods. These models are then compared using the deviance information criterion. The methodology is illustrated with an analysis of alcohol and drug use in adolescents using data from the Great Smoky Mountains Study.