bluuebunny/crossref_metadata_2025 huggingface dataset:
Formation of amyloid aggregates from human lysozyme and its disease‐associated variants using hydrostatic pressure
Authors: Felice Fernanda G. De , Vieira Marcelo N. N. , Meirelles M. Nazareth L. , Morozova‐Roche Ludmilla A. , Dobson Christopher M. , Ferreira Sérgio T.
Published: May 2004

Formation of amyloid deposits from the Ile56Thr or Asp67His variants of human lysozyme is a hallmark of autosomal hereditary systemic amyloidosis. It has recently been shown that amyloid fibrils can be formed in vitro from wild‐type (WT), I56T, or D67H lysozyme variants upon prolonged incubation at acidic pH and elevated temperatures (1). Here, we have used hydrostatic pressure as a tool to generate amyloidogenic states of WT and variant lysozymes at physiological pH. WT or variant lysozyme samples were initially compressed to 3.5 kbar (at 57°C, pH 7.4). Decompression led to the formation of amyloid fibrils, protofibrils, or globular aggregates, as indicated by light scattering, thioflavin T fluorescence, and transmission electron microscopy analysis. Increased 1‐anilinonaphthalene‐8‐sulfonate binding to the proteins was also observed, indicating exposure of hydrophobic surface area. Thus, pressure appears to induce a conformational state of lysozyme that aggregates readily upon decompression. These results support the notion that amyloid aggregation results from the formation of partially unfolded protein conformations and suggest that pressure may be a useful tool for the generation of the amyloidogenic conformations of lysozyme and other proteins.
HIV associated neurodegeneration requires p53 in neurons and microglia
Authors: Garden Gwenn A. , Guo Weiqun , Jayadev Suman , Tun Christina , Balcaitis Stephanie , Choi Jo , Montine Thomas J. , Möller Thomas , Morrison Richard S.
Published: May 2004

HIV infection of the central nervous system leads to HIV‐associated dementia (HAD) in a substantial subset of infected individuals. The pathogenesis of neuronal dysfunction in HAD is not well understood, but previous studies have demonstrated evidence for activation of apoptotic pathways. The tumor suppressor transcription factor p53 is an apical mediator of neuronal apoptosis following a variety of injurious stimuli. To determine whether p53 participates in HAD, we exposed cerebrocortical cultures from wild‐type and p53 deficient mice to the neurotoxic HIV envelope protein gp120. Using neuron/microglia co‐culture of mixed p53 genotype, we observed that both neurons and microglia require p53 for gp120 induced neuronal apoptosis. Additionally, accumulation of p53 protein in neurons was recently reported in post‐ mortem cortical tissue from a small group of HAD patients. Using a much larger cohort of HAD cases, we extend this finding and report that p53 protein also increases in non‐neuronal cells, including microglia. Taken together these findings demonstrate a novel role for p53 in the microglial response to gp120. Additionally, these findings, in conjunction with a recent report that monocytes expressing HIV‐Tat also secrete neurotoxins that promote p53 activation, suggest that distinct HIV proteins may converge on the p53 pathway to promote neurotoxicity.
Use of the Vacuum‐Assisted Closure Device in Enhancing Closure of a Massive Skull Defect
Authors: Marathe Umesh S. , Sniezek Joseph C.
Published: May 2004

Objectives/Hypothesis: The objective was to describe a novel technique for reconstructing the cranial vertex without the use of free tissue transfer.

Study Design: Case report, literature review, and discussion.

Methods: A 50‐year‐old woman presented from a remote Pacific Island community with a 12 × 14‐cm, necrotic, grossly contaminated eccrine gland carcinoma of the cranial vertex that extended through the calvarium but did not invade the dura. Following tumor extirpation, the resulting bony defect was 10 × 12 cm in size, with a concomitant scalp defect of 14 × 16 cm. Free tissue transfer was impossible because of severe intimal peripheral vascular disease, posing a challenging reconstructive dilemma. After tumor resection, the bony edges were covered with local scalp flaps and the vacuum‐assisted closure device was placed over the wound at a constant setting of −50 mm Hg. The vacuum‐assisted closure device was changed three times per week for 3 weeks.

Results: A thick, 1‐cm bed of granulation tissue developed over the dura, allowing temporary coverage by a split‐thickness skin graft, and the scalp defect decreased in size by approximately 25%. The patient did not develop meningitis, headache, or localized infection as a result of placement of the vacuum‐assisted closure device and tolerated the vacuum‐assisted closure well. After a requisite period of healing, tissue expanders and calvarial reconstruction will be performed.

Conclusion: Use of the vacuum‐assisted closure device is a safe, reliable adjunct in the closure of large cranial defects with exposed dura and offers a novel reconstructive option for complex defects of the head and neck.
Management of Cerebrospinal Fluid Rhinorrhea: The Medical College of Wisconsin Experience
Authors: Lindstrom D. Richard , Toohill Robert J. , Loehrl Todd A. , Smith Timothy L.
Published: May 2004

Introduction: The management of cerebrospinal fluid (CSF) rhinorrhea has evolved in recent years. The purpose of this comprehensive retrospective study is to assess issues related to the management of skull base defects associated with CSF rhinorrhea involving the nose and paranasal sinuses.

Methods: A retrospective review of CSF leak management was conducted. This study included patients with CSF rhinorrhea managed by the Department of Otolaryngology, Medical College of Wisconsin, Milwaukee, WI, from 1992 to 2002. Data collected included site of leak, surgical approach, and any recurrence of leak.

Results: Fifty‐seven CSF leaks occurred in 53 patients with CSF rhinorrhea originating from the nose or paranasal sinuses. Twenty‐eight of the 53 had iatrogenic injuries resulting in CSF rhinorrhea, 16 had leaks from trauma, and 13 developed spontaneous CSF leaks. Ten patients responded to nonoperative management with bed rest with or without lumbar drain placement. Forty‐three patients with 47 leaks underwent surgical repair of CSF rhinorrhea, of which 38 resolved after initial repair. Five of these patients developed recurrent CSF leaks at the repair site but resolved with subsequent surgery. Of these, two initially presented with spontaneous CSF leaks, one patient had a gunshot wound with massive skull base injury, and two recurred after repair of an iatrogenic injury. Factors associated with failure included lateral sphenoid leaks and elevated body mass index (BMI).

Discussion: Multiple approaches to the management of CSF rhinorrhea can be successful. An endoscopic repair results in resolution of CSF rhinor‐rhea in the majority of cases. Patients with spontaneous CSF rhinorrhea, elevated BMI, lateral sphenoid leaks, and extensive skull base defects are at increased risk for recurrence. Alternative management options may need to be considered in these cases.
Vibration With the Canalith Repositioning Maneuver: A Prospective Randomized Study to Determine Efficacy
Authors: Macias John D. , Ellensohn Andrea , Massingale Shelly , Gerkin Richard
Published: May 2004

Objectives/Hypothesis: The objective was to determine whether the inclusion of vibration and additional treatment cycles has an effect on short‐ and long‐term success rates in the treatment of benign paroxysmal positional vertigo with the canalith repositioning maneuver.

Study Design: Prospective randomized study of patients treated at a tertiary vestibular rehabilitation center.

Methods: Variables identified for statistical analysis included patient age, gender, vibration used, and canalith repositioning cycles. Analysis using Student t test, χ2 test, Kaplan‐Meier curves with log rank test, and Cox proportional hazards regression was performed.

Results: One hundred two patients with benign paroxysmal positional vertigo treated over a 1‐year period (August 2001–August 2002) were randomly assigned to receive the canalith repositioning maneuver with or without vibration. Average duration of follow‐up was 9.44 months. The single treatment success rate was 93.1%. To relieve symptoms, 29.4% of patients required more than one canalith repositioning cycle. The relapse rate was 30.5%. Thirty‐nine patients were assigned to the canalith repositioning group with vibration, and 63 to the canalith repositioning group without vibration. There was no statistical difference in age, gender, initial success rates, or relapse rates between the canalith repositioning groups with and without vibration. On average, patients required 1.38 canalith repositioning cycles for successful treatment. Vibration did not affect the number of canalith repositioning cycles required to convert the Dix‐Hallpike test result to normal. The need for additional canalith repositioning cycles had no statistical effect on initial treatment success or relapse rates.

Conclusion: Vibration provided no additional benefit in initial treatment success or in reducing long‐term relapse rates when included in the canalith repositioning maneuver. Many patients with benign paroxysmal positional vertigo require more than one canalith repositioning cycle at the time of initial treatment to relieve symptoms, but this does not indicate a higher likelihood for recurrence. No variable predicted a higher rate of recurrence.
Cathepsin Gene Expression Profile in Rat Acute Pneumococcal Otitis Media
Authors: Li‐Korotky Ha‐Sheng , Swarts J. Douglas , Hebda Patricia A. , Doyle William J.
Published: May 2004

Objectives/Hypothesis: Acute otitis media, often caused by infection with Streptococcus pneumoniae, is characterized by inflammation of the middle ear mucosa. A prominent feature of the host response to bacterial infection of the middle ear mucosa is an influx of inflammatory cells that contributes to the local pool of inflammatory mediators by releasing additional inflammatory chemicals, which in turn cause further tissue injury. The objective was to identify candidate effector and signaling molecules involved in acute otitis media pathogenesis caused by S pneumoniae infection.

Study Design: Male Sprague‐Dawley rats were randomly assigned to 1 of 5 groups, including 1 control group without treatment, 2 placebo groups (12 and 48 hours) and 2 infected groups (12 and 48 hours). The rat middle ear was bilaterally inoculated with either 25 μL of tryptic soy broth (TSB group) or 25 μL of TSB containing approximately 1.24 × 1010 cfu/mL of S pneumonias type 6A (SP group). Rats were killed at 12 and 48 hours after inoculation and the middle ear mucosa was collected. Total RNA was extracted and pooled from each group for gene expression assays.

Methods: Gene expression profiles for rat middle ear mucosa at 12 and 48 hours after S pneumoniae or placebo inoculation were constructed using microarray technology (Clontech Atlas Rat 1.2 Array, 1176 cDNAs). Genes of interest were further validated by real‐time polymerize chain reaction.

Results: Middle ear mucosa expression of a gene cluster encoding the lysosomal cysteine proteases, cathepsins B (Ctsb), L (Ctsl), and K (Ctsk), was modified after S pneumoniae challenge. Specifically, at 12 hours, Ctsk and Ctsl messenger RNA that was abundantly expressed in the normal middle ear mucosa was decreased, whereas Ctsb transcript was induced. The changes in Ctsb and Ctsk gene expression were sustained at 48 hours.

Conclusion: The constitutive expression of Ctsk and Ctsl messenger RNA in normal middle ear mucosa supports a function in the maintenance of middle ear mucosa homeostasis, and their downregulation as an early event in acute otitis media may reflect a disruption in that function. The induction of Ctsb messenger RNA in the infected middle ear mucosa suggests a role in early tissue injury; thus, Ctsb may represent a potential target for molecular diagnostics and/or rational intervention during the development of acute otitis media.
Facial Translocation Approach in the Management of Central Skull Base and Infratemporal Tumors
Authors: Suárez Carlos , Llorente José L. , Muñoz Cristina , García Luis A. , Rodrigo Juan P.
Published: May 2004

Objectives/Hypothesis: The objectives were to systematize the indications of various types of facial translocation and to present a technical modification to avoid some sequelae of this approach.

Study Design: Retrospective analysis was made of patients treated with different types of facial translocation approach to resect nasopharyngeal, infratemporal, and sinonasal tumors.

Methods: Thirty‐nine patients underwent facial translocation approaches for neoplasms originally involving the nasopharynx (27) infratemporal fossa (7), and nasal cavity (5). Of the 21 malignant tumors, 2 were stage T2, 5 were stage T3, and 14 were stage T4. From the entire series of patients, 10 received a unilateral medial translocation, 3 a bilateral medial translocation, 25 a standard facial translocation, and 1 an extended medial facial translocation.

Results: Fifteen patients (38%) developed some kind of complication, such as wound infection (nine cases) and osteomyelitis and cerebrospinal fluid leak (five cases each). Two patients died as a result of postoperative complications (5.2%). Overall 5‐year survival for malignant tumors was 43%. Neither the histological appearance of the tumor nor the T stage influenced the survival of patients. Survival of patients with intracranial involvement was significantly decreased compared with patients with involvement of other areas (P = .0003).

Conclusion: The facial translocation approach offers an excellent exposure in tumors with large degree of involvement of the nasopharynx, infratemporal fossa, nasal cavity, and maxillary sinus. More limited osteotomies are indicated in smaller tumors. The use of midfacial degloving minimizes the number of sequelae of these approaches.
Extracorporeal Lithotripsy for Salivary Calculi: A Long‐Term Clinical Experience
Authors: Capaccio Pasquale , Ottaviani Francesco , Manzo Raffaele , Schindler Antonio , Cesana Bruno
Published: May 2004

Objectives/Hypothesis: The objective was to assess in a large series of patients with a long‐term clinical follow‐up the validity of extracorporeal electromagnetic shock wave lithotripsy as a minimally invasive therapy for sialolithiasis.

Study Design: Consecutive patient series.

Methods: Three hundred twenty‐two consecutive symptomatic outpatients with single or multiple calculi in the submandibular (234 patients) or parotid (88 patients) gland underwent a complete extracorporeal electromagnetic shock wave lithotripsy treatment. Treatment results were classified into three groups: successful result with complete ultrasonographic elimination of the stone after lithotripsy, successful result with residual ultrasonographic fragments that were less than 2 mm in diameter, and unsuccessful result with residual ultrasonographic fragments that were greater than 2 mm in diameter. Univariate and multivariate statistical analyses were performed.

Results: Complete elimination of the stone was achieved in 45% of patients. On ultrasonography, residual fragments (<2 mm in diameter) were detected in 27.3% of patients, and persisting fragments greater than 2 mm in diameter were assessed in 27.7% of patients. In 3.1% of patients, all with submandibular gland stones, sialoadenectomy was performed. Recurrence of calculi in the treated gland was observed during a median follow‐up period of 57 months in four patients with complete ultrasonographic clearance of the stone occurring 10 to 58 months after lithotripsy. Univariate analysis showed that a favorable treatment result was significantly associated with the younger age of the patients (≤46 y), parotid and intraductal localization of the stone, diameter of the stone (≤7 mm), and number of therapeutic sessions (≤6). On multivariate analysis, the age of the patient, parotid site of the stone, stone diameter, number of therapeutic sessions, and number of shock waves were associated with favorable outcome.

Conclusion: Extracorporeal electromagnetic shock wave lithotripsy is to be considered an efficient, minimally invasive treatment modality for salivary calculi.
Difluoromethylornithine‐Induced Reversible Hearing Loss Across a Wide Frequency Range
Authors: Smith Mark C. , Tinling Steve , Doyle Karen Jo
Published: May 2004

Objectives: Alpha‐difluoromethylornithine (DFMO) is an antineoplastic agent that causes reversible hearing loss (HL) by an unknown mechanism. Previous neonatal gerbil studies have identified a dosing regimen of 1 g/kg per day of DFMO given for 3 weeks that results in reversible HL on click‐evoked auditory brainstem response (ABR). The objectives of this study are 1) to measure HL and recovery at several frequencies in neonatal gerbils after DFMO therapy at two different dosing regimens and 2) to identify any effects of DFMO on cochlear histology.

Study Design: Prospective, nonrandomized, experimental design with placebo controls.

Methods: ABR to tone pips at 2, 4, 8, 16, and 32 kHz were recorded on 62 21‐day‐old Mongolian gerbils after daily subcutaneous injections of DFMO (group A at 1 g/kg, group B at 750 mg/kg) or saline from day 3 to day 20 after birth. Thirty‐seven animals were retested after a 3‐week drug‐free recovery period. Twenty‐seven animals were killed for analysis of cochlear histology.

Results: Animals that were administered DFMO demonstrated higher ABR thresholds across all five frequencies, with mean threshold differences of 21 to 29 dB in group A and 11 to 17 dB in group B as compared with controls. Higher thresholds were demonstrated at higher frequencies. Fewer side effects were noted at the lower dose. After a 3‐week drug‐free recovery period, auditory thresholds returned to pretreatment levels. No significant cochlear structural abnormalities were identified under light microscopy.

Conclusion: An 18‐day regimen of 750 mg/kg per day of DFMO given subcutaneously in neonatal gerbils causes minimal side effects with broad‐frequency HL that, after 3 weeks of recovery, is fully reversible.
John Watt's map of the Clyde
Authors: Hills R. L.
Published: May 2004

John Smeaton was engaged from 1755 to 1761 in an abortive attempt to improve the navigation of the river Clyde up to Glasgow. His volumes of Civil and Mechanical Engineering Designs in the Library of the Royal Society contain the maps and plans of the scheme. One is entitled ‘The River of Clyde surveyed by John Watt’. Although surveyed by John Watt in 1734, it was only published posthumously by his nephew James Watt, the famous steam engine improver, in 1759 who revised it with the assistance of his own father and brother. James Watt had helped survey the Clyde in conjunction with Smeaton's schemes in 1758.

The background of Smeaton's work is outlined and the story of the revision of the map and its printing in Edinburgh covered. A second edition was run off in 1794 when John Rennie discovered the engraved copper plate at the Edinburgh printers.
The 1997 Wilkins Lecture: Erasmus Darwin, the Lunaticks and evolution
Authors: King-Hele D.
Published: May 2004

Long ago, I suggested that Erasmus Darwin ‘achieved more in a wider range of intellectual disciplines than anyone since’. This remark has not yet been contradicted; and that is perhaps enough to justify the choice of Erasmus Darwin as the subject of the Wilkins Lecture for 1997. I shall run quickly through his varied talents, comment on his personality and then outline his life and achievements. As an addition to the life story, I shall include glances at those of his many friends who together formed the Lunar Society of Birmingham, so called because it met at the time of the full moon; they are of course the ‘Lunaticks’ of my title. To conclude, I shall look more closely at one of his many interests, explaining how he came to believe in biological evolution (as we now call it) and then had to keep quiet about it for 20 years before eventually championing it in public.
The Marketing Mix Redefined and Mapped
Authors: Vignali Claudio , Davies B.J.
Published: May 2004

Addresses the question of how the Marketing Mix framework can be used to
analyse the competitive standing of a business organization and how the
outcome of this analysis can then be translated into practical tactics
which capitalize on the organization′s strengths. The MIXMAP model
developed as a guide for marketing this transition from the strategic to
the tactical level.
The Extended Manufacturing Enterprise Paradigm
Authors: O′Neill Henrique , Sackett Peter
Published: May 2004

Models able to describe state of the art practice are fundamental to
understanding the manufacturing phenomenon. A study of innovative
current practices enables us to foresee the emergence of a new
manufacturing paradigm: the Extended Enterprise. This arises from the
need to satisfy customers who are increasingly demanding tailored
products with world class capability in every functional aspect. The
Extended Enterprise is made both possible and viable by the progress
made in manufacturing processes and information technology. It demands
the development of a new management philosophy and particularly new
organizational structures. Presents a reference model for the Extended
Enterprise, and compares the characteristics of this paradigm against
the Mass and Lean manufacturing philosophies. Describes the results of a
study that analyses the development of co‐operation mechanisms in the
aerospace industry.
Raiding the postmodern pantry
Authors: O’Donohoe Stephanie
Published: May 2004

While analysts of postmodernism have feasted on marketing practices, the marketing discipline has been slow to acquire a taste for postmodernism. Offers marketers a taste of what it has to offer by examining the concept of intertextuality and demonstrating its reliance to advertising texts and their production and consumption. Drawing on a qualitative study of young adults, shows how their descriptions and experiences of particular ads shaped and were shaped by their experiences of other texts. Considers the implications of intertextuality for consumers’ attitudes, involvement and literacy with respect to advertising, for the link between ad and brand consumption, and the relationship between marketing theory and practice.
Beyond ethnography
Authors: Brownlie Douglas
Published: May 2004

This paper is about marketing accounting. It is about reading marketing writing and writing marketing reading and what calls them into being. It is about our “ab‐outing” practices; those signifying practices by means of which we week to capture a piece of the world and show it off, wrapped in a suitable tale of discovery, in a cabinet in the museum of marketing knowledge. You may wonder why should we bother, since without those representation practices and textual conventions how could we be sure that the objects on display were real, not fakes; that our representations were true images of objects in the real world, not mere simulations of simulations? Do you find comfort in the view that marketing discourse organizes in such a way as to sustain the convention that objects in the marketing world “out there” are antecedent to our images of them? And does it discomfort you to recognize the ideas of Garfinkel (1967) being used to suggest that marketing accounts are constituent features of the settings we make observable? Whatever your answers, how textual organization persuades and makes real is a point worth considering. I think this is a timely project, as we warm to qualitative methods, especially ethnography, on the (mis)understanding that they can reveal truer, deeper, thicker insights into the real world. For it is not possible to avoid the problem of representation in this way, as Geertz (1973) reminds us in his invitation to reflexive ethnographic inquiry.
Existential consumption and irrational desire
Authors: Elliott Richard
Published: May 2004

In postmodernity, consumption is a prime site for the negotiation of conflicting themes of freedom and control. Explores the consumption of symbolic meaning through five consumption dialectics: the material versus the symbolic, the social versus the self, desire versus satisfaction, rationality versus irrationality, and creativity versus constraint. Argues that consumers are engaged in authentic choices in the construction and communication of self and social meanings, and that these consumption choices can be conceptualized as the exercise of existential freedom, even if constrained by inequalities in the economic system and by ideological hegemony.
Learning to share, sharing to learn
Authors: Collinson Vivienne
Published: May 2004

This paper argues that conditions supporting dissemination (sharing) of teachers' learning are necessary for school change and organizational learning. Based on a qualitative study that explored dissemination of teachers' learning within a multi‐school computer technology project, the paper identifies 43 factors that motivate teachers' sharing and 35 factors that restrain their sharing in schools. The paper posits that in the short‐term, it may be easier to encourage dissemination by reducing restraining factors than by working to increase motivating factors. In the long term, however, the attitudes and beliefs underlying the motivating factors must be addressed. This paper also offers a table of participants' suggestions for administrators to encourage teachers to share their learning with colleagues.
Likelihood Ratios for Evaluating DNA Evidence When the Suspect is Found Through a Database Search
Authors: Stockmarr Anders
Published: May 2004

Summary.A crime has been committed, and a DNA profile of the perpetrator is obtained from the crime scene. A suspect with a matching profile is found. The problem of evaluating this DNA evidence in a forensic context, when the suspect is found through a database search, is analysed through a likelihood approach. The recommendations of the National Research Council of the U.S. are derived in this setting as the proper way of evaluating the evidence when finiteness of the population of possible perpetrators is not taken into account. When a finite population of possible perpetrators may be assumed, it is possible to take account of the sampling process that resulted in the actual database, so one can deal with the problem where a large proportion of the possible perpetrators belongs to the database in question. It is shown that the last approach does not in general result in a greater weight being assigned to the evidence, though it does when a sufficiently large amount of the possible perpetrators are in the database. The value of the likelihood ratio corresponding to the probable cause setting constitutes an upper bound for this weight, and the upper bound is only attained when all but one of the possible perpetrators are in the database.
Kriging with Nonparametric Variance Function Estimation
Authors: Opsomer J. D. , Ruppert D. , Wand M. P. , Holst U. , Hössjer O.
Published: May 2004

Summary. A method for fitting regression models to data that exhibit spatial correlation and heteroskedas‐ticity is proposed. It is well known that ignoring a nonconstant variance does not bias least‐squares estimates of regression parameters; thus, data analysts are easily lead to the false belief that moderate heteroskedas‐ticity can generally be ignored. Unfortunately, ignoring nonconstant variance when fitting variograms canseriously bias estimated correlation functions. By modeling heteroskedasticity and standardizing by estimated standard deviations, our approach eliminates this bias in the correlations. A combination of parametric and nonparametric regression techniques is used to iteratively estimate the various components of the model. The approach is demonstrated on a large data set of predicted nitrogen runoff from agricultural lands in the Midwest and Northern Plains regions of the U.S.A. For this data set, the model comprises three main components: (1) the mean function, which includes farming practice variables, local soil and climate characteristics, and the nitrogen application treatment, is assumed to be linear in the parameters and is fitted by generalized least squares; (2) the variance function, which contains a local and a spatial component whose shapes are left unspecified, is estimated by local linear regression; and (3) the spatial correlation function is estimated by fitting a parametric variogram model to the standardized residuals, with the standardization adjusting the variogram for the presence of heteroskedasticity. The fitting of these three components is iterated until convergence. The model provides an improved fit to the data compared with a previous model that ignored the heteroskedasticity and the spatial correlation.
Estimation of the Correlation Between Nutrient Intake Measures Under Restricted Sampling
Authors: Wang C. Y. , Anderson Garnet L. , Prentice Ross L.
Published: May 2004

Summary. Food frequency questionnaires (FFQs) are commonly used to assess dietary intake in epidemiologic research. To evaluate the FFQ reliability, the commonly used approach is to estimate the correlation coefficient between the data given in FFQ and those in food records (for example, 4‐day food records [4DFR]) for nutrients of interest. However, in a dietary intervention study, a criterion for eligibility may be to select participants who have baseline FFQ‐measured dietary intake of percent energy from fat above a prespecified quantity. Other instruments, such as the 4DFR, may be subsequently administrated only to eligible participants. Under these circumstances, analysis without adjusting for the restricted population will usually lead to biased estimation of correlation coefficients and other parameters of interest. In this paper, we apply likelihood‐based and multiple imputation (MI) methods to accommodate such incomplete data obtained as a result of the study design. A simulation study is conducted to examine finite sample performance of various estimators. We note that both the MI estimate and the maximum likelihood (ML) estimate based on a bivariate‐normal model are not sensitive to departures from this normality assumption. This led us to investigate robustness properties of the ML estimator analytically. We present some data analyses from a dietary assessment study from the Women's Health Initiative to illustrate the methods.
Valid Inference in Random Effects Meta‐Analysis
Authors: Follmann Dean A. , Proschan Michael A.
Published: May 2004

Summary. The standard approach to inference for random effects meta‐analysis relies on approximating the null distribution of a test statistic by a standard normal distribution. This approximation is asymptotic on k, the number of studies, and can be substantially in error in medical meta‐analyses, which often have only a few studies. This paper proposes permutation and ad hoc methods for testing with the random effects model. Under the group permutation method, we randomly switch the treatment and control group labels in each trial. This idea is similar to using a permutation distribution for a community intervention trial where communities are randomized in pairs. The permutation method theoretically controls the type I error rate for typical meta‐analyses scenarios. We also suggest two ad hoc procedures. Our first suggestion is to use a t‐reference distribution with k ‐ 1 degrees of freedom rather than a standard normal distribution for the usual random effects test statistic. We also investigate the use of a simple t‐statistic on the reported treatment effects.
Modeling a Poisson Forest in Variable Elevations: A Nonparametric Bayesian Approach
Authors: Heikkinen Juha , Arjas Elja
Published: May 2004

Summary. A nonparametric Bayesian formulation is given to the problem of modeling nonhomogeneous spatial point patterns influenced by concomitant variables. Only incomplete information on the concomitant variables is assumed, consisting of a relatively small number of point measurements. Residual variation, caused by other unmeasured influential factors, is modeled in terms of a spatially varying baseline intensity function. A Markov chain Monte Carlo scheme is proposed for the simultaneous nonparametric estimation of each unknown function in the model. The suggested method is illustrated by reanalysing a data set in Rathbun (1996, Biometrics52, 226–242), and the estimated models are compared with those obtained by Rathbun.
Using a Mixed Effects Model to Estimate Geographic Variation in Cancer Rates
Authors: Pennello Gene A. , Devesa Susan S. , Gail Mitchell H.
Published: May 2004

Summary. Commonly used methods for depicting geographic variation in cancer rates are based on rankings. They identify where the rates are high and low but do not indicate the magnitude of the rates nor their variability. Yet such measures of variability may be useful in suggesting which types of cancer warrant further analytic studies of localized risk factors. We consider a mixed effects model in which the logarithm of the mean Poisson rate is additive in fixed stratum effects (e.g., age effects) and in logarithms of random relative risk effects associated with geographic areas. These random effects are assumed to follow a gamma distribution with unit mean and variance l/α, similar to Clayton and Kaldor (1987, Biometrics43, 671–681). We present maximum likelihood and method‐of‐moments estimates with standard errors for inference on α−1/2, the relative risk standard deviation (RRSD). The moment estimates rely on only the first two moments of the Poisson and gamma distributions but have larger standard errors than the maximum like‐lihood estimates. We compare these estimates with other measures of variability. Several examples suggest that the RRSD estimates have advantages compared to other measures of variability.
A Unifying Family of Group Sequential Test Designs
Authors: Kittelson John M. , Emerson Scott S.
Published: May 2004

Summary. Currently, the design of group sequential clinical trials requires choosing among several distinct design categories, design scales, and strategies for determining stopping rules. This approach can limit the design selection process so that clinical issues are not fully addressed. This paper describes a family of designs that unifies previous approaches and allows continuous movement among the previous categories. This unified approach facilitates the process of tailoring the design to address important clinical issues. The unified family of designs is constructed from a generalization of a four‐boundary group sequential design in which the shape and location of each boundary can be independently specified. Methods for implementing the design using error‐spending functions are described. Examples illustrating the use of the design family are also presented.
Assessing Distributions of Estimated Drug Shelf Lives in Stability Analysis
Authors: Sun Yanqing , Chow Shein‐Chung , Li Gang , Chen Keh‐Wei
Published: May 2004

Summary. A stability study is usually conducted to ensure that a drug product can meet the approved specifications prior to its expiration dating period (shelf life). Several approaches for determination of drug shelf life assuming random batches have been proposed. In this paper, we examine sampling distributions of the estimated shelf lives proposed by Shao and Chow (1994, Biometrics50, 753–763). An application to some stability data from the pharmaceutical industry is presented.
Estimating Equations for Parameters in Stochastic Growth Models from Tag–Recapture Data
Authors: Wang You‐Gan
Published: May 2004

Summary. James (1991, Biometrics47, 1519–1530) constructed unbiased estimating functions for estimating the two parameters in the von Bertalanffy growth curve from tag‐recapture data. This paper provides unbiased estimating functions for a class of growth models that incorporate stochastic components and explanatory variables. A simulation study using seasonal growth models indicates that the proposed method works well while the least‐squares methods that are commonly used in the literature may produce substantially biased estimates. The proposed model and method are also applied to real data from tagged rock lobsters to assess the possible seasonal effect on growth.
Estimation of Population Size Based on Additive Hazards Models for Continuous‐Time Recapture Experiments
Authors: Yip Paul S. F. , Zhou Yong , Lin D. Y. , Fang Xiang‐Zhong
Published: May 2004

Summary.We use the semiparametric additive hazards model to formulate the effects of individual covariates on the capture rates in the continuous‐time capture–recapture experiment, and then construct a Horvitz–Thompson‐type estimator for the unknown population size. The resulting estimator is consistent and asymptotically normal with an easily estimated variance. Simulation studies show that the asymptotic approximations are adequate for practical use when the average capture probabilities exceed .5. Ignoring covariates would underestimate the population size and the coverage probability is poor. A wildlife example is provided.
Modeling Daily and Subdaily Cycles in Rat Sleep Data
Authors: Qiu Peihua , Chappell Rick , Obermeyer William , Benca Ruth
Published: May 2004

Summary. We developed a statistical model for rat sleep–wake behavior over the 24‐hour day; this model could be used for animals exposed to shorter cycles of light and dark conditions. Rat behavior was classified either as “wake” or “sleep,” as determined by analysis of electrophysiological data. The proposed model consists of three parts: the first two explain cyclic effects relating to the lighting conditions, whereas the last part reflects any acyclic effect. Hypothesis tests were conducted on the magnitude of the parts. The model also accounts for correlated errors.
An Application of Isotonic Longitudinal Marginal Regression to Monitoring the Healing Process
Authors: Fahrmeir Ludwig , Gieger Christian , Heumann Christian
Published: May 2004

Summary.This paper discusses marginal regression for repeated ordinal measurements that are isotonic over time. Such data are often observed in longitudinal studies on healing processes in which, due to recovery, the status of patients only improves or remains the same. We show how this prior information can be used to construct appropriate and parsimoniously parametrized marginal models. As a second aspect, we also incorporate nonparametric fitting of covariate effects via a penalized quasi‐likelihood or general estimating equation approach. We illustrate our methods by an application to sports‐related injuries.
The Stratified Petersen Estimator with A Known Number of Unread Tags
Authors: Schwarz Carl J. , Andrews Myra , Link Michael R.
Published: May 2004

Summary. The Petersen estimator estimator of abundance can be biased when the assumption of homogeneous capture probability or homogeneous recapture probability is violated. Often this heterogeneity is related to the time or place of capture or recapture, and if these can be stratified, the stratified Petersen estimator reduces the bias caused by this heterogeneity. In some experiments, not all the recovered tagged animals can be examined, and only a subsample has its stratum of release and recovery determined. We develop methods for this modified experiment and apply them to estimate the number of salmon returning to spawn in a river in British Columbia, Canada.
Empirical Bayes Estimation for Combinations of Multivariate Bioassays
Authors: Chen D. G. , Carter E. M. , Hubert J. J. , Kim P. T.
Published: May 2004

Summary. This article presents a new empirical Bayes estimator (EBE) and a shrinkage estimator for determining the relative potency from several multivariate bioassays by incorporating prior information on the model parameters based on Jeffreys' rules. The EBE can account for any extra variability among the bioassays, and if this extra variability is 0, then the EBE reduces to the maximum likelihood estimator for combinations of multivariate bioassays. The shrinkage estimator turns out to be a compromise of the prior information and the estimator from each multivariate bioassay, with the weights depending on the prior variance.
Improved Error Bounds for Genetic Distances from Dna Sequences
Authors: McGuire Gráinne , Prentice Michael J. , Wright Frank
Published: May 2004

Summary. The genetic distance between two DNA sequences may be measured by the average number of nucleotide substitutions per position that has occurred since the two sequences diverged from a common ancestor. Estimates of this quantity can be derived from Markov models for the substitution process, while the variances are estimated using the delta method and confidence intervals calculated assuming normality. However, when the sampling distribution of the estimator deviates from normality, such intervals will not be accurate. For simple one‐parameter models of nucleotide substitution, we propose a transformation of normal confidence intervals, which yields an almost exact approximation to the true confidence intervals of the distance estimators. To calculate confidence intervals for more complicated models, we propose the saddlepoint approximation. A simulation study shows that the saddlepoint‐derived confidence intervals are a real improvement over existing methods.
Confidence Bands for Cumulative Incidence Curves Under the Additive Risk Model
Authors: Shen Yu , Cheng S. C.
Published: May 2004

Summary.In the context of competing risks, the cumulative incidence function is often used to summarize the cause‐specific failure‐time data. As an alternative to the proportional hazards model, the additive risk model is used to investigate covariate effects by specifying that the subject‐specific hazard function is the sum of a baseline hazard function and a regression function of covariates. Based on such a formulation, we present an approach to constructing simultaneous confidence intervals for the cause‐specific cumulative incidence function of patients with given risk factors. A melanoma data set is used for the purpose of illustration.
Fitting A Regression Model for Genotype‐By‐Environment Data on Heading Dates in Grasses by Methods for Nonlinear Mixed Models
Authors: Piepho Hans‐Peter
Published: May 2004

Summary. The analysis of agricultural crop variety trials is usually complicated by the presence of genotype‐by‐environment interaction. A number of methods and models have been proposed to tackle this problem. One of the most common methods is the regression approach due to Yates and Cochran (1938, Journal of Agricultural Science28, 556–580), in which performances of genotypes in the environments are regressed onto environmental means. The underlying regression model contains a multiplicative term with two unknown parameters (one for genotypes and one for environments). In the present paper, the model is modified by exchanging the role of genotypes and environments. Various diagnostic plots show that this modified model is adequate for a data set on heading dates in the grass species Dactylis glomerata. If environments are considered as a random factor while genotypes are taken as fixed, the model falls into the class of nonlinear mixed models. Recently, a number of procedures have been suggested for this class of models, which are based on first‐order Taylor series expansion. Alternatively, the model can be estimated by maximum likelihood. This paper discusses the application of these methods for estimating parameters of the model.
A Multivariate Test of Interaction for Use in Clinical Trials
Authors: Follmann Dean A. , Proschan Michael A.
Published: May 2004

Summary.An important issue in clinical trials is whether the effect of treatment is essentially homogeneous as a function of baseline covariates. Covariates that have the potential for an interaction with treatment may be suspected on the basis of treatment mechanism or may be known risk factors, as it is often thought that the sickest patients may benefit most from treatment. If disease severity is more accurately determined by a collection of baseline covariates rather than a single risk factor, methods that examine each covariate in turn for interaction may be inadequate. We propose a procedure whereby treatment interaction is examined along a single severity index that is a linear combination of baseline covariates. Formally, we derive a likelihood ratio test based on the null β0=β1versus the alternative aβ=β1, whereX′βk(k= 0,1) corresponds to the severity index in armkand X is a vector of baseline covariates. While our explicit test requires a Gaussian response, it can be readily implemented whenever the estimates of β0,β1are approximately multivariate normal. For example, it is appropriate for large clinical trials where βkis based on a logisitic or Cox regression of response onX.
Statistical Inference for Serial Dilution Assay Data
Authors: Lee Mei‐Ling Ting , Whitmore G. A.
Published: May 2004

Summary. Serial dilution assays are widely employed for estimating substance concentrations and minimum inhibitory concentrations. The Poisson‐Bernoulli model for such assays is appropriate for count data but not for continuous measurements that are encountered in applications involving substance concentrations. This paper presents practical inference methods based on a log‐normal model and illustrates these methods using a case application involving bacterial toxins.
Latent Model for Correlated Binary Data with Diagnostic Error
Authors: Shih Joanna H. , Albert Paul S.
Published: May 2004

Summary. We propose a methodology for modeling correlated binary data measured with diagnostic error. A shared random effect is used to induce correlations in repeated true latent binary outcomes and in observed responses and to link the probability of a true positive outcome with the probability of having a diagnosis error. We evaluate the performance of our proposed approach through simulations and compare it with an ad hoc approach. The methodology is illustrated with data from a study that assessed the probability of corneal arcus n patients with familial hypercholesterolemia.
Estimating Equations for Removal Data Analysis
Authors: Wang You‐Gan
Published: May 2004

Summary.We consider the problem of estimating a population size from successive catches taken during a removal experiment and propose two estimating functions approaches, the traditional quasi‐likelihood (TQL) approach for dependent observations and the conditional quasi‐likelihood (CQL) approach using the conditional mean and conditional variance of the catch given previous catches. Asymptotic covariance of the estimates and the relationship between the two methods are derived. Simulation results and application to the catch data from smallmouth bass show that the proposed estimating functions perform better than other existing methods, especially in the presence of overdispersion.
The Variance for the Disequilibrium Coefficient in the Individual Hardy–Weinberg Test
Authors: Chen John J. , Thomson GlenysM
Published: May 2004

Summary. It is of interest to detect the deviation from Hardy–Weinberg proportion (HWP) for a particular heterozygote. Hernández and Weir (1989, Biometrics45, 53–70) suggested a disequilibrium coefficient approach and proposed a 1‐d.f.2 test. This note derives the appropriate variance under the null hypothesis for performing this individual HWP test. Examples of applying the test to human genetic disease data are presented.
On the Use of Historical Control Data for Trend Test in Carcinogenicity Studies
Authors: Sun Jianguo
Published: May 2004

Summary. Historical control data are often available in carcinogenicity studies and are included for testing dose effects in current studies. A new method is developed for incorporating the historical control information into a dose effect test. The method generalizes the test procedures proposed by Tarone (1982, Biometrics38, 215–220) and Ibrahim and Ryan (1996, Biometrics52, 1478–1485) by taking into account the variation resulting from parameter estimation based on historical data. Two examples are discussed for illustrating the proposed method.