bluuebunny/crossref_metadata_2025 huggingface dataset:
Low‐energy electron microscopy of layer spacings and quantum electronic structure of ultrathin films
Authors: Man Icarus K. H. , Altman M. S.
Published: January 2005

Laterally resolved measurements of the quantum size effect in electron reflectivity are made with low‐energy electron microscopy on Cu films on a W(110) surface. These measurements discriminate quantum interference peaks (QIPs) from regions of different film thickness. A Kronig–Penney model and a phase accumulation model are used to analyse QIPs to obtain average layer spacings for different film thicknesses and unoccupied band structure above the vacuum level. The average layer spacing is found to slightly exceed the strained layer spacing predicted by elasticity theory. The experimentally determined E(k) also agree with theoretical band structure from the Brillouin zone centre to the zone edge in the ΓL direction. Copyright © 2005 John Wiley & Sons, Ltd.
Nanomagnetism studies with spin‐polarized low‐energy electron microscopy and x‐ray magnetic circular dichroism photoemission electron microscopy
Authors: Zdyb R. , Locatelli A. , Heun S. , Cherifi S. , Belkhou R. , Bauer E.
Published: January 2005

The spin reorientation transition (SRT) of ultrathin FeCo alloy films on an Au(111) surface and the magnetic/structural phase transition of epitaxial MnAs films on a GaAs(100) surface are studied by two electron microscopic techniques with very high surface sensitivity, i.e. spin‐polarized low‐energy electron microscopy (SPLEEM) and x‐ray magnetic circular dichroism photoemission electron microscopy (XMCDPEEM), combined with low‐energy electron microscopy (LEEM) and low‐energy electron diffraction (LEED), respectively. A new SRT mechanism is found and the interrelation between ferromagnetism and structure is elucidated. Copyright © 2005 John Wiley & Sons, Ltd.
PEEM is a suitable tool for absolute work function measurements
Authors: Li W. Y. , Goto K. , Shimizu R.
Published: January 2005

Based on Einstein's photoelectric principle, the absolute work function was measured with a special modified photoemission electron microscope. The work function of the sample was determined by measuring the threshold of the photoelectron emission. The wavelength of ultraviolet rays was swept with an energy resolution of 1 nm. The numbers of excited electrons were counted by the counting system, using an output of a CCD camera to observe the spots on the fluorescent screen. The typical system background in the absence of UV light was measured from 0.1 to 0.4 cps. The photoemission threshold was determined by the intersection of the background and the signal in a semi‐log plot. The tentative work function of high‐purity single‐crystals of silver ((100), (110), (111)) and polycrystalline silver have been measured at 300 K to be 4.34(3), 4.25(3), 4.45(3) and 4.32(3) eV, respectively. Copyright © 2005 John Wiley & Sons, Ltd.
Phase transmission electron microscopy with aberration correction based on active defocus modulation: dynamic observation of surface atom movement
Authors: Takai Yoshizo , Nishikata Kentarou , Kawasaki Tadahiro , Kimura Yoshihide
Published: January 2005

We have developed a phase transmission electron microscopy system that enables real‐time observation of spherical aberration‐free phase images based on active defocus modulation. With the use of this system, the cooperative movement of atoms on an Au(011) reconstructed surface was clearly observed at an atomic level. Relaxation of stress in a deformed crystal was also observed when slipping of (111) atom planes occurred. The dynamic behaviour of an atom‐sized Au wire that was elongated in the [001] direction was observed at a time resolution of 1/30 s, and its behaviour was different from that of a wire elongated in the [011] direction, which was observed in a previous study. Copyright © 2005 John Wiley & Sons, Ltd.
Development of digital waveform measurement system for coincidence transmission electron microscopy
Authors: Nishinaka Kenichi , Kimura Yoshihide , Takai Yoshizo
Published: January 2005

We have been developing a new analytical transmission electron microscope for coincidence transmission electron microscopy (TEM) that in principle enables the observation of elemental mapping images of trace elements. In the present paper, we report a new digital waveform measurement system for x‐ray detection that has been newly developed and installed, instead of an analogue coincidence detection system used in our previous work, to shorten the measurement time. The high‐speed measurement system based on a digital waveform fitting technique improves successfully the time resolution of coincidence TEM from 110 to 80 ns, leading to a 30% reduction of the total measurement time compared with that of the previous system. Copyright © 2005 John Wiley & Sons, Ltd.
Transmission electron microscopy study of low‐energy ion‐induced damaged layer
Authors: Kato J. , Nagatomi T. , Takai Y.
Published: January 2005

A low‐energy Ar+ ion‐induced damaged layer on a GaAs surface was investigated using transmission electron microscopy. The dependence of the thickness of the damaged layer on the incident energy and angle of primary ions was studied. The primary energies of Ar+ ions were 200, 100 and 50 eV, which were adjusted by setting the accelerating voltages at 200, 100 and 50 V, respectively. The energies of primary Ar+ ions were measured by a laboratory‐made compact retarding‐field analyser, confirming that the peak energies were ∼180, ∼88 and ∼44 eV for accelerating voltages of 200, 100 and 50 V, respectively. The angles of incidence were 90°, 60° and 30° from the sample surface. The thickness of the damaged layer was ∼4.3 nm for 200 eV Ar+ ion irradiation at the incident angle of 90°. By lowering the primary energy from 200 to 50 eV and setting the incident angle at 30°, the thickness of the damaged layer was reduced to ∼1.5 nm. The present results confirmed that lowering the primary energy of ions to 50 eV and a glancing incidence are significantly effective for achieving higher depth resolution in sputter depth profiling. Copyright © 2005 John Wiley & Sons, Ltd.
Surface characterization of float glass related to changes in the optical properties after reheating
Authors: Hayashi Yasuo , Akiyama Ryoji , Kudo Masahiro
Published: January 2005

Commercial soda‐lime float glass samples, exhibiting different levels of their haze indices after reheating, have been investigated in terms of their surface morphology and surface composition. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) observations confirm that the origin of the increase in the haze indices is due to the formation of roughness on the bottom face of the glass, which has been described as ‘wrinkling’. Tin depth profiles in the bottom face of the float glass, with and without reheating, were measured by means of SIMS and XPS. It was found that a tin‐enriched layer was formed at the surface, due to the migration of tin towards the surface during reheating. There was a linear correlation between the amount of tin enriched at the surface and the haze index after reheating. This observation indicates that the wrinkling is caused by the surface segregation of tin. Furthermore, SIMS depth profiles of iron at the bottom face have revealed that the amount of tin enriched at the surface is inversely correlated to the surface iron concentration. The surface iron concentration is dependent not only on the concentration in the bulk glass but also on the iron concentration in the tin bath and on the atmosphere used during the float process. In particular, iron as an impurity in the tin bath can penetrate into the bottom face of float glass. These analytical results, which have led to the successful improvement of the thermal durability of float glass, are discussed in detail. Copyright © 2001 John Wiley & Sons, Ltd.
Evaluation of surface preparation methods for glass
Authors: Mellott N. P. , Brantley S. L. , Hamilton J. P. , Pantano C. G.
Published: January 2005

In this study, methods of surface preparation by polishing, fiber‐drawing, melt‐casting and chemical etching were evaluated with x‐ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) for a variety of alkali and alkaline earth aluminosilicate glasses. Freshly polished glass surfaces were exposed to a variety of chemical etchants (NaOH, NH4OH and HF) and the resulting surface composition and morphology are reported. The polishing and etching parameters were optimized to obtain a smooth surface (root‐mean‐square (RMS) roughness of ≤3 nm) and a surface composition as close as possible to the bulk composition. In addition, glass melt and fiber surfaces were examined to investigate the effect of thermal processes on surface composition and morphology. It is shown that polishing can alter the surface composition of these multicomponent glasses, and that post‐etching of the polished surface to expose the bulk composition is plagued by preferential leaching, contamination and/or roughening. The most significant conclusion is that there is a strong dependence of these surface compositional modifications upon the specific glass; even within specific glass systems, the polish/etch procedure must be modified to yield a surface with the bulk composition. On the other hand, the smoothness of fibers and melt‐cast surfaces is ideally suited to AFM and depth profiling; their surface compositions can be close to the bulk values, but careful attention to the annealing conditions is required to achieve this. Copyright © 2001 John Wiley & Sons, Ltd.
Low‐power r.f. plasma oxidation of aluminium
Authors: Rider A. N. , Lamb R. N. , Koch M. H.
Published: January 2005

Valence‐band and core‐level XPS have been used to characterize the structure and growth of aluminium oxidized in a low‐radiofrequency plasma. A change in the oxygen/aluminium ratio as a function of the metal substrate temperature during the plasma treatment correlated with changes in the valence band. Valence‐band width and shape indicated that the films were characteristic of γ‐alumina. The change in shape of the high‐binding‐energy component of the band suggested that structural changes occurred to the film as a function of temperature. Plasma film growth could be described in terms of the Cabrera–Mott theory of field‐assisted diffusion, with reaction velocities being higher than thermal oxidation rates reported in the literature. The reduction in the activation energy for plasma film growth was consistent with anion migration in a network‐forming oxide. © For and on behalf of the Commonwealth of Australia 2001. Published by John Wiley & Sons, Ltd.
AES and SAM microanalysis of structure ceramics by thinning and coating the backside
Authors: Yu Ling , Jin Deling
Published: January 2005

The preparation of thin specimens from bulk ceramic materials and coating the reverse side of the specimens with conductive material was used effectively to minimize the charging effects on ceramic surfaces during AES and Scanning Auger Microscopy (SAM) analysis. The technique allowed AES and SAM analysis to be carried out with analysis areas of a few tens of nanometres in size. The decrease of surface charging by this technique results from the transition of a primary electron beam interaction volume (VA) from an insulating region (VI) to the conductive coating region (VC) after thinning of the specimens. This reduces the number of electrons remaining in the insulating region and thus surface charging is reduced. Three structure ceramic bulk materials were prepared using this thinning technique and analysed by high‐energy resolution AES and SAM: (Y, La)‐doped silicon nitride; Dy‐doped Sialon; and alumina composite reinforced with silicon carbide whiskers. It is observed clearly in the grains of silicon nitride and the Sialon system that the kinetic energies of Si LVV and Si KLL shift to 84 and 1613 eV, respectively, and Si LVV is shifted further to ∼80 eV in the intergranular phases of the silicon nitride system as the nitrogen atoms are replaced by oxygen to produce N–Si–O bonding. Nitrogen was detected at the interfaces of alumina and the silicon carbide whiskers. The difference and distribution of composition in solid solution phases and intergranular phases are shown also in the SAM images and AES spectra. Copyright © 2001 John Wiley & Sons, Ltd.
Visualization of the intermediates in a uniform DNA condensation system by tapping mode atomic force microscopy
Authors: Liu Dage , Wang Chen , Lin Zhang , Li Junwei , Xu Bo , Wei Zhongqin , Wang Zhigang , Bai Chunli
Published: January 2005

In this work, we report observation of the fine structure of cobalt‐ hexammine‐induced DNA condensates by tapping mode atomic force microscopy (AFM). A uniform system with minimum fluctuations of concentration was obtained by introducing a slow‐evaporation method, which enables investigation of the intermediate structures in DNA condensation. Some toroid condensates had well‐defined small globule subunits; some other condensates were composed of nodular sections with gauze‐like complexes spreading around at the outskirts; typical images revealed badly assembled toroidal condensates composed of small globules with a fraction of loosely associated globules dotted in the gauze‐like complexes spreading around the badly‐assembled part of the toroid. These observations indicate that DNA condensation seems to involve five major stages: initial rapid association of chains to form gauze‐like complexes; collapse of these gauze‐like complexes at some critical sizes; growth of the critical nucleus by accretion, formation of rods by aggregation of condensed particles; and association of rod‐like condensates to form toroids. The results may shed light on uncovering the physical mechanism of DNA condensation by multivalent cations. Copyright © 2001 John Wiley & Sons, Ltd.
Combining components of quality of life to increase precision and evaluate trade‐offs
Authors: Lumley T. , Simes R. J. , Gebski V. , Hudson H. M.
Published: January 2005

Methods for combining measurements on multiple dimensions of quality of life can reduce the dimensionality of the data and increase the precision of estimation. When the dimensions are weighted according to their importance to patients, the resulting estimate is clinically useful and provides a step towards a true utility estimate. We derive two such weighting methods using linear regression on a measure of overall quality of life and demonstrate their usefulness in the analysis of quality of life data from two clinical trials of cancer therapies. Procedures for transforming the quality of life measures into utility measures are demonstrated. Copyright © 2001 John Wiley & Sons, Ltd.
Intention‐to‐treat: methods for dealing with missing values in clinical trials of progressively deteriorating diseases
Authors: Unnebrink Kristina , Windeler Jürgen
Published: January 2005

Since it came up in the 1960s, the principle of intention‐to‐treat (ITT) has become widely accepted for the analysis of controlled clinical trials. In this context the question of how to perform such an analysis in the presence of missing information about the main endpoint is of major importance. Uncritical use of several ad hoc strategies for dealing with missing values is common in the practice of clinical trials. On the other hand, little is known about possible dangers and problems of applying these strategies. We therefore performed a detailed investigation of different methods for dealing with missing values in order to develop recommendations for their practical use. A simulation study was performed investigating possible consequences on type I error and power of applying different methods for dealing with missing values. The simulations were based on a clinical trial of osteoporosis, a progressively deteriorating disease. The strategies examined can be roughly classified into numerical imputation strategies (last observation carried forward, mean and regression based methods) and non‐parametric strategies (rank and dichotomization based methods). Different drop‐out mechanisms and different types of progression of disease are considered. The type I error increases drastically for the different strategies, especially if the courses of disease vary between treatment groups. The loss in power can be substantial. There is no strategy which is adequate for all different combinations of drop‐out mechanisms, drop‐out rates and courses of disease over time. For drop‐out rates less than 20 per cent and similar courses of disease in the treatment groups, missing values might be replaced by the mean of the other group, or counted as treatment failures after dichotomization of the endpoint. For larger drop‐out rates or less similar courses of disease, no adequate recommendations can be given. Because of the drastic consequences of increasing drop‐out rates, it has to be a primary goal in clinical trials to keep missing values to a minimum. Unobserved information cannot be reliably regained by any methodological resources. As there are no strategies for universal use, reasons for the choice of a certain method have to be provided when designing and analysing clinical trials. Copyright © 2001 John Wiley & Sons, Ltd.
Quantifying and documenting prior beliefs in clinical trials
Authors: Chaloner Kathryn , Rhame Frank S.
Published: January 2005

Collecting and documenting subjective prior beliefs from knowledgeable clinicians about the potential results of a clinical trial has many advantages. Two large trials of prophylactic treatments in an HIV‐positive population are used as examples. The trials recruited patients of primary care physicians and compared treatments which were in use in clinical practice. Opinions about these trials were elicited from 58 practising HIV clinicians. It is shown how the documented opinions can be used to augment the monitoring process; the prior opinions are updated with interim data using approximate Bayesian methods to give posterior opinions incorporating interim results. These posterior opinions can be used by the monitoring board to anticipate the clinicians' reaction to the results. Eliciting prior beliefs is also ethically important for documenting the nature of the uncertainty or equipoise. Important information is provided for the informed consent process and Institutional Review Board (IRB). Copyright © 2001 John Wiley & Sons, Ltd.
Multilevel growth curve models with covariate effects: application to recovery after stroke
Authors: Tilling Kate , Sterne Jonathan A. C. , Wolfe Charles D. A.
Published: January 2005

In measuring the progression of, or recovery from, a disease an individual's outcome may be assessed on a number of occasions. A model of the relationship between outcome and time since disease occurred which accounts for patient characteristics could be used to describe patterns of recovery, to predict outcome for a patient, or to evaluate health interventions. We use multilevel models to analyse such data, focusing on the choice of powers of time both for mean outcome and covariate effects. We give equations for predicted outcome and corresponding standard errors (i) based only on baseline characteristics, and (ii) by conditioning on previous outcomes for an individual. In a study of 331 stroke patients, outcome was measured approximately 0, 2,4,6 and 12 months after stroke. Patient characteristics included age, sex, and pre‐stroke handicap, together with stroke‐severity indicators (presence of limb deficit, dysphasia, dysarthria or incontinence). Of these, only the effects of age, dysphasia and presence of deficit varied with time. Conditioning on previous observations improved the accuracy of predictions. The outcome variable clearly had a skewed distribution, and the model residuals showed evidence of non‐Normality. We discuss alternative models for non‐Normal data, and show that, here, the standard (Normal errors) multilevel model gives equivalent parameter estimates and predictions to those obtained from alternative models. Copyright © 2001 John Wiley & Sons, Ltd.
Bootstrap‐type confidence intervals for quantiles of the survival distribution
Authors: Hutson Alan D.
Published: January 2005

In this paper we outline and illustrate an easy to program method for analytically calculating both parametric and non‐parametric bootstrap‐type confidence intervals for quantiles of the survival distribution based on right censored data. This new approach allows for the incorporation of covariates within the framework of parametric models. The procedure is based upon the notion of fractional order statistics and is carried forth using a simple beta transformation of the estimated survival function (parametric or non‐parametric). It is the only direct method currently available in the sense that all other methods are based on inverting test statistics or employing confidence intervals for other survival quantities. We illustrate that the new method has favourable coverage probabilities for median confidence intervals as compared to six other competing methods. Copyright © 2001 John Wiley & Sons, Ltd.
Methods for testing equality of means of health care costs in a paired design study
Authors: Zhou Xiao‐Hua , Li Chunming , Gao Sujuan , Tierney William M.
Published: January 2005

In this paper we propose five new tests for the equality of paired means of health care costs. The first two tests are the parametric tests, a Z‐score test and a likelihood ratio test, both derived under the bivariate normality assumption for the log‐transformed costs. The third test (Z‐score with jack‐knife) is a semi‐parametric Z‐score method, which only requires marginal log‐normal assumptions. The last two tests are the non‐parametric bootstrap tests: one is based on a t‐test statistic, and the other is based on Johnson's modified t‐test statistic. We conduct a simulation study to compare the performance of these tests, along with some commonly used tests when the sample size is small to moderate. The simulation results demonstrate that the commonly used paired t‐test on the log‐scale and the Wilcoxon signed rank for differences of the two original scales can yield type I error rates larger than the preset nominal levels. The commonly used paired t‐test on the original data performs well with slightly skewed data, but can yield inaccurate results when two populations have different skewness. The likelihood ratio test, the parametric and semi‐parametric Z‐score tests all have very good type I error control with the likelihood ratio test being the best. However, the semi‐parametric Z‐score test requires less distributional assumptions than the two parametric tests. The percentile‐t bootstrap test and bootstrapped Johnson's modified t‐test have better type I error control than the paired t‐test on the original‐scale and Johnson's modified t‐test, respectively. Combining with the propensity‐score method, we can also apply the proposed methods to test the mean equality of two cost outcomes in the presence of confounders. Our two applications are from health services research. In the first one, we want to know the effect of Medicaid reimbursement policy change on outpatient health care costs. The second one is to evaluate the effect of a hospitalist programme on health care costs in an observational study, and the imbalanced covariates between intervention and control patients are taken into account using a propensity score approach. Copyright © 2001 John Wiley & Sons, Ltd.
Regression analysis of group testing samples
Authors: Xie Minge
Published: January 2005

This paper develops a general regression methodology that relates the group testing responses to individual covariate information. It can be used to study samples from a group testing procedure and to deal with a wide range of regression problems. A detailed illustration of the methodology is provided for a group testing procedure proposed by Gastwirth and Hammick. To demonstrate the utility of the method, simulation studies are performed on an HIV antibody testing data set published by Nusbacher et al. Copyright © 2001 John Wiley & Sons, Ltd.
Multinomial analysis of smoothed HIV back‐calculation models incorporating uncertainty in the AIDS incidence
Authors: Bellocco Rino , Pagano Marcello
Published: January 2005

Back‐calculation models, developed to reconstruct the past trend of human immunodeficiency virus (HIV) and to project future acquired immunodeficiency syndrome incidence (AIDS), are usually and unrealistically based on the assumption that the observed AIDS counts are independently distributed according to a Poisson process. In contrast, we argue that a multinomial framework is more suitable to this situation, leading to a natural covariance structure. The ill‐conditioned nature of the problem is solved by modelling the HIV parameters according to a cubic spline function to reduce the dimensionality of the parameter space and obtain smoother parameter estimates. We applied a regression spline technique which yields to a computationally stable basis incorporating the incubation period in the new design matrix. We directly incorporate the reporting delay distribution in the AIDS incidence data, leading to a more complex formulation of the variance and covariance model that is adapted to the iteratively reweighted least square (IRLS) algorithm. In this case we obtain more accurate estimates of the standard error of the HIV incidence, especially in the most recent time. Our model, which uses a cubic spline reparameterization based on a multinomial probability distribution, is applied to the AIDS epidemic data in Italy. Copyright © John Wiley & Sons, Ltd.
Some issues in resolution of diagnostic tests using an imperfect gold standard
Authors: Hawkins Douglas M. , Garrett James A. , Stephenson Betty
Published: January 2005

As a subject's true disease status is seldom known with certainty, it is necessary to compare the performance of new diagnostic tests with those of a currently accepted but imperfect ‘gold standard’. Errors made by the gold standard mean that the sensitivity and specificity calculated for the new test are biased, and do not correctly estimate the new method's sensitivity and specificity. The traditional approach to this problem was ‘discrepant resolution’, in which the subjects for whom the two methods disagreed were subjected to a third ‘resolver’ test. Recent work has pointed out that this does not automatically solve the problem. A sounder approach goes beyond the discordant test results and tests at least some of the subjects with concordant results with the resolver also. This leaves some issues unresolved. One is the basic question of the direction of biases in various estimators. We point out that this question does not have a simple universal answer. Another issue, if one is to test a sample of the subjects with concordant results rather than all cases, is how to compute estimates and standard errors of the measures of test performance, notably sensitivity and specificity of the test method relative to the resolver. Expressions for these standard errors are given and illustrated with a numeric example. It is shown that using just a sample of subjects with concordant results may lead to great savings in assays. The design issue of how many concordant cells to test depends on the numbers of concordants and discordants. The formulae given show how to evaluate impact of different choices for these numbers and hence settle on a design that gives the required precision of estimates. Copyright © 2001 John Wiley & Sons, Ltd.
The use of mixture models for identifying high risks in disease mapping
Authors: Militino A. F. , Ugarte M. D. , Dean C. B.
Published: January 2005

Conventional approaches for estimating risks in disease mapping or mortality studies are based on Poisson inference. Frequently, overdispersion is present and this extra variability is modelled by introducing random effects. In this paper we compare two computationally simple approaches for incorporating random effects: one based on a non‐parametric mixture model assuming that the population arises from a discrete mixture of Poisson distributions, and the second using a Poisson‐normal mixture model which allows for spatial autocorrelation. The comparison is focused on how well each of these methods identify the regions which have high risks. Such identification is important because policy makers may wish to target regions associated with such extreme risks for financial assistance while epidemiologists may wish to target such regions for further study. The Poisson‐normal mixture model is presented from both a frequentist, or empirical Bayes, and a fully Bayesian point of view. We compare results obtained with the parametric and non‐parametric models specifically in terms of detecting extreme mortality risks, using infant mortality data of British Columbia, Canada, for the period 1981–1985, breast cancer data from Sardinia, for the period 1983–1987, and Scottish lip cancer data for 1975–1980. However, we also investigate the performance of these models in a simulation study. The key finding is that discrete mixture models seem to be able to locate regions which experience high risks; normal mixture models also work well in this regard, and perform substantially better when spatial autocorrelation is present. Copyright © 2001 John Wiley & Sons, Ltd.
Simultaneous modelling of operative mortality and long‐term survival after coronary artery bypass surgery
Authors: Ghahramani M. , Dean C. B. , Spinelli J. J.
Published: January 2005

Typical analyses of lifetime data treat the time to death or failure as the response variable and use a variety of modelling strategies such as proportional hazards or fully parametric, to investigate the relationship between the response and covariates. In certain circumstances it may be more natural to view the distribution of the response variable as consisting of two or more parts since the survival curve appears segmented. This article addresses such a scenario and we propose a model for simultaneously investigating the effects of covariates over the two segments. The model is an analogue of that proposed by Lambert for zero‐inflated Poisson regression. The application is central to the model development and is concerned with survival after coronary artery bypass surgery. Here operative mortality, defined as death within 30 days after surgery, and long‐term mortality, are viewed as distinct outcomes. For the application considered, the survivor function displays much steeper descent during the first 30 days after surgery, that is, for operative mortality, than after this period. An investigation of the effects of covariates on operative and long‐term mortality after coronary artery bypass surgery illustrates the usefulness of the proposed model. Copyright © 2001 John Wiley & Sons, Ltd.
Using the overdispersed exponential family to estimate the distribution of usual daily intakes of people aged between 18 and 28 in Taiwan
Authors: Chang Hsing‐Yi , Suchindran Chirayath M. , Pan Wen‐Harn
Published: January 2005

Assessment of usual dietary intake of a population is essential to understand the nutrition status of the population. Methods like 24‐hour dietary recall and food records are commonly used for this task. However, within‐individual variation exists in the food record data. Methods considering measurement errors have been used to evaluate the association between nutrient intakes and diseases. Few have been devoted to estimating the distribution of usual daily intakes. This paper proposes applying the formulation of the overdispersed exponential family to estimate the distribution of usual nutrient intake and applies the adjustments developed by Liu to reduce the variance of the distribution. The proposed method has the advantages of working on the original scale of data and implementation convenience. The adjustment of the variance is carried out by dividing the variance into within‐individual variance and among‐individual variance. The adjusted variance, then, is used to estimate the distribution of the usual daily intake. Sampling weights are considered in all the steps, except the estimation of the ratio of within to among variance. The data for this study are from the Nutritional and Health Survey in Taiwan conducted between 1993 and 1996 (NAHSIT, 1993–1996). An independent external set of data for people aged between 18 and 28 years (49 males and 20 females) is used to estimate the ratio of within to among individual variance. Due to the availability of data in estimating the ratio of within to among individual variance, 430 males and 422 females in the NAHSIT sample are used to estimate the distribution of usual daily intakes for people aged between 18 and 28 in Taiwan. The distribution also allows us to estimate the proportion of people who do not meet the recommended daily nutrient allowance (RDNA). The results show that the intakes of calcium and vitamin E of this group of people fall far below RDNA. Copyright © 2001 John Wiley Sons, Ltd.
Estimating HIV incidence rates from age prevalence data in epidemic situations
Authors: Williams Brian , Gouws Eleanor , Wilkinson David , Karim Salim Abdool
Published: January 2005

We present a method of estimating HIV incidence rates in epidemic situations from data on age‐specific prevalence and changes in the overall prevalence over time. The method is applied to women attending antenatal clinics in Hlabisa, a rural district of KwaZulu/Natal, South Africa, where transmission of HIV is overwhelmingly through heterosexual contact. A model which gives age‐specific prevalence rates in the presence of a progressing epidemic is fitted to prevalence data for 1998 using maximum likelihood methods and used to derive the age‐specific incidence. Error estimates are obtained using a Monte Carlo procedure. Although the method is quite general some simplifying assumptions are made concerning the form of the risk function and sensitivity analyses are performed to explore the importance of these assumptions. The analysis shows that in 1998 the annual incidence of infection per susceptible woman increased from 5.4 per cent (3.3–8.5 per cent; here and elsewhere ranges give 95 per cent confidence limits) at age 15 years to 24.5 per cent (20.6–29.1 per cent) at age 22 years and declined to 1.3 per cent (0.5–2.9 per cent) at age 50 years; standardized to a uniform age distribution, the overall incidence per susceptible woman aged 15 to 59 was 11.4 per cent (10.0–13.1 per cent); per women in the population it was 8.4 per cent (7.3–9.5 per cent). Standardized to the age distribution of the female population the average incidence per woman was 9.6 per cent (8.4–11.0 per cent); standardized to the age distribution of women attending antenatal clinics, it was 11.3 per cent (9.8–13.3 per cent). The estimated incidence depends on the values used for the epidemic growth rate and the AIDS related mortality. To ensure that, for this population, errors in these two parameters change the age specific estimates of the annual incidence by less than the standard deviation of the estimates of the age specific incidence, the AIDS related mortality should be known to within ±50 per cent and the epidemic growth rate to within ±25 per cent, both of which conditions are met. In the absence of cohort studies to measure the incidence of HIV infection directly, useful estimates of the age‐specific incidence can be obtained from cross‐sectional, age‐specific prevalence data and repeat cross‐sectional data on the overall prevalence of HIV infection. Several assumptions were made because of the lack of data but sensitivity analyses show that they are unlikely to affect the overall estimates significantly. These estimates are important in assessing the magnitude of the public health problem, for designing vaccine trials and for evaluating the impact of interventions. Copyright © 2001 John Wiley & Sons, Ltd.
An improved method of evaluating drug effect in a multiple dose clinical trial
Authors: Shen Liji
Published: January 2005

In drug development, finding an optimal dose is normally carried out in a phase II trial. A phase III trial will then be conducted to demonstrate that the selected dose is efficacious and safe. As choosing a dose from the phase II trial which has the highest observed response rate could overestimate the true response rate of the selected dose, the data from the phase II study cannot be simply pooled with the data from the phase III study in a final analysis. Therefore, a solution to the overestimation problem needs to be found so that the information obtained from phase II dose finding clinical trials can appropriately be combined with the data in the phase III study. In this paper, the potential overestimation in a multiple dose clinical trial is assessed and a method for correcting this bias is proposed. Simulations show that stepwise over‐correction, the proposed method, is better than methods such as Bonferroni's procedure. Copyright © 2001 John Wiley & Sons, Ltd.
Sample size calculations for clustered binary data
Authors: Jung Sin‐Ho , Kang Seung‐Ho , Ahn Chul
Published: January 2005

In this paper we propose a sample size calculation method for testing on a binomial proportion when binary observations are dependent within clusters. In estimating the binomial proportion in clustered binary data, two weighting systems have been popular: equal weights to clusters and equal weights to units within clusters. When the number of units varies cluster by cluster, performance of these two weighting systems depends on the extent of correlation among units within each cluster. In addition to them, we will also use an optimal weighting method that minimizes the variance of the estimator. A sample size formula is derived for each of the estimators with different weighting schemes. We apply these methods to the sample size calculation for the sensitivity of a periodontal diagnostic test. Simulation studies are conducted to evaluate a finite sample performance of the three estimators. We also assess the influence of misspecified input parameter values on the calculated sample size. The optimal estimator requires equal or smaller sample sizes and is more robust to the misspecification of an input parameter than those assigning equal weights to units or clusters. Copyright © 2001 John Wiley & Sons, Ltd.
Phase specific analysis of herpes zoster associated pain data: a new statistical approach
Authors: Arani Ramin B. , Soong Seng‐Jaw , Weiss Heidi L. , Wood Martin J. , Fiddian Paul A. , Gnann John W. , Whitley Richard
Published: January 2005

Herpes zoster or shingles is a frequent occurrence in both elderly individuals and immunocompromised hosts. The pain associated with herpes zoster is the most debilitating complication of the disease. It can be described as acute pain and post‐herpetic neuralgia or zoster associated pain (ZAP). The latter definition encompasses pain from the onset of disease through its resolution and provides a convenient analytic tool for evaluation of antiviral therapy. A heuristic examination of ZAP historical data suggests the existence of three phases of pain resolution: the acute, subacute and chronic phases. The subacute and chronic phases comprise the post‐herpetic neuralgia (PHN) stage. Common analytic methods, such as a Kaplan–Meier survival function or a Cox's model, have been used to assess the pain. However, such approaches do not adequately allow for phase comparison. Notably, in the clinical trial setting the comparison of specific treatment effects on the latter stages of pain are of the greatest medical relevance since this is the most debilitating phase of the illness. In order to incorporate the phase‐specific information in the modelling of time to cessation of ZAP, we assumed the hazard function was a stepwise constant. Utilizing the full likelihood function, we obtained the maximum likelihood estimate for the transition times (that is, change‐points), and other parameters of medical importance. The standard error of the change‐point estimates were obtained through a bootstrapping method. The asymptotic properties of the parameter estimates are also discussed. Hence, the rates of pain resolution across all phases can be examined in order to precisely define the existence of multiple phases. In addition, the covariates effect can be examined across phases and populations, thereby allowing us to translate potential efficacy of a standard therapy to different populations. These results can be utilized in the design of clinical trials or in targeting the outcome for a specific phase while controlling for the effect of other variables. Copyright © 2001 John Wiley & Sons, Ltd.
Improving the fit of bivariate smoothing splines when estimating longitudinal immunological and virological markers in HIV patients with individual antiretroviral treatment strategies
Authors: Brown Elizabeth R. , MaWhinney Samantha , Jones Richard H. , Kafadar Karen , Young Benjamin
Published: January 2005

CD4+ lymphocyte count and HIV RNA plasma viral load are longitudinally monitored in patients with HIV infection. Because data collection intervals may be unequally spaced and these markers experience high within‐patient variability, they may be smoothed before use in subsequent models. Estimation strategies must be able to accommodate the drastic changes in viral load which may occur when an individual's treatment strategy is updated. Because these treatment changes are not regimented, these dynamics cannot be modelled using standard methods. We propose univariate and bivariate cubic smoothing splines to fit CD4+ count and viral load over time. The method is developed using state space equations, and the Kalman filter is used to calculate the log‐likelihood. Non‐linear optimization is used to obtain the maximum likelihood estimates. A modification of the Kalman filter allows non‐informative or diffuse priors at the initial observation. Since treatment changes are expected to alter the shape of the curve, we further extend the Kalman filter to permit greater flexibility in the smoothing spline at these time points. The method produces smoothed estimates of the viral load and CD4+ count curves over time. Copyright © 2001 John Wiley & Sons, Ltd.
Parametric modelling of neonatal mortality in relation to size at birth
Authors: Cheung Yin Bun , Yip Paul S. F. , Karlberg Johan P. E.
Published: January 2005

We use a richly parameterized model to analyse the effects of shortness and thinness at birth on neonatal mortality in Swedish live‐born singletons. The model captures the hazard of neonatal mortality according to the function α×exp(−γ×t)+δ, where t represents age. Covariates are allowed to simultaneously influence the initial excess hazard, the rate of decay, and the long‐term hazard. Among term newborns, birth length for gestational age had a stronger effect on the long‐term hazard and a weaker effect on the initial excess hazard than the Ponderal index. The initial excess hazard associated with a low Ponderal index tended to decay quickly. Among preterm newborns, a higher birth length for gestational age was associated with lower initial and long‐term hazards, and with a faster rate of decay of the initial excess hazard. In contrast, the Ponderal index was not associated with the long‐term hazard. We discuss the interpretability of the model and its potential use in neonatology and medical demography. We also compare the model to a Cox model with time‐dependent covariates. Copyright © 2001 John Wiley & Sons, Ltd.
Effects of covariance model assumptions on hypothesis tests for repeated measurements: analysis of ovarian hormone data and pituitary‐pteryomaxillary distance data
Authors: Park Taesung , Park Jin‐Kyung , Davis Charles S.
Published: January 2005

In the analysis of repeated measurements, multivariate methods which account for the correlations among the observations from the same experimental unit are widely used. Two commonly‐used multivariate methods are the unstructured multivariate approach and the mixed model approach. The unstructured multivariate approach uses MANOVA types of models and does not require assumptions on the covariance structure. The mixed model approach uses multivariate linear models with random effects and requires covariance structure assumptions. In this paper, we describe the characteristics of tests based on these two methods of analysis and investigate the performance of these tests. We focus particularly on tests for group effects and parallelism of response profiles. Copyright © 2001 John Wiley & Sons, Ltd.
Optimal design for linear interpolation of curves
Authors: Wang Jixian
Published: January 2005

Non‐parametric procedures are often used for the analysis of pharmacokinetic trials. Fewer design procedures are available for non‐parametric estimation than for parametric estimation. Linear interpolation is widely used for curve estimation in pharmacokinetic trials, where often only sparse sampling is feasible. Current design procedures for smoothing or local fit are not suitable as they are based on asymptotic properties and the bias of the estimate is ignored. This paper proposes optimal designs that minimize the mean squared error of linear interpolation. Optimal designs for three situations are considered. The first situation is single curve estimation based on an ordinary non‐linear model. The second is estimating several curves in a non‐linear mixed model setting using an average mean squared error as the design criterion. The third situation is destructive sampling where estimating the average curve is the main purpose. In the first situation, the design results in the best linear interpolation when the variance is constant. For the destructive sampling design, an algorithm based on approximations is proposed. This algorithm can be programmed in a common statistical package. Numerical examples are used to illustrate the design procedure. Copyright © 2001 John Wiley & Sons, Ltd.
Estimation for paired binomial data with application to radiation therapy
Authors: Taylor Jeremy M. G. , Weiss Robert E. , Li Wenzhi , Hsu Chiu‐Hsieh , Suwinski Rafal
Published: January 2005

We compare and contrast several different methods for estimating the effect of treatment when responses are paired binomial observations. The ratio of binomial probabilities is the parameter of interest, while the binomial probabilities are nuisance parameters which may vary between pairs. The application is a meta‐analysis of the treatment of rectal cancer, with observations in each study indicating the number of recurrences of the cancer in each of two groups, one with radiation therapy and one without. The ratio of the probabilities of recurrence in the radiation to non‐radiation groups is of substantive interest, and is modelled as a logistic or complementary log‐log function of an unknown linear combination of the covariates. The three methods we consider are maximum likelihood, a Bayesian approach and an approach based on estimating equations. For the MLE and Bayesian approach the potentially large number of nuisance parameters are estimated together with the parameters of interest, whereas for the estimating equation approach only the parameters of interest are estimated. A simulation study is performed to compare the methods and evaluate the impact of overdispersion. Copyright 2001 John Wiley & Sons, Ltd.
Data augmentation priors for Bayesian and semi‐Bayes analyses of conditional‐logistic and proportional‐hazards regression
Authors: Greenland Sander , Christensen Ronald
Published: January 2005

Data augmentation priors have a long history in Bayesian data analysis. Formulae for such priors have been derived for generalized linear models, but their accuracy depends on two approximation steps. This note presents a method for using offsets as well as scaling factors to improve the accuracy of the approximations in logistic regression. This method produces an exceptionally simple form of data augmentation that allows it to be used with any standard package for conditional‐logistic or proportional‐hazards regression to perform Bayesian and semi‐Bayes analyses of matched and survival data. The method is illustrated with an analysis of a matched case‐control study of diet and breast cancer. Copyright © 2001 John Wiley & Sons, Ltd.