bluuebunny/crossref_metadata_2025 huggingface dataset:
A Finite Element Model to Identify Electrode Influence on Current Distribution in the Skin
Authors: Sha Ning , Kenney Laurence P.J. , Heller Ben W. , Barker Anthony T. , Howard David , Moatamedi Moji
Published: August 2008

Abstract:  Discomfort experienced during surface functional electrical stimulation (FES) is thought to be partly a result of localized high current density in the skin underneath the stimulating electrode. This article describes a finite element (FE) model to predict skin current density distribution in the region of the electrode during stimulation and its application to the identification of electrode properties that may act to reduce sensation. The FE model results show that the peak current density was located in an area immediately under the stratum corneum, adjacent to a sweat duct. A simulation of surface FES via a high‐resistivity electrode showed a reduction in this peak current density, when compared to that with a low‐resistivity electrode.
Modification of Reflex Responses to Lumbar Posterior Root Stimulation by Motor Tasks in Healthy Subjects
Authors: Hofstoetter Ursula S. , Minassian Karen , Hofer Christian , Mayr Winfried , Rattay Frank , Dimitrijevic Milan R.
Published: August 2008

Abstract:  Dynamic task‐dependent regulation of reflexes controlled by the central nervous system plays an integral part in neurocontrol of locomotion. Such modifications of sensory‐motor transmission can be studied by conditioning a test reflex with specific motor tasks. To elicit short‐latency test reflexes, we applied a novel transcutaneous spinal cord stimulation technique that depolarizes large‐diameter posterior root afferents. These responses, termed posterior root‐muscle (PRM) reflexes, are equivalent to the monosynaptic Hoffmann (H)‐reflex but can be evoked in several muscles simultaneously. We elicited PRM reflexes in quadriceps, hamstrings, tibialis anterior, and triceps surae in subjects with intact nervous system. During three different conditioning‐test paradigms in a standing position, that is, volitional unilateral single‐ and multi‐joint lower limb movements and leaning backward/forward, we recorded characteristic movement‐induced modulations of PRM reflexes in the thigh and leg muscle groups. We could thus demonstrate that monosynaptic PRM reflexes in functional extensor and flexor muscles of the thigh and leg can be elicited in upright standing subjects and can be modulated during the execution of postural maneuvers. The significance is that transcutaneous posterior root stimulation allows extending H‐reflex studies of a single muscle to the assessment of synaptic transmission of two‐neuron reflex arcs at multiple segmental levels simultaneously.
Results of Electromyostimulation Therapy in Obstructive Sleep Apnea
Authors: Ludwig Arwed
Published: August 2008

Abstract: Innovative muscle stimulation techniques have become alternatives for therapy of obstructive sleep apnea syndrome breathing disorders. In group I, an individually shaped mouth floor electrode (IME) and in group II, an individually adaptable multi‐point electrode (MPE) on a silicone carrier has been used for electromyostimulation (EMS) therapy in patients with obstructive sleep apnea. The enoral‐cutaneous EMS was carried out with the low‐frequency stimulation apparatus I‐pulse over a period of 8 weeks, two times daily for 30 min during daytime hours only. In group III, the patients used EMS therapy for half a year continuously. Before and after stimulation treatment, three‐dimensional volumetric sonographical measurement of the geniohyoid muscle was carried out. All patients (n = 14) totally applied the EMS therapy. Under IME and MPE application after 4 weeks of EMS therapy, a median volume increase of 19.6% (minimum 9.7%, maximum 27.9%) was registered, the median after 8 weeks IME was 27.6% and in MPE 24.0%). No significant difference (analysis of variance type:P > 0.05) between electrodes could be found. In all groups, a reduction of the muscle length of 4.7% was proved. In groups I and II after 26 weeks, the volume was near baseline before stimulation (+4.3%). In the third group, the increase of volume persisted (+29.4%) over the observation period of 12–26 weeks. Opposed to established stimulation techniques, a threefold effectiveness enhancement could be verified by using both individually adaptable electrodes. The EMS therapy should be carried out as continuous long‐term therapy or as interval therapy.
Gene therapy in epilepsy
Authors: Riban Véronique , Fitzsimons Helen L. , During Matthew J.
Published: August 2008

Results from animal models suggest gene therapy is a promising new approach for the treatment of epilepsy. Several candidate genes such as neuropeptide Y and galanin have been demonstrated in preclinical studies to have a positive effect on seizure activity. For a successful gene therapy‐based treatment, efficient delivery of a transgene to target neurons is also essential. To this end, advances have been made in the areas of cell transplantation and in the development of recombinant viral vectors for gene delivery. Recombinant adeno‐associated viral (rAAV) vectors in particular show promise for gene therapy of neurological disorders due to their neuronal tropism, lack of toxicity, and stable persistence in neurons, which results in robust, long‐term expression of the transgene. rAAV vectors have been recently used in phase I clinical trials of Parkinson's disease with an excellent safety profile.

Prior to commencement of phase I trials for gene therapy of epilepsy, further preclinical studies are ongoing including evaluation of the therapeutic benefit in chronic models of epileptogenesis, as well as assessment of safety in toxicological studies.
Spatial localization and time‐dependant changes of electrographic high frequency oscillations in human temporal lobe epilepsy
Authors: Khosravani Houman , Mehrotra Nikhil , Rigby Michael , Hader Walter J. , Pinnegar C. Robert , Pillay Neelan , Wiebe Samuel , Federico Paolo
Published: August 2008

Purpose:  High frequency oscillations (HFOs) >200 Hz are believed to be associated with epileptic processes. The spatial distribution of HFOs and their evolution over time leading up to seizure onset is unknown. Also, recording HFOs through conventional intracranial electrodes is not well established. We therefore wished to determine whether HFOs could be recorded using commercially available depth macroelectrodes. We also examined the spatial distribution and temporal progression of HFOs during the transition to seizure activity.

Methods:  Intracranial electroencephalography (EEG) recordings of 19 seizures were obtained from seven patients with temporal lobe epilepsy using commercial depth or subdural electrodes. EEG recordings were analyzed for frequency content in five spectral bands spanning DC‐500 Hz. We examined the spatial distribution of the different spectral bands 5 s before and 5 s after seizure onset. Temporal changes in the spectral bands were studied in the 30‐s period leading up to seizure onset.

Results:  Three main observations were made. First, HFOs (100–500 Hz) can be recorded using commercial depth and subdural grid electrodes. Second, HFOs, but not <100 Hz oscillations, were localized to channels of ictal onset (100–200, 400–500 Hz, p < 0.05; 300–400 Hz, p < 0.001). Third, temporal analysis showed increased HFO power for approximately 8 s prior to electrographic onset (p < 0.05).

Conclusions:  These results suggest that HFOs can be recorded by depth macroelectrodes. Also, HFOs are localized to the region of primary ictal onset and can exhibit increased power during the transition to seizure. Thus, HFOs likely represent important precursors to seizure initiation.
Neuropsychological Characteristics of Italian Children With Fetal Alcohol Spectrum Disorders
Authors: Aragón Alfredo S. , Coriale Giovanna , Fiorentino Daniela , Kalberg Wendy O. , Buckley David , Phillip Gossage J. , Ceccanti Mauro , Mitchell Elisha R. , May Philip A.
Published: August 2008

Background:  Children with fetal alcohol spectrum disorders (FASD) display many problems ranging from deficits in intelligence to behavioral difficulties. Thus, many studies have aimed at defining the neuropsychological characteristics of children with FASD. The current article describes the neuropsychological characteristics of Italian children with severe diagnosis within FASD and compares them with controls. It was expected that intellectual functioning, language comprehension, academic skills, and inattention/hyperactivity would discriminate children with FASD from randomly selected peers without FASD.

Methods:  This article presents data from a second cohort of children examined in 2005 as part of an in‐school epidemiological study of FASD in Italy. Of 80 children, 23 diagnosed with a FASD, and 57 randomly selected control children from the same first‐grade classes, participated. After screening for FASD via growth and dysmorphology, the children were administered a test of general intelligence (WISC‐R) as well as tests of nonverbal reasoning (Raven Colored Progressive Matrices), language comprehension (Rustioni), academic achievement (IPDA), and problem behavior (Disruptive Behavior Disorder Rating Scale).

Results:  Children diagnosed with a FASD achieved lower scores than control children on Verbal, Performance, and Full Scale IQ. Profile analysis of the WISC‐R indicates overall differences between the groups. However, some intact functioning within the FASD group was found, as the Similarities and Vocabulary subtests were similar to the controls. After an alpha adjustment to 0.004, the Block Design, Object Assembly, and Mazes subtests were significantly different from controls. On tests of nonverbal reasoning, language comprehension, and academic achievement, the children with a FASD scored significantly lower. Moreover, teachers rated children with a severe diagnosis within FASD as showing more inattentive symptoms than controls, while hyperactive/impulsive characteristics among children with a FASD were comparable with the control children. Significant correlations between head circumference, child dysmorphology, WISC‐R, and Raven CPM scores are also reported.

Conclusions:  This study indicates that a sample of Italian children with a FASD, when compared with control children, display poorer functioning on measures of general intelligence, nonverbal reasoning, academic achievement, and teacher‐rated problem behaviors. The findings also contribute to the formulation of a neuropsychological profile of children diagnosed with a FASD.
Incidence of Cardiovascular and Cerebrovascular Disease in Danish Men and Women With a Prolonged Heavy Alcohol Intake
Authors: Hvidtfeldt Ulla Arthur , Frederiksen Marie Engholm , Thygesen Lau Caspar , Kamper‐Jørgensen Mads , Becker Ulrik , Grønbæk Morten
Published: August 2008

Background:  Several epidemiological studies have found U‐ or J‐shaped relationships between alcohol intake and cardiovascular conditions. The influence of heavy drinking is, however, sparsely studied. The objective of the present study was to examine whether alcohol addicts have higher incidence rates of cardio‐ and cerebrovascular diseases than the population in general.

Methods:  The cohort comprised 19,185 subjects (15,368 men and 3,817 women) who attended outpatient clinics for alcohol abusers within the Copenhagen Hospital Corporation (1954 to 1992). Incidence rates were standardized (SIR) according to sex, age and calendar time to compare subjects’ cardio‐ and cerebrovascular incidence with that of the general population of Copenhagen.

Results:  During the period 1977 to 2001 a total of 9,397 events of cardio‐ and cerebrovascular disease were observed. In both men and women, statistically significant higher incidence rates than would be expected in a standard population were observed for cardiovascular diseases (e.g., ischemic heart diseases, men: SIR = 1.76; 95% CI 1.69–1.83; women: SIR = 2.44; 95% CI 2.19–2.73) and cerebrovascular diseases (e.g., hemorrhagic stroke, men: SIR = 2.71; 95% CI 2.45–2.99; women: SIR = 2.77; 95% CI 2.18–3.48).

Conclusions:  The study indicates increased risks of cardio‐ and cerebrovascular diseases in subjects with an excessive alcohol intake.
Toward Sustainable Nanoproducts
Authors: Şengül Hatice , Theis Thomas L. , Ghosh Siddhartha
Published: August 2008

Sustainable development of nanotechnology will inevitably require incorporation of life cycle thinking to analyze environmental impacts of nanomanufacturing. While many concerns have been raised regarding the human and ecological health effects of and benefits from using nanoproducts, relatively little attention has been given to the manufacturing phase. Unlike many conventional manufacturing techniques, nanomanufacturing techniques require unique facility and process design as well as operation and control. Accordingly, the environmental burden of most nanomanufacturing techniques may be more profound than that of many other conventional techniques. This article reports on a comprehensive review of the current state of technologies used in the manufacture of nanostructured materials in order to identify those attributes that contribute to environmental impacts. It provides a preliminary analysis of significant attributes of commonly used nanomanufacturing techniques, including strict material purity requirements, less tolerance for defects, low process yields and material utilization efficiencies, repetitive processing steps, the need for specialized environments (such as high temperatures or cryogenic processing), the use of toxic chemicals and solvents, the need for moderate to high vacuum, the use or generation of greenhouse gases, high energy and water consumption, and the potential for chemical exposure.
Radiofrequency and Pulsed Radiofrequency Treatment of Chronic Pain Syndromes: The Available Evidence
Authors: Van Boxem Koen , Van Eerd Maarten , Brinkhuize Tjinta , Patijn Jacob , Van Kleef Maarten , Van Zundert Jan
Published: August 2008

There are currently 6 reviews on (pulsed) radiofrequency (RF) for the management of spinal pain. Two reviews on interventional pain management techniques in general also discuss RF. The outcomes of those reviews depend on the type of studies included and the opinion of the reviewers, which may result in different evidence levels.

Radiofrequency denervation at the cervical and lumbar level has produced the most solid evidence. The differences in treatment outcome registered in the 5 randomized controlled trials (RCTs) regarding lumbar facet denervation can be attributed to differences in patient selection and/or inappropriate technique. There is not sufficient evidence supporting the use of RF facet denervation for the management of cervicogenic headache. The studies examining the management of cervical radicular pain suggest a comparable efficacy for RF and pulsed RF (PRF). The PRF treatment is supposed to be safer and therefore should be preferred. The superiority of RF treatment adjacent to the lumbar dorsal root ganglion for the management of lumbar radicular pain has not been demonstrated in an RCT.

Information regarding RF treatment of sacroiliac joint pain is accumulating. No randomized sham‐controlled trials on the value of RF treatment of the Gasserian ganglion for the management of idiopathic trigeminal neuralgia have been published. One RCT indicates superiority of RF over PRF for the management of idiopathic trigeminal neuralgia. Future research to confirm or deny the efficacy of (P)RF should be conducted in carefully selected patient populations. The tests used for patient inclusion in such a trial could potentially help the clinician in selecting patients for this type of treatment. The value of PRF treatment of the peripheral nerves also needs to be confirmed in well‐designed trials.
Testing only donors with a prior history of pregnancy or transfusion is a logical and cost‐effective transfusion‐related acute lung injury prevention strategy
Authors: Powers Amy , Stowell Christopher P. , Dzik Walter H. , Saidman Susan L. , Lee Hang , Makar Robert S.
Published: August 2008

BACKGROUND: Transfusion‐related acute lung injury (TRALI) is the leading cause of transfusion‐related fatality reported to the Food and Drug Administration. Donor screening may reduce TRALI risk. This study sought to compare the efficacy and safety of different TRALI risk‐reduction strategies at a hospital‐based donor center.

STUDY DESIGN AND METHODS: Samples from 1053 donors who answered questions regarding pregnancy and transfusion history were tested for HLA Class I and II antibodies using a flow cytometry–based screening assay. Donor history was compared with the presence of HLA alloantibodies. These data were used to model several TRALI risk‐reduction strategies. The medical records of patients transfused fresh‐frozen plasma (FFP) from highly alloimmunized donors were retrospectively reviewed for TRALI.

RESULTS: HLA alloimmunization was observed among 25.4 percent (256/1009) of all female donors and among 12.0 percent (3/25) of those male donors who gave a history of prior transfusion. Prior pregnancy, reported by 52.6 percent (531/1009) of females, correlated significantly with HLA alloimmunization (p < 0.0001). The rate of HLA alloimmunization increased with parity. A positive pregnancy history was a sensitive (87.9%) screen for HLA alloimmunization with a negative predictive value of 93.5 percent (95% confidence interval, 91.3%‐95.7%). Although 5.9 percent (27/459) of nulliparous, untransfused females demonstrated a positive screening test, only 1 percent (7/459) had a confirmed HLA alloantibody. Transfusion of FFP from donors found retrospectively to be highly alloimmunized led to reactions suggestive of TRALI in 2 of 26 recipients.

CONCLUSIONS: Donor history is a reliable predictor of HLA alloimmunization. Testing only donors with a prior history of pregnancy or transfusion is a logical and cost‐effective TRALI prevention strategy.
Foreign Share, Insurance Density, and Penetration: An Analysis of the International Life Insurance Market
Authors: Ma Yu‐Luen , Pope Nat
Published: August 2008

Abstract 

Recent trends toward liberalization and deregulation have sparked significant interest in the topic of international insurers' participation in foreign markets. This research develops a profile of foreign national market characteristics that attract international life insurer participation and additionally, empirically assesses the value that international participation has to the host market. Characteristics that are found to be statistically significant with respect to international participation include high levels of trade liberalization and/or low insurer market share concentration, high levels of national wealth, and high levels of government expenditure on social security retirement benefits. With respect to the benefits such participation provides, we see that the presence of international life insurers share positive relationships with both life insurance consumption and the magnitude of the role life insurance plays within the broader national economy of those host markets.
The Hungarian Insurance Market: Economic Transition in the Insurance Sector
Authors: Venard Bertrand , Halek Martin , Dorfman Mark S.
Published: August 2008

Abstract

This article analyzes Hungary's insurance sector as an important part of the country's economic transition from a centrally planned economy to a market economy. It details the historic economic development of the Hungarian insurance market from a state monopoly to a competitive insurance market where foreign‐owned insurance companies have a dominant market share.
Optimal Observation Times in Experimental Epidemic Processes
Authors: Cook Alex R. , Gibson Gavin J. , Gilligan Christopher A.
Published: August 2008

SummaryThis article describes a method for choosing observation times for stochastic processes to maximise the expected information about their parameters. Two commonly used models for epidemiological processes are considered: a simple death process and a susceptible‐infected (SI) epidemic process with dual sources for infection spreading within and from outwith the population. The search for the optimal design uses Bayesian computational methods to explore the joint parameter‐data‐design space, combined with a method known asmoment closureto approximate the likelihood to make the acceptance step efficient. For the processes considered, a small number of optimally chosen observations are shown to yield almost as much information as much more intensively observed schemes that are commonly used in epidemiological experiments. Analysis of the simple death process allows a comparison between the full Bayesian approach and locally optimal designs around a point estimate from the prior based on asymptotic results. The robustness of the approach to misspecified priors is demonstrated for the SI epidemic process, for which the computational intractability of the likelihood precludes locally optimal designs. We show that optimal designs derived by the Bayesian approach are similar for observational studies of a single epidemic and for studies involving replicated epidemics in independent subpopulations. Different optima result, however, when the objective is to maximise the gain in information based on informative and non‐informative priors: this has implications when an experiment is designed to convince a naïve or sceptical observer rather than consolidate the belief of an informed observer. Some extensions to the methods, including the selection of information criteria and extension to other epidemic processes with transition probabilities, are briefly addressed.
Modeling Nonhomogeneous Markov Processes via Time Transformation
Authors: Hubbard R. A. , Inoue L. Y. T. , Fann J. R.
Published: August 2008

Summary Longitudinal studies are a powerful tool for characterizing the course of chronic disease. These studies are usually carried out with subjects observed at periodic visits giving rise to panel data. Under this observation scheme the exact times of disease state transitions and sequence of disease states visited are unknown and Markov process models are often used to describe disease progression. Most applications of Markov process models rely on the assumption of time homogeneity, that is, that the transition rates are constant over time. This assumption is not satisfied when transition rates depend on time from the process origin. However, limited statistical tools are available for dealing with nonhomogeneity. We propose models in which the time scale of a nonhomogeneous Markov process is transformed to an operational time scale on which the process is homogeneous. We develop a method for jointly estimating the time transformation and the transition intensity matrix for the time transformed homogeneous process. We assess maximum likelihood estimation using the Fisher scoring algorithm via simulation studies and compare performance of our method to homogeneous and piecewise homogeneous models. We apply our methodology to a study of delirium progression in a cohort of stem cell transplantation recipients and show that our method identifies temporal trends in delirium incidence and recovery.
A Test for Constant Fatality Rate of an Emerging Epidemic: With Applications to Severe Acute Respiratory Syndrome in Hong Kong and Beijing
Authors: Lam K. F. , Deshpande J. V. , Lau E. H. Y. , Naik‐Nimbalkar U. V. , Yip P. S. F. , Xu Ying
Published: August 2008

Summary The etiology, pathogenesis, and prognosis for a newly emerging disease are generally unknown to clinicians. Effective interventions and treatments at the earliest possible times are warranted to suppress the fatality of the disease to a minimum, and inappropriate treatments should be abolished. In this situation, the ability to extract most information out of the data available is critical so that important decisions can be made. Ineffectiveness of the treatment can be reflected by a constant fatality over time while effective treatment normally leads to a decreasing fatality rate. A statistical test for constant fatality over time is proposed in this article. The proposed statistic is shown to converge to a Brownian motion asymptotically under the null hypothesis. With the special features of the Brownian motion, we are able to analyze the first passage time distribution based on a sequential tests approach. This allows the null hypothesis of constant fatality rate to be rejected at the earliest possible time when adequate statistical evidence accumulates. Simulation studies show that the performance of the proposed test is good and it is extremely sensitive in picking up decreasing fatality rate. The proposed test is applied to the severe acute respiratory syndrome data in Hong Kong and Beijing.
On the Bayesian Estimation of a Closed Population Size in the Presence of Heterogeneity and Model Uncertainty
Authors: King R. , Brooks S. P.
Published: August 2008

Summary We consider the estimation of the size of a closed population, often of interest for wild animal populations, using a capture–recapture study. The estimate of the total population size can be very sensitive to the choice of model used to fit to the data. We consider a Bayesian approach, in which we consider all eight plausible models initially described by Otis et al. (1978, Wildlife Monographs62, 1–135) within a single framework, including models containing an individual heterogeneity component. We show how we are able to obtain a model‐averaged estimate of the total population, incorporating both parameter and model uncertainty. To illustrate the methodology we initially perform a simulation study and analyze two datasets where the population size is known, before considering a real example relating to a population of dolphins off northeast Scotland.
Clustered Mixed Nonhomogeneous Poisson Process Spline Models for the Analysis of Recurrent Event Panel Data
Authors: Nielsen J. D. , Dean C. B.
Published: August 2008

Summary A flexible semiparametric model for analyzing longitudinal panel count data arising from mixtures is presented. Panel count data refers here to count data on recurrent events collected as the number of events that have occurred within specific follow‐up periods. The model assumes that the counts for each subject are generated by mixtures of nonhomogeneous Poisson processes with smooth intensity functions modeled with penalized splines. Time‐dependent covariate effects are also incorporated into the process intensity using splines. Discrete mixtures of these nonhomogeneous Poisson process spline models extract functional information from underlying clusters representing hidden subpopulations. The motivating application is an experiment to test the effectiveness of pheromones in disrupting the mating pattern of the cherry bark tortrix moth. Mature moths arise from hidden, but distinct, subpopulations and monitoring the subpopulation responses was of interest. Within‐cluster random effects are used to account for correlation structures and heterogeneity common to this type of data. An estimating equation approach to inference requiring only low moment assumptions is developed and the finite sample properties of the proposed estimating functions are investigated empirically by simulation.
Maximum Likelihood Ratio Tests for Comparing the Discriminatory Ability of Biomarkers Subject to Limit of Detection
Authors: Vexler Albert , Liu Aiyi , Eliseeva Ekaterina , Schisterman Enrique F.
Published: August 2008

Summary In this article, we consider comparing the areas under correlated receiver operating characteristic (ROC) curves of diagnostic biomarkers whose measurements are subject to a limit of detection (LOD), a source of measurement error from instruments' sensitivity in epidemiological studies. We propose and examine the likelihood ratio tests with operating characteristics that are easily obtained by classical maximum likelihood methodology.
Estimating a Predator‐Prey Dynamical Model with the Parameter Cascades Method
Authors: Cao Jiguo , Fussmann Gregor F. , Ramsay James O.
Published: August 2008

Summary Ordinary differential equations (ODEs) are widely used in ecology to describe the dynamical behavior of systems of interacting populations. However, systems of ODEs rarely provide quantitative solutions that are close to real field observations or experimental data because natural systems are subject to environmental and demographic noise and ecologists are often uncertain about the correct parameterization. In this article we introduce “parameter cascades” as an improved method to estimate ODE parameters such that the corresponding ODE solutions fit the real data well. This method is based on the modified penalized smoothing with the penalty defined by ODEs and a generalization of profiled estimation, which leads to fast estimation and good precision for ODE parameters from noisy data. This method is applied to a set of ODEs originally developed to describe an experimental predator–prey system that undergoes oscillatory dynamics. The new parameterization considerably improves the fit of the ODE model to the experimental data sets. At the same time, our method reveals that important structural assumptions that underlie the original ODE model are essentially correct. The mathematical formulations of the two nonlinear interaction terms (functional responses) that link the ODEs in the predator–prey model are validated by estimating the functional responses nonparametrically from the real data. We suggest two major applications of “parameter cascades” to ecological modeling: It can be used to estimate parameters when original data are noisy, missing, or when no reliable priori estimates are available; it can help to validate the structural soundness of the mathematical modeling approach.
Conditional Generalized Estimating Equations for the Analysis of Clustered and Longitudinal Data
Authors: Goetgeluk Sylvie , Vansteelandt Stijn
Published: August 2008

Summary A common and important problem in clustered sampling designs is that the effect of within‐cluster exposures (i.e., exposures that vary within clusters) on outcome may be confounded by both measured and unmeasured cluster‐level factors (i.e., measurements that do not vary within clusters). When some of these are ill/not accounted for, estimation of this effect through population‐averaged models or random‐effects models may introduce bias. We accommodate this by developing a general theory for the analysis of clustered data, which enables consistent and asymptotically normal estimation of the effects of within‐cluster exposures in the presence of cluster‐level confounders. Semiparametric efficient estimators are obtained by solving so‐called conditional generalized estimating equations. We compare this approach with a popular proposal by Neuhaus and Kalbfleisch (1998, Biometrics54, 638–645) who separate the exposure effect into a within‐ and a between‐cluster component within a random intercept model. We find that the latter approach yields consistent and efficient estimators when the model is linear, but is less flexible in terms of model specification. Under nonlinear models, this approach may yield inconsistent and inefficient estimators, though with little bias in most practical settings.
Estimating Cumulative Treatment Effects in the Presence of Nonproportional Hazards
Authors: Wei Guanghui , Schaubel Douglas E.
Published: August 2008

SummaryOften in medical studies of time to an event, the treatment effect is not constant over time. In the context of Cox regression modeling, the most frequent solution is to apply a model that assumes the treatment effect is either piecewise constant or varies smoothly over time, i.e., the Cox nonproportional hazards model. This approach has at least two major limitations. First, it is generally difficult to assess whether the parametric form chosen for the treatment effect is correct. Second, in the presence of nonproportional hazards, investigators are usually more interested in the cumulative than the instantaneous treatment effect (e.g., determining if and when the survival functions cross). Therefore, we propose an estimator for the aggregate treatment effect in the presence of nonproportional hazards. Our estimator is based on the treatment‐specific baseline cumulative hazards estimated under a stratified Cox model. No functional form for the nonproportionality need be assumed. Asymptotic properties of the proposed estimators are derived, and the finite‐sample properties are assessed in simulation studies. Pointwise and simultaneous confidence bands of the estimator can be computed. The proposed method is applied to data from a national organ failure registry.
Robust Covariate‐Adjusted Log‐Rank Statistics and Corresponding Sample Size Formula for Recurrent Events Data
Authors: Song Rui , Kosorok Michael R. , Cai Jianwen
Published: August 2008

Summary Recurrent events data are frequently encountered in clinical trials. This article develops robust covariate‐adjusted log‐rank statistics applied to recurrent events data with arbitrary numbers of events under independent censoring and the corresponding sample size formula. The proposed log‐rank tests are robust with respect to different data‐generating processes and are adjusted for predictive covariates. It reduces to the Kong and Slud (1997, Biometrika84, 847–862) setting in the case of a single event. The sample size formula is derived based on the asymptotic normality of the covariate‐adjusted log‐rank statistics under certain local alternatives and a working model for baseline covariates in the recurrent event data context. When the effect size is small and the baseline covariates do not contain significant information about event times, it reduces to the same form as that of Schoenfeld (1983, Biometrics39, 499–503) for cases of a single event or independent event times within a subject. We carry out simulations to study the control of type I error and the comparison of powers between several methods in finite samples. The proposed sample size formula is illustrated using data from an rhDNase study.
Fitting Conditional Survival Models to Meta‐Analytic Data by Using a Transformation Toward Mixed‐Effects Models
Authors: Massonnet Goele , Janssen Paul , Burzykowski Tomasz
Published: August 2008

Summary Frailty models are widely used to model clustered survival data. Classical ways to fit frailty models are likelihood‐based. We propose an alternative approach in which the original problem of “fitting a frailty model” is reformulated into the problem of “fitting a linear mixed model” using model transformation. We show that the transformation idea also works for multivariate proportional odds models and for multivariate additive risks models. It therefore bridges segregated methodologies as it provides a general way to fit conditional models for multivariate survival data by using mixed models methodology. To study the specific features of the proposed method we focus on frailty models. Based on a simulation study, we show that the proposed method provides a good and simple alternative for fitting frailty models for data sets with a sufficiently large number of clusters and moderate to large sample sizes within covariate‐level subgroups in the clusters. The proposed method is applied to data from 27 randomized trials in advanced colorectal cancer, which are available through the Meta‐Analysis Group in Cancer.
On the Nonidentifiability of Population Sizes
Authors: Mao Chang Xuan
Published: August 2008

Summary When a nonparametric mixture model is adopted to deal with the heterogeneity among individual capture probabilities, the population size is nonidentifiable (Link, 2003, Biometrics59, 1123–1130). Holzmann, Munk, and Zucchini (2006, Biometrics62, 934–936) discussed the conditions under which a subfamily of mixing distributions is identifiable. Link (2006, Biometrics92, 936–939) found that the nonidentifiability occurs across identifiable subfamilies. It is shown that there is a subfamily in which each mixing distribution is determined by its mixture, and the population size admits estimable lower bounds that can be used to construct lower confidence limits.
Characterization of Co‐Doped Silica for Improved Hydrothermal Stability and Application to Hydrogen Separation Membranes at High Temperatures
Authors: Igi Ryosuke , Yoshioka Tomohisa , Ikuhara Yumi H. , Iwamoto Yuji , Tsuru Toshinori
Published: August 2008

Co‐doped silica sol solutions with varying Co composition (Co/(Si+Co)=10–50 mol%) were prepared from tetraethoxysilane and Co(NO3)2·6H2O. Subsequently, these solutions were used in the preparation of hydrogen separation microporous membranes with enhanced hydrothermal stability at 500°C under a steam pressure of 300 kPa. At Co concentrations >33%, the XRD pattern and peak intensity of the Co‐doped silica preparations were similar and were not dependent on Co composition, suggesting that Co was incorporated into the silica network. The best H2 permeation performance in a steam atmosphere (500°C; steam pressure, 300 kPa) was obtained using silica doped with approximately 30 mol% Co. Co‐doped silica membranes (Co 33 mol%) fired at 600°C under a steam partial pressure of 90 kPa showed stable gaseous permeances and a H2 permeance of approximately 2.00–4.00 × 10−6 m3(STP)·(m·s·kPa)−1 with a selectivity of 250–730 (H2/N2), even after 60 h of exposure to steam (steam pressure, 300 kPa) at 500°C.
Solid‐State Synthesis of Nanocrystalline BaTiO3: Reaction Kinetics and Powder Properties
Authors: Buscaglia Maria Teresa , Bassoli Marta , Buscaglia Vincenzo , Vormberg Reinhard
Published: August 2008

The formation of BaTiO3 nanoparticles by a solid‐state reaction between nanocrystalline raw materials BaCO3 and TiO2 was studied as a function of temperature (400°–800°C), time (1–24 h), and titania particle size (15 and 30 nm). The reaction starts at 500°C and a high reaction rate is already observed at 600°C for the finest titania, with up to 90% conversion after 2 h. Two main reaction stages were observed at 600°–700°C. The first step is dominated by nucleation and growth of BaTiO3 at the TiO2–BaCO3 contact points and at the TiO2 surface. Surface diffusion of BaCO3 is, most likely, the prevailing mass transport mechanism responsible for the rapid formation of BaTiO3, even in the absence of a significant contribution from lattice diffusion. The second stage begins when the residual TiO2 cores are completely covered by the product phase. For longer times, the reaction can only proceed by the slower lattice diffusion, resulting in a strong decrease of the reaction rate. Single‐phase BaTiO3 nanopowders with a specific surface area of 12–15 m2/g, an average particle size of 70–85 nm, a relative density of 96.5%–98.3%, and a tetragonality of 1.005 were obtained by calcination at 700°–800°C. Critical parameters in the preparation of ultrafine powders by solid‐state reactions are the particle size of both raw materials, the absence of large hard agglomerates, and the homogeneity of the mixture. The use of fine raw materials and optimization of the reaction conditions make mechanical activation unnecessary.
Metal Ions as Probes for Characterization of Geopolymer Materials
Authors: Bortnovsky Oleg , Dědeček Jiri , Tvarůžková Zdenka , Sobalík Zdeněk , Šubrt Jan
Published: August 2008

Ion exchange of Na+ions in a geopolymer by Cs+, NH4+, and Co2+was used to characterize the accessibility of the inner volume of a Na‐geopolymer (Si/Al 1.8) and the size of the rings controlling the mobility of cations in the geopolymer matrix. Ultraviolet (UV)—visible (vis) spectroscopy of Co2+ions in the Co2+‐exchanged geopolymer was used to characterize the local geometry of the Co2+ions and the regularity and shape of local structures accommodating these Co2+ions in the geopolymer matrix. Na‐geopolymers exhibit ion‐exchange properties similar to those of zeolites. All Na+ions balancing Al atoms of the network of the as‐prepared geopolymer could be replaced (ion‐exchanged) by NH4+or Co2+ions. By analogy to zeolites, this indicates that all the Al atoms are accessible through rings containing at least eight Al and Si atoms. Co2+ions in the geopolymer network are accommodated in two regular types of deformed six‐membered or eight‐membered rings. As indicated by the lower extent of Cs+exchange, only one‐half of the Al atoms are simultaneously accessible through 10‐membered or larger rings. This indicates that neither regular alumosilicate six‐membered rings nor the hexagonal prisms typical of some zeolitic structures are present in the geopolymer network.
Synthesis, Characterization, and Pyrolytic Conversion of a Novel Liquid Polycarbosilane
Authors: Fang Yunhui , Huang Muhe , Yu Zhaoju , Xia Haiping , Chen Lifu , Zhang Ying , Zhang Litong
Published: August 2008

Partially ethynyl‐substituted ethynylhydridopolycarbosilane (EHPCS) is prepared by Grignard coupling of chloromethyltrichlorosilane, chloromethylmethyldichlorosilane, and ethynylmagnesium bromide, followed by reduction with lithium aluminum hydride. The as‐synthesized EHPCS, with a hyperbranched structure and an approximate formula of [SiH1.35(CH3)0.37(C≡CH)0.28CH2]n, has been characterized by GPC, FT‐IR, and 1H, 13C, and 29Si NMR. The EHPCS can be cured readily in an inert atmosphere at 140°C for 6 h. Pyrolysis behavior and structure evolution of the cured EHPCS were studied by means of thermal gravimetric analysis‐differential scanning calormetry, FT‐IR, X‐ray diffraction, and elemental analysis. It is suggested that hydrosilylation, ethynyl group polymerization, dehydrocoupling, and demethanation are involved in the cross‐linking of EHPCS. The polymer–ceramic conversion is complete at 900°C, and it gives a stoichiometric and amorphous silicon carbide (SiC) with a yield of 78%. Further heating at 1200°C induces partial crystallization, forming locally ordered SiC4. The characteristic peaks of β‐SiC are observable above 1600°C.
Study of the Float Glass Melting Process: Combining Fluid Dynamics Simulation and Glass Homogeneity Inspection
Authors: Feng Zhijun , Li Dongchun , Qin Guoqiang , Liu Shimin
Published: August 2008

The simulations of fluid dynamics in a float glass furnace are performed by using the FLOTRAN module of ANSYS software. The velocity, turbulent kinetic energy, and density distribution of the fluids are determined. Three flowing cycle modes of the fluids are revealed, and this accounts for the heterogeneity in the glasses solidified from the fluids flowing out of the furnace. The simulation results are evaluated with the experimental measurements obtained via the side stripe image technique. The comparison of the simulation and experimental results reveals remarkable consistency.
Hydrothermal Synthesis YbMnO3 and LuMnO3 Platelets
Authors: Zhu Gangqiang , Liu Peng , Liu Yun , Miao Hongyan , Zhou Jianping
Published: August 2008

Single‐crystalline YbMnO3 and LuMnO3 platelets have been successfully synthesized via a simple hydrothermal process at 250°C for 24 h. X‐ray diffraction, scanning electron microscopy, energy‐dispersive X‐ray spectroscopy, transmission electron microscopy, and selected area electron diffraction patterns were used to characterize the as‐synthesized samples. The result reveals that both of the as‐synthesized YbMnO3 and LuMnO3 are of hexagonal phase. The effect of treatment time on the phase of the final products has been studied, and a possible formation mechanism of YbMnO3 and LuMnO3 is proposed.
Recommendations from the Society for Academic Emergency Medicine (SAEM) Taskforce on Women in Academic Emergency Medicine
Authors: Kuhn Gloria J. , Abbuhl Stephanie B. , Clem Kathleen J. ,   for the Society for Academic Emergency Medicine (SAEM) Taskforce for Women in Academic Emergency Medicine
Published: August 2008

The Society for Academic Emergency Medicine (SAEM) convened a taskforce to study issues pertaining to women in academic emergency medicine (EM). The charge to the Taskforce was to “Create a document for the SAEM Board of Directors that defines and describes the unique recruitment, retention, and advancement needs for women in academic emergency medicine.” To this end, the Taskforce and authors reviewed the literature to highlight key data points in understanding this issue and made recommendations for individuals at four levels of leadership and accountability: leadership of national EM organizations, medical school deans, department chairs, and individual women faculty members. The broad range of individuals targeted for recommendations reflects the interdependent and shared responsibility required to address changes in the culture of academic EM. The following method was used to determine the recommendations: 1) Taskforce members discussed career barriers and potential solutions that could improve the recruitment, retention, and advancement of women in academic EM; 2) the authors reviewed recommendations in the literature by national consensus groups and experts in the field to validate the recommendations of Taskforce members and the authors; and 3) final recommendations were sent to all Taskforce members to obtain and incorporate additional comments and ensure a consensus. This article contains those recommendations and cites the relevant literature addressing this topic.
Availability and Quality of Computed Tomography and Magnetic Resonance Imaging Equipment in U.S. Emergency Departments
Authors: Ginde Adit A. , Foianini Anthony , Renner Daniel M. , Valley Morgan , Camargo, Jr Carlos A.
Published: August 2008

Objectives:  The objective was to determine the availability and quality of computed tomography (CT) and magnetic resonance imaging (MRI) equipment in U.S. emergency departments (EDs). The authors hypothesized that smaller, rural EDs have less availability and lower‐quality equipment.

Methods:  This was a random selection of 262 (5%) U.S. EDs from the 2005 National Emergency Department Inventories (NEDI)‐USA (http://www.emnet‐usa.org/). The authors telephoned radiology technicians about the presence of CT and MRI equipment, availability for ED imaging, and number of slices for the available CT scanners. The analysis was stratified by site characteristics.

Results:  The authors collected data from 260 institutions (99% response). In this random sample of EDs, the median annual patient visit volume was 19,872 (interquartile range = 6,788 to 35,757), 28% (95% confidence interval [CI] = 22% to 33%) were rural, and 27% (95% CI = 21% to 32%) participated in the Critical Access Hospital program. CT scanners were present in 249 (96%) institutions, and of these, 235 (94%) had 24/7 access for ED patients. CT scanner resolution varied: 28% had 1–4 slice, 33% had 5–16 slice, and 39% had a more than 16 slice. On‐site MRI was available for 171 (66%) institutions, and mobile MRI for 53 (20%). Smaller, rural, and critical access hospitals had lower CT and MRI availability and less access to higher‐resolution CT scanners.

Conclusions:  Although access to CT imaging was high (>90%), CT resolution and access to MRI were variable. Based on observed differences, the availability and quality of imaging equipment may vary by ED size and location.
From the Emergency Department to Vital Statistics: Cause of Death Uncertain
Authors: Keirns Carla C. , Carr Brendan G.
Published: August 2008

Vital statistics are widely used to evaluate trends in health and illness, inform policy, and allocate resources among health priorities. Literature comparing autopsies to clinical death certification has shown that the clinical “cause of death” certification is inaccurate or incomplete in many cases. Short of increasing autopsies, however, these studies have proposed few improvements. Using the case of death certification in the emergency department (ED), the authors analyzed the current approach to death certification. The authors propose the following to improve the quality of data: 1) acceptance of the declaration “manner of death, natural; cause of death, uncertain”; 2) training for physicians in the selection of appropriate underlying causes of death and “chains of causation”; and 3) participation of physicians with ongoing relationships to the patient in the certification process.