bluuebunny/crossref_metadata_2025_split huggingface dataset:
Software utilities for the interpretation of mass spectrometric data of glycoconjugates: application to glycosphingolipids of human serum
Authors: Souady Jamal , Dadimov Denis , Kirsch Stephan , Bindila Laura , Peter‐Katalinić Jasna , Vakhrushev Sergey Y. 
Published: March 2010

AbstractGlycosphingolipids (GSLs) are major components of the outer leaflet of the cell membrane. These lipids are involved in many cell surface events and show disease‐related expression changes. GSLs could thus serve as useful targets for biomarker discovery. The GSL structure is characterized by two entities: a hydrophilic glycan and a hydrophobic ceramide moiety. Both components exhibit numerous structural variations, the combination of which results in a large diversity of GSL structures that can potentially exist. Mass spectrometry (MS) is a powerful tool for high‐throughput analysis of GSL expression analysis and structural elucidation. Yet, the assignment of GSL structures using MS data is tedious and demands highly specialized expertise. SysBioWare, a software platform developed for MS data evaluation in glycomics, was here applied for the MS analysis of human serum GSLs. The program was tuned to provide automated compositional assignment, supporting a variety of glycan and ceramide structures. Upon in silico fragmentation, the masses of predicted ions arising from cleavages in the glycan as well as the ceramide moiety were calculated, thus enabling structural characterization of both entities. Validation of proposed structures was achieved by matching in silico calculated fragment ions with those of experimental MS/MS data. These results indicate that SysBioWare can facilitate data interpretation and, furthermore, help the user to deal with large sets of data by supporting management of MS and non‐MS data. SysBioWare has the potential to be a powerful tool for high‐throughput glycosphingolipidomics in clinical applications. Copyright © 2010 John Wiley & Sons, Ltd.
Kinetics of ethanol decay in mouth‐ and nose‐exhaled breath measured on‐line by selected ion flow tube mass spectrometry following varying doses of alcohol
Authors: Smith David , Pysanenko Andriy , Španěl Patrik 
Published: March 2010

AbstractA study has been carried out of the decay of ethanol in mouth‐exhaled and nose‐exhaled breath of two healthy volunteers following the ingestion of various doses of alcohol at different dilutions in water. Concurrent analyses of sequential single breath exhalations from the two volunteers were carried out using selected ion flow tube mass spectrometry, SIFT‐MS, on‐line and in real time continuously over some 200 min following each alcohol dose by simply switching sampling between the two volunteers. Thus, the time interval between breath exhalations was only a few minutes, and this results in well‐defined decay curves. Inspection of the mouth‐exhaled and nose‐exhaled breath data shows that mouth contamination of ethanol diminished to insignificant levels after a few minutes. The detailed results of the analyses of nose‐exhaled breath show that the peak levels and the decay rates of breath ethanol are dependent on the ethanol dose and the volume of ethanol/water mixture ingested. From these data, both the efficiency of the first‐pass metabolism of ethanol and the indications of gastric emptying rates at the various doses and ingested volumes have been obtained for the two volunteers. Additionally and simultaneously, acetaldehyde, acetic acid and acetone were measured in each single breath exhalation. Acetaldehyde, the primary product of ethanol metabolism, is seen to track the breath ethanol. Acetic acid, a possible secondary product of this metabolism, was detected in the exhaled breath, but was shown to largely originate in the oral cavity. Breath acetone was seen to increase over the long period of measurement due to the depletion of nutrients. Copyright © 2010 John Wiley & Sons, Ltd.
The dual test: Safeguarding p‐value combination tests for adaptive designs
Authors: Burman Carl‐Fredrik , Lisovskaja Vera 
Published: March 2010

AbstractMany modern adaptive designs apply an analysis where p‐values from different stages are weighted together to an overall hypothesis test. One merit of this combination approach is that the design can be made very flexible. However, combination tests violate the sufficiency and conditionality principles. As a consequence, combination tests may lead to absurd conclusions, such as ‘proving’ a positive effect while the average effect is negative. We explore the possibility of modifying the test so that such illogical conclusions are no longer possible. The dual test requires both the weighted combination test and a naïve test, ignoring the adaptations, to be statistically significant. The result is that the flexibility and type I error level control of the combination test are preserved, while the naïve test adds a safeguard against unconvincing results. The dual test is, by construction, at least as conservative as the combination test. However, many design changes will not lead to any power loss. A typical situation where the combination approach can be used is two‐stage sample size reestimation (SSR). For this case, we give a complete specification of all sample size modifications for which the two tests are equally powerful. We also study the overall power loss for some suggested SSR rules. Rules based on conditional power generally lead to ignorable power loss while a decision analytic approach exhibits clear discrepancies between the two tests. Copyright © 2010 John Wiley & Sons, Ltd.
Estimation of population attributable fraction (PAF) for disease occurrence in a cohort study design
Authors: Laaksonen M. A. , Härkänen T. , Knekt P. , Virtala E. , Oja H. 
Published: March 2010

AbstractThe population attributable fraction (PAF) is a useful measure for describing the expected change in an outcome if its risk factors are modified. Cohort studies allow researchers to assess the predictive value of the risk factor modification on the incidence of the outcome during a certain follow‐up. Estimation of PAF for both mortality and morbidity in cohort studies with censored survival data has been developed in the recent years. So far, however, censoring due to death in the estimation of PAF for morbidity has been ignored, resulting in estimation of a quantity which is not relevant in practice as some people are likely to die during the follow‐up. The risk factors related to the disease incidence may also be related to mortality, and modification of these risk factors is likely to delay the occurrence of both events. Thus, censoring due to death and the impact of risk factor modification must be considered when estimating PAF for disease incidence. We consider both and introduce two measures of disease burden: PAF for the incidence of disease during lifetime and PAF for the prevalence of disease in the population at a certain time. We demonstrate how consideration of censoring due to death changes the estimated PAF for disease incidence and its confidence interval. This underlines the importance of choosing a correct PAF measure depending on the outcome of interest and the risk factors of interest to obtain accurate and interpretable results. Copyright © 2010 John Wiley & Sons, Ltd.
Toxicity‐evaluation designs for phase I/II cancer immunotherapy trials
Authors: Messer Karen , Natarajan Loki , Ball Edward D. , Lane Thomas A. 
Published: March 2010

AbstractObjectives: To facilitate more efficient Phase I/II cancer immunotherapy trials by incorporating statistically rigorous safety analysis.Setting: The standard Phase I oncology trial is designed to find the maximum tolerated dose (MTD) in a setting where serious drug‐related toxicity is expected. However, many newer agents hope to show the efficacy without increasing the background rate of adverse events. Formal statistical designs in this setting are needed.Results: The Phase I/II toxicity‐evaluation design is suitable when the therapeutic dose is expected to be well below the MTD. In Phase I, the design enrolls multiple cohorts at the target dose, possibly after an initial dose titration stage, and tests a formal safety hypothesis using a standard 3 + 3 enrollment scheme. Phase I serves as an interim safety analysis before proceeding to Phase II efficacy testing. We give an exact upper confidence limit on the toxicity rate at the therapeutic dose using the combined Phase I/II toxicity data, as well as the maximum likelihood estimate of the toxicity rate. We describe an example where the design has been used for a Phase I/II trial of immunotherapy in leukemia.Conclusions: Phase I/II toxicity‐evaluation designs are simple to execute and may be suitable for some cancer immunotherapy trials. We show how to compute power, expected sample size, and expected number of dose‐limiting toxicities, as well as the maximum likelihood estimator and exact small sample confidence intervals for the toxicity rate at the therapeutic dose. More flexible designs are briefly discussed. Copyright © 2010 John Wiley & Sons, Ltd.
Comparison of state occupation, entry, exit and waiting times in two or more groups based on current status data in a multistate model
Authors: Lan Ling , Datta Somnath 
Published: March 2010

AbstractWe propose mean absolute distance‐based nonparametric bootstrap tests comparing the occupation probabilities, entry, exit and waiting times in a given state in two or more groups in a multistate model. The state occupied is determined at a single inspection time for each individual. Nonparametric monotonic regression and smoothing are used to uniquely define the various marginal estimators for each group which are then compared via a mean absolute distance criterion. A detailed simulation study shows that the proposed tests all have close to nominal size and reasonable power. An illustrative application to a pubertal development data set obtained from the NHANES III (Analytic and Reporting Guidelines: The Third National Health and Nutrition Examination Survey (1988–94). Hyattsville, MD: National Center for Health Statistics, Centers for Disease Control and Prevention, 1997) is also presented. Copyright © 2010 John Wiley & Sons, Ltd.
Modelling multiple sources of dissemination bias in meta‐analysis
Authors: Bowden Jack , Jackson Dan , Thompson Simon G. 
Published: March 2010

AbstractAsymmetry in the funnel plot for a meta‐analysis suggests the presence of dissemination bias. This may be caused by publication bias through the decisions of journal editors, by selective reporting of research results by authors or by a combination of both. Typically, study results that are statistically significant or have larger estimated effect sizes are more likely to appear in the published literature, hence giving a biased picture of the evidence‐base. Previous statistical approaches for addressing dissemination bias have assumed only a single selection mechanism. Here we consider a more realistic scenario in which multiple dissemination processes, involving both the publishing authors and journals, are operating. In practical applications, the methods can be used to provide sensitivity analyses for the potential effects of multiple dissemination biases operating in meta‐analysis. Copyright © 2010 John Wiley & Sons, Ltd.
A covariate‐adjustment regression model approach to noninferiority margin definition
Authors: Nie Lei , Soon Guoxing 
Published: March 2010

AbstractTo maintain the interpretability of the effect of experimental treatment (EXP) obtained from a noninferiority trial, current statistical approaches often require the constancy assumption. This assumption typically requires that the control treatment effect in the population of the active control trial is the same as its effect presented in the population of the historical trial. To prevent constancy assumption violation, clinical trial sponsors were recommended to make sure that the design of the active control trial is as close to the design of the historical trial as possible. However, these rigorous requirements are rarely fulfilled in practice. The inevitable discrepancies between the historical trial and the active control trial have led to debates on many controversial issues. Without support from a well‐developed quantitative method to determine the impact of the discrepancies on the constancy assumption violation, a correct judgment seems difficult. In this paper, we present a covariate‐adjustment generalized linear regression model approach to achieve two goals: (1) to quantify the impact of population difference between the historical trial and the active control trial on the degree of constancy assumption violation and (2) to redefine the active control treatment effect in the active control trial population if the quantification suggests an unacceptable violation. Through achieving goal (1), we examine whether or not a population difference leads to an unacceptable violation. Through achieving goal (2), we redefine the noninferiority margin if the violation is unacceptable. This approach allows us to correctly determine the effect of EXP in the noninferiority trial population when constancy assumption is violated due to the population difference. We illustrate the covariate‐adjustment approach through a case study. Copyright © 2010 John Wiley & Sons, Ltd.
Cognition and dorsolateral prefrontal cortex volume in corticosteroid‐treated patients given lamotrigine
Authors: Husain Saira , Kuzminski Samuel , Shad Mujeeb U. , Gabrielson Barry , Bret Mary E. , Osuji I. Julian , Brown E. Sherwood 
Published: March 2010

AbstractIn addition to changes in declarative memory and the hippocampus, corticosteroid excess is associated with prefrontal cortex changes. We previously reported that patients receiving exogenous corticosteroid therapy had impaired performance on prefrontal cortex‐related tasks, including working memory and executive functioning tasks. Glutamate release inhibitors attenuate corticosteroid‐effects on the hippocampus in both animal and human models. Twenty‐eight outpatients receiving chronic prednisone therapy for transplant rejection or other medical conditions were randomized to lamotrigine (a glutamate release inhibitor) or placebo for 24 weeks. Dorsolateral prefrontal cortex (DLPFC) volume was manually traced from MRI scans by trained staff members. Cognition was examined using the Stroop Color Word Test (SCWT), Delis‐Kaplan Executive Function System (D‐KEFS) and the Trail Making Test. Groups were compared using analysis of covariance. Consistent with prior findings in corticosteroid‐treated patients, baseline cognitive function was in the low normal range. At baseline, prednisone duration showed a trend towards negative correlation with SCWT and D‐KEFS inhibition switching time error scores, and DLPFC volume showed a trend towards a positive correlation with SCWT scores. No significant between‐group differences in outcomes were observed following lamotrigine therapy. Thus, this study found lamotrigine to not be associated with either positive or negative effects on cognition or DLPFC volume. Copyright © 2010 John Wiley & Sons, Ltd.
Effect of minamata disease status and the perception of unfairness on ill health and inequalities in health amongst residents of Shiranui sea communities
Authors: Ushijima Kayo , Sung Woncheol , Kawakita Minoru , Tanaka Shiro , Mukai Yoshito , Tamura Kenji , Tanaka Mika , Maruyama Sadami 
Published: March 2010

AbstractMinamata disease (MD) is a neurological disorder caused by eating seafood contaminated with methylmercury, first identified in 1956 in Japan. However, reports of ill health related to MD increased sharply following a ruling by the Supreme Court in 2004. We performed logistic regression analyses to examine the relationship between MD specific socioeconomic status (MD status) and health inequalities amongst residents of Shiranui sea communities. Data were collected by two‐stratified sampling of residents 40–79 years old in 172 postal code areas on the Shiranui sea coast. A questionnaire was distributed to eligible subjects (n = 2100) and collected at a later visit or by mail. Two self‐reported health outcomes were examined: MD‐related physical symptoms (MDRS) and the 12‐item General Health Questionnaire (GHQ‐12). We classified the 1546 respondents according to MD status: Early and Recent (received MD compensation before and after the Supreme Court decision, respectively) and Not Yet (yet to receive compensation). Adjusting for confounding factors, Early and Recent was significantly associated with elevated MDRS and GHQ‐12 compared with Not Yet. After further adjusting for perception of unfairness, the inequality between Early and Recent was reduced. Efforts to improve the population's health in these areas should consider health effects of MD status and perception of unfairness. Copyright ? 2010 John Wiley & Sons, Ltd.
Does subnational region matter? Foreign affiliate performance in the United states and China
Authors: Chan Christine M. , Makino Shige , Isobe Takehiko 
Published: March 2010

AbstractThis study examines the extent to which subnational regions can explain foreign affiliate performance in two host country settings, the United States and China, the world's two largest economies at polar ends of the economic spectrum (i.e., an advanced versus an emerging economy). Our results suggest that the subnational region is significant in explaining foreign affiliate performance, thus confirming its importance as an additional unit of analysis for firm performance. This study also shows that the effects of subnational region are far stronger in China than they are in the United States, thus suggesting that regional differences are more critical in their explanatory power for firm performance in emerging economies than they are in advanced economies. Copyright © 2010 John Wiley & Sons, Ltd.
High Intracellular Iron Oxide Nanoparticle Concentrations Affect Cellular Cytoskeleton and Focal Adhesion Kinase‐Mediated Signaling
Authors: Soenen Stefaan J. H. , Nuytten Nele , De Meyer Simon F. , De Smedt Stefaan C. , De Cuyper Marcel 
Published: March 2010

AbstractIron oxide nanoparticle internalization exerts detrimental effects on cell physiology for a variety of particles, but little is known about the mechanism involved. The effects of high intracellular levels of four types of iron oxide particles (Resovist, Endorem, very small organic particles, and magnetoliposomes (MLs)) on the viability and physiology of murine C17.2 neural progenitor cells and human blood outgrowth endothelial cells are reported. The particles diminish cellular proliferation and affect the actin cytoskeleton and microtubule network architectures as well as focal adhesion formation and maturation. The extent of the effects correlates with the intracellular concentration (= iron mass) of the particles, with the biggest effects for Resovist and MLs at the highest concentration (1000 µg Fe mL−1). Similarly, the expression of focal adhesion kinase (FAK) and the amount of activated kinase (pY397‐FAK) are affected. The data suggest that high levels of perinuclear localized iron oxide nanoparticles diminish the efficiency of protein expression and sterically hinder the mature actin fibers, and could have detrimental effects on cell migration and differentiation.
Building an automated and self‐configurable emulation testbed for grid applications
Authors: Calheiros Rodrigo N. , Buyya Rajkumar , De Rose César A. F. 
Published: March 2010

AbstractDistributed systems, such as grids, are composed of geographically distributed computing elements that belong to multiple administrative domains and are controlled by multiple entities. It is unlikely that testers are able to acquire repeatedly the same resources, for the same amount of time, and under the same network conditions, which are paramount requirements for enabling reproducible and controlled tests in software under development. An alternative to experiments in real testbeds is the use of emulation tools, which allow the software to run in an environment that behaves like a distributed system. Although advances in virtualization technology allowed the development of efficient emulators, few efforts were put in making operation of such emulators easier. This paper presents the design and the development of the Automated Emulation Framework that allows automatic mapping of virtual machines to hosts, virtual machine deployment, network configuration, and proactive management and reconfiguration of the virtual infrastructure. Copyright © 2010 John Wiley & Sons, Ltd.
Generalizable safety annotations for specification of failure patterns
Authors: Wolforth Ian , Walker Martin , Grunske Lars , Papadopoulos Yiannis 
Published: March 2010

AbstractComponents in programmable systems often exhibit patterns of failure that are independent of function or system context. In this paper, we show that it is possible to capture, and reuse where appropriate, such patterns for the purposes of system safety analysis. We describe a language that enables abstract specification of failure behaviour and define the syntax and semantics of this language. The language extends concepts originally defined in HiP‐HOPS, a technique that enables a largely automated form of compositional system safety analysis. The paper describes how this language can be used to describe component failure patterns and demonstrates how it can be applied using a simple fuel system example. The approach is evaluated on a set of retrospective industrial case studies, where data‐mining and reverse engineering techniques are applied in order to identify hidden patterns in legacy safety analyses. Results show clear potential for practical use of patterns in HiP‐HOPS. We argue that careful specification and reuse of failure patterns in conjunction with a tool that automates Fault Tree and Failure Modes and Effects Analysis can help to simplify complex safety assessments. Copyright © 2010 John Wiley & Sons, Ltd.
Erfahrungen zur Modellierung und Bewertung von Eisenbahnbrücken mit Resonanzrisiko
Authors: Marx Steffen , Geißler Karsten 
Published: March 2010

AbstractBrücken im Bereich des Hochgeschwindigkeitsverkehrs sind teilweise aufgrund der hohen dynamischen Beanspruchungen mit möglicherweise auftretender Resonanz außerhalb unseres bisherigen Erfahrungsbereiches. Mit dieser Problematik ist bereits im Entwurfsstadium äußerst sensibel umzugehen. Es genügen manchmal nur kleine konstruktive Kniffe, um das dynamische Verhalten zu verbessern.In folgendem Beitrag werden für diese Bauwerke insbesondere die Fragen der zutreffenden Modellierung der Einwirkungen und des Tragwerkes sowie die Bewertung der Berechnungsergebnisse beispielhaft anhand mehrerer Großbauvorhaben sowie anhand von Bestandsbauwerken angesprochen. Dabei werden nicht nur die Probleme der Tragfähigkeit sondern auch die der Ermüdungssicherheit diskutiert, da sowohl die Schwingbeiwerte als auch die Betriebslastfaktoren bei Resonanz nicht mehr zutreffend sind.Experiences with modeling and evaluation of railway bridges with risk of resonance. So far no experiences could be accomplished with bridges in the field of high‐speed trains due to high stresses with possible appearances of resonance. This issue has to be treated very sensitive from the design stage on. Little tricks will help to improve the dynamic performance.This contribution deals with the modeling of the impacts and the structure of the high speed train bridges as well as the evaluation of results of calculations. Problems of ultimate limit strength and fatigue strength are being discussed for some examples because dynamic factors as well as working load factors are no longer correct if resonance is occuring.