bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial testing of the VEGFR inhibitor AZD2171 by the pediatric preclinical testing program
Authors: Maris John M. , Courtright Joshua , Houghton Peter J. , Morton Christopher L. , Gorlick Richard , Kolb E. Anders , Lock Richard , Tajbakhsh Mayamin , Reynolds C. Patrick , Keir Stephen T. , Wu Jianrong , Smith Malcolm A. 
Published: April 2007

AbstractBackgroundInhibition of vascular endothelial growth factor mediated signaling shows promise as an antiangiogenic strategy for solid tumors. AZD2171 is a potent and relatively selective inhibitor of the vascular endothelial growth factor (VEGF) receptor family that is orally bioavailable. This study was designed to screen for antitumor activity of AZD2171 against the in vitro and in vivo childhood cancer preclinical models of the Pediatric Preclinical Testing Program (PPTP).ProceduresAZD2171 was tested at concentrations from 0.1 nM to 1.0 µM against the in vitro panel and was tested against the in vivo tumor panels using a 6‐week exposure to daily gavage administration of AZD2171 (3 or 6 mg/kg) or vehicle.ResultsOne of 22 cell lines evaluated was sensitive to AZD2171 in vitro (maximum concentration 1 µM). Evidence of in vivo antitumor activity (primarily tumor growth delay) was observed in 78% of solid tumor xenografts (3/3 rhabdoid, 2/3 Wilms', 3/3 Ewing's, 5/5 rhabdomyosarcoma, 1/3 medulloblastoma, 2/4 glioblastoma, 5/6 neuroblastoma, 4/5 osteosarcoma). Objective responses (both complete responses) were observed in two of 32 (6%) solid tumor xenografts (a rhabdoid xenograft and an osteosarcoma xenograft). No activity was observed against 7 acute lymphoblastic leukemia models.ConclusionsAZD2171 demonstrated broad tumor growth inhibition against the PPTP's solid tumor xenografts and much less commonly induced tumor regression. This pattern of in vivo activity, combined with the disassociation of in vitro and in vivo efficacy, are consistent with AZD2171 inhibiting growth of the PPTP's solid tumor xenografts primarily through an anti‐angiogenesis mechanism of action. Pediatr Blood Cancer 2008;50:581–587. © 2007 Wiley‐Liss, Inc.
Fetus in fetu—from prenatal ultrasound and MRI diagnosis to postnatal confirmation
Authors: Hui Pui Wah , Lam Tina Poy Wing , Chan Kwong Leung , Lee Chin Peng 
Published: April 2007

AbstractWe report a case of fetus in fetu presented as a complex intra‐abdominal heterogeneous cystic lesion during ultrasound examination of the fetus at 25 weeks of gestation. Progressive growth of this mass was noted in the prenatal period. Fetal magnetic resonance imaging provided additional information to aid in the prenatal diagnosis. This allows proper counselling for the parents and helps to plan the postnatal management. Surgical excision was carried out in the early neonatal period and the diagnosis of fetus in fetu was confirmed. Copyright © 2007 John Wiley & Sons, Ltd.
Characteristics and quality of adverse drug reaction reports by pharmacists in Norway
Authors: Gedde‐Dahl Ane , Harg Pernille , Stenberg‐Nilsen Hanne , Buajordet Marit , Granas Anne Gerd , Horn Anne Marie 
Published: April 2007

AbstractPurposeTo evaluate the characteristics and quality of adverse drug reaction (ADR) reports submitted by pharmacists, and thereby assess the possible contribution of pharmacists to the spontaneous reporting system for ADRs in Norway.MethodsAn open, prospective study was conducted where dispensing pharmacists from 39 pharmacies were encouraged to report ADRs over a 3‐month period. The submitted ADR reports were compared to reports by physicians from the same time period. All reports were evaluated for selected characteristics, that is distribution of Anatomical Therapeutic Chemical (ATC) classification codes of suspected drugs, distribution of ADRs according to system‐organ classes and the quality of the reports.ResultsA total of 118 reports covering 274 ADRs received from the pharmacists were compared to 109 ADR reports with 304 ADRs submitted by physicians. Pharmacists more often reported ADRs related to cardiovascular drugs, alimentary tract and metabolism drugs and respiratory drugs, whereas physicians more frequently reported ADRs related to musculoskeletal drugs and antineoplastic and immunomodulating agents. ADRs reported by pharmacists more frequently described gastrointestinal reactions while physicians reported more ADRs in relation to the cardiovascular and blood system. Whereas 68% of the physicians' reports were classified as serious, only 5% of the pharmacists' reports were serious. More than 50% of the reports submitted by pharmacists concerned ADRs following a generic substitution, in contrast to only 2% of the physicians' reports. The pharmacists' reports were found to be of a lower documentation grade. However, there was no substantial difference in a subjective assessment of the quality of information in the reports submitted by the two categories of health professionals.ConclusionsPharmacists submit valuable ADR reports which provide information complimentary to physicians' reports. This emphasises that pharmacist ADR reporting might constitute an important addition to the spontaneous reporting system. Copyright © 2007 John Wiley & Sons, Ltd.
Hydrogels as smart biomaterials
Authors: Kopeček Jindřich , Yang Jiyuan 
Published: April 2007

AbstractHydrogels were the first biomaterials rationally designed for human use. Beginning with the pioneering work of Wichterle and Lím on three‐dimensional polymers that swell in water, we review the design, synthesis, properties, and applications of hydrogels. The field of hydrogels has moved forward at a dramatic pace. The development of suitable synthetic methods encompassing traditional chemistry to molecular biology has been used in the design of hydrogels mimicking basic processes of living systems. Stimuli‐sensitive hydrogels, hydrogels with controlled degradability, genetically engineered poly(amino acid) polymers reversibly self‐assembling in precisely defined three‐dimensional structures, and hybrid polymers composed of two distinct classes of molecules are just some examples of these exciting novel biomaterials. The biocompatibility of hydrogels and their applications from implants to nanomaterials are also reviewed. Copyright © 2007 Society of Chemical Industry
Hard yet Tough Nanocomposite Coatings – Present Status and Future Trends
Authors: Zhang Sam , Wang Hui Li , Ong Soon‐Eng , Sun Deen , Bui Xuan Lam 
Published: April 2007

AbstractToughness and hardness are important aspects for coating applications in manufacturing industry. Extensive theoretical and experimental efforts have been made to synthesize and study nanocomposite coatings with super hardness and high toughness. The materials can be hardened through various or combined hardening mechanisms. However, for engineering applications, coating toughness is as important as, if not more than, super hardness. At present, there is neither a standard test procedure, nor a standalone methodology for the assessment of thin film toughness. The determination of the toughness is still a difficult task, and very much a fully open problem. In this article, we review the hardening and toughening mechanisms of nanocomposite films, and the toughness characterization techniques. Based on these reviews, an outlook will be presented in the concluding remarks.magnified image
Atmospheric‐Pressure Plasmas for Wide‐Area Thin‐Film Deposition and Etching
Authors: Hopfe Volkmar , Sheel David W. 
Published: April 2007

AbstractThe present paper is focused on coating technologies compatible with industrial requirements, particularly on atmospheric pressure plasma technologies which are compatible with scaling to wide substrate widths (≥0.5 m). The AP‐PECVD reactors are designed for continuous air‐to‐air processing, and can be used for deposition of non‐oxide films. Two thermal methods for atmospheric pressure processing are considered: microwave CVD and DC ArcJet‐CVD. Typical thin film growth rates for PECVD are in the range of 5–100 nm · s−1 (static) and up to 2 nm · m · s−1 (dynamic). The rates for plasma chemical etching are typically 10 times higher. A complimentary lower energy plasma source based on dielectric barrier glow discharge plasma CVD has also been explored. Developments are underway to explore uses for the coating technology, for example scratch resistant coatings on metals, barrier layers, self‐clean functional surfaces and antireflective coatings. Coating materials range from silica, titania, aluminium oxide, metal composite layers, carbon and silicon nitride. Layer properties are close to data known from low pressure PECVD. Plasma chemical etching has been developed for crystalline silicon photovoltaics. The surface textures strongly change with the precursors and the plasma parameters used.magnified image
The value of latent class analysis in medical diagnosis
Authors: Rindskopf David , Rindskopf Wallace 
Published: April 2007

AbstractAssessment of the value of diagnostic indicators such as symptoms and laboratory tests results from calculation of the sensitivity and specificity of the indicators. Knowledge of the rate of occurrence of the disease allows for additional calculations of the error rates in using an indicator. These calculations are accurate only when the data on which they are based are reliable. If the diagnosis, which is used as the criterion for computing the sensitivity and specificity, is not accurate, then the resulting calculations will be in error. We show how a statistical method, latent class analysis, allows for the estimation of the characteristics of indicators even when an accurate diagnosis is unavailable. In addition, the method deals with several indicators at once, and provides a way to combine the information from all the indicators to make a diagnosis.
Cause‐deleted proportional mortality analysis and the healthy worker effect
Authors: Walter S. D. 
Published: April 2007

AbstractThis paper evaluates the relationships between various indices of proportional mortality, used in occupational and other settings where denominator data are unavailable. In particular, we examine the necessary conditions for validity of the proportional mortality ratio (PMR) and mortality odds ratio (MOR) as estimates of the standardized mortality ratio (SMR), in general and for the situation where one considers only a subset of deaths, with certain causes of death deleted from the data. We may exclude data in this way to avoid the inflationary effect on the PMRs for some causes of death (e.g. cancer) that results from a ‘healthy worker effect’ for other causes of death (e.g. heart disease). We find that cause‐deleted PMRs and MORs may be unbiased estimates of their corresponding SMR, and these indices appear most useful for specific hazards of employment or relatively infrequent causes of death.
Assessment of stratum‐covariate interactions in Cox's proportional hazards regression model
Authors: Thall Peter F. , Lachin John M. 
Published: April 2007

AbstractWe assess stratum (e.g. treatment) interactions with covariates and with the baseline hazard function in the proportional hazards (PH) regression model for lifetime data. We consider models incorporating stratum interactions both with and without stratification of the risk sets in the likelihood function, and describe likelihood ratio statistics for tests of the presence of these interactions. We also present step‐down methods for building reduced models which include stratum‐specific parameters corresponding to covariates which interact with treatment. We apply PH models with such interactions to a clinical trial of DES in the treatment of prostate cancer to determine optimal treatment conditional on each patient's covariates.
Case‐control studies for estimation of the natural history of preclinical disease from screening data
Authors: Brookmeyer R. , Day N. E. , Moss S. 
Published: April 2007

AbstractThe duration of the detectable preclinical phase of disease, which we call the sojourn time, is an important quantity to consider when recommending frequency of screens and investigating the natural history of the disease. In this paper, we propose a matched case‐control methodology for screening data for joint estimation of the sojourn time distribution and the false negative rate of the screening test. The approach is based on a conditional likelihood for matched sets that involves a comparison of the screening histories of cases and controls. We illustrate the methodology with the data from the Aberdeen screening programme for cervical cancer by the Pap smear. We consider a number of different parametric forms for the sojourn time distribution.
The use of an extended baseline period in the evaluation of treatment in a longitudinal duchenne muscular dystrophy trial
Authors: Madsen K. S. , Miller J. P. , Province M. A. 
Published: April 2007

AbstractA trial of Duchenne muscular dystrophy involved tracking boys of all ages through a one‐year baseline period, followed by a one‐year trial of leucine versus placebo treatment. In this paper we develop a model for a total‐muscle‐strength score that uses the data of the extended baseline period in the evaluation of the leucine treatment. The model is based on a polynomial growth curve in age whose coefficients can vary according to treatment or phase. Maximum likelihood estimates of the parameters of the model are obtained from use of the EM algorithm. We propose tests for the adequacy of the model as well as for treatment effects. A quadratic model appears the most parsimonious fit to the data and there is no evidence of any leucine effect on scores. We examine the asymptotic power of the test for treatment effect and compare it with that of a simpler analysis.
Censoring distributions as a measure of follow‐up in survival analysis
Authors: Korn Edward L. 
Published: April 2007

AbstractThe mean or median of the follow‐up times as a measure of the quality or completeness of the follow‐up in a survival analysis can sometimes be misleading—a more severe disease will have shorter follow‐up times because of earlier deaths. We suggest here that estimates of the censoring distribution provide a more useful measure of the follow‐up. This paper gives estimation procedures for both grouped‐time (cohort) data and continuous data, and provides an application.
Considerations of statistical power in the shared‐haplotypes test
Authors: Ewens W. J. 
Published: April 2007

AbstractThis paper considers statistical power properties of a test of whether a disease is caused by a recessive gene, using data on HLA sharing properties of affected sibs. It is found that the test has very poor power characteristics, and in particular we are sometimes just as likely to accept the hypothesis that the gene is recessive when it is dominant as when it is truly recessive.
A method for combining results from several prospective epidemiologic studies
Authors: Dyer Alan R. 
Published: April 2007

AbstractAn approach to the problem of a single study lacking adequate power to examine an important question is to combine the data from several studies to allow a more powerful test of the hypothesis in question. The present paper describes a method used by the International Collaborative Group to pool data on 54,492 men aged 40–69 from 10 population studies in 7 countries to examine the association between cholesterol level and risk of death from cancer. Furthermore, there was a suggestion that the inverse association observed in some studies might be the result of an effect of undetected cancer on cholesterol level, rather than an increase in cancer risk resulting from low cholesterol levels. This paper describes the process for selection of the method used to evaluate this possibility over other potential approaches and the results obtained in the analysis of the International Collaborative Group data that support this hypothesis. This report also indicates how one might expect some of the analyses described to compare with analyses based on a discrete version of the Cox proportional hazards model.
Estimation of normal ranges of clinical laboratory data
Authors: Tango Toshiro 
Published: April 2007

AbstractThis paper proposes a new procedure for estimating normal ranges of clinical laboratory tests, which can be applied to data with possibly more than one outlier from healthy subjects. The proposed procedure determines the optimal model among a class of models in which it is assumed that (1) an observed distribution of ‘normal values’ can be transformed to the Gaussian form by one of several specified transformations, and (2) if there exist outliers among the data, then each of the transformed outliers also follows a Gaussian distribution with different mean from, but the same variance as, the transformed distribution of normal values. The optimal model is defined as the best combination of the transformation to normality and the number of outliers identified, and is selected by the Akaike information criterion (AIC). Our procedure is illustrated with data from 200 healthy male subjects on 25 laboratory tests.
Discrimination and other statistical intervals for the interpretation of in vivo patient monitoring data
Authors: Kost Gerald J. 
Published: April 2007

AbstractA calibration line is used to define the relationship between a new clinical technique and a standard in vitro laboratory methodology. Discrimination intervals quantify the reliability of inverse estimates obtained from the calibration line. Applied to transcutaneous P monitoring, a new in vivo measurement, discrimination intervals for inverse estimates of arterial P range in size from 10 to 50 torr (1.33–6.67 kPa), or more, depending on the values of statistical parameters selected. Discrimination interval analysis shows that the inverse estimates are more reliable near the means. Also, it indicates that the primary value of transcutaneous P monitoring lies not in providing accurate inverse estimates of arterial P, but instead, in monitoring short‐term clinical trends.
The use of glim and the bootstrap in assessing a clinical trial of two drugs
Authors: Mapleson W. W. 
Published: April 2007

AbstractAn approach is described for estimating the dose of a new drug which is equipotent to an established dose of an old drug. The approach is basically that of the parallel‐line assay but it can allow for concomitant variables and, by exploiting the facilities available in the statistical computer package GLIM (generalized linear interactive modelling), the approach can be applied when the residuals conform to one of a number of distributions and, with suitable safeguards, to continuous, discrete and even ‘scored’ responses. In some circumstances, it is necessary to obtain confidence limits by Efron's ‘bootstrap’ technique. The method is illustrated with results from a trial of two premedicant drugs in children.
A simulation study of three sequential methods for the comparison of two treatment groups when the response criterion is censored
Authors: Benichou Jacques , Chastang Claude 
Published: April 2007

AbstractThree recent sequential methods, group sequential analysis (GSA), the sequential probability ratio test (SPRT) and the triangular test (TT) are well suited to randomized clinical trials with a censored response criterion, as they do not require matched pairs of patients.We undertook a simulation study to investigate their statistical properties and to compare these three methods with the fixed‐sample design. Our results suggest that (i) the three methods have the expected statistical properties for size and power; (ii) they allow an important reduction of the average number of events before stopping, except with GSA when there is no treatment difference; (iii) the triangular test (closed design) appears the optimal design, as the variance of the number of events is smaller than with the sequential probability ratio test (open design) and (iv) analysis after every twenty new events does not alter the statistical properties of these sequential methods and enhances their usefulness.
Assessing the performance and clinical impact of a computerized prognostic system in severe head injury
Authors: Murray G. D. , Murray L. S. , Barlow P. , Teasdale G. M. , Jennett W. B. 
Published: April 2007

AbstractThe ability to predict outcome in the early stages of severe head injury would have several uses. A computerized system which has been developed in Glasgow to assist clinicians in this task, based on information from over 2500 severely head‐injured patients, is described, with particular attention to the testing of the statistical properties of the system, and, more importantly, the assessment of its clinical impact.
Application of statistical decision theory to treatment choices: Implications for the design and analysis of clinical trials
Authors: Simes R. J. 
Published: April 2007

AbstractThis paper explores the application of statistical decision theory to treatment choices in cancer which involve difficult value judgements in weighing beneficial and deleterious outcomes of treatment. Strengths and weaknesses of using decision theory are illustrated by considering the problem of selecting chemotherapy in advanced ovarian cancer. The paper includes an assessment of individual preferences in 27 volunteers and a discussion of some problems in utility assessment. An alternative approach, using threshold analysis, is presented in which the results of the decision analysis are expressed as a function of utility parameters. By knowing what sets of utilities favour each treatment, the assessment of patient preferences can then be focused on important differences of treatment options. The implications of these results for the design and analysis of clinical trials are discussed.
A counting process approach to the analysis of the course of non‐Hodgkin's lymphoma
Authors: Mau Jochen , Steinke Berthold 
Published: April 2007

AbstractNon‐Hodgkin's lymphoma is a neoplastic disease with a course including remission and relapse. Therefore, a mortality analysis of overall survival time alone may conceal important differences between the forces of mortality (hazard functions) associated with distinct states of active disease, for example pre‐remission state and first relapse. Further, prognostic factors for overall survival time may fail to contribute significantly to the pre‐remission force of mortality. Our approach to analysis is based on a non‐homogeneous Markov illness‐death process as a stochastic model of the course of disease. It exploits the statistical theory of counting processes.
Selection of variables using ‘independence bayes’ in computer‐aided diagnosis of upper gastrointestinal bleeding
Authors: Ohmann C. , Künneke M. , Zaczyk R. , Thon K. , Lorenz W. 
Published: April 2007

AbstractIn this paper two problems of computer‐aided diagnosis with ‘independence Bayes’ were investigated: selection of variables and monotonicity in performance as the number of measurements is increased. Using prospective data from patients with upper gastrointestinal bleeding, the stepwise forward selection approach maximizing the apparent diagnostic accuracy was analysed with respect to different kinds of bias in estimation of the true diagnostic accuracy and to the stability of the number and type of variables selected. The results of this study suggest first that the selection of variables should be evaluated against the estimated true diagnostic accuracy obtained using all variables, and secondly that the results of a single selected sequence may be severely biased.