bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two‐treatment comparison based on joint toxicity and efficacy ordered alternatives in cancer trials
Authors: Letierce Alexia , Tubert‐Bitter Pascale , Kramar Andrew , Maccario Jean 
Published: March 2003

AbstractThe primary goal of anticancer treatments is to attain efficacy, however toxicity could affect the course of the therapy. Methods have been proposed for comparing two treatments on the basis of the joint distribution for safety and efficacy outcomes, but they do not take into account the cumulative doses of drugs (chemotherapy) or radiation (radiotherapy) received by each patient. Moreover, these methods assume a parametric form for the joint distribution. In this paper we define a multi‐dimensional parameter including toxicity and efficacy outcomes and the dose at which one, none or both occur. Each patient is classified into an ordered category depending on the order of occurrence of these two criteria: the sooner the patient benefits from efficacy and/or the later he/she experiences toxicity, the better is the treatment. We then apply likelihood ratio tests with ordered alternatives. This procedure requires constrained maximum likelihood estimation via isotonic regression. A large set of simulations compares the proposed tests to other more usual tests and the results show a good power and a satisfactory type I error control. Our approach is illustrated with a multi‐centre randomized clinical trial involving patients with metastatic non‐seminomatous germ cell tumours. Copyright © 2003 John Wiley & Sons, Ltd.
Assessing non‐inferiority of a new treatment in a three‐arm clinical trial including a placebo
Authors: Pigeot Iris , Schäfer Juliane , Röhmel Joachim , Hauschke Dieter 
Published: March 2003

AbstractIn non‐inferiority trials, where non‐inferiority of a new experimental drug compared to an active control has to be shown, it may be advisable to use an additional placebo group for internal validation if ethically justifiable. The focus of this paper is on such designs. Assuming normality and homogeneity of variances we will derive a statistical test procedure which turns out to be equivalent to the assessment based on Fieller's confidence interval. Based on the power function of this test, sample size calculations are carried out to achieve a given power. Additionally, the optimal allocation of the total sample size is derived. As an alternative to this parametric procedure, the bootstrap percentile interval is discussed and finally compared with Fieller's confidence interval in a study on mildly asthmatic patients. Copyright © 2003 John Wiley & Sons, Ltd.
Kullback–Leibler divergence for evaluating bioequivalence
Authors: Dragalin Vladimir , Fedorov Valerii , Patterson Scott , Jones Byron 
Published: March 2003

AbstractIn this paper we propose a methodology for evaluating the bioequivalence of two formulations of a drug that encompasses not only average bioequivalence (ABE), but also the more recently introduced measures of population bioequivalence (PBE) and individual bioequivalence (IBE). The latter two measures are concerned with prescribability (PBE) and switchability (IBE). The main idea is to use the Kullback–Leibler divergence (KLD) as a measure of discrepancy between the distributions of the two formulations. Two formulations are declared bioequivalent if the upper bound of a level‐αconfidence interval for the KLD is less than a given goalpost to be set by a regulator. This new methodology overcomes many of the disadvantages of the corresponding measures recommended by the FDA. In particular the KLD: (i) possesses the natural hierarchical property that IBE⟹PBE⟹ABE; (ii) satisfies the properties of a true distance metric; (iii) is invariant to monotonic transformations of the data; (iv) generalizes easily to the multivariate case where equivalence on more than one parameter (for example, AUC, Cmax and Tmax) is required; and (v) is applicable over a wide range of distributions of the response variable (for example, those in the exponential family). The performance of the KLD relative to the metric proposed in guidance by the FDA for the evaluation of individual bioequivalence is evaluated using a simulation study. Previously published retrospective analyses using the FDA‐proposed metric are contrasted with those based on the KLD. It is concluded that the KLD is a viable alternative to the FDA‐proposed metric and that its mathematical and statistical properties make it a readily interpretable measure of the differences between formulations. Copyright © 2003 John Wiley & Sons, Ltd.
Assessing individual bioequivalence using the structural equation model
Authors: Carrasco Josep‐Lluís , Jover Lluís 
Published: March 2003

AbstractThe structural equation model (SEM) is introduced as a useful approach for assessing individual bio‐equivalence. SEM parameters are estimated using a partial likelihood analysis and the hypotheses of individual bioequivalence is evaluated in a disaggregate way, testing separately the hypothesis concerning SEM parameters, and assessing the overall hypothesis of individual bioequivalence using the intersection‐union principle. Limits of bioequivalence for SEM parameters are proposed and a power analysis is carried out. Copyright © 2003 John Wiley & Sons, Ltd.
Paradigmatic metamorphosis and organizational development
Authors: Yolles Maurice , Guo Kaijun 
Published: March 2003

AbstractParadigms metamorphose when they develop a new frame of reference. Two examples of paradigmatic metamorphosis are examined that together can be argued to formulate an evolutionary approach to managerial cybernetics. Organization Development (OD) is a well‐established soft methodology used extensively to engineer cultural change in organizations. OD can be set within Viable Systems Theory (VST), itself a conceptual development of the managerial cybernetic theory that underlies the Viable Systems Model (VSM). To illustrate this, a frame of reference is created that looks at systemic transformational processes. VST can operate as a general framework for this within which OD, VSM, and indeed the principles of Habermas's theory of communicative action can be embedded. A result of this exploration is to show how a managerial cybernetic form of OD can be developed to improve the way organizations can be diagnosed in complex change situations that must be managed. Copyright © 2003 John Wiley & Sons, Ltd.
Systems thinking and the disclosure of a technological society: some philosophical reflections
Authors: Strijbos Sytse 
Published: March 2003

AbstractThis paper resulted from an interdisciplinary research project named ‘Disclosive Systems Thinking’ that aimed at stimulating cooperation and exchange between research in systems methodology on the one hand and philosophy, particularly philosophy of technology, on the other. Against the background of the history of the philosophy of technology, a proposal is made for an ‘integrative’ approach to technology. Two ideas are introduced that are fundamental to an integrative philosophy of technology. First, emphasis is laid on the systems dimensions of modern technology. Sociotechnical systems are identified as the environment of our lives in a modern ‘technological’ society. Second, the idea of the ‘disclosure’ of a technological society is advanced as implying a process of structuring and restructuring the variety of systems in our technological society in a way that contributes to the opening up of human life. Finally, ‘disclosive systems thinking’ is proposed as a practice‐oriented systems methodology that differs fundamentally both from ‘hard’ and ‘soft’ systems thinking in its view on normativity and human values. Copyright © 2003 John Wiley & Sons, Ltd.
Mexico
Authors: Hise Richard T. , Solano‐Méndez Roberto , Gresham Larry G. 
Published: March 2003

AbstractNot understanding the cultural aspects of doing business overseas can jeopardize the success of international
negotiations, entry strategies, joint ventures, technology transfer, marketing, and human resources. This
article reports a study of the perceptions of U.S. and Mexican executives concerning the importance of 15
cultural dimensions of doing business in Mexico (our second largest trading partner). It found that,
whereas Mexican executives believed more strongly than U.S. executives that the cultural dimensions of doing
business in Mexico were more important than the product or service offered and the accompanying terms of sale,
the U.S. executives, surprisingly, assigned higher levels of importance to the 15 cultural variables. Both
Mexican and U.S. executives strongly agreed on which of the 15 variables were most important. All eight
subgroups of U.S. executives assigned higher levels of importance to the 15 cultural aspects of doing business
in Mexico than did their Mexican counterparts. When four comparisons of the executives of the eight subsets of
U.S. companies‐large vs. small, border location vs. nonborder location, doing business in Mexico vs. not
doing business there, and doing business there more than 5 years (pre‐NAFTA) vs. doing business
there 5 years or less (post‐NAFTA)—were made of the level of importance they attached to
the cultural variables, no significant differences were found. Based on the study's findings, implications
for doing business in Mexico are indicated. © 2003 Wiley Periodicals, Inc.
FDI in CEECs: How do Western investors survive?
Authors: Fabry Nathalie H. , Zeghni Sylvain H. 
Published: March 2003

AbstractThis article emphasizes that knowledge transfer across a firm's boundaries, in a transition context,
implies a specific involvement of Western investors. They need to promote specific relationships within
affiliates. This article emphasizes two points. First, partners have few common practices and do not share the
same perception of the firm. This is the problem with building new capabilities. Second, Western firms have to
mobilize organizational resources to build efficient affiliates (new human resources management,
introduction of new functions, management by expatriates). Setting up new management rules to run an
affiliate in transition countries is costly and often underestimated by foreign investors. © 2003 Wiley
Periodicals, Inc.
Making international marketing decisions under WTO rules
Authors: Denis Jean‐Emile 
Published: March 2003

AbstractWith the conclusion of the Uruguay Round and the establishment of the World Trade Organization
(WTO) in April 1994, a comprehensive set of rules emerged that affect in a pervasive manner the
activities of firms on foreign markets. This body of rules is overwhelmingly presented in the literature from a
trade policy or legal viewpoint. The result is that, for many marketers, WTO rules are somewhat confusing, and
their impact on international business operation is difficult to assess. This paper is purely analytical and
does not aim to provide any contribution to international marketing theory. Its purpose is to identify which
rules, among the many the WTO system encompasses, are of direct concern to firms. It aims to expose in a
straightforward manner how they may be coped with or taken advantage of by international marketers. It focuses
on WTO measures, which deal with so‐called international marketing mix decisions, namely decisions
pertaining to (1) entry and international distribution, (2) product and service,
(3) pricing, and (4) international communication. Commitments made during the WTO Fourth
Ministerial Conference in Doha (November 9–14, 2001) that are relevant to issues raised in this
paper are accounted for. © 2003 Wiley Periodicals, Inc.
Doing business in China: Culture and practice
Authors: Stoltenberg Clyde D. 
Published: March 2003

AbstractMing‐Jer Chen. 2001. Inside Chinese Business: A Guide for Managers Worldwide. Boston:
Harvard Business School Press. 234 pages.John B. Stuttard. 2000. The New Silk Road: Secrets of Business Success in China Today. New
York: John Wiley & Sons. 144 pages.Yadong Luo. 2000. Strategy, Structure, and Performance of MNCs in China. Westport, CT:
Quorum Books. 302 pages.Maria Lai‐Ling Lam. 2000. Working With Chinese Expatriates in Business Negotiations:
Portraits, Issues, and Applications. Westport, CT: Quorum Books. 188 pages.
Genotoxicity of water extracts from the River Yamuna at Mathura, India
Authors: Aleem Asma , Malik Abdul 
Published: March 2003

AbstractWater samples were collected from the River Yamuna at Mathura, India, and concentrated by using XAD resins (Amberlite XAD‐4 and XAD‐8) and liquid–liquid extraction procedures. The genotoxicities of the extracted water samples were evaluated by the Ames Salmonella/mammalian microsome test, DNA repair of defective mutants, and bacteriophage λ systems. The results of the Salmonella test demonstrated that the XAD‐concentrated water samples had maximum mutagenicity with the TA98 strain, both with and without metabolic activation. The XAD‐concentrated water samples collected in the summer showed maximum mutagenic responses compared with those collected in other seasons, whereas the liquid–liquid extracted samples exhibited maximum mutagenic activity during the postmonsoon season. The damage brought about during DNA repair of defective mutants in the presence of XAD‐concentrated water samples was found to be remarkably high compared with the liquid–liquid extracted water samples at a dose level of 20 μL/mL of culture. All the mutants invariably exhibited significant decline in their colony‐forming units compared with their isogenic wild‐type counterparts. Survival was decreased by 86.7% and 65.1% in the polA− strain after 6 h of treatment with XAD‐concentrated and liquid–liquid extracted water samples, respectively. A significant decrease in the survival of bacteriophage λ was also observed when treated with test samples. The damage was more pronounced in lexA mutants when the phage was treated with XAD‐concentrated samples. The recA, lexA, and polA mutants of E. coli K‐12 were found to be sensitive to the test samples, suggesting damage to the DNA of exposed cells as well as to the role of recA+, lexA+, and polA+ genes in coping with the hazardous effect of the pollutants. The results demonstrated substantial genotoxicity and mutagenicity in the water samples tested. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 69–77, 2003.
Inhibition of CYP 1A2–dependent MROD activity in rat liver microsomes: An explanation of the hepatic sequestration of a limited subset of halogenated aromatic hydrocarbons
Authors: Chen Jin Jun , Chen Guo Sheng , Bunce Nigel J. 
Published: March 2003

AbstractMany classes of halogenated aromatic compounds (HACs) are highly lipophilic environmental contaminants that exert toxic effects via the Ah receptor signal transduction pathway and whose metabolism generally involves monooxygenase enzymes of the CYP 1A family. Despite their lipophilicity, a high proportion of the body burden of certain polychlorinated dibenzo‐p‐dioxins and coplanar polychlorinated biphenyls is sequestered in liver, a process believed to involve CYP 1A2. In this work we examined HAC‐induced inhibition of the demethylation of 7‐methoxyresorufin, a process that is selectively catalyzed by CYP 1A2. 2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin, 3,3′,4,4′‐tetrachlorobiphenyl (PCB 77) and 3,3′,4,4′,5‐pentachlorobiphenyl (PCB 126) were found to be strong competitive inhibitors of methoxyresorufin‐O‐demethylase activity, consistent with the high ability of hepatic tissue to sequester these compounds selectively. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 115–119, 2003
An investigation of the role of vitamin E in the protection of mice against microcystin toxicity
Authors: Gehringer Michelle M. , Govender Sharlene , Shah Mrinal , Downing Timothy G. 
Published: March 2003

AbstractThe presence of cyanobacterial toxins in drinking and recreational waters represents a potential public health risk. Microcystin‐LR (MC‐LR) is a potent cyclic heptapeptide hepatotoxin produced by the blue‐green alga Microcystis aeruginosa. Chemoprotectant studies have indicated that membrane‐active antioxidants such as vitamin E may offer protection against microcystin toxicity. This study investigated the effect of vitamin E supplementation on microcystin toxicity in mouse liver. Groups of mice were fed vitamin E supplements (8.33 or 33.3 U/mouse/day) for 4 weeks, with intraperitoneal doses of MC‐LR extract (70% LD50) every 3 days from day 8. The potential benefits of vitamin E were evaluated based on lipid peroxidation, alanine transaminase (ALT), and glutathione S‐transferase (GST) levels. Vitamin E supplementation at 33.3 U/mouse/day offered some protection against lipid peroxidation induced by repeated exposure to MC‐LR extract and limited both the toxin‐induced increase in ALT leakage and decrease in GST activity. Vitamin E supplementation at 66.6 U/mouse/day significantly increased the time to death and reduced the increase in liver percentage body weight induced in mice given a lethal dose challenge of MC‐LR extract. Therefore, vitamin E, taken as a dietary supplement, may have a protective effect against chronic exposure to MC‐LR. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 142–148, 2003.
Estimation of microcystins in the freshwater fish Oreochromis niloticus in an Egyptian fish farm containing a Microcystis bloom
Authors: Mohamed Zakaria A. , Carmichael Wayne W. , Hussein Ahmed A. 
Published: March 2003

AbstractMicrocystins (MCYSTs) that accumulated in different organs of the freshwater fish Oreochromis niloticus, collected from a fish farm in Egypt containing heavy blooms of Microcystis aeruginosa, were investigated using an enzyme‐linked immunosorbent assay (ELISA). The distribution of MCYSTs in the organs varied significantly. The highest MCYST level was recorded in the guts (821 ng/g fresh weight), followed by the livers (531.8 ng/g) and kidneys (400 ng/g). Smaller amounts of MCYST were detected in muscles (102 ng/g). The present study suggests that fish farms should be monitored for the presence of toxic cyanobacterial blooms to minimize the exposure of fish to potent hepatotoxins. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 137–141, 2003
The addition of activin A and inhibin A measurement to uterine artery Doppler velocimetry to improve the early prediction of pre‐eclampsia
Authors: Florio P. , Reis F. M. , Pezzani I. , Luisi S. , Severi F. M. , Petraglia F. 
Published: March 2003

AbstractObjectiveTo evaluate whether the measurement of maternal serum activin A and inhibin A adds any clinically relevant information for the prediction of pre‐eclampsia in women with altered uterine artery Doppler velocimetry at 24 weeks of gestation.MethodsThis was a prospective, controlled, hospital‐based study involving 58 asymptomatic pregnant women at 24 weeks' gestation in whom a diastolic notch of the uterine artery waveform was noted at routine Doppler examination. Doppler assessment of the uterine artery waveform and measurement of maternal activin A and inhibin A serum levels by specific two‐site enzyme immunoassays were performed. The cut‐off points for defining ‘high’ serum activin A and inhibin A levels for prediction of pre‐eclampsia were chosen by receiver–operating characteristics (ROC) curve analysis. The probability of developing pre‐eclampsia was calculated for several combinations of results of hormone testing.ResultsActivin A and inhibin A levels were higher in patients who developed pre‐eclampsia (n = 18; mean ± standarderror: 2.69 ± 0.35 ng/mL and 131.2 ± 22.7 pg/mL, respectively) than in those who did not present with pre‐eclampsia at follow‐up (n = 40; activin A: 1.79 ± 0.18 ng/mL and inhibin A: 91.9 ± 6.2 pg/mL; P < 0.05). Activin A at the cut‐off value of 1.7 multiples of the median (MoM) achieved a sensitivity of 61% and a specificity of 89%, whereas inhibin A at the cut‐off value of 1.8 MoM combined a sensitivity of 39% with a specificity of 92% for prediction of pre‐eclampsia. The probability of pre‐eclampsia was 31% in the whole study population, 86% if both activin A and inhibin A were elevated and 17% if both hormone markers were unaltered.ConclusionThe measurement of serum activin A and inhibin A levels may add significant prognostic information for predicting pre‐eclampsia in pregnant women showing specific Doppler alterations in the late second trimester. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.
Comparison of color Doppler uterine artery indices in a population at high risk for adverse outcome at 24 weeks' gestation
Authors: Albaiges G. , Missfelder‐Lobos H. , Parra M. , Lees C. , Cooper D. , Nicolaides K. H. 
Published: March 2003

AbstractObjectiveTo compare uterine artery Doppler velocity and impedance indices in the presence and absence of uterine artery waveform notches, in the prediction of adverse pregnancy outcome in high‐risk women.MethodsOne hundred and fifty‐seven women identified at Doppler screening as being at ‘high risk’ underwent a further uterine artery Doppler assessment at 24 weeks' gestation. Pulsatility and resistance indices and minimum, time averaged and time averaged maximum velocities were measured, and the presence of bilateral notches noted. Adverse outcomes were pre‐eclampsia, birth weight less than the tenth centile, placental abruption and intrauterine death. The best cut‐off for each parameter was assessed by univariate logistic regression, and the comparative performance of the screening parameters was assessed using kappa values.ResultsThe best performing index in the presence of bilateral notches was mean resistance index, for a cut‐off of 0.67, giving a kappa value of 0.65. Mean pulsatility index and lowest pulsatility index performed similarly well, both with kappa values of 0.58. All velocity indices apart from lowest minimum velocity had kappa values of < 0.4. When indices were analyzed, irrespective of notch status, mean resistance and mean pulsatility indices performed similarly, with kappa values of 0.49 and 0.46, respectively; mean minimum velocity had a kappa value of 0.4.ConclusionsIn a high‐risk population, uterine artery Doppler mean resistance indices perform better than do velocity indices in the prediction of adverse pregnancy outcome, irrespective of notch status. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.
Prenatal ultrasound diagnosis of Nager syndrome
Authors: Paladini D. , Tartaglione A. , Lamberti A. , Lapadula C. , Martinelli P. 
Published: March 2003

AbstractNager syndrome, or acrofacial dysostosis, is a rare malformation complex characterized by facial anomalies (external ear abnormalities and micrognathia) and limb defects (radial hypoplasia and absence of the thumb and/or other digits). Since its first description in 1948, more than 80 cases have been reported in the pediatric literature. However, there is only one previous report on the prenatal recognition of the syndrome, which was at 30 weeks of gestation. We report here a further case of Nager syndrome, prospectively diagnosed at 23 weeks of gestation. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.