bluuebunny/crossref_metadata_2025_split huggingface dataset:
A three‐stage clinical trial design for rare disorders
Authors: Honkanen Visa E. A. , Siegel Andrew F. , Szalai John Paul , Berger Vance , Feldman Brian M. , Siegel Jeffrey N. 
Published: January 2005

AbstractMany clinical trials of uncommon diseases are underpowered because of the difficulty of recruiting adequate numbers of subjects. We propose a clinical trial design with improved statistical power compared to the traditional randomized trial for use in clinical trials of rare diseases. The three‐stage clinical trial design consists of an initial randomized placebo‐controlled stage, a randomized withdrawal stage for subjects who responded, and a third randomized stage for placebo non‐responders who subsequently respond to treatment. Test level and power were assessed by computer‐intensive exact calculations. The three‐stage clinical trial design was found to be consistently superior to the traditional randomized trial design in all cases examined, with sample sizes typically reduced by 20 per cent to 30 per cent while maintaining comparable power. When a treatment clearly superior to placebo was considered, our design reached a power of 75 per cent with a sample of 21 patients compared with the 52 needed to attain this power when only a randomized controlled trial was used. In situations where patient numbers are limited, a three‐stage clinical trial design may be a more powerful design than the traditional randomized trial for detecting clinical benefits. Copyright © 2001 John Wiley & Sons, Ltd.
Assessment of equivalence on multiple endpoints
Authors: Quan Hui , Bolognese Jim , Yuan Weiying 
Published: January 2005

AbstractSome clinical trials aim to demonstrate therapeutic equivalence on multiple primary endpoints. For example, therapeutic equivalence studies of agents for the treatment of osteoarthritis use several primary endpoints including investigator's global assessment of disease activity, patient's global assessment of response to therapy, and pain. In this paper, thoughts on simultaneous equivalence assessment on three endpoints are presented. As pointed out by Berger and Hsu (1996), the conventional intersection‐union test can be conservative. Simulation and computation are conducted to provide an insight on the conservativeness. We also provide a method to lower the confidence level and at the same time maintain the type I error when endpoints have normal distributions and are independent. If, in a particular analysis, the goal is to demonstrate equivalence on as many endpoints as possible, a step‐up procedure can be used for selecting those endpoints for which equivalence may be demonstrated. This step‐up procedure at the same time controls experimentwise error rate. The techniques are illustrated by a data example. Copyright © 2001 John Wiley & Sons, Ltd.
The applications of capture‐recapture models to epidemiological data
Authors: Chao Anne , Tsay P. K. , Lin Sheng‐Hsiang , Shau Wen‐Yi , Chao Day‐Yu 
Published: January 2005

AbstractCapture‐recapture methodology, originally developed for estimating demographic parameters of animal populations, has been applied to human populations. This tutorial reviews various closed capture‐recapture models which are applicable to ascertainment data for estimating the size of a target population based on several incomplete lists of individuals. Most epidemiological approaches merging different lists and eliminating duplicate cases are likely to be biased downwards. That is, the final merged list misses those who are in the population but were not ascertained in any of the lists. If there are no matching errors, then the duplicate information collected from a capture‐recapture experiment can be used to estimate the number of missed under proper assumptions. Three approaches and their associated estimation procedures are introduced: ecological models; log‐linear models, and the sample coverage approach. Each approach has its unique way of incorporating two types of source dependencies: local (list) dependence and dependence due to heterogeneity. An interactive program, CARE (for capture‐recapture) developed by the authors is demonstrated using four real data sets. One set of data deals with infection by the acute hepatitis A virus in an outbreak in Taiwan; the other three sets are ascertainment data on diabetes, spina bifida and infants' congenital anomaly discussed in the literature. These data sets provide examples to show the usefulness of the capture‐recapture method in correcting for under‐ascertainment. The limitations of the methodology and some cautionary remarks are also discussed. Copyright © 2001 John Wiley & Sons, Ltd.
The internationalization and performance of SMEs
Authors: Lu Jane W. , Beamish Paul W. 
Published: January 2005

AbstractWe discuss and explore the effects of internationalization, an entrepreneurial strategy employed by small and medium‐sized enterprises (SMEs), on firm performance. Using concepts derived from the international business and entrepreneurship literatures, we develop four hypotheses that relate the extent of foreign direct investment (FDI) and exporting activity, and the relative use of alliances, to the corporate performance of internationalizing SMEs. Using a sample of 164 Japanese SMEs to test these hypotheses, we find that the positive impact of internationalization on performance extends primarily from the extent of a firm's FDI activity. We also find evidence consistent with the perspective that firms face a liability of foreignness. When firms first begin FDI activity, profitability declines, but greater levels of FDI are associated with higher performance. Exporting moderates the relationship FDI has with performance, as pursuing a strategy of high exporting concurrent with high FDI is less profitable than one that involves lower levels of exports when FDI levels are high. Finally, we find that alliances with partners with local knowledge can be an effective strategy to overcome the deficiencies SMEs face in resources and capabilities, when they expand into international markets. Copyright © 2001 John Wiley & Sons, Ltd.
Resource‐based strategy and managerial power in networks of internationally dispersed technology units
Authors: Medcof John W. 
Published: January 2005

AbstractA linking of the Resource Based View of the firm, Resource Dependency Theory and the Vroom‐Yetton model of leadership is used to show that when important technical (R&D) resources are located offshore for strategic and efficiency reasons, resource‐based power goes with them. The extra‐national technology units that embody those strategically important resources should be managed with inclusive methods that respect that power shift. Theoretical, empirical and managerial implications are drawn from this analysis. Copyright © 2001 John Wiley & Sons, Ltd.
Consensus formation during strategic change
Authors: Markóczy Lívia 
Published: January 2005

AbstractThis paper offers a refined conceptualization of consensus formation and demonstrates in three organizations how this conceptualization enables us to uncover new patterns of consensus building. It describes a longitudinal study which investigated consensus formation in three organizations undergoing major strategic change. The study explored whether consensus building occurred during the strategic change and, if so, how. Initial participants of consensus were also investigated as well as changes in the scope of participants in consensus. Consensus building did occur, but contrary to some views less through an increase in the strength of consensus and more through an increase in the scope of consensus. Additionally, initial consensus was not located among members of the top management team, but more within an interest group whose members benefited from the given direction of the change. Copyright © 2001 John Wiley & Sons, Ltd.
Compositional gaps and downward spirals in international joint venture management groups
Authors: Hambrick Donald C. , Li Jiatao , Xin Katherine , Tsui Anne S. 
Published: January 2005

AbstractWe argue that compositional gaps in international joint venture (IJV) management groups, along parent company lines, will accentuate distinct managerial coalitions. Such gaps can occur on dimensions of observable demography, less apparent demography, or psychological characteristics. While compositional gaps in IJV management groups can provide the basis for healthy substantive conflict, such gaps—particularly if they are large—also tend to induce relationship conflict and heighten substantive conflict beyond its beneficial range. This can set off a downward spiral of relationship conflict, substantive conflict, and behavioral disintegration in the group. These harmful group processes further interact reciprocally with any tensions that might exist between the IJV parents, engendering a second downward spiral. Our model has implications for the performance of international joint ventures, and it serves as a foundation for designing interventions to avoid the downward spirals we portray. Copyright © 2001 John Wiley & Sons, Ltd.
Marketing's contribution to the implementation of business strategy: an empirical analysis
Authors: Slater Stanley F. , Olson Eric M. 
Published: January 2005

AbstractThis paper describes a study that assesses the performance implications of matching marketing strategy to business strategy. In order to conduct this study we first reviewed the literature on marketing strategy to identify its key dimensions. We then conducted a survey of 1000 senior marketing executives about the strategic marketing practices adopted in their respective firms or business units, and developed scales to describe 11 strategic marketing activities. We next performed a K‐means cluster analysis using these scales to develop a taxonomy of marketing strategy types consisting of: Aggressive Marketers, Mass Marketers, Marketing Minimizers, and Value Marketers. We then observed that superior performance at the firm or SBU level was achieved when specific marketing strategy types were matched with appropriate Miles and Snow (1978) business strategy types. Copyright © 2001 John Wiley & Sons, Ltd.
Are aliens green? Assessing foreign establishments' environmental conduct in the United states
Authors: King Andrew A. , Shaver J. Myles 
Published: January 2005

AbstractPrevious research has found that foreign‐owned establishments often lack specific capabilities needed to respond to local business conditions and are held to a higher standard by local stakeholders. These establishments compensate, however, by possessing offsetting capabilities such as technological excellence. In this article, we investigate how these conflicting forces shape the environmental conduct of foreign‐owned facilities. Using data from the Environmental Protection Agency, we find that foreign‐owned establishments generate more waste yet manage more waste than U.S.‐owned establishments. We also find evidence that both domestic and foreign‐owned firms generate more waste if they operate multiple facilities across multiple jurisdictions in the United States. Copyright © 2001 John Wiley & Sons, Ltd.
Architectural support in industry: a reflection using C‐POSH
Authors: Bril R. J. , Krikhaar R. L. , Postma A. 
Published: January 2005

AbstractSoftware architecture plays a vital role in the development (and hence maintenance) of large complex systems (containing millions of lines of code) with a long lifetime. It is therefore required that the software architecture is also maintained, i.e., sufficiently documented, clearly communicated, and explicitly controlled during its life‐cycle. In our experience, these requirements cannot be met without appropriate support.Commercial‐off‐the‐shelf support for architectural maintenance is still scarcely available, if at all, implying the need to develop appropriate proprietary means. In this paper, we reflect upon software architecture maintenance taken within three organizations within Philips that develop professional systems. We extensively describe the experience gained with introducing and embedding of architectural support in these three organizations. We focus on architectural support in the area of software architecture recovery, visualization, analysis, and verification.In our experience, the support must be carried by a number of pillars of software development, and all of these pillars have to go through a change process to ensure sustainable embedding. Managing these changes requires several key roles to be fulfilled in the organization: a champion, a company angel, a change agent, and a target. We call our reflection model C‐POSH, which is an acronym for Change management of the four identified pillars of software development: Process, Organization, Software development environment, and Humans. Our experiences will be presented in terms of the C‐POSH model. Copyright © 2005 John Wiley & Sons, Ltd.
Ethological resolution of behavioural topography and D1‐like versus D2‐like agonist responses in congenic D5 dopamine receptor mutants: Identification of D5:D2‐like interactions
Authors: O'Sullivan Gerard J. , Kinsella Anthony , Sibley David R. , Tighe Orna , Croke David T. , Waddington John L. 
Published: January 2005

AbstractThe phenotypic ethogram of congenic dopamine D5 receptor “knockout” mice was evaluated. Each individual topography of behaviour within the natural repertoire was assessed over the extended course of initial exploration of and subsequent habituation to the environment, and following challenge with a series of D1‐like agonists. Over initial exploration, D5‐null mice evidenced a modest reduction in locomotion and a modest increase in sifting. Subsequent habituation revealed additional phenotypic effects, primarily overall reduction in grooming and delayed habituation of rearing. Among D1‐like agonists, A 68930 stimulates both adenylyl cyclase and a putative D1‐like receptor coupled to stimulation of phospholipase C‐mediated phosphoinositide hydrolysis; conversely, SK&F 83959 stimulates phosphoinositide hydrolysis but not adenylyl cyclase while SK&F 83822 stimulates adenylyl cyclase but not phosphoinositide hydrolysis. Though programmed grooming syntax and episodic seizure activity induced by A 68930 and SK&F 83822 were unaltered, grooming induced by SK&F 83959 was reduced in D5 mutants. Stereotyped, ponderous locomotion induced by the D2‐like agonist RU 24213 was enhanced in D5 mutants. Phenotypic and pharmacological characterisation of congenic D5‐null mice at an ethological level identifies novel functional roles for the D5 receptor in mediating discrete topographies of behaviour relating to exploration, sequential motor coordination, and how these processes change over the course of interaction with and habituation to the environment. Additionally, they indicate the involvement of phosphoinositide hydrolysis and D5:D2‐like interactions in regulating these processes. Synapse 55:201–211, 2005. Published 2005 Wiley‐Liss, Inc.
Modulation of dopamine release by striatal 5‐HT2C receptors
Authors: Alex Katherine D. , Yavanian Gregory J. , McFarlane Hewlet G. , Pluto Charles P. , Pehek Elizabeth A. 
Published: January 2005

AbstractPrevious work has demonstrated that dopamine (DA) transmission is regulated by serotonin‐2C (5‐HT2C) receptors but the site(s) in the brain where these receptors are localized is not known. The present work utilized in vivo microdialysis to investigate the modulation of DA release by 5‐HT2C receptors localized in the nerve terminal regions of the mesocortical and nigrostriatal DA pathways. Microdialysis probes implanted in the striatum or the prefrontal cortex (PFC) measured dialysate DA concentrations, while the selective 5‐HT2B/2C inverse agonist SB 206553 was given locally by reverse dialysis into these terminal regions. Additionally, the effects of the 5‐HT2C agonist mCPP on striatal DA were measured. Local administration of SB 206553 (0.1‐100 μM) into the striatum increased DA efflux in a concentration‐dependent manner. Systemic administration of mCPP (1.0 mg/kg i.p.) decreased striatal DA and attenuated the SB 206553‐induced increase. In contrast, infusion of SB 206553 (0.1–500 μM) by reverse dialysis into the PFC had no significant effect on basal DA efflux in this region. Additionally, high concentrations of SB 206553 had no effect on high potassium (K+)‐stimulated DA release in the PFC. These data contribute to a body of evidence indicating that 5‐HT2C receptors inhibit nigrostriatal dopaminergic transmission. In addition, the results suggest that the nigrostriatal system is regulated by 5‐HT2C receptors localized in the dorsal striatum. Elucidating the mechanisms by which serotonin (5‐HT) modulates striatal and prefrontocortical DA concentrations may lead to improvements in the treatment of diverse syndromes such as schizophrenia, Parkinson's disease, anxiety, drug abuse, and/or depression. Synapse 55:242–251, 2005. Published 2005 Wiley‐Liss, Inc.
Modafinil enhances the increase of extracellular serotonin levels induced by the antidepressant drugs fluoxetine and imipramine: A dual probe microdialysis study in awake rat
Authors: Ferraro Luca , Fuxe Kjell , Agnati Luigi , Tanganelli Sergio , Tomasini Maria Cristina , Antonelli Tiziana 
Published: January 2005

AbstractIn view of a postulated role of the vigilance‐promoting drug modafinil in depression, the interaction of modafinil and two classical antidepressant drugs, fluoxetine and imipramine, were studied in 5‐HT levels in the dorsal raphe‐cortical system using dual‐probe microdialysis. Fluoxetine (1–10 mg/kg) dose‐dependently increased dorsal raphe‐cortical 5‐HT levels. Modafinil at a very low dose (3 mg/kg), by itself ineffective, enhanced the fluoxetine (5 mg/kg)‐induced increases of 5‐HT levels in both brain areas. A synergistic interaction was observed in the prefrontal cortex with fluoxetine (1 mg/kg) in terms of 5‐HT release, but not in the dorsal raphe. Imipramine (1.3 mg/kg) increased 5‐HT levels in the dorsal raphe, but not in the prefrontal cortex, while the higher doses (10.9–21.8 mg/kg) caused substantial increases in both brain areas. Modafinil (3 mg/kg), injected before imipramine (1.3 mg/kg), which by itself was ineffective on cortical 5‐HT levels, increased cortical 5‐HT levels. On other hand, modafinil failed to affect the high‐dose imipramine (10.9 mg/kg)‐induced increase of 5‐HT levels in the prefrontal cortex and the imipramine (1.3; 10.9 mg/kg)‐induced increase of 5‐HT levels in the dorsal raphe nucleus. These results demonstrate that modafinil in low doses enhances the acute effects of fluoxetine and imipramine on 5‐HT levels in the dorsal raphe nucleus (fluoxetine only) and especially in the prefrontal cortex of the awake rat. These findings suggest a therapeutic potential of low doses of modafinil in the treatment of depression when combined with low doses of classical antidepressants, especially by increasing 5‐HT transmission in cortical regions. Synapse 55:230–241, 2005. © 2005 Wiley‐Liss, Inc.
Simplified quantification of cerebral A1 adenosine receptors using [18F]CPFPX and PET: Analyses based on venous blood sampling
Authors: Meyer Philipp T. , Elmenhorst David , Zilles Karl , Bauer Andreas 
Published: January 2005

Abstract[18F]CPFPX was proposed as a novel ligand for in vivo quantification of cerebral A1 adenosine receptors (A1AR) using positron emission tomography (PET). The present study investigates the applicability of non‐invasive non‐compartment analyses to quantify the [18F]CPFPX total distribution volume (DV) without arterial blood sampling. Five healthy volunteers underwent dynamic PET (90 min) with arterial and venous blood sampling after [18F]CPFPX bolus injection. Area under curve (AUC) analysis and Logan's graphical analysis (GA) were performed employing venous blood samples as non‐invasive analyses. AUC analysis without data extrapolation (AUCr) and venous GA were also applied on voxel‐level to generate parametric images. A conventional two‐tissue compartment model (2TCM) using arterial blood samples served as reference method. Regional DV estimates provided by venous AUC and GA analyses and 2TCM demonstrated very high agreement (venous AUC vs. 2TCM: r2 = 0.968, linear regression slope = 0.943; venous GA vs. 2TCM: r2 = 0.972, slope = 0.906). Although on voxel‐level the venous AUCr and GA analyses were affected by a slight negative bias, they were still very highly correlated with the 2TCM (voxel‐wise venous AUCr vs. 2TCM: r2 = 0.969, slope = 0.858; voxel‐wise venous GA vs. 2TCM: r2 = 0.959, slope = 0.867). The proposed non‐invasive analysis methods (particularly venous GA) allow reliable quantification of human [18F]CPFPX PET studies. In populations with altered metabolic/kinetic properties, the applicability of venous sampling has to be separately verified. The applicability of [18F]CPFPX PET in basic and clinical neurosciences will be considerably enhanced by the avoidance of arterial blood sampling. Synapse 55:212–223, 2005. © 2005 Wiley‐Liss, Inc.
Behaviour of [11C]R(−)‐ and [11C]S(+)‐rolipram in vitro and in vivo, and their use as PET radiotracers for the quantificative assay of PDE4
Authors: Parker Christine A. , Matthews Julian C. , Gunn Roger N. , Martarello Laurent , Cunningham Vincent J. , Dommett David , Knibb Stephen T. , Bender Dirk , Jakobsen Steen , Brown John , Gee Antony D. 
Published: January 2005

AbstractCyclic AMP (cAMP) is a continually produced nucleotide which is inactivated by hydrolysis to 5′AMP via phosphodiesterase 4 (PDE4) enzymes. Rolipram is a selective PDE4 inhibitor which exists in two enantiomeric forms, R(−) and S(+). Both of these enantiomers have previously been labelled with carbon‐11 and used as positron emission tomography (PET) ligands for measuring PDE4 expression and function, and indirectly to explore the function of the cAMP second messenger, in vivo, using PET. The aim of these studies was to relate the in vitro affinities of the two rolipram enantiomers using standard pharmacological assays with the in vivo behaviour of the two enantiomers using PET. In vitro competition assays were performed using rat cortical membranes and [3H]R(−)‐ and [3H]S(+)‐rolipram with increasing concentrations of either unlabelled R(−)‐ or S(+)‐rolipram. In vivo, a series of PET studies were performed in the porcine brain using [11C]R(−)‐rolipram with co‐administration of increasing doses of either unlabelled R(−)‐ or S(+)‐rolipram. Additional in vivo PET studies were performed using [11C]S(+)‐rolipram with saturating doses of rolipram. In all studies, R(−)‐rolipram exhibited a higher affinity for the PDE4 enzyme than S(+)‐rolipram. The calculated affinity ratios were 7.97 from the in vitro studies; 12.5 from the in vivo studies using [11C]R(−)‐rolipram; and 14.7 from the in vivo studies using [11C]S(+)‐rolipram. To conclude, the in vitro affinities of R(−)‐ and S(+)‐rolipram predict their apparent in vivo behaviour in the porcine brain, as measured by PET. Synapse 55:270–279, 2005. © 2005 Wiley‐Liss, Inc.