bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knowledge Stocks and Information Flows in New Product Development*
Authors: Kyriakopoulos Kyriakos , De Ruyter Ko 
Published: November 2004

abstract Although firms increasingly invest in systems (e.g. ISO, knowledge centres, IT systems) for utilizing stored knowledge and acquiring market information during new product development, few manage to benefit from these investments. To explore this issue, we suggest that firms rely on two distinct types of knowledge stocks– procedural and declarative memory – that affect new product short‐term financial performance and creativity in distinct ways. Additionally, we suggest that internal or external information flows can have distinct moderating impact on the memory types–product outcomes relationship. Our empirical study of product development activities indicates that there is an inverted U‐shaped relationship between procedural memory and product outcomes as well as a positive relationship between declarative memory and financial performance. Also procedural and declarative memory may work in a complementary fashion enhancing both outcomes. Finally, procedural memory is found to reduce the value of internal or external information flows for product creativity. These findings have important implications for the organizational knowledge, capabilities, and product development literatures as well as for practice and they open ways for future research.
Rethinking the Business School*
Authors: Starkey Ken , Hatchuel Armand , Tempest Sue 
Published: November 2004

abstract It is ironic that at a moment in history when the business school seems to be enjoying unparalleled success, the role of the business school is being increasingly questioned by some of its leading professors. We examine the debate about the business school and its evolution. While sympathetic to the criticisms levied against the business school we nevertheless suggest a positive future if the business school can build upon its potentially unique position as knowledge space.
Delayed Hospital Discharge and Mental Health: The Policy Implications of Recent Research
Authors: Glasby Jon , Lester Helen 
Published: November 2004

Abstract In 2003, the Community Care (Delayed Discharges etc.) Act introduced charges for social services departments unable to discharge patients from hospital within agreed timescales. As details of this reimbursement policy have begun to emerge, it has become apparent that the new system may also be extended to mental health services. In response, this narrative review of the literature on delayed hospital discharges and mental health reports findings from 12 studies, which raise important and timely concerns about the feasibility of reimbursement. Although a significant number of people experience delayed discharges from acute psychiatric services, the task of defining delayed discharges is complex and subjective, dependent on the professional background and seniority of the person making the judgement. Reasons behind delayed discharges are also multi‐factorial in nature and cannot be attributed to social services departments alone.
Complicated Problems, Complicated Solutions? Homelessness and Joined‐up Policy Responses
Authors: Roche Martin 
Published: November 2004

AbstractThe government has recently signalled its determination to address both the symptoms and causes of homelessness through the introduction of new legislation requiring local authorities within England and Wales to develop strategic approaches to addressing this issue. Moreover, in common with many other areas of social provision in recent years, the “joining‐up” of services has been identified as a central tenet of these new approaches. In the case of homelessness, then, experience gleaned from other policy fields may prove an invaluable resource, in terms both of guiding approaches and in avoiding potential pitfalls. This paper examines the findings from a study undertaken within one Midlands city to investigate this assumption. Based upon evidence from this study it is suggested that, while precedent can offer this particular policy area valuable lessons, homelessness is an issue which, due to its multi‐dimensionality, offers new and unique challenges of its own.
Ultrasound detection of spontaneous hepato‐cellular carcinomas in X/myc bitransgenic mice
Authors: Mai W. , Barraud L. , Lefrancois L. , Scoazec J.Y. , Guerret S. , Vray D. , Merle P. , Vitvitski‐Trepo L. , Trepo C. , Janier M.F. 
Published: November 2004

Abstract: Aims: To evaluate trans‐abdominal ultrasound for the detection of Hepatocellular carcinoma (HCC) in a bitrasgenic murine (X/myc) model using a commercially available high‐frequency ultrasound unit.Methods: Sixty‐one female animals were included in this study. These animals were submitted to a single ultrasound examination of the liver under general anesthesia (isoflurane), and then euthanized. Results of ultrasound were compared with necropsy and histopathology.Results: The lesions demonstrated a fairly consistent aspect (oval‐ or round‐shaped, well‐defined hypoechoic homogeneous lesions), and lesions as small as 2 mm were identified. For detection of hepatic nodules per mouse the sensitivity was 75%, the specificity was 100% and the accuracy was 88.5%. For detection of hepatic focal lesions per lesions the overall sensitivity was 60%, the specificity was 97%, and the accuracy was 75.9%. Contrast‐enhanced harmonic ultrasound imaging did not improve the identification of the lesions in our experimental conditions.Conclusion: High‐frequency ultrasound appears to be an efficient tool allowing new possibilities to use this animal model and evaluate new therapies in longitudinal studies, which are much more powerful.
Risk factors for hepatocellular carcinoma in Hepatitis C patients with sustained virologic response to interferon therapy
Authors: Iwasaki Yoshiaki , Takaguchi Kouichi , Ikeda Hiroshi , Makino Yasuhiro , Araki Yasuyuki , Ando Masaharu , Kobashi Haruhiko , Kobatake Toshitsugu , Tanaka Ryoji , Tomita Minoru , Senoh Tomonori , Kawaguchi Mitsuhiko , Shimoe Toshinari , Manabe Koji , Kita Keiji , Shimamura Junnosuke , Sakaguchi Kohsaku , Shiratori Yasushi 
Published: November 2004

Abstract:
Background: Although a variety of papers demonstrated inhibited hepatocarcinogenesis with interferon (IFN) therapy for chronic hepatitis C, a small number of hepatocellular carcinomas (HCCs) were still observed even in sustained virologic responders.Aims: To clarify factors affecting the development of HCC, we analyzed the frequency of HCC in sustained virologic responders over a long‐term observation period.Methods: Seven hundred and ninety‐two out of the 2623 IFN‐treated hepatitis C patients who had undergone liver biopsy showed sustained virologic response. Screening for development of HCC was performed periodically during an average follow‐up of 5.1 years. Fibrosis of the pretreatment liver biopsy sample was graded. Risk factors for HCC were analyzed by using Cox proportional hazards regression.Results: Of 792 patients, 23 developed HCC. Univariate analysis showed that stage of hepatic fibrosis, age, and alcohol consumption were significantly associated with a risk of HCC (P<0.001). There was a significant difference in the cumulative incidence between patients stratified according to these variables (P<0.001).Conclusions: Pretreatment hepatic fibrosis score, age, and alcohol consumption may affect development of HCC even in sustained virologic responders. Thus, patients with these factors should be carefully followed even after eradication of the virus.
Loss of cooperative function of transforming growth factor‐β signaling proteins, smad3 with embryonic liver fodrin, a β‐spectrin, in primary biliary cirrhosis
Authors: Mishra Bibhuti , Tang Yi , Katuri Varalakshmi , Fleury Tom , Said Anan H , Rashid Asif , Jogunoori Wilma , Mishra Lopa 
Published: November 2004

Abstract: Modulation of fibrogenesis, epithelial, and mesenchymal cell fates are prominent effects of transforming growth factor‐β (TGF‐β) signaling by Smad proteins. We have previously shown that Smad2 and Smad3 insufficiency leads to a loss of bile ducts. In addition, Smad3/4 activity is mediated by embryonic liver fodrin (ELF), a β‐Spectrin. In mouse elf−/− mutants and in liver explant cultures, loss of ELF function results in T lymphocytic proliferation and absent intrahepatic bile ducts. A similar phenotype is seen in a number of cholestatic diseases with progressive loss of intrahepatic bile ducts and fibrosis. However, the expression patterns of Smads or role of ELF in cholestatic and fibrotic liver diseases are not yet known.Methods/results: We investigated the role of ELF in primary biliary cirrhosis (PBC), autoimmune hepatitis C, chronic viral hepatitis and in livers from mice deficient in Smad2/Smad3. We generated elf+/− mutant mice and analyzed for chronic liver disease and hepatocellular cancer (HCC) from 6 to 12 months. Perturbations in ELF expression were consistently seen only in PBC tissues. ELF expression was similarly aberrant in tissues from Smad2+/−/Smad3+/− mutant mice. Further studies indicated that ELF mislocalization is correlated with aberrant localization of Smad3 in some PBC tissues. Thirteen of 17 elf+/− mutant mice developed steatosis, fibrosis, hepatic dysplasia, with HCC in two mice.Conclusions: These results suggest that a compromised cytoarchitecture and polarized trafficking of TGF‐β signaling molecules, ELF and Smad3 are involved in the pathogenesis of PBC as well as HCC.
Hepatitis B virus reactivation in breast cancer patients undergoing cytotoxic chemotherapy and the role of preemptive lamivudine administration
Authors: Dai M. S. , Wu P. F. , Shyu R. Y. , Lu J. J. , Chao T. Y. 
Published: November 2004

Abstract: Background: Recent data suggest that hepatitis B virus (HBV) reactivation develops in 41% of breast cancer (BC) patients carrying HBV after chemotherapy. Our study aimed to determine the role of preemptive use of lamivudine in BC patients undergoing chemotherapy.Patients and methods: The test group consisted of 11 female patients with BC who were seropositive for hepatitis B surface antigen (HBsAg). Of these, 10 patients were treated in an adjuvant setting and one for metastatic disease. Lamivudine was given from the start of chemotherapy and was maintained until 1 month after the last infusion of chemotherapy. The control group consisted of nine historical BC patients carrying HBV and received similar systemic chemotherapy without preemptive lamivudine. Variables including HBsAg, HBV envelope antigen, anti‐HBV envelope antibody, serial serum alanine transaminase (ALT), quantitative HBV viral DNA analysis, and HBV‐DNA precore promoter and precore sequence were monitored. Test for emergence of mutant strains, notably nucleotide 550, was performed 6 months after the completion of chemotherapy.Results: All patients tolerated lamivudine well without development of evident HBV reactivation or overt hepatitis. Serum ALT remained unchanged without rebound hepatitis after cessation of chemotherapy and withdrawal of lamivudine. No emergence of lamivudine‐selective resistant strain (so‐called tyrosine–methionine–aspartate–aspartate mutations) was observed.Conclusions: Our results encourage preemptive use of lamivudine for prevention of HBV reactivation in patients who need short‐term chemotherapy.
Vigorous response of cytotoxic T lymphocytes associated with systemic activation of CD8+ T lymphocytes in fulminant hepatitis B
Authors: Kondo Y. , Kobayashi K. , Asabe S. , Shiina M. , Niitsuma H. , Ueno Y. , Kobayashi T. , Shimosegawa T. 
Published: November 2004

Abstract: Background: Fulminant hepatitis is a clinical syndrome characterized by sudden and severe liver dysfunction.Methods: We analyzed two patients with a superacute form of fulminant hepatitis B and compared findings with those of four patients with acute self‐limited hepatitis B, two patients with acute exacerbation of chronic hepatitis B and four healthy individuals.Results: In fulminant hepatitis, an increased population of human leukocyte antigen (HLA)‐DR+ CD8+ lymphocytes was observed in peripheral blood by flow cytometry, which was accompanied by the presence of HLA‐DRhi lymphocytes. The phenotype of CD8+ T lymphocytes from patients with fulminant hepatitis was mostly that of the effector T lymphocytes in peripheral blood, whereas lymphocytes with CD45RA− CCR7− phenotype dominated in the liver of these patients. A larger population of hepatitis B virus (HBV)‐specific cytotoxic T lymphocytes (CTLs) appeared in peripheral circulation of the fulminant hepatitis patients compared with that in a patient with acute hepatitis. HBV‐specific CTLs were highly concentrated in the liver, although epitopes recognized by these CTLs in the peripheral blood and in the liver were similar. Peripheral CTLs were mostly functional as indicated by intracellular perforin and interferon‐γ.Conclusions: These results suggest the presence of vigorous activation of CD8+ T cells in vivo in fulminant hepatitis and the necessity of extensive therapy in patients with this disease.
Imatinib mesylate induces apoptosis in human cholangiocarcinoma cells
Authors: Chiorean Mihnea V. , Guicciardi Maria Eugenia , Yoon Jung‐Hwan , Bronk Steven F. , Kaufmanns Scott H. , Gores Gregory J. 
Published: November 2004

Abstract: Background: Cholangiocarcinoma is a highly malignant, usually fatal cancer with limited therapeutic options. Receptor tyrosine kinases contribute to the development and progression of this cancer. The relatively selective tyrosine kinase inhibitor imatinib mesylate (STI‐571 or Gleevec®) has recently been licensed. However, the ability of this drug to inhibit signal transduction and induce apoptosis in human cholangiocarcinoma cells is incompletely studied. Thus, our goal was to examine the ability of STI‐571 to induce apoptosis in KMCH‐1 cells, a human cholangiocarcinoma cell line.Methods: Apoptosis was assessed morphologically and also biochemically by measuring caspase activity and the mitochondrial membrane potential. STI‐571 induced apoptosis and inhibited growth of KMCH‐1 cells in a time‐ and concentration‐dependent manner. The induction of apoptosis was accompanied by mitochondrial depolarization followed by a 4.5‐fold increase in caspase activation and was abrogated by the pancaspase inhibitor z‐VAD(OMe)‐fmk. Interestingly, cholangiocarcinoma cells do not express detectable PDGFR, c‐Abl or c‐Kit, which are protein kinases known to be directly inhibited by STI‐571. However, a significant decrease in epidermal growth factor receptor (EGFR) and focal adhesion kinase (FAK) phosphorylation was observed following treatment with STI‐571. This decrease in EGFR and FAK phosphorylation was associated with a reduction in Akt activity resulting in loss of Mcl‐1, a potent anti‐apoptotic Bcl‐2 family protein.Conclusions: these results indicate that STI‐571 induces caspase‐dependent apoptosis in a human cholangiocarcinoma cell line and suggest that STI‐571 might warrant further investigation as a possible agent for treatment of human cholangiocarcinoma.
SCALING OF MULTIPLICITY DISTRIBUTIONS AND COLLISION DYNAMICS IN e+e− AND pp INTERACTIONS
Authors: GAŹDZICKI M. , SZWED R. , WROCHNA G. , WRÓBLEWSKI A.K. 
Published: November 2004

The scaling properties of multiplicity distributions for e+e− and pp collisions are summarized. It is shown that in both cases the distributions have a lognormal shape. Possible relations between e+e− and pp collision dynamics are discussed in a framework scaling properties of multiplicity distributions. The form of the energy dependence of mean multiplicity is obtained as a consequence of the multiplicity scaling.
PECULIARITY OF SUPERCONDUCTIVITY IN A METAL WITH A SPIRAL MAGNETIC STRUCTURE
Authors: IZYUMOV YU. A. , LAPTEV V. M. 
Published: November 2004

Superconductivity states in a metal with existing spiral magnetic structure is studied. s-d exchange interaction of the conduction electrons with localized spins forming the magnetic ordering is treated in the framework of the strong coupling theory of superconductivity. Two separate factors are taken into account which influence the possibility of coexistence of superconductivity and magnetic ordering: electron-magnon interaction, as well as a modification of the electron spectrum due to its interaction with the static magnetic structure. The gap function is a 2 × 2 matrix with respect to the band indexes of hybridized electron states with up and down spins. The linearized Eliasberg's type equations for diagonal and off-diagonal elements are separated. Off-diagonal and diagonal elements correspond to quasisinglet and quasitriplet pairings respectively. As a direct consequence of violation of the time reversal invariance due to magnetic ordering, the diagonal gap function does not have a definite parity with respect to frequency. For this situation a moment method is developed for a calculation of the superconducting transition temperature in the limit of weak s-d-exchange coupling.
CORRELATION BETWEEN OPTICAL DEFECT DENSITY AND SPIN DENSITY IN AMORPHOUS SILICON CARBIDE
Authors: DEMICHELIS F. , PIRRI C.F. , TRESSO E. 
Published: November 2004

Amorphous silicon carbide (a-SiC:H) films deposited by different techniques under different deposition conditions have been submitted to photo-thermal deflection and photoacoustic spectroscopy (PDS and PAS) and electron spin resonance (ESR) measurements in order to obtain, through the trend of low energy absorption coefficient and the density of spins, information on the nature, energy and number of defects. The results obtained from the two techniques are often in disagreement since the dangling bond density generally does not scale with the integrated defect density. In order to explain the discrepancy the absorption coefficient has been calculated, following the Tauc model, in the three regions of fundamental absorption, Urbach tail and excess absorption. An expression for the density of defects has been obtained which depends on the integrated excess absorption coefficient through a proportionality factor.
ASSESSING PROXIMITY TO FRUITION: A CASE STUDY OF PHASES IN CASE TECHNOLOGY TRANSFER
Authors: CORBITT GAIL F. , NORMAN RONALD J. , BUTLER MARK C. 
Published: November 2004

Using the Lewin theory of planned change as a theoretical model, this study tests three hypotheses related to the three phase approach to change. An Action Research Model is used to gather data from 75 participants in CASE technology transfer in the Information Systems Department of a large insurance company. Five groups of people representing management and various levels of CASE usage participated in the study. In addition to group discussion, standardized questionnaires and individual Force Field Analyses are used to collect the data. In general the null hypotheses are rejected. The results appear to support at least three stages of change during CASE technology transfer. The groups differed with respect to content and magnitude of problems in the environment. In addition, during the moving phase it appears users may actually be more disillusioned with the change than non-users, however, the nature of the forces is more personal and indicates that they are personally involved with the move. While these people may be more negative than non-users, they are also moving closer to full implementation than those who have not started the moving process.
Therapeutic monitoring of immunosuppressant drugs. Where are we?
Authors: Wallemacq Pierre E. 
Published: November 2004

AbstractThe emergence of specific immunosuppressive drugs (cyclosporine, tacrolimus, mycophenolate mofetil and sirolimus) during the last two decades has contributed dramatically to the success of organ transplantation. However, optimum balance between therapeutic efficacy and the occurrence of side effects has been a real challenge for physicians, mainly due to inter- and intra-patient variability arising from pharmacokinetic, pharmacogenetic and pharmacodynamic individual properties. Therapeutic drug monitoring, defined as the measurement and interpretation of concentrations of these drugs in biological fluids, with as a final objective the prediction of organ responses, became an integral part of transplant protocols. New analytical techniques became available with different performances in terms of specificity and sensitivity. In addition, there has been progress in understanding the mechanisms of action of these drugs that have implications for the development of better monitoring strategies and for their coprescription. The purpose of this review is to examine the current strategies in use for the therapeutic drug monitoring of immunosuppressant drugs and to discuss some of the factors that impinge on the monitoring of these drugs.
Therapeutic drug monitoring of non-tricyclic antidepressant drugs
Authors: Mitchell Philip B. 
Published: November 2004

AbstractTherapeutic drug monitoring (TDM) of many of the tricyclic antidepressants (TCAs) has been demonstrated to be of clear clinical value. This article reviews studies of TDM for the selective serotonin reuptake inhibitors (SSRIs) and other non-tricyclic antidepressants such as venlafaxine, nefazodone, trazodone, mianserin and bupropion. No definitive therapeutic concentrations have been demonstrated for these agents, nor have levels indicative of toxicity been reported. The major benefit of TDM for these agents would appear to be in the assessment of the apparently treatment-refractory depressed patient, to determine whether such lack of response is related to inadequate levels that would suggest either poor compliance, ultra-rapid metabolism, or drug interactions leading to induction of metabolising enzymes. Potential future applications of TDM, in conjunction with genotyping of cytochrome P450 enzymes and pharmacogenomic evaluations, are discussed.
Therapeutic drug monitoring of old and newer anti-epileptic drugs
Authors: Neels Hugo M. , Sierens Ann C. , Naelaerts Kristine , Scharpé Simon L. , Hatfield George M. , Lambert Willy E. 
Published: November 2004

AbstractThe aim of the present paper is to provide information concerning the setting up and interpretation of therapeutic drug monitoring (TDM) for anti-epileptic drugs. The potential value of TDM for these drugs (including carbamazepine, clobazam, clonazepam, ethosuximide, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pheneturide, phenobarbital, phenytoin, primidone, tiagabine, topiramate, valproic acid, vigabatrin and zonisamide) is discussed in relation to their mode of action, drug interactions and their pharmacokinetic properties. The review is based upon available literature data and on observations from our clinical practice. Up until approximately 15 years ago anti-epileptic therapeutics were restricted to a very few drugs that were developed in the first half of the 20th century. Unfortunately, many patients were refractory to these drugs and a new generation of drugs has been developed, mostly as add-on therapy. Although the efficacy of the newer drugs is no better, there is an apparent improvement in drug tolerance, combined with a diminished potential for adverse drug interactions. All new anticonvulsant drugs have undergone extensive clinical studies, but information on the relationship between plasma concentrations and effects is scarce for many of these drugs. Wide ranges in concentrations have been published for seizure control and toxicity. Few studies have been undertaken to establish the concentration-effect relationship. This review shows that TDM may be helpful for a number of these newer drugs.
Pharmacogenomic genotyping methodologies
Authors: Jannetto Paul J. , Laleli-Sahin Elvan , Wong Steven H. 
Published: November 2004

Abstract“Personalized medicine” based on an individual’s genetic makeup is slowly becoming a reality as pharmacogenomics moves from the research setting to the clinical laboratory. Concordance studies between genotype and phenotype have shown that inherited mutations in several key drug-metabolizing enzymes, such as cytochrome P450 (