bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical guidelines online: do they improve compliance?
Authors: Williams J G , Cheung W Y , Price D E , Tansey R , Russell I T , Duane P D , Al-Ismail S A , Wani M A 
Published: July 2004

Abstract
Background: The introduction of intranet services in a district general hospital provided an opportunity to put evidence based national guidelines online to facilitate access and promote application of best practice in acute medical care. This study evaluated the effectiveness of this approach.
Method: Local guidelines were made available online at ward terminals after they had been distributed in paper form. An interrupted time series design was used to evaluate the impact on compliance with three preselected guidelines, which addressed the management of suspected deep vein thrombosis, upper gastrointestinal bleeding, and stroke. This was supplemented by a qualitative assessment of the views of medical staff.
Results: There was a significant increase in the adherence to the guidelines for stroke when they were made available online, but this was not demonstrable for deep vein thrombosis or upper gastrointestinal bleeding.
Qualitative interviews with junior medical staff and consultants after the study was completed revealed that there was confusion regarding the application of the guidelines for deep vein thrombosis and little active support from the gastroenterologists for the guidelines for upper gastrointestinal bleeding. The stroke guidelines were actively promoted by their author and widely supported.
Conclusion: Making guidelines available online will not be effective unless they are actively promoted and represent a consensus view.
An approach to drug induced delirium in the elderly
Authors: Alagiakrishnan K , Wiens C A 
Published: July 2004

Abstract
Drugs have been associated with the development of delirium in the elderly. Successful treatment of delirium depends on identifying the reversible contributing factors, and drugs are the most common reversible cause of delirium. Anticholinergic medications, benzodiazepines, and narcotics in high doses are common causes of drug induced delirium. This article provides an approach for clinicians to prevent, recognise, and manage drug induced delirium. It also reviews the mechanisms for this condition, especially the neurotransmitter imbalances involving acetylcholine, dopamine, and gamma aminobutyric acid and discusses the age related changes that may contribute to altered pharmacological effects which have a role in delirium. Specific interventions for high risk elderly with the goal of preventing drug induced delirium are discussed.
Severe acute respiratory syndrome (SARS): epidemiology and clinical features
Authors: Hui D S C , Chan M C H , Wu A K , Ng P C 
Published: July 2004

Abstract
Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease with a significant morbidity and mortality. The major clinical features include persistent fever, chills/rigor, myalgia, malaise, dry cough, headache, and dyspnoea. Older subjects may present without the typical febrile response. Common laboratory features include lymphopenia, thrombocytopenia, raised alanine transaminases, lactate dehydrogenase, and creatine kinase. The constellation of compatible clinical and laboratory findings, together with certain characteristic radiological features and lack of clinical response to broad spectrum antibiotics, should arouse suspicion of SARS. Measurement of serum RNA by real time reverse transcriptase-polymerase chain reaction technique has a detection rate of 75%–80% in the first week of the illness.
The Integrity of Polymer Composites during and after Fire
Authors: Gibson A. G. , Wright P. N. H. , Wu Y. -S. , Mouritz A. P. , Mathys Z. , Gardiner C. P. 
Published: July 2004

This paper reports on changes to the mechanical properties of woven glass laminates with polyester, vinyl ester and phenolic resins during fire exposure. Two sets of experiments were carried out. First, unstressed laminates were exposed to a constant one-sided heat flux (50 kW m 2) for various times, and the residual post-fire strength at room temperature was reported. In a second series of experiments, laminates were tested under load. The times corresponding to a given loss of properties were 2-3 times shorter than in the previous case. It was found in both cases that modes of loading involving compressive stress were more adversely affected by fire exposure than those involving tension. A simple ‘two-layer’ model is proposed, in which the laminate is assumed to comprise (i) an unaffected layer with virgin properties and (ii) a heat-affected layer with zero properties. For residual properties after fire, the ‘effective’ thickness of undamaged laminate was calculated using this model and compared with measured values. A thermal model was employed to predict the temperature and the residual resin profile through the laminate versus time. Comparing the model predictions with the measured values of effective laminate thickness enabled simple criteria to be developed for determining the position of the ‘boundary’ between heat-affected and undamaged material. For post-fire integrity of unloaded laminates, this boundary corresponds to a Residual Resin Content (RRC) of 80%, a criterion that applies to all the resin types tested. For polyester laminate under load in fire, the boundary in compressive loading (buckling failure) appears to correspond to the point where the resin reaches 170 C. In tensile loading, significant strength is retained, because of the residual strength of the glass reinforcement. The model was used to produce predictions for ‘generic’ composite laminates in fire.
Fast Design of Mixing Sections by Means of Network Theory
Authors: Hennes Jochen , Michaeli Walter 
Published: July 2004

Single-screw extruders make use of mixing and shearing sections to ensure good thermal and mechanical homogeneity at high mass throughput rates. Nowadays, these sections are usually designed empirically or with very simple estimation formulas. Therefore, important interpretation criteria, like pressure loss, temperature increase, average shear rate or residence time profile are only determined very inaccurately. The 3D finite-element analysis (FEA) can determine these parameters very precisely, but with very long computation times. The network theory allows an economic calculation with a sufficient accuracy of the aforementioned data. This paper describes the modeling of extruder mixing sections and the solution of these models by means of the network theory.
One Size Does Not Fit All: Global Equity Compensation in the New World
Authors: Dunn Bill 
Published: July 2004

Global companies have historically relied on stock options to compensate their workforce. Because of the fallout from recent corporate governance breakdowns, the use of corporate equity in compensation programs now faces new pressures. Furthermore, U.S. and international accounting changes will increase the cost of delivering stock options, forcing companies to rethink how they deliver equity-based compensation. Making these compensation delivery changes is especially challenging for global companies, which must consider a wide array of complex global and local issues before modifying the delivery approach. As companies respond to the changing accounting rules as well as shifting market conditions, they must resist making quick decisions relating to the implementation of equity-based compensation plans. Instead, new delivery approaches must be analyzed in the context of their global limitations and cultural effectiveness. Boardroom actions must be supported by input from the many organizational stakeholders who have responsibility for operating the plan and who will be held accountable for plan costs and effectiveness. With this input, these plans can be structured in a way that achieves a company’s human resource and financial objectives.
Building an ROI Business Case for Enterprise Compensation Management Solutions
Authors: Dobbs Kevin M. 
Published: July 2004

A new breed of technology, called Enterprise Compensation Management (ECM) is automating the compensation process to help organizations acquire, manage and optimize workforces, in addition to enabling true manager self-reliance. By utilizing an ECM solution to optimize employee compensation on an enterprise level, surveyed companies reported greater workforce effectiveness, better execution of pay-for-performance strategies, increased productivity and substantial financial savings. This article seeks to provide a conceptual framework to assist in quantifying the financial and strategic benefits that companies can expect to achieve from ECM solutions. It also provides detailed survey results from a wide-range of companies that have evaluated and implemented ECM solutions-examining the 5-step ROI Methodology companies can follow when building an ECM business case.
Social Pedagogy and Care
Authors: Cameron Claire 
Published: July 2004

• Summary: Although social pedagogy is unfamiliar in the UK, in many European countries it is the main discipline underpinning residential care work with children and young people. Social pedagogy is about the relationship of the individual to society and a pedagogic method of working in residential care is about how to achieve the integration of disadvantaged young people into the wider society in which they live. • Findings: This article argues, using an exploratory cross-national study of social pedagogy, that pedagogic practice offers a unified, coherent and holistic approach to working in residential care. Vignette data from two countries, Denmark and Germany, are used to provide practice examples. A remarkable consensus of views about practice emerged from the tutors, practitioners and students who took part. Young people’s views were also sought, and these largely concurred with the approaches advocated by the adult informants. • Applications: Three themes are discussed which illuminate the pedagogic approach: the active vs the passive child; physical care or contact; and heart, brains and hands working in combination. Some questions for English policy, training and practice are posed.
Developing the Concept of Professional Advocacy
Authors: Dalrymple Jane 
Published: July 2004

• Summary: This article examines the development of child and youth advocacy through an analysis of the meaning of professionalization and argues that a culture of advocacy is needed to facilitate the development of professional advocacy expertise. • Findings: The fragmented development of child and youth advocacy in England and Wales has accelerated within the modernizing agenda of New Labour. While child and youth advocacy competes with other imperatives in the provision of health and social care services, advocates seek to develop professional status in order to ensure effectively the involvement of children and young people in decision making. The nature of advocacy practice creates resistance to traditional models of professionalization but a committed practitioner model, recognizing advocacy expertise, enables advocacy to develop in a way that does not compromise its role. • Applications: Debates about the professionalization of child and youth advocacy are ongoing, particularly with the publication of advocacy standards in England and Wales. This article contributes to the discussion and suggests a model for developing the theory and practice of child and youth advocacy.
The Place of Writing in Social Work
Authors: Heron Gavin , Murray Rowena 
Published: July 2004

• Summary: Despite the rhetoric surrounding the merits of practitioners’ contributions, writing for publication in social work continues to be an activity dominated by academics. Furthermore, it could be argued that the influence of the Research Assessment Exercise (RAE) is reshaping what can be considered as quality research. This article examines the nature of writing for publication within social work and gives particular focus to residential child care, where the problem is most striking, although this discussion will have relevance for professionals in other social work settings. We argue that without greater involvement of practitioners, quality research may be quite narrowly defined. • Findings: There would appear to be minimal discussion of the absence of practitioner writing in the social work literature. The causes for this absence have not been fully explored; potential factors, such as inequality, barriers to writing and current education and training programmes, have not been addressed as fully as in other professions. • Applications: This focus on academic writing shows the need for a more inclusive approach to social work practice and research. There is a need for further discussion of strategies to involve residential child care practitioners in research.
A20 protects endothelial cells from TNF-, Fas-, and NK-mediated cell death by inhibiting caspase 8 activation
Authors: Daniel Soizic , Arvelo Maria B. , Patel Virendra I. , Longo Christopher R. , Shrikhande Gautam , Shukri Tala , Mahiou Jerome , Sun David W. , Mottley Christina , Grey Shane T. , Ferran Christiane 
Published: July 2004

AbstractA20 is a stress response gene in endothelial cells (ECs). A20 serves a dual cytoprotective function, protecting from tumor necrosis factor (TNF)–mediated apoptosis and inhibiting inflammation via blockade of the transcription factor nuclear factor–κB (NF-κB). In this study, we evaluated the molecular basis of the cytoprotective function of A20 in EC cultures and questioned whether its protective effect extends beyond TNF to other apoptotic and necrotic stimuli. Our data demonstrate that A20 targets the TNF apoptotic pathway by inhibiting proteolytic cleavage of apical caspases 8 and 2, executioner caspases 3 and 6, Bid cleavage, and release of cytochrome c, thus preserving mitochondrion integrity. A20 also protects from Fas/CD95 and significantly blunts natural killer cell–mediated EC apoptosis by inhibiting caspase 8 activation. In addition to protecting ECs from apoptotic stimuli, A20 safeguards ECs from complement-mediated necrosis. These data demonstrate, for the first time, that the cytoprotective effect of A20 in ECs is not limited to TNF-triggered apoptosis. Rather, A20 affords broad EC protective functions by effectively shutting down cell death pathways initiated by inflammatory and immune offenders.
Variable sensitivity of FLT3 activation loop mutations to the small molecule tyrosine kinase inhibitor MLN518
Authors: Clark Jennifer J. , Cools Jan , Curley David P. , Yu Jin-Chen , Lokker Nathalie A. , Giese Neill A. , Gilliland D. Gary 
Published: July 2004

Abstract
FLT3 is constitutively activated by internal tandem duplications (ITDs) in the juxtamembrane domain or by activation loop mutations in acute myeloid leukemia (AML). We tested the sensitivity of 8 activation loop mutations to the small molecule FLT3 inhibitor, MLN518. Each FLT3 activation loop mutant, including D835Y, D835A, D835E, D835H, D835N, D835V, D835del, and I836del, transformed Ba/F3 cells to factor-independent proliferation and had constitutive tyrosine kinase activation, as assessed by FLT3 autophosphorylation and activation of downstream effectors, including STAT5 and ERK. MLN518 inhibited FLT3 autophosphorylation and phosphorylation of STAT5 and ERK in FLT3-ITD-transformed Ba/F3 cells with an IC50 (50% inhibition of cell viability) of approximately 500 nM. However, there was a broad spectrum of sensitivity among the 8 activation loop mutants, with IC50 ranging from approximately 500 nM to more than 10 μM for the inhibition of phosphorylation of FLT3, STAT5, and ERK. The relative sensitivity of the mutants to MLN518 in biochemical assays correlated with the cellular IC50 for cytokine-independent proliferation of FLT3-transformed Ba/F3 cells in the presence of MLN518. Thus, certain activation loop mutations in FLT3 simultaneously confer resistance to small molecule inhibitors. These findings have implications for the evaluation of responses in clinical trials with FLT3 inhibitors and provide a strategy to screen for compounds that can overcome resistance.
Gene expression profiles at diagnosis in de novo childhood AML patients identify FLT3 mutations with good clinical outcomes
Authors: Lacayo Norman J. , Meshinchi Soheil , Kinnunen Paivi , Yu Ron , Wang Yan , Stuber Christianna M. , Douglas Lorrie , Wahab Romina , Becton David L. , Weinstein Howard , Chang Myron N. , Willman Cheryl L. , Radich Jerald P. , Tibshirani Robert , Ravindranath Yaddanapudi , Sikic Branimir I. , Dahl Gary V. 
Published: July 2004

AbstractFms-like tyrosine kinase 3 (FLT3) mutations are associated with unfavorable outcomes in children with acute myeloid leukemia (AML). We used DNA microarrays to identify gene expression profiles related to FLT3 status and outcome in childhood AML. Among 81 diagnostic specimens, 36 had FLT3 mutations (FLT3-MUs), 24 with internal tandem duplications (ITDs) and 12 with activating loop mutations (ALMs). In addition, 8 of 19 specimens from patients with relapses had FLT3-MUs. Predictive analysis of microarrays (PAM) identified genes that differentiated FLT3-ITD from FLT3-ALM and FLT3 wild-type (FLT3-WT) cases. Among the 42 specimens with FLT3-MUs, PAM identified 128 genes that correlated with clinical outcome. Event-free survival (EFS) in FLT3-MU patients with a favorable signature was 45% versus 5% for those with an unfavorable signature (P = .018). Among FLT3-MU specimens, high expression of the RUNX3 gene and low expression of the ATRX gene were associated with inferior outcome. The ratio of RUNX3 to ATRX expression was used to classify FLT3-MU cases into 3 EFS groups: 70%, 37%, and 0% for low, intermediate, and high ratios, respectively (P &lt; .0001). Thus, gene expression profiling identified AML patients with divergent prognoses within the FLT3-MU group, and the RUNX3 to ATRX expression ratio should be a useful prognostic indicator in these patients. (Blood. 2004;104:2646-2654)
Expression of BLyS and its receptors in B-cell non-Hodgkin lymphoma: correlation with disease activity and patient outcome
Authors: Novak Anne J. , Grote Deanna M. , Stenson Mary , Ziesmer Steven C. , Witzig Thomas E. , Habermann Thomas M. , Harder Brandon , Ristow Kay M. , Bram Richard J. , Jelinek Diane F. , Gross Jane A. , Ansell Stephen M. 
Published: July 2004

Abstract
BLyS, recently shown to be critical for survival of normal B cells, has been found to be elevated in a number of immune disease models. A role for BLyS in the survival of malignant B cells has also been revealed and we therefore sought to identify a role for BLyS and its receptors in non-Hodgkin lymphoma (NHL). We found that tumor cells from all NHL histologic subtypes expressed one or more of 3 known receptors (BCMA, TACI, and BAFF-R) for BLyS; however, the pattern of expression was variable. We provide evidence that BLyS is expressed in tumors from patients with NHL and that BLyS levels increase as tumors transform to a more aggressive phenotype. Additionally, we provide evidence that serum BLyS levels are elevated in a subgroup of patients with NHL. In patients with de novo large B-cell lymphoma, a high BLyS level correlated with a poorer median overall survival, the presence of constitutional symptoms, and elevated values of lactic dehydrogenase. When BLyS levels were correlated with response to therapy in all patients, responding patients had a significantly lower BLyS level than those with progressive disease. In summary, we found that BLyS and its receptors represent a potentially important therapeutic target in B-cell lymphoma.
Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump
Authors: Burger Herman , van Tol Hans , Boersma Antonius W. M. , Brok Mariël , Wiemer Erik A. C. , Stoter Gerrit , Nooter Kees 
Published: July 2004

Abstract
Imatinib mesylate (STI571), a potent tyrosine kinase inhibitor, is successfully used in the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors. However, the intended chronic oral administration of imatinib may lead to development of cellular resistance and subsequent treatment failure. Indeed, several molecular mechanisms leading to imatinib resistance have already been reported, including overexpression of the MDR1/ABCB1 drug pump. We examined whether imatinib is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump that is frequently overexpressed in human tumors. Using a panel of well-defined BCRP-overexpressing cell lines, we provide the first evidence that imatinib is a substrate for BCRP, that it competes with mitoxantrone for drug export, and that BCRP-mediated efflux can be reversed by the fumitremorgin C analog Ko-143. Since BCRP is highly expressed in the gastrointestinal tract, BCRP might not only play a role in cellular resistance of tumor cells but also influence the gastrointestinal absorption of imatinib.
Improved outcome for children with acute lymphoblastic leukemia: results of Total Therapy Study XIIIB at St Jude Children's Research Hospital
Authors: Pui Ching-Hon , Sandlund John T. , Pei Deqing , Campana Dario , Rivera Gaston K. , Ribeiro Raul C. , Rubnitz Jeffrey E. , Razzouk Bassem I. , Howard Scott C. , Hudson Melissa M. , Cheng Cheng , Kun Larry E. , Raimondi Susana C. , Behm Frederick G. , Downing James R. , Relling Mary V. , Evans William E. 
Published: July 2004

Abstract
St Jude Total Therapy Study XIIIB for childhood acute lymphoblastic leukemia (ALL) incorporated more stringent risk classification, early intensification of intrathecal chemotherapy, reinduction treatment, and the addition of dexamethasone to postremission therapy to increase the proportion of event-free survivors without jeopardizing their quality of life. Cranial irradiation was reserved for the 12% of patients who had T-cell ALL and a presenting leukocyte count of 100 × 109/L or more, or CNS-3 (5 or more leukocytes/μL with identifiable blast cells in an atraumatic sample or the presence of cranial nerve palsy) status. Among the 247 consecutive patients enrolled in the study, 117 were classified as having lower-risk leukemia and received mainly antimetabolite-based continuation therapy; the 130 cases with higher-risk leukemia received more intensive continuation chemotherapy with multiple drug pairs administered in weekly rotation. The 5-year event-free survival estimate was 80.8% ± 2.6% (SE); the 8-year rate was 78.6% ± 5.8%. The 5-year cumulative risk of an isolated central nervous system (CNS) relapse was 1.7% ± 0.8%, and that of isolated plus combined CNS relapse was 3.0% ± 1.1%. The 5-year cumulative risks of etoposide-related myeloid malignancies were 1.8% ± 1.3% in the lower-risk patients who received a cumulative dose of 1.2 g/m2 and 5.0% ± 2.0% in the higher-risk patients who received a cumulative dose of up to 14.4 g/m2 (P = .18). Independent adverse prognostic features included the presence of MLL-AF4 or BCR-ABL fusion gene and minimal residual leukemia of 0.01% or more at the end of the 6-week remission induction phase. Our results suggest the efficacy of early intensification of intrathecal chemotherapy and provide the basis for studies omitting cranial irradiation altogether. (Blood. 2004;104:2690-2696)