bluuebunny/crossref_metadata_2025 huggingface dataset:
The Americanization of Australian Planning
Authors: Freestone Robert
Published: July 2004

A broad-brush survey of American influences on the development of Australian planning thought over the past century is presented. Set within a wider appreciation of the Americanization of Australian society, and drawing on cross-cultural urbanism and the international diffusion of planning ideas, the article chronologically explores a series of Australian encounters with American planning from the city beautiful era to the new urbanism. Parallels between American and Australian stories are clearly striking, but a major theme to emerge is the adaptation of American models to new spatial and social settings and the tensions embedded within these encounters. The borrowing process was not uncritical. Many interactions ended unhappily with planning ideology restlessly moving on to new panaceas.
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

A20 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

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

Fms-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 < .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

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

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

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)
Limits of HLA mismatching in unrelated hematopoietic cell transplantation
Authors: Petersdorf Effie W. , Anasetti Claudio , Martin Paul J. , Gooley Ted , Radich Jerald , Malkki Mari , Woolfrey Ann , Smith Anajane , Mickelson Eric , Hansen John A.
Published: July 2004

HLA matching between the donor and recipient improves the success of unrelated hematopoietic cell transplantation (HCT). Matched donors are available for only a minority of patients. Further information is needed to evaluate the limits of HLA mismatching. We examined the association of mortality with HLA-A, -B, -C, -DRB1, and -DQB1 mismatching in 948 patients who received a T-replete unrelated HCT for treatment of a marrow disorder. A single HLA allele or antigen mismatch was associated with increased mortality among patients with chronic myeloid leukemia (CML) within 2 years after diagnosis compared to patients with no HLA mismatch, but not among those with more advanced malignancy. In particular, a single HLA-C mismatch conferred increased risk of mortality compared to matches. There was a suggestion for increased mortality with multiple mismatches involving HLA-DQB1 compared to multiple mismatches not involving HLA-DQB1. Donors with a single HLA allele or antigen mismatch may be used for HCT when a fully matched donor is not available for patients with diseases that do not permit time for a lengthy search. Whenever possible, HLA-C mismatches should be avoided for patients with early stage CML, and HLA-DQB1 mismatches should be avoided for patients with multiple mismatches.
Anti-CD20 monoclonal antibody treatment in 6 patients with therapy-refractory chronic graft-versus-host disease
Authors: Canninga-van Dijk Marijke R. , van der Straaten Hanneke M. , Fijnheer Rob , Sanders Cornelus J. , van den Tweel Jan G. , Verdonck Leo F.
Published: July 2004

Chronic graft-versus-host disease (cGVHD) is an important determinant of long-term morbidity and mortality in allogeneic stem cell transplantation patients. Because cGVHD has clinical, histologic, and laboratory findings of autoimmune diseases and anti–B-cell therapy has shown efficacy in autoimmune diseases, we hypothesized that monoclonal anti-CD20 antibody therapy might improve patients with cGVHD. We treated 5 men and 1 woman with therapy-refractory extensive cGVHD with anti-CD20 monoclonal antibody. Intravenous infusion was given at a weekly dose of 375 mg/m2 for 4 weeks. In case of incomplete clinical response, additional courses of 4 weeks were given. Five patients responded to treatment with marked clinical, biochemical, and histologic improvement. One patient failed to respond. Anti-CD20 monoclonal antibody seems to be effective in cGVHD. A controlled trial is mandatory to confirm these results. The outcome of this study suggests a participating role of B cells in the pathogenesis of cGVHD.
Relevance Theory and the in second language acquisition
Authors: Žegarac Vlad
Published: July 2004

This article considers the implications of Sperber and Wilson’s (1986/95) Relevance Theory for the acquisition of English the by second language (L2) learners whose first language (L1) does not have an article system. On the one hand, Relevance Theory provides an explicit characterization of the semantics of the, which suggests ways of devising more accurate guidelines for teaching/learning than are available in current textbooks. On the other hand, Relevance Theoretic assumptions about human communication together with some effects of transfer from L1 provide the basis for a number of predictions about the types of L2 learners’ errors in the use of the.I argue that data from previous research (Trenkić, 2002) lend support to these predictions, and I try to show that examples drawn from the data I have collected provide evidence for the view that L2 learning is not influenced only by general pragmatic principles and hypotheses about L2 based on transfer from L1, but that learners also devise and test tacit hypotheses which are idiosyncratic to them.
Relevance mapping: a study of second language learners’ processing of syntactically ambiguous sentences in English
Authors: Ying H. G.
Published: July 2004

Forty adult Chinese-speaking learners of English and 20 native speakers of American English participated in a study of second language learners’ interpretation of syntactically ambiguous sentences involving that-clauses that could potentially be interpreted as complements or as relative clause. Two sentence interpretation tasks suggest that the principle of relevance constrained the interpretations. The learners showed a preference for interpreting the that-clause as a complement in the first task, using fewer syntactic nodes because it involved less processing effort. In the second task, however, the learners showed a preference for the relative clause reading, suggesting that the procedural information encoded by preceding referential sentences had the effect of reducing the overall processing effort required and of guiding the second language (L2) learners towards the intended contextual effects.
Interpretation of reflexive anaphora in second language VP-ellipsis: Relevance Theory and paradigms of explanation
Authors: Sequeiros Xosé Rosales
Published: July 2004

This article explores second language (L2) learners’ interpretation of reflexive anaphora in VP-Ellipsis by critiquing the work of Ying (2003), who applies Relevance Theory to explain elliptical anaphora. It argues against four claims made in his analysis: that L2 learners apply maximal relevance in anaphoric interpretation; that a procedural account of the impact of referential sentences on VP-ellipsis disambiguation is appropriate; that an account of anaphoric interpretation preferences should be based on processing cost; and that differences in experimental results between intermediate and advanced L2 learners are due to the use of different comprehension strategies (see Sperber, 1994). Instead, it argues: that it is not maximal but rather optimal relevance that is at work; that the key in disambiguating anaphora in VP-elliptical sentences is the achievement of an optimally relevant interpretation; that the role of contextual assumptions in anaphora resolution is to enable L2 learners to derive enough contextual effects to make it worth their effort and, in doing so, identifying (as a side effect) what they take to have been the intended referent; and that what is crucial in the use of comprehension strategies is not processing effort, but rather consistency with the second principle of relevance. Overall, all these factors provide the basis for an alternative and more comprehensive explanation of the experimental results discussed by Ying.
Exploring the relationships between theories of second language acquisition and Relevance Theory
Authors: de Paiva Beatriz Mariz Maia , Foster-Cohen Susan H.
Published: July 2004

This article explores a number of points at which Relevance Theory makes a useful contribution to second language theoretical models, specifically those of Bialystok and Schmidt and their respective notions of ‘analysis’, ‘control’ and ‘noticing’.It is suggested that the inferential mechanisms of Relevance Theory can account for the contingencies of communicative interaction without which pragmatic negotiations do not make sense, and thus can complement such information-processing accounts through the notions of ‘manifestness’ and the balance between ‘effort’ and ‘effect’.Further research is called for into the integration of information-processing concepts and Relevance Theoretical insights as part of a complex theoretical architecture capable of capturing the rich diversity of pragmatic development in second language acquisition.
Older people's views about home as a place of care at the end of life
Authors: Gott Merryn , Seymour Jane , Bellamy Gary , Clark David , Ahmedzai Sam
Published: July 2004

Objectives: To explore the attitudes of older people towards home as a place of care when dying. Design: A two-phase qualitative study using focus groups and semi-structured interviews. Participants: Eight focus group discussions were held with 32 participants recruited from six purposively selected community groups representing older people in Sheffield, UK. A further 16 men and 29 women participated in semi-structured interviews. Results: Participants identified that home was more than a physical location, representing familiarity, comfort and the presence of loved ones. While participants anticipated that home would be their ideal place of care during dying, practical and moral problems associated with it were recognised by many. Some had no informal carer. Others did not want to be a ‘burden’ to family and friends, or were worried about these witnessing their suffering. Those who had children did not wish them to deliver care that was unduly intimate. Concerns were expressed about the quality of care that could be delivered at home, particularly in relation to accommodating health technologies and providing adequate symptom relief. Worries were also expressed about those living in poor material circumstances. Mixed views were expressed about the presence of professional carers within the home. Although they were seen to provide much needed support for the informal carer, the presence of ‘strangers’ was regarded by some as intrusive and compromising the ideal of ‘home’. Discussion: Older people perceive factors they associate with ‘home’ as crucial to a good death, most notably presence of friends and family, but many anticipate that they would prefer to be cared for elsewhere when dying. These findings run counter to assumptions that the medicalised, institutional death cannot be a ‘good death’. It is important that dying in hospital is not demonized, but rather efforts made to examine how institutional deaths can take on a more meaningful quality.
Falls in hospices: a cancer network observational study of fall rates and risk factors
Authors: Pearse Hazel , Nicholson Lucy , Bennett Mike
Published: July 2004

Falls have been identified as a problem in frail patient populations, but their risk factors have not been studied prospectively in the hospice setting. We calculated fall rates in three hospices in the Yorkshire region, identified risk factors for falls based on previous studies in elderly patients, and then carried out a prospective study of inpatients in two of these hospices. We compared these risk factors in patients who subsequently fell with patients that did not fall during the study period. Information was recorded on 102 admissions. Twelve patients fell, generating 23 falls; six patients fell more than once. Significant risk factors for falling were cognitive impairment, low systolic lying and standing blood pressure, visual impairment and age over 80. Males with these risk factors fell more often than female patients with these risk factors. Strategies to prevent falls in hospice inpatients need to be directed appropriately towards patients with cognitive and visual impairment and low systolic blood pressure.
Research methodology: cancer cachexia syndrome
Authors: Dahele Max , Fearon Kch
Published: July 2004

Cachexia is a syndrome and therefore does not have a specific definition. Patients are characterized by the presence of anorexia, early satiety, weight loss, weakness, anaemia and oedema. These features occur to a variable extent in different patients and may change in severity during the course of a patient's illness. The multifactorial origin of cachexia precludes a uniform pathophysiological definition. Taken together these factors have hindered clinical studies both at a fundamental level and in terms of the introduction of effective therapy.

The advent of novel therapeutic targets (e.g., ubiquitin-proteasome pathway) and biological response modifiers has opened possibilities for new clinical trials in cachexia. Regulatory authorities feel it is important not only to demonstrate efficacy in terms of patients' nutritional status (e.g., lean body mass) but also functional status (e.g., performance status). This article reviews current methods to assess the latter. Methods focused on measuring physical activity level (e.g., doubly labelled water technique or physical activity meters) promise objective data which can be readily interpreted in terms of clinically meaningful benefit.
Dying and defibrillation: a shocking experience
Authors: Nambisan Vinod , Chao David
Published: July 2004

Palliative Care physicians are frequently involved in the care of patients with significant comorbidity and often have to take coexisting conditions into account when treating patients. An example of an area in which this is particularly relevant and will undoubtedly increase is presented with the case report of a patient with terminal metastatic lung carcinoma and an Implantable Cardioverter Defibrillator (ICD) in place. The role of the ICD in preventing the patient from dying comfortably is discussed, as are means of deactivating the device. We conclude that patients with ICDs and terminal disease should have the issue of deactivation addressed at the earliest possible opportunity as practical difficulties may arise in the emergency setting, especially in the nonhospital environment.
The UNESCO Biosphere Reserve Concept as a Tool for Urban Sustainability: The CUBES Cape Town Case Study
Authors: STANVLIET R , JACKSON J , DAVIS G , DE SWARDT C , MOKHOELE J , THOM Q , LANE B D
Published: July 2004

Abstract: The Cape Town Case Study (CTCS) was a multi‐institutional collaborative project initiated by CUBES, a knowledge networking initiative of UNESCO's Ecological Sciences Division and the Earth Institute at Columbia University. Cape Town was selected as a CUBES site on the basis of its high biological and cultural significance, together with its demonstrated leadership in promoting urban sustainability. The CTCS was conducted by the Cape Town Urban Biosphere Group, a cross‐disciplinary group of specialists drawn from national, provincial, municipal, and civil society institutions, mandated to examine the potential value of the UNESCO Biosphere Reserve concept as a tool for environmental management, social inclusion, and poverty alleviation in Cape Town. This article provides a contextualization of the CTCS and its collaborative process. It also reviews the biosphere reserve concept relative to urban sustainability objectives and proposes a more functional application of that concept in an urban context. A detailed analysis of key initiatives at the interface of conservation and poverty alleviation is provided in table format. Drawing on an examination of successful sustainability initiatives in Cape Town, specific recommendations are made for future application of the biosphere reserve concept in an urban context, as well as a model by which urban areas might affiliate with the UNESCO World Network of Biosphere Reserves, and criteria for such affiliation.
Improving Air Quality in Megacities: Mexico City Case Study
Authors: MOLINA LUISA T. , MOLINA MARIO J.
Published: July 2004

Abstract: The development and effective implementation of solutions to the air pollution problems in the Mexico City Metropolitan Area is essential to guarantee the health and welfare of its inhabitants. To achieve this, it is essential to have the active and informed participation of the civil society, the academic community, the private sector, and the government, because dealing with pollution requires the use of different strategies in multiple fields of action. The Mexico City case study brings together health, transportation, administration, and many other interdisciplinary approaches to understanding and defeating air pollution. Although focused on the Mexico City area, the work conducted under this case study has significance for developing nations generally. Although policies to reduce air pollution should be based on the best available scientific knowledge, political will and capacity must transform this knowledge into action. This case study has developed a series of recommendations emphasizing the interaction between different disciplines that have provided the foundation for the 10‐year air quality management program prepared by the Mexican Metropolitan Environmental Commission.
Health in the Urban Environment: Experience from Dar es Salaam/Tanzania
Authors: LORENZ NICOLAUS , MTASIWA DEO
Published: July 2004

Abstract: Dar es Salaam is a typical example of the rapid urbanization process in sub‐Saharan Africa. Health problems in the city are tremendous and reflect the epidemiologic transition, with the emergence of chronic diseases, as well as the prevailing problems related to infectious diseases. Not surprisingly, HIV/AIDS has become a major determinant of health. Public health services have been strengthened in the past 12 years through the support of a bilateral program called the Dar es Salaam Urban Health Project (DUHP). The program was jointly funded by the Government of Tanzania and the Swiss Agency for Development and Cooperation. The focus of the program shifted from the initial rehabilitation of the health infrastructure to a strengthening of the management capacities of the public health care delivery system. The basis for the collaboration and complementarity between public and private health care providers has been created. Partly thanks to the success of the DUHP, the health system has become the spearhead and testing ground for core health sector reforms and has had a substantial influence on the introduction of a donor‐supported sectorwide approach in the health sector in Tanzania. Perhaps most importantly, the foundations have been laid for a more democratic health system in which both the staff and the population are involved.
The Application of the Biosphere Reserve Concept to Urban Areas: The Case of Green Rooftops for Habitat Network in Seoul
Authors: KIM KWI‐GON
Published: July 2004

Abstract: This article consists of two parts. The first shows how the principles of the ecosystem approach can be applied to green rooftops, and the second attempts to illustrate it through a case study. In particular, it suggests new approaches and techniques for creation of green rooftops in a perspective of urban habitat network and urban biosphere reserve. To endow urban rooftops with the roles and functions of urban habitat network and urban biosphere reserve, it is necessary to apply “an ecosystem approach to urban management.” In this article, an ecosystem approach to urban management is illustrated with Seoul as an example. The Habitat Network in Seoul will be reviewed with a focus on the model suggested by MAB Urban Group. Then, the roles and functions of Myeongdong UNESCO Green Rooftop and its possible contribution to building the Seoul Urban Biosphere Network will be described. The UNESCO Green Rooftop is 628 m2 and was created on the 12th floor rooftop of UNESCO Building in Myeongdong 2‐ga, Jung‐ku, Seoul. In the green rooftop, which was created with goals of securing green areas and biotopes in downtown, creating an urban econetwork, securing a base for urban ecosystem study and environment education, and disseminating an idea of coexistence between nature and humankind, wetland, meadow, scrub and woodland, wall revegetation, and a vegetable field are created. Also, rainwater recycling facilities and a solar energy water circulation system were set up. Rest facilities including observation and education facilities were built. Based on the Seoul example, as well as urban biosphere reserve models suggested by the MAB Urban Group, we suggest several principles to be applied for a green rooftops to qualify as a category of urban biosphere reserves.
Application of the Biosphere Reserve Concept to Urban Areas: The Case of São Paulo City Green Belt Biosphere Reserve, Brazil—São Paulo Forest Institute: A Case Study for UNESCO
Authors: MORAES VICTOR RODRIGO ANTONIO BRAGA , COSTA NETO JOAQUIM DE BRITTO , NACIB AB'SÁBER AZIZ , SERRANO ONDALVA , DOMINGOS MARISA , PIRES BELY CLEMENTE CAMACHO , AMAZONAS MAURICIO , MORAES VICTOR MAURO ANTONIO
Published: July 2004

Abstract: This report attempts to bring together contributions from technicians and scientists studying and dealing with the manifold aspects of the São Paulo City Green Belt Biosphere Reserve. It will highlight the understanding by UNESCO of the important role that biosphere reserves can play in the urban setting.
Written in Stone: Memory and Reconciliation Intersecting the Urban Biosphere
Authors: KOHEN MARTHA
Published: July 2004

Abstract: The article describes the process of planning the Memorial of Disappeared Detained Citizens in the City of Montevideo, Uruguay, the construction of which was completed in January 2003. It explores the role that memory, planning, and reconciliation carried out in the public realm can play in the context of an urban environment. It describes the procedures and involvement of different social agents in the achievement of a significant landmark where social healing is promoted in parallel to the materialization of the construction of the Memorial, the necessary interaction between the natural and the human dimensions, and how these relate to the city as a biosphere.
Sustainability, Survivability, and the Paradox of New Orleans
Authors: CAMPANELLA RICHARD , ETHERIDGE DANIEL , MEFFERT DOUGLAS J.
Published: July 2004

Abstract: Some precepts of the urban sustainability movement derive from the premise that economic expansion, population growth, and physical sprawl lead to a decline in quality of life, ecological damage, and eventual unsustainability. But what about cities that are failing—losing population, losing investment, losing infrastructure, even losing land? This article challenges conventional sustainability concepts, usually derived from the experiences of ascending cities, with the notion of survivability that confronts declining cities. Should troubled cities, such as New Orleans, located on the eroding Gulf of Mexico coastal region of the state of Louisiana, be held to different sustainability standards? Could urban expansion, in some cases, actually stem environmental degradation and enhance survivability?
The Biology and Clinical Relevance of the PTEN Tumor Suppressor Pathway
Authors: Sansal Isabelle , Sellers William R.
Published: July 2004

Genetic alterations targeting the PTEN tumor suppressor gene are among the most frequently noted somatic mutations in human cancers. Such lesions have been noted in cancers of the prostate and endometrium and in glioblastoma multiforme, among many others. Moreover, germline mutation of PTEN leads to the development of the related hereditary cancer predisposition syndromes, Cowden disease, and Bannayan-Zonana syndrome, wherein breast and thyroid cancer incidence is elevated. The protein product, PTEN, is a lipid phosphatase, the enzymatic activity of which primarily serves to remove phosphate groups from key intracellular phosphoinositide signaling molecules. This activity normally serves to restrict growth and survival signals by limiting activity of the phosphoinositide-3 kinase (PI3K) pathway. Multiple lines of evidence support the notion that this function is critical to the ability of PTEN to maintain cell homeostasis. Indeed, the absence of functional PTEN in cancer cells leads to constitutive activation of downstream components of the PI3K pathway including the Akt and mTOR kinases. In model organisms, inactivation of these kinases can reverse the effects of PTEN loss. These data raise the possibility that drugs targeting these kinases, or PI3K itself, might have significant therapeutic activity in PTEN-null cancers. Akt kinase inhibitors are still in development; however, as a first test of this hypothesis, phase I and phase II trials of inhibitors of mTOR, namely, rapamycin and rapamycin analogs are underway.
Post-Treatment Change in Serum Estrone Predicts Mammographic Percent Density Changes in Women Who Received Combination Estrogen and Progestin in the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial
Authors: Ursin Giske , Palla Shana L. , Reboussin Beth A. , Slone Stacey , Wasilauskas Carol , Pike Malcolm C. , Greendale Gail A.
Published: July 2004

Purpose

Postmenopausal estrogen and progestin therapy (EPT) increases mammographic percent density and breast cancer risk substantially more than does estrogen therapy alone. We determined whether increases in serum estrone as a function of treatment predict increases in mammographic percent density.

Methods

We measured mammographic percent density and serum estrone levels in participants in the Postmenopausal Estrogen/Progestin Interventions Trial who were randomly assigned to receive conjugated equine estrogens (CEE) 0.625 mg/d; CEE and medroxyprogesterone acetate (MPA) 10 mg on days 1 to 12 per 28-day cycle; CEE and MPA 2.5 mg/d; or CEE and micronized progesterone (MP) 200 mg on days 1 to 12 per 28-day cycle. We used linear regression to determine whether serum estrone changes predicted mammographic percent density changes from baseline to 1 year.

Results

Mammographic percent density increased with increasing change in estrone level in the EPT groups, but not in the CEE group. Combined, the mammographic percent density in the three EPT groups demonstrated an absolute increase of 2.95% per 100 pg/mL increase in serum estrone level (P = .0003). The absolute increases were 4.09% (P = .0018) in the CEE + MPA continuous group, 2.79% (P = .0292) in the CEE + MPA cyclical group, and 1.40% (P = .36) in the CEE + MP group, but the differences among the EPT groups were not statistically significant.

Conclusion

Greater increase in serum estrone level as a function of treatment is a significant predictor of increase in mammographic percent density in women randomly assigned to the combination of estrogen and progestin.
Gene Expression Alterations in Prostate Cancer Predicting Tumor Aggression and Preceding Development of Malignancy
Authors: Yu Yan Ping , Landsittel Douglas , Jing Ling , Nelson Joel , Ren Baoguo , Liu Lijun , McDonald Courtney , Thomas Ryan , Dhir Rajiv , Finkelstein Sydney , Michalopoulos George , Becich Michael , Luo Jian-Hua
Published: July 2004

Purpose

The incidence of prostate cancer is frequent, occurring in almost one-third of men older than 45 years. Only a fraction of the cases reach the stages displaying clinical significance. Despite the advances in our understanding of prostate carcinogenesis and disease progression, our knowledge of this disease is still fragmented. Identification of the genes and patterns of gene expression will provide a more cohesive picture of prostate cancer biology.

Patients and Methods

In this study, we performed a comprehensive gene expression analysis on 152 human samples including prostate cancer tissues, prostate tissues adjacent to tumor, and organ donor prostate tissues, obtained from men of various ages, using the Affymetrix (Santa Clara, CA) U95a, U95b, and U95c chip sets (37,777 genes and expression sequence tags).

Results

Our results confirm an alteration of gene expression in prostate cancer when comparing with nontumor adjacent prostate tissues. However, our study also indicates that the gene expression pattern in tissues adjacent to cancer is so substantially altered that it resembles a cancer field effect.

Conclusion

We also found that gene expression patterns can be used to predict the aggressiveness of prostate cancer using a novel model.
Central Nervous System Atypical Teratoid/Rhabdoid Tumor: Results of Therapy in Children Enrolled in a Registry
Authors: Hilden Joanne M. , Meerbaum Sharon , Burger Peter , Finlay Jonathan , Janss Anna , Scheithauer Bernd W. , Walter Andrew W. , Rorke Lucy B. , Biegel Jaclyn A.
Published: July 2004

Purpose

Atypical teratoid/rhabdoid tumor (AT/RT) of the CNS is an extremely rare and aggressive tumor of early childhood. The poor outcome with conventional infant brain tumor therapy has resulted in a lack of clear treatment guidelines. A registry has been established to create an outcomes database and to facilitate biology studies for this tumor.

Materials and Methods

A standardized data sheet was provided to treating physicians listing the reports that were to be sent to the registry for abstraction. Follow-up information was sought twice yearly.

Results

Information was complete for 42 patients. Median age at diagnosis was 24 months. Nine patients (21%) had disseminated disease at diagnosis. Sixteen tumors were infratentorial; 26 were supratentorial. Twenty patients (48%) received a primary complete resection. Primary therapy included chemotherapy in all patients, radiotherapy in 13 patients (31%), stem-cell rescue in 13 patients (31%), and intrathecal chemotherapy in 16 patients (38%). Recurrent or progressive disease was reported in nine and 19 patients, respectively. Twenty-seven patients (64%) are dead of disease (3 to 62 months from diagnosis) and one patient died of toxicity. Fourteen patients (33%) show no evidence of disease (9.5 to 96 months from diagnosis). The median survival is 16.75 months and the median event-free survival is 10 months.

Conclusion

Aggressive therapy has prolonged the natural history in a subset of children. Prospective multi-institutional and national clinical trials designed specifically for AT/RT are needed. Enrollment onto the AT/RT registry should be continued.
Outcome of Allogeneic Hematopoietic Stem-Cell Transplantation in Adult Patients With Acute Lymphoblastic Leukemia: No Difference in Related Compared With Unrelated Transplant in First Complete Remission
Authors: Kiehl Michael G. , Kraut Ludwig , Schwerdtfeger Rainer , Hertenstein Bernd , Remberger Mats , Kroeger Nicolaus , Stelljes Mathias , Bornhaeuser Martin , Martin Hans , Scheid Christoph , Ganser Arnold , Zander Axel R. , Kienast Joachim , Ehninger Gerhard , Hoelzer Dieter , Diehl Volker , Fauser Axel A. , Ringden Olle
Published: July 2004

Purpose

The role of unrelated allogeneic stem-cell transplantation in acute lymphoblastic leukemia (ALL) patients is still not clear, and only limited data are available from the literature. We analyzed factors affecting clinical outcome of ALL patients receiving a related or unrelated stem-cell graft from matched donors.

Patients and Methods

The total study population was 264 adult patients receiving a myeloablative allogeneic stem-cell transplant for ALL at nine bone marrow transplantation centers between 1990 and 2002. Of these, 221 patients receiving a matched related or unrelated graft were analyzed. One hundred forty-eight patients received transplantation in complete remission; 62 patients were in relapse; and 11 patients were refractory to chemotherapy before transplant. Fifty percent of patients received bone marrow, and 50% received peripheral blood stem cell from a human leukocyte antigen–identical related (n = 103), or matched unrelated (n = 118) donor.

Results

Disease-free survival (DFS) at 5 years was 28%, with 76 patients (34%) still alive (2.2 to 103 months post-transplantation), and 145 deceased (65 relapses, transplant-related mortality, 45%). We observed an advantage regarding DFS in favor of patients receiving transplantation during their first complete remission (CR) in comparison with patients receiving transplantation in or after second CR (P = .014) or who relapsed (P < .001). We observed a clear trend toward improved survival in favor of B-lineage ALL patients compared with T-lineage ALL patients (P = .052), and Philadelphia chromosome–positive patients had no poorer outcome than Philadelphia chromosome–negative patients. Total-body irradiation–based conditioning improved DFS in comparison with busulfan (P = .041).

Conclusion

Myeloablative matched related or matched unrelated allogeneic hematopoietic stem-cell transplantation in ALL patients should be performed in first CR.
Gabapentin for Neuropathic Cancer Pain: A Randomized Controlled Trial From the Gabapentin Cancer Pain Study Group
Authors: Caraceni Augusto , Zecca Ernesto , Bonezzi Cesare , Arcuri Edoardo , Tur Ricardo Yaya , Maltoni Marco , Visentin Marco , Gorni Giovanna , Martini Cinzia , Tirelli Walter , Barbieri Massimo , De Conno Franco
Published: July 2004

Purpose

To determine the analgesic effect of the addition of gabapentin to opioids in the management of neuropathic cancer pain.

Patients and Methods

One hundred twenty-one consecutive patients with neuropathic pain due to cancer, partially controlled with systemic opioids, participated in a multicenter, randomized, double-blind, placebo-controlled, parallel-design, 10-day trial from August 1999 to May 2002. Gabapentin was titrated from 600 mg/d to 1,800 mg/d in addition to stable opioid dose. Extra opioid doses were available as needed. Zero to 10 numerical scale was used to rate average daily pain. The average pain score over the whole follow-up period was used as main outcome measure. Secondary outcome measures were: intensity of burning pain, shooting/lancinating pain, dysesthesias (also scored on 0 to 10 numerical scale), number of daily episodes of lancinating pain, presence of allodynia, and daily extra doses of opiod analgesics.

Results

Overall, 79 patients received gabapentin and 58 (73%) completed the study; 41 patients received placebo and 31 (76%) completed the study. Analysis of covariance (ANCOVA) on the intent-to-treat population showed a significant difference of average pain intensity between gabapentin (pain score, 4.6) and placebo group (pain score, 5.4; P = .0250). Among secondary outcome measures, dysesthesia score showed a statistically significant difference (P = .0077; ANCOVA on modified intent-to-treat population = 115 patients with at least 3 days of pain assessments). Reasons for withdrawing patients from the trial were adverse events in six patients (7.6%) receiving gabapentin and in three patients receiving placebo (7.3%).

Conclusion

Gabapentin is effective in improving analgesia in patients with neuropathic cancer pain already treated with opioids.
Clinical and Immunologic Effects of Subcutaneously Administered Interleukin-12 and Interferon Alfa-2b: Phase I Trial of Patients With Metastatic Renal Cell Carcinoma or Malignant Melanoma
Authors: Alatrash Gheath , Hutson Thomas E. , Molto Luis , Richmond Amy , Nemec Cheryl , Mekhail Tarek , Elson Paul , Tannenbaum Charles , Olencki Thomas , Finke James , Bukowski Ronald M.
Published: July 2004

Purpose

Interleukin-12 (IL-12) and interferon alfa-2b (IFN-α-2b) are pleiotropic cytokines with activity in renal cell carcinoma (RCC) and malignant melanoma (MM) as single agents. Preclinical studies suggest concurrent administration may have synergistic antitumor effects. We conducted a phase I trial of concurrent subcutaneous (SC) administration of IL-12 and IFN-α-2b in patients with metastatic RCC or MM to determine toxicity, maximum-tolerated dose, preliminary efficacy, and effects on chemokine/cytokine gene expression in peripheral blood mononuclear cells (PBMCs).

Patients and Methods

Cohorts of three to six patients were treated with escalating doses of IL-12 (dose I, 100 ng/kg; dose II, 300 ng/kg; dose III, 500 ng/kg; dose IV, 500 ng/kg SC) given twice weekly and IFN-α-2b (dose I, 1.0 MU/m2; dose II, 1.0 MU/m2; dose III, 1.0 MU/m2; dose IV, 3.0 MU/m2SC) three times weekly in 4-week cycles. Effects on gene expression were assessed by reverse transcriptase polymerase chain reaction.

Results

Twenty-six patients (19 with RCC, seven with MM) were accrued at dose levels I (n = 3), II (n = 3), III (n = 13), and IV (n = 7). Dose-limiting toxicity included grades 3 and 4 hepatotoxicity and neutropenia/leukopenia. Patients received a median of three cycles of treatment. Two patients with RCC and one patient with MM had partial responses. Median survival was 13.8 months. Reverse transcriptase polymerase chain reaction on PBMCs revealed induction of IP-10, Mig, B7.1 (CD80), interleukin-5, and interferon gamma in selected patients.

Conclusion

Concurrent SC administration of IL-12 and IFN-α-2b is possible at the dose levels utilized. Recommended doses for phase II trials are 500 ng/kg IL-12 and 1.0 MU/m2IFN-α-2b. Consistent induction of IP-10 and Mig, as well as variable induction of B7.1, interleukin-5, and interferon gamma expression was noted in PBMCs.