bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Study
Authors: Lance Charles E. , Woehr David J. , Meade Adam W.
Published: June 2007

Three major reviews of the assessment center (AC) construct-validity literature have disagreed as to the most appropriate analytic model for AC postexercise dimension ratings. We report a Monte Carlo study addressing the following questions: (a) To what extent does the “true” model (i.e., the model that generated the data) actually appear to fit the data well? (b) To what extent can a model appear to fit the data well even though it is the wrong model? and (c) Is model fit actually a useful empirical criterion for judging which model is most likely the population model? Results suggest that “true” models may not always appear as the best fitting models, whereas “false” models sometimes appear to offer better fit than the true models. Implications for the study of AC construct validity are discussed.
Controlling Nuisance Variables by Using a Matched-Groups Design
Authors: Breaugh James A. , Arnold Jessalyn
Published: June 2007

In this article, the authors provide an introduction to the use of a matched-groups design as a strategy for controlling nuisance variables. Building on the insightful comments of Campbell and Kenny and of Meehl, the authors utilized Monte Carlo simulations to highlight three major limitations of this control strategy (i.e., regression toward different means, systematic unmatching, and the generalizability of results) that they believe have received insufficient attention by researchers. Particular attention is given to how the effect of regression toward different means can result in researchers' drawing erroneous conclusions from their data. Recommendations for researchers considering the use of a matched-groups design are provided.
Contextualizing Methods Choice in Organizational Research
Authors: Buchanan David A. , Bryman Alan
Published: June 2007

The field of organizational research displays three trends: widening boundaries, a multiparadigmatic profile, and methodological inventiveness. Choice of research methods, shaped by aims, epistemological concerns, and norms of practice, is thus also influenced by organizational, historical, political, ethical, evidential, and personal factors, typically treated as problems to be overcome. This article argues that those factors constitute a system of inevitable influences and that this contextualization of methods choice has three implications. First, it is difficult to argue that methods choice depends exclusively on links to research aims; choice involves a more complex, interdependent set of considerations. Second, it is difficult to view method as merely a technique for snapping reality into focus; choices of method frame the data windows through which phenomena are observed, influencing interpretative schemas and theoretical development. Third, research competence thus involves addressing coherently the organizational, historical, political, ethical, evidential, and personal factors relevant to an investigation.
Deconstructing Scholarship
Authors: Partington David , Jenkins Mark
Published: June 2007

Understanding the variety of different ways in which citations contribute to scholarly writing is an important part of the tacit knowledge possessed by experienced researchers. There is, however, little published work to help novice researchers develop this aspect of their craft. To address this issue, we present a framework of citation usage derived from inductive analysis of a selection of published articles and emphasize its relevance for research methods topics. This framework provides a template for structuring citation usage in academic research and a useful developmental tool for novice researchers.
On Measuring Individual Knowledge in Organizations
Authors: Borgatti Stephen P. , Carboni Inga
Published: June 2007

How can knowledge held by individuals and groups be accurately measured when the a priori ``right'' answers are unknown? This article presents a promising new approach, based on anthropological consensus theory, to solving this common research problem. Using a unique data set, we compare the consensus approach with more traditional approaches (e.g., standardized testing). The results suggest that a consensus-based method may be a highly accurate way to estimate knowledge levels in a number of settings.
A New Winning Formula?
Authors: de Lange Sarah L.
Published: June 2007

In an updated version of his well-known work on the radical right, Kitschelt attributes the persistent success of this type of party to a new winning formula. Where the radical right first campaigned on a neo-liberal and authoritarian programme, it now presents a more centrist economic position. The article tests this idea through a reconstruction of the positions of the French Front National, the Flemish Vlaams Blok and the Dutch Lijst Pim Fortuyn, and establishes that some, but not all, radical right parties make use of the new winning formula. Moreover, innovative analysis of the positions of radical right parties in West European party systems reveals that Kitschelt's theory needs to be improved on several points, most notably when it comes to the definition of concepts and the operationalization of dimensions.
Candidates or Parties?
Authors: Marsh Michael
Published: June 2007

Under many electoral systems, voters can choose between candidates, and, under some systems, between candidates of the same party — a situation that makes it possible for candidates to seek a personal vote. Studies of some countries have shown how personal voting is apparent in the success of particular types of candidates, notably incumbents, but there is little systematic study of personal motives among the electors themselves. The single transferable vote system (STV) used in Ireland certainly allows electors to choose between candidates as well as parties and therefore is seen as providing a strong incentive for candidates to seek personal votes. While aggregate evidence from election results has pointed to the primary importance of party, survey data have suggested that close to a majority of voters are primarily candidate-centred. In this article, an extensive set of instruments contained in the 2002 Irish election study is used to explore the extent to which voters decide on candidate-centred factors as opposed to party-centred factors. It is shown that a substantial minority decide on the basis of candidate factors, and typical models of Irish electoral behaviour have not accommodated the heterogeneity that results from this mix of motives. However, direct questions about motives probably underestimate the extent of party-centred voting.
Legislation On Political Parties
Authors: Karvonen Lauri
Published: June 2007

This is a comprehensive study of the special legislation on political parties around the world. In a survey conducted in late 2003, 39 party laws (PLs) identified among the world's states were subjected to a systematic content analysis which confirmed the hypothesis that PLs regulate political parties differently depending on the democratic status of the respective countries. In non-democratic states, regimes tend to use PLs to restrict the freedom of their opponents, while in newly democratized states, democratic regimes use the law to counteract lingering anti-democratic tendencies. In some stable democracies, the PL is primarily a prerequisite for regulation of public party subsidies and political finance. The article concludes with some reflections on PLs in established democratic states.
The Comparative Politics of Communist Euroscepticism in France, Italy and Spain
Authors: Benedetto Giacomo , Quaglia Lucia
Published: June 2007

In this work, we compare the Euroscepticism of three West European parties from the same party family: the Communists. We address the questions of how the parties of France, Italy and Spain have adapted to the process of European integration and also the factors that have affected their different responses over time. The French and Italian parties have moved away from Euroscepticism to softer or even pro-integration approaches, whereas the Spanish Communists (PCE) have never been Eurosceptic. Party response to Europe is affected by international, national and party-specific factors, which have different degrees of explanatory power. During the early decades of European integration, international factors, first and foremost the relationship with Moscow, contributed to the Euroscepticism of Western Communists. Nevertheless, as with other party families and types, the Communists have responded to vote- and coalition-seeking opportunities.
Psychotherapy and the Cultural Concept of the Person
Authors: Kirmayer Laurence J.
Published: June 2007

Psychotherapies are distinguished from other forms of symbolic healing by their emphasis on explicit talk about the self. Every system of psychotherapy thus depends on implicit models of the self, which in turn, are based on cultural concepts of the person. The cultural concept of the person that underwrites most forms of psychotherapy is based on Euro-American values of individualism. This individualistic and egocentric concept of the person can be contrasted with more sociocentric, ecocentric or cosmocentric views, which understand the person in relation to the social world, the environment, and the cosmos. Intercultural psychotherapy must consider the cultural concept of the person implicit in therapeutic discourse and practice to determine how well it fits or conflicts with the concepts, values and way of life of the patient.
A Cross-National Study of the Stigmatization of Severe Psychiatric Illness: Historical Review, Methodological Considerations and Development of the Questionnaire
Authors: Littlewood Roland , Jadhav Sushrut , Ryder Andrew G.
Published: June 2007

Despite their potential significance for public policy and health provision in different societies, popular conceptualizations of and social responses to severe psychiatric illness remain relatively unexamined. Two general research procedures may be identified: (1) the anthropological approach uses ethnographic methods to look at explicit categorizations, and (2) the sociological approach employs quantitative survey methods to examine the public `stigma' of psychiatric illness. This article reviews methodological and conceptual approaches to the study of stigma and describes the development of an ethnographically grounded questionnaire to examine `stigmatization' from data in different cultures. The difficulties of achieving cross-cultural comparability of meaning are discussed and the psychometric properties of the instrument are presented.
`The Moment I Became Born-again the Pain Disappeared': The Healing of Devastating War Memories in Born-again Churches in Mbarara District, Southwest Uganda
Authors: Tankink Marian
Published: June 2007

In southwest Uganda, many people who suffer from devastating war experiences become born-again Christians. This article describes the therapeutic functions of the churches and the experiential transformations associated with becoming born-again. The discourse of the born-again churches gives people another orientation toward the future, based on the Bible, that also provides them with a different perception of the past. Whereas people remain silent about their war experiences in everday life, the churches offer their members a public space to express their suffering. In these churches, feelings of trust and solidarity are restored. Many aspects of the churches' activities can also be found in western trauma therapies.
Finding Help: Turkish-speaking Refugees and Migrants with a History of Psychosis
Authors: Leavey Gerard , Guvenir Taner , Haase-Casanovas Silvia , Dein Simon
Published: June 2007

There is a large population of Turkish-speaking migrants living in London, many of whom are refugees (Enneli , Modood, & Bradley, 2005). Primary care and secondary mental health services have consistently reported poor continuity of care among patients from this community. The aim of this study was to explore the possible interconnection of causal attributions and pathways into care among Turkish-speaking, mainly Kurdish, patients with a past history of psychosis. Narratives of illness were elicited from informants. Physical symptomatology was a prominent feature of presentation in this group. These patients did not discuss their health problems conceptualized as uniform `models' of illness, but rather in an attributional style that emphasized the experience of traumatic life events, often related to the overarching problem of exile and settlement. Childhood and family issues of poverty and domestic violence were often raised by patients, but tended to be backgrounded as having little contributory significance. These patients sought intervention, serially or in combination, from a diverse range of practitioners, including private healthcare and traditional healers or hocas. Their explanatory models of illness were complex and fragmentary and the relationship between explanations and help seeking is seldom linear. The implications of these findings for health services are discussed.
A Reconstruction of the Ethos of Science
Authors: Kalleberg Ragnvald
Published: June 2007

Merton's early analysis of the ethos of science has gained increased relevance because recent developments — such as commercialization of research — have undermined basic norms, like impartiality. It is desirable to uphold the institutional realism in Merton's sociology of science in order to grasp contemporary challenges. But central elements in his analytical approach have also to be revised or rejected, especially his nomological conception of explanations, non-cognitivism in normative issues, and failure adequately to conceptualize Homo sociologicus as a reasoner. Reasoners present and discuss cognitive claims, related both to descriptive and normative validity. Merton's analysis of an ethos of science should be evaluated as a reconstructive type of empirical analysis where the goal is insight and adequate identification of phenomena. Several critics denying the existence of Mertonian norms tacitly presuppose the validity of the norms, thereby entangling themselves in self-defeating contradictions. As an unintended consequence, these critics confirm the existence of a fundamental ethos of science.
Merton's `Norms' in Political and Intellectual Context
Authors: Turner Stephen
Published: June 2007

Merton's two papers on the norms of science were written in a period of intense political activity in science, and responded to this context, using conceptual tools from classical sociology and Harvard thinking of the time. The basic reasoning was Weberian: science and politics each had a different ethos. One target was the Left view of science as a model for society. Another was the view of the American Left that complex societies required regulation, but that science should be free of control. Merton pictured science as already intensely policed, but threatened by the conflict between its special ethos and potential democratic demands, and requiring protection. This was a `liberal' argument, but Merton used the language of the Left to present it.
Catching up with Robert Merton
Authors: Barnes Barry
Published: June 2007

Sociologists of science today take it for granted that science is a collective activity in a profound sense, and it was above all Robert Merton who established this at a time when a misconceived individualistic perspective was generally used to address it. Current work on science, whether as institution, normative order, moral community, sub-culture, set of peers or status group, is indebted to Merton's account of the norms of science, or else to his analysis of the system of honorific reward through which the norms are sustained. This paper concentrates on the second topic. How is normative order sustained in the sciences? It will reinforce Merton's original insight that no explanation of this is possible in terms of individual calculative action; show how Merton's alternative sociological approach can be linked to traditional sociological thought and particularly to Weber's account of status groups; and show also how more recent sociological work relates to Merton's now that his work has become a recognized resource in that same tradition.
Some Historical Roots of the Ethos of Science
Authors: Huff Toby E.
Published: June 2007

This comparative and historical examination of the ethos of science finds significant examples of the Mertonian ethos in university discussions from the 12th through the 14th century. The institutionalization of naturalistic inquiry based on Aristotelian modes of argument and demonstration was unique to Western Europe and did not occur in China or the Islamic Middle East. Nevertheless, Merton's writings on the ethos show no indication of his relying upon the rich historical evidence of Europe when formulating his famous conception.
Making public education popular
Authors: Arben Fox Russell
Published: June 2007

Michael J. Apple$quoteright$s book constitutes, among many other things, an ambitious rethinking of what will be necessary to make the ideal of egalitarian public schooling more appealing to those parents who have, in recent years, found their beliefs and criticisms most readily responded to by various `conservative modernizers' and other enemies of public education. Rather than treating all those who make attacks on public schooling in the same way, Apple proposes that educators develop ways to alter the structure of public schools so as to draw in the support of at least some of their critics, particularly those whose criticisms arise from concerns about the perceived opposition between public schooling and religious and parental authority. The question then becomes how to accommodate such charter and community schools within the public education ideal.
The `right' education in Europe: When the obvious is not so obvious!
Authors: Novoa Antonio
Published: June 2007

In this article I begin by addressing three ways of thinking that are deeply influencing educational policies, not only at the European Union level, but also inside each Member State. Then, I move into a more detailed explanation of these influences, raising three main arguments: (i) employability as a problem for each citizen; (ii) comparability as a new mode of governance; (iii) mobility as a means to imagine European citizenship.The whole text is built around the new programme, Education & Training 20I0, which constitutes a kind of $space$quoteleftumbrella' for the political intervention of the European Union in the field of education.
Reading Michael Apple — the sociological imagination at work
Authors: Ball Stephen J.
Published: June 2007

This article discusses Michael Apple's contribution to the sociology of education and education policy analysis and the politics of education. It focuses on ways of `reading' Apple as an intellectual and an activist and looks at the trajectory of his work over a long and illustrious career.
Multiculturalism and rationality
Authors: Siegel Harvey
Published: June 2007

Do cultures differ with respect to judgments of rationality? If so, does it follow that rationality is culturally specific, or that cultures have their own `rationalities'? If so, does it further follow that the philosophical status or worthiness of multiculturalism as a social value or ideal varies from culture to culture? In this article I consider the relationship between rationality and multiculturalism; offer a characterization of the latter that enables it to survive Stanley Fish$quoteright$s claim that `no one could possibly be a multiculturalist in any interesting and coherent sense'; criticize Richard Shweder$quoteright$s case for `divergent rationality'; and argue for a `universalistic', culture-independent understanding of rationality.
Umbilical cord blood transplantation after nonmyeloablative conditioning: impact on transplantation outcomes in 110 adults with hematologic disease
Authors: Brunstein Claudio G. , Barker Juliet N. , Weisdorf Daniel J. , DeFor Todd E. , Miller Jeffrey S. , Blazar Bruce R. , McGlave Philip B. , Wagner John E.
Published: June 2007

We evaluated the efficacy of umbilical cord blood (UCB) in the setting of a nonmyeloablative regimen consisting of fludarabine (200 mg/m2), cyclophosphamide (50 mg/kg), and a single fraction of total body irradiation (200 cGy) with cyclosporine and mycophenolate mofetil for posttransplantation immunoprophylaxis. The target cell dose for the UCB graft was 3.0 × 107 nucleated cells/kg, resulting in the selection of a second partially human leukocyte antigen-matched UCB unit in 85%. One hundred ten patients with hematologic disease were enrolled. Neutrophil recovery was achieved in 92% at a median of 12 days. Incidences of grades III and IV acute and chronic graft-versus-host disease (GVHD) were 22% and 23%, respectively. Transplantation-related mortality was 26% at 3 years. Survival and event-free survival (EFS) at 3 years were 45% and 38%, respectively. Favorable risk factors for survival were absence of high-risk clinical features (Karnofsky 50-60, serious organ dysfunction, recent fungal infection, P < .01) and absence of severe GVHD (P = .04), and favorable risk factors for EFS were absence of high-risk clinical features (P < .01) and use of 2 UCB units (P = .07). These findings support the use of UCB after a nonmyeloablative conditioning as a strategy for extending the availability of transplantation therapy, particularly for older patients.
Hematopoietic stem-cell gene therapy of hemophilia A incorporating a porcine factor VIII transgene and nonmyeloablative conditioning regimens
Authors: Ide Lucienne M. , Gangadharan Bagirath , Chiang Kuang-Yueh , Doering Christopher B. , Spencer H. Trent
Published: June 2007

Insufficient expression of factor VIII (fVIII) is a major hurdle in the development of successful nucleic acid treatments for hemophilia. However, we recently showed that under myeloablative and reduced-intensity total body irradiation (TBI) conditioning, transplantation of hematopoietic stem cells (HSCs) transduced with recombinant retroviruses containing B domain–deleted porcine fVIII (BDDpfVIII) sequences provides curative fVIII levels in a hemophilia A mouse model. In the current study, we tested BDDpfVIII activity after nonmyeloablative conditioning with busulfan, cyclophosphamide, or fludarabine and immunosuppressive agents CTLA4-Ig + anti-CD40L or anti-(murine)thymocyte serum (ATS). ATS is similar in action to anti-(human)thymocyte globulin (ATG), which is used clinically with busulfan in bone marrow transplantations to increase donor cell engraftment. Mice conditioned with busulfan + ATS and that received a transplant of BDDpfVIII-transduced stem-cell antigen 1-positive cells exhibited moderate levels of donor cell chimerism (between 20% and 60%) and achieved sustained fVIII levels more than 1 U/mL. Similar results were observed in mice preimmunized with human fVIII and conditioned with 5 Gy TBI + ATS or busulfan + ATS. These data demonstrate that it is possible to achieve sufficient fVIII expression after transplantation of BDDpfVIII-transduced HSCs following low-toxicity pretransplantation conditioning with targeted immunosuppression, potentially even in the context of preexisting inhibitors.
Nonhemolytic antigen loss from red blood cells requires cooperative binding of multiple antibodies recognizing different epitopes
Authors: Zimring James C. , Cadwell Chantel M. , Chadwick Traci E. , Spitalnik Steven L. , Schirmer David A. , Wu Tao , Parkos Charles A. , Hillyer Christopher D.
Published: June 2007

Transfusion of crossmatch-incompatible red blood cells (RBCs) can result in antibody-mediated hemolysis. However, in some patients, crossmatch-incompatible RBCs lose the incompatible antigen from their surface, and then circulate normally (“antigen loss”). Although antigen loss has been reported in the settings of autoimmune hemolytic anemia and transfusion of crossmatch-incompatible RBCs, mechanistic understanding of this phenomenon is limited. Using an in vivo murine model of antigen loss, we report that, unlike polyclonal antisera, monoclonal antibodies did not induce antigen loss. However, the combination of 2 monoclonal antibodies that recognized separate epitopes on the same antigen induced antigen loss. This was not due to an increased number of Fc domains bound to the cell surface, because antigen loss still occurred when combining intact monoclonal IgG and F(ab′)2 fragments recognizing different epitopes. Together, these data lead to the hypothesis that antigen-antibody crosslinking is required for nonhemolytic antigen loss to occur.
Virulence phenotypes of low-passage clinical isolates of Nontypeable Haemophilus influenzae assessed using the chinchilla laniger model of otitis media
Authors: Buchinsky Farrel J , Forbes Michael L , Hayes Jay D , Shen Kai , Ezzo Suzanne , Compliment James , Hogg Justin , Hiller N Luisa , Hu Fen Ze , Post J Christopher , Ehrlich Garth D
Published: June 2007

Background

The nontypeable Haemophilus influenzae (NTHi) are associated with a spectrum of respiratory mucosal infections including: acute otitis media (AOM); chronic otitis media with effusion (COME); otorrhea; locally invasive diseases such as mastoiditis; as well as a range of systemic disease states, suggesting a wide range of virulence phenotypes. Genomic studies have demonstrated that each clinical strain contains a unique genic distribution from a population-based supragenome, the distributed genome hypothesis. These diverse clinical and genotypic findings suggest that each NTHi strain possesses a unique set of virulence factors that contributes to the course of the disease.

Results

The local and systemic virulence patterns of ten genomically characterized low-passage clinical NTHi strains (PittAA – PittJJ) obtained from children with COME or otorrhea were stratified using the chinchilla model of otitis media (OM). Each isolate was used to bilaterally inoculate six animals and thereafter clinical assessments were carried out daily for 8 days by blinded observers. There was no statistical difference in the time it took for any of the 10 NTHi strains to induce otologic (local) disease with respect to any or all of the other strains, however the differences in time to maximal local disease and the severity of local disease were both significant between the strains. Parameters of systemic disease indicated that the strains were not all equivalent: time to development of the systemic disease, maximal systemic scores and mortality were all statistically different among the strains. PittGG induced 100% mortality while PittBB, PittCC, and PittEE produced no mortality. Overall Pitt GG, PittII, and Pitt FF produced the most rapid and most severe local and systemic disease. A post hoc determination of the clinical origins of the 10 NTHi strains revealed that these three strains were of otorrheic origin, whereas the other 7 were from patients with COME.

Conclusion

Collectively these data suggest that the chinchilla OM model is useful for discriminating between otorrheic and COME NTHi strains as to their disease-producing potential in humans, and combined with whole genome analyses, point the way towards identifying classes of virulence genes.
Symptom burden among patients with Renal Cell Carcinoma (RCC): content for a symptom index
Authors: Harding Gale , Cella David , Robinson Don , Mahadevia Parthiv J , Clark Jason , Revicki Dennis A
Published: June 2007

Background

Renal cell carcinoma (RCC) has multiple symptoms stemming from disease and treatments. There are few validated scales for evaluating RCC symptoms.

Methods

A national cross-sectional study of adult RCC patients was conducted from October to December 2003 to define patient-reported RCC symptomology. Participants were asked open-ended questions regarding their signs and symptoms and completed an 86-item pilot questionnaire of physical and psychological symptoms. Patients were asked to rate the relevancy and clarity of each pilot question using a 5-point Likert scale. Subsequent open-ended caregiver interviews and a provider panel relevance ranking contributed additional information.

Results

The average age of the participants (n = 31) was 55 years; 55% of patients were male, 74% had attended college, and 97% were Caucasian. The five most frequent symptoms among localized-stage patients (n = 14) were irritability (79%), pain (71%), fatigue (71%), worry (71%), and sleep disturbance (64%). Among metastatic patients (n = 17), the five most frequent symptoms were fatigue (82%), weakness (65%), worry (65%), shortness of breath (53%), and irritability (53%). More than 50% of localized and metastatic-stage patients reported pain, weakness, fatigue, sleep disturbance, urinary frequency, worry, and mood disorders as being moderately to highly relevant.

Conclusion

A brief, self-administered RCC Symptom Index was created that captures the relevant signs and symptoms of both localized and metastatic patients. Pending additional content validation, the Index can be used to assess the signs and symptoms of RCC and the clinical benefit resulting from RCC treatment.
Null Effect of Antidepressants on the Astrocytes-Mediated Proliferation of Hippocampal Progenitor Cells in vitro
Authors: Ko Hyoung-Gon , Lee Sung Joong , Son Hyeon , Kaang Bong-Kiun
Published: June 2007

Background:

It is well known that antidepressants increase neurogenesis in the dentate gyrus of the hippocampus. The increase of neurogenesis might contribute to the behavioral effects of antidepressants. However, the mechanism by which antidepressants increase hippocampal neurogenesis is largely unknown. It has been recently reported that astroglia induce the neurogenesis of the hippocampal neural progenitor cells (NPCs). Therefore, we hypothesized that antidepressants may act on astrocytes, and this in turn induces neurogenesis of NPCs.

Results:

To examine this hypothesis, we used two co-culture systems, i.e., a contact-independent Banker culture and a contact-dependent overlay co-culture. In both of these systems, in comparison with naïve astrocytes, antidepressant-treated astrocytes did not further increase the proliferation of NPCs.

Conclusion:

These results suggest that astrocytes increase the proliferation of hippocampal NPCs, however, this may not be directly involved in the antidepressant-induced proliferation of NPCs.
Prognostic Factors for Survival in Adult Patients With Recurrent Glioma Enrolled Onto the New Approaches to Brain Tumor Therapy CNS Consortium Phase I and II Clinical Trials
Authors: Carson Kathryn A. , Grossman Stuart A. , Fisher Joy D. , Shaw Edward G.
Published: June 2007

Purpose

Prognostic factor analyses have proven useful in predicting outcome in patients with newly diagnosed malignant glioma. Similar analyses in patients with recurrent glioma could affect the design and conduct of clinical trials substantially.

Patients and Methods

Between 1995 and 2002, 333 adults with recurrent gliomas were enrolled onto 10 phase I or II trials of systemic or local therapy. The studies had similar inclusion criteria and were conducted within the New Approaches to Brain Tumor Therapy CNS Consortium. Ninety-three percent of the patients have died. Cox proportional hazards (PH) regression and recursive partitioning analysis (RPA) were performed to identify prognostic factors.

Results

Factors associated with an increased risk of death were increased age, lower Karnofsky performance score (KPS), initial and on-study histologies of glioblastoma multiforme (GBM), corticosteroid use, shorter time from original diagnosis to recurrence, and tumor outside frontal lobe. The final PH model included initial histology of GBM (relative risk [RR] = 2.01), 10-year increase in age (RR = 1.23), KPS less than 80 (RR = 1.54), and corticosteroid use (RR = 1.49). RPA resulted in seven classes. Median survival time was poorest in non-GBM patients with KPS less than 80 or GBM patients, age ≥ 50 years, corticosteroid use (4.4 months; 95% CI, 3.6 to 5.4 months); median survival was best in patients with initial histology other than GBM with KPS ≥ 80 and tumor confined to the frontal lobe (25.7 months; 95% CI, 18.7 to 52.5), and was 7.0 months (95% CI, 6.2 to 8.0 months) for all patients.

Conclusion

Initial histology, age, KPS, and corticosteroid use are prognostic for survival in recurrent glioma patients. To allow comparisons across phase II trials, enrollment criteria may need to be restricted.
Leuprorelin Acetate Every-3-Months Depot Versus Cyclophosphamide, Methotrexate, and Fluorouracil As Adjuvant Treatment in Premenopausal Patients With Node-Positive Breast Cancer: The TABLE Study
Authors: Schmid Peter , Untch Michael , Kossé Valentin , Bondar Grigorij , Vassiljev Leonid , Tarutinov Valerie , Lehmann Ute , Maubach Lutz , Meurer Juergen , Wallwiener Diethelm , Possinger Kurt
Published: June 2007

Purpose

Ovarian suppression with luteinizing hormone–releasing hormone (LHRH) agonists is an effective adjuvant treatment for premenopausal women with estrogen receptor (ER) –positive breast cancer. Whereas monthly LHRH agonist therapy has been well established, the value of every-3-months (3-monthly) formulations is unclear.

Patients and Methods

This randomized phase III trial was performed to compare the 3-monthly depot LHRH agonist leuprorelin acetate (LAD-3M; n = 299) and chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF; n = 300) in pre- or perimenopausal patients with ER-positive, node-positive breast cancer.

Results

With a median follow-up of 5.8 years, recurrence-free survival was similar for patients treated with LAD-3M or CMF (hazard ratio [HR], 1.19; 95% CI, 0.94 to 1.51; P = .15). There was no substantial heterogeneity in the relative treatment effect among subgroups defined by age, progesterone receptor (PR) status, nodal status, hormone levels, or menstrual recovery after treatment. Exploratory overall survival analysis favored LAD-3M (HR, 1.50; 95% CI, 1.13 to 1.99; P = .005). Chemotherapy-related adverse effects such as nausea, vomiting, and alopecia were more common with CMF, whereas symptoms of estrogen suppression such as hot flushes and sweating were initially more pronounced with LAD-3M.

Conclusion

The 3-monthly depot LHRH-agonist leuprorelin acetate is an effective adjuvant treatment in premenopausal patients with hormone receptor–positive, node-positive breast cancer that is not inferior to CMF.
Meta-Analyses of Chemotherapy for Locally Advanced and Metastatic Pancreatic Cancer
Authors: Sultana Asma , Smith Catrin Tudur , Cunningham David , Starling Naureen , Neoptolemos John P. , Ghaneh Paula
Published: June 2007

Purpose

There are a large number of randomized controlled trials involving chemotherapy in the management of advanced pancreatic cancer. Several chemotherapeutic agents, either alone or in combination with other chemotherapy or novel agents, have been used. The aim of these meta-analyses was to examine the different therapeutic approaches, and the comparisons examined were as follows: chemotherapy versus best supportive care; fluorouracil (FU) versus FU combination chemotherapy; gemcitabine versus FU; and gemcitabine versus gemcitabine combination chemotherapy.

Methods

Relevant trials were identified by searching databases, trial registers, and conference proceedings. The primary end point was overall survival.

Results

One hundred thirteen randomized controlled trials were identified, of which 51 trials involving 9,970 patients met the inclusion criteria. Chemotherapy improved survival compared with best supportive care (hazard ratio [HR] = 0.64; 95% CI, 0.42 to 0.98). FU-based combination chemotherapy did not result in better overall survival compared with FU alone (HR = 0.94; 95% CI, 0.82 to 1.08). There was insufficient evidence of a survival difference between gemcitabine and FU, but the wide CI includes clinically important differences in both directions, making a clear conclusion difficult (HR = 0.75; 95% CI, 0.42 to 1.31). Survival was improved after gemcitabine combination chemotherapy compared with gemcitabine alone (HR = 0.91; 95% CI, 0.85 to 0.97).

Conclusion

There was a significant survival benefit for chemotherapy over best supportive care and gemcitabine combinations over gemcitabine alone. This supports the use of gemcitabine-based combination chemotherapy in the treatment of advanced pancreatic cancer.
Intratumoral Balance of Regulatory and Cytotoxic T Cells Is Associated With Prognosis of Hepatocellular Carcinoma After Resection
Authors: Gao Qiang , Qiu Shuang-Jian , Fan Jia , Zhou Jian , Wang Xiao-Ying , Xiao Yong-Sheng , Xu Yang , Li Yi-Wei , Tang Zhao-You
Published: June 2007

Purpose

To investigate the prognostic value of tumor-infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs), in hepatocellular carcinoma (HCC) patients after resection.

Patients and Methods

CD3+, CD4+, CD8+, Foxp3-positive, and granzyme B-positive TILs were assessed by immunohistochemistry in tissue microarrays containing HCC from 302 patients. Prognostic effects of low- or high-density TIL subsets were evaluated by Cox regression and Kaplan-Meier analysis using median values as cutoff.

Results

CD3+, CD4+, CD8+ TILs were associated with neither overall survival (OS) nor disease-free survival (DFS). The presence of low intratumoral Tregs in combination with high intratumoral activated CD8+ cytotoxic cells (CTLs), a balance toward CTLs, was an independent prognostic factor for both improved DFS (P = .001) and OS (P < .0001). Five-year OS and DFS rates were only 24.1% and 19.8% for the group with intratumoral high Tregs and low activated CTLs, compared with 64.0% and 59.4% for the group with intratumoral low Tregs and high activated CTLs, respectively. Either intratumoral Tregs alone (P = .001) or intratumoral activated CTLs (P = .001) alone is also an independent predictor for OS. In addition, high Tregs density was associated with both absence of tumor encapsulation (P = .032) and presence of tumor vascular invasion (P = .031).

Conclusion

Tregs are associated with HCC invasiveness, and intratumoral balance of regulatory and cytotoxic T cells is a promising independent predictor for recurrence and survival in HCC. A combination of depletion of Tregs and concomitant stimulation of effector T cells may be an effective immunotherapy to reduce recurrence and prolong survival after surgery.
Prognostic Significance of 99mTc Hynic-rh-Annexin V Scintigraphy During Platinum-Based Chemotherapy in Advanced Lung Cancer
Authors: Kartachova Marina , van Zandwijk Nico , Burgers Sjaak , van Tinteren Harm , Verheij Marcel , Valdés Olmos Renato Alfredo
Published: June 2007

Purpose

The purpose of this study was to evaluate if sequential 99mTc Hynic-rh- annexin V scintigraphy (TAS) can predict outcome in patients with advanced lung cancer, shortly after the start of platinum-based chemotherapy.

Patients and Methods

In 16 consecutive chemotherapy-naive patients with advanced stage non–small-cell lung cancer scheduled for platinum-based chemotherapy, TAS was performed before and within 48 hours after the start of therapy. Chemotherapy-induced changes in tumor annexin V uptake, calculated as maximum count per pixel and expressed as percentage to baseline value, were compared with treatment response determined according to Response Evaluation Criteria in Solid Tumors.

Results

A significant correlation (r2 = 0.86; P = .0001) was found between annexin V metabolic changes and treatment outcome. All patients with notably increased annexin V tumor uptake showed complete or partial response. Less prominently increased or decreased uptake correlated with stable or progressive disease.

Conclusion

TAS is a promising test to predict tumor response in patients with advanced lung cancer early in the course of platinum-based chemotherapy.
UGT1A1Promoter Genotype Correlates With SN-38 Pharmacokinetics, but Not Severe Toxicity in Patients Receiving Low-Dose Irinotecan
Authors: Stewart Clinton F. , Panetta John C. , O'Shaughnessy Melinda A. , Throm Stacy L. , Fraga Charles H. , Owens Thandranese , Liu Tiebin , Billups Catherine , Rodriguez-Galindo Carlos , Gajjar Amar , Furman Wayne L. , McGregor Lisa M.
Published: June 2007

Purpose

To study the association between UDP-glucuronosyltransferase 1A1 (UGT1A1) genotypes and severe toxicity as well as irinotecan disposition in pediatric patients with solid tumors receiving low-dose, protracted irinotecan (15 to 75 mg/m2daily for 5 days for 2 consecutive weeks).

Patients and Methods

Seventy-four patients on five institutional clinical trials received irinotecan (15 to 75 mg/m2) daily intravenously or orally for 5 days for 2 consecutive weeks. Genomic DNA was genotyped for UGT1A1*28, and patients were designated as 6/6, 6/7, or 7/7 depending on the number of TA repeats in the UGT1A1 promoter region. Patients were evaluated for gastrointestinal and hematologic toxicity, as well as baseline and maximal serum bilirubin levels. Toxicity and pharmacokinetic results were evaluated during courses 1 and 2 of irinotecan therapy.

Results

The frequencies of 6/6, 6/7, and 7/7 genotypes were 27 (36.5%), 36 (48.6%), and 9 (12.2%) of 74 patients, respectively. Patients with 7/7 genotype had a statistically greater baseline total bilirubin than patients with 6/6 or 6/7 genotype (P = .005). UGT1A1*28 genotype was not associated with grade 3 and 4 neutropenia (P = .21 for course 1; P = .23 for course 2) or diarrhea (P = .176 for course 1; P = .87 for course 2). However, patients with the 7/7 genotype tended to have higher SN-38 area under the plasma time-concentration curve (AUC) values and lower SN-38G/SN-38 AUC ratios.

Conclusion

Severe toxicity was not increased in pediatric patients with the 7/7 genotype when treated with a low-dose protracted schedule of irinotecan. Therefore, UGT1A1 genotyping is not a useful prognostic indicator of severe toxicity for patients treated with this irinotecan dosage and schedule.
Phase II Study of Erlotinib in Advanced Non–Small-Cell Lung Cancer After Failure of Gefitinib
Authors: Cho Byoung Chul , Im Chong-Kun , Park Moo-Suk , Kim Se Kyu , Chang Joon , Park Jong Pil , Choi Hye Jin , Kim Yu Jin , Shin Sang-Joon , Sohn Joo Hyuk , Kim Hoguen , Kim Joo Hang
Published: June 2007

Purpose

This study was designed to evaluate the efficacy and toxicity of erlotinib in patients with advanced non–small-cell lung cancer (NSCLC) who experienced disease progression after treatment with gefitinib.

Patients and Methods

The study included stage IIIB/IV recurrent or metastatic NSCLC patients who received two or three prior chemotherapy regimens and showed progressive disease within 4 months of gefitinib therapy discontinuation. Patients received erlotinib 150 mg/d until disease progression or unacceptable toxicity. Epidermal growth factor receptor (EGFR) mutations and other genetic abnormalities were analyzed from available tumor samples.

Results

Patient and disease characteristics (N = 21) included median age 56 years; number of prior chemotherapy regimens (three; n = 11); female sex (n = 11); adenocarcinoma (n = 15); and never-smoker status (n = 11). Among the 17 patients with tumor samples available, EGFR mutations were detected in five. The disease control rate (DCR) and response rate (RR) for all patients were 28.6% and 9.5%, respectively. The median duration of disease control was 125 days. The median time to progression and overall survival were 60 days and 158 days, respectively. Patients who had stable disease (SD) while receiving gefitinib showed significantly higher DCR (75% v 17.6% in non-SD patients; P = .050) and RR (50.0% v 0% in non-SD patients; P = .029). Among 17 patients with biomarker results available, those lacking EGFR mutations who had SD while receiving gefitinib showed significantly higher DCR and RR.

Conclusion

Erlotinib seems to be a potential therapeutic option for the treatment of advanced NSCLC patients with wild-type EGFR who had SD while receiving gefitinib.
Randomized Trial of the Combination of Lomeguatrib and Temozolomide Compared With Temozolomide Alone in Chemotherapy Naive Patients With Metastatic Cutaneous Melanoma
Authors: Ranson Malcolm , Hersey Peter , Thompson Damien , Beith Jane , McArthur Grant A. , Haydon Andrew , Davis Ian D. , Kefford Richard F. , Mortimer Peter , Harris Peter A. , Baka Sofia , Seebaran Augustus , Sabharwal Ami , Watson Amanda J. , Margison Geoffrey P. , Middleton Mark R.
Published: June 2007

Purpose

To evaluate tumor response, pharmacodynamic effects, and safety of a combination of lomeguatrib (LM), an O6-methylguanine DNA-methyltransferase (MGMT) inactivator, and temozolomide (TMZ), TMZ alone, and LM/TMZ after disease progression on TMZ alone in patients with advanced melanoma.

Patients and Methods

Patients with unresectable stage III or IV cutaneous melanoma who had no prior systemic chemotherapy were randomly assigned to receive either 40 to 80 mg LM and 125 mg/m2 TMZ or 200 mg/m2 TMZ on days 1 through 5 of each 28-day treatment cycle. Drugs were administered orally for up to six cycles of treatment. Patients on TMZ alone were offered LM/TMZ at progression, if fit enough to receive treatment.

Results

One hundred four patients were enrolled, with 52 in each trial arm. Twenty-seven TMZ-treated patients received LM/TMZ after progression on TMZ. Unexpectedly, analysis of tumor biopsies showed rapid recovery of MGMT after LM/TMZ with 40 mg/d LM. Therefore, doses of LM were escalated to 60 then 80 mg/d. Tumor response rates were 13.5% with LM/TMZ and 17.3% with TMZ alone. No patient responded to LM/TMZ having progressed through TMZ. Median time to disease progression was 65.5 days for LM/TMZ and 68 days for TMZ. All treatments were well tolerated, although hematologic and gastrointestinal adverse events were common. A higher incidence of hematological adverse events was observed in the LM/TMZ combination arm.

Conclusion

The efficacy of LM and TMZ in the current dosing schedule is similar to that of TMZ alone. To maintain MGMT depletion in tumor dosing of LM needs to be continued beyond that of TMZ.
Coculture with Primary Visceral Rat Adipocytes from Control But Not Streptozotocin-Induced Diabetic Animals Increases Glucose Uptake in Rat Skeletal Muscle Cells: Role of Adiponectin
Authors: Vu Vivian , Kim Wi , Fang Xiangping , Liu Yuan-Tao , Xu Aimin , Sweeney Gary
Published: June 2007

We developed a coculture system comprising primary rat adipocytes and L6 rat skeletal muscle cells to allow investigation of the effects of physiologically relevant mixtures of adipokines. We observed that coculture, or adipocyte-conditioned media, increased glucose uptake in muscle cells. An adipokine that could potentially mediate this effect is adiponectin, and we demonstrated that small interfering RNA-mediated knockdown of adiponectin receptor-2 in muscle cells reduced the uptake of glucose upon coculture with primary rat adipocytes. Analysis of coculture media by ELISA indicated total adiponectin concentration of up to 1 μg/ml, and Western blotting and gel filtration analysis demonstrated that the adipokine profile was hexamer greater than high molecular weight much greater than trimer. We used the streptozotocin-induced rat model of diabetes and found that high-molecular-weight adiponectin levels decreased in comparison with control animals and this correlated with the fact that diabetic rat-derived primary adipocytes in coculture did not stimulate glucose uptake to the same extent as control adipocytes. Coculture induced phosphorylation of AMP-activated protein kinase (T172) and interestingly also insulin receptor substrate-1 (Y612) and Akt (T308 & S473), which could be attenuated after adiponectin receptor-2-small interfering RNA treatment. In summary, we believe that this coculture system represents an excellent model to study the effects of primary adipocyte-derived adipokine mixtures on skeletal muscle metabolism, and here we have established that in the context of physiologically relevant mixtures of adipokines, adiponectin may be an important determinant of positive cross talk between adipocytes and skeletal muscle.