bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors influencing prescribing decisions in the treatment of depression: a social judgement theory approach
Authors: Smith Liz , Gilhooly Ken , Walker Anne
Published: December 2002

The under‐diagnosis and inappropriate treatment of depression in primary care has become a serious public health problem despite the development of many clinical guidelines to guide recognition and treatment of the disorder. This study aims to investigate decision‐making processes and to identify factors which influence general practitioners' (GPs) prescribing decisions and how these factors differ from those the guidelines recommend. Brunswik's lens model, from Social Judgement Theory (SJT), was employed to explore individual treatment decision policies of 40 GPs in the Grampian region of Scotland for 20 case vignettes. These individual policies were then aggregated and compared with those derived from guideline recommendations; important differences emerged between the two in the utilization of cues and there was considerable variation between GPs' policies. Guidelines placed more importance on the duration of symptoms whereas GPs gave weight also to particular symptoms, such as ‘thoughts of suicide’ and ‘sleep disturbance’ and patient treatment preference. GPs prescribed antidepressants at a greater rate than was recommended by the guidelines. The findings have important implications for implementation strategies, which maybe developed to accompany clinical guidelines. Copyright © 2002 John Wiley & Sons, Ltd.
Children's reports of emotionally laden events: adapting the interview to the child
Authors: Salmon Karen , Roncolato Wendy , Gleitzman Melanie
Published: December 2002

This study examined the influence of expressive vocabulary and temperament on children's verbal reports about emotionally laden events in different interview conditions. In one of three conditions, 58 children aged between 5 and 7 years were interviewed about a time they had felt happy and a time they had felt scared. The interview conditions were: drawing, in which they were asked to draw and tell; re‐enactment, in which they were asked to re‐enact and tell; and verbal, in which they were simply asked to tell. The principal finding was that, whereas for children in the verbal interview condition expressive vocabulary was associated with the amount of information reported and for children in the re‐enactment condition, temperament had a moderate association with the amount reported, for children in the drawing interview condition, neither temperament nor expressive language was associated with the amount of information reported. Children in the drawing condition reported more information than those in the other two interview conditions. The possible mechanisms underlying these findings and their implications for interviewing children in clinical contexts are discussed. Copyright © 2002 John Wiley & Sons, Ltd.
Distortion of autobiographical memories
Authors: Niedźwieńska Agnieszka
Published: December 2002

The aim of the present study was to create the conditions of real discussion concerning the past in an experimental setting and examine their effect on subsequent recollections of autobiographical events. Sixty first‐year Jagiellonian University students described two important autobiographical events twice. In between the two recall sessions, participants from the experimental group viewed two films. The first was a short televised account of the two events; the second was a corresponding videotaped description of the personal experiences of a young woman. In addition, participants were asked to imagine what she had been talking about. Most of the participants from the experimental group incorporated elements of the woman's description into their own subsequent accounts. In spite of this, they rated the vividness and the accuracy of their posttest memories as very high. The results are discussed in terms of source misattribution as a distortion mechanism in episodic memory. Copyright © 2002 John Wiley & Sons, Ltd.
Affecting the perception of verbal cues to deception
Authors: Strömwall Leif A. , Anders Granhag Pär
Published: December 2002

An important but overlooked factor in deception detection research is how the perception of verbal cues to deception can be affected by situational factors. This study examined how participants' (N = 200) perceptions were influenced by presentation mode (Experiments 1 and 2) and repeated exposure/assessment (Experiment 3). As predicted, presentation mode affected the perception of several verbal cues. Participants who watched a videotaped testimony rated the degree of the cues richness of detail, completeness, logical structure and plausibility, higher than those who read the transcript of the same testimony. Furthermore, repeated exposure to the testimony, in combination with repeated assessments, lowered the participants' ratings of the verbal cues. People's perception of the verbal content of a testimony can thus be affected by situational factors. The results are discussed in psycho‐legal terms. Copyright © 2002 John Wiley & Sons, Ltd.
Creating coherence out of chaos? Children's narratives of emotionally positive and negative events
Authors: Fivush Robyn , Hazzard Ann , McDermott Sales Jessica , Sarfati Deborah , Brown Trina
Published: December 2002

The ways in which children narrate about emotionally negative events is intricately linked to the ways in which they create meaning and, ultimately, cope with such experiences. In this study we interviewed 5‐ to 12‐year‐old children growing up in violent communities about both emotionally positive and negative experiences. Children were able to report a great deal of information about both types of events, but they reported more objects and people, and used more descriptive detail, when narrating positive experiences. In contrast, children included more information about their thoughts and emotions when narrating negative experiences, and recounted these experiences more coherently. Few differences were found as a function of children's age, time since the events occurred, reported family discussion about the events, level of exposure to community violence or level of child behaviour problems. Implications of these findings for how children strive to create meaning out of the stressful events of their lives are discussed. Copyright © 2002 John Wiley & Sons, Ltd.
Source monitoring and suggestibility to misinformation: adult age‐related differences
Authors: Mitchell Karen J. , Johnson Marcia K. , Mather Mara
Published: December 2002

We compared young and older adults' source monitoring performance on an explicit source identification test using the misinformation paradigm. Several age‐related differences in source memory were demonstrated: (a) older adults were more likely than were young adults to say that they saw information that was actually only suggested to them; (b) older adults were more confident in their false memories than were young adults; (c) older adults were less confident in their accurate memory for the source of information than were young adults. Together, the data suggest that older adults either lacked or failed to use helpful diagnostic source information (e.g. perceptual details or temporal information), and that their confidence in their false memories reflected an over‐weighting of semantic information. Copyright © 2002 John Wiley & Sons, Ltd.
Comparison of slow‐ and rapid‐cooling protocols for early‐cleavage‐stage Macaca fascicularis embryos
Authors: Curnow E.C. , Kuleshova L.L. , Shaw J.M. , Hayes E.S.
Published: December 2002

Cryostorage of nonhuman primate embryos by time‐consuming slow‐cooling methods is often limited to early cleavage stages. Effective rapid‐cooling methods have been developed for many species and represent valuable tools for laboratory‐ and field‐based studies of nonhuman primate reproductive biology. However, few rapid‐cooling protocols have been applied to nonhuman primate embryos in terms of comparing various developmental stages. Here we compare slow cooling vs. two‐ and three‐step rapid cooling of two‐, four‐, and eight‐cell Macaca fascicularis (Mf) embryos. Rapid cooling was conducted in open pulled straws (OPS) using cooling solutions containing reduced quantities of ethylene glycol (EG) and supplemented with either of two high‐molecular‐weight polymers, ficoll and dextran. The survival of the slow‐cooled embryos, but not the rapid‐cooled embryos, was independent of embryonic stage at cryostorage. Slow cooling was associated with greater cell survival (82%) post thaw compared to warming following rapid cooling (18–29%). Slow cooling resulted in a high proportion of embryo survival (18/20; 90%) and cleavage (15/18; 83%) post thaw. Rapid cooling resulted in significantly reduced percentages of embryo survival (26–32%) and embryo cleavage in culture (29–38%) after warming. Conventional slow cooling was more effective than the rapid‐cooling protocols employed in this study for cryopreservation of early‐cleavage‐stage Mf embryos. Am. J. Primatol. 58:169–174, 2002. © 2002 Wiley‐Liss, Inc.
Incident of intense aggression by chimpanzees against an infant from another group in Mahale Mountains National Park, Tanzania
Authors: Kutsukake Nobuyuki , Matsusaka Takahisa
Published: December 2002

We document here an unusual case of intense aggression against an infant male from another group by chimpanzees (Pan troglodytes schweinfurthii) of the Mahale Mountains National Park, in Tanzania. Adult males of the study group collectively attacked an unknown male infant. Although an unknown female, probably the mother, tried to retrieve him, the infant was seriously injured and most likely died. During this incident, the unknown female attacked and injured two researchers. After the aggressive encounter, it was found that six of the nine adult males in the study group were wounded. Attacking the extragroup male infant may have the effect of weakening the future power of the neighboring group, leading to better access to resources and enhanced safety in the future for the study group. Am. J. Primatol. 58:175–180, 2002. © 2002 Wiley‐Liss, Inc.
Navigating between Scylla and Charybdis: Mitochondria are both precedented and novel targets for drug development
Authors: Howell Neil
Published: December 2002

Biotechnology companies frequently struggle to convince potential partners or investors that the company's research is cutting‐edge, but not so novel as to be an unattractive risk. MitoKor is a biotechnology company that focuses on the development of drugs that act on mitochondrial targets. From a review of the scientific literature, it is clear that a number of drugs act on mitochondrial pathways although that site of action was usually not recognized or understood during early‐stage development. At the same time, only a small fraction of all mitochondrial proteins have been identified. Therefore, it appears that mitochondria are a source of both novel and precedented drug targets. With the rapid pace of scientific research, it will be a continuing challenge for biotechnology companies to navigate between being too novel and not being novel enough. Drug Dev. Res. 57:75–82, 2002. © 2002 Wiley‐Liss, Inc.
Biotech and pharma: State of the relationship in the new millennium
Authors: Cunningham Brian C.
Published: December 2002

The relationship between biotech and big pharma is undergoing a sea change. Pharmaceutical companies are failing to turn out significant numbers of new drugs from their internal R&D efforts and must increasingly fill their pipelines by in‐licensing products from biotech companies. Conversely, biotech is more prolific than ever, with the number of approved drugs and late‐stage clinical candidates ballooning in the last few years. However, spurred by changes in the marketplace, including the emergence of new potential partners such as clinical service organizations (CSOs) as well as infusions of capital from the financial market boom of 2000, biotech companies are retaining greater control of their drug candidates and opting for new types of marketing alliances that may or may not include big pharmaceutical concerns. If pharma wants to remain a marketing partner of choice in this new climate, it must fundamentally change the way it views and deals with biotech. Drug Dev. Res. 57:97–102, 2002. © 2002 Wiley‐Liss, Inc.
The importance of interviewing in building a successful biotech (or other) company
Authors: Simmerman Shelley B.
Published: December 2002

In a market where no company—regardless of size (Enron) or industry (yes, even biotech)—can afford to lose face, time, or its competitive edge, both leaders and followers at all levels of the organizational structure are being called upon to not only give more, but to believe in more, to stand for more, and to be certain of less while doing so. Building and maintaining the momentum needed to keep up in this kind of environment is a tough job, requiring multiple skill sets, and it cannot be tackled by those at the top alone. Hiring people up and down the chain who can provide not simply a strong set of technical skills, but also emotional strength and relationship savvy, can make the difference between success and failure. One of the areas in which technical skills play such a critical role and are so highly sought, often at the expense of the more social skills, is the biotech/pharmaceutical industry, and yet even science is no longer immune to the pitfalls of hiring an unbalanced staff. I believe, and hope to show you how, conducting interviews that are designed to assess more than a candidate's technical skills will yield a richer employee base that is capable of making not only the intellectual contribution, but the emotional contribution today's companies cannot survive without. Drug Dev. Res. 57:103–105, 2002. © 2002 Wiley‐Liss, Inc.
Remote attack detection method in IDA: MLSI‐based intrusion detection with discriminant analysis
Authors: Asaka Midori , Onabuta Takefumi , Inoue Tadashi , Okazawa Shunji , Goto Shigeki
Published: December 2002

In order to detect intrusions, IDA (Intrusion Detection Agent system) initially monitors system logs in order to discover an MLSI—which is a certain event which in many cases occurs during an intrusion. If an MLSI is found, then IDA judges whether the MLSI is accompanied by an intrusion. We adopt discriminant analysis to analyze information after IDA detects an MLSI in a remote attack. Discriminant analysis provides a classification function that allows IDA to separate intrusive activities from nonintrusive activities. Using discriminant analysis, we can detect intrusions by analyzing only a part of the system calls occurring on a host machine, and we can determine whether an unknown sample is an intrusion. In this paper, we explain in detail how we perform discriminant analysis to detect intrusions, and evaluate the classification function. We also describe how to extract a sample from system logs, which is necessary to implement the discriminant analysis function in IDA. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 86(4): 50–62, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.10053
A security method for passive double star optical access systems
Authors: Miki Noriki , Kumozaki Kiyomi , Ueda Hiromi , Watanabe Ryuichi
Published: December 2002

In a passive double star optical access system, an optical line terminal and multiple subscriber units are connected in a Point to Multi‐Point (P‐MP) configuration. In this case, the downstream signals from the optical line terminal are broadcast and delivered to all of the subscribers. Therefore, security is necessary for the communication of each subscriber to be protected from the other subscribers. In this paper, of the previously proposed encryption methods, we focus on stream ciphers that feature a compact cryptography circuit and are affected slightly by the bit errors generated in the transmission path, define the unique conditions of this system, and propose an encryption method for downstream signals that satisfies these system conditions. This new proposed encryption method features strengthening resistance to attack by using the upstream signal as the key and can be implemented in a small‐scale circuit. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 86(4): 42–49, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.10068
A study of digital optical signal multiplexing technique using short pulse amplitude modulation
Authors: Yamamoto Hiroaki , Numata Kazunori , Morikura Susumu
Published: December 2002

As an optical multiplexing system to be applied to the uplink of a passive optical network, the authors propose short pulse amplitude modulation as a form of optical CDM. Although this method has the attractive feature that no timing control and wavelength control is necessary, the number of multiplexed optical signals is limited by the optical beat interference. In this paper, the signal‐to‐noise ratio and the number of optical signals that can be multiplexed are theoretically discussed when digital signals are transmitted with short pulse amplitude modulation in the case where the DFB‐LDs with identical wavelengths are used as the optical sources and the optical beat interference is generated within the signal bandwidth. It is found that the number of optical signals that can be multiplexed is 8 when the signal speed is 100 Mb/s and the amount of chirp in the LD is 280 MHz/mA. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 86(4): 35–41, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.10075
Base station polarization diversity antenna for private mobile communications
Authors: Mori Kikuo , Moriyama Eimatsu , Arai Hiroyuki
Published: December 2002

Antennas for private mobile communications are required to have enhanced performance and miniaturization in order to deal with high‐performance mobile communications for the next generation. In this paper, with regard to the polarization diversity H antenna using the correlation between polarizations proposed as a base station antenna, the results of an analysis of the structure, characteristics, and effectiveness of the polarization diversity H‐type antenna in an actual environment obtained from field experiments are presented. The polarization diversity H antenna has a turnstile H element for the horizontal polarization and a dipole for the vertical polarization. The optimum shapes of each polarization antenna are derived. Also, in the diversity configuration, a structure optimizing the directivity and mutual coupling is derived. A field experiment is carried out at 150 MHz, the frequency presently used for operations. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 86(4): 10–18, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.10078
Mobile packet data communication network and its implementation
Authors: Onuki Masafumi , Sugiyama Kazuo , Sasada Koji , Fujiya Hiroshi
Published: December 2002

The authors intended to realize Internet access by mobile terminal and billing by the amount of information, as well as improvement of the spectrum efficiency in air access. For those purposes, they developed the PDC packet mobile communication system. That system realizes a data rate of 28.8 kb/s, which is at most 3 times the conventional link switching (9.6 kb/s), by realizing three‐slot parallel access in 3 ch TDMA. The network realized the service combining voice and packet, with a flexible structure independent of the user protocol. It has the feature that the access link is provided to the Internet service provider and the user LAN, as well as the open interface to connect multiple providers. This paper discusses the core network architecture of the PDC packet communication system. The requirement for the core network is described first. Then the mobility control, the data transfer control, and the system/protocol configuration are discussed. Lastly, the developed system is evaluated from the viewpoint of performance. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 86(4): 72–85, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.1159
Simulation analysis methods for mobile communication network traffic characteristics evaluations
Authors: Okamoto Masaki , Yoshida Yutaka
Published: December 2002

The traffic in the mobile communication network is increasing very rapidly, and intensive studies seek to enlarge the capacity of the network. In mobile communication, the moving characteristics and the communication characteristics of the mobile terminal have a large effect on the traffic characteristics, which makes the analysis difficult. In this paper, the service area is divided into unit areas called mobility zones, and each mobile terminal is assumed to perform a random walk among the mobility zones. It is also assumed that the mobile terminal takes one of the communication states (idle and communicating). Certain time distributions are assumed for the residence time and the duration of communicating state of the mobile terminal. The state of the communication network is represented by two expressions, and simulation procedures are proposed based on those expressions. Last, in order to demonstrate the usefulness of the proposed analysis, several examples of analysis are presented for the mobile communication network models. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 86(4): 86–93, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.1160
Performance modeling and evaluation of Web systems with proxy caching
Authors: Fujita Yasuyuki , Murata Masayuki , Miyahara Hideo
Published: December 2002

With the rapid expansion of Internet use and the recent development of multimedia, improving the quality of the Internet is becoming a crucial issue. To construct a network system with high performance for cost, an effective analysis must be made of the characteristics of the traffic flowing on the network, the processing performance of the Web server, and the processing performance of the proxy server with caching functions, and the resources must be allocated with good balance. In this paper, we present a modeling and performance evaluation of an entire Web system, including the Web server and proxy server. In particular, this paper presents basic data on the processing performance of the caching function of the proxy server acquired by benchmarking. A model of processing performance is presented. Then, taking account of past results, a performance evaluation model for the entire Web based on the newly constructed model is presented. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 86(4): 94–106, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.1161
Exploring feminist evaluation: The ground from which we rise
Authors: Sielbeck‐Bowen Kathryn A. , Brisolara Sharon , Seigart Denise , Tischler Camille , Whitmore Elizabeth
Published: December 2002

This chapter is the fruit of discussions among several evaluators with feminist inclinations. The authors explore numerous ideas or guidelines pertinent to feminist inquiry and begin the conversation that continues throughout this volume.
Gender matters: Feminist research in educational evaluation
Authors: Pillow Wanda S.
Published: December 2002

The key insights and shifts in first‐, second‐, and third‐wave feminism are examined, along with the impact on methodological thinking of what may be broadly termed “race‐based” feminisms, lesbian theory, postcolonial feminist theory, and post‐structuralism. This overview provides a present‐day portrait of where feminist theory is now and the continued importance of paying attention to gender, particularly in education.
Feminist evaluation and the inclusion of difference
Authors: Ward Hood Denice , Cassaro Denice A.
Published: December 2002

The potential impacts that issues of race/ethnicity, sex/gender, and class have for the evaluation enterprise are complex. These characteristics intersect in multifaceted ways, particularly in the context of a social/political enterprise such as program evaluation. This chapter presents a modest effort at acknowledgment and understanding.
Reflections on a job done: Well?
Authors: Ward Kristin J.
Published: December 2002

Seven guidelines for conducting feminist program evaluation are presented in the context of an evaluation of an adolescent gender violence prevention program. The methods and challenges of incorporating these guidelines are discussed.
Revisioning the process: A case study in feminist program evaluation
Authors: Beardsley Rebecca M. , Hughes Miller Michelle
Published: December 2002

Attention to the interpersonal and relational processes of feminist evaluation is overdue. In this chapter, we describe three aspects of a negotiated evaluation process, based on our experience as team members charged with the evaluation of a women's substance abuse prevention program.
Doing feminist evaluation with men: Achieving objectivity in a sexual health needs assessment
Authors: Truman Carole
Published: December 2002

Feminist approaches to research and evaluation have provided invaluable strategies that have been used to better understand women's lives. This chapter provides an account of how principles of objectivity developed within a feminist evaluation can be used to explore the sexual health needs of men who have sex with men.
Feminist evaluation in the international development context
Authors: Bamberger Michael , Podems Donna R.
Published: December 2002

This chapter reviews U.S. and other Western researchers' treatment of issues affecting women in evaluations of the impacts of international development assistance. In most cases, the evaluations do not adopt a specifically feminist approach but rather a women‐in‐development (WID) or, more recently, a gender approach. The authors discuss the extent to which these approaches address feminist research concerns and how a more explicitly feminist approach could strengthen the evaluation design.
Beginning the conversation
Authors: Sielbeck‐Bowen Kathryn A. , Brisolara Sharon , Seigart Denise , Tischler Camille , Whitmore Elizabeth
Published: December 2002

This chapter completes the volume with reflections on what we have learned from this exploration and what pathways we must now follow.
Expanding resources: Benefits to colleges and universities
Authors: Larrance Anneke J.
Published: December 2002

Consortial arrangements afford the opportunity for colleges and universities to leverage resources jointly so that the end result produces more than the member could have accomplished single‐handedly.
Partnerships with K–12 education
Authors: Druckman Rosanne , Peterson Lorna M. , Thrasher M. Sue
Published: December 2002

Higher education consortia are forming K–12 partnerships and alliances that are linking with individual public schools and their school systems.
Facilitating economic development through strategic alliances
Authors: Noftsinger John B.
Published: December 2002

Economic development provides an opportunity for higher education institutions to collaborate on public service programs that contribute to national, regional, and community vitality.
Consortia and institutional partnerships for community development
Authors: Williams Mitchell R.
Published: December 2002

Community development initiatives offer special opportunities for partnerships among institutions of higher education.
Leveraging higher education for workforce development
Authors: Horgan Thomas R.
Published: December 2002

Leveraging higher education resources to build a state's workforce takes dedicated commitments from business, education, and public policy leaders. Consortia can play an important role as facilitator and convener.
Technology partnerships for faculty: Case studies and lesson learned
Authors: Anderson Wayne , Bonefas Suzanne
Published: December 2002

Faculty‐technology partnerships can be a valuable method by which faculty from different institutions and disciplines share their expertise to enhance teaching and learning.
Creating networks through interinstitutional faculty collaboration
Authors: Marino Sarah R.
Published: December 2002

Consortia can develop, support, and sustain long‐term interinstitutional faculty collaboration through a variety of structural models.
Academic library consortia in transition
Authors: Alberico Ralph
Published: December 2002

Library consortia are in a state of transformation as technology enables the development of virtual libraries while expanding opportunities for sharing printed works.
Consortium purchasing
Authors: Bishop Jake E.
Published: December 2002

Purchasing as a profession has changed from buying things to managing processes, and the change has enhanced the use of consortium or group purchasing as a cost‐effective tool.
Cooperation and alliances: Higher education and the use of television
Authors: Dotolo Lawrence G.
Published: December 2002

Consortia can use television to serve the educational needs of the community and at the same time form strategic alliances with other agencies to enhance their efforts to meet the demands of their clientele.
Assessing a consortium's effectiveness
Authors: Peterson Lorna M.
Published: December 2002

The benefits of cooperation through consortium arrangements extend beyond dollars saved.
Inhibitory effect of p27KIP1 gene transfer on head and neck squamous cell carcinoma cell lines
Authors: Koh Tae‐Yong , Park Seok‐Woo , Park Kyung‐Ho , Lee Sang‐Goo , Seol Jae‐Goo , Lee Dong‐Wook , Lee Choon‐Taek , Heo Dae‐Seog , Kim Kwang‐Hyun , Sung Myung‐Whun
Published: December 2002

Background.

Although p27 gene mutations are rarely found in cancer, the level of p27 protein expression decreases during tumor development. In several tumors, including laryngeal cancer, decreased expression of p27 is associated with a poor prognosis.

Methods.

The proliferation‐inhibitory effect of p27 gene transfer on human head and neck squamous cell carcinoma (HNSCC) cell lines (SNU‐1041, SNU‐1066, and SNU‐1076) by adenoviral vector was investigated.

Results.

On transduction of the human HNSCC cell line with adenovirus‐p27 (Ad‐p27), a high level of p27 expression and increase of cyclin D1 and E were observed. Cell cycle analysis showed a marked decrease in the proportion of cells in S phase and an increase in G1 phase. Soft agar clonogenic assay showed a marked decrease in clonogenicity.

Conclusion.

These results suggested that overexpression of p27 could show proliferation‐inhibitory effects on HNSCC cell lines. Thus, gene therapy using adenovirus‐p27 seemed to have a potential to develop into a new cancer gene therapy modality. © 2002 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003
Transcervical superior mediastinal lymphadenectomy in the management of papillary thyroid carcinoma
Authors: Khoo Mark L. C. , Freeman Jeremy L.
Published: December 2002

Aim.

Surgery is the treatment of choice for lymph node metastases in papillary thyroid carcinoma. When adequately treated by surgical extirpation, the presence of lymph node involvement does not seem to have a negative impact on cure rates or survival. Surgical lymphadenectomy for metastatic papillary thyroid carcinoma has been well described for both the central and the lateral compartments of the neck. Superior mediastinal lymphadenectomy, however, has only sporadically been mentioned. We describe our experience with transcervical superior mediastinal lymphadenectomy (TSML) that avoids the morbidity of the traditional sternal split.

Materials and Methods.

This retrospective analysis included 30 patients (24 women and 6 men; age range, 17–72 years) who underwent TSML by the senior author (JLF) for papillary carcinoma metastatic to the superior mediastinum between 1985 and 1999. Histopathologic examination confirmed positive nodes in all the mediastinal dissections. All patients received postoperative I131.

Results.

All the patients are alive after a median follow‐up of 5 years (range, 1–14 years). Twenty‐nine of 30 patients remain free of disease, whereas one patient is alive with lung and bone metastases. No patient has had local or regional relapse. The only significant complication was a high incidence of temporary (70%) and later permanent (50%) hypoparathyroidism.

Conclusions.

TSML is a safe and effective treatment for superior mediastinal metastases in papillary thyroid carcinoma. © 2002 Wiley Periodicals, Inc. Head Neck 24: 000–000, 2002
Prognostic impact of reoxygenation in advanced cancer of the head and neck during the initial course of chemoradiation or radiotherapy alone
Authors: Dietz Andreas , Vanselow Bernhard , Rudat Volker , Conradt Christian , Weidauer Hagen , Kallinowski Friedrich , Dollner Ralph
Published: December 2002

Background.

Previous studies have shown that radiation of hypoxic tumors can result in reoxygenation phenomenon. The relevance of this phenomenon for prognosis is unclear. This study analyzes whether the presence of hypoxia, or the extent to which reoxygenation occurs during the initial phase of primary chemoradiation or radiotherapy, can predict the clinical outcome in advanced tumors of the head and neck.

Methods.

The distribution of oxygen partial pressures was determined using pO2 histography (Kimoc 6650, Sigma pO2‐Histograph, Eppendorf, Hamburg, Germany). In cervical lymph node metastases of 37 patients with advanced carcinoma of the head and neck (stage IV, UICC), these values were determined before the start of primary chemoradiation or radiotherapy alone (pO2x). Thirty‐two of 37 patients were reexamined after 1 week of therapy, and measurements were taken again in the same nodes (pO2y). The results obtained from these measurements were correlated with both, the initial response to therapy and follow‐up results (43 months).

Results.

In all patients, pronounced hypoxia (median pO2, 3.2 mmHg) was found before therapy. In 19 of 32 patients, chemoradiation/radiotherapy induced reoxygenation (ΔO2 = pO2y − pO2x), with median ΔpO2 increasing to 6.5 mmHg after 1 week (p = .049). The group of patients with a complete or partial response showed only a slight increase of median ΔpO2 (1 mmHg) compared with a strong reoxygenation effect in the group of patients with no change (mean value of median ΔpO2 = 10.3 mmHg; p = .0062). The group of patients with ΔpO2 values lower than median showed significantly better survival rates compared with the other group (p = .036).

Conclusion.

These data suggest that reoxygenation under therapy may have prognostic relevance in patients with advanced carcinoma of the head and neck treated by primary chemoradiation or radiation therapy. Remarkably, however, a poor outcome was associated with a higher degree of reoxygenation. © 2002 Wiley Periodicals, Inc. Head Neck 24: 000–000, 2002
The treatment of squamous cell carcinoma of the tonsil with neck node metastases
Authors: Jones Andrew Simpson , Fenton John Eugene , Husband David John
Published: December 2002

Background.

Patients with tonsillar carcinoma and neck nodes seen at the clinic are not an uncommon occurrence in head and neck practice. Over the years, treatment has ranged from radical jaw neck dissection to radical neck dissection for the nodes and primary radiotherapy to the primary site. Much controversy exists as to which treatment modality yields the best survival. Certainly, surgery to the oropharynx leads to gross morbidity, with problems of swallowing, speech, and cosmesis, although it has been claimed that radiotherapy with neck dissection yields a lower cure rate.

Methods.

We investigated a retrospective series of 96 patients all of whom had squamous cell carcinoma of the tonsil and associated lymph node metastases. Of these, 44 primary tumors were treated with surgery and 52 with irradiation. All 44 patients in the surgery group had a radical neck dissection, as did all but 12 in the radiotherapy group.

Results.

Of the tabulations, patients in good general condition were more likely to receive primary surgery. Overall cause‐specific survival for all patients was 69%. Multiple logistic regression revealed no associations; thus, the radiotherapy and surgery groups were well matched. Five‐year actuarial survival for those having irradiation was 74%. The five‐year survival for the group receiving surgery was 63% (p= .4372). This lack of difference between survival for surgery and radiotherapy was confirmed using Cox's proportional hazards model.

Conclusion.

We conclude that tonsillar carcinoma with lymph nodes can be safely treated by applying appropriate radiotherapy to the tonsillar region and treating the neck with radical surgery, if the disease is more than N1. © 2002 Wiley Periodicals, Inc. Head Neck 24: 000–000, 2002
Targeting epidermal growth factor receptor in head and neck cancer
Authors: Ford Allison Carter , Grandis Jennifer Rubin
Published: December 2002

It is well known that growth factors play an important role in normal cell proliferation by means of stimulation of growth factor receptors located on the surface of cells. Tumor cells express high levels of growth factor receptors that can theoretically serve as therapeutic targets in cancer treatment. Tyrosine kinase (type 1) growth factor receptors include the family of erbB receptors. The most extensively studied receptor in the erbB family is the human epidermal growth factor receptor (EGFR), also known as erbB1. Studies have shown that overexpression of EGFR is involved in the development and progression of head and neck squamous cell carcinoma (HNSCC). Blocking this receptor in HNSCC cell lines and animal models inhibits tumor growth. Strategies have been developed to target EGFR, including monoclonal antibodies, tyrosine kinase–specific inhibitors, ligand‐linked immunotoxins, and antisense approaches. Laboratory studies and clinical trials are under way to explore the safety and efficacy of these various approaches in a variety of cancers, including HNSCC. Preliminary results from early phase clinical trials are encouraging and may lead to the incorporation of these EGFR targeting strategies into the management of HNSCC. © 2002 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003
Health‐related quality of life of children with acute lymphoblastic leukaemia: Comparisons and correlations between parent and clinician reports
Authors: Waters Elizabeth B. , Wake Melissa A. , Hesketh Kylie D. , Ashley David M. , Smibert Elizabeth
Published: December 2002

The improving prognosis for children with cancer refocusses attention to long‐term outcomes with an emphasis on quality of life. Few studies have examined relationships and differences in reported results between the parent, child and clinician. We examined parent‐proxy and clinician‐reported functional status and health‐related quality of life for children and adolescents with acute lymphoblastic leukemia (ALL). Children and adolescents, 5–18 years, in the maintenance phase of treatment for ALL attending the Haematology/Oncology outpatient clinic at the Royal Children's Hospital, Melbourne, were eligible. Measures included: 1) parent‐reported functional health and well‐being (Child Health Questionnaire [CHQ]); 2) parent‐reported condition specific quality of life (Pediatric Cancer Quality of Life inventory [PCQL]); 3) clinician ratings of physical and psychosocial health; and 4) clinical indicators. Insufficient numbers of older patients prohibited collection of adolescent self‐reports. We had a 94% response and 31 participants. Mean time since diagnosis: 1.5 (SD 0.4) years. Parents reported significantly lower functioning and well‐being than population norms for all CHQ scales, whereas cancer‐specific quality of life was comparable to PCQL norms. Clinician reports of the child's global physical and psychosocial health were moderately associated with each other (rs = 0.56, p < 0.001), and with the parent‐reported physical (rs = 0.47, p < 0.01) and psychosocial (rs = 0.56, p < 0.001) CHQ summary scores. Clinician reports of the child's psychosocial health were not associated with any clinical indicators reported regularly. The results demonstrate that the social, physical and emotional health and well‐being of children with ALL is significantly poorer than the health of their community‐based peers. Routinely collected indicators of clinical progress conceal the psychosocial burden of ALL. Data on health, well‐being and quality of life can easily be incorporated into clinical care. © 2002 Wiley‐Liss, Inc.
TCDD‐dependent downregulation of γ‐catenin in rat liver epithelial cells (WB‐F344)
Authors: Dietrich Cornelia , Faust Dagmar , Moskwa Matthias , Kunz Anja , Bock Karl‐Walter , Oesch Franz
Published: December 2002

TCDD (2,3,7,8‐tetrachlorodibenzo‐p‐dioxin) is the most potent tumor promoter ever tested in rodents. Although it is known that most of the effects of TCDD are mediated by binding to the aryl hydrocarbon receptor (AHR), the mechanisms leading to tumor promotion still remain to be elucidated. Loss of contact‐inhibition is a characteristic hallmark in tumorigenesis. In WB‐F344 cells, TCDD induces a release from contact‐inhibition manifested by a 2‐ to 3‐fold increase in DNA‐synthesis and the emergence of foci when TCDD (1 nM) is given to confluent cells. We focussed our interest on potential cell membrane proteins mediating contact‐inhibition in WB‐F344 cells, namely E‐cadherin, α,‐ β,‐ and γ‐catenin (plakoglobin). Using indirect immunofluorescence, E‐cadherin, α‐, β‐ and γ‐catenin were detected at cell adhesion sites in untreated, confluent cells. After TCDD‐exposure, γ‐catenin was exclusively localized in the cytoplasm whereas localization of E‐cadherin, α‐ and β‐catenin remained unaffected. Cytoplasmic γ‐catenin could be extracted by Triton X‐100 treatment, demonstrating that γ‐catenin was no longer bound to the actin cytoskeleton. Western blot analysis showed downregulation of γ‐catenin protein levels. This effect was not blocked by pre‐incubation with the selective proteasome inhibitor MG‐132, indicating that proteolytical degradation of γ‐catenin by the proteasome system was not increased by TCDD. Because mRNA‐levels of γ‐catenin were markedly diminished after TCDD‐exposure, we conclude that transcriptional downregulation or destabilization of the mRNA contributes to the decrease in γ‐catenin protein levels in response to TCDD. Because γ‐catenin is considered to be a tumor suppressor, our findings might give more insight into the tumor promoting actions of TCDD. © 2002 Wiley‐Liss, Inc.
Potent activity of soluble B7RP‐1‐Fc in therapy of murine tumors in syngeneic hosts
Authors: Ara Gulshan , Baher Angelo , Storm Neal , Horan Tom , Baikalov Claudia , Brisan Emil , Camacho Reuben , Moore Alison , Goldman Hartt , Kohno Tadahiko , Cattley Russell C. , Van Gwyneth , Gaida Kevin , Zhang Ming , Whoriskey John S. , Fong David , Yoshinaga Steven K.
Published: December 2002

We have characterized a receptor:ligand pair, ICOS:B7RP‐1, that is structurally and functionally related to CD28:B7.1/2. We reported previously that B7RP‐1 costimulates T cell proliferation and immune responses (Yoshinaga et al., Nature 1999;402:827–32; Guo et al., J Immunol 2001;166:5578–84; Yoshinaga et al., Int Immunol 2000;12:1439–47). We report that B7RP‐1‐Fc causes rejection or growth inhibition of Meth A, SA‐1 and EMT6 tumors in syngeneic mice. Established Meth A tumors were rejected effectively with a single dose of B7RP‐1‐Fc, however, the treatment was less effective on larger tumors. Mice that rejected Meth A tumors previously by Day 30, also rejected a subsequent Meth A challenge on Day 60, without additional B7RP‐1‐Fc treatment, indicating a long‐lived memory response. Tumor cells believed to be less immunogenic, such as P815 and EL‐4 cells, were less responsive to this treatment. The EL‐4 responsiveness to the B7RP‐1‐Fc treatment was enhanced, however, by pre‐treatment of the mice with cyclophosphamide. As expected, T cells appeared to be targeted by B7RP‐1‐Fc treatment. Thus, the administration of soluble B7RP‐1‐Fc may have therapeutic value in generating or enhancing anti‐tumor activity in a clinical setting. © 2002 Wiley‐Liss, Inc.
Multiple meningiomas: Investigating the molecular basis of sporadic and familial forms
Authors: Heinrich Bianca , Hartmann Christian , Stemmer‐Rachamimov Anat O. , Louis David N. , MacCollin Mia
Published: December 2002

Meningiomas are common tumors of the coverings of the central nervous system (CNS), comprising 20% of intracranial neoplasms. The only genes known to be associated with sporadic meningiomas are NF2 on chromosome 22 and the related cytoskeleton element DAL‐1 on chromosome 18. Between 1 and 8% of patients with meningiomas develop multiple meningiomas, a trait transmitted occasionally in an autosomal dominant fashion. We investigated the DAL‐1 and NF2 loci in 7 unrelated multiple meningioma patients without clinical evidence of NF2 by mutational and pathological analysis. Five novel intragenic microsatellite polymorphisms were developed for specific detection of loss of heterozygosity (LOH) at the DAL‐1 locus. Three of 7 patients had affected relatives and all affected individuals were female. No tumors from familial patients were of a fibroblastic subtype. Truncating NF2 mutations were detected in 3 tumor specimens, but were not present in the corresponding blood samples. Two tumors showed LOH at the NF2 locus. All tumors showing mutations at the NF2 locus originated from patients without affected relatives and were of the fibroblastic subtype. Five non‐truncating alterations in the DAL‐1 gene were found, however, LOH of chromosome 18 markers was not seen in any tumor. In contrast to the NF2 results, all DAL‐1 alterations were found in paired blood specimens. Our findings provide further evidence that the molecular basis of sporadic and familial multiple meningiomas is fundamentally different and extend this dichotomy to pathologic subtypes. DAL‐1 does not function as a true tumor suppressor in these patients. © 2002 Wiley‐Liss, Inc.
Natural killer, but not natural killer T, cells play a necessary role in the promotion of an innate antitumor response induced by IL‐18
Authors: Hashimoto Wataru , Tanaka Fumiaki , Robbins Paul D. , Taniguchi Masaru , Okamura Haruki , Lotze Michael T. , Tahara Hideaki
Published: December 2002

IL‐18 administration promotes innate immunity resulting in significant antitumor effects in multiple murine tumor models. Here, we examined the effector population mediating the innate immunity. Most NK cells and some NKT cells express IL‐18Rs without prior stimulation (65% positive in NK cells, 18% positive in NKT cells), though few naive T cells do. In vivo depletion of NK cells, but not NKT cells, using AsGM1 antibody significantly reduces IL‐18‐induced cytotoxicity. However, NK‐like activity of hepatic MNCs for the NK target YAC‐1 was present in Vα 14 NKT cell–deficient animals. Furthermore, administration of rIL‐18 greatly reduced B16 pulmonary metastases in vivo in NKT cell–deficient animals. When sorted NK and NKT cells were exposed to IL‐18 in vitro, NK cells showed more IFN‐γ production and cytolysis against YAC‐1 than NKT cells in response to IL‐18. These results are consistent with the notion that NK cells, but not NKT cells, are the major effectors in IL‐18‐induced innate immunity. © 2002 Wiley‐Liss, Inc.