bluuebunny/crossref_metadata_2025 huggingface dataset:
Constructing Shared Understanding
Authors: Jacobs Claus D. , Heracleous Loizos Th.
Published: May 2006

The authors present a novel metaphorical approach to organization development, the use of embodied metaphors, and in so doing extend current understandings and uses of metaphor in organization development (OD). The authors discuss an intervention technology that emphasizes induced rather than naturally occurring metaphors, builds on a developed theoretical base of collaborative diagnostic technologies, and can be employed in a targeted manner for issue diagnosis and intervention. Implications for the use of embodied metaphors in OD are discussed.
A German ‘Heimat’ further east and in the Baltic region?
Authors: Ludewig Alexandra
Published: May 2006

Since the fall of the Berlin Wall, unification and the subsequent reinvention of the nation, German filmmakers have revisited their country's ‘Heimatfilm’ traditions with a view to placing themselves creatively in the context of its intellectual and artistic heritage. However, German directors like Ute Badura, Volker Koepp, Andreas Dresen, Peter Welz and Andreas Kleinert, choose an Eastern setting for their films – rather than alpine or heath landscapes – as they ascribe symbolic value to the Baltic region and former German territories in the East. In many instances their films culminate at the sea which stands for the rough elements of nature as experienced in numero u s maritime disasters in the untamed tidal waters of Germany's limited coastline. The ocean drives home the message that the only certainty in life is change. But why did they choose the contested Eastern German territories and the Baltic Sea? Is this reorientation and paradigm shift in the Heimat genre from the west to the east a rapprochement or, rather, a territorial claim? Are the shores of the Baltic Sea perhaps expressing a yearning for former German territories further east that were lost after 1945? This article will probe several interpretations of the Baltic shore as a cinematic motif.
Hepatitis C Virus Infection Among Homeless Men Referred From a Community Clinic
Authors: Nyamathi Adeline M. , Dixon Elizabeth L. , Wiley Dorothy , Christiani Ashley , Lowe Ann
Published: May 2006

In this study of factors related to Hepatitis C virus (HCV) infection in 104 homeless HCV-infected men and 94 uninfected homeless men, findings reveal that homeless men with HCV infection are older and more likely to be cocaine injectors than those not infected. Moreover, the sharing of needles, use of injected cocaine during the past 6 months, previous incarceration, veteran status, fair or poor health, and having multiple tattoos are also associated with HCV infection. Reports of having completed the HBV vaccination series, weekly marijuana use, and snorting cocaine or methamphetamine are negatively associated with HCV infection. Among men not reporting lifetime injection drug use, factors such as sharing toothbrushes, having multiple tattoos, being in fair or poor health, and past incarceration are associated with HCV infection. These findings may need to be considered when making screening decisions and counseling homeless male patients about HCV.
Spanish Academic Publishing in Sociology
Authors: Morató Arturo Rodríguez
Published: May 2006

This article analyses the situation of publications in the realm of sociology in Spain. On the one hand, it looks at the development of Spanish sociological production and its public over time in relation to the process of the discipline's institutionalization ie country. On the other hand, it examines comparatively the different editorial sectors that have to do with Spanish sociological work: the commercial, institutional and university sectors. Finally, the article demonstrates that by contrast with the Anglo-Saxon model of editing, Spanish sociological editing suffers from less of an editorial drive for the initiation of projects and the promotion of published works, as well as from less rewarding relationships between authors and editors. This unsatisfying situation is interpreted in relation to certain weaknesses of the Spanish sociological community that can be attributed to the problematic institutionalization of sociology in Spain.
Catastrophic Antiphospholipid Syndrome
Authors: Vora Setu K. , Asherson Ronald A. , Erkan Doruk
Published: May 2006

Catastrophic antiphospholipid syndrome is a rapidly progressive life-threatening disease that causes multiple organ thromboses and dysfunction in the presence of antiphospholipid antibodies. A high index of clinical suspicion and careful investigation are required to make an early diagnosis so that treatment with anticoagulation and corticosteroids can be initiated; plasma exchange and/or intravenous immunoglobulins can be added if the life-threatening condition persists. Despite aggressive treatment and intensive care unit management, patients with catastrophic antiphospholipid syndrome have a 48% mortality rate, primarily attributable to cardiopulmonary failure. This article reviews the current information on the etiopathogenesis, clinical manifestations, diagnosis, management, and prognosis of catastrophic antiphospholipid syndrome.
Urban Adolescent Mothers Exposed to Community, Family, and Partner Violence
Authors: Kennedy Angie C. , Bennett Larry
Published: May 2006

Using a risk and resilience perspective, the authors assessed urban adolescent mothers’ exposure to community, family, and partner violence and analyzed the relationships between cumulative violence exposure and multiple school outcomes, within the context of welfare reforms. Positive attitude toward school and social support were examined as moderators of violence exposure on school outcomes. The authors pilot tested the questionnaire with 10 participants, then surveyed 120 adolescent mothers regarding their violence exposure, school performance and participation, positive attitude toward school, and social support. Results indicate very high rates of lifetime exposure to violence; intercorrelations and regression analyses indicate that as violence exposure increases, school outcomes tend to worsen, with positive attitude toward school found to be a significant moderator of the effects of exposure to community violence on behavior problems in school. Implications for researchers, practitioners, school policies and programs, and welfare policies and programs conclude the article.
The Role of Victim-Offender Relationship in Women’s Sexual Assault Experiences
Authors: Ullman Sarah E. , Filipas Henrietta H. , Townsend Stephanie M. , Starzynski Laura L.
Published: May 2006

This study’s goal is to identify differences in background, assault, and postassault factors according to the victim-offender relationship. A mail survey is conducted with more than 1,000 female sexual assault survivors (response rate 90%) recruited from college, community, and mental health agency sources. Stranger assailants are associated with a greater victim perceived life threat, more severe sexual assaults, and ethnic minority victims. Positive social reactions do not vary according to the victim-offender relationship, but stranger victims report more negative social reactions from others than do victims of acquaintances or romantic partners. Assaults by strangers and relatives are associated with more posttraumatic stress disorder (PTSD) symptoms than assaults by acquaintances and romantic partners. As expected, survivors’ social cognitive responses to rape and social reactions from support providers are stronger correlates of PTSD symptoms than demographic or assault characteristics in general, but correlates vary across victim-offender relationship groups.
Environmental Reform in the Electricity Sector
Authors: D’Sa Antonette , Murthy K. V. Narasimha
Published: May 2006

This article analyzes the challenges to effective environmental protection in the power sectors of China and India. Its analytical framework consists of identification of environmental policies and regulations affecting electricity generation, assessment of problems faced when implementing these policies and regulations, and finally recommendations for surmounting the barriers encountered. Environmental issues in the electricity sector have been addressed directly, through laws and governmental orders, and indirectly, through policies on alternative technologies and efficiency improvement. However, successful environmental regulation has been hampered in these large developing countries by the compelling need for energy and the consequent rapid increase in electricity generation. Solutions to these problems lie in combinations of cleaner and more-efficient generation, appropriate control equipment, and more-efficient end-use devices. Among factors that facilitate effective adoption of these solutions are state prioritization, fiscal and financial incentives, appropriate technological choices, institutional involvement, integrated planning, public participation, and international commitments.
Transboundary Perspectives on Managing Indonesia’s Fires
Authors: Mayer Judith
Published: May 2006

This study explores initiatives in Indonesia, Singapore, and Malaysia to eliminate transboundary “haze” in Southeast Asia and the fires in Indonesia that are its major cause. It outlines reforms and technical programs to improve fire management and reduce smoke pollution and examines the scope for cooperation and conflict among these parties to the Association of South East Asian Nations (ASEAN) Agreement on Transboundary Haze Pollution. The study analyzes how changing administrative structures affect success of fire management and pollution control programs and explains how developing the effective fire management in Indonesia necessary to eliminate transboundary haze will depend on a combination of political will, legal reform, and administrative coordination. Although the ASEAN Haze Agreement lacks enforceable mandatory provisions, it remains a useful vehicle for international pressure and regional cooperation to eliminate transboundary pollution.
Evaluation of the Computerized Assessment System for Psychotherapy Evaluation and Research (CASPER) as a Measure of Treatment Effectiveness With Psychiatric Inpatients
Authors: Kinnaman Joanna E. Strong , Farrell Albert D. , Bisconer Sarah W.
Published: May 2006

Assessment procedures to evaluate inpatient treatment effectiveness can provide information to inform clinical practice. The Computerized Assessment System for Psychotherapy Evaluation and Research (CASPER) represents a standardized approach to assess patients’ target problems that combines elements of individualized and nomothetic approaches. Although previous evaluations of CASPER with other patient populations have been encouraging, its use as a measure of change with an inpatient population has not been examined. In this study, 75 psychiatric inpatients completed CASPER and the Behavior and Symptom Identification Scale-32 (BASIS-32) at hospital admission and discharge. Results supported the concurrent validity of CASPER as a measure of pre- and posttreatment functioning and suggested that CASPER may provide a sensitive measure of change during inpatient treatment. Findings also supported the notion that patients’ ratings of the extent to which their treatment focused on the problems they identified as a high priority were related to their overall treatment satisfaction.
Psychometric Properties of an Abbreviated Instrument of the Five-Factor Model
Authors: Mullins-Sweatt Stephanie N. , Jamerson Janetta E. , Samuel Douglas B. , Olson David R. , Widiger Thomas A.
Published: May 2006

Brief measures of the five-factor model (FFM) have been developed but none include an assessment of facets within each domain. The purpose of this study was to examine the validity of a simple, one-page, facet-level description of the FFM. Five data collections were completed to assess the reliability and the convergent and discriminant validity of the rating form with other measures of the FFM and to replicate correlations with measures of maladaptive personality functioning that have been obtained with more extensive measures. Results appeared to support the validity of the FFM rating form (FFMRF) because it obtained relatively good internal consistency, convergent validity, and discriminant validity. In addition, self-descriptions of persons in terms of the FFMRF related to maladaptive personality traits in a manner that was consistent with theoretical expectations. Negative findings and limitations of the rating form also are discussed.
Depression as Measured by the Beck Depression Inventory-II Among Injecting Drug Users
Authors: Johnson Mark E. , Neal David B. , Brems Christiane , Fisher Dennis G.
Published: May 2006

This study conducts a confirmatory factor analysis of the Beck Depression Inventory-II (BDI-II) with a sample of 598 individuals who reported recent injecting drug use. Findings indicate that out of four models tested, the best model for this sample is a three-factor solution (somatic, affective, and cognitive) previously reported by Buckley, Parker, and Heggie. The findings that nearly 50% of participants provided BDI-II scores indicating significant depressive symptomatology reveals that these individuals are in need of treatment for their psychiatric symptoms as well as substance use. Somatic symptoms are endorsed more strongly than affective or cognitive symptoms of depression, suggesting a possible, but yet poorly defined, relationship between depressive symptomatology and drug use that centers on shared somatic symptomatology.
Foucault’s Law: The Crime and Disorder Act 1998
Authors: Smith Roger
Published: May 2006

This article draws on the theories of Michel Foucault to develop a particular characterisation of the Crime and Disorder Act 1998. In short, it is argued that Foucault’s historical portrayal of the penal system finds clear and strong echoes in the recent UK criminal justice legislation. The development of sophisticated techniques of discipline and control found in key aspects of the 1998 Act reflects his description of finely graded and systematically applied interventions in the context of delinquent (and pre-delinquent) behaviour. The implications of this are considered, both for the burgeoning machinery of youth justice, and also for young people who are likely to be subjected to these intensified forms of coercive practice.
Questioning New Labour’s Youth Justice Strategy: A review article
Authors: Jones Denis W
Published: May 2006

The Crime and Disorder Act 1998 and Part 1 of the Youth Justice and Criminal Evidence Act 1999 enshrine New Labour’s youth justice strategy for England and Wales. Some have claimed that this is just a development of the previous Conservative government’s ideas. This article sets out to challenge this, and show the unique development of Labour thinking over the past decade, and then bring together, in the form of a review article, a wide range of published academic critique of the main components of the new legislation.
Policy Transfers and ‘What Works’: Some Reflections on Comparative Youth Justice
Authors: Muncie John
Published: May 2006

This article explores the implications for youth justice in England and Wales of borrowing other states’ penal initiatives in the pursuit of a pragmatic ‘what works’ agenda in crime prevention and reducing re-offending. It is argued that whilst the policy transfer of elements of restorative justice from the likes of Australasia and Scotland has the potential to radically rethink current practice its implementation is partial and piecemeal. The dominant recurrent influence remains that of American inspired punitive justice. Meanwhile some important lessons in child protection, diversion and decarceration from Europe are ignored. The adoption of ‘what works’ is highly selective and in itself provides a dubious basis for reform. What superficially appears as a new open-mindedness to learn from academic evaluation and ‘best practice’ world-wide, masks the fundamentally political and ideological nature of contemporary youth justice policy.
‘There Must be Some Way of Dealing with Kids’: Young Offenders, Public Attitudes and Policy Change
Authors: Allen Rob
Published: May 2006

New Labour’s youth justice reforms have left progressives disappointed by a failure to take more radical steps to raise the age of criminal responsibility and phase out penal custody. This paper argues that the basic punitive orientation governing youth justice policy was established in the early 1990s, in the wake of concern about persistent juvenile offenders and the high-profile James Bulger case. The punitive orientation of policy is apparently supported by public opinion, or at least the perception of public opinion held by policy makers. The paper summarises what is known about public attitudes to adult and juvenile offenders and suggests a strategy to increase understanding and raise the level of debate, which are prerequisites for any fundamental change in policy orientation.
Practising in a Context of Ambivalence: The Challenge for Youth Justice Workers
Authors: Eadie Tina , Canton Rob
Published: May 2006

Practitioners have always recognised those they work with as young people in need as well as offenders. The political imperative to be ‘tough on crime’ has distorted this perception, while managerialist approaches, believing that accountability demands minimal discretion, have made it harder for practitioners to do justice to the diversity of individuals’ circumstances. This article suggests that there is no inherent contradiction between good, consistent service delivery and wide (though not unbounded) discretion. Arguing that best practice requires both high accountability and wide discretion, it warns that an uncritical implementation of National Standards could lead to unfair and ineffective practice.
Chaos, Containment and Change: Responding to Persistent Offending by Young People
Authors: McNeill Fergus , Batchelor Susan
Published: May 2006

This article reviews policy developments in Scotland concerning ‘persistent young offenders’ and then describes the design of a study intended to assist a local planning group in developing its response. The key findings of a review of casefiles of young people involved in persistent offending are reported. It emerges that youth crime and young people involved in offending are more complex and heterogeneous than is sometimes assumed. This, along with a review of some literature about desistance from offending, reaffirms the need for properly individualised interventions. Studies of ‘desisters’ suggest the centrality of effective and engaging working relationships in this process. However, these studies also re-assert the significance of the social contexts of workers’ efforts to bring ‘change’ out of ‘chaos’. We conclude therefore that the ‘new correctionalism’ must be tempered with appreciation of the social exclusion of young people who offend.
Living with Final Warnings: Making the Best of a Bad Job?
Authors: Bateman Tim
Published: May 2006

This article examines the final warning scheme from a number of perspectives. In the first place it considers the rationale for the abolition of police cautioning for children and young people and subjects it to critique. It then reviews the recent evidence that has a bearing on the likely impact of the scheme in terms of the prevention of offending. Finally, some unintended consequences of the new system, with particular reference to its implementation, are identified, and some related observations regarding the potential implications for practitioners are discussed.
Still Children First? Developments in Youth Justice in Wales
Authors: Cross Noel , Evans Jonathan , Minkes John
Published: May 2006

This paper examines some emerging evidence in relation to the impact of recent organisational changes in the delivery of youth justice services, and the implementation of National Standards for youth justice, on occupational culture in work with young offenders. It considers the potential conflict between traditional child centred youth justice practice and the new priorities set for Youth Offending Teams (YOTs) by the Youth Justice Board for England and Wales, and it draws attention to the possibility of a divergence in philosophy and practice between Wales and England. The paper highlights the uneasy philosophical differences that co-exist within YOTs, and it explores the respective perceptions of qualified practitioners and social work students on placement, concerning the state of current practice. Finally, the implications for those involved in the education and training of social work students are briefly considered.
Changing Youth Justice
Authors: Pitts John
Published: May 2006

This article contends that the depoliticisation of its knowledge base, and greater openness to alternative perspectives on the part of policy makers, could only benefit the development of the youth justice system in England and Wales. It argues that an open-minded reappraisal of ‘welfarism’ and ‘progressive minimalism’, rejected by New Labour on essentially ideological grounds, could offer solutions to some of the problems presently confronting the Youth Offending Teams (YOTs), the Juvenile Secure Estate, and the Youth Justice Board for England and Wales (YJB).
Evidence-Based Youth Justice? Some Valuable Lessons from an Evaluation for the Youth Justice Board
Authors: Wilcox Aidan
Published: May 2006

This article explores the reasons behind government support for the evidence-based approach and considers the limitations of this concept. In the criminal justice field the government has made repeated claims that it is using evidence to help inform policy. Drawing on the experience of an evaluation of restorative justice (RJ) projects - commissioned by the Youth Justice Board for England and Wales (YJB) - the article concludes that, in this instance, the YJB by-passed an evidence-based approach and gave more priority to developing practice than to the needs of rigorous evaluation. On a more positive note, it is argued that the YJB has recognised the tension between the needs of dynamic policy development and the requirements of rigorous evaluation, and its recent approach to evaluation signals a move towards the latter.
What Do We Want? The ‘SHAPE’ Campaign and the Reform of Youth Justice
Authors: Pitts John
Published: May 2006

This paper considers how the stated objectives of the recently launched SHAPE campaign to reform youth justice in England and Wales might be concretised, and its strategy refined, in the light of recent research evidence and the present government’s political imperatives and administrative priorities.
Rethinking Youth Prostitution: National Provision at the Margins of Child Protection and Youth Justice
Authors: Phoenix Joanna
Published: May 2006

In March 2000, the Department of Health and the Home Office issued guidance fundamentally altering policy and practice with regard to young people in prostitution.1Instead of being arrested and punished for prostitution-related offences, those under 18 years old were to be thought of as children ‘in need’ and offered welfare-based interventions. The practice that has developed in the last three years has offered interventions that are located within both child protection and youth justice work. This article examines these changes in order to generate insights about the changing nature of youth justice. In particular, it is argued that the drive to manage the risks posed by young people in prostitution to specific organisations, takes precedence over either the desire to care for, or the demand to punish them. Through an analysis of how practitioners and policy makers responsible for implementing this new approach to youth prostitution talk about ‘risk’ and ‘responsibility’, ‘liability’, ‘protection’ and ‘punishment’, the article argues that the contradiction between care and control has been re-interpreted, such that there is noticeable blurring of the boundaries between welfare and punishment at the margins of youth justice work.
Requirements for Communication in the Courtroom: A Comparative Perspective on the Youth Court in England/Wales and The Netherlands
Authors: Weijers Ido
Published: May 2006

The UK Government’s White Paper ‘No More Excuses’ (Home Office, 1997) set out plans for changing the culture of the Youth Court. This article focuses on one crucial aspect of the reform plans: the idea that magistrates need to engage with young offenders and their families. After a theoretical analysis of the foundation and justification for a special youth court, the article presents some findings concerning differences between the communication cultures of English/Welsh and Dutch Youth Courts. The article concludes by questioning the basic assumption of the White Paper, that fundamental changes could be realised without structural reform.
Promoting Prevention: A Multi-agency Initiative to Prevent Youth Offending Through Consultation in Swansea Schools
Authors: Haines Kevin , Case Stephen
Published: May 2006

The purpose of this article is to set out Swansea’s response to the Crime and Disorder Act 1998 and related matters, which encompasses an explicitly universal, positive and young person-focused approach to crime prevention. This stands in contrast to more controlling or punitive practices developed elsewhere. Research into the multi-agency, multiple intervention Promoting Preventionprogramme has utilised an interactive, computer-based questionnaire with young people aged 11-15 to identify risk and protective factors associated with youth offending in Swansea. This has enabled the Promoting Preventionsteering group to begin to target appropriate interventions to reduce and prevent youth offending, as reflected in the decrease in official offending locally.
The Extent and Nature of Work with Adolescents Who Have Sexual Behaviour Problems: Findings from a Survey of Youth Offending Teams in England and Wales
Authors: Masson Helen , Hackett Simon
Published: May 2006

This article describes a survey of Youth Offending Teams (YOTs) in England and Wales, conducted during 2002-2003, which explored the extent and nature of YOT responses to adolescents who are exhibiting sexually problematic behaviour. The methodological approach adopted is outlined and then the main findings of the survey are discussed, with reference to relevant literature, reports and governmental publications about adolescent sexual aggression. The findings cover the extent of YOT involvement in this area of work; the characteristics of the young people worked with; policies and procedures; systems for referral, assessment and intervention and issues of concern to the respondents.
Reducing Child Imprisonment: A Systemic Challenge1
Authors: Bateman Tim
Published: May 2006

This article seeks to make explicit the obstacles to reducing child custody in order to understand better what is required of an effective decarcerative strategy. It argues that a punitive turn, with its origins in the early 1990s, was responsible both for a subsequent inflation of the numbers of children in custodial establishments and for a range of systemic changes which serve to maintain the population of the juvenile secure estate at high levels. Thus, although recent efforts to reduce custody have tended to focus on provision of robust and credible community based programmes, rates of diversion, shifts in the tariff and movements in practitioner attitude are as important as programmatic concerns to the success, or otherwise, of initiatives designed to function as alternatives to custody.
Developments in Response to Youthful Anti-Social Behaviour
Authors: Stone Nigel
Published: May 2006

This Commentary seeks to provide an update on a range of statutory initiatives to regulate and contain young persons that have recently been subject to tempering judicial interpretation.
Predicting Criminality? Risk Factors, Neighbourhood Influence and Desistance
Authors: Webster Colin , MacDonald Robert , Simpson Mark
Published: May 2006

Using qualitative biographical data from a longitudinal study of youth transitions, criminal careers and desistance, this paper casts doubt on the veracity and predictive power of risk assessment devices such as Asset and OASys. These devices, and the research on which they are based, suggest that earlier and current childhood and teenage influences trigger and sustain later re-offending. In contrast, we argue that focus must be shifted to contingent risk factors that accrue in late teenage and young adulthood. Secondly, risk assessment and criminal career research has ignored the influence that unforeseen and unforeseeable processes of neighbourhood destabilization and life events have in criminal careers and their cessation.
Young People, Mentoring and Social Inclusion
Authors: Newburn Tim , Shiner Michael
Published: May 2006

Mentoring is the latest in a long line of interventions with disaffected young people that is believed to hold considerable promise. However, the expansion of mentoring schemes in recent years has been based more on faith in what are perceived to be the merits of the approach rather than on robust empirical evidence that mentoring actually brings about the benefits expected of it. This paper reports the results of the largest British study of mentoring to date. Built around a longitudinal survey and depth interviews with programme workers and participants, the research sought to measure the impact of a particular group of mentoring programmes. The evidence from the study suggests that the programmes were particularly successful in increasing young people’s involvement in education, training and work, but less successful in reducing offending. This is unsurprising, we argue, given that much of the core content of the programmes centred on education, training and work and contained relatively little activity focused on the avowed aim of reducing offending. Moreover the programmes were generally under-theorised, failing to provide an explicit model of how and why change was to be brought about. The danger for these and similar programmes is that they will be perceived to fail to deliver and, despite their promise, will become the latest ‘silver bullet’ to be talked up and then cast aside.
The Politicization of Youth Crime in Scotland and the Rise of the ‘Burberry Court’
Authors: Piacentini Laura , Walters Reece
Published: May 2006

In 2003, the youth justice system in Scotland entered a new phase with the introduction of a pilot youth court. The processing of persistent 16 and 17 year old (and serious 15 year olds) represented a stark deviation from a ‘child centred’ and needs-oriented state apparatus for dealing with young offenders to one based on deeds and individual responsibility. This article, based on an evaluation funded by the Scottish Executive, is the first to provide a critical appraisal of this youth justice reform. It examines the views of the judiciary and young offenders and reveals that the pilot youth court in Scotland represents a punitive excursion that poses serious concerns for due process, human rights and net widening.
Characterization of the TCL-1 transgenic mouse as a preclinical drug development tool for human chronic lymphocytic leukemia
Authors: Johnson Amy J. , Lucas David M. , Muthusamy Natarajan , Smith Lisa L. , Edwards Ryan B. , De Lay Michael D. , Croce Carlo M. , Grever Michael R. , Byrd John C.
Published: May 2006

Drug development in human chronic lymphocytic leukemia (CLL) has been limited by lack of a suitable animal model to adequately assess pharmacologic properties relevant to clinical application. A recently described TCL-1 transgenic mouse develops a chronic B-cell CD5+ leukemia that might be useful for such studies. Following confirmation of the natural history of this leukemia in the transgenic mice, we demonstrated that the transformed murine lymphocytes express relevant therapeutic targets (Bcl-2, Mcl-1, AKT, PDK1, and DNMT1), wild-type p53 status, and in vitro sensitivity to therapeutic agents relevant to the treatment of human CLL. We then demonstrated the in vivo clinical activity of low-dose fludarabine in transgenic TCL-1 mice with active leukemia. These studies demonstrated both early reduction in blood-lymphocyte count and spleen size and prolongation of survival (P = .046) compared with control mice. Similar to human CLL, an emergence of resistance was noted with fludarabine treatment in vivo. Overall, these studies suggest that the TCL-1 transgenic leukemia mouse model has similar clinical and therapeutic response properties to human CLL and may therefore serve as a useful in vivo tool to screen new drugs for subsequent development in CLL.
Alpha-4 integrins and VCAM-1, but not MAdCAM-1, are essential for recruitment of mast cell progenitors to the inflamed lung
Authors: Abonia J. Pablo , Hallgren Jenny , Jones Tatiana , Shi Tong , Xu Yuhui , Koni Pandelakis , Flavell Richard A. , Boyce Joshua A. , Austen K. Frank , Gurish Michael F.
Published: May 2006

Normal mouse lungs lack appreciable numbers of mast cells (MCs) or MC progenitors (MCp's), yet the appearance of mature MCs in the tracheobronchial epithelial surface is a characteristic of allergic, T-cell-dependent pulmonary inflammation. We hypothesized that pulmonary inflammation would recruit MCp's to inflamed lungs and that this recruitment would be regulated by distinct adhesion pathways. Ovalbumin-sensitized and challenged mice had a greater than 28-fold increase in the number of MCp's in the lungs. In mice lacking endothelial vascular cell adhesion molecule 1 (VCAM-1) and in wild-type mice administered blocking monoclonal antibody (mAb) to VCAM-1 but not to mucosal addressin CAM-1 (MadCAM-1), recruitment of MCp's to the inflamed lung was reduced by greater than 75%. Analysis of the integrin receptors for VCAM-1 showed that in β7 integrin-deficient mice, recruitment was reduced 73% relative to wild-type controls, and in either BALB/c or C57BL/6 mice, mAb blocking of α4, β1, or β7 integrins inhibited the recruitment of MCp's to the inflamed lung. Thus, VCAM-1 interactions with both α4β1 and α4β7 integrins are essential for the recruitment and expansion of the MCp populations in the lung during antigen-induced pulmonary inflammation. Furthermore, the MCp is currently unique among inflammatory cells in its partial dependence on α4β7 integrins for lung recruitment.
K-SPMM: a database of murine spermatogenic promoters modules & motifs
Authors: Lu Yi , Platts Adrian E , Ostermeier G Charles , Krawetz Stephen A
Published: May 2006

Background

Understanding the regulatory processes that coordinate the cascade of gene expression leading to male gamete development has proven challenging. Research has been hindered in part by an incomplete picture of the regulatory elements that are both characteristic of and distinctive to the broad population of spermatogenically expressed genes.

Description

K-SPMM, a database of murineSpermatogenicPromotersModules andMotifs, has been developed as a web-based resource for the comparative analysis of promoter regions and their constituent elements in developing male germ cells. The system contains data on 7,551 genes and 11,715 putative promoter regions in Sertoli cells, spermatogonia, spermatocytes and spermatids.K-SPMMprovides a detailed portrait of promoter site components, ranging from broad distributions of transcription factor binding sites to graphical illustrations of dimeric modules with respect to individual transcription start sites. Binding sites are identified through their similarities to position weight matrices catalogued in either the JASPAR or the TRANSFAC transcription factor archives. A flexible search function allows sub-populations of promoters to be identified on the basis of their presence in any of the four cell-types, their association with a list of genes or their component transcription-factor families.

Conclusion

This system can now be used independently or in conjunction with other databases of gene expression as a powerful aid to research networks of co-regulation. We illustrate this with respect to the spermiogenically active protamine locus in which binding sites are predicted that align well with biologically foot-printed protein binding domains.

Availability

http://klab.med.wayne.edu/kspmm/
A hidden Markov model approach for determining expression from genomic tiling micro arrays
Authors: Munch Kasper , Gardner Paul P , Arctander Peter , Krogh Anders
Published: May 2006

Background

Genomic tiling micro arrays have great potential for identifying previously undiscovered coding as well as non-coding transcription. To-date, however, analyses of these data have been performed in an ad hoc fashion.

Results

We present a probabilistic procedure, ExpressHMM, that adaptively models tiling data prior to predicting expression on genomic sequence. A hidden Markov model (HMM) is used to model the distributions of tiling array probe scores in expressed and non-expressed regions. The HMM is trained on sets of probes mapped to regions of annotated expression and non-expression. Subsequently, prediction of transcribed fragments is made on tiled genomic sequence. The prediction is accompanied by an expression probability curve for visual inspection of the supporting evidence. We test ExpressHMM on data from the Cheng et al. (2005) tiling array experiments on ten Human chromosomes [1]. Results can be downloaded and viewed from our web site [2].

Conclusion

The value of adaptive modelling of fluorescence scores prior to categorisation into expressed and non-expressed probes is demonstrated. Our results indicate that our adaptive approach is superior to the previous analysis in terms of nucleotide sensitivity and transfrag specificity.
Direct and heterologous approaches to identify the LET-756/FGF interactome
Authors: Popovici Cornel , Berda Yael , Conchonaud Fabien , Harbis Aurélie , Birnbaum Daniel , Roubin Régine
Published: May 2006

Background

Fibroblast growth factors (FGFs) are multifunctional proteins that play important roles in cell communication, proliferation and differentiation. However, many aspects of their activities are not well defined. LET-756, one of the two C. elegans FGFs, is expressed throughout development and is essential for worm development. It is both expressed in the nucleus and secreted.

Results

To identify nuclear factors associated with LET-756, we used three approaches. First, we screened a two-hybrid cDNA library derived from mixed stages worms and from a normalized library, using LET-756 as bait. This direct approach allowed the identification of several binding partners that play various roles in the nucleus/nucleolus, such as PAL-1, a transcription regulator, or RPS-16, a component of the small ribosomal subunit. The interactions were validated by co-immunoprecipitation and determination of their site of occurrence in mammalian cells. Second, because patterns of protein interactions may be conserved throughout species, we searched for orthologs of known mammalian interactors and measured binary interaction with these predicted candidates. We found KIN-3 and KIN-10, the orthologs of CK2α and CK2β, as new partners of LET-756. Third, following the assumption that recognition motifs mediating protein interaction may be conserved between species, we screened a two-hybrid cDNA human library using LET-756 as bait. Among the few FGF partners detected was 14-3-3β. In support of this interaction we showed that the two 14-3-3β orthologous proteins, FTT-1 and FTT-2/PAR-5, interacted with LET-756.

Conclusion

We have conducted the first extensive search for LET-756 interactors using a multi-directional approach and established the first interaction map of LET-756/FGF with other FGF binding proteins from other species. The interactors identified play various roles in developmental process or basic biochemical events such as ribosome biogenesis.
SNP-SNP interactions in breast cancer susceptibility
Authors: Onay Venüs Ümmiye , Briollais Laurent , Knight Julia A , Shi Ellen , Wang Yuanyuan , Wells Sean , Li Hong , Rajendram Isaac , Andrulis Irene L , Ozcelik Hilmi
Published: May 2006

Background

Breast cancer predisposition genes identified to date (e.g., BRCA1 and BRCA2) are responsible for less than 5% of all breast cancer cases. Many studies have shown that the cancer risks associated with individual commonly occurring single nucleotide polymorphisms (SNPs) are incremental. However, polygenic models suggest that multiple commonly occurring low to modestly penetrant SNPs of cancer related genes might have a greater effect on a disease when considered in combination.

Methods

In an attempt to identify the breast cancer risk conferred by SNP interactions, we have studied 19 SNPs from genes involved in major cancer related pathways. All SNPs were genotyped by TaqMan 5'nuclease assay. The association between the case-control status and each individual SNP, measured by the odds ratio and its corresponding 95% confidence interval, was estimated using unconditional logistic regression models. At the second stage, two-way interactions were investigated using multivariate logistic models. The robustness of the interactions, which were observed among SNPs with stronger functional evidence, was assessed using a bootstrap approach, and correction for multiple testing based on the false discovery rate (FDR) principle.

Results

None of these SNPs contributed to breast cancer risk individually. However, we have demonstrated evidence for gene-gene (SNP-SNP) interaction among these SNPs, which were associated with increased breast cancer risk. Our study suggests cross talk between the SNPs of the DNA repair and immune system (XPD-[Lys751Gln] and IL10-[G(-1082)A]), cell cycle and estrogen metabolism (CCND1-[Pro241Pro] and COMT-[Met108/158Val]), cell cycle and DNA repair (BARD1-[Pro24Ser] and XPD-[Lys751Gln]), and within carcinogen metabolism (GSTP1-[Ile105Val] and COMT-[Met108/158Val]) pathways.

Conclusion

The importance of these pathways and their communication in breast cancer predisposition has been emphasized previously, but their biological interactions through SNPs have not been described. The strategy used here has the potential to identify complex biological links among breast cancer genes and processes. This will provide novel biological information, which will ultimately improve breast cancer risk management.
Randomized pilot study to disseminate caries-control services in dentist offices
Authors: Grembowski David , Spiekerman Charles , del Aguila Michael A , Anderson Maxwell , Reynolds Debra , Ellersick Allison , Foster James , Choate Leslie
Published: May 2006

Background

To determine whether education and financial incentives increased dentists' delivery of fluoride varnish and sealants to at risk children covered by capitation dental insurance in Washington state (U.S.).

Methods

In 1999, 53 dental offices in Washington Dental Service's capitation dental plan were invited to participate in the study, and consenting offices were randomized to intervention (n = 9) and control (n = 10) groups. Offices recruited 689 capitation children aged 6–14 and at risk for caries, who were followed for 2 years. Intervention offices received provider education and fee-for-service reimbursement for delivering fluoride varnish and sealants. Insurance records were used to calculate office service rates for fluoride, sealants, and restorations. Parents completed mail surveys after follow-up to measure their children's dental utilization, dental satisfaction, dental fear and oral health status. Regression models estimated differences in service rates between intervention and control offices, and compared survey measures between groups.

Results

Nineteen offices (34%) consented to participate in the study. Fluoride and sealant rates were greater in the intervention offices than the control offices, but the differences were not statistically significant. Restoration rates were lower in the intervention offices than the control offices. Parents in the intervention group reported their children had less dental fear than control group parents.

Conclusion

Due to low dentist participation the study lacked power to detect an intervention effect on dentists' delivery of caries-control services. The intervention may have reduced children's dental fear.
Compensation by tumor suppressor genes during retinal development in mice and humans
Authors: Donovan Stacy L , Schweers Brett , Martins Rodrigo , Johnson Dianna , Dyer Michael A
Published: May 2006

Background

TheRB1gene was the first tumor suppressor gene cloned from humans by studying genetic lesions in families with retinoblastoma. Children who inherit one defective copy of theRB1gene have an increased susceptibility to retinoblastoma. Several years after the identification of the humanRB1gene, a targeted deletion ofRbwas generated in mice. Mice with one defective copy of theRbgene do not develop retinoblastoma. In this manuscript, we explore the different roles of the Rb family in human and mouse retinal development in order to better understand the species-specific difference in retinoblastoma susceptibility.

Results

We found that the Rb family of proteins (Rb, p107 and p130) are expressed in a dynamic manner during mouse retinal development. The primary Rb family member expressed in proliferating embryonic retinal progenitor cells in mice is p107, which is required for appropriate cell cycle exit during retinogenesis. The primary Rb family member expressed in proliferating postnatal retinal progenitor cells is Rb. p130 protein is expressed redundantly with Rb in postmitotic cells of the inner nuclear layer and the ganglion cell layer of the mouse retina. When Rb is inactivated in an acute or chronic manner during mouse retinal development, p107 is upregulated in a compensatory manner. Similarly, when p107 is inactivated in the mouse retina, Rb is upregulated. No changes in p130 expression were seen when p107, Rb or both were inactivated in the developing mouse retina. In the human retina, RB1 was the primary family member expressed throughout development. There was very little if any p107 expressed in the developing human retina. In contrast to the developing mouse retina, whenRB1was acutely inactivated in the developing human fetal retina, p107 was not upregulated in a compensatory manner.

Conclusion

We propose that intrinsic genetic compensation between Rb and p107 prevents retinoblastoma in Rb- or p107-deficient mice, but this compensation does not occur in humans. Together, these data suggest a model that explains why humans are susceptible to retinoblastoma followingRB1loss, but mice require bothRbandp107gene inactivation.