bluuebunny/crossref_metadata_2025 huggingface dataset:
Antisocial behaviour legislation meets children's services: challenging perspectives on children, parents and the state
Authors: Tisdall E. Kay M.
Published: January 2006

The balance between children, parents, and the state shifts in its nature over time and indeed is not necessarily consistent in, nor across, policy arenas. This paper examines one such shift, where the introduction of antisocial behaviour legislation has clashed with that of children's welfare services. The Antisocial Behaviour etc. (Scotland) Act 2004 reifies distinctions between deserving and undeserving children, between good and bad parents, and between troubled and troublesome children. It demonstrates certain continuities in constructions of childhood and parenthood – i.e. children as the responsibility of their parents – but also much change – i.e. the ‘competent child’ largely replaces the ‘needy child’. The state, in its various forms, must be able to intervene over an increased breadth of behaviour and to patrol public space. The ‘community’ gains a legal place, through new appeals to the state to control public space and to control the behaviour of children.
New Labour and the politics of antisocial behaviour
Authors: Squires Peter
Published: January 2006

Tackling Anti-Social Behaviour (ASB) has rapidly become a key issue for the government. It was recently given central place in the 2004–2008 Home Office Strategic Plan, the Prime Minister being prompted to describe, in broad ideological terms, his government's ‘crusade’ against the anti-social within a ‘new consensus’ on criminal justice. Yet ‘ antisocial behaviour’ is often treated as if it were something new; a unique aspect of late modernity. Typically neglected are both the history of the concept itself and alternative understandings of the young, often disadvantaged, people who are the most frequent recipients of the ‘anti-social’ label. The article develops a critical analysis of the political and ideological significance of the problematization of ASB and the criminalization of social policy associated with enforcement driven ASB strategies.
Development, crime prevention and social policy in post-apartheid South Africa
Authors: Dixon Bill
Published: January 2006

Crime has gained an extraordinary pre-eminence among the social problems of our age, and preventing it has become a priority for many governments around the world. This has led to some significant normative disagreements about the relationship between crime prevention and social policy. Different bodies of work warn against both the ‘criminalization of social policy’ and the ‘socialization of crime prevention’. The more integrated notion of ‘social police’ put forward 200 years ago by Patrick Colquhoun, and the complex relationships between crime prevention, social policy and development that emerge from policy documents published in South Africa since 1994, suggest that, under certain circumstances, crime prevention may indeed be a legitimate goal of social policy, but that a principled approach to deciding its relative priority in the development process is needed if crime is not to be allowed to trump all other social problems.
An ‘inclusive’ society: a ‘leap forward’ for Māori in New Zealand?
Authors: Humpage Louise
Published: January 2006

Existing literature, which has emerged largely from Europe and Britain, suggests that the concepts of social exclusion and inclusion are fundamentally limited when accounting for ‘difference’. This paper extends this literature by considering the way in which a social exclusion/inclusion discourse has played out in a ‘white settler’ society where the ‘difference’ embodied by the highly ‘excluded’ indigenous population is a central concern for social policy. The paper argues that the goal of an ‘inclusive society’, which has framed New Zealand social policy since 1999, promotes an equal opportunity approach that sits in tension with the specific needs and rights of MØaori as indigenous peoples and partners in the 1840 Treaty of Waitangi. The ambiguous consequences of this goal highlight the need for settler societies to develop policy that reflects their own socio-political circumstances, rather than simply adopt policy discourses that are popular internationally.
Critical policy evaluation and the question of values: a psychosocial approach
Authors: Taylor David
Published: January 2006

This paper proposes a tentative approach to critical policy evaluation. It does so through a central focus on values. It suggests that emerging psychosocial approaches to welfare provide a useful way of considering values associated with the subjective dimension of welfare. Evaluation is presented as discursively constructed within political, scientific and popular discourses. It is a socially situated practice, whose meaning and methodology are contested by politicians, policy-makers, evaluation commissioners, welfare practitioners, professional evaluators and users of services. Contestation is approached as a methodological issue and a question of power. In this respect, evaluation is seen as part of a governance strategy but the argument seeks to avoid the tendency towards functionalism of some recent accounts of evaluation as governance. Instead, the question is approached by considering the role of values in evaluation. The article seeks to relate what are referred to as the internal valuesthat guide evaluation practice with the external values of political critique.
The future of critical psychiatry
Authors: Hopton John
Published: January 2006

The aim of this paper is to outline an agenda for critiques of psychiatry and other mainstream ideologies of mental health for the 21st century. While the heyday of anti-psychiatry was the period from the 1960s to the 1970s, new critiques of psychiatry, clinical psychology and psychotherapy continued to emerge throughout the last two decades of the 20th century. Some of these – not least those that emerged from the mental health service users’ movement – echoed the themes of earlier critics such as R. D. Laing and Thomas Szasz by questioning the legitimacy of diagnoses and therapeutic interventions. Others focused on anti-racist and/or feminist perspectives. This paper suggests that, in the wake of developments in biological psychiatry and socio-biology as well as clinical advances in psychopharmacology and the rise of Evidence Based Psychiatry, critical psychiatry has a new role. This role is less adversarial than that of the so-called anti-psychiatry of the 1960s and 1970s and less concerned with challenging basic assumptions about the causes of mental distress. The critical psychiatry of the 21st century can best serve the interests of service users by ensuring that service users’ rights to autonomy, fairness and freedom of choice are not overlooked due to a preoccupation with the science of Evidence Based Psychiatry.
Repair Effectiveness Studies on Impact Damaged Sandwich Composite Constructions
Authors: Raju M. , Reddy C. Rajasekhar , Swamy M. R. Narasimha , Giridhar G. , Srikanth L. , Prakash M. Rajendra , Rao R. M. V. G. K.
Published: January 2006

Experimental studies were carried out using sandwich composite panel specimens, consisting of both polyurethane foam core (PUF) and aramid honeycomb core (Nomex) type constructions. These specimens were subjected to impact damage at energy levels ranging between 7.56 and 15.6 J. A ply-drop-patching technique was employed to repair the impact damaged sandwich specimens. The undamaged (virgin), impact damaged, and repaired specimens were then subjected to flexural (four point bending) and edgewise compression tests and strength recoveries were measured to determine the efficacy of the repair technique employed. In flexure, strength recoveries of up to 97% in PUF core and 90% in honeycomb core sandwich specimens were realized after repair, whereas in compression, the corresponding values were up to 90% in PUF core and 88% in honeycomb core sandwich specimens. A repair effectiveness factor (Ref) has been conceived and introduced to quantify the efficiency of the repair technique. Further, the repair quality was assessed using a simple NDT method prior to subjecting the sandwich specimens for destructive tests.
The Geometrical Effects of Bumps on the Fatigue Life of Flip-chip Packages by Taguchi Method
Authors: Jong Wen-Ren , Chen Shia-Chung , Tsai Hsin-Chun , Chiu Chien-Chia , Chang Hsiu-Tao
Published: January 2006

This study employs the coupled field method of thermal analysis with the structural method to simulate the thermal conduction and mechanical behaviors of flip-chip packages. The full, one-quarter symmetrical, one-eighth symmetrical, and stripped finite element models are analyzed by thermal shock test in the temperature loading range of 55–125° C. Engelmaier's model is used to study the issues of fatigue life of these models. The results reveal that the one-eighth symmetrical model can save CPU time, and still retain the accuracy of analysis. Furthermore, this study investigates the geometrical dimensions of bumps regarding the effects and the reliability of flip-chip bumps by means of one-eighth symmetrical finite element model with CAE analysis under the loading of cyclic temperature. The Taguchi method is employed to find the optimum upper diameter, lower diameter, height, and width of bumps in this research. There is a novel concept that the climbing height of underfill is considered as the noise factor since it has an impact on the fatigue life of flip-chip packages. Analysis of variance is used to examine the contribution of these geometric parameters with respect to fatigue life of solder bumps. It is found that the influence of climbing height of underfill is more significant on the fatigue life of flip-chip bumps and the width of the solder bump is the most important factor.
Anisotropic Laminar Piezocomposite Actuator Incorporating Machined PMN–PT Single-crystal Fibers
Authors: Wilkie W. Keats , Inman Daniel J. , Lloyd Justin M. , High James W.
Published: January 2006

The design, fabrication, and testing of a flexible, laminar, anisotropic piezoelectric composite actuator utilizing machined PMN–32%PT single-crystal fibers is presented. The device consists of a layer of rectangular single-crystal piezoelectric fibers in an epoxy matrix, packaged between interdigitated electrode polyimide films. Quasistatic freestrain measurements of the single-crystal device are compared with measurements from geometrically identical specimens incorporating polycrystalline PZT-5A and PZT-5H piezoceramic fibers. Free-strain actuation of the single-crystal actuator at low bipolar electric fields (±250 V/mm) is ≈400% greater than that of the baseline PZT-5A piezoceramic device, and ≈200% greater than that of the PZT-5H device. Free-strain actuation under high unipolar electric fields (0–4 kV/mm) is 200% of the PZT-5A baseline device, and 150% of the PZT-5H alternate piezoceramic device. Performance increases at low field are qualitatively consistent with predicted increases based on scaling the low-field d33 piezoelectric constants of the respective piezoelectric materials. High-field increases are much less than scaled d33 estimates, but appear consistent with high-field free-strain measurements reported for similar bulk single-crystal and piezoceramic compositions. Measurements of single-crystal actuator capacitance and coupling coefficient are also provided. These properties were poorly predicted using scaled bulk material dielectric and coupling coefficient data. Rule-of-mixture calculations of the effective elastic properties of the single-crystal device and estimated actuation work energy densities are also presented. Results indicate longitudinal stiffnesses significantly lower (50% less) than either piezoceramic device. This suggests that single-crystal piezocomposite actuators will be best suited to low induced-stress, high strain, and deflection applications.
A Smart Health Monitoring System with Application to Welded Structures using Piezoceramic and Fiber Optic Transducers
Authors: Kim Myung-Hyun
Published: January 2006

Large welded structures, including ships and offshore structures, are normally in operation under cyclic fatigue loadings. These structures include many geometric as well as material discontinuities due to weld joints, and the fatigue strength at these hot spots is of critical importance for the structural performance. In the past, various Non-Destructive Evaluation (NDE) techniques have been developed to detect fatigue cracks and to estimate their location and size. However, important limitations of most of the existing NDE methods are that they are off-line; the normal operation of the structure has to be interrupted and the device often has to be disassembled. In this context, a new impedance-based structural health monitoring system employing piezoceramic transducers is developed with a special interest in applying the technique for welded structural members in ship and offshore structures. In particular, the impedance-based structural health monitoring technique that employs the coupling effect of piezoceramic (PZT) materials and structures is investigated. Moreover, a preliminary study of using fiber Bragg grating (FBG) type optical fiber sensors for the stress measurement of a typical weld structure is investigated. The final goal is to extend the fiber optic sensor technique for the global and local stress measurements of ship or offshore structures.
Self-sensing of Damage in Carbon Fiber Polymer–Matrix Composite Cylinder by Electrical Resistance Measurement
Authors: Wang Shoukai , Chung D. D. L. , Chung Jaycee H.
Published: January 2006

Self-sensing of damage, as attained by electrical resistance measurement, was found to be effective in a carbon fiber polymer–matrix composite cylinder made by filament winding. Resistance was measured in the axial, radial, oblique, and circumferential directions by using circumferential or axial electrical contacts on the outer and/or inner surfaces of the cylinder. Minor damage upon drop impact at 10 J or below caused the radial resistance to decrease irreversibly, whereas major damage upon drop impact above 10 J caused the radial, oblique, and axial resistances to increase irreversibly. The circumferential resistance ratio (ratio of the circumferential resistance of a damaged area to that away from the damaged area) was most sensitive, increasing monotonically with impact energy >1.4 J.
High levels of circulating CD34 cells, dacrocytes, clonal hematopoiesis, and JAK2 mutation differentiate myelofibrosis with myeloid metaplasia from secondary myelofibrosis associated with pulmonary hypertension
Authors: Popat Uday , Frost Adaani , Liu Enli , Guan Yongli , Durette April , Reddy Vishnu , Prchal Josef T.
Published: January 2006

We studied 25 patients with myelofibrosis with myeloid metaplasia and 19 patients with secondary myelofibrosis associated with pulmonary hypertension (PH). In these 2 groups, we compared the peripheral-blood CD34 count, the clonality of granulocytes and platelets in peripheral blood, the mutational status of the JAK2 kinase gene, and the morphology of the peripheral blood and bone marrow. We found that the following were distinctive features of myelofibrosis with myeloid metaplasia but not of secondary myelofibrosis due to PH: high circulating CD34 cell count, the presence of clonal platelets and granulocytes and of peripheral-blood dacrocytes, and a JAK2 1849G>T (V617F) mutation. We conclude that these are intrinsic features of clonal progenitors present in patients with myelofibrosis due to myeloproliferative disorders and that these features are not due to the abnormal marrow architecture seen in secondary myelofibrosis.
Vasoactive intestinal peptide induces regulatory dendritic cells that prevent acute graft-versus-host disease while maintaining the graft-versus-tumor response
Authors: Chorny Alejo , Gonzalez-Rey Elena , Fernandez-Martin Amelia , Ganea Doina , Delgado Mario
Published: January 2006

Acute graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in patients undergoing allogeneic bone marrow transplantation (BMT) for the treatment of leukemia and other immunogenetic disorders. The use of tolerogenic dendritic cells (DCs) that induce the generation/activation of regulatory T (Tr) cells for the treatment of acute GVHD following allogeneic BMT has been recently established. Therefore, the identification of factors that contribute to the development of tolerogenic DCs is highly relevant. We report on the use of the known immunosuppressive neuropeptide, the vasoactive intestinal peptide (VIP), as a new approach to induce tolerogenic DCs with the capacity to prevent acute GVHD. DCs differentiated in the presence of VIP impair allogeneic haplotype-specific responses of donor CD4+ cells in mice given transplants by inducing the generation of Tr cells in the graft. VIP-induced tolerogenic DCs did not abrogate the graft-versus-leukemia response presumably by not affecting the cytotoxicity of transplanted T cells against the leukemic cells. Therefore, the inclusion of VIP-induced tolerogenic DCs in future therapeutic regimens may minimize the dependence on nonspecific immunosuppressive drugs used currently as antirejection therapy, and facilitate the successful transplantation from mismatched donors, by reducing the deleterious consequences of acute GVHD and extending the applicability of BMT.
Activated CD4+CD25+ T cells selectively kill B lymphocytes
Authors: Zhao Dong-Mei , Thornton Angela M. , DiPaolo Richard J. , Shevach Ethan M.
Published: January 2006

The suppressive capacity of naturally occurring mouse CD4+CD25+ T cells on T-cell activation has been well documented. The present study is focused on the interaction of CD4+CD25+ T cells and B cells. By coculturing preactivated CD4+CD25+ T cells with B cells in the presence of polyclonal B-cell activators, we found that B-cell proliferation was significantly suppressed. The suppression of B-cell proliferation was due to increased cell death caused by the CD4+CD25+ T cells in a cell-contact–dependent manner. The induction of B-cell death is not mediated by Fas–Fas ligand pathway, but surprisingly, depends on the up-regulation of perforin and granzymes in the CD4+CD25+ T cells. Furthermore, activated CD4+CD25+ T cells preferentially killed antigen-presenting but not bystander B cells. Our results demonstrate that CD4+CD25+ T cells can act directly on B cells and suggest that the prevention of autoimmunity by CD4+CD25+ T cells can be explained, at least in part, by the direct regulation of B-cell function.
Characteristics and Outcome of Diffuse Large B-Cell Lymphoma in Hepatitis C Virus–Positive Patients in LNH 93 and LNH 98 Groupe d'Etude des Lymphomes de l'Adulte Programs
Authors: Besson Caroline , Canioni Danielle , Lepage Eric , Pol Stanislas , Morel Pierre , Lederlin Pierre , Van Hoof Achiel , Tilly Hervé , Gaulard Philippe , Coiffier Bertrand , Gisselbrecht Christian , Brousse Nicole , Reyes Félix , Hermine Olivier
Published: January 2006

Purpose

Epidemiologic studies show an association between hepatitis C virus (HCV) and B-cell non-Hodgkin's lymphoma (NHL). Treatment and outcome of patients with diffuse large-cell lymphoma (DLCL) and HCV infection are still a matter of debate.

Patients and Methods

We studied the HCV-positive patients with B-cell DLCL included in the Groupe d'Etude des Lymphomes de l'Adulte (GELA) programs LNH 93 and LNH 98. They were compared with the other patients with DLCL included in these programs. HCV infection prevalence was 0.5% (26 of 5,586 patients).

Results

Histologic types of HCV-positive DLCL were more frequently transformed from low-grade lymphoma than DLCL in HCV-negative patients (32% v 6%, P = .02). This is also supported by more frequent spleen involvement in HCV-positive patients (46% v 17%, P < .001). HCV-positive patients had more frequently elevated lactate dehydrogenase levels than other patients (77% v 55%, P = .02). Outcome of HCV-positive patients was poorer for overall survival (P = .02) but not for event-free survival (P = .13). After matching on age and prognosis factors, at 2 years of follow-up, the overall survival was 56% (95% CI, 33% to 76%) among HCV-positive patients, versus 80% (70% to 89%), and the event-free survival was 53% (33% to 72%) versus 74% (64% to 84%). The short-term hepatic toxicity of chemotherapy was strongly increased among HCV-positive patients. After exclusion of the two subjects with chronic hepatitis B virus infection, the overall proportion of subjects undergoing hepatic toxicity was 65% (15 of 23 patients).

Conclusion

HCV-positive patients with DLCL differ from other patients both at presentation and during chemotherapy. Specific protocols evaluating antiviral therapy should be designed for these patients.
BAALC Expression and FLT3 Internal Tandem Duplication Mutations in Acute Myeloid Leukemia Patients With Normal Cytogenetics: Prognostic Implications
Authors: Baldus Claudia D. , Thiede Christian , Soucek Silke , Bloomfield Clara D. , Thiel Eckhard , Ehninger Gerhard
Published: January 2006

Purpose

Evaluate the impact of BAALC (brain and acute leukemia, cytoplasmic), a gene whose expression has been associated with adverse outcome in acute myeloid leukemia (AML) with normal cytogenetics, and FLT3 internal tandem duplication (ITD) mutations as independent prognostic factors in a larger study.

Patients and Methods

BAALC expression was determined by real-time reverse transcriptase polymerase chain reaction in pretreatment blood samples of 307 adults ≤ 60 years of age with AML with normal cytogenetics. Patients were dichotomized at BAALC's median expression into low and high expressers. The FLT3 ITD mutant:wild-type ratio was determined by fragment analysis.

Results

Compared with low-BAALC patients, high-BAALC patients had a higher rate of primary resistant leukemia (16% v 6%; P = .006). High BAALC expression was associated with a higher cumulative incidence of relapse (CIR; P = .018) and an inferior overall survival (OS; 3-year OS, 36% v 54%; P = .001). On multivariable analysis, high BAALC was independently predictive of resistant disease (P = .019), and high BAALC as well as a high FLT3 mutant:wild-type ratio were confirmed as the only factors predicting a high CIR (BAALC, P = .03; FLT3, P = .01) and inferior OS (BAALC, P = .001; FLT3, P = .012).

Conclusion

This study strengthens BAALC expression as one of the most important prognostic factors in AML patients with normal cytogenetics. BAALC expression and FLT3 mutation status should assist in tailoring induction and postremission therapies.
Prognostic Biomarkers in Diffuse Large B-Cell Lymphoma
Authors: Lossos Izidore S. , Morgensztern Daniel
Published: January 2006

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. Although it represents a curable disease, less than half of the patients are cured with conventional chemotherapy. The highly variable outcome reflects a heterogeneous group of tumors, with different genetic abnormalities and response to therapy. The International Prognostic Index (IPI) is useful in predicting the outcome of DLBCL patients. However, patients with identical IPI still exhibit marked variability in survival, suggesting the presence of significant residual heterogeneity within each IPI category. The discovery of specific genetic alterations and the assessment of protein expression led to the identification of multiple novel single molecular markers capable of predicting the outcome of DLBCL patients independently of clinical variables. The recent application of DNA microarrays and tissue array technologies allowed a better understanding of the biology of lymphoma and the development of novel diagnostic tools capable of improving the current models for outcome prediction. However, much confusion exists in the literature regarding the importance of different prognostic biomarkers and their applicability in routine practice. This review summarizes the recent advances in our understanding of prognostic biomarkers in DLBCL and discusses whether this is the right time for biomarkers-guided risk-adjusted therapy.
Endogenous Markers of Two Separate Hypoxia Response Pathways (hypoxia inducible factor 2 alpha and carbonic anhydrase 9) Are Associated With Radiotherapy Failure in Head and Neck Cancer Patients Recruited in the CHART Randomized Trial
Authors: Koukourakis Michael I. , Bentzen Søren M. , Giatromanolaki Alexandra , Wilson George D. , Daley Frances M. , Saunders Michele I. , Dische Stanley , Sivridis Efthimios , Harris Adrian L.
Published: January 2006

Purpose

Randomized controlled trials have generally shown a benefit from accelerated radiotherapy in head and neck squamous cell carcinoma (HNSCC). However, the large randomized United Kingdom trial CHART (Continuous Hyperfractionated Accelerated Radiotherapy) failed to show a benefit of strongly accelerated over standard radiotherapy (RT) in 918 patients with HNSCC. In this study, we investigated the impact of tumor hypoxia on the outcome of HNSCC patients in the CHART trial. There are two distinct hypoxia inducible factors (HIFs) that control different gene response pathways and we assessed them both with endogenous markers of hypoxia, hypoxia inducible factor HIF-2 alpha (HIF-2) and carbonic anhydrase CA9, an indicator of HIF-1 alpha (HIF-1) function.

Methods

Tissue from pre-RT biopsies performed in 198 of 918 patients recruited was analyzed for the immunohistochemical expression of HIF-2 and CA9.

Results

A significant association of high HIF2 and of high CA9 reactivity with poor locoregional control (P < .0001 and P = .0002, respectively) and poor survival (P = .0004 and 0.002, respectively) was noted. In multivariate analysis, HIF-2 and CA9 maintained their independent prognostic significance. Coexpression of both pathways had an additive effect, supporting their independent role. The uni-directional hypothesis, that a benefit from randomization to CHART should be seen in the nonhypoxic tumors, was supported by the data (one-tailed P = .04).

Conclusion

Expression of endogenous markers of hypoxia for the HIF-1 and HIF-2 pathway is strongly associated with radiotherapy failure. Using immunohistochemical methods it is possible to identify subgroups of HNSCC patients who are highly curable with radiotherapy, or who are excellent candidates for clinical trials on hypoxia-targeting drugs in two distinct pathways.
BCL2 Expression Is a Prognostic Marker for the Activated B-Cell–Like Type of Diffuse Large B-Cell Lymphoma
Authors: Iqbal Javeed , Neppalli Vishala T. , Wright George , Dave Bhavana J. , Horsman Douglas E. , Rosenwald Andreas , Lynch James , Hans Christine P. , Weisenburger Dennis D. , Greiner Timothy C. , Gascoyne Randy D. , Campo Elias , Ott German , Müller-Hermelink H. Konrad , Delabie Jan , Jaffe Elaine S. , Grogan Thomas M. , Connors Joseph M. , Vose Julie M. , Armitage James O. , Staudt Louis M. , Chan Wing C.
Published: January 2006

Background

The role of BCL2 as a predictor of survival in diffuse large B-cell lymphoma (DLBCL) is controversial. DLBCL is heterogeneous, and the expression of BCL2 is variable within the two major subgroups of DLBCL, germinal center B-cell–like (GCB) and activated B-cell–like (ABC) DLBCL, as well as primary mediastinal DLBCL.

Patients and Methods

In this study, we investigated the correlation of BCL2 expression with survival in the two major subgroups of DLBCL, as well as the mechanisms of BCL2 expression.

Results

There was no significant correlation between BCL2 protein expression and overall survival within the GCB subgroup, but BCL2 expression had a significant adverse effect on overall survival within the ABC subgroup (P = .008). This correlation was also observed at the mRNA level (P < .04). The difference remained significant when the analyses were performed at different cutoff values. The t(14;18) was frequently observed in the GCB subgroup and was highly associated with BCL2 expression. Patients with ABC DLBCL did not exhibit t(14;18) but had a markedly higher frequency of chromosome 18q21 amplification, on which BCL2 resides. Thus, alternative mechanisms such as 18q21 amplification or activation of the nuclear factor-kappa B pathway, as reported previously, seem to be mainly responsible for the upregulation of BCL2 expression in the ABC subgroup.

Conclusion

Treating all DLBCL as a single entity ignores the mechanistic differences in BCL2 upregulation and obscures the prognostic significance of BCL2 expression. Hence, the significance of BCL2 and other biomarkers should be assessed in the context of DLBCL subgroups in future studies.
Additional Genetic High-Risk Features Such As 11q Deletion, 17p Deletion, and V3-21 Usage Characterize Discordance of ZAP-70 and VH Mutation Status in Chronic Lymphocytic Leukemia
Authors: Kröber Alexander , Bloehdorn Johannes , Hafner Sebastian , Bühler Andreas , Seiler Till , Kienle Dirk , Winkler Dirk , Bangerter Markus , Schlenk Richard F. , Benner Axel , Lichter Peter , Döhner Hartmut , Stilgenbauer Stephan
Published: January 2006

Purpose

Immunoglobulin heavy chain variable-region (VH) gene mutation status and zeta-associated protein 70 (ZAP-70) expression are correlated in chronic lymphocytic leukemia (CLL), but their concordance is variable. The goal of this study was to elucidate additional factors potentially characterizing their discordance.

Patients and Methods

We evaluated ZAP-70 expression by flow cytometry, VH status by DNA sequencing, and genomic aberrations by fluorescence in situ hybridization in 148 CLL patients. The parameters were analyzed for their associations and their individual prognostic impact.

Results

ZAP-70 expression and VH mutation status were strongly associated in CLL without additional genetic high-risk-features as defined by the absence of 11q or 17p deletion and V3-21 usage (concordance 84%). In contrast, the proportion of discordant cases was significantly higher (39%), if such additional genetic high-risk features were present. Discordant cases with V3-21 usage were almost exclusively ZAP-70 positive and VH mutated (89%), whereas all but one of the discordant cases with high-risk aberrations were ZAP-70 negative and VH unmutated (92%). By multivariate regression analysis, two models were developed, which both include high-risk genomic aberrations and, alternatively, VH mutation status and V3-21 usage or ZAP-70 expression as independent outcome predictors.

Conclusion

There were characteristic modes of discordance between ZAP-70 and VH mutation status depending on the presence or absence of additional genetic high-risk features such as 11q and 17p deletion or V3-21 usage. Although the biologic background for these findings is yet to be determined, these data have biologic and clinical implications regarding ZAP-70 as a pathogenic factor and outcome predictor, respectively.
Thromboembolism in Hospitalized Neutropenic Cancer Patients
Authors: Khorana Alok A. , Francis Charles W. , Culakova Eva , Fisher Richard I. , Kuderer Nicole M. , Lyman Gary H.
Published: January 2006

Purpose

Cancer is associated with thrombosis, but the frequency of thromboembolism in hospitalized cancer patients receiving current chemotherapy regimens is not known. We investigated venous and arterial thromboembolism and associated outcomes in hospitalized cancer patients actively receiving therapy, as identified by neutropenia.

Methods

We conducted a retrospective cohort study using the discharge database of the University HealthSystem Consortium. This included 66,106 adult neutropenic cancer patients with 88,074 hospitalizations between 1995 and 2002 at 115 medical centers in the United States.

Results

Thromboembolism was reported in 5,272 patients (8%), with 5.4% patients developing venous thromboembolism and 1.5% developing arterial thromboembolism during the first hospitalization. Patients with lymphoma and leukemia accounted for one third of venous and nearly one half of arterial events. Clinical variables most frequently associated with thromboembolism were age ≥ 65 years; primary site of cancer, including lung, GI, gynecologic, and brain; and comorbidities, including infection, pulmonary and renal disease, and obesity. In-hospital mortality was significantly greater in patients with venous (odds ratio [OR] = 2.01; 95% CI, 1.83 to 2.22) or arterial thromboembolism (OR = 5.04; 95% CI, 4.38 to 5.79). From 1995 to 2002, there was a 36% increase in venous events and a 124% increase in arterial events (P < .0001 for trend).

Conclusion

Thromboembolism is frequent in hospitalized neutropenic cancer patients, including in perceived low-risk subgroups such as patients with hematologic malignancies and nonmetastatic disease, and seems to be increasing. Thromboembolism is associated with increased in-hospital mortality. Increased efforts at thromboprophylaxis are warranted.
MKLP1 requires specific domains for its dendritic targeting
Authors: Xu Xiaohui , He Cheng , Zhang Zhaohuan , Chen Yizhang
Published: January 2006

The mitotic kinesin-like protein 1 (MKLP1) is specifically localized to the dendrite of the developed neuron, but its targeting mechanism is still unclear. In this study, the role of distinct domains of MKLP1 in dendritic targeting was investigated by producing a series of enhanced green fluorescent protein (eGFP)-tagged MKLP1 and its variant mutations, and studying the distribution of these molecules in cultured primary hippocampal neurons using fluorescence microscopy. We have found that: (a) full-length MKLP1(1-856)-eGFP was distributed to the dendrite of hippocampal neurons, not the axon; (b) deletion of the `motor' domain prevented the dendritic distribution; (c) deletion of the `tail' domain caused axonal appearance; (d) mutants devoid of the `stalk' domain were still specifically distributed to the dendrite. The results indicate that the motor and tail regions of MKLP1 are important and significant for its localization to the dendrites. We also discuss the difference between the targeting of membrane-anchoring proteins and the kinesin-like protein.
Cytoskeletal dynamics and cell signaling during planar polarity establishment in theDrosophilaembryonic denticle
Authors: Price Meredith H. , Roberts David M. , McCartney Brooke M. , Jezuit Erin , Peifer Mark
Published: January 2006

Many epithelial cells are polarized along the plane of the epithelium, a property termed planar cell polarity. The Drosophila wing and eye imaginal discs are the premier models of this process. Many proteins required for polarity establishment and its translation into cytoskeletal polarity were identified from studies of those tissues. More recently, several vertebrate tissues have been shown to exhibit planar cell polarity. Striking similarities and differences have been observed when different tissues exhibiting planar cell polarity are compared. Here we describe a new tissue exhibiting planar cell polarity – the denticles, hair-like projections of the Drosophila embryonic epidermis. We describe in real time the changes in the actin cytoskeleton that underlie denticle development, and compare this with the localization of microtubules, revealing new aspects of cytoskeletal dynamics that may have more general applicability. We present an initial characterization of the localization of several actin regulators during denticle development. We find that several core planar cell polarity proteins are asymmetrically localized during the process. Finally, we define roles for the canonical Wingless and Hedgehog pathways and for core planar cell polarity proteins in denticle polarity.
Oculodentodigital dysplasia connexin43 mutations result in non-functional connexin hemichannels and gap junctions in C6 glioma cells
Authors: Lai Albert , Le Dung-Nghi , Paznekas William A. , Gifford Wes D. , Jabs Ethylin Wang , Charles Andrew C.
Published: January 2006

Oculodentodigital dysplasia (ODDD) is a rare developmental disorder characterized by craniofacial and limb abnormalities. Over 35 separate mutations in human connexin43 (Cx43) causing ODDD have been identified. Several mutations are also associated with central nervous system involvement, including white-matter changes detected by magnetic resonance imaging. As Cx43 is abundantly expressed in astrocytes, we hypothesized that the mutant Cx43 proteins that produce neurological dysfunction have abnormal functional characteristics in astrocytes. To understand how ODDD-associated mutations affect Cx43 signaling in cells of glial origin, we conducted studies in rat C6 glioma cells, a communication-deficient glial cell line that expresses low levels of Cx43. We generated stable cell lines expressing enhanced yellow fluorescent protein (eYFP)-tagged human Cx43 constructs encoding wild-type and six eYFP-tagged mutant Cx43 mutants: Y17S, G21R, A40V, F52dup, L90V and I130T. Of these, Y17S, L90V and I130T are associated with neurological abnormalities. We found that all mutants could be detected on the cell surface. Y17S, G21R, A40V, L90V and I130T formed triton-resistant plaques representing gap junctions, although the relative ability to form plaques was decreased in these mutants compared with the wild type. F52dup formed dramatically reduced numbers of plaques. Propidium iodide uptake experiments demonstrated that all mutants were associated with reduced connexin hemichannel function compared with wild type. Scrape-loading experiments performed on the same stable cell lines showed reduced gap junctional dye transfer in all mutants compared with the wild type. These studies demonstrated that ODDD-associated Cx43 mutations result in non-functional connexin hemichannels and gap junction functions in a glial cell line regardless of whether the particular mutant is associated with neurological dysfunction.
The major vault protein is responsive to and interferes with interferon-γ-mediated STAT1 signals
Authors: Steiner Elisabeth , Holzmann Klaus , Pirker Christine , Elbling Leonilla , Micksche Michael , Sutterlüty Hedwig , Berger Walter
Published: January 2006

The major vault protein (MVP) is the main component of vaults, large ribonucleoprotein particles implicated in the regulation of cellular signaling cascades and multidrug resistance. Here, we identify MVP as an interferon γ (IFN-γ)-inducible protein. Treatment with IFN-γ resulted in a significant upregulation of MVP promoter activity as well as mRNA and protein levels. Activation of MVP expression by IFN-γ involved transcriptional upregulation through the JAK/STAT pathway based on an interaction of STAT1 with an interferon-γ-activated site (GAS) within the proximal MVP promoter. Mutation of this site distinctly reduced basal as well as IFN-γ-stimulated MVP transcription. IFN-γ also significantly enhanced the translation rate of MVP. Ectopic MVP overexpression in the MVP-negative lung cancer cell model H65 led to a downregulation of three known IFN-γ-regulated genes, namely ICAM-1, CD13 and CD36. Additionally, presence of MVP in H65 cells blocked both basal and IFN-γ-induced ICAM-1 expression whereas downmodulation of endogenous MVP levels by shRNA enhanced IFN-γ-induced ICAM-1 expression in U373 glioblastoma cells. MVP-mediated IFN-γ insensitivity was accompanied by significantly reduced STAT1 phosphorylation at Y701 and diminished translocation of STAT1 into the nucleus. Summarizing, we identify MVP as an IFN-γ-responsive gene interfering with IFN-γ-activated JAK/STAT signals. These data further substantiate that the vault particle functions as a general interaction platform for cellular signaling cascades.
Ontogeny of mantle musculature and implications for jet locomotion in oval squidSepioteuthis lessoniana
Authors: Thompson Joseph T. , Kier William M.
Published: January 2006

We examined the relationship between mantle muscle structure and mantle kinematics in an ontogenetic series (5-85 mm dorsal mantle length) of oval squid, Sepioteuthis lessoniana. Thick filament length increased during growth in the mantle muscle fibres that power jet locomotion (i.e. the circular muscles). The thick filament length of both the superficial mitochondria-rich (SMR; analogous to vertebrate red muscle fibres) and central mitochondria-poor (CMP; analogous to vertebrate white muscle fibres) circular muscles increased significantly during ontogeny. Thick filaments in the SMR circular muscle fibres of newly hatched squid (N=5) ranged from 0.7 to 1.4 μm and averaged 1.0 μm, while the thick filaments of the SMR fibres of the largest squids (N=4) studied ranged from 1.2 to 3.4μm and averaged 1.9 μm. The ontogeny of thick filament length in the CMP circular muscle fibres showed a similar trend. The range for hatchling CMP circular muscles was 0.7-1.4 μm, with an average of 1.0 μm, whereas the range and average for the largest squids studied were 0.9-2.2 μm and 1.5μm, respectively. Within an individual hatchling, we noted no significant differences between the thick filament lengths of the SMR and CMP fibres. Within an individual juvenile, the thick filaments of the SMR fibres were∼25% longer than the CMP fibres. The change in thick filament length may alter the contractile properties of the circular muscles and may also result in a decrease in the rate of mantle contraction during jetting. In escape-jet locomotion, the maximum rate of mantle contraction was highest in newly hatched squid and declined during ontogeny. The maximum rate of mantle contraction varied from 7-13 muscle lengths per second in newly hatched squid(N=14) and from 3-5 muscle lengths per second in the largest squids(N=35) studied.
Children recalling an event repeatedly: Effects on RM and CBCA scores
Authors: Granhag Par Anders , Strömwall Leif A. , Landström Sara
Published: January 2006

Purpose. The fact that abused children often talk about their experiences before entering the legal system is a neglected factor in terms of the validation of different reliability assessment techniques. Hence, the present study investigated the extent to which the scores of the reality monitoring technique (RM) and the criteria‐based content analysis technique (CBCA) were affected by the number of times children recalled an experienced or an imagined event.

Method. Children (aged 12–13 years, N – 80) participated in an experiment where half the sample experienced a real event (an interaction with a stranger outside his car) and then recalled it either one or four times (over a period of 14 days), and the other half imagined the same event and thereafter recalled it either one or four times. The statements given at the final (or only) recall session were analysed with both CBCA and RM.

Results. The results revealed that, on a multivariate level, both the CBCA and RM sets of criteria discriminated between truthful and fabricated statements. The total RM score (but not the total CBCA score) discriminated reliably between truthful and fabricated statements. Furthermore, RM (but not CBCA) were sensitive to the number of times the experienced or imagined event was recalled: increased presence of criteria after repeated recall.

Conclusions. The results were rather promising for the RM and less so for the CBCA. Furthermore, we found that the number of recalls moderated the effectiveness of the techniques. Hence, when assessing the reliability of a child's memory, it is crucial to learn about the history of the first documented statement.
Predicting expert social science testimony in criminal prosecutions of historic child sexual abuse
Authors: Connolly Deborah A. , Price Heather L. , Read J. Don
Published: January 2006

Purpose. Recently courts in several Common Law jurisdictions have been faced with the daunting task of adjudicating criminal complaints of child sexual assault that are alleged to have occurred in the distant past (historic child sexual abuse; HCSA). In the present data set, alleged offences ended between 2 and 48 years before the trial. These cases, which involve claims of repressed memory and continuous memory for the offence, raise many issues that hitherto had only rarely been faced by criminal courts and that are within the realm of issues studied by social scientists. In this paper we explore variables that predict the presence of a social science expert, called by the prosecution or the defence or an expert called by both sides.

Methods. A total of 2,064 actual criminal cases involving HCSA were coded on a variety of variables that were then used to predict the presence of an expert at trial and to predict the presence of an expert to evaluate the perpetrator for sentencing.

Results. Six variables predicted the presence of an expert at trial: offence description, frequency of abuse, complainant/accused relationship, complainant age, presence of repression, and complainant gender. Seven variables predicted the presence of an expert at sentencing: offence description, frequency of abuse, length of delay to trial, presence of threat, trial date, plea, and age difference between complainant and accused.

Conclusions. We use these archival data to generate hypotheses concerning the observed predictors of the use of expert testimony by courts in HCSA cases. The objective is to encourage more controlled studies of the particular case characteristics about which courts seek guidance from social scientists.
An examination of the questioning styles of police officers and caregivers when interviewing children with intellectual disabilities
Authors: Agnew Sarah E. , Powell Martine B. , Snow Pamela C.
Published: January 2006

Purpose. This research provided a detailed analysis of the types of questions and verbal strategies used by police officers and caregivers when interviewing children with intellectual disabilities about events.

Method. Twenty eight children aged 9 to 13 years with a mild or moderate intellectual disability participated in a staged event at their school. Each child was then interviewed on separate occasions by the child's primary caregiver and by a police officer who was authorized to conduct investigative interviews with children.

Results. While the approach used by the police officers was broadly consistent with best‐practice recommendations (i.e. their interviews contained few leading, coercive or negative strategies), they frequently interrupted the child's account and used relatively few minimal encouragers and other strategies designed to keep the child talking. The caregivers used a high proportion of direct, leading and coercive strategies to elicit information from their children. Even when caregivers used open‐ended questions, their children provided less event‐related information than they did to the police interviewers.

Conclusion. The quality of evidence obtained from children with intellectual disabilities is likely to be dependent (albeit in part) on the degree to which police interviewers adhere to best‐practice guidelines, as well as the children's general experience with an open‐ended style of communication.
A conceptual care model for individualized care approach in cardiac rehabilitation – combining both illness representation and self‐efficacy
Authors: Lau‐Walker Margaret
Published: January 2006

Purpose This paper analyses the two prominent psychological theories of patient response – illness representation and self‐efficacy – and explore the possibilities of the development of a conceptual individualized care model that would make use of both theories.

Methods Analysis of the literature established common themes that were used as the basis to form a conceptual framework intended to assist in the joint application of these theories to therapeutic settings.

Results Both theories emphasize personal experience, pre‐construction of self, individual response to illness and treatment, and that the patients' beliefs are more influential in their recovery than the severity of the illness. Where the theories are most divergent is their application to therapeutic interventions, which reflects the different sources of influence that each theory emphasizes. Based on their similarities and differences it is possible to integrate the two theories into a conceptual care model.

Conclusion The Interactive Care Model combines both theories of patient response and provides an explicit framework for further research into the design of effective therapeutic interventions in rehabilitation care.