Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly expresses EBNA3A with conserved CD8+ T-cell epitopes

Post-transplantation lymphoproliferative disorders (PTLD) arise in the immunosuppressed and are frequently Epstein-Barr virus (EBV) associated. The most common PTLD histological sub-type is diffuse large B-cell lymphoma (EBV+DLBCL-PTLD). Restoration of EBV-specific T-cell immunity can induce EBV+DLBCL-PTLD regression. The most frequent B-cell lymphoma in the immunocompetent is also DLBCL. ‘EBV-positive DLBCL of the elderly’ (EBV+DLBCL) is a rare but well-recognized DLBCL entity that occurs in the overtly immunocompetent, that has an adverse outcome relative to EBV-negative DLBCL. Unlike PTLD (which is classified as viral latency III), literature suggests EBV+DLBCL is typically latency II, i.e. expression is limited to the immuno-subdominant EBNA1, LMP1 and LMP2 EBV-proteins. If correct, this would be a major impediment for T-cell immunotherapeutic strategies. Unexpectedly we observed EBV+DLBCL-PTLD and EBV+DLBCL both shared features consistent with type III EBV-latency, including expression of the immuno-dominant EBNA3A protein. Extensive analysis showed frequent polymorphisms in EBNA1 and LMP1 functionally defined CD8+ T-cell epitope encoding regions, whereas EBNA3A polymorphisms were very rare making this an attractive immunotherapy target. As with EBV+DLBCL-PTLD, the antigen presenting machinery within lymphomatous nodes was intact. EBV+DLBCL express EBNA3A suggesting it is amenable to immunotherapeutic strategies.

Teacher leadership : interns crossing to the domain of higher professional learning with mentors?

Over the last two decades, the notion of teacher leadership has emerged as a key concept in both the teaching and leadership literature. While researchers have not reached consensus regarding a definition, there has been some agreement that teacher leadership can operate at both a formal and informal level in schools and that it includes leadership of an instructional, organisational and professional development nature (York-Barr & Duke, 2004). Teacher leadership is a construct that tends not to be applied to pre-service teachers as interns, but is more often connected with the professional role of mentors who collaborate with them as they make the transition to being a beginning teacher. We argue that teacher leadership should be recognised as a professional and career goal during this formative learning phase and that interns should be expected to overtly demonstrate signs, albeit early ones, of leadership in instruction and other professional areas of development. The aim of this paper is to explore the extent to which teacher education interns at one university in Queensland reported on activities that may be deemed to be ‘teacher leadership.’ The research approach used in this study was an examination of 145 reflective reports written in 2008 by final Bachelor of Education (primary) pre-service teachers. These reports recorded the pre-service teachers’ perceptions of their professional learning with a school-based mentor in response to four outcomes of internship that were scaffolded by their mentor or initiated by them. These outcomes formed the bases of our research questions into the professional learning of the interns and included, ‘increased knowledge and capacity to teach within the total world of work as a teacher;’ ‘to work autonomously and interdependently’; to make ‘growth in critical reflectivity’, and the ‘ability to initiate professional development with the mentoring process’. Using the approaches of the constant comparative method of Strauss and Corbin (1998) key categories of experiences emerged. These categories were then identified as belonging to main meta-category labelled as ‘teacher leadership.’ Our research findings revealed that five dimensions of teacher leadership – effective practice in schools; school curriculum work; professional development of colleagues; parent and community involvement; and contributions to the profession – were evident in the written reports by interns. Not surprisingly, the mentor/intern relationship was the main vehicle for enabling the intern to learn about teaching and leadership. The paper concludes with some key implications for developers of preservice education programmes regarding the need for teacher leadership to be part of the discourse of these programmes.

Stigma reported by nurses related to those experiencing drug and alcohol dependency : a phemonenological study

Alcohol and drug dependency is a widespread health and social issue encountered by registered nurses in contemporary practice. A study aiming to describe the experiences of registered nurses working in an alcohol and drug unit in South East Queensland was implemented. Data were analysed via Giorgi’s phenomenological method and an unexpected but significant finding highlighted the frustration felt by registered nurses regarding experiences of stigma they identified in their daily work encounters. Secondary analysis confirmed the phenomenon of stigma with three themes: (1) inappropriate judgement; (2) advocacy; and (3) education. Resultantly, findings concluded registered nurses’ working in this field need to become advocates for their clients, ensuring professional conduct is upheld at all times. This paper recommends that stigma could be addressed by incorporating alcohol and other drug dependency subjects and clinical placements into the curriculum of the Bachelor of Nursing degrees, and in-services for all practising registered nurses.

Selective accumulation of virus-specific CD8+ T cells within the peripheral blood stem cell compartment

The absence of cellular immunity is central to the pathogenesis of herpesvirus-mediated diseases after allogeneic hemopoietic stem cell transplantation (HSCT). For both bone marrow (BM)– and granulocyte-colony stimulating factor–mobilized peripheral blood stem cells (PBSCs) HSCT, donor-derived Epstein-Barr virus (EBV) and cytomegalovirus (CMV) peptide–specific CD8+ T cells clones undergo early expansion and persist long-term, with additional diversification arising from novel antigen-specific clones from donor-derived progenitors. Whether BM or PBSC is the superior source of antiviral CD8+ T cells is unclear. Given that PBSC has largely replaced BM as a source of stem cells for HSCT, it is unlikely that herpesvirus effector T-cell reconstitution will ever be compared prospectively. PBSC grafts contain 10 to 30 times more T cells than BM and a randomized study found proven viral infections were more frequent in BM than PBSC recipients, suggesting viral-specific T-cell immunity is enhanced in PBSC. Recently Moss showed in lung cancer patients that herpesvirus-specific BM-derived CD8+ T cells have unique homing properties relative to herpesvirus-specific CD8+ T cells present in unmobilized peripheral blood (PB). Immunodominant EBV-lytic peptide–specific CD8+ T cells were enriched in BM but were reduced for CMV peptide–specific CD8+ T cells relative to PB. EBV-latent peptide–specific CD8+ T cells were equivalent, which has relevance in the context of posttransplantation lymphoproliferative disorder for which impaired EBV-latent CD8+ T-cell immunity is a risk-factor. A comparison of herpesvirus-specific cellular immunity in PBSC versus PB has yet to be performed.

Older Australians and the Internet

In late 2009, Sandra Haukka secured funding from the auDA Foundation to explore what older Australians who never or rarely use the Internet (referred to as ‘non-users’) know about the types of online products and services available to them, and how they might use these products and services to improve their daily life. This project aims to support current and future strategies and initiatives by: 1) exploring the extent to which non-users are aware of the types and benefits of online products and services, (such as e-shopping, e-banking, e-health, social networking, and general browsing and research) as well as their interest in them b) identifying how the Internet can improve the daily life of older Australians c) reviewing the effectiveness of support and services designed to educate and encourage older people to engage with the Internet d) recommending strategies that aim to raise non-user awareness of current and emerging online products and services, and provide non-users with the skills and knowledge needed to use those products and services that they believe can improve their daily life. The Productive Ageing Centre at National Seniors Australia, and Professor Trevor Barr from Swinburne University provided the project with in-kind support.

Incidence and geographic distribution of endemic Burkitt lymphoma in northern Uganda revisited

Endemic Burkitt lymphoma (BL) is etiologically associated with Epstein-Barr virus (EBV) and ecologically linked to Plasmodium falciparum malaria. However, these infections imperfectly correlate with BL epidemiology. To obtain recent epidemiological data, we studied district- and county-specific BL incidence and standardized incidence ratios using data collected from 1997 through 2006 at Lacor Hospital in northern Uganda, where studies were last done more than 30 years ago. Among 500 patients, median age was 6 years (inter-quartile range 5-8) and male-to-female ratio was 1.8:1. Among those known, most presented with abdominal (56%, M: F 1.4:1) vs. only facial tumors (35%, M: F 3.0:1). Abdominal tumors occurred in older (mean age: 7.0 vs. 6.0 years; p<0.001) and more frequently in female children (68% vs. 50%; OR 2.2, 95% CI 1.5-3.5). The age-standardized incidence was 2.4 per 100,000, being 0.6 in 1-4 year olds, 4.1 in 5-9 year olds and 2.8 in 10-14 year olds and varied 3-4-fold across districts. The incidence was lower in districts that were far from Lacor and higher in districts that were close to Lacor. While districts close to Lacor were also more urbanized, the incidence was higher in the nearby perirural areas. We highlight high BL incidence and geographic variation in neighboring districts in northern Uganda. While distance from Lacor clearly influenced the patterns, the incidence was lower in municipal than in surrounding rural areas. Jaw tumors were characterized by young age and male gender, but presentation has shifted away from facial to mostly abdominal. Keywords: Africa, cancer, malaria, Epstein-Barr virus, clustering, epidemiology

A randomised, feasibility trial of a tele-health intervention for Acute Coronary Syndrome patients with depression ('MoodCare')

Background Coronary heart disease (CHD) and depression are leading causes of disease burden globally and the two often co-exist. Depression is common after Myocardial Infarction (MI) and it has been estimated that 15-35% of patients experience depressive symptoms. Co-morbid depression can impair health related quality of life (HRQOL), decrease medication adherence and appropriate utilisation of health services, lead to increased morbidity and suicide risk, and is associated with poorer CHD risk factor profiles and reduced survival. We aim to determine the feasibility of conducting a randomised, multi-centre trial designed to compare a tele-health program (MoodCare) for depression and CHD secondary prevention, with Usual Care (UC). Methods Over 1600 patients admitted after index admission for Acute Coronary Syndrome (ACS) are being screened for depression at six metropolitan hospitals in the Australian states of Victoria and Queensland. Consenting participants are then contacted at two weeks post-discharge for baseline assessment. One hundred eligible participants are to be randomised to an intervention or a usual medical care control group (50 per group). The intervention consists of up to 10 × 30-40 minute structured telephone sessions, delivered by registered psychologists, commencing within two weeks of baseline screening. The intervention focuses on depression management, lifestyle factors (physical activity, healthy eating, smoking cessation, alcohol intake), medication adherence and managing co-morbidities. Data collection occurs at baseline (Time 1), 6 months (post-intervention) (Time 2), 12 months (Time 3) and 24 months follow-up for longer term effects (Time 4). We are comparing depression (Cardiac Depression Scale [CDS]) and HRQOL (Short Form-12 [SF-12]) scores between treatment and UC groups, assessing the feasibility of the program through patient acceptability and exploring long term maintenance effects. A cost-effectiveness analysis of the costs and outcomes for patients in the intervention and control groups is being conducted from the perspective of health care costs to the government. Discussion This manuscript presents the protocol for a randomised, multi-centre trial to evaluate the feasibility of a tele-based depression management and CHD secondary prevention program for ACS patients. The results of this trial will provide valuable new information about potential psychological and wellbeing benefits, cost-effectiveness and acceptability of an innovative tele-based depression management and secondary prevention program for CHD patients experiencing depression.

Generation and characterisation of Cisplatin-resistant non-small cell lung cancer cell lines displaying a stem-like signature

Introduction: Inherent and acquired cisplatin resistance reduces the effectiveness of this agent in the management of non-small cell lung cancer (NSCLC). Understanding the molecular mechanisms underlying this process may result in the development of novel agents to enhance the sensitivity of cisplatin. Methods: An isogenic model of cisplatin resistance was generated in a panel of NSCLC cell lines (A549, SKMES-1, MOR, H460). Over a period of twelve months, cisplatin resistant (CisR) cell lines were derived from original, age-matched parent cells (PT) and subsequently characterized. Proliferation (MTT) and clonogenic survival assays (crystal violet) were carried out between PT and CisR cells. Cellular response to cisplatin-induced apoptosis and cell cycle distribution were examined by FACS analysis. A panel of cancer stem cell and pluripotent markers was examined in addition to the EMT proteins, c-Met and β-catenin. Cisplatin-DNA adduct formation, DNA damage (γH2AX) and cellular platinum uptake (ICP-MS) was also assessed. Results: Characterisation studies demonstrated a decreased proliferative capacity of lung tumour cells in response to cisplatin, increased resistance to cisplatin-induced cell death, accumulation of resistant cells in the G0/G1 phase of the cell cycle and enhanced clonogenic survival ability. Moreover, resistant cells displayed a putative stem-like signature with increased expression of CD133+/CD44+cells and increased ALDH activity relative to their corresponding parental cells. The stem cell markers, Nanog, Oct-4 and SOX-2, were significantly upregulated as were the EMT markers, c-Met and β-catenin. While resistant sublines demonstrated decreased uptake of cisplatin in response to treatment, reduced cisplatin-GpG DNA adduct formation and significantly decreased γH2AX foci were observed compared to parental cell lines. Conclusion: Our results identified cisplatin resistant subpopulations of NSCLC cells with a putative stem-like signature, providing a further understanding of the cellular events associated with the cisplatin resistance phenotype in lung cancer. © 2013 Barr et al.

The cancer stem-cell hypothesis : its emerging role in lung cancer biology and its relevance for future therapy

The cancer stem-cell (CSC) hypothesis suggests that there is a small subset of cancer cells that are responsible for tumor initiation and growth, possessing properties such as indefinite self-renewal, slow replication, intrinsic resistance to chemotherapy and radiotherapy, and an ability to give rise to differentiated progeny. Through the use of xenotransplantation assays, putative CSCs have been identified in many cancers, often identified by markers usually expressed in normal stem cells. This is also the case in lung cancer, and the accumulated data on side population cells, CD133, CD166, CD44 and ALDH1 are beginning to clarify the true phenotype of the lung cancer stem cell. Furthermore, it is now clear that many of the pathways of normal stem cells, which guide cellular proliferation, differentiation, and apoptosis are also prominent in CSCs; the Hedgehog (Hh), Notch, and Wnt signaling pathways being notable examples. The CSC hypothesis suggests that there is a small reservoir of cells within the tumor, which are resistant to many standard therapies, and can give rise to new tumors in the form of metastases or relapses after apparent tumor regression. Therapeutic interventions that target CSC pathways are still in their infancy and clinical data of their efficacy remain limited. However Smoothened inhibitors, gamma-secretase inhibitors, anti-DLL4 antagonists, Wnt antagonists, and CBP/β-catenin inhibitors have all shown promising anticancer effects in early studies. The evidence to support the emerging picture of a lung cancer CSC phenotype and the development of novel therapeutic strategies to target CSCs are described in this review.

Adaptive radiotherapy for virally mediated head and neck cancer

Introduction: Clinical investigation has revealed a subgroup of head and neck cancers that are virally mediated. The relationship between nasopharyngeal cancer and Epstein Barr Virus (EBV) has long been established and more recently, the association between oropharyngeal cancer and Human Papillomavirus (HPV) has been revealed1,2 These cancers often present with nodal involvement and generally respond well to radiation treatment, evidenced by tumour regression1. This results in the need for treatment plan adaptation or re-planning in a subset of patients. Adaptive techniques allow the target region of the radiotherapy treatment plan to be altered in accordance with treatment-induced changes to ensure that under or over dosing does not occur3. It also assists in limiting potential overdosing of surrounding critical normal tissues4. We sought to identify a high-risk group based on nodal size to be evaluated in a future prospective adaptive radiotherapy trial. Method: Between 2005-2010, 121 patients with virally mediated, node positive nasopharyngeal (EBV positive) or oropharyngeal (HPV positive) cancers, receiving curative intent radiotherapy treatment were reviewed. Patients were analysed based on maximum size of the dominant node at diagnosis with a view to grouping them in varying risk categories to determine the need of re-planning. The frequency and timing of the re-planning scans were also evaluated. Results: Sixteen nasopharyngeal and 105 oropharyngeal tumours were reviewed. Twenty-five (21%) patients underwent a re-planning CT at a median of 22 (range, 0-29) fractions with 1 patient requiring re-planning prior to the commencement of treatment. Based on the analysis, patients were subsequently placed into risk categories; ≤35mm (Group 1), 36-45mm (Group 2), ≥46mm (Group 3). Re-planning CT’s were performed in Group 1- 8/68 (11.8%), Group 2- 4/28 (14.3%), Group 3- 13/25 (52%). Conclusion: In this series, patients with virally mediated head and neck cancer and nodal size > 46mm appear to be a high-risk group for the need of re-planning during a course of curative radiotherapy. This finding will now be tested in a prospective adaptive radiotherapy study. ‘Real World’ Implications: This research identifies predictive factors for those patients with virally mediated head and neck cancer that will benefit most from treatment adaptation. This will assist in minimising the side effects experienced by these patients thereby improving their quality of life after treatment.

Perceived social support and community adaptation in schizophrenia

Prompted by the continuing transition to community care, mental health nurses are considering the role of social support in community adaptation. This article demonstrates the importance of distinguishing between kinds of social support and presents findings from the first round data of a longitudinal study of community adaptation in 156 people with schizophrenia conducted in Brisbane, Australia. All clients were interviewed using the relevant subscales of the Diagnostic Interview Schedule to confirm a primary diagnosis of schizophrenia. The study set out to investigate the relationship between community adaptation and social support. Community adaptation was measured with the Brief Psychiatric Rating Scale (BPRS), the Life Skills Profile (LSP) and measures of dissatisfaction with life and problems in daily living developed by the authors. Social support was measured with the Arizona Social Support Interview Schedule (ASSIS). The BPRS and ASSIS were incorporated into a client interview conducted by trained interviewers. The LSP was completed on each client by an informal carer (parent, relative or friend) or a professional carer (case manager or other health professional) nominated by the client. Hierarchical regression analysis was used to examine the relationship between community adaptation and four sets of social support variables. Given the order in which variables were entered in regression equations, a set of perceived social support variables was found to account for the largest unique variance of four measures of community adaptation in 96 people with schizophrenia for whom complete data are available from the first round of the three-wave longitudinal study. A set of the subjective experiences of the clients accounted for the largest unique variance in measures of symptomatology, life skills, dissatisfaction with life, and problems in daily living. Sets of community support, household support and functional variables accounted for less variance. Implications for mental health nursing practice are considered.

Nutrient removal from wastewaters using high performance materials

Return side streams from anaerobic digesters and dewatering facilities at wastewater treatment plants (WWTPs) contribute a significant proportion of the total nitrogen load on a mainstream process. Similarly, significant phosphate loads are also recirculated in biological nutrient removal (BNR) wastewater treatment plants. Ion exchange using a new material, known by the name MesoLite, shows strong potential for the removal of ammonia from these side streams and an opportunity to concurrently reduce phosphate levels. A pilot plant was designed and operated for several months on an ammonia rich centrate from a dewatering centrifuge at the Oxley Creek WWTP, Brisbane, Australia. The system operated with a detention time in the order of one hour and was operated for between 12 and 24 hours prior to regeneration with a sodium rich solution. The same pilot plant was used to demonstrate removal of phosphate from an abattoir wastewater stream at similar flow rates. Using MesoLite materials, >90% reduction of ammonia was achieved in the centrate side stream. A full-scale process would reduce the total nitrogen load at the Oxley Creek WWTP by at least 18%. This reduction in nitrogen load consequently improves the TKN/COD ratio of the influent and enhances the nitrogen removal performance of the biological nutrient removal process.