A double-blind randomised controlled trial of a natural oil-based emulsion containing allantoin versus aqueous cream for managing radiation-induced skin reactions in patients with cancer

Background: Radiation-induced skin reaction (RISR) is one of the most common and distressing side effects of radiotherapy in patients with cancer. It is featured with swelling, redness, itching, pain, breaks in skin, discomfort, and a burning sensation. There is a lack of convincing evidence supporting any single practice in the prevention or management of RISR. Methods/Designs: This double-blinded randomised controlled trial aims to investigate the effects of a natural oil-based emulsion containing allantoin (as known as Moogoo Udder Cream®) versus aqueous cream in reducing RISR, improving pain, itching and quality of life in this patient group. One group will receive Moogoo Udder Cream®. Another group will receive aqueous cream. Outcome measures will be collected using patient self-administered questionnaire, interviewer administered questionnaire and clinician assessment at commencement of radiotherapy, weekly during radiotherapy, and four weeks after the completion of radiotherapy. Discussion: Despite advances of radiologic advances and supportive care, RISR are still not well managed. There is a lack of efficacious interventions in managing RISR. While anecdotal evidence suggests that Moogoo Udder Cream® may be effective in managing RISR, research is needed to substantiate this claim. This paper presents the design of a double blind randomised controlled trial that will evaluate the effects of Moogoo Udder Cream® versus aqueous cream for managing in RISR in patients with cancer. Trial registration: ACTRN 12612000568819

The roles of the preproghrelin-derived peptides - ghrelin, desacyl ghrelin and obestatin - in prostate cancer

Prostate cancer is the second most common cause of cancer related deaths in Western men. Despite the significant improvements in current treatment techniques, there is no cure for advanced metastatic, castrate-resistant disease. Early detection and prevention of progression to a castrate-resistant state may provide new strategies to improve survival. A number of growth factors have been shown to act in an autocrine/paracrine manner to modulate prostate cancer tumour growth. Our laboratory has previously shown that ghrelin and its receptors (the functional GHS-R1a and the non-functional GHS-R1b) are expressed in prostate cancer specimens and cell lines. We have shown that ghrelin increases cell proliferation in the PC3 and LNCaP prostate cancer cell lines through activation of ERK1/2, suggesting that ghrelin could regulate prostate cancer cell growth and play a role in the progression of the disease. Ghrelin is a 28 amino-acid peptide hormone, identified to be the natural ligand of the growth hormone secretagogue receptor (GHS-R1a). It is well characterised as a growth hormone releasing and as an orexigenic peptide that stimulates appetite and feeding and regulates energy expenditure and bodyweight. In addition to its orexigenic properties, ghrelin has been shown to play a regulatory role in a number of systems, including the reproductive, immune and cardiovascular systems and may play a role in a number of pathological conditions such as chronic heart failure, anorexia, cachexia, obesity, diabetes and cancer. In cancer, ghrelin and its receptor are expressed in a range of tumours and cancer cell lines and ghrelin has been demonstrated to modulate cell proliferation, apoptosis, migration and invasion in some cell types. The ghrelin gene (GHRL) encodes preproghrelin peptide, which is processed to produce three currently known functional peptides - ghrelin, desacyl ghrelin and obestatin. Prohormone convertases (PCs) have been shown to cleave the preproghrelin peptide into two primary products - the 28 amino acid peptide, ghrelin, and the remaining 117 amino acid C-terminal peptide, C-ghrelin. C-ghrelin can then be further processed to produce the 23 amino acid peptide, obestatin. Ghrelin circulates in two different forms - an octanoylated form (known as ghrelin) and a non-octanoylated form, desacyl ghrelin. The unique post-translational addition of octanoic acid to the serine 3 residue of the propeptide chain to form acylated ghrelin is catalysed by ghrelin O-acyltransferase (GOAT). This modification is necessary for binding of ghrelin to its only known functional receptor, the GHS-R1a. As desacyl ghrelin cannot bind and activate the GHS-R1a, it was initially thought to be an inactive peptide, despite the fact that it circulates at much higher levels than ghrelin. Further research has demonstrated that desacyl ghrelin is biologically active and shares some of the actions of ghrelin, as well as having some opposing and distinct roles. Interestingly, both ghrelin and desacyl ghrelin have been shown to modulate apoptosis, cell differentiation and proliferation in some cell types, and to stimulate cell proliferation through activation of ERK1/2 and PI3K/Akt pathways. The third known peptide product of the ghrelin preprohormone, obestatin, was initially thought to oppose the actions of ghrelin in appetite regulation and food intake and to mediate its effects through the G protein-coupled receptor 39 (GPR39). Subsequent research failed to reproduce the initial findings, however, and the possible anorexigenic effects of obestatin, as well as the identity of its receptor, remain unclear. Obestatin plays some important physiological roles, including roles in improving memory, the inhibition of thirst and anxiety, increased secretion of pancreatic juice, and regulation of cell proliferation, survival, apoptosis and differentiation. Preliminary studies have also shown that obestatin stimulates cell proliferation in some cell types through activation of ERK1/2, Akt and PKC pathways. Overall, however, at the commencement of this PhD project, relatively little was known regarding the functions and mechanisms of action of the preproghrelin-derived functional peptides in modulating prostate cancer cell proliferation. The roles of obestatin, and desacyl ghrelin as potential growth factors had not previously been investigated, and the potential expression and regulation of the preproghrelin processing enzymes, GOAT and prohormone convertases was unknown in prostate cancer cell lines. Therefore, the overall objectives of this study were to: 1. investigate the effects of obestatin on cell proliferation and signaling in prostate cancer cell lines 2. compare the effects of desacyl ghrelin and ghrelin on cell proliferation and signaling in prostate cancer cell lines 3. investigate whether prostate cancer cell lines possess the necessary enzymatic machinery to produce ghrelin and desacyl ghrelin and if these peptides can regulate GOAT expression Our laboratory has previously shown that ghrelin stimulates cell proliferation in the PC3 and LNCaP prostate cancer cell line through activation of the ERK1/2 pathway. In this study it has been demonstrated that treatments with either ghrelin, desacyl ghrelin or obestatin over 72 hours significantly increased cell proliferation in the PC3 prostate cancer cell line but had no significant effect in the RWPE-1 transformed normal prostate cell line. Ghrelin (1000nM) stimulated cell proliferation in the PC3 prostate cancer cell line by 31.66 6.68% (p<0.01) with the WST-1 method, and 13.55 5.68% (p<0.05) with the CyQUANT assay. Desacyl ghrelin (1000nM) increased cell proliferation in PC3 cells by 21.73 2.62% (p<0.01) (WST-1), and 15.46 7.05% (p<0.05) (CyQUANT) above untreated control. Obestatin (1000nM) induced a 28.37 7.47% (p<0.01) (WST-1) and 12.14 7.47% (p<0.05) (CyQUANT) significant increase in cell proliferation in the PC3 prostate cancer cell line. Ghrelin and desacyl ghrelin treatments stimulated Akt and ERK phosphorylation across a range of concentrations (p<0.01). Obestatin treatment significantly stimulated Akt, ERK and PKC phosphorylation (p<0.05). Through the use of specific inhibitors, the MAPK inhibitor U0126 and the Akt1/2 kinase inhibitor, it was demonstrated that ghrelin- and obestatin-induced cell proliferation in the PC3 prostate cancer cell line is mediated through activation of ERK1/2 and Akt pathways. Although desacyl ghrelin significantly stimulated Akt and ERK phosphorylation, U0126 failed to prevent desacyl ghrelin-induced cell proliferation suggesting ghrelin and desacyl ghrelin might act through different mechanisms to increase cell proliferation. Ghrelin and desacyl ghrelin have shown a proliferative effect in osteoblasts, pancreatic -cells and cardiomyocytes through activation of ERK1/2 and PI3K/Akt pathways. Here it has been shown that ghrelin and its non-acylated form exert the same function and stimulate cell proliferation in the PC3 prostate cancer cell line through activation of the Akt pathway. Ghrelin-induced proliferation was also mediated through activation of the ERK1/2 pathway, however, desacyl ghrelin seems to stimulate cell proliferation in an ERK1/2-independent manner. As desacyl ghrelin does not bind and activate GHSR1a, the only known functional ghrelin receptor, the finding that both ghrelin and desacyl ghrelin stimulate cell proliferation in the PC3 cell line suggests that these peptides could be acting through the yet unidentified alternative ghrelin receptor in this cell type. Obestatin treatment also stimulated PKC phosphorylation, however, a direct role for this pathway in stimulating cell proliferation could not be proven using available PKC pathway inhibitors, as they caused significant cell death over the extended timeframe of the cell proliferation assays. Obestatin has been shown to stimulate cell proliferation through activation of PKC isoforms in human retinal epithelial cells and in the human gastric cancer cell line KATO-III. We have demonstrated that all of the prostate-derived cell lines examined (PC3, LNCaP, DU145, 22Rv1, RWPE-1 and RWPE-2) expressed GOAT and at least one of the prohormone convertases, which are known to cleave the proghrelin peptide, PC1/3, PC2 and furin, at the mRNA level. These cells, therefore, are likely to possess the necessary machinery to cleave the preproghrelin protein and to produce the mature ghrelin and desacyl ghrelin peptides. In addition to prohormone convertases, the presence of octanoic acid is essential for acylated ghrelin production. In this study octanoic acid supplementation significantly increased cell proliferation in the PC3 prostate cancer cell line by over 20% compared to untreated controls (p<0.01), but surprisingly, not in the DU145, LNCaP or 22Rv1 prostate cancer cell lines or in the RWPE-1 and RWPE-2 prostate-derived cell lines. In addition, we demonstrated that exogenous ghrelin induced a statistically significant two-fold decrease in GOAT mRNA expression in the PC3 cell line (p<0.05), suggesting that ghrelin could pontentially downregulate its own acylation and, therefore, regulate the balance between ghrelin and desacyl ghrelin. This was not observed, however, in the DU145 and LNCaP prostate cancer cell lines. The GOAT-ghrelin system represents a direct link between ingested nutrients and regulation of ghrelin production and the ghrelin/desacyl ghrelin ratio. Regulation of ghrelin acylation is a potentially attractive and desirable tool for the development of better therapies for a number of pathological conditions where ghrelin has been shown to play a key role. The finding that desacyl ghrelin stimulates cell proliferation in the PC3 prostate cancer cell line, and responds to ghrelin in the same way, suggests that this cell line expresses an alternative ghrelin receptor. Although all the cell lines examined expressed both GHS-R1a and GHS-R1b mRNA, it remains uncertain whether these cell lines express the unidentified alternative ghrelin receptor. It is possible that the varied responses seen could be due to the expression of different ghrelin receptors in different cell lines. In addition to GOAT, prohormone convertases and octanoic acid availability may regulate the production of different peptides from the ghrelin preprohormone. The studies presented in this thesis provide significant new information regarding the roles and mechanisms of action of the preproghrelin-derived peptides, ghrelin, desacyl ghrelin and obestatin, in modulating prostate cancer cell line proliferation. A number of key questions remain to be resolved, however, including the identification of the alternative ghrelin/desacyl ghrelin receptor, the identification of the obestatin receptor, a clarification of the signaling mechanisms which mediate cell proliferation in response to obestatin treatment and a better understanding of the regulation at both the gene and post-translational levels of functional peptide generation. Further studies investigating the role of the ghrelin axis using in vivo prostate cancer models may be warranted. Until these issues are determined, the potential for the ghrelin axis, to be recognised as a novel useful target for therapy for cancer or other pathologies will be uncertain.

Risk taking by motorcyclists : rider training and stages of change

Motorcyclists in Australia have been found to be 30 times more likely to be killed per kilometre travelled than car occupants and 40 times more likely to be seriously injured. One approach to preventing motorcycle-related injury is through training and education. While there is traditionally a major focus on developing riding skills during training for motorcyclists, there is also a need for training to promote safe riding to reduce subsequent risk taking. The Transtheoretical Model, commonly known as the ‘Stages of Change’ model, provides a rationale to support incremental behaviour change for risky riding that may be facilitated through motorcycle rider training and education. A sample of 438 learner motorcyclists attended a rider training program in Queensland, Australia, with the stages of change to adopt a safe riding mindset and safe riding practices being measured upon commencement of the course (Time 1) and then again upon completion (Time 2). A small subset of the original sample (n=45) responded at follow up 24 months post training (Time 3). Consistent with the aims of training, results showed a significant shift from the contemplation stage to the subsequent stages of change for participants between Time 1 and Time 2. Progression to the later stages in the model was found for the subset of participants that responded at the Time 3 follow up. Issues of questionnaire design and the utility of the Transtheoretical Model for motorcycle rider training are discussed.

Toward a shopping typology of primary male grocery shoppers

Purpose – The purpose of this paper is to segment primary male grocery shoppers based on store and product attribute evaluations. A rich profile for each segment is developed. These developed contemporary shopper typologies are contrasted against earlier works. Design/methodology/approach – Data of 280 male grocery shoppers was attained by a survey questionnaire. Factor analysis, cluster analysis and ANOVA were employed to develop specific segments of male shoppers. Findings – Four distinct cohorts of male shoppers emerge from the data of eight constructs, measured by 46 items. One new shopper type, not found in earlier typology literature, emerged from this research. This shopper presented as young, well educated, at the commencement of their career and family lifecycle, attracted by a strong value offer and willingness to share the family food shopping responsibilities. Practical implications – Research outcomes encourage supermarket retailers to implement targeted marketing and rationalized operational strategies that deliver on attributes of importance. Originality/value – This research makes a contribution to segmentation literature and grocery retail practice in several ways. It presents the first retail typology of male supermarket shoppers, employing a cluster analysis technique. The research provides insights into the modern family food shopping behaviour of men, a channel in which men are now recognised as equal contributors. The research provides the basis for further gender comparative and cross-contextual studies.

Does the use of store-and-forward telehealth systems improve outcomes for clinicians managing diabetic foot ulcers? : A pilot study

Diabetic foot ulcers are one of the most hospitalised diabetes complications and contribute to many leg amputations. Trained diabetic foot teams and specialists managing diabetic foot ulcers have demonstrated reductions in amputations and hospitalisation by up to 90%. Few such teams exist in Australia. Thus, access is limited for all geographical populations and may somewhat explain the high rates of hospitalisation. Aim: This pilot study aims to analyse if local clinicians managing diabetic foot complications report improved access to diabetic foot specialists and outcomes with the introduction of a telehealth store-and-forward system. Method: A store-and-forward telehealth system was implemented in six different Queensland locations between August 2009 and February 2010. Sites were offered ad hoc and/or fortnightly telehealth access to a diabetic foot speciality service. A survey was sent six months following commencement of the trial to the 14 eligible clinicians involved in the trial to gauge clinical perception of the telehealth system. Results: Eight participants returned the surveys. The majority of responding clinicians reported that the telehealth system was easy to use (100%), improved their access to diabetic foot speciality services (75%), improved upskilling of local diabetes service staff (100%), and improved patient outcomes (100%). Conclusion: This pilot study suggests that clinicians found the use of a telehealth store-and-forward system very useful in improving access to speciality services, clinical skills and patient outcomes. This study supports the recommendation that telehealth systems should be made available for diabetic foot ulcer management.

Looking Yonder : Longitudinal Research and Evaluation of the Yonder Participative Arts-based Learning Model Report 2010-2012

Since 2007, KITE Arts Education Program @ QPAC has been engaged in a series of arts and drama-based experiences for students in selected primary schools on the edges of Brisbane and in regional Queensland. The in-school workshop experiences of the program have culminated in a performance by the children for their school community, parents and carers at the Queensland Performing Arts Centre or a regional cultural venue. In conducting an analysis of the Yonder project, the researcher aimed to provide evidence of outcomes brought about through participation by schools, school staff, students and their communities in the Yonder project. To develop longitudinal data project initiators, participants were interviewed at six-monthly intervals to establish patterns of engagement and participation. The report analyses arts-based workshops conducted by the teacher artist in edge-city Brisbane and a regional centre; interviews with teachers and school administrators from the participating schools; interviews with teacher artist and professional artists; interviews with community partners; teacher professional development workshops; community-based workshops; performance outcomes that were the culminating events of the workshop program; student work samples and student reflections on the program. This document covers data and project outputs from February 2010 to July 2012. There have been five iterations of the Yonder project since its commencement in mid-2009 — three in regional Queensland (February–April 2010; February–May 2011; February–May 2012) and two in edge-city1 Brisbane (July–September 2010; August–October 2011). This report is a result of a research partnership between Queensland Performing Arts Centre and Queensland University of Technology (QUT) Creative Industries Faculty(Drama).

Axial length and choroidal thickness changes accompanying prolonged accommodation in myopes and emmetropes

The time course of elongation and recovery of axial length associated with a 30 minute accommodative task was studied using optical low coherence reflectometry in a population of young adult myopic (n = 37) and emmetropic (n = 22) subjects. Ten of the 59 subjects were excluded from analysis either due to inconsistent accommodative response, or incomplete anterior biometry data. Those subjects with valid data (n = 49) were found to exhibit a significant axial elongation immediately following the commencement of a 30 minute, 4 D accommodation task, which was sustained for the duration of the task, and ¬was evident to a lesser extent immediately following task cessation. During the accommodation task, on average, the myopic subjects exhibited 22 ± 34 µm, and the emmetropic subjects 6 ± 22 µm of axial elongation, however the differences in axial elongation between the myopic and emmetropic subjects were not statistically significant (p = 0.136). Immediately following the completion of the task, the myopic subjects still exhibited an axial elongation (mean magnitude 12 ± 28 µm), that was significantly greater (p < 0.05) than the changes in axial length observed in the emmetropic subjects (mean change -3 ± 16 µm). Axial length had returned to baseline levels 10 minutes after completion of the accommodation task. The time for recovery from accommodation-induced axial elongation was greater in myopes, which may reflect differences in the biomechanical properties of the globe associated with refractive error. Changes in subfoveal choroidal thickness were able to be measured in 37 of the 59 subjects, and a small amount of choroidal thinning was observed during the accommodation task that was statistically significant in the myopic subjects (p < 0.05). These subfoveal choroidal changes could account for some but not all of the increased axial length during accommodation.

The relationship between fundamental movement skills and self-reported physical activity during Finnish junior high school

Background: Previous studies have shown that fundamental movement skills (FMS) and physical activity are related. Specifically, earlier studies have demonstrated that the ability to perform a variety of FMS increases the likelihood of children participating in a range of physical activities throughout their lives. To date, however, there have not been studies focused on the development of, or the relationship between, these variables through junior high school (that is, between the ages of 13 and 15). Such studies might provide important insights into the relationships between FMS and physical activity during adolescence, and suggest ways to design more effective physical education programmes for adolescents. Purpose: The main purposes of the study are: (1) to investigate the development of the students' self-reported physical activity and FMS from Grade 7 to Grade 9, (2) to analyse the associations among the students' FMS and self-reported physical activity through junior high school, (3) to analyse whether there are gender differences in research tasks one and/or two. Participants and setting: The participants in the study were 152 Finnish students, aged 13 and enrolled in Grade 7 at the commencement of the study. The sample included 66 girls and 86 boys who were drawn from three junior high schools in Middle Finland. Research design and data collection: Both the FMS tests and questionnaires pertaining to self-reported physical activity were completed annually during a 3 year period: in August (when the participants were in Grade 7), January (Grade 8), and in May (Grade 9). Data analysis: Repeated measures multivariate analysis of variances (MANOVAs) were used to analyse the interaction between gender and time (three measurement points) in FMS test sumscores and self-reported physical activity scores. The relationships between self-reported physical activity scores and fundamental movement skill sumscores through junior high school were analysed using Structural Equation Modelling (SEM) with LISREL 8.80 software. Findings: The MANOVA for self-reported physical activity demonstrated that both genders' physical activity decreased through junior high school. The MANOVA for the FMS revealed that the boys' FMS sumscore increased whereas the girls' skills decreased through junior high school. The SEM and squared multiple correlations revealed FMS in Grades 7 and 8 as well as physical activity in Grade 9 explained FMS in Grade 9. The portion of prediction was 69% for the girls and 55% for the boys. Additionally, physical activity measured in Grade 7 and FMS measured in Grade 9 explained physical activity in Grade 9. The portion of prediction was 12% for the girls and 29% for the boys. In the boys' group, three additional paths were found; FMS in Grade 7 explained physical activity in Grade 9, physical activity in Grade 7 explained FMS in Grade 8, and physical activity in Grade 7 explained physical activity in Grade 8. Conclusions: The study suggests that supporting and encouraging FMS and physical activity are co-related and when considering combined scores there is a greater likelihood of healthy lifelong outcomes. Therefore, the conclusion can be drawn that FMS curriculum in school-based PE is a plausible way to ensure good lifelong outcomes. Earlier studies support that school physical education plays an important role in developing students FMS and is in a position to thwart the typical decline of physical activity in adolescence. These concepts are particularly important for adolescent girls as this group reflects the greatest decline in physical activity during the adolescent period.

Rolling in the aisles : a comparative study of male and female grocery shopper typologies

The purpose of this paper is to segment male and female grocery shoppers based on store and product attribute evaluations. A rich profile for each segment is developed. Gender comparisons are operationalised and these developed contemporary shopper typologies are further contrasted against earlier works. Data of 560 grocery shoppers was attained by a survey questionnaire. Factor analysis, cluster analysis and ANOVA were employed to develop specific segments of shoppers. Four distinct cohorts of male shoppers and three cohorts of female shoppers emerge from the data of eight constructs, measured by 46 items. One new shopper type, not found in earlier typology literature, emerged from this research. This shopper presented as a young, well educated, at the commencement of their career and family lifecycle, attracted by a strong value offer and willingness to share the family food shopping responsibilities. This research makes a contribution to segmentation literature and grocery retail practice in several ways. It presents the first retail typology of male supermarket shoppers, employing a cluster analysis technique. Comparisons between male and female grocery shopping typologies are accordingly facilitated. The research provides insights into the modern family food shopping behaviour of men; a channel in which men are now recognised as equal contributors. Research outcomes encourage supermarket retailers to implement targeted marketing and rationalized operational strategies that deliver on attributes of importance. Finally, this research provides the basis for further cross-cultural, cross-contextual comparative studies.

The Australian Consumer Law

Reform of Australia’s inconsistent Commonwealth, State and Territory consumer laws is now a reality. The 1 January 2011 commencement of the Australian Consumer Law (ACL), within the Competition and Consumer Act 2010, is the culmination of a long process of consultation. Unifying and rationalising the plethora of laws, this new Act sees the disappearance of the “Trade Practices Act” and the amendment of a raft of State and Territory legislation; the new national regime informed by them operates in their stead. This is indisputably the most comprehensive change in the history of the Trade Practices Act 1974. This book aims to assist practitioners, academics and students understand the Australian Consumer Law regime and its impact. It summarises the history and constitutional basis of the ACL, explaining how the ACL will be implemented, amended and enforced. In addition it explores how the various general and specific protections interrelate, and the scope of their overlap, and considers the content of the ACL, and the principal changes from the provisions of the Trade Practices Act.

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.

Adaptive radiotherapy for virally mediated head and neck cancer

Purpose: Virally mediated head and neck cancers (VMHNC) often present with nodal involvement, and are generally considered radioresponsive, resulting in the need for a re-planning CT during radiotherapy (RT) in a subset of patients. We sought to identify a high-risk group based on nodal size to be evaluated in a future prospective adaptive RT trial. Methodology: Between 2005-2010, 121 patients with virally-mediated, node positive nasopharyngeal (EBV positive) or oropharyngeal (HPV positive) cancers, receiving curative intent RT were reviewed. Patients were analysed based on maximum size of the dominant node with a view to grouping them in varying risk categories for 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 3 groups; ≤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%). Sample size did not allow statistical analysis to detect a significant difference or exclusion of a lack of difference between the 3 groups. Conclusion: In this series, patients with VMHNC and nodal size > 46mm appear to be a high-risk group for the need of re-planning during a course of definitive radiotherapy. This finding will now be tested in a prospective adaptive RT study.

Adaptive radiotherapy for virally mediated head and neck cancer

Purpose: Virally mediated head and neck cancers (VMHNC) often present with nodal involvement, and are generally considered radioresponsive, resulting in the need for a re-planning CT during radiotherapy (RT) in a subset of patients. We sought to identify a high-risk group based on nodal size to be evaluated in a future prospective adaptive RT trial. Methodology: Between 2005-2010, 121 patients with virally-mediated, node positive nasopharyngeal (EBV positive) or oropharyngeal (HPV positive) cancers, receiving curative intent RT were reviewed. Patients were analysed based on maximum size of the dominant node with a view to grouping them in varying risk categories for 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 3 groups; ≤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%). Sample size did not allow statistical analysis to detect a significant difference or exclusion of a lack of difference between the 3 groups. Conclusion: In this series, patients with VMHNC and nodal size > 46mm appear to be a high-risk group for the need of re-planning during a course of definitive radiotherapy. This finding will now be tested in a prospective adaptive RT study.

Adaptive radiotherapy for virally mediated head and neck cancer

Purpose: Virally mediated head and neck cancers (VMHNC) often present with nodal involvement, and are generally considered radioresponsive, resulting in the need for plan adaptation during radiotherapy in a subset of patients. We sought to identify a high-risk group based on pre-treatment nodal size to be evaluated in a future prospective adaptive radiotherapy trial. Methodology: Between 2005-2010, 121 patients with virally-mediated, node positive nasopharyngeal or oropharyngeal cancers, receiving definitive radiotherapy 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 for 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 3 groups defined by pre-treatment nodal size; ≤ 35mm (Group 1), 36-45mm (Group 2), ≥ 46mm (Group 3). Applying these groups to the patient cohort, 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 VMHNC and nodal size > 46mm appear to be a high-risk group for the need of plan adaptation during a course of definitive radiotherapy. This finding will now be tested in a prospective adaptive radiotherapy study.

Histological and morphometric lesions in the pre-clinical, developmental phase of insulin-induced laminitis in Standardbred horses

Lamellar pathology in experimentally-induced equine laminitis associated with euglycaemic hyperinsulinaemia is substantial by the acute, clinical phase (∼48 h post-induction). However, lamellar pathology of the developmental, pre-clinical phase requires evaluation. The aim of this study was to analyse lamellar lesions both qualitatively and quantitatively, 6, 12 and 24 h after the commencement of hyperinsulinaemia. Histological and histomorphometrical analyses of lamellar pathology at each time-point included assessment of lamellar length and width, epidermal cell proliferation and death, basement membrane (BM) pathology and leucocyte infiltration. Archived lamellar tissue from control horses and those with acute, insulin-induced laminitis (48 h) was also assessed for cellular proliferative activity by counting the number of cells showing positive nuclear immuno labelling for TPX2. Decreased secondary epidermal lamellar (SEL) width and increased histomorphological evidence of SEL epidermal basal (and supra-basal) cell death occurred early in disease progression (6 h). Increased cellular proliferation in SELs, infiltration of the dermis with small numbers of leucocytes and BM damage occurred later (24 and 48 h). Some lesions, such as narrowing of the SELs, were progressive over this time period (6–48 h). Cellular pathology preceded leucocyte infiltration and BM pathology, indicating that the latter changes may be secondary or downstream events in hyperinsulinaemic laminitis.