Methodologies for measuring research impact for a new interdisciplinary institute

Interdisciplinary research is often funded by national government initiatives or large corporate sponsorship, and as such, demands periodic reporting on the use of those funds. For reasons of accountability, governance and communication to the tax payer, knowledge of the outcomes of the research need to be measured and understood. The interdisciplinary approach to research raises many challenges for impact reporting. This presentation will consider what are the best practice workflow models and methodologies.Novel methodologies that can be added to the usual metrics of academic publications include analysis of percentage share of total publications in a subject or keyword field, calculating most cited publication in a key phrase category, analysis of who has cited or reviewed the work, and benchmarking of this data against others in that same category. At QUT, interest in how collaborative networking is trending in a research theme has led to the creation of some useful co-authorship graphs that demonstrate the network positions of authors and the strength of their scientific collaborations within a group. The scale of international collaborations is also worth including in the assessment. However, despite all of the tools and techniques available, the most useful way a researcher can help themselves and the process is to set up and maintain their researcher identifier and profile.

Are in vitro estimates of cell diffusivity and cell proliferation rate sensitive to assay geometry?

Cells respond to various biochemical and physical cues during wound–healing and tumour progression. In vitro assays used to study these processes are typically conducted in one particular geometry and it is unclear how the assay geometry affects the capacity of cell populations to spread, or whether the relevant mechanisms, such as cell motility and cell proliferation, are somehow sensitive to the geometry of the assay. In this work we use a circular barrier assay to characterise the spreading of cell populations in two different geometries. Assay 1 describes a tumour–like geometry where a cell population spreads outwards into an open space. Assay 2 describes a wound–like geometry where a cell population spreads inwards to close a void. We use a combination of discrete and continuum mathematical models and automated image processing methods to obtain independent estimates of the effective cell diffusivity, D, and the effective cell proliferation rate, λ. Using our parameterised mathematical model we confirm that our estimates of D and λ accurately predict the time–evolution of the location of the leading edge and the cell density profiles for both assay 1 and assay 2. Our work suggests that the effective cell diffusivity is up to 50% lower for assay 2 compared to assay 1, whereas the effective cell proliferation rate is up to 30% lower for assay 2 compared to assay 1.

Patient perspectives of the impact and long-term management of lymphoedema

Lymphoedema following cancer treatment is characterized by swelling, and adversely influences mobility, function and quality of life. There is no cure, but without treatment lymphedema may progress. Since lymphedema treatment options are costly and time consuming, understanding the influence of these, and other potential barriers, on treatment adherence is vital in reducing the public health burden of lymphedema. Complex physical therapy and compression are supported by scientific evidence and patients also perceive these treatments as effective for improving symptoms and function. Multiple treatments may be required to treat all aspects of the condition. Patients and health professionals should consider effect and costs when identifying optimal treatment strategies.

The orphan nuclear receptor LRH-1 promotes breast cancer motility and invasion

The orphan nuclear receptor liver receptor homologue-1 (LRH-1) has roles in the development, cholesterol and bile acid homeostasis, and steroidogenesis. It also enhances proliferation and cell cycle progression of cancer cells. In breast cancer, LRH-1 expression is associated with invasive breast cancer; positively correlates with ERα status and aromatase activity; and promotes oestrogen-dependent cell proliferation. However, the mechanism of action of LRH-1 in breast cancer epithelial cells is still not clear. By silencing or over-expressing LRH-1 in ER-positive MCF-7 and ER-negative MDA-MB-231 breast cancer cells, we have demonstrated that LRH-1 promotes motility and cell invasiveness. Similar effects were observed in the non-tumourigenic mammary epithelial cell line, MCF-10A. Remodelling of the actin cytoskeleton and E-cadherin cleavage was observed with LRH-1 over-expression, contributing to increased migratory and invasive properties. Additionally, in LRH-1 over-expressing cells, the truncation of the 120 kDa E-cadherin to the inactive 97 kDa form was observed. These post-translational modifications in E-cadherin may be associated with LRH-1-dependent changes to matrix metalloproteinase 9 expression. These findings suggest a new role of LRH-1 in promoting migration and invasion in breast cancer, independent of oestrogen sensitivity. Therefore, LRH-1 may represent a new target for breast cancer therapeutics.

The biology of breast tumor progression : acquisition of hormone independence and resistance to cytotoxic drugs

Many breast tumors appear to follow a predictable clinical pattern, being initially responsive to endocrine therapy and to cytotoxic chemotherapy but ultimately exhibiting a phenotype resistant to both modalities. Using the MCF-7 human breast cancer cell line as an example of an 'early' phenotype (estrogen and progesterone receptor positive, steroid responsive, low metastatic potential), we have isolated and characterized a series of hormone-independent but hormone-responsive variants (MIII and MCF7/LCC1). However, these variants remain responsive to both antiestrogens and cytotoxic drugs (methotrexate and colchicine). MIII and MCF7/LCCl cells appear to mimic some of the critical aspects of the early progression to a more aggressive phenotype. An examination of the phenotype of these cells suggests that some hormone-independent breast cancer cells are derived from hormone-dependent parental cells. The development of a hormone-independent phenotype can arise independently of acquisition of a cytotoxic drug resistant phenotype.

Nanoparticles in cancer imaging and therapy

Nanoparticle contrast agents offer the potential to significantly improve existing methods of cancer diagnosis and treatment. Advantages include biocompatibility, selective accumulation in tumor cells, and reduced toxicity. Considerable research is underway into the use of nanoparticles as enhancement agents for radiation therapy and photodynamic therapy, where they may be used to deliver treatment agents, produce localized enhancements in radiation dose and selectively target tumor cells for localized damage. This paper reviews the current status of nanoparticles for cancer treatment and presents preliminary results of a pilot study investigating titanium dioxide nanoparticles for dual-mode enhancement of computed tomography (CT) imaging and kilovoltage radiation therapy. Although titanium dioxide produced noticeable image contrast enhancement in the CT scans, more sensitive detectors are needed to determine whether the nanoparticles can also produce localized dose enhancement for targeted radiation therapy.

Expression profile of endothelin 1 and its receptor endothelin receptor A in papillary thyroid carcinoma and their correlations with clinicopathologic characteristics

The endothelin axis is a group of signaling molecules and their receptors that have been implicated in vascularization of cancers, with their expression being observed to change in different cancer types. In this research, we examined the expression of endothelin 1 and endothelin receptor A at the protein and messenger RNA (mRNA) levels in 123 papillary thyroid carcinomas and 40 matched lymph nodes with metastatic papillary thyroid carcinomas. We found altered endothelin axis mRNA expression in several clinicopathologic parameters with increased endothelin 1 expression in thyroid papillary carcinoma showing stromal calcification, cancers in men, and primary cancers with lymph node metastases. Increased endothelin receptor A mRNA expression was noted in the larger cancers. There is a significant correlation between expression of endothelin receptor A and endothelin 1 in papillary thyroid carcinoma. Both endothelin receptor A and endothelin 1 mRNA expressions were significantly higher in metastatic carcinoma in the lymph node than in primary thyroid cancer. The metastatic carcinoma in the lymph node had increased expression compared with matched primary thyroid carcinoma. Expressions of endothelin 1 and endothelin receptor A were also documented as being high at the protein level. Our results indicate that in thyroid cancer, endothelin 1 and endothelin receptor A are associated with growth in advanced stages and lymph node metastases, likely through known angiogenic linkages. Targeting the endothelin axis may be useful in planning angiogenesis therapy for thyroid cancer.

Carcinoma ex pleomorphic adenoma : a comprehensive review of clinical, pathological and molecular data

Carcinoma ex pleomorphic adenoma (Ca ex PA) is a carcinoma arising from a primary or recurrent benign pleomorphic adenoma. It often poses a diagnostic challenge to clinicians and pathologists. This study intends to review the literature and highlight the current clinical and molecular perspectives about this entity. The most common clinical presentation of CA ex PA is of a firm mass in the parotid gland. The proportion of adenoma and carcinoma components determines the macroscopic features of this neoplasm. The entity is difficult to diagnose pre-operatively. Pathologic assessment is the gold standard for making the diagnosis. Treatment for Ca ex PA often involves an ablative surgical procedure which may be followed by radiotherapy. Overall, patients with Ca ex PA have a poor prognosis. Accurate diagnosis and aggressive surgical management of patients presenting with Ca ex PA can increase their survival rates. Molecular studies have revealed that the development of Ca ex PA follows a multi-step model of carcinogenesis, with the progressive loss of heterozygosity at chromosomal arms 8q, then 12q and finally 17p. There are specific candidate genes in these regions that are associated with particular stages in the progression of Ca ex PA. In addition, many genes which regulate tumour suppression, cell cycle control, growth factors and cell-cell adhesion play a role in the development and progression of Ca ex PA. It is hopeful that these molecular data can give clues for the diagnosis and management of the disease.

Diagnostic potential of saliva : state of the art and future applications [Potenziale diagnostico della saliva: stato dell’arte e applicazioni future]

Over the past 10 years, the use of saliva as a diagnostic fluid has gained attention and has become a translational research success story. Some of the current nanotechnologies have been demonstrated to have the analytical sensitivity required for the use of saliva as a diagnostic medium to detect and predict disease progression. However, these technologies have not yet been integrated into current clinical practice and work flow. As a diagnostic fluid, saliva offers advantages over serum because it can be collected noninvasively by individuals with modest training, and it offers a cost-effective approach for the screening of large populations. Gland-specific saliva can also be used for diagnosis of pathology specific to one of the major salivary glands. There is minimal risk of contracting infections during saliva collection, and saliva can be used in clinically challenging situations, such as obtaining samples from children or handicapped or anxious patients, in whom blood sampling could be a difficult act to perform. In this review we highlight the production of and secretion of saliva, the salivary proteome, transportation of biomolecules from blood capillaries to salivary glands, and the diagnostic potential of saliva for use in detection of cardiovascular disease and oral and breast cancers. We also highlight the barriers to application of saliva testing and its advancement in clinical settings. Saliva has the potential to become a first-line diagnostic sample of choice owing to the advancements in detection technologies coupled with combinations of biomolecules with clinical relevance.

Prevalence of malnutrition, obesity and nutritional risk of Australian paediatric inpatients: A national one-day snapshot

Aim Low prevalence rates of malnutrition at 2.5% to 4% have previously been reported in two tertiary paediatric Australian hospitals. The current study is the first to measure the prevalence of malnutrition, obesity and nutritional risk of paediatric inpatients in multiple hospitals throughout Australia. Methods Malnutrition, obesity and nutritional risk prevalence were investigated in 832 and 570 paediatric inpatients, respectively, in eight tertiary paediatric hospitals and eight regional hospitals across Australia on a single day. Malnutrition and obesity prevalence was determined using z-scores and body mass index (BMI) percentiles. High nutritional risk was determined as a Paediatric Yorkhill Malnutrition Score of 2 or more. Results The prevalence rates of malnourished, wasted, stunted, overweight and obese paediatric patients were 15%, 13.8%, 11.9%, 8.8% and 9.9%, respectively. Patients who identified as Aboriginal and Torres Strait Islander were more likely to have lower height-for-age z-scores (P < 0.01); however, BMI and weight-for-age z-scores were not significantly different. Children who were younger, from regional hospitals or with a primary diagnosis of cardiac disease or cystic fibrosis had significantly lower anthropometric z-scores (P = 0.05). Forty-four per cent of patients were identified as at high nutritional risk and requiring further nutritional assessment. Conclusions The prevalence of malnutrition and nutritional risk of Australian paediatric inpatients on a given day was much higher when compared with the healthy population. In contrast, the proportion of overweight and obese patients was less.

Investigation of fiducial marker and soft-tissue image guidance techniques in prostate radiation therapy

This thesis examines and compares imaging methods used during the radiotherapy treatment of prostate cancer. The studies found that radiation therapists were able to localise and target the prostate consistently with planar imaging techniques and that the use of small gold markers in the prostate reduced the variation in prostate localisation when using volumetric imaging. It was concluded that larger safety margins are required when using volumetric imaging without gold markers.

The ongoing significance of national media systems in the context of media globalization

This article argues that the concept of national media systems, and the comparative study of media systems, institutions, and practices, retains relevance in an era of media globalization and technological convergence. It considers various critiques of ‘media systems’ theories, such as those which view the concept of ‘system’ as a legacy of an outdated positivism and those which argue that the media globalization is weakening the relevance of nation-states in structuring the field of media cultures and practices. It argues for the continuing centrality of nation-states to media processes, and the ongoing significance of the national space in an age of media globalization, with reference to case studies of Internet policies in China, Brazil, and Australia. These studies indicate that nation-states remain critical actors in media governance and that domestic actors largely shape the central dynamics of media policies, even where media technologies and platforms enable global flows of media content.

Tissue engineering of a morphologically and functionally intact humanized bone organ for bone metastasis research

The aim of this thesis was to establish an individualized, patient-specific diagnostic and therapeutic preclinical disease model for bone metastasis research. Tissue engineering of humanized bone within mice allowed the development of a humanized immune system in the host animal. This novel platform makes it possible to analyze the growth of human cancer cells in human bone in the presence of human immune cells.

EVERSUN: A phase 2 trial of alternating sunitinib and everolimus as first-line therapy for advanced renal cell carcinoma

Background We hypothesised that alternating inhibitors of the vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin pathways would delay the development of resistance in advanced renal cell carcinoma (aRCC). Patients and methods A single-arm, two-stage, multicentre, phase 2 trial to determine the activity, feasibility, and safety of 12-week cycles of sunitinib 50 mg daily 4 weeks on / 2 weeks off, alternating with everolimus 10 mg daily for 5 weeks on / 1 week off, until disease progression or prohibitive toxicity in favourable or intermediate-risk aRCC. The primary end point was proportion alive and progression-free at 6 months (PFS6m). The secondary end points were feasibility, tumour response, overall survival (OS), and adverse events (AEs). The correlative objective was to assess biomarkers and correlate with clinical outcome. Results We recruited 55 eligible participants from September 2010 to August 2012. Demographics: mean age 61, 71% male, favourable risk 16%, intermediate risk 84%. Cycle 2 commenced within 14 weeks for 80% of participants; 64% received ≥22 weeks of alternating therapy; 78% received ≥22 weeks of any treatment. PFS6m was 29/55 (53%; 95% confidence interval [CI] 40% to 66%). Tumour response rate was 7/55 (13%; 95% CI 4% to 22%, all partial responses). After median follow-up of 20 months, 47 of 55 (86%) had progressed with a median progression-free survival of 8 months (95% CI 5–10), and 30 of 55 (55%) had died with a median OS of 17 months (95% CI 12–undefined). AEs were consistent with those expected for each single agent. No convincing prognostic biomarkers were identified. Conclusions The EVERSUN regimen was feasible and safe, but its activity did not meet pre-specified values to warrant further research. This supports the current approach of continuing anti-VEGF therapy until progression or prohibitive toxicity before changing treatment.

A model to explain specific cellular communications and cellular harmony: - a hypothesis of coupled cells and interactive coupling molecules

Background The various cell types and their relative numbers in multicellular organisms are controlled by growth factors and related extracellular molecules which affect genetic expression pathways. However, these substances may have both/either inhibitory and/or stimulatory effects on cell division and cell differentiation depending on the cellular environment. It is not known how cells respond to these substances in such an ambiguous way. Many cellular effects have been investigated and reported using cell culture from cancer cell lines in an effort to define normal cellular behaviour using these abnormal cells. A model is offered to explain the harmony of cellular life in multicellular organisms involving interacting extracellular substances. Methods A basic model was proposed based on asymmetric cell division and evidence to support the hypothetical model was accumulated from the literature. In particular, relevant evidence was selected for the Insulin-Like Growth Factor system from the published data, especially from certain cell lines, to support the model. The evidence has been selective in an attempt to provide a picture of normal cellular responses, derived from the cell lines. Results The formation of a pair of coupled cells by asymmetric cell division is an integral part of the model as is the interaction of couplet molecules derived from these cells. Each couplet cell will have a receptor to measure the amount of the couplet molecule produced by the other cell; each cell will be receptor-positive or receptor-negative for the respective receptors. The couplet molecules will form a binary complex whose level is also measured by the cell. The hypothesis is heavily supported by selective collection of circumstantial evidence and by some direct evidence. The basic model can be expanded to other cellular interactions. Conclusions These couplet cells and interacting couplet molecules can be viewed as a mechanism that provides a controlled and balanced division-of-labour between the two progeny cells, and, in turn, their progeny. The presence or absence of a particular receptor for a couplet molecule will define a cell type and the presence or absence of many such receptors will define the cell types of the progeny within cell lineages.