Molecular and structural basis of androgen receptor responses to dihydrotestosterone, medroxyprogesterone acetate and Δ4-tibolone

Medroxyprogesterone acetate (MPA) has widely been used in hormone replacement therapy (HRT), and is associated with an increased risk of breast cancer, possibly due to disruption of androgen receptor (AR) signaling. In contrast, the synthetic HRT Tibolone does not increase breast density, and is rapidly metabolized to estrogenic 3α-OH-tibolone and 3β-OH-tibolone, and a delta-4 isomer (Δ4-TIB) that has both androgenic and progestagenic properties. Here, we show that 5α-dihydrotestosterone (DHT) and Δ4-TIB, but not MPA, stabilize AR protein levels, initiate specific AR intramolecular interactions critical for AR transcriptional regulation, and increase proliferation of AR positive MDA-MB-453 breast cancer cells. Structural modeling and molecular dynamic simulation indicate that Δ4-TIB induces a more stable AR structure than does DHT, and MPA a less stable one. Microarray expression analyses confirms that the molecular actions of Δ4-TIB more closely resembles DHT in breast cancer cells than either ligand does to MPA.

Teaching pharmacy students how to manage effectively in a highly competitive environment

Aims To evaluate if a revamped business management course for 4th year undergraduate pharmacy students had achieved the course aims of not only improving pharmacy students’ perceived understanding of pharmacy business management topics but also increasing their confidence in their business management knowledge and skills. Background Student feedback from previous years had indicated that the cohort had struggled to translate theoretical business management concepts learned in the classroom into practice in the workplace. To address this problem the course has been changed to a ‘flipped classroom’ format with face-to-face time focusing on case-based scenarios and interactive classroom discussion with some role plays. Method Both course assessment throughout the semester and a student survey informed the evaluation process. Results After completing the course, students felt they had increased their knowledge of business management concepts but many indicated that they lacked the confidence to undertake basic management functions. Conclusions Further course restructuring is required with a greater focus on skills development.

Engaging creativity through an action learning and action research process to develop an Indigenous art exhibition

In most art exhibitions, the creative part of the exhibition is assumed to be the artworks on display. But for the Capricornia Arts Mob’s first collective art exhibition in Rockhampton during NAIDOC Week in 2012, the process of developing the exhibition became the focus of creative action learning and action research. In working together to produce a multi-media exhibition, we learned about the collaborative processes and time required to develop a combined exhibition. We applied Indigenous ways of working – including yarning, cultural respect, cultural protocols, mentoring young people, providing a culturally safe working environment and sharing both time and food – to develop our first collective art exhibition. We developed a process that allowed us to ask deep questions, engage in a joint journey of learning, and develop our collective story. This paper explores the processes that the Capricornia Arts Mob used to develop the exhibition for NAIDOC 2012.

Assessing the property market impact of stigma removal : high voltage overhead transmission lines removal in Wellington, NZ

This thesis advances the understanding of the impact of stigma on property values. A case study in Wellington, New Zealand, enabled hedonic modelling and an empirical analysis to determine the impact of the stigma from the high voltage transmission line structure and how long the stigma remained after removal. The results reveal a substantial difference between the discount applied to individual properties while the structure is in place, as compared to the overall increase in neighbourhood value once the structure, which created the stigma, is removed.

Paracrine interactions between LNCaP prostate cancer cells and bioengineered bone in 3D in vitro culture reflect molecular changes during bone metastasis

As microenvironmental factors such as three-dimensionality and cell–matrix interactions are increasingly being acknowledged by cancer biologists, more complex 3D in vitro models are being developed to study tumorigenesis and cancer progression. To better understand the pathophysiology of bone metastasis, we have established and validated a 3D indirect co-culture model to investigate the paracrine interactions between prostate cancer (PCa) cells and human osteoblasts. Co-culture of the human PCa, LNCaP cells embedded within polyethylene glycol hydrogels with human osteoblasts in the form of a tissue engineered bone construct (TEB), resulted in reduced proliferation of LNCaP cells. LNCaP cells in both monoculture and co-culture were responsive to the androgen analog, R1881, as indicated by an increase in the expression (mRNA and/or protein induction) of androgen-regulated genes including prostate specific antigen and fatty acid synthase. Microarray gene expression analysis further revealed an up-regulation of bone markers and other genes associated with skeletal and vasculature development and a significant activation of transforming growth factor β1 downstream genes in LNCaP cells after co-culture with TEB. LNCaP cells co-cultured with TEB also unexpectedly showed similar changes in classical androgen-responsive genes under androgen-deprived conditions not seen in LNCaP monocultures. The molecular changes of LNCaP cells after co-culturing with TEBs suggest that osteoblasts exert a paracrine effect that may promote osteomimicry and modulate the expression of androgen-responsive genes in LNCaP cells. Taken together, we have presented a novel 3D in vitro model that allows the study of cellular and molecular changes occurring in PCa cells and osteoblasts that are relevant to metastatic colonization of bone. This unique in vitro model could also facilitate cancer biologists to dissect specific biological hypotheses via extensive genomic or proteomic assessments to further our understanding of the PCa-bone crosstalk.

Too much of a good thing?: An investigation into overparenting

This project investigated the concept of overparenting, parenting which over uses valued parenting practices, such as protection and care for offspring. It established a clearer definition of overparenting as related to school-aged children, created a measure of overparenting, and showed that overparenting actions/beliefs to do with homework may impact on a child/adolescent's sense of responsibility for their academic achievements. Previously, most parenting research and education focussed on parenting approaches which deliver insufficient effort for children. This project showed that excessive responsiveness or assistance may also be detrimental.

Combining expert opinions in prior elicitation

We consider the problem of combining opinions from different experts in an explicitly model-based way to construct a valid subjective prior in a Bayesian statistical approach. We propose a generic approach by considering a hierarchical model accounting for various sources of variation as well as accounting for potential dependence between experts. We apply this approach to two problems. The first problem deals with a food risk assessment problem involving modelling dose-response for Listeria monocytogenes contamination of mice. Two hierarchical levels of variation are considered (between and within experts) with a complex mathematical situation due to the use of an indirect probit regression. The second concerns the time taken by PhD students to submit their thesis in a particular school. It illustrates a complex situation where three hierarchical levels of variation are modelled but with a simpler underlying probability distribution (log-Normal).

Lung recruitment and endotracheal suction in ventilated preterm infants measured with electrical impedance tomography

Aims Although suctioning is a standard airway maintenance procedure, there are significant associated risks, such as loss of lung volume due to high negative suction pressures. This study aims to assess the extent and duration of change in end-expiratory level (EEL) resulting from endotracheal tube (ETT) suction and to examine the relationship between EEL and regional lung ventilation in ventilated preterm infants with respiratory distress syndrome. Methods A prospective observational clinical study of the effect of ETT suction on 20 non-muscle-relaxed preterm infants with respiratory distress syndrome (RDS) on conventional mechanical ventilation was conducted in a neonatal intensive care unit. Ventilation distribution was measured with regional impedance amplitudes and EEL using electrical impedance tomography. Results ETT suction resulted in a significant increase in EEL post-suction (P < 0.01). Regionally, anterior EEL decreased and posterior EEL increased post-suction, suggesting heterogeneity. Tidal volume was significantly lower in volume-guarantee ventilation compared with pressure-controlled ventilation (P = 0.04). Conclusions ETT suction in non-muscle-relaxed and ventilated preterm infants with RDS results in significant lung volume increase that is maintained for at least 90 min. Regional differences in distribution of ventilation with ETT suction suggest that the behaviour of the lung is heterogeneous in nature.

Models of social media adoption in emergency management organisations

Recent natural disasters such as the Haitian earthquake 2011, the South East Queensland floods 2011, the Japanese earthquake and tsunami 2011 and Hurricane Sandy in the United States of America in 2012, have seen social media platforms changing the face of emergency management communications, not only in times of crisis and also during business-as-usual operations. With social media being such an important and powerful communication tool, especially for emergency management organisations, the question arises as to whether the use of social media in these organisations emerged by considered strategic design or more as a reactive response to a new and popular communication channel. This paper provides insight into how the social media function has been positioned, staffed and managed in organisations throughout the world, with a particular focus on how these factors influence the style of communication used on social media platforms. This study has identified that the social media function falls on a continuum between two polarised models, namely the authoritative one-way communication approach and the more interactive approach that seeks to network and engage with the community through multi-way communication. Factors such the size of the organisation; dedicated resourcing of the social media function; organisational culture and mission statement; the presence of a social media champion within the organisation; management style and knowledge about social media play a key role in determining where on the continuum organisations sit in relation to their social media capability. This review, together with a forthcoming survey of Australian emergency management organisations and local governments, will fill a gap in the current body of knowledge about the evolution, positioning and usage of social media in organisations working in the emergency management field in Australia. These findings will be fed back to Industry for potential inclusion in future strategies and practices.

Transforming the future of treatment for ovarian cancer

As for many other cancers, metastasis is the leading cause of death of patients with ovarian cancer. Vigorous basic and clinical research is being performed to initiate more efficacious treatment strategies to improve the poor outcome of women with this cancer. Current treatment for ovarian cancer includes advanced cyto-reductive surgery and traditional platinum and taxane combined chemotherapy. Clinical trials using novel cytotoxic reagents and tyrosine kinase inhibitors have also been progressing. In parallel, the application of robust unbiased high throughput research platforms using transcriptomic and proteomic approaches has identified that not only individual cell signalling pathways, but a network of molecular pathways, play an important role in the biology of ovarian cancer. Furthermore, intensive genomic and epigenetic analyses have also revealed single nucleotide polymorphisms associated with risk and/or aetiology of this cancer including patient response to treatment. Taken together, these approaches, that are advancing our understanding, will have an impact on the generation of new therapeutic approaches and strategies for improving the outcome and quality of life of patients with ovarian cancer in the near future.

Experience has no shadow

This research is situated in the field of practice-led research investigating embodied perspectives on the performance of dance making. In the stock of choreographic literature, the celebrated ‘creativity’ label is associated predominantly with the choreographer and is discussed in terms of product rather than process (Lussier-Ley and Durand-Bush 2009; Hennessey 2003). A reliance on the mystery of inspiration or choreographic genius (Penty 1998) for the production of ‘great’ dance works does not acknowledge the complex and timely process common in the creation of dance (Mace and Ward 2002) nor provide a true representation of the creative contributors (Farrer 2014). The failure to attribute creative impulses and skills to dancers is reminiscent of a time when they were thought of only as instruments in the creative process not active participants and collaborators (Jowitt 2001a; H’Doubler 1957). This project asked the question, to what end do dancers contribute to choreography and how is this contribution valued and recognised? Dancers are integral to the creative process. The research found that the scope of a dancers’ creative involvement in the development of a new work is dependent on: the individual choreographers approach to creating movement; the relationship between dancer and choreographer, and dancer and fellow company members; and the dancers collaborative skills and interpretive skills, versatility, and initiative. Recognition and attribution of dancers’ creative input is dependent on a choreographer’s viewpoint, generosity, and prior creative experiences. The work was created as a part of the Ausdance Queensland 2010 Bell Tower III Choreographic Residency program. Applicants were peer reviewed and vetted by a panel of local and national dance producers. The creative work was presented at the Judith Wright Centre for Live Arts. The project was funded by Ausdance Queensland and Arts Queensland. https://es-es.facebook.com/events/106661226023025/?hc_location=stream

Pro bono partnerships in environmental law : enhancing outcomes for universities and CLCs

CLE can be a life-changing event in a law student’s education. It can open their eyes to the day-to-day operation of justice and provide them with examples of possible career paths they may never have thought existed. Yet it can also provide long-term benefits for CLCs and academics. Recent CLE models have moved towards partnerships with external organisations and away from on-site legal clinics. Some examples have exhibited success with a multidisciplinary approach involving students from non-law disciplines to provide a holistic approach to a CLC’s needs. Such a multidisciplinary approach is of particular benefit in community lawyering clinics where students are engaged in social change lawyering. The QUT/EDO partnership presents a new model in the environmental clinic landscape in Australia. Initial feedback suggests that the clinic has assisted students in gaining insight into the access to justice issues arising from mining activities and to raise the level of understanding and awareness among community members of their legal rights to protect the environment. Looking at ways to increase partnerships between universities and CLCs is of vital importance in the future, given recent federal government CLC funding cuts. The legal clinic model has great potential to evolve and contribute in ensuring the continued operation of legal initiatives to protect the environment in the public interest.

Homelessness and leaving care : the experiences of young adults in Queensland and Victoria, and implications for practice

This research first asks ‘What happens when young people leave state care?’ in respect of Victoria and Queensland and second ‘What are the service support implications of this?’ A number of methods were used to explore these questions including semi-structured interviews with 27 young adults aged 19-23 years who had been homeless or at risk of homelessness, and focus groups with young people and service providers. This study provides support for the proposition that young people should be proactively and voluntarily involved in periodic monitoring of their lived experience post care and linkage of this monitoring to the activation of timely support. The great majority of young people involved in this study thought this was not only desirable but important. Whilst some young people will be in close contact with leaving care services many others will not. New research is recommended to develop a mentoring and support activation process using participatory monitoring and action research methods. This type of approach reflects the importance of utilising processes with young people in care and leaving care which acknowledge their personhood and capacity to contribute voluntarily to the processes which seek to support them.

A pilot study to assess the appropriateness of prescribing from a collaborative pharmacist prescribing study in a surgical pre admission clinic

Background Current evidence to support non-medical prescribing is predominantly qualitative, with little evaluation of appropriateness. This study aims to evaluate the appropriateness of prescribing, and significance of omissions, from a doctor pharmacist collaborative prescribing model in an elective surgery pre admission clinic (PAC). Method A modified version of the Medication Appropriate Index (MAI) was developed, piloted and subsequently used by an expert panel, comprised of a surgeon, anaesthetist, clinical pharmacologist, pharmacist, resident medical officer (RMO) and clinical nurse. The tool was used to rate the appropriateness of prescribing of medications, and the significance of omissions in a 5% sample (N=19) of the total cohort from a randomised, controlled two arm trial of doctor-pharmacist collaborative prescribing. Results When reviewer assessments were combined, 32 out of 294 (10.9%) medications assessed for appropriateness in the control arm were classed as inappropriate, compared to 13 of 266 (4.9%) in the intervention arm. Out of 89 regular medications in the control arm, 25 (28%) were omitted from the medication charts, compared to 1 out of 55 (2%) in the intervention arm (p<0.001, fishers exact) On average, 52% of omissions in the control arm were judged to have potential for patient harm or ward inconvenience. Conclusion For the appropriateness of prescribing, overall results were similar between arms, as judged by individual panel members. Medication charts in the control arm contained significantly more omissions than in the intervention arm, a number of which were rated by the panel members as having the potential for patient harm or ward inconvenience.