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  • Heart failure affects approximately 1-3% of Western society. There is currently no cure and treatments largely delay disease progression. Consequently, there is great interest in identifying strategies that can improve cardiac function and reverse some of the negative consequences associated with heart failure. This thesis investigates the cardioprotective properties of a gene activated in the athlete’s heart [phosphoinositide 3-kinase (PI3K), p110α] in a setting of heart failure. Two double-transgenic mouse models were generated to assess the role of PI3K in a setting of cardiac stress (dilated cardiomyopathy, DCM). Mice either expressing a constitutively active mutant of PI3K (p110α) (caPI3K) or a dominant negative mutant of PI3K (p110α) (dnPI3K) were crossed with a transgenic mouse model of DCM [due to over-expression of mammalian sterile 20-like kinase 1 (Mst1)]. Increasing PI3K activity in the DCM model (caPI3K-Mst1) improved lifespan and cardiac function, whereas decreasing PI3K activity in the DCM model (dnPI3K-Mst1) had an adverse effect. The cardioprotective properties of PI3K (p110α) were mediated, at least in part, by the kinase Akt. Using the dnPI3K-Mst1 model, I was able to show that reduced PI3K (p110α) activity increases the heart’s susceptibility to atrial fibrillation (AF, the most common arrhythmia in cardiology departments worldwide). dnPI3K-Mst1 mice displayed overt atrial remodelling, varying degrees of conduction blockade and developed spontaneous AF. To assess a possible link between PI3K activity and AF in humans, PI3K (p110α) activity was measured in atrial appendages of patients with AF (acute or chronic) and compared to patients without AF. PI3K (p110α) activity was lower in patients with AF compared to patients in sinus rhythm. These results suggest that reduced PI3K (p110α) makes the heart more susceptible to the development of AF. Thus, strategies or agents that can activate PI3K (p110α) specifically in the heart may represent a useful therapeutic approach for AF. An unanticipated but novel finding was the observation that female dnPI3K-Mst1 mice showed faster disease progression than males. Prior to menopause, females are normally protected against cardiovascular disease compared with males. In contrast, in settings of aging, diabetes or hypertension [associated with depressed or defective PI3K (p110α) activity] females are more prone to cardiac disease than males. Taken together with my results, this suggests that there may be an interaction between PI3K (p110α) and estrogen, and that this interaction is essential for the cardioprotection seen in pre-menopausal women. Data obtained from dnPI3K-Mst1 mice suggests that PI3K (p110α) plays an important role in mediating cardioprotection in females. Unexpectedly, ovariectomy had a beneficial effect on the cardiac phenotype of Mst1 mice, but no significant effect in caPI3K-Mst1 or dnPI3K-Mst1 mice. The mechanisms responsible for these phenotypes will require further investigation. In summary, this thesis presents compelling evidence to support investigation into therapeutics that activate components of the PI3K (p110α) signalling pathway in a setting of cardiac stress.
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  • NetZero Brochure
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  • This macro is designed to work with 4 channel confocal images where channel 1 is a nuclear stain and the other three channels are RNAscope puncta stains. The macro extracts the nuclei and classifies cells as positive or negative for each RNAscope marker based on a user defined cuttoff. Individual cells are also processed to count the raw number of RNAscope spots for each channel.
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  • The August 2019 edition of FLEET News recaps FLEET's Lindau travellers (UQ, RMIT, ANU), introduces a new unit the Centre is running on future computing at secondary-school level (with contributions from members from across the Centre), and covers new discoveries in excitonic insulators (UOW) and semiconductor-TMDs (Monash). For other FLEET Newsletters see http://www.fleet.org.au/blog/fleet-news-subscribers/ or @FLEETCentre
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  • Our two page briefs are designed to provide a snapshot of key terms and definitions, legislation, services and research towards preventing family violence. The briefs are provided in PDF format. To access this information in additional accessible formats, please email monashgfv@gmail.com Access more of our research briefs on our website at: https://arts.monash.edu/gender-and-family-violence/research-briefs
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  • Our two page briefs are designed to provide a snapshot of key terms and definitions, legislation, services and research towards preventing family violence. The briefs are provided in PDF format. To access this information in additional accessible formats, please email monashgfv@gmail.com Access more of our research briefs on our website at: https://arts.monash.edu/gender-and-family-violence/research-briefs
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  • This tool has been written for 3 reasons:To help people with disability to talk about their own money.To tell people where to get help if somebody is not using their money in the right way.To help people who want to help people with disability know what questions to ask.Support workers and other people, such as trusted friends or neighbours, can use this tool to help people with disability. The tool can also be used by workers whose job it is to help people whose money is not being used in the right way.Sometimes when people don’t use your money in the right way it is family violence. If people are not using your money in the right way there might be other family violence happening too. Using these questions might help you to think about whether somebody is not using your money in the right way. There are people who think that not using your money in the right way is OK. It is not OK and you should know that there are things to do and people who can help to stop it from happening.The research team would like to thank the women who participated in the focus groups and final consultation as well as those who shared their stories with us for the original ANROWS-funded research upon which this project is based. We would also like to extend our thanks to the numerous stakeholders and experts who contributed so generously during the focus groups and afterwards.We thank the Victorian Women’s Benevolent Trust for funding this project as part of their small grants program in 2018-2019. We would also like to acknowledge the ANROWS funding for Women Disability and Violence: Creating Access to Justice that began this work and we would like to thank members of the research team with whom we worked on this project, Dr Claire Spivakovsky and Professor Jude McCulloch from Monash University, Kara Beavis from Oueensland University of Technology, and Dr Jessica Cadwallader, Meredith Lea and Therese Sands from People with Disability Australia.
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  • IntroductionIn September 2015, Cricket Victoria recognised the Melbourne All Abilities Cricket Association (MAACA) as their 77th association. Cricket Victoria and MACCA are now providing opportunities for people with an intellectual disability to play in a regular, structured and organised cricket competition, moving from sampling to sustainability. In March 2019, Cricket Victoria commissioned researchers from Monash University’s Faculty of Education to undertake an evaluation of the work of MAACA. The evaluation responded to three key research questions: 1. What are the experiences of people with disabilities and their families of participating in MAACA? 2. How have clubs facilitated these experiences? and 3. How do they anticipated the Association will develop in the future? Evaluation Approach The evaluation adopted a mixed method approach, utilising telephone interviews with MAACA administrators and club volunteers, surveys with players and face-to-face interviews or focus groups with players and their families. In total, the research team undertook 11 telephone interviews with club based volunteers and conducted interviews or focus groups with 15 players three of which identified as women. Five parents also took part in the focus groups. 32 players responded to the survey across 6 clubs with an estimated response rate of 26%.
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  • Our two page briefs are designed to provide a snapshot of key terms and definitions, legislation, services and research towards preventing family violence. The briefs are provided in PDF format. To access this information in additional accessible formats, please email monashgfv@gmail.com Access more of our research briefs on our website at: https://arts.monash.edu/gender-and-family-violence/research-briefs
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  • Childhood symptoms of trauma are consistent with symptoms of high-functioning autism spectrum disorder (ASD). However, while researchers are working towards diagnostic accuracy between ASD and posttraumatic stress disorder (PTSD), equally research is needed exploring shared intervention practices between ASD and PTSD. This article aims to provide a combined framework for understanding and applying trauma-informed principles and interventions for children with ASD, PTSD, and related challenges within the school setting. The proposed framework includes six pillars of emotion awareness and regulation, relationships and communication, collaboration and choice, presentation and triggers, behaviour regulation, and learning challenges. The integrated approach is hypothesised to improve teacher awareness and school practices in response to children exposed to trauma and those with neurodevelopmental disability.
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