Cinema : an invention without a future? The career prospects for first-time feature film directors in the Australian Film Industry

University of Technology Sydney. Faculty of Arts and Social Sciences.The initiative for this research project first emerged from a set of statistics, which appeared on the Screen Australia website in 2011 with no accompanying explanation. Over a thirty-year timeframe, the figures showed that almost 66% of feature film directors make only one feature film. The question of how feature film directors build a sustainable career within this sector formed the foundation of this study. This research project involved a series of qualitative case studies, which focused on trying to reach an understanding of what constitutes the ‘essentials’ of a director’s career. An online survey was used to capture and measure some quantifiable data: Gender; educational level and duration; type of education; preference for course content; and professional experience were some of the targeted data categories. Drawing on concepts from critical theory, political economy, education, and filmmaking disciplines the study examines the way that workers make a career in a precarious and uncertain industry. The results show that prospective feature film directors start out with a high degree of optimism and are adept at positioning themselves through a range of strategies which ensures that they can make a living by utilising their knowledge of the ways in which the entire film and television sector operates. The study concludes that the primary barrier to an individual career and an extensive body of work seems to be due chiefly to the restrictions imposed on production levels by government policy settings and general economic volatility

Right care, right time, right place: improving outcomes for people with spinal cord injury through early access to intervention and improved access to specialised care: study protocol

Background: Traumatic spinal cord injury is a devastating condition impacting adversely on the health and wellbeing, functioning and independence, social participation and quality of life of the injured person. In Australia, there are approximately 15 new cases per million population per year; economic burden estimates suggest 2 billion dollars annually. For optimal patient outcomes expert consensus recommends expeditious transfer (“24 hours) in a Spinal Cord Injury Unit. Examining current health service and clinical intervention pathways in this Australian population-based sample, in relation to their outcomes, will provide an understanding of factors associated with patient flow, resource utilisation and cost, and patient and family quality of life. Barriers to streamlined effective early-care pathways and facilitators of optimal treatment for these patients will be identified

Entrepreneurial search dynamics: reflection paper

The intended objectives of Smartspec Work Package 1 are firstly to identify related variety and value chain components within EU regions to inform specialisation choices and secondly, to identify the role of organisations and their interaction for the development of entrepreneurial discovery and to assess the role of network connectivity in facilitating intra- and extra-regional asset combination. In order to examine the various questions regarding the network and institutional factors enhancing or mitigating entrepreneurial search processes, in this work package we employ a twin-track multimethodology approach comprised of two parallel streams of enquiry, one of which is primarily empirical and quantitative in nature, and one of which is rather more conceptual and qualitative in nature. Each of these parallel streams of work is designed to progress and develop alongside the other, with various junctures built into the programme for mutual reflection and cross-fertilisation of ideas

Middle Preclassic Period Maya Greenstone Triangulates : Forms, Contexts, and Geology of a Unique Mesoamerican Groundstone Artifact Type

Over the past twenty years our understanding of the Middle Preclassic (900–300 BCE) period has become much clearer through archaeological investigations at a number of sites located in the Upper Belize River Valley region of the eastern Maya Lowlands. While the picture of Middle Preclassic Maya life, including their material culture, has sharpened, there are aspects that remain uninvestigated. One artifact type, identified as greenstone triangulates, has been found at several Belize Valley sites and in a variety of contexts. Although a number of these multifaceted, polished groundstone items have been recovered, little research has focused on their distribution and function in the archaeological record. An evaluation of these items from primary contexts provides data for determining how they were used in daily social and/or ritual activities throughout the lowlands. Comparative data from other regions of Mesoamerica are also discussed. A detailed geological and petrographic pilot study of a sample of greenstone triangulates is provided, pointing conclusively to early, long-distance and complex exchange networks in exotic raw materials

Understanding a Low Vitamin D State in the Context of COVID-19

While a low vitamin D state has been associated with an increased risk of infection by SARS-CoV-2 in addition to an increased severity of COVID-19 disease, a causal role is not yet established. Here, we review the evidence relating to i) vitamin D and its role in SARS-CoV-2 infection and COVID-19 disease ii) the vitamin D status in the Irish adult population iii) the use of supplemental vitamin D to treat a deficient status and iv) the application of the Bradford-Hill causation criteria. We conclude that reverse causality probably makes a minimal contribution to the presence of low vitamin D states in the setting of COVID-19. Applying the Bradford-Hill criteria, however, the collective literature supports a causal association between low vitamin D status, SARS-CoV-2 infection, and severe COVID-19 (respiratory failure, requirement for ventilation and mortality). A biologically plausible rationale exists for these findings, given vitamin D’s role in immune regulation. The thresholds which define low, deficient, and replete vitamin D states vary according to the disease studied, underscoring the complexities for determining the goals for supplementation. All are currently unknown in the setting of COVID-19. The design of vitamin D randomised controlled trials is notoriously problematic and these trials commonly fail for a number of behavioural and methodological reasons. In Ireland, as in most other countries, low vitamin D status is common in older adults, adults in institutions, and with obesity, dark skin, low UVB exposure, diabetes and low socio-economic status. Physiological vitamin D levels for optimal immune function are considerably higher than those that can be achieved from food and sunlight exposure alone in Ireland. A window exists in which a significant number of adults could benefit from vitamin D supplementation, not least because of recent data demonstrating an association between vitamin D status and COVID-19. During the COVID pandemic, we believe that supplementation with 20-25ug (800–1000 IU)/day or more may be required for adults with apparently normal immune systems to improve immunity against SARS-CoV-2. We expect that higher monitored doses of 37.5–50 ug (1,500–2,000)/day may be needed for vulnerable groups (e.g., those with obesity, darker skin, diabetes mellitus and older adults). Such doses are within the safe daily intakes cited by international advisory agencies

IL‐4 induces proliferation in prostate cancer PC3 cells under nutrient‐depletion stress through the activation of the JNK‐pathway and survivin up‐regulation

Interleukin (IL)‐4 plays a critical role in the regulation of immune responses and has been detected at high levels in the tumor microenvironment of cancer patients where it correlates with the grade of malignancy. The direct effect of IL‐4 on cancer cells has been associated with increased cell survival; however, its role in cancer cell proliferation and related mechanisms is still unclear. Here it was shown that in a nutrient‐depleted environment, IL‐4 induces proliferation in prostate cancer PC3 cells. In these cells, under nutrient‐depletion stress, IL‐4 activates mitogen‐activated protein kinases (MAPKs), including Erk, p38, and JNK. Using MAP‐signaling‐specific inhibitors, it was shown that IL‐4‐induced proliferation is mediated by JNK activation. In fact, JNK‐inhibitor‐V (JNKi‐V) stunted IL‐4‐mediated cell proliferation. Furthermore, it was found that IL‐4 induces survivin up‐regulation in nutrient‐depleted cancer cells. Using survivin‐short‐hairpin‐RNAs (shRNAs), it was demonstrated that in this milieu survivin expression above a threshold limit is critical to the mechanism of IL‐4‐mediated proliferation. In addition, the significance of survivin up‐regulation in a stressed environment was assessed in prostate cancer mouse xenografts. It was found that survivin knockdown decreases tumor progression in correlation with cancer cell proliferation. Furthermore, under nutrient depletion stress, IL ‐4 could induce proliferation in cancer cells from multiple origins: MDA‐MB‐231 (breast), A253 (head and neck), and SKOV‐3 (ovarian). Overall, these findings suggest that in a tumor microenvironment under stress conditions, IL‐4 triggers a simultaneous activation of the JNK‐pathway and the up‐regulation of survivin turning on a cancer proliferation mechanism. J. Cell. Biochem. 113: 1569–1580, 2012. © 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90542/1/24025_ftp.pd

Entrepreneurial search dynamics: reflection paper

The intended objectives of Smartspec Work Package 1 are firstly to identify related variety and value chain components within EU regions to inform specialisation choices and secondly, to identify the role of organisations and their interaction for the development of entrepreneurial discovery and to assess the role of network connectivity in facilitating intra- and extra-regional asset combination. In order to examine the various questions regarding the network and institutional factors enhancing or mitigating entrepreneurial search processes, in this work package we employ a twin-track multimethodology approach comprised of two parallel streams of enquiry, one of which is primarily empirical and quantitative in nature, and one of which is rather more conceptual and qualitative in nature. Each of these parallel streams of work is designed to progress and develop alongside the other, with various junctures built into the programme for mutual reflection and cross-fertilisation of ideas

Development of a Cx46 Targeting Strategy for Cancer Stem Cells

Gap-junction-mediated cell-cell communication enables tumor cells to synchronize complex processes. We previously found that glioblastoma cancer stem cells (CSCs) express higher levels of the gap junction protein Cx46 compared to non-stem tumor cells (non-CSCs) and that this was necessary and sufficient for CSC maintenance. To understand the mechanism underlying this requirement, we use point mutants to disrupt specific functions of Cx46 and find that Cx46-mediated gap-junction coupling is critical for CSCs. To develop a Cx46 targeting strategy, we screen a clinically relevant small molecule library and identify clofazimine as an inhibitor of Cx46-specific cell-cell communication. Clofazimine attenuates proliferation, self-renewal, and tumor growth and synergizes with temozolomide to induce apoptosis. Although clofazimine does not cross the blood-brain barrier, the combination of clofazimine derivatives optimized for brain penetrance with standard-of-care therapies may target glioblastoma CSCs. Furthermore, these results demonstrate the importance of targeting cell-cell communication as an anti-cancer therapy

Towards a literary account of mental health from James’ Principles of Psychology

YesThe field of mental health tends to treat its literary metaphors as literal realities with the concomitant loss of vague “feelings of tendency” in “unusual experiences”. I develop this argument through the prism of William James’ (1890) “The Principles of Psychology”. In the first part of the paper, I reflect upon the relevance of James’ “The Psychologist’s Fallacy” to a literary account of mental health. In the second part of the paper, I develop the argument that “connotations” and “feelings of tendency” are central to resolving some of the more difficult challenges of this fallacy. I proceed to do this in James’ spirit of generating imaginative metaphors to understand experience. Curiously, however, mental health presents a strange paradox in William James’ (1890) Principles of Psychology. He constructs an elaborate conception of the “empirical self” and “stream of thought” but chooses not to use these to understand unusual experiences – largely relying instead on the concept of a “secondary self.” In this article, I attempt to make more use of James’ central division between the “stream of thought” and the “empirical self” to understand unusual experiences. I suggest that they can be usefully understood using the loose metaphor of a “binary star” where the “secondary self” can be seen as an “accretion disk” around one of the stars. Understood as literary rather the literal, this metaphor is quite different to more unitary models of self-breakdown in mental health, particularly in its separation of “self” from “the stream of thought” and I suggest it has the potential to start a re-imagination of the academic discourse around mental health

Tissue Glucocorticoid Metabolism in Adrenal Insufficiency:A Prospective Study of Dual-release Hydrocortisone Therapy

Background: Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI because of the nonphysiological pattern of current immediate release hydrocortisone (IR-HC) replacement therapy. The use of a once-daily dual-release hydrocortisone (DR-HC) preparation, (Plenadren®), offers a more physiological cortisol profile and may alter corticosteroid metabolism in vivo.Study Design and Methods: Prospective crossover study assessing the impact of 12 weeks of DR-HC on systemic GC metabolism (urinary steroid metabolome profiling), cortisol activation in the liver (cortisone acetate challenge test), and subcutaneous adipose tissue (microdialysis, biopsy for gene expression analysis) in 51 patients with AI (primary and secondary) in comparison to IR-HC treatment and age- and BMI-matched controls.Results: Patients with AI receiving IR-HC had a higher median 24-hour urinary excretion of cortisol compared with healthy controls (72.1 µg/24 hours [IQR 43.6-124.2] vs 51.9 µg/24 hours [35.5-72.3], P = .02), with lower global activity of 11β-HSD2 and higher 5-alpha reductase activity. Following the switch from IR-HC to DR-HC therapy, there was a significant reduction in urinary cortisol and total GC metabolite excretion, which was most significant in the evening. There was an increase in 11β-HSD2 activity. Hepatic 11β-HSD1 activity was not significantly altered after switching to DR-HC, but there was a significant reduction in the expression and activity of 11β-HSD1 in subcutaneous adipose tissue.Conclusion: Using comprehensive in vivo techniques, we have demonstrated abnormalities in corticosteroid metabolism in patients with primary and secondary AI receiving IR-HC. This dysregulation of pre-receptor glucocorticoid metabolism results in enhanced glucocorticoid activation in adipose tissue, which was ameliorated by treatment with DR-HC