Targeting amino acid transport in metastatic castration-resistant prostate cancer : effects on cell cycle, cell growth, and tumor development

Background L-type amino acid transporters (LATs) uptake neutral amino acids including L-leucine into cells, stimulating mammalian target of rapamycin complex 1 signaling and protein synthesis. LAT1 and LAT3 are overexpressed at different stages of prostate cancer, and they are responsible for increasing nutrients and stimulating cell growth. Methods We examined LAT3 protein expression in human prostate cancer tissue microarrays. LAT function was inhibited using a leucine analog (BCH) in androgen-dependent and -independent environments, with gene expression analyzed by microarray. A PC-3 xenograft mouse model was used to study the effects of inhibiting LAT1 and LAT3 expression. Results were analyzed with the Mann-Whitney U or Fisher exact tests. All statistical tests were two-sided. Results LAT3 protein was expressed at all stages of prostate cancer, with a statistically significant decrease in expression after 4–7 months of neoadjuvant hormone therapy (4–7 month mean = 1.571; 95% confidence interval = 1.155 to 1.987 vs 0 month = 2.098; 95% confidence interval = 1.962 to 2.235; P = .0187). Inhibition of LAT function led to activating transcription factor 4–mediated upregulation of amino acid transporters including ASCT1, ASCT2, and 4F2hc, all of which were also regulated via the androgen receptor. LAT inhibition suppressed M-phase cell cycle genes regulated by E2F family transcription factors including critical castration-resistant prostate cancer regulatory genes UBE2C, CDC20, and CDK1. In silico analysis of BCH-downregulated genes showed that 90.9% are statistically significantly upregulated in metastatic castration-resistant prostate cancer. Finally, LAT1 or LAT3 knockdown in xenografts inhibited tumor growth, cell cycle progression, and spontaneous metastasis in vivo. Conclusion Inhibition of LAT transporters may provide a novel therapeutic target in metastatic castration-resistant prostate cancer, via suppression of mammalian target of rapamycin complex 1 activity and M-phase cell cycle genes.

The development of shared understandings of assessment policy : travelling between global and local contexts

In this paper, teachers’ enactment of assessment policy within demands for accountability and consistency of teacher judgements is considered. Evidence is drawn from a qualitative study involving 50 middle school teachers from Queensland, Australia, who participated in online social moderation meetings with teachers located in dispersed areas around the state. The study presents how travelling policy is embedded in local histories and cultures, in particular within systems of accountability; and the different layers of what may be considered ‘local’. The paper examines the intersections of travelling and embedded policy, and global and local contexts as these are enacted through online moderation meetings.

Social media, data analytics and videogames development : Halfbrick case study

Social media platforms are of interest to interactive entertainment companies for a number of reasons. They can operate as a platform for deploying games, as a tool for communicating with customers and potential customers, and can provide analytics on how players utilize the; game providing immediate feedback on design decisions and changes. However, as ongoing research with Australian developer Halfbrick, creators of $2 , demonstrates, the use of these platforms is not universally seen as a positive. The incorporation of Big Data into already innovative development practices has the potential to cause tension between designers, whilst the platform also challenges the traditional business model, relying on micro-transactions rather than an up-front payment and a substantial shift in design philosophy to take advantage of the social aspects of platforms such as Facebook.

Career Development in Childhood and Adolescence

"In the past few years, many career theorists have noted the dearth of literature in the area of career development in childhood and adolescence. A growing need for integrating theory and research on the early stages of vocational development within a systemic, life-span developmental approach has been articulated. This volume, the first book dedicated to career development of children and adolescents, provides a broad and comprehensive overview of the current knowledge about the key career processes that take place in this age group. Each of the eighteen chapters represents an in-depth examination of a specific aspect of career development with a focus on integrating modern career theory and ongoing research and further developing theory-practice connections in understanding child and adolescent career behaviour. Twenty-six authors, leading experts from eight countries, provide a state-of-the-art summary of the current thinking in the field and outline directions for future empirical work and practice."--publisher website

Improving PLDA speaker verification with limited development data

This paper analyses the probabilistic linear discriminant analysis (PLDA) speaker verification approach with limited development data. This paper investigates the use of the median as the central tendency of a speaker’s i-vector representation, and the effectiveness of weighted discriminative techniques on the performance of state-of-the-art length-normalised Gaussian PLDA (GPLDA) speaker verification systems. The analysis within shows that the median (using a median fisher discriminator (MFD)) provides a better representation of a speaker when the number of representative i-vectors available during development is reduced, and that further, usage of the pair-wise weighting approach in weighted LDA and weighted MFD provides further improvement in limited development conditions. Best performance is obtained using a weighted MFD approach, which shows over 10% improvement in EER over the baseline GPLDA system on mismatched and interview-interview conditions.

Development of hospital disaster resilience : conceptual framework and potential measurement

Objective Despite ‘hospital resilience’ gaining prominence in recent years, it remains poorly defined. This article aims to define hospital resilience, build a preliminary conceptual framework and highlight possible approaches to measurement. Methods Searches were conducted of the commonly used health databases to identify relevant literature and reports. Search terms included ‘resilience and framework or model’ or ‘evaluation or assess or measure and hospital and disaster or emergency or mass casualty and resilience or capacity or preparedness or response or safety’. Articles were retrieved that focussed on disaster resilience frameworks and the evaluation of various hospital capacities. Result A total of 1480 potentially eligible publications were retrieved initially but the final analysis was conducted on 47 articles, which appeared to contribute to the study objectives. Four disaster resilience frameworks and 11 evaluation instruments of hospital disaster capacity were included. Discussion and conclusion Hospital resilience is a comprehensive concept derived from existing disaster resilience frameworks. It has four key domains: hospital safety; disaster preparedness and resources; continuity of essential medical services; recovery and adaptation. These domains were categorised according to four criteria, namely, robustness, redundancy, resourcefulness and rapidity. A conceptual understanding of hospital resilience is essential for an intellectual basis for an integrated approach to system development. This article (1) defines hospital resilience; (2) constructs conceptual framework (including key domains); (3) proposes comprehensive measures for possible inclusion in an evaluation instrument, and; (4) develops a matrix of critical issues to enhance hospital resilience to cope with future disasters.

Consumer perceptions of trade show effectiveness : scale development and validation within a B2C context

Purpose This paper develops and estimates a model to measure consumer perceptions of trade show effectiveness. Design/methodology/approach Data were collected at three separate B2C trade shows. Study 1 (n=47) involved field interviews with data subjected to qualitative item generation and content analysis. Study 2 data (n=147) were subjected to exploratory factor analysis and item-total correlation to identify a preliminary factor structure for the effectiveness construct and to test for reliability. In Study 3 (n=592), confirmatory factor analysis was undertaken to more rigorously test the factor structure and generalise across industries. Validity testing was also performed. Findings A three-dimensional factor structure for assessing consumer visitors’ perceptions of trade show effectiveness was produced incorporating research, operational, and entertainment components. Research limitations/implications Data were collected in Australia and results may not generalise across cultural boundaries. Practical implications The resulting measurement model may be used as a reliable post-hoc diagnostic tool to identify areas of trade show effectiveness where specific performance improvements are needed. Results indicate that exhibitors and organisers of B2C trade shows should consider effectiveness as a multidimensional phenomenon with entertainment, product / industry research, and the facilitation of purchase decision-making processes and problem resolution being key objectives for consumer attendees. These elements of effectiveness should each be addressed by exhibitors and organisers in planning their displays and events. Originality/value This is the first study to provide an empirically valid model for assessing trade show effectiveness from the consumer visitor’s perspective.

Improving dental and medical students’ psychological health using a self-development coaching program : a pilot study

Introduction: Dental and medical students worldwide, including in Saudi Arabia, have been reported to have a high incidence of poor psychological health, such as depression, stress, anxiety, and lowlife satisfaction. Self-development coaching programs have become an increasingly popular way to improve individuals’ lives. However, few studies have evaluated the psychological effects of such programs among dental and medical students. Moreover, no studies have been conducted on self-development coaching programs in Saudi Arabia. Aims: The aim of this study was to assess the feasibility of a larger study via a pilot study and to acquire preliminary findings about the effectiveness of a self-development coaching program on psychological health among dental and medical students in Saudi Arabia. Methods: A pre-post interventional study design was used to test a self-development coaching program (How to be an Ultra-Super Student) with a sample of medical students (n=17) at Umm Al-Qura University at Saudi Arabia. The outcome measures were students’ psychological distress (depression, anxiety, and stress), life satisfaction, self-efficacy, the coach, and coaching program characteristics. Results: The study showed that there was a significant improvement in depression (p=0.04), self-efficacy (p=0.02), and satisfaction with life (p=0.04), which supported the feasibility of a large study in the future. Conclusions: The study’s findings encourage the implementation of a randomized, controlled trial study with a larger sample to further test the effectiveness of using self-development coaching programs with medical and dental students in Saudi Arabia to improve their psychological health.

The development of a carrying capacity assessment model for the Australian socio-environmental context

A key aim of this research was to highlight how society's understanding of constraints to the productive capacity of its resource base is vital to its long-term survival. This was achieved through the development of an online model, the Carrying Capacity Dashboard. The Dashboard was developed to estimate how much land Australian populations require for the production of their food, textiles, timber and liquid fuel. Findings reveal that Australia's estimated carrying capacity is currently over 40 million people but longer-term and more regional analyses suggest a much smaller number. Carrying capacity assessment also indicates that optimal resource security is to be found in balancing both small and large-scale self-sufficiency.

The Gothenburg Recommendations on Education for Sustainable Development

This document calls on governments, civil society and in particular educators to prioritize processes that develop and strengthen education for sustainable development (ESD). The world has changed since the UN World Summit on Sustainable Development in 2002. While there have been significant initiatives and progress has been made, the scale of effort is still overshadowed by the scope of the problem. For instance, human-induced climate change is creating a long-lasting ecological crisis with severe economic and social consequences. Recently the global economic crisis has drawn attention to the problem of borrowing from resources that do not exist. Poverty, conflict and social injustice remain critical issues on the global agenda. A renewed sense of commitment to the UN Decade of Education for Sustainable Development 2005-2014 is required. Formal, informal and non-formal education and learning processes for sustainability must be strengthened and prioritized. This document supports and builds on the concepts and values that are put forward within UNESCO’s International Implementation Scheme for Education for Sustainable Development and in the Earth Charter. The purpose of ESD is to reorient education in order to contribute to a sustainable future for the common good of present and future generations. ESD recognizes the interdependence of environmental, social and economic perspectives and the dependence of humanity on a healthy biosphere. Participation and involvement are necessary components of ESD, with an emphasis on empowerment and agency for active citizenship, human rights and societal change. Re-orientation is necessary at all levels and in all phases of education, and encompasses community learning, thus making ESD a wider process challenging the form and purpose of education itself.

Australian pharmacists' understanding of their continuing professional development obligations

Background The adoption of continuing professional development (CPD) in Australia is still relatively new [expand]. There is limited information on how Australian pharmacists have engaged with the CPD requirements for registration. Aim To explore Australian registered pharmacists’ understanding and engagement with the requirement for CPD credits for registration. Method The Pharmacy Board of Australia’s CPD requirements for registration was used as a guide to design an online survey to ascertain Australian pharmacists understanding and engagement in the acquisition of CPD credits for registration. Results A total of 278 pharmacists responded to the survey – 66% were female and 30% were male (4% did not disclose their gender). 63% of respondents felt that it would not be difficult to acquire 40 CPD credits annually; with pharmacists identifying that Group 1 activities were a preferred way of acquiring CPD credits. The majority of pharmacists (91%) believed that they knew what the current CPD requirements for general registration are and 77% felt that there has been enough guidance provided to assist them. Despite this, 26% of participants had never used self directed learning plans and 38% did not know how to undertake self-directed learning. 76% of participants were under the common misconception that CPD is synonymous with continuing education. Conclusion The majority of registered pharmacists believe they understand and can engage in the acquisition of CPD credits for registration. However, some aspects of the process was not understood. The key link of how this process aims to develop individual practice needs to be further developed within the profession.

The construction of parents as learners about pre-school children’s development

The concept of the lifelong learner—the idea that people should be active learners throughout the lifespan—has since the 1990s gained importance in public policy. Governments in relatively wealthy countries have made the argument that the economic future of nations is tied to the ongoing participation of citizens in learning opportunities that will assist them to participate fully in society and increase their chances of employment in changing workforce conditions. More recently, policy attention has focused on the other end of the lifespan, the first years of life. With the early years now recognised as crucial for later educational success, policy attention has also focused on the importance of parenting in the early years. In the UK and Australia, for example, the effects of state interventions to facilitate ‘good parenting’ and pre-school children’s ‘readiness’ for formal schooling have been felt in a range of settings including community health services, the home and the pre-school (Gillies, 2005; Nichols & Jurvansuu, 2008; Millei & Lee, 2007; Vincent, Ball & Braun, 2010). In Australia, government policy has explicitly proposed a model of parenting as a learning process, and has urged people to cultivate their identities as learners in order to carry out their responsibilities as parents. In part the policy objectives have been to support parents to ensure that all children get a healthy and successful start to life...

Sustainable creative career development pathways for young people in Tanzania : a case study

Tanzania has a rich and diverse cultural history based in community cultural life. However, at present, young people have limited opportunity to exploit this richness of traditional knowledge and engage in creative jobs as their means of future sustainable employment. Hence, the significant challenge remains: how to integrate and enhance the traditional knowledge in a learning strategy, while there is no “inter-ministerial action and institutional mechanisms” (United Nations 2008, 33-35) to promote creative employment for young people. This article reports on a case study that examined how the two Ministries of Culture and Education might work together to support Tanzania’s young people to secure, and engage successfully in creative jobs. The case study employed mixed methods, incorporating questionnaires, interviews and focus groups. The study was undertaken in Dar-Es-Salaam, Mwanza, Bagamoyo, Dodoma, Lindi and Morogoro from July to October, 2012. This paper discusses some of the issues and argues that there is no practical utilization of traditional knowledge and skills in “putting education to work” (UNESCO 2012, 170) for the better prospects of young people and to reveal the story of their lives. Although this study is specific to Tanzania, the case may also apply to other developing countries.