Role of intratumoural heterogeneity in cancer drug resistance : molecular and clinical perspectives

Drug resistance continues to be a major barrier to the delivery of curative therapies in cancer. Historically, drug resistance has been associated with over-expression of drug transporters, changes in drug kinetics or amplification of drug targets. However, the emergence of resistance in patients treated with new-targeted therapies has provided new insight into the complexities underlying cancer drug resistance. Recent data now implicate intratumoural heterogeneity as a major driver of drug resistance. Single cell sequencing studies that identified multiple genetically distinct variants within human tumours clearly demonstrate the heterogeneous nature of human tumours. The major contributors to intratumoural heterogeneity are (i) genetic variation, (ii) stochastic processes, (iii) the microenvironment and (iv) cell and tissue plasticity. Each of these factors impacts on drug sensitivity. To deliver curative therapies to patients, modification of current therapeutic strategies to include methods that estimate intratumoural heterogeneity and plasticity will be essential.

Evaluations of BIM : frameworks and perspectives

This paper examines the evaluation of BIM-enabled projects. It provides a critical review of the three main areas of measurement, namely technology, organization/people and process. Using two documented case studies of BIM implementation, the paper illustrates the benefits realized by project owners and contractors, and illustrates a lack of attention relative to contextual factors affecting the adoption and deployment of BIM. The paper has three main contributions. First, it identifies and discusses the lack of and difficulty surrounding standardized assessment methods for evaluating BIM-enabled projects. Second, it proposes a conceptual model that includes contextual attributes and demonstrates how the proposed framework reaches beyond simple evaluation to encompass the documentation of BIM’s benefits, lessons learned, challenges and adopted solutions. Third, it shows how the framework can account for existing business processes, organizational process assets, and enterprise level factors. The paper aims to provide a conceptual basis for evaluation and a starting point for benchmarking.

miR-126 in human cancers : clinical roles and current perspectives

miR-126 has been implicated in the processes of inflammation and angiogenesis. Through these processes, miR-126 is implicated in cancer biology, but its role there has not been well reviewed. The aim of this review is to examine the molecular mechanisms and clinicopathological significance of miR-126 in human cancers. miR-126 was shown to have roles in cancers of the gastrointestinal tract, genital tracts, breast, thyroid, lung and some other cancers. Its expression was suppressed in most of the cancers studied. The molecular mechanisms that are known to cause aberrant expression of miR-126 include alterations in gene sequence, epigenetic modification and alteration of dicer abundance. miR-126 can inhibit progression of some cancers via negative control of proliferation, migration, invasion, and cell survival. In some instances, however, miR-126 supports cancer progression via promotion of blood vessel formation. Downregulation of miR-126 induces cancer cell proliferation, migration, and invasion via targeting specific oncogenes. Also, reduced levels of miR-126 are a significant predictor of poor survival of patients in many cancers. In addition, miR-126 can alter a multitude of cellular mechanisms in cancer pathogenesis via suppressing gene translation of numerous validated targets such as PI3K, KRAS, EGFL7, CRK, ADAM9, HOXA9, IRS-1, SOX-2, SLC7A5 and VEGF. To conclude, miR-126 is commonly down-regulated in cancer, most likely due to its ability to inhibit cancer cell growth, adhesion, migration, and invasion through suppressing a range of important gene targets. Understanding these mechanisms by which miR-126 is involved with cancer pathogenesis will be useful in the development of therapeutic targets for the management of patients with cancer.

The Politics of Urban Cultural Policy : Global Perspectives

The Politics of Urban Cultural Policy brings together a range of international experts to critically analyze the ways that governmental actors and non-governmental entities attempt to influence the production and implementation of urban policies directed at the arts, culture, and creative activity. Presenting a global set of case studies that span five continents and 22 cities, the essays in this book advance our understanding of how the dynamic interplay between economic and political context, institutional arrangements, and social networks affect urban cultural policy-making and the ways that these policies impact urban development and influence urban governance. The volume comparatively studies urban cultural policy-making in a diverse set of contexts, analyzes the positive and negative outcomes of policy for different constituencies, and identifies the most effective policy directions, emerging political challenges, and most promising opportunities for building effective cultural policy coalitions. The volume provides a comprehensive and in-depth engagement with the political process of urban cultural policy and urban development studies around the world. It will be of interest to students and researchers interested in urban planning, urban studies and cultural studies.

Signet-ring cell carcinoma of colorectum : current perspectives and molecular biology

PURPOSE Colorectal signet-ring cell carcinoma (SRCC) is rare, and very little detailed information on the molecular biology of the disease is available. METHODS The literature on the clinical, pathological and, in particular, the molecular biology of this rare entity was critically reviewed. The reviewed articles take into account a total of 1,817 cases of SRCC, but only 143 cases have molecular data available. The characteristics of two patients with colorectal SRCC were also discussed. RESULTS Colorectal SRCC mostly occurs in younger patients, is larger and has different site predilection compared with conventional colorectal adenocarcinoma. It can occur as one of the synchronous cancers in the colorectum. The cancer is usually diagnosed at advanced stages because of the late manifestation of symptoms, and aggressive treatment strategy is required. Limited reports in the literature have shown that the variant of colorectal cancer demonstrated a different pattern of genetic alterations of common growth kinase-related oncogenes (K-ras, BRAF), tumour suppressor genes (p53, p16), gene methylation and cell adhesion-related genes related to the Wingless signalling pathway (E-cadherin and beta-catenin) from conventional colorectal adenocarcinoma. Colorectal SRCC also showed high expression of mucin-related genes and genes related to the gastrointestinal system. There was also a higher prevalence of microsatellite instability-high tumours and low Cox-2 expression in colorectal SRCC as opposed to conventional adenocarcinoma. CONCLUSIONS Colorectal SRCC has unique molecular pathological features. The unique molecular profiles in SRCC may provide molecular-based improvements to patient management in colorectal SRCC.

Research in Early Childhood Education for Sustainability : International Perspectives and Provocations

Sustainability is a global issue that urgently needs addressing, the most serious consequences of which concern children and future generations. This insightful research text tackles one of the most significant contemporary issues of our times – the nexus between society and environment – and how early childhood education can contribute to sustainable living. By offering international and multidisciplinary research perspectives on Early Childhood Education for Sustainability, each chapter explores and investigates the complex topic of sustainability and its relationship to early childhood education. A particular emphasis that runs through this text is young children as empowered citizens, capable of both contributing to and creating change for sustainability. The chapter authors work from, or are aligned with, a transformative education paradigm that suggests the socio-constructivist frameworks currently underpinning Early Childhood Education require reframing in light of the social transformations necessary to address humanity’s unsustainable, unjust and unhealthy living patterns. This research text is designed to be provocative and challenging; in so doing it seeks to encourage exploration of current understandings about Early Childhood Education for Sustainability, offers new dimensions for more deeply informed practice, and proposes avenues for further research in this field.

Information Experience : New Perspectives and Research Directions

In this closing chapter the editors review key themes that have emerged through the book. We recognize the varied and dynamic nature of information experience across multiple contexts, and present our own conceptualization of information experience. Finally, we consider possible future directions for information experience research.

Information Experience : Contemporary Perspectives

The purpose of this book is to open a conversation on the idea of information experience, which we understand to be a complex, multidimensional engagement with information. In developing the book we invited colleagues to propose a chapter on any aspect of information experience, for example conceptual, methodological or empirical. We invited them to express their interpretation of information experience, to contribute to the development of this concept. The book has thus become a vehicle for interested researchers and practitioners to explore their thinking around information experience, including relationships between information experience, learning experience, user experience and similar constructs. It represents a collective awareness of information experience in contemporary research and practice. Through this sharing of multiple perspectives, our insights into possible ways of interpreting information experience, and its relationship to other concepts in information research and practice, is enhanced. In this chapter, we introduce the idea of information experience. We also outline the book and its chapters, and bring together some emerging alternative views and approaches to this important idea.

What works and why? Early childhood professionals' perspectives on effective early childhood education and care services for Indigenous families

Investment in early childhood education and care (ECEC) programs is a cornerstone policy of the Australian Government directed toward increasing the educational opportunities and life chances made available to Australian Aboriginal and Torres Strait Islander (Indigenous) children. Yet, ECEC programs are not always effective in supporting sustained attendance of Indigenous families. A site-case analysis of Mount Isa, Queensland was conducted to identify program features that engage and support attendance of Indigenous families. This first study, reports the perspectives of early childhood professionals from across the entire range of group-based licensed (kindergarten and long day care) and non-licensed (playgroups, parent-child education) programs (n=19). Early childhood professionals reported that Indigenous families preferred non-licensed over licensed programs. Reasons suggested for this choice were that non-licensed services provided integration with family supports, were responsive to family circumstance and had a stronger focus on relationship building. Implications for policy and service provision are discussed.

Current trends and challenges for sport and exercise psychology – What now for our discipline?

With an ever changing landscape including National Registration, endorsed areas of practice, establishment of Sport and Exercise Psychology coordinators within National Sporting Organisations, changes to the National and State Sporting Insitutions, this forum looks to explore through collegiate discussion the impacts, current and future implications for our profession across training, supervision, research and applied practice in Australia.

Women IN Sport or Women OR Sport - The search for work/sport/life balance.

The current ‘holy grail’ for our health and well-being centres around the search for, and establishment of, a work/life balance. For many individuals, this appears to be an ever-elusive goal – forever slipping from our grasp as we juggle the day-to-day battle for our attention and time from an array of sources. When we add the word ‘Women’ to this mix, often the number of sources related to these demands multiplies in alignment with the number of roles we fill. To take this to even another level, consider the addition of the words ‘Sport’ or ‘Elite Athlete’ to ‘Women’ and ‘Work/Life Balance’, and the search for the ‘holy grail’ becomes more literal! Many sportswomen at the elite level face significant challenges in balancing working to support themselves and/or their families, studying to lay the foundations of a post-sport career, (often) spending the equivalent of full-time hours training towards their sporting goals, and additionally investing in the things that are important for them outside of these two areas – the ‘Life’ component. Getting the work/life balance ‘balanced’ has been suggested to be a key component of investing in our health and well-being. The same is applicable to sportswomen, with the added suggestion that if the balance between work/sport/life is achieved, this can positively impact upon sporting performance itself. These ideas and observations will be explored via experience within the Australian elite sporting environment from a psychologist’s perspective, with questions and invitations for further discussion.

The contribution of sport and performance psychology to coaching

The role of the sport and performance psychologists offers an historical base to many of the conceptualizations, strategies and tools currently utilized by coaches and coaching psychologists. The world of elite sport and performance offers little room for negativity, little tolerance for cognitions, emotions and behaviours that are less than optimal; in an environment that sets high expectation, makes obvious comparisons and is driven by competition; all within inflexible timelines and with harsh consequences for those that don’t make the grade. From this context the presenters will reflect on their development, challenges and expertise; offering ideas and tools that translate into the coaching arena.

The dynamics of expertise acquisition in sport : the role of affective learning design

Objectives The aim of this position paper is to discuss the role of affect in designing learning experiences to enhance expertise acquisition in sport. The design of learning environments and athlete development programmes are predicated on the successful sampling and simulation of competitive performance conditions during practice. This premise is captured by the concept of representative learning design, founded on an ecological dynamics approach to developing skill in sport, and based on the individual-environment relationship. In this paper we discuss how the effective development of expertise in sport could be enhanced by the consideration of affective constraints in the representative design of learning experiences. Conclusions Based on previous theoretical modelling and practical examples we delineate two key principles of Affective Learning Design: (i) the design of emotion-laden learning experiences that effectively simulate the constraints of performance environments in sport; (ii) recognising individualised emotional and coordination tendencies that are associated with different periods of learning. Considering the role of affect in learning environments has clear implications for how sport psychologists, athletes and coaches might collaborate to enhance the acquisition of expertise in sport.

Perspectives about exercise from adults with venous leg ulcers : an exploratory study

Objective Exercise has the potential to offer a range of health benefits in addition to improving healing outcomes for people with venous leg ulcers. However despite evidence based recommendations, most of these individuals do not engage in regular exercise. The aim of this study was to gain an understanding of the perspectives of adults with venous leg ulcers, in relation to exercise. Method This was a qualitative design using semi-structured interviews and discussions. Ten participants with venous leg ulceration volunteered to participate. Recruitment was through a specialist wound clinic. Verbatim data were collected by an experienced moderator using a semi-structured guide. Data saturation was reached after three group discussions and two interviews. A random selection of transcripts was sent back to the participants for verification. Thematic content analysis was used to determine major themes and categories. Two transcripts were independently analysed, categories and themes independently developed, cross checked and found comparable. Remaining transcripts were analysed using developed categories and codes. Results Regardless of their current exercise routine, participants reported exercising prior to venous leg ulceration and expressed an interest in either becoming active or maintaining an active lifestyle. Overall four themes emerged from the findings: i) participant understanding of the relationship between chronic venous insufficiency and exercise patterns, ii) fear of harm impacts upon positive beliefs and attitudes to exercise, iii) perceived factors limit exercise and iv) structured management facilitates exercise. Conclusion The value of exercise in improving outcomes in venous leg ulcers lies in its capacity to promote venous return and reduce the risk of secondary conditions in this population. Despite motivation and interest in being exercise active, people with venous leg ulcers report many obstacles. Further exploration of mechanisms that assist this patient population and promote understanding about management of barriers, coupled with promotion of enabling factors is vital for improving their exercise participation.

Demand Response for Residential Appliances in a Smart Electricity Distribution Network: Utility and Customer Perspectives

This thesis introduces advanced Demand Response algorithms for residential appliances to provide benefits for both utility and customers. The algorithms are engaged in scheduling appliances appropriately in a critical peak day to alleviate network peak, adverse voltage conditions and wholesale price spikes also reducing the cost of residential energy consumption. Initially, a demand response technique via customer reward is proposed, where the utility controls appliances to achieve network improvement. Then, an improved real-time pricing scheme is introduced and customers are supported by energy management schedulers to actively participate in it. Finally, the demand response algorithm is improved to provide frequency regulation services.