The roles of the preproghrelin-derived peptides - ghrelin, desacyl ghrelin and obestatin - in prostate cancer

Prostate cancer is the second most common cause of cancer related deaths in Western men. Despite the significant improvements in current treatment techniques, there is no cure for advanced metastatic, castrate-resistant disease. Early detection and prevention of progression to a castrate-resistant state may provide new strategies to improve survival. A number of growth factors have been shown to act in an autocrine/paracrine manner to modulate prostate cancer tumour growth. Our laboratory has previously shown that ghrelin and its receptors (the functional GHS-R1a and the non-functional GHS-R1b) are expressed in prostate cancer specimens and cell lines. We have shown that ghrelin increases cell proliferation in the PC3 and LNCaP prostate cancer cell lines through activation of ERK1/2, suggesting that ghrelin could regulate prostate cancer cell growth and play a role in the progression of the disease. Ghrelin is a 28 amino-acid peptide hormone, identified to be the natural ligand of the growth hormone secretagogue receptor (GHS-R1a). It is well characterised as a growth hormone releasing and as an orexigenic peptide that stimulates appetite and feeding and regulates energy expenditure and bodyweight. In addition to its orexigenic properties, ghrelin has been shown to play a regulatory role in a number of systems, including the reproductive, immune and cardiovascular systems and may play a role in a number of pathological conditions such as chronic heart failure, anorexia, cachexia, obesity, diabetes and cancer. In cancer, ghrelin and its receptor are expressed in a range of tumours and cancer cell lines and ghrelin has been demonstrated to modulate cell proliferation, apoptosis, migration and invasion in some cell types. The ghrelin gene (GHRL) encodes preproghrelin peptide, which is processed to produce three currently known functional peptides - ghrelin, desacyl ghrelin and obestatin. Prohormone convertases (PCs) have been shown to cleave the preproghrelin peptide into two primary products - the 28 amino acid peptide, ghrelin, and the remaining 117 amino acid C-terminal peptide, C-ghrelin. C-ghrelin can then be further processed to produce the 23 amino acid peptide, obestatin. Ghrelin circulates in two different forms - an octanoylated form (known as ghrelin) and a non-octanoylated form, desacyl ghrelin. The unique post-translational addition of octanoic acid to the serine 3 residue of the propeptide chain to form acylated ghrelin is catalysed by ghrelin O-acyltransferase (GOAT). This modification is necessary for binding of ghrelin to its only known functional receptor, the GHS-R1a. As desacyl ghrelin cannot bind and activate the GHS-R1a, it was initially thought to be an inactive peptide, despite the fact that it circulates at much higher levels than ghrelin. Further research has demonstrated that desacyl ghrelin is biologically active and shares some of the actions of ghrelin, as well as having some opposing and distinct roles. Interestingly, both ghrelin and desacyl ghrelin have been shown to modulate apoptosis, cell differentiation and proliferation in some cell types, and to stimulate cell proliferation through activation of ERK1/2 and PI3K/Akt pathways. The third known peptide product of the ghrelin preprohormone, obestatin, was initially thought to oppose the actions of ghrelin in appetite regulation and food intake and to mediate its effects through the G protein-coupled receptor 39 (GPR39). Subsequent research failed to reproduce the initial findings, however, and the possible anorexigenic effects of obestatin, as well as the identity of its receptor, remain unclear. Obestatin plays some important physiological roles, including roles in improving memory, the inhibition of thirst and anxiety, increased secretion of pancreatic juice, and regulation of cell proliferation, survival, apoptosis and differentiation. Preliminary studies have also shown that obestatin stimulates cell proliferation in some cell types through activation of ERK1/2, Akt and PKC pathways. Overall, however, at the commencement of this PhD project, relatively little was known regarding the functions and mechanisms of action of the preproghrelin-derived functional peptides in modulating prostate cancer cell proliferation. The roles of obestatin, and desacyl ghrelin as potential growth factors had not previously been investigated, and the potential expression and regulation of the preproghrelin processing enzymes, GOAT and prohormone convertases was unknown in prostate cancer cell lines. Therefore, the overall objectives of this study were to: 1. investigate the effects of obestatin on cell proliferation and signaling in prostate cancer cell lines 2. compare the effects of desacyl ghrelin and ghrelin on cell proliferation and signaling in prostate cancer cell lines 3. investigate whether prostate cancer cell lines possess the necessary enzymatic machinery to produce ghrelin and desacyl ghrelin and if these peptides can regulate GOAT expression Our laboratory has previously shown that ghrelin stimulates cell proliferation in the PC3 and LNCaP prostate cancer cell line through activation of the ERK1/2 pathway. In this study it has been demonstrated that treatments with either ghrelin, desacyl ghrelin or obestatin over 72 hours significantly increased cell proliferation in the PC3 prostate cancer cell line but had no significant effect in the RWPE-1 transformed normal prostate cell line. Ghrelin (1000nM) stimulated cell proliferation in the PC3 prostate cancer cell line by 31.66 6.68% (p<0.01) with the WST-1 method, and 13.55 5.68% (p<0.05) with the CyQUANT assay. Desacyl ghrelin (1000nM) increased cell proliferation in PC3 cells by 21.73 2.62% (p<0.01) (WST-1), and 15.46 7.05% (p<0.05) (CyQUANT) above untreated control. Obestatin (1000nM) induced a 28.37 7.47% (p<0.01) (WST-1) and 12.14 7.47% (p<0.05) (CyQUANT) significant increase in cell proliferation in the PC3 prostate cancer cell line. Ghrelin and desacyl ghrelin treatments stimulated Akt and ERK phosphorylation across a range of concentrations (p<0.01). Obestatin treatment significantly stimulated Akt, ERK and PKC phosphorylation (p<0.05). Through the use of specific inhibitors, the MAPK inhibitor U0126 and the Akt1/2 kinase inhibitor, it was demonstrated that ghrelin- and obestatin-induced cell proliferation in the PC3 prostate cancer cell line is mediated through activation of ERK1/2 and Akt pathways. Although desacyl ghrelin significantly stimulated Akt and ERK phosphorylation, U0126 failed to prevent desacyl ghrelin-induced cell proliferation suggesting ghrelin and desacyl ghrelin might act through different mechanisms to increase cell proliferation. Ghrelin and desacyl ghrelin have shown a proliferative effect in osteoblasts, pancreatic -cells and cardiomyocytes through activation of ERK1/2 and PI3K/Akt pathways. Here it has been shown that ghrelin and its non-acylated form exert the same function and stimulate cell proliferation in the PC3 prostate cancer cell line through activation of the Akt pathway. Ghrelin-induced proliferation was also mediated through activation of the ERK1/2 pathway, however, desacyl ghrelin seems to stimulate cell proliferation in an ERK1/2-independent manner. As desacyl ghrelin does not bind and activate GHSR1a, the only known functional ghrelin receptor, the finding that both ghrelin and desacyl ghrelin stimulate cell proliferation in the PC3 cell line suggests that these peptides could be acting through the yet unidentified alternative ghrelin receptor in this cell type. Obestatin treatment also stimulated PKC phosphorylation, however, a direct role for this pathway in stimulating cell proliferation could not be proven using available PKC pathway inhibitors, as they caused significant cell death over the extended timeframe of the cell proliferation assays. Obestatin has been shown to stimulate cell proliferation through activation of PKC isoforms in human retinal epithelial cells and in the human gastric cancer cell line KATO-III. We have demonstrated that all of the prostate-derived cell lines examined (PC3, LNCaP, DU145, 22Rv1, RWPE-1 and RWPE-2) expressed GOAT and at least one of the prohormone convertases, which are known to cleave the proghrelin peptide, PC1/3, PC2 and furin, at the mRNA level. These cells, therefore, are likely to possess the necessary machinery to cleave the preproghrelin protein and to produce the mature ghrelin and desacyl ghrelin peptides. In addition to prohormone convertases, the presence of octanoic acid is essential for acylated ghrelin production. In this study octanoic acid supplementation significantly increased cell proliferation in the PC3 prostate cancer cell line by over 20% compared to untreated controls (p<0.01), but surprisingly, not in the DU145, LNCaP or 22Rv1 prostate cancer cell lines or in the RWPE-1 and RWPE-2 prostate-derived cell lines. In addition, we demonstrated that exogenous ghrelin induced a statistically significant two-fold decrease in GOAT mRNA expression in the PC3 cell line (p<0.05), suggesting that ghrelin could pontentially downregulate its own acylation and, therefore, regulate the balance between ghrelin and desacyl ghrelin. This was not observed, however, in the DU145 and LNCaP prostate cancer cell lines. The GOAT-ghrelin system represents a direct link between ingested nutrients and regulation of ghrelin production and the ghrelin/desacyl ghrelin ratio. Regulation of ghrelin acylation is a potentially attractive and desirable tool for the development of better therapies for a number of pathological conditions where ghrelin has been shown to play a key role. The finding that desacyl ghrelin stimulates cell proliferation in the PC3 prostate cancer cell line, and responds to ghrelin in the same way, suggests that this cell line expresses an alternative ghrelin receptor. Although all the cell lines examined expressed both GHS-R1a and GHS-R1b mRNA, it remains uncertain whether these cell lines express the unidentified alternative ghrelin receptor. It is possible that the varied responses seen could be due to the expression of different ghrelin receptors in different cell lines. In addition to GOAT, prohormone convertases and octanoic acid availability may regulate the production of different peptides from the ghrelin preprohormone. The studies presented in this thesis provide significant new information regarding the roles and mechanisms of action of the preproghrelin-derived peptides, ghrelin, desacyl ghrelin and obestatin, in modulating prostate cancer cell line proliferation. A number of key questions remain to be resolved, however, including the identification of the alternative ghrelin/desacyl ghrelin receptor, the identification of the obestatin receptor, a clarification of the signaling mechanisms which mediate cell proliferation in response to obestatin treatment and a better understanding of the regulation at both the gene and post-translational levels of functional peptide generation. Further studies investigating the role of the ghrelin axis using in vivo prostate cancer models may be warranted. Until these issues are determined, the potential for the ghrelin axis, to be recognised as a novel useful target for therapy for cancer or other pathologies will be uncertain.

Cultural safety : cultural considerations

Over the course of your nursing professional education, you will study the developmental tasks and the principles of health promotion across the life span. You will learn to conduct numerous assessments, such as a complete health history, a psycho-social history, a mental health assessment, a nutritional assessment, a pain assessment, a suicide risk assessment and a physical examination of a patient. However, depending on your reactions to the person there may be wide variations in the information you gather in these assessments and in the findings of the physical examination. In the 1980s there was a change in western nurse education that recognised the interaction between culture and health and since then many nursing degrees include cultural considerations in their Bachelor Programs. It is now imperative that you, as a health care provider, come to understand how culture influences health care.

Whe' yu' from?

"Whe' yu' from?" The question was put to me as I wandered, camera in hand, in the old square of Spanish Town, Jamaica's former capital. The local man, lounging in the shade of one of the colonial Georgian buildings that enclose the square, was mildly curious about what he took to be a typical white tourish photgraphing the sights of the decayed historic town. At that time, my home was in Kingston where i lived with my wife and baby son. I was then working in the Jamaican Government Town Planning Department in a job that took me all over the island. Turning to my questioner, I replied, "Kingston". There was a brief pause, and then the man spoke again: "No Man! Whe' yu' really from?" I still have difficulties when asked this question. Where am I from? What does this question mean? Does it refer to where I was born, where I spent my previous life or where I live now? Does it have a broader meaning, an enquiry about my origins in terms of background and previous experience? The following chapters are my attempt to answer these questions for my own satisfaction and, I hope, for the amusement of others who may be interested in the life of an ordinary English boy whose dream to travel and see the world was realized in ways he could not possibly have imagined. Finding an appropriate title for this book was difficult. Thursday's Child, North and South and War and Peace all came to mind but, unfortunately for me, those titles had been appropriated by other writers. Thursdays's Child is quite a popular book title, presumably because people who were born on that day and, in the words of the nursery rhyme, had 'far to go', are especially likely to have travellers' tales to tell or life stories of the rags-to-riches variety. Born on a Thursday, I have travelled a lot and I suppose that I have gone far in life. Coming from a working class family, I 'got on' by 'getting a good education' and a 'good job'. I decided against adding to the list of Thursday's Children. North and South would have reflected my life in Britain, spent in both the North and South of England, and my later years, divided between the Northern and Southern Hemispheres of the globe, as well as in countries commonly referred to as the 'advanced' North and the 'underdeveloped' South. North and South has already been appropriated by Mrs Gaskell, something that did not deter one popular American writer from using the title for a book of his. My memories of World War Two and the years afterwards made War and Peace a possible candidate, but readers expectnig an epic tale of Tolstoyan proportions may have been disappointed. To my knowledge, no other book has the title "Whe' Yu' From?". I am grateful to the Jamaican man whose question lingered in my memory and provided the title of this memoir, written decades later. This book is a word picture. It is, in a sense, a self-portrait, and like all portraits, it captures something of the character, it attempts to tell the truth, but it is not the whole truth. This is because it is not my intention to write my entire life story; rather I wish to tell about some of the things in my experience of life that have seemed important or interesting to me. Unlike a painted portrait, the picture I have created is intended to suggest the passage of time. While, for most of us in Western society, time is linear and unidirectional, like the flight of an arrov or the trajectory of a bullet, memory rearranges things, calling up images of the past in no particular order, making connections that may link events in various patterns, circular, web-like, superimposed. The stream of consciousness is very unlike that of streams we encounter in the physical world. Connections are made in all directions; thoughts hop back and forth in time and space, from topic to topic. My book is a composition drawn from periods, events and thoughts as I remember them. Like life itself, it is made up of patches, some good, some bad, but in my experience, always fascinating. In recording my memories, I have been as accurate as possible. Little of what I have written is about spectacular sights and strange customs. Much of it focuses on my more modest explorations includng observations of everyday things that have attracted my attention. Reading through the chapters, I am struck by my childhood freedom to roam and engage in 'dangerous' activities like climbing trees and playing beside streams, things that many children today are no longer allowed to enjoy. Also noticeable is the survival of traditions and superstitions from the distant past. Obvious too, is my preoccupation with place names, both official ones that appear on maps and sign boards and those used by locals and children, names rarely seen in print. If there is any uniting theme to be found in what I have written, it must be my education in the fields, woods and streets of my English homeland, in the various other countries in which I have lived and travelled, as well as more formally from books and in classrooms. Much of my book is concerned with people and places. Many of the people I mention are among those who have been, and often have remained, important and close to me. Others I remember from only the briefest of encounters, but they remain in my memory because of some specific incident or circumstance that fixed a lasting image in my mind. Some of my closest friends and relatives, however, appear nowhere in these pages or they receive only the slightest mention. This is not because they played an unimportant roles in my life. It is because this book is not the whole story. Among those whe receive little or no mention are some who are especially close to me, with whom I have shared happy and sad times and who have shown me and my family much kindness, giving support when this was needed. Some I have known since childhood and have popped up at various times in my life, often in different parts of the world. Although years may pass without me seeing them, in an important sense they are always with me. These people know who they are. I hope that they know how much I love and appreciate them. When writing my memoir, I consulted a few of the people mentioned in this book, but in the main, I have relied on my own memory, asided by daiary and notebook entries and old correspondence. In the preparation of this manuscript, I benefited greatly from the expert advice and encouragement of Neil Marr of BeWrite Books. My wife Anne, inspiration for this book, also contributed in the valuable role of critic. She has my undying gratitude.

From slum to suburbia : examining a spectrum of planned and unplanned urban morphology in humid sub-tropical regions of the world

The current rapid urban growth throughout the world manifests in various ways and historically cities have grown, similarly, alternately or simultaneously between planned extensions and organic informal settlements (Mumford, 1989). Within cities different urban morphological regions can reveal different contexts of economic growth and/or periods of dramatic social/technological change (Whitehand, 2001, 105). Morpho-typological study of alternate contexts can present alternative models and contribute to the present discourse which questions traditional paradigms of urban planning and design (Todes et al, 2010). In this study a series of cities are examined as a preliminary exploration into the urban morphology of cities in ‘humid subtropical’ climates. From an initial set of twenty, six cities were selected: Sao Paulo, Brazil; Jacksonville, USA; Maputo, Mozambique; Kanpur, India; Hong Kong, China; and Brisbane, Australia. The urban form was analysed from satellite imagery at a constant scale. Urban morphological regions (types) were identified as those demonstrating particular consistant characteristics of form (density, typology and pattern) different to their surroundings when examined at a constant scale. This analysis was correlated against existing data and literature discussing the proliferation of two types of urban development, ‘informal settlement’ (defined here as self-organised communities identifiable but not always synonymous with ‘slums’) and ‘suburbia’ (defined here as master planned communities of generally detached houses prevalent in western society) - the extreme ends of a hypothetical spectrum from ‘planned’ to ‘spontaneous’ urban development. Preliminary results show some cities contain a wide variety of urban form ranging from the highly organic ‘self-organised’ type to the highly planned ‘master planned community’ (in the case of Sao Paulo) while others tend to fall at one end of the planning spectrum or the other (more planned in the cases of Brisbane and Jacksonville; and both highly planned and highly organic in the case of Maputo). Further research will examine the social, economical and political drivers and controls which lead to this diversity or homogeneity of urban form and speculates on the role of self-organisation as a process for the adaptation of urban form.

Unpacking the micro-macro nexus: narratives of suffering and hope among refugees from Burma recently settled in Australia

Narratives of forced migration are open to a variety of interpretations. In mental health, refugee narratives of arduous journeys in the face of systemic macro socio-political forces are often transformed from this context into a medicalized micro context of inner individual worlds. Both the dominant pathogenic lens of trauma studies and the growing salutogenic lens embodied in resilience research, often reflect a western cultural idiom of focusing on the individualized nature of these phenomena. Using qualitative data collected from refugees from Burma now settling in Australia, the article emphasizes the need for a more reflexive and expansive account of both suffering and hope within refugee narratives. It recounts these narratives within a conceptual framework which acknowledges the importance of the connections between the micro individual experience and the macro, socio-political context. This is not only a question of political principle, but also a matter of listening to the voice of those who know most about the relationship between macro forces of human rights violations and their impact on individual, family and community trajectories.

Emergent innovation through the co-evolution of informal and formal media economies

Well-established distinctions between amateur and professional are blurring as the impact of social media, changes in cultural consumption, and crises in copyright industries’ business models are felt across society and economy. I call this the increasingly rapid co-evolution of the formal market and informal household sectors and analyse it through the concept of ‘social network markets’ – individual choices are made on the basis of other’s choices and such networked preferencing is enhanced by the growing ubiquity of social media platforms. This may allow us better to understand sources of disruption and innovation in audiovisual production and distribution in wealthy Western markets which are as significant as those posed by informal practices outside the West. I examine what is happening around the monetization and professionalization of online video (YouTube, for example) and the socialization of professional production strategies (transmedia, for example) as innovation from the margins.

Combination of MEK-ERK inhibitor and hyaluronic acid has a synergistic effect on anti-hypertrophic and pro-chondrogenic activities in osteoarthritis treatment

We hypothesised that a potentially disease-modifying osteoarthritis (OA) drug such as hyaluronic acid (HA) given in combination with anti-inflammatory signalling agents such as mitogen-activated protein kinase kinase–extracellular signal-regulated kinase (MEK-ERK) signalling inhibitor (U0126) could result in additive or synergistic effects on preventing the degeneration of articular cartilage. Chondrocyte differentiation and hypertrophy were evaluated using human OA primary cells treated with either HA or U0126, or the combination of HA + U0126. Cartilage degeneration in menisectomy (MSX) induced rat OA model was investigated by intra-articular delivery of either HA or U0126, or the combination of HA + U0126. Histology, immunostaining, RT-qPCR, Western blotting and zymography were performed to assess the expression of cartilage matrix proteins and hypertrophic markers. Phosphorylated ERK (pERK)1/2-positive chondrocytes were significantly higher in OA samples compared with those in healthy control suggesting the pathological role of that pathway in OA. It was noted that HA + U0126 significantly reduced the levels of pERK, chondrocyte hypertrophic markers (COL10 and RUNX2) and degenerative markers (ADAMTs5 and MMP-13), however, increased the levels of chondrogenic markers (COL2) compared to untreated or the application of HA or U0126 alone. In agreement with the results in vitro, intra-articular delivery of HA + U0126 showed significant therapeutic improvement of cartilage in rat MSX OA model compared with untreated or the application of HA or U0126 alone. Our study suggests that the combination of HA and MEK-ERK inhibition has a synergistic effect on preventing cartilage degeneration.

Corporate social responsibility and the parameters of dialogue with vulnerable others

This article presents a case study of corporate dialogue with vulnerable others. Dialogue with marginalized external groups is increasingly presented in the business literature as the key to making corporate social responsibility possible in particular through corporate learning. Corporate public communications at the same time promote community engagement as a core aspect of corporate social responsibility. This article examines the possibilities for and conditions underpinning corporate dialogue with marginalized stakeholders as occurred around the unexpected and sudden closure in January 2009 of the AU$2.2 billion BHP Billiton Ravensthorpe Nickel mine in rural Western Australia. In doing so we draw on John Roberts’ notion of dialogue with vulnerable others, and apply a discourse analysis approach to data spanning corporate public communications and interviews with residents affected by the decision to close the mine. In presenting this case study we contribute to the as yet limited organizational research concerned directly with marginalized stakeholders and argue that corporate social responsibility discourse and vulnerable other dialogue not only affirms the primacy of business interests but also co-opts vulnerable others in the pursuit of these interests. In conclusion we consider case study implications for critical understandings of corporate dialogue with vulnerable others.

Provincialising Perth? : Satellite television and the Chinese in Perth

Relocated people habitually seek the familiar within their new social milieus as a means of easing their transition into ways strange and alien. However, from networks and food to everyday customs, efforts to hold on to such home comforts are often viewed with a measure of hostile disdain and regarded as preludes to the formation of ethnic enclaves. Through a pilot study on the access of satellite television by mainland Chinese migrants in Perth, Western Australia, this chapter seeks to shed some light on how migrants understand and employ these comforting strategies and how Chinese-Australians are using technology to achieve a sense of sanctuary from the views and habits of Australians while (re)constructing and articulating multiple belongings in their new homes.

Lateral movements in composite high-rise buildings under seismic action

Daring human nature has already led to the construction of high-rise buildings in naturally challenging geological regions and in worse environments of the world. However; literature review divulges that there is a lag in research of certain generic principles and rules for the prediction of lateral movement in multistorey construction. The present competitive trend orders the best possible used of available construction material and resources. Hence; the mixed used of reinforced concrete with structural steel is gaining prevalence day by day. This paper investigates the effects of Seismic load on composite multistorey building provided with core wall and trusses through FEM modelling. The results showed that increased rigidity corresponds to lower period of vibration and hence higher seismic forces. Since Seismic action is a function of mass and response acceleration, therefore; mass increment generate higher earthquake load and thus cause higher impact base shear and overturning movement. Whereas; wind force depends on building exposed, larger the plan dimension greater is the wind impact. Nonetheless; outriggers trusses noticeably contribute, in improving the serviceability of structure subjected to wind and earthquake forces.

Malay Kingship in Kedah : Religion, Trade, and Society

The book probes and examines traditional sources of royal power and control, as well as indigenous socio-political systems in the Malay world. It is focused on the north-western Malaysian Sultanate of Kedah which is acknowledged as the oldest unbroken independent kingship line in the ‘Malay and Islamic world’ with 1,000 years of history. Little scholarly attention has been paid to its pre-modern history, society, religion, system of government and unique geographic situation, potentially controlling both land and sea lines of communication into the remainder of Southeast Asia. It will thus provide the first comprehensive treatment in English, or other languages, on Kedah’s pre-modern and nineteenth century historiography and can provide a foundation for comparative studies of the various Malay states which is presently lacking. The proposed book also sheds much needed light on a range of important topics in Malay history including: Kedah and the northern Melaka Straits history, colonial expansion and rivalry, Southeast Asian history and politics, interregional migration and the influence of the sea peoples or orang laut, traditional Malay socio-political and economic life, Islamic influences and the course of Thai-Malay relations. The book attempts to offer a new understanding, not only of Kedah, but of the political and cultural development of the entire Malay world and of its relationships with the broader forces in both its continental and maritime settings. It argues that Kedah does not seem to follow, and in fact, often seems to contradict what has been commonly been accepted as the “typical model” of the traditional Malay state. Thus it concludes that the ruling dynasty has historically exploited a wide range of unique environmental conditions, local traditions, global spiritual trends and economic forces to preserve and strengthen its political position. The scope and theme of book The Kedah Sultanate is the oldest unbroken independent kingship lines in the “Malay world” with 1,000 years of history, and arguably one of the oldest in the Islamic world. In this study I examine key geopolitical and spiritual attributes of Malay kingship that have traditionally cemented the ruler, the peoples, and the environment. Brief description of the primary audience for the book: There is little written in English or Malay on Kedah’s pre twentieth century history. The available sources only look at certain aspects of Kedah’s history, are outdated or are confined to a specific period often outside the scope of the book. It is therefore anticipated that the readership and market for the book includes: • Scholars of Southeast Asian history, Islam, kingship, trade. • Academics & Historians (including: Asian, Thai history, Islamic, Maritime, Persian, South Asian, Southeast Asian and Colonial) • Libraries • Students, particularly those in Malaysia (especially the states of Kedah, Perlis and Penang), Thailand and Singapore. • Universities • Scholars and students in Political Science & International Relations

The Convergent Media Policy Moment

This paper will consider some of the wider contextual and policy questions arising out of four major public inquiries that took place in Australia over 2011–2012: the Convergence Review, the National Classification Scheme Review, the Independent Media Inquiry (Finkelstein Review) and the National Cultural Policy. This paper considers whether we are now witnessing a ‘convergent media policy moment’ akin to the ‘cultural policy moment’ theorized by Australian cultural researchers in the early 1990s, and the limitations of various approaches to understanding policy – including critiques of neoliberalism – in understanding such shifts. It notes the rise of ‘soft law’ as a means of addressing the challenges of regulatory design in an era of rapid media change, with consideration of two cases: the approach to media influence taken in the Convergence Review, and the concept of ‘deeming’ developed in the National Classification Scheme Review.

A new approach for trip generation estimation for TIA

Transport Impact Assessment (TIA) -Generally a short range transport planning activity -Assess transport impacts of new developments or expansions -Present solutions to mitigate impacts Problems with TIA Process -Private vehicles focus (i.e. Veh Trip Ends) -Proxy variables (e.g. 100sqm GFA) -Trip generation rates (e.g. VTE/proxy) -Little info/guidance on trip chaining effects -Little info/guidance on non-PV modes Requires significant professional judgment

Justifiability of littering : an empirical investigation

This paper investigates the relationship between voluntary participation in environmental organisations and the justifiability of littering behaviour. Previous empirical work regarding determinants of littering and littering behaviour remains scarce, particularly in socio-economic analysis. We address these deficiencies, demonstrating a strong empirical link between environmental participation and reduced public littering in the European Values Survey (EVS) data for 30 Western and Eastern European countries. The results suggest that membership in environmental organisations is related to a stronger commitment to anti-littering behaviour, thereby supporting improved environmental quality.

The pedagogical, linguistic and content features of popular English language learning websites in China : a framework for analysis and design

As increasing numbers of Chinese language learners choose to learn English online (CNNIC, 2012), there is a need to investigate popular websites and their language learning designs. This paper reports on the first stage of a study that analysed the pedagogical, linguistic and content features of 25 Chinese English Language Learning (ELL) websites ranked according to their value and importance to users. The website ranking was undertaken using a system known as PageRank. The aim of the study was to identify the features characterising popular sites as opposed to those of less popular sites for the purpose of producing a framework for ELL website design in the Chinese context. The study found that a pedagogical focus with developmental instructional materials accommodating diverse proficiency levels was a major contributor to website popularity. Chinese language use for translations and teaching directives and intermediate level English for learning materials were also significant features. Content topics included Anglophone/Western and non-Anglophone/Eastern contexts. Overall, popular websites were distinguished by their mediation of access to and scaffolded support for ELL.