Integrated analysis of epigenomic and genomic changes by DNA methylation dependent mechanisms provides potential novel biomarkers for prostate cancer

Epigenetic silencing mediated by CpG methylation is a common feature of many cancers. Characterizing aberrant DNA methylation changes associated with tumor progression may identify potential prognostic markers for prostate cancer (PCa). We treated two PCa cell lines, 22Rv1 and DU-145 with the demethylating agent 5-Aza 2’–deoxycitidine (DAC) and global methylation status was analyzed by performing methylation-sensitive restriction enzyme based differential methylation hybridization strategy followed by genome-wide CpG methylation array profiling. In addition, we examined gene expression changes using a custom microarray. Gene Set Enrichment Analysis (GSEA) identified the most significantly dysregulated pathways. In addition, we assessed methylation status of candidate genes that showed reduced CpG methylation and increased gene expression after DAC treatment, in Gleason score (GS) 8 vs. GS6 patients using three independent cohorts of patients; the publically available The Cancer Genome Atlas (TCGA) dataset, and two separate patient cohorts. Our analysis, by integrating methylation and gene expression in PCa cell lines, combined with patient tumor data, identified novel potential biomarkers for PCa patients. These markers may help elucidate the pathogenesis of PCa and represent potential prognostic markers for PCa patients.

An e-support firm's response to local e-readiness and the global e-business environment

The purpose of this study is to understand a small e-support firm’s response to the local e-readiness and the global e-business environment in a developing context. E-Support firms provide Web development and consultancy services to user organizations, assisting them in their uptake and maintenance of their Internet applications. Within the e-readiness research area, little is known about e-support firms, particularly in connection with their interaction with their local and the global e-business environment. As yet the emphasis on e-readiness studies has been at the national level. Nevertheless, the e-support sector is very significant in the successful adoption and diffusion of the Internet and related applications in any economy. It is thus important to understand how such firms relate to their e-business environments.That said, this study draws on the interpretive case study of a small e-support firm in Ghana, a developing context, to investigate the firm’s response to the e-readiness level of the local and the global e-business environment. Findings show that the firm could employ resources from the global environment to address most of the infrastructural challenges posed by a relatively poor local e-readiness context. However, its attempt to transfer advanced e-business technologies from the global e-business environment to the local e-business context did not succeed. This chapter offers implications for practice and research concerning the notion of reconciling local and global e-business environments in the small e-support sector.

Achieving enterprise integration through software customization : part II-enacting the strategy

In part 1 of this update, we put forward the argument that integration in ERP based environments can be achieved in ways other than adopting a software configuration only approach. We drew on evidence from two large ERP implementations to show how, despite the cost implications, some customization, if carefully managed, could prove helpful. In this, the final part of the update, we discuss the benefits, and potential pitfalls, involved in enacting a non-standard based integration strategy. This requires attention to a) broadening the integration definition; b) bringing legacy practices forward and c) developing a customization based integration strategy.

In for the long haul : family business succession at HaulageCo

This is a case about family business succession. Because many successions fail, the 'problem of succession' is a key issue in the family business field (see Aronoff 1998; Bird eta/. 2002; Dyer & Sanchez 1998; Sharma 2004; Zalu·a & Sharma 2004). Indeed, from the non-family business literature, we know one third of relay successions - like this case where there is an identified successor - will fail, with the prospective CEO leaving before succeeding the incumbent CEO (Cmmella & Shen 2001). Research on next generation family business members is limited. Successor ath·ibutes (Chrisman, Chua & Sharma 1998; Sharma & Rao 2000), as well as various characteristics such as socialisation (Garcia-Aivmez, L6pez-Sintas & Gonzalvo 2002) a11d gender (Haberman & Danes 2007; Vera & Dean 2005) have all been considered to play a role. So too have successor intentions (Stavrou & Swiercz 1998), motivation (Le Breton-Miller, Miller & Steier 2004), commitment (Sharma & Irving 2005) and transformation from follower to leadership (Cater & Justis 2009). In this case, by outlining the socialisation of the successors, explanations of their motivations for joining a11d their current employment we can begin to see some of the underlying mechanisms at work motivating the next generation to join and stay in the family business.

The topography of multiple drug use among adolescent Australians : findings from the National Drug Strategy Household Survey

Introduction and aims: Despite evidence that many Australian adolescents have considerable experience with various drug types, little is known about the extent to which adolescents use multiple substances. The aim of this study was to examine the degree of clustering of drug types within individuals, and the extent to which demographic and psychosocial predictors are related to cluster membership. Design and method: A sample of 1402 adolescents aged 12-17. years were extracted from the Australian 2007 National Drug Strategy Household Survey. Extracted data included lifetime use of 10 substances, gender, psychological distress, physical health, perceived peer substance use, socioeconomic disadvantage, and regionality. Latent class analysis was used to determine clusters, and multinomial logistic regression employed to examine predictors of cluster membership. Result: There were 3 latent classes. The great majority (79.6%) of adolescents used alcohol only, 18.3% were limited range multidrug users (encompassing alcohol, tobacco, and marijuana), and 2% were extended range multidrug users. Perceived peer drug use and psychological distress predicted limited and extended multiple drug use. Psychological distress was a more significant predictor of extended multidrug use compared to limited multidrug use. Discussion and conclusion: In the Australian school-based prevention setting, a very strong focus on alcohol use and the linkages between alcohol, tobacco and marijuana are warranted. Psychological distress may be an important target for screening and early intervention for adolescents who use multiple drugs.

An urban design perspective to classify knowledge precincts : a typological analysis of global best practices

Purpose: The paper seeks to investigate emerging knowledge precincts under the urban design lens in order to identify recurrent spatial patterns of urban forms and functions to gather an understanding of physical aspects that contribute to the creation of place quality. Scope: This paper focuses on the physical design and layout of specific precincts. Although socio-economic and other factors come into play imparting the distinctiveness; this paper only focuses on the spatial dimensions. Method: The research first develops a design typology framework through the lead of literature, and then utilizes it to identify recurrent elements in knowledge precinct design in order to develop taxonomy of patterns and layouts. Results: The research reported in this paper provides preliminary insights into the various form and functional factors playing role in the design of knowledge precincts and evaluates the elements that contribute to the success of these urban interventions. Recommendations: The paper recommends the use of particular design-based solutions in order to enhance the place making in knowledge precincts. Conclusions: The study concludes that despite the locational, regulatory and other contextual differences, the underlying driving principle of providing place quality to people leads to the emergence of identifiable spatial patterns across the knowledge precincts.

Marx as a Critical Discourse Analyst : The Genesis of a Critical Method and its Relevance to the Critique of Global Capital (with Phil Graham)

In this paper we identify elements in Marx’s economic and political writings that are relevant to contemporary critical discourse analysis (CDA). We argue that Marx can be seen to be engaging in a form of discourse analysis. We identify the elements in Marx’s historical materialist method that support such a perspective, and exemplify these in longitudinal comparison of Marx’s texts.

Global dissemination of a multidrug resistant Escherichia coli clone

Escherichia coli sequence type 131 (ST131) is a globally disseminated, multidrug resistant (MDR) clone responsible for a high proportion of urinary tract and bloodstream infections. The rapid emergence and successful spread of E. coli ST131 is strongly associated with several factors, including resistance to fluoroquinolones, high virulence gene content, the possession of the type 1 fimbriae FimH30 allele, and the production of the CTX-M-15 extended spectrum β-lactamase (ESBL). Here, we used genome sequencing to examine the molecular epidemiology of a collection of E. coli ST131 strains isolated from six distinct geographical locations across the world spanning 2000–2011. The global phylogeny of E. coli ST131, determined from whole-genome sequence data, revealed a single lineage of E. coli ST131 distinct from other extraintestinal E. coli strains within the B2 phylogroup. Three closely related E. coli ST131 sublineages were identified, with little association to geographic origin. The majority of single-nucleotide variants associated with each of the sublineages were due to recombination in regions adjacent to mobile genetic elements (MGEs). The most prevalent sublineage of ST131 strains was characterized by fluoroquinolone resistance, and a distinct virulence factor and MGE profile. Four different variants of the CTX-M ESBL–resistance gene were identified in our ST131 strains, with acquisition of CTX-M-15 representing a defining feature of a discrete but geographically dispersed ST131 sublineage. This study confirms the global dispersal of a single E. coli ST131 clone and demonstrates the role of MGEs and recombination in the evolution of this important MDR pathogen.

Biological monitoring and Biological Limit Values (BLV): the strategy of the European Union

Occupational standards concerning allowable concentrations of chemical compounds in the ambient air of workplaces have been established in several countries worldwide. With the integration of the European Union (EU), there has been a need of establishing harmonised Occupational Exposure Limits (OEL). The European Commission Directive 95/320/EC of 12 July 1995 has given the tasks to a Scientific Committee for Occupational Exposure Limits (SCOEL) to propose, based on scientific data and where appropriate, occupational limit values which may include the 8-h time-weighted average (TWA), short-term limits/excursion limits (STEL) and Biological Limit Values (BLVs). In 2000, the European Union issued a list of 62 chemical substances with Occupational Exposure Limits. Of these, 25 substances received a "skin" notation, indicating that toxicologically significant amounts may be taken up via the skin. For such substances, monitoring of concentrations in ambient air may not be sufficient, and biological monitoring strategies appear of potential importance in the medical surveillance of exposed workers. Recent progress has been made with respect to formulation of a strategy related to health-based BLVs.

Global Human Trafficking : Critical Issues and Contexts

Human trafficking has moved from relative obscurity to a major area of research, policy and teaching over the past ten years. Research has sprung from criminology, public policy, women’s and gender studies, sociology, anthropology, and law, but has been somewhat hindered by the failure of scholars to engage beyond their own disciplines and favoured methodologies. Recent research has begun to improve efforts to understand the causes of the problem, the experiences of victims, policy efforts, and their consequences in specific cultural and historical contexts. Global Human Trafficking: Critical issues and contexts foregrounds recent empirical work on human trafficking from an interdisciplinary, critical perspective. The collection includes classroom-friendly features, such as introductory chapters that provide essential background for understanding the trafficking literature, textboxes explaining key concepts, discussion questions for each chapter, and lists of additional resources, including films, websites, and additional readings for each chapter. The authors include both eminent and emerging scholars from around the world, drawn from law, anthropology, criminology, sociology, cultural studies, and political science and the book will be useful for undergraduate and graduate courses in these areas, as well as for scholars interested in trafficking.

From styling to strategy : transforming an Australian manufacturing SME's perception of design

This thesis explores the shift in perception of design from a styling and product-focused tool, towards a holistic strategic approach within a small to medium sized manufacturing company. This research is significant because it demonstrates how design tools and approaches can be used within business to translate theory into operational, strategic and cultural outcomes. The outcomes of this research will encourage other businesses to take on similar design-led projects with the ultimate goal of employing design as a means to create a sustainable competitive advantage.