Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer

We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival “neuronal” subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, long non-coding RNA (lncRNA), and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma in situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments. A multiplatform analysis of 412 muscle-invasive bladder cancer patients provides insights into mutational profiles with prognostic value and establishes a framework associating distinct tumor subtypes with clinical options

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although the MYC oncogene has been implicated in cancer, a systematic assessment of alterations of MYC, related transcription factors, and co-regulatory proteins, forming the proximal MYC network (PMN), across human cancers is lacking. Using computational approaches, we define genomic and proteomic features associated with MYC and the PMN across the 33 cancers of The Cancer Genome Atlas. Pan-cancer, 28% of all samples had at least one of the MYC paralogs amplified. In contrast, the MYC antagonists MGA and MNT were the most frequently mutated or deleted members, proposing a role as tumor suppressors. MYC alterations were mutually exclusive with PIK3CA, PTEN, APC, or BRAF alterations, suggesting that MYC is a distinct oncogenic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such as immune response and growth factor signaling; chromatin, translation, and DNA replication/repair were conserved pan-cancer. This analysis reveals insights into MYC biology and is a reference for biomarkers and therapeutics for cancers with alterations of MYC or the PMN. We present a computational study determining the frequency and extent of alterations of the MYC network across the 33 human cancers of TCGA. These data, together with MYC, positively correlated pathways as well as mutually exclusive cancer genes, will be a resource for understanding MYC-driven cancers and designing of therapeutics

Insider Perspectives vs. Public Perceptions of ICT: toward policy for enhancing female student participation in academic pathways to professional careers in ICT

This article reports findings of a national online survey of Australian women employed in Information and Communication Technology (ICT)-related careers. The Women in ICT Industry Survey was the culminating stage of a larger Australian Research Council Linkage Grant project investigating factors associated with low and declining female participation rates in professional-level ICT pathways. The survey comprised a mix of forced-choice and open-ended short-response items, and was completed by 272 Australian women. Application of K-means cluster analysis to forced-choice item responses revealed three discrete groupings of female ICT professionals. Overall, respondents reported that their ICT career was rewarding, provided opportunities and challenges, and was beneficial to society. Respondents generally disagreed with Queensland high school girls’ perceptions that ICT is boring, sedentary, and not relevant to their future career directions. They also disagreed that the industry fits the prevailing negative stereotype of being populated by ‘geeks’ and ‘nerds’. Divergent opinions centered mainly around participants’ confidence in their own technical ability, whether they would encourage young women to enter the ICT industry, and how they perceived and responded to industrial issues of equality and management approachability. These findings support suggestions for a range of policy and curriculum initiatives designed to enable more positive experiences of computing in school, and to optimize ICT career pathways in tandem with furthering wider educational ends.\ud \ud \u

Strategy-as-Power:Ambiguity, Contradiction and the Exercise of Power in a UK Building Society

'Strategy-as-practice (s-a-p) scholars have urged us to attend to the messy realities of strategy so as to increase the relevance of research for practitioners. This article, whilsts recognising the need to focus on what managers do, develops a critique of this literature. It argues that the s-a-p approach (Whittington, Jarzabkowski, Johnson, Balogun) and the earlier 'Power School' (Mintzberg, Pettigrew, Pfeffer) share much in common as both present power as the possession of management. This overstates the ability of managers to control others whilst understating the scope for resistance. Second, it asserts that both approaches would benefit from greater sensitivity towards the unequal context through which strategies emerge and that they serve, in part, to reproduce. Third, the article provides an empirical case study of strategy in a UK Building Society. It attends to how power is exercised in ambiguous and contradictory ways that both supports and thwarts managerial endeavours. Through considering the uncertainty that results from this, the case reflects on the possibilities for resistance. The central argument is that if we explore practice only from management's perspective, then we are in danger of not only reinforcing the status quo but also of being irrelevant to practitioners and wider constituents