Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: Results from two phase I studies

Purpose: PTK787/ZK 222584 (PTK/ZK), an orally active inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, inhibits VEGF-mediated angiogenesis. The pharmacodynamic effects of PTK/ZK were evaluated by assessing changes in contrast-enhancement parameters of metastatic liver lesions using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with advanced colorectal cancer treated in two ongoing, dose-escalating phase I studies. Patients and Methods: Twenty-six patients had DCE-MRI performed at baseline, day 2, and at the end of each 28-day cycle. Doses of oral PTK/ZK ranged from 50 to 2000 mg once daily. Tumor permeability and vascularity were assessed by calculating the bidirectional transfer constant (Ki). The percentage of baseline Ki (% of baseline Ki) at each time point was compared with pharmacokinetic and clinical end points. Results: A significant negative correlation exists between the % of baseline Ki and increase in PTK/ZK oral dose and plasma levels (P = .01 for oral dose; P = .0001 for area under the plasma concentration curve at day 2). Patients with a best response of stable disease had a significantly greater reduction in Ki at both day 2 and at the end of cycle 1 compared with progressors (mean difference in % of baseline Ki, 47%, P = .004%; and 51%, P = .006; respectively). The difference in % of baseline Ki remained statistically significant after adjusting for baseline WHO performance status. Conclusion: These findings should help to define a biologically active dose of PTK/ZK. These results suggest that DCE-MRI may be a useful biomarker for defining the pharmacological response and dose of angiogenesis inhibitiors, such as PTK/ZK, for further clinical development. © 2003 by American Society of Clinical Oncology.

Assessment of inflammatory burden contralateral to the symptomatic carotid stenosis using high-resolution ultrasmall, superparamagnetic iron oxide-enhanced MRI

BACKGROUND AND PURPOSE It is well known that the vulnerable atheromatous plaque has a thin, fibrous cap and large lipid core with associated inflammation. This inflammation can be detected on MRI with use of a contrast medium, Sinerem, an ultrasmall superparamagnetic iron oxide (USPIO). Although the incidence of macrophage activity in asymptomatic disease appears low, we aimed to explore the incidence of MRI-defined inflammation in asymptomatic plaques in patients with known contralateral symptomatic disease. METHODS Twenty symptomatic patients underwent multisequence MRI before and 36 hours after USPIO infusion. Images were manually segmented into quadrants, and the signal change in each quadrant was calculated after USPIO administration. A mixed mathematical model was developed to compare the mean signal change across all quadrants in the 2 groups. Patients had a mean symptomatic stenosis of 77% compared with 46% on their asymptomatic side, as measured by conventional angiography. RESULTS There were 11 (55%) men, and the median age was 72 years (range, 53 to 84 years). All patients had risk factors consistent with severe atherosclerotic disease. All symptomatic carotid stenoses had inflammation, as evaluated by USPIO-enhanced imaging. On the contralateral sides, inflammatory activity was found in 19 (95%) patients. Contralaterally, there were 163 quadrants (57%) with a signal loss after USPIO when compared with 217 quadrants (71%) on the symptomatic side (P=0.007). CONCLUSIONS - This study adds weight to the argument that atherosclerosis is a truly systemic disease. It suggests that investigation of the contralateral side in patients with symptomatic carotid stenosis can demonstrate inflammation in 95% of plaques, despite a mean stenosis of only 46%. Thus, inflammatory activity may be a significant risk factor in asymptomatic disease in patients who have known contralateral symptomatic disease. Patients with symptomatic carotid disease should have their contralateral carotid artery followed up.

Framing sexual harassment through media representations

This article examines mainstream news media texts reporting sexual harassment in four industrialized countries. The study first identifies the aspects of sexual harassment cases considered newsworthy by asking how the media texts characterize such cases. Second, the study illuminates the discourses evident in these texts, which are theorized as a mode by which understandings of workplace gender (in)equality shape, and are shaped by, individuals, organizations and the community. The analysis reveals that the media most frequently reports “classic” sexual harassment and emphasizes scandalous allegations and overtly sexualized conduct. The hegemony of a discourse of sexual harassment as an individualized problem of inappropriate employee behavior is also evident. By contrast, discourses presenting sexual harassment as a systemic issue, or as symptomatic of broader gender inequality, are less frequent. We argue that these media representations limit opportunities to frame sexual harassment as dynamic, complex, and part of the practice of gendering in and beyond organizational boundaries.

Histories of user-generated content : between formal and informal media economies

Debates about user-generated content (UGC) often depend on a contrast with its normative opposite, the professionally produced content that is supported and sustained by commercial media businesses or public organisations. UGC is seen to appear within or in opposition to professional media, often as a disruptive, creative, change-making force. Our suggestion is to position UGC not in opposition to professional or "producer media", or in hybridised forms of subjective combination with it (the so-called "pro-sumer" or "pro-am" system), but in relation to different criteria, namely the formal and informal elements in media industries. In this article, we set out a framework for the comparative and historical analysis of UGC systems and their relations with other formal and informal media activity, illustrated with examples ranging from games to talkback radio. We also consider the policy implications that emerge from a historicised reading of UGC as a recurring dynamic within media industries, rather than a manifestation of consumer agency specific to digital cultures.

National and state-level politics on social media : Twitter, Australian political discussions, and the online commentariat

This paper examines the use of Twitter for long-term discussions around Australian politics, at national and state levels, tracking two hashtags during 2012: #auspol, denoting national political topics, and #wapol, which provides a case study of state politics (representing Western Australia). The long-term data collection provides the opportunity to analyse how the Twitter audience responds to Australian politics: which themes attract the most attention and which accounts act as focal points for these discussions. The paper highlights differences in the coverage of state and national politics. For #auspol, a small number of accounts are responsible for the majority of tweets, with politicians invoked but not directly contributing to the discussion. In contrast, #wapol stimulates a much lower level of tweeting. This example also demonstrates that, in addition to citizen accounts, traditional participants within political debate, such as politicians and journalists, are among the active contributors to state-oriented discussions on Twitter.

Digital literacies: Understanding the literate practices of refugee kids in an Afterschool Media Club

Since the 2000s, teachers in an increasing number of Australian schools have been learning how to support students with refugee backgrounds. For some of these students, entry into the Australian school system is not easy. English literacy is integral to some of the challenges confronting the students. In response, educators have been developing and researching ways of engaging with the students’ language and literacy learning. Much of the focus has been on traditional print-based school literacies. In contrast, I look here at student engagement in digital literacies in an after-school media club. Several concepts from the theory of French sociologist, Pierre Bourdieu are useful for understanding the position of students of refugee background in the Australian school system. Like other conflict theories, Bourdieusian theory has sometimes been criticised as ‘pessimistic’, that is, for suggesting that schools necessarily reproduce social disadvantage. However, others have used Bourdieusian theory to analyse and critique the reproductive work of schooling for groups of students who experience educational disadvantage. I align myself with this latter tradition. Specifically, I use Bourdieu’s triad of concepts to explain aspects of the literacy education experiences of some young people of refugee background: field, capital and habitus. In particular, I look at questions of the legitimation of students’ competences as capital in literate fields within and beyond the school context. Data are drawn from an Australian Research Council-funded project, Digital Learning and Print Literacy: A design experiment for the reform of low socio-economic, culturally diverse schools (2009-14). The data analysed in this chapter include interviews and observations relating to the participation of two Congolese girls in an after school media club. Implications are drawn for teachers of literacy in culturally and linguistically diverse contexts. Consideration is made of early childhood, primary and secondary settings.

Social media(tion) and the reshaping of public/private boundaries in employment relations

Tensions surrounding social media in the employment relationship are increasingly evident in the media, public rhetoric, and courts and employment tribunals. Yet the underlying causes and dimensions of these tensions have remained largely unexplored. This article firstly reviews the available literature addressing social media and employment, outlining three primary sources of contestation: profiling, disparaging posts and blogs, and private use of social media during work time. In each area, the key dynamics and underlying concerns of the central actors involved are identified. The article then seeks to canvas explanations for these forms of contestation associated with social media at work. It is argued that the architecture of social media disrupts traditional relations in organisational life by driving employer and employee actions that (re)shape and (re)constitute the boundaries between public and private spheres. Although employers and employees are using the same social technologies, their respective concerns about and points of entry to these technologies, in contrast to traditional manifestations of conflict and resistance, are asymmetric. The article concludes with a representational summary of the relative legitimacy of concerns for organisational actors and outlines areas for future research.

Re-theorizing the “digital divide”: Identifying dimensions of social exclusion in contemporary media technologies

The digital divide is the disparancy in access to information, in the ability to communicate, and in the capacity to make information and communication serve full participation in the information society. Indeed, the conversation about the digital divide has developed over the last decade from a focus on connectivity and access to information and communication technologies, to a conversation that encompasses the ability to use them and to the utility that usage provides (Wei et al., 2011). However, this conversation, while transitioning from technology to the skills of the people that use them and to the fruits of their use is limited in its ability to take into account the social role of information and communication technologies (ICTs). One successful attempt in conceptualizing the social impact of the differences in access to and utilization of digital communication technologies, was developed by van Dijk (2005) whose sequential model for analyzing the divide states that: 1. Categorical inequalities in society produce an unequal distribution of resources; 2. An unequal distribution of resources causes unequal access to digital technologies; 3. Unequal access to digital technologies also depends on the characteristics of these technologies; 4. Unequal access to digital technologies brings about unequal participation in society; 5. Unequal participation in society reinforces categorical inequalities and unequal distributions of resources.” (p. 15) As van Dijk’s model demonstrates, the divide’s impact is the exclusion of individuals from participation. Still left to be defined are the “categorical inequalities,” the “resources,” the “characteristics of digital technologies,” and the different levels of “access” that result in differentiated levels of participation, as these change over time due to the evolving nature of technology and the dynamics of society. And most importantly, the meaning of “participation” in contemporary society needs to be determined as it is differentiated levels of participation that are the result of the divide and the engine of the ever-growing disparities. Our argument is structured in the following manner: We first claim that contemporary digital media differ from the previous generation of ICTs along four dimensions: They offer an abundance of information resources and communication channels when compared to the relative paucity of both in the past; they offer mobility as opposed to the stationary nature of their predecessors; they are interactive in that they provide users with the capability to design their own media environments in contrast to the dictated environs of previous architectures; and, they allow users to communicate utilizing multi forms of mediation, unlike the uniformity of sound or word that limited users in the past. We then submit that involvement in the information society calls for egalitarian access to all four dimensions of the user experience that make contemporary media different from their predecessors and that the ability to experience all four affects the levels in which humans partake in the shaping of society. The model being cyclical, we then discuss how lower levels of participation contribute to the enhancement of social inequalities. Finally, we discuss why participation is needed in order to achieve full membership in the information society and what political philosophy should govern policy solutions targeting the re-inclusion of those digitally excluded.

Media futures: A review essay on'The Future of Reputation','TV Futures', and'The Future of the Internet and How to Stop It'

In his 1987 book, The Media Lab: Inventing the Future at MIT, Stewart Brand provides an insight into the visions of the future of the media in the 1970s and 1980s. 1 He notes that Nicolas Negroponte made a compelling case for the foundation of a media laboratory at MIT with diagrams detailing the convergence of three sectors of the media—the broadcast and motion picture industry; the print and publishing industry; and the computer industry. Stewart Brand commented: ‘If Negroponte was right and communications technologies really are converging, you would look for signs that technological homogenisation was dissolving old boundaries out of existence, and you would expect an explosion of new media where those boundaries used to be’. Two decades later, technology developers, media analysts and lawyers have become excited about the latest phase of media convergence. In 2006, the faddish Time Magazine heralded the arrival of various Web 2.0 social networking services: You can learn more about how Americans live just by looking at the backgrounds of YouTube videos—those rumpled bedrooms and toy‐strewn basement rec rooms—than you could from 1,000 hours of network television. And we didn’t just watch, we also worked. Like crazy. We made Facebook profiles and Second Life avatars and reviewed books at Amazon and recorded podcasts. We blogged about our candidates losing and wrote songs about getting dumped. We camcordered bombing runs and built open‐source software. America loves its solitary geniuses—its Einsteins, its Edisons, its Jobses—but those lonely dreamers may have to learn to play with others. Car companies are running open design contests. Reuters is carrying blog postings alongside its regular news feed. Microsoft is working overtime to fend off user‐created Linux. We’re looking at an explosion of productivity and innovation, and it’s just getting started, as millions of minds that would otherwise have drowned in obscurity get backhauled into the global intellectual economy. The magazine announced that Time’s Person of the Year was ‘You’, the everyman and everywoman consumer ‘for seizing the reins of the global media, for founding and framing the new digital democracy, for working for nothing and beating the pros at their own game’. This review essay considers three recent books, which have explored the legal dimensions of new media. In contrast to the unbridled exuberance of Time Magazine, this series of legal works displays an anxious trepidation about the legal ramifications associated with the rise of social networking services. In his tour de force, The Future of Reputation: Gossip, Rumor, and Privacy on the Internet, Daniel Solove considers the implications of social networking services, such as Facebook and YouTube, for the legal protection of reputation under privacy law and defamation law. Andrew Kenyon’s edited collection, TV Futures: Digital Television Policy in Australia, explores the intersection between media law and copyright law in the regulation of digital television and Internet videos. In The Future of the Internet and How to Stop It, Jonathan Zittrain explores the impact of ‘generative’ technologies and ‘tethered applications’—considering everything from the Apple Mac and the iPhone to the One Laptop per Child programme.

A second order control-volume finite-element least-squares strategy for simulating diffusion in strongly anisotropic media

An unstructured mesh �nite volume discretisation method for simulating di�usion in anisotropic media in two-dimensional space is discussed. This technique is considered as an extension of the fully implicit hybrid control-volume �nite-element method and it retains the local continuity of the ux at the control volume faces. A least squares function recon- struction technique together with a new ux decomposition strategy is used to obtain an accurate ux approximation at the control volume face, ensuring that the overall accuracy of the spatial discretisation maintains second order. This paper highlights that the new technique coincides with the traditional shape function technique when the correction term is neglected and that it signi�cantly increases the accuracy of the previous linear scheme on coarse meshes when applied to media that exhibit very strong to extreme anisotropy ratios. It is concluded that the method can be used on both regular and irregular meshes, and appears independent of the mesh quality.