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.

Aboriginality and the Northern Territory intervention

Architects and supporters of the Northern Territory Emergency Response (the intervention) mobilised a range of ideas about Aboriginality to introduce and justify the policy program. These representations link Aboriginality to abuse of Aboriginal children, establishing a debate about the nature and future of Aboriginality in a context that limits the discursive authority of Aboriginal people. Aboriginality is represented as savage and in need of settler-imposed control, and also primitive and in need of development. These constructions understand Aboriginality temporally, situating it in the past but providing moral justification for coercing Indigenous people into the settler present. Aboriginality is also constructed spatially in this discourse, with prescribed communities framed as the location of both authentic Aboriginality and of threatening disorder. The intervention is framed as extending settler authority over this troubling terrain, containing and redeeming Aboriginality through inclusion in the settler nation’s moral order.

The vanishing endpoint of settler colonialism

In this paper, we interrogate the way that narratives about the unfolding of settler colonialism through time are encoded in recent Australian Indigenous policy frameworks. We argue that the postcolonial image of a single transformative moment of radical political break is embedded in Australian policy frameworks, but is deployed in ways that fuse this idea with the moment of colonial completion and in so doing assist the colonial project. By merging the moment of decolonisation and the moment of colonial completion, temporal narratives mobilise conservative and progressive settler voices towards colonial goals. We identify three recent policy approaches: reconciliation, neoliberal contractualism and intervention, and interrogate the narratives of the present and future that they reflect and deploy. We argue these unacknowledged stories of the colonial future must be contested, so that debates about how settler and Indigenous people might live together differently across time are not foreclosed.

Aboriginality and the Northern Territory intervention

This thesis examines the construction of Aboriginality in recent public policy reasoning through identifying representations deployed by architects and supporters of the Commonwealth’s 2007 Northern Territory Emergency Response (the intervention). Debate about the Northern Territory intervention was explicitly situated in relation to a range of ideas about appropriate Government policy towards Indigenous people, and particularly about the nature, role, status, value and future of Aboriginality and of Aboriginal people and Torres Strait Islanders. This project involves analysis of constructions of Aboriginality deployed in texts created and circulated to explain and justify the policy program. The aim of the project is to identify the ideas about Aboriginality deployed by the intervention’s architects and supporters, and to examine the effects and implications of these discourses for political relationships between Indigenous people and settlers in Australia. This thesis will argue that advocates of the Northern Territory intervention construct Aboriginality in a range of important ways that reassert and reinforce the legitimacy of the settler colonial order and the project of Australian nationhood, and operate to limit Aboriginal claims. Specifically, it is argued that in linking Aboriginality to the abuse of Aboriginal children, the intervention’s advocates and supporters establish a political debate about the nature and future of Aboriginality within a discursive terrain in which the authority and perspectives of Indigenous people are problematised. Aboriginality is constructed in this process as both temporally and spatially separated from settler society, and in need of coercive integration into mainstream economic and political arrangements. Aboriginality is depicted by settler advocates of intervention as an anachronism, with Aboriginal people and cultures understood as primitive and/or savage precursors to settlers who are represented as modern and civilised. As such, the communities seen as the authentic home or location of Aboriginality represent a threat to Aboriginal children as well as to settlers. These constructions function to obscure the violence of the settler order, provide justification or moral rehabilitation for the colonising project, and reassert the sovereignty of the settler state. The resolution offered by the intervention’s advocates is a performance or enactment of settler sovereignty, representing a claim over and through both the territory of Aboriginal people and the discursive terrain of nationhood.

On the beach : exploring the complex egalitarianism of the Australian beach

Australia, internationally, is known as a beach loving country, particularly in popular culture. The beach did not figure significantly in academic discussion before the 1980s when Fiske, Hodge, and Turner (1987, 54) researched the beach as a space of myth, seeing it as an integral part of the modern Australian identity. One common myth in Australia is that the beach is an equaliser, a place of multiple ethnicities, shapes, sizes, and genders (Dutton, 1985). I agree that the beach remains a significant aspect of Australian identity; however, limiting its meaning to a mythic space contributing to a homogenous national identity is not adequate. This paper will explore how Australian texts comment on or challenge the myth of the beach as an egalitarian space. I argue that recent Australian texts show a more complex, layered representation of this concept; and that the beach also in this respect can no longer be understood as a myth transcending difference.

Developmental lessons from the Capricornia Arts Mob (CAM)

The Capricornia Arts Mob (CAM) is a collective of Aboriginal and Torres Strait Islander visual artists, sculptors, photographers, carvers and writers based in the Rockhampton region of Central Queensland. This paper explores the early development of CAM, identifies some of the lessons its members have learned about working together, and considers its role as a regional artists’ collective. The authors identify that traditional Indigenous practices, such as yarning and the sharing of food, have helped to facilitate the emergence of CAM as a vibrant, challenging, eclectic artistic family. They recognise the cultural challenges faced by the collective – including finding a culturally appropriate place to meet and work, and the cross-cultural issues that can emerge within Aboriginal and Torres Strait Islander groups. In just 18 months, CAM has held successful exhibitions and developed public artworks. It is a strong part of regional Queensland’s arts scene, which supports emerging artists and provides a space to celebrate and support Indigenous art.

‘Time for a change in direction’ : using Indigenous knowledges as the driving force for change

We live in a time of change, of rapid change in some cases. Regardless of where we live as Indigenous peoples we see this, feel this, know this and understand this. Yet how do we manage this? At times Indigenous knowledge and Western knowledge are aligned and at other times diametrically opposed. This is also the case when examining how Indigenous knowledges are viewed, accessed and used even when politicians, governments and institutions are searching for answers and solutions for Indigenous people and for broader Australian society. Sometimes we have witnessed Indigenous knowledges too far down the back, at the bottom of the list and even disregarded. In some cases Indigenous peoples and our knowledges have been positioned as the victims of modernity. Imagine if we could draw on the strength of Indigenous knowledges as the driving force to change direction or for change. We can do this. This paper will explore some of the ways we might do this and bring about an improved society for all peoples.

Commentary on Nutrition and older Indigenous Australians : service delivery implications in remote communities. A narrative review

Indigenous Australians are the most socially and economically disadvantaged population group in Australia and have the poorest health status. The statistics describe and highlight the degree of sicknesses and disadvantage along with lower life expectancy, elevated mortality rate and increased risk of cardiovascular disease, cancer, diabetes, respiratory disease and kidney disease. While these statistics reflect poor health status and a high level of illness within Indigenous communities, it is known that individual, family and community behaviours play a key role in Indigenous health and wellbeing outcomes. These behavioural issues include use of tobacco, alcohol and other substances along with lack of physical activity and poor nutrition. The paper Nutrition and older Indigenous Australians: Service delivery implications in remote communities. A narrative view explores some of the issues specific to nutrition. Bronwyn Fredericks was invited to provide this commentary by the Editor of the Australasian Journal on Aging.

Always “tasty”, regardless: Art, chocolate and Indigenous Australians

This paper examines race and colour through the metaphor of chocolate. The authors use the metaphor of chocolate to question why some Aboriginal people are chosen ahead of others, with the choosing done by non-Indigenous people, perhaps on the basis of who is most likely to be “soft-centred”, agreeable, and pliable. The authors discuss the development of the Hot Chocolate art exhibition in Adelaide in 2012, with a particular focus on the works of Pamela CroftWarcon. The exhibition combined chocolate (the food), lyrics from Hot Chocolate (the band), and chocolate (the metaphor for skin colour) to encourage visitors to question their assumptions about representations of Aboriginal people in Australia.

Homocysteine concentrations lowered following dietary intervention in an aboriginal community

Low circulating folate concentrations lead to elevations of plasma homocysteine. Even mild elevations of plasma homocysteine are associated with significantly increased risk of cardiovascular disease (CVD). Available evidence suggests that poor nutrition contributes to excessive premature CVD mortality in Australian Aboriginal people. The aim of the present study was to examine the effect of a nutrition intervention program conducted in an Aboriginal community on plasma homocysteine concentrations in a community-based cohort. From 1989, a health and nutrition project was developed, implemented and evaluated with the people of a remote Aboriginal community. Plasma homocysteine concentrations were measured in a community-based cohort of 14 men and 21 women screened at baseline, 6 months and 12 months. From baseline to 6 months there was a fall in mean plasma homocysteine of over 2|mol/L (P = 0.006) but no further change thereafter (P = 0.433). These changes were associated with a significant increase in red cell folate concentration from baseline to 6 months (P < 0.001) and a further increase from 6 to 12 months (P < 0.001). In multiple regression analysis, change in homocysteine concentration from baseline to 6 months was predicted by change in red cell folate (P = 0.002) and baseline homocysteine (P < 0.001) concentrations, but not by age, gender or baseline red cell folate concentration. We conclude that modest improvements in dietary quality among populations with poor nutrition (and limited disposable income) can lead to reductions in CVD risk.

Increase in prevalence of obesity and diabetes and decrease in plasma cholesterol in a central Australian Aboriginal community

Objective: To document change in prevalence of obesity, diabetes and other cardiovascular diease (CVD) risk factors, and trends in dietary macronutrient intake, over an eight-year period in a rural Aboriginal community in central Australia. Design: Sequential cross-sectional community surveys in 1987, 1991 and 1995. Subjects: All adults (15 years and over) in the community were invited to participate. In 1987, 1991 and 1995, 335 (87% of eligible adults), 331 (76%) and 304 (68%), respectively, were surveyed. Main outcome measures: Body mass index and waist : hip ratio; blood glucose level and glucose tolerance; fasting total and high density lipoprotein (HDL) cholesterol and triglyceride levels; and apparent dietary intake (estimated by the store turnover method). Intervention: A community-based nutrition awareness and healthy lifestyle program, 1988-1990. Results: At the eight-year follow-up, the odds ratios (95% CIs) for CVD risk factors relative to baseline were obesity, 1.84 (1.28-2.66); diabetes, 1.83 (1.11-3.03); hypercholesterolaemia, 0.29 (0.20-0.42); and dyslipidaemia (high triglyceride plus low HDL cholesterol level), 4.54 (2.84-7.29). In younger women (15-24 years), there was a trebling in obesity prevalence and a four- to fivefold increase in diabetes prevalence. Store turnover data suggested a relative reduction in the consumption of refined carbohydrates and saturated fats. Conclusion: Interventions targeting nutritional factors alone are unlikely to greatly alter trends towards increasing prevalences of obesity and diabetes. In communities where healthy food choices are limited, the role of regular physical activity in improving metabolic fitness may also need to be emphasised.

The effect of retail store managers on aboriginal diet in remote communities

Key nutrient densities of the diet of two remote northern coastal Aboriginal communities were measured using the store-turnover method during the periods that three store managers were responsible for each store respectively. Individual store managers were a greater determinant of nutrient density than the community itself. Furthermore, nutrient densities tended to be highest in both communities when their stores were administered by one particular store manager. The results support the notion that store managers wield considerable power over the food supply of remote Aboriginal communities, and raise questions concerning the ability of Aboriginal community members to influence their own food supplies in retail stores. However, the study also confirms that store managers can be important allies in efforts to improve Aboriginal dietary intake.

Queer, student, activism

Queer student activists are a visible aspect of Australian tertiary communities. This chapter explores the findings of interviews with eight queer student in which they discuss their understandings of queer student activism and the way they see the university setting shaping the production queer student media. The findings draw out two themes: visibility and access and participation. These discussions illustrate how the intersections of queer, student, activism, and their associated contexts, create a particular type of activism. This chapter thus contributes to queer history by demonstrating how one specific cultural subset does queer activism.