Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment : the M77001 study group

Purpose: This randomized, multicenter trial compared first-line trastuzumab plus docetaxel versus docetaxel alone in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Patients and Methods: Patients were randomly assigned to six cycles of docetaxel 100 mg/m 2 every 3 weeks, with or without trastuzumab 4 mg/kg loading dose followed by 2 mg/kg weekly until disease progression. Results: A total of 186 patients received at least one dose of the study drug. Trastuzumab plus docetaxel was significantly superior to docetaxel alone in terms of overall response rate (61% v 34%; P = .0002), overall survival (median, 31.2 v 22.7 months; P = .0325), time to disease progression (median, 11.7 v 6.1 months; P = .0001), time to treatment failure (median, 9.8 v 5.3 months; P = .0001), and duration of response (median, 11.7 v 5.7 months; P = .009). There was little difference in the number and severity of adverse events between the arms. Grade 3 to 4 neutropenia was seen more commonly with the combination (32%) than with docetaxel alone (22%), and there was a slightly higher incidence of febrile neutropenia in the combination arm (23% v 17%). One patient in the combination arm experienced symptomatic heart failure (1%). Another patient experienced symptomatic heart failure 5 months after discontinuation of trastuzumab because of disease progression, while being treated with an investigational anthracycline for 4 months. Conclusion: Trastuzumab combined with docetaxel is superior to docetaxel alone as first-line treatment of patients with HER2-positive MBC in terms of overall survival, response rate, response duration, time to progression, and time to treatment failure, with little additional toxicity. © 2005 by American Society of Clinical Oncology.

Women in prison : where are we going?

Female imprisonment rates have dramatically increased over the last two decades at state, national and international levels. This paper reviews women's imprisonment in Australia and looks at sentence management and programs, highlighting the critical issues which impact daily on female inmates.

Neoliberal issues in public education

We finished penning this special issue and sending it to press on martin Luther King Jr. Day. We take pause, honoring Martin Luther King's memory and we are dedicating this project to his profound vision as a public intellectual and world activist for whom two of his breakthrough ideas are particularly relevant to this collection. The guest editors, along with the contributors, are reinforcing his messages for the current and future eras that "leadership is the action of ideas to make change, through the agency of individuals" (p. 74) and that "Injustice anywhere is a threat to justice everywhere" (p. 75) (see Temes 1996).

Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma : clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study

Background The effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in patients with malignant pleural mesothelioma have, to our knowledge, not been assessed in a randomised trial. We aimed to assess the clinical outcomes of patients who were randomly assigned to EPP or no EPP in the context of trimodal therapy in the Mesothelioma and Radical Surgery (MARS) feasibility study. Methods MARS was a multicentre randomised controlled trial in 12 UK hospitals. Patients aged 18 years or older who had pathologically confirmed mesothelioma and were deemed fit enough to undergo trimodal therapy were included. In a prerandomisation registration phase, all patients underwent induction platinum-based chemotherapy followed by clinical review. After further consent, patients were randomly assigned (1:1) to EPP followed by postoperative hemithorax irradiation or to no EPP. Randomisation was done centrally with computer-generated permuted blocks stratified by surgical centre. The main endpoints were feasibility of randomly assigning 50 patients in 1 year (results detailed in another report), proportion randomised who received treatment, proportion eligible (registered) who proceeded to randomisation, perioperative mortality, and quality of life. Patients and investigators were not masked to treatment allocation. This is the principal report of the MARS study; all patients have been recruited. Analyses were by intention to treat. This trial is registered, number ISRCTN95583524. Findings Between Oct 1, 2005, and Nov 3, 2008, 112 patients were registered and 50 were subsequently randomly assigned: 24 to EPP and 26 to no EPP. The main reasons for not proceeding to randomisation were disease progression (33 patients), inoperability (five patients), and patient choice (19 patients). EPP was completed satisfactorily in 16 of 24 patients assigned to EPP; in five patients EPP was not started and in three patients it was abandoned. Two patients in the EPP group died within 30 days and a further patient died without leaving hospital. One patient in the no EPP group died perioperatively after receiving EPP off trial in a non-MARS centre. The hazard ratio [HR] for overall survival between the EPP and no EPP groups was 1·90 (95% CI 0·92-3·93; exact p=0·082), and after adjustment for sex, histological subtype, stage, and age at randomisation the HR was 2·75 (1·21-6·26; p=0·016). Median survival was 14·4 months (5·3-18·7) for the EPP group and 19·5 months (13·4 to time not yet reached) for the no EPP group. Of the 49 randomly assigned patients who consented to quality of life assessment (EPP n=23; no EPP n=26), 12 patients in the EPP group and 19 in the no EPP group completed the quality of life questionnaires. Although median quality of life scores were lower in the EPP group than the no EPP group, no significant differences between groups were reported in the quality of life analyses. There were ten serious adverse events reported in the EPP group and two in the no EPP group. Interpretation In view of the high morbidity associated with EPP in this trial and in other non-randomised studies a larger study is not feasible. These data, although limited, suggest that radical surgery in the form of EPP within trimodal therapy offers no benefit and possibly harms patients. Funding Cancer Research UK (CRUK/04/003), the June Hancock Mesothelioma Research Fund, and Guy's and St Thomas' NHS Foundation Trust. © 2011 Elsevier Ltd.

Learning in 140 characters : microblogging for professional learning

This thesis investigated how microblogging, a form of online social networking, was being employed by educators to support their professional learning. The study found that educators who participate in microblogging engage in a wide range of behaviours, with certain behaviours and activities commonly exhibited. An advantage of microblogging as a professional learning tool is its ability to link educators globally to exchange ideas from different perspectives and to share resources and teaching practices. Educators who microblog have access to relevant and timely learning that is not constrained by time or distance and can be tailored to meet their individual needs.

What factors influence nurses’ assessment practices? Development of the Barriers to Nurses’ use of Physical Assessment Scale

Aim To develop and psychometrically test the Barriers to Nurses’ use of Physical Assessment Scale. Background There is growing evidence of failure to recognise hospitalised patients at risk of clinical deterioration, in part due to inadequate physical assessment by nurses. Yet, little is known about the barriers to nurses’ use of physical assessment in the acute hospital setting and no validated scales have been published. Design Instrument development study. Method Scale development was based on a comprehensive literature review, focus groups, expert review and psychometric evaluation. The scale was administered to 434 acute care registered nurses working at a large Australian teaching hospital between June and July 2013. Psychometric analysis included factor analysis, model fit statistics and reliability testing. Results The final scale was reduced to 38 items representing seven factors, together accounting for 57.7% of the variance: (1) reliance on others and technology, (2) lack of time and interruptions, (3) ward culture, (4) lack of confidence, (5) lack of nursing role models, (6) lack of influence on patient care, and; (7) specialty area. Internal reliability ranged from .70 to .86. Conclusion Findings provide initial evidence for the validity and reliability of the Barriers to Nurses’ use of Physical Assessment Scale and point to the importance of understanding the organisational determinants of nurses’ assessment practices. The new scale has potential clinical and research applications to support nursing assessment in acute care settings.

Posttraumatic stress disorder and traumatic stress : from bench to bedside, from war to disaster

War is a tragic event and its mental health consequences can be profound. Recent studies indicate substantial rates of posttraumatic stress disorder and other behavioral alterations because of war exposure. Understanding the psychological, behavioral, and neurobiological mechanism of mental health and behavioral changes related to war exposure is critical to helping those in need of care. Substantial work to encourage bench to bedside to community knowledge and communication is a core component of addressing this world health need.

PTSD and traumatic stress : from gene to community and bench to bedside

Individuals and communities are exposed to traumatic events, those that are accidents or naturally occurring and those that are intentional or human made. Although resilience is the expected response, for some, posttraumatic stress disorder may be the outcome. Brain models of PTSD require understanding the phenomenology of the disorder and the brain “break down” that occurs. Among several models, importantly, is the perspective that PTSD is a “forgetting” disorder. Other elements in the onset and triggers of PTSD can identify further models to examine at the bench. New studies of the 5-HT2A receptor, the glucocorticoid receptor, p11, mitochondrial genes and cannabinoids are bringing new perspectives to understanding brain function in PTSD. Effective treatments indicate areas for bench research on the mechanisms of the disorder.

Adaptation and change in Queensland’s rangelands : cell grazing as an emerging ideology of pastoral-ecology

Does the current global political economic framework, or more specifically, the cost-price squeeze associated with primary production, restrict the choices of Australian cattle graziers in moving to more sustainable practices? It has often been argued by primary producers and academics, alike, that current terms of trade have resulted in reduced profitability at the property level, and as such, have made it difficult for landholders to shift to practices which are environmentally sustainable. Whilst there is mounting evidence that this is case, there is also evidence that some graziers have been able to adapt to the prevailing market conditions through an ideological as well as ‘practice’ shift. Findings from qualitative research in Central Queensland, Australia has highlighted how ‘cell grazing’ departs from the traditional or conventional aspects of grazing which can be described as productivist, to an approach closely approximating Lang and Heasman’s (2004) ‘ecologically integrated paradigm’. It is argued that cell grazing is, at present, a marginal activity that requires an ideological and cultural shift, as well as an investment in new infrastructure, however, current cell grazing activities may also demonstrate that beef grazing has the potential to be both economically and environmentally sustainable.

Multifunctional agriculture in policy and practice? A comparative analysis of Norway and Australia

Ideals of productivist agriculture in the Western world have faded as the unintended consequences of intensive agriculture and pastoralism have contributed to rural decline and environmental problems. In Norway and Australia, there has been an increasing acceptance of the equal importance of social and environmental sustainability as well as economic sustainability. Alongside this shift is a belief that primary production needs to move away from an intensive, productivist-based agriculture to one that may be defined as post-productivist. In this paper, we argue that the dualism of productivism and post-productivism as concepts on agricultural policy regimes are too simplistic and discuss whether multifunctional agriculture is a better concept for a comparison of rural primary production at two extreme points of the scale, the market-oriented, liberalistic Australian agriculture and the market-protected small-scale Norwegian agriculture. We argue that multifunctionality in Australia rates relatively weakly as an ideology or policy and even less as a discourse or practice and hence is situated toward a ‘weak’ end of a continuum of a level of multifunctional agriculture. In Norwegian agriculture, multifunctional agriculture has thrived within a protectionist setting with the support of the public, the state and agricultural actors. In this sense it is very clearly a policy, practice and discourse that aims to preserve and conserve rural spaces, the cultural landscape, the farming way of life and food safety. Norway is as such situated toward a ‘strong’ end of a continuum of a level of multifunctional agriculture.

Urban Food Security, Urban Resilience and Climate Change

The growing importance of logistics in increasingly globalised production and consumption systems strengthens the case for explicit consideration of the climate risks that may impact on the operation of ports in the future, as well as the formulation of adaptation responses that act to enhance their resilience. Within a logistics chain, seaports are functional nodes of significant strategic importance, and are considered as critical gateways linking local and national supply chains to global markets. However, they are more likely to be exposed to vagaries of climate-related extreme events due to their coastal locations. As such, they need to be adaptive and respond to the projected impacts of climate change, in particular extreme weather events. These impacts are especially important in the logistics context as they could result in varying degrees of business interruption; including business closure in the worst case scenario. Since trans-shipment of freight for both the import and export of goods and raw materials has a significant impact on Australia’s sustained economic growth it was considered important to undertake a study of port functional assets, to assess their vulnerability to climate change, to model the potential impacts of climate-related extreme events, and to highlight possible adaptation responses.

Supermarkets and private standards : unintended consequences of the audit ritual

Recent scholarship has considered the implications of the rise of voluntary private standards in food and the role of private actors in a rapidly evolving, de-facto ‘mandatory’ sphere of governance. Standards are an important element of this globalising private sphere, but are an element that has been relatively peripheral in analyses of power in agri-food systems. Sociological thought has countered orthodox views of standards as simple tools of measurement, instead understanding their function as a governance mechanism that transforms many things, and people, during processes of standardisation. In a case study of the Australian retail supermarket duopoly and the proprietary standards required for market access this paper foregrounds retailers as standard owners and their role in third-party auditing and certification. Interview data from primary research into Australia’s food standards captures the multifaceted role supermarkets play as standard-owners, who are found to impinge on the independence of third-party certification while enforcing rigorous audit practices. We show how standard owners, in attempting to standardize the audit process, generate tensions within certification practices in a unique example of ritualism around audit. In examining standards to understand power in contemporary food governance, it is shown that retailers are drawn beyond standard-setting into certification and enforcement, that is characterized by a web of institutions and actors whose power to influence outcomes is uneven.

The Impacts of Climate Change on Australia’s Food Production and Export

The global food system is undergoing unprecedented change. With population increases, demands for food globally will continue to rise at the same time that agricultural environments are compromised through urban encroachment, climate change and environmental degradation. Australia has long identified itself as an agricultural exporting nation—but what will its capacity be in feeding an increasing global population as it also comes to terms with extreme climatic events such as the floods, fires and droughts, and reduced water availability, experienced in recent decades? This chapter traces the history of Australian agricultural exports and evaluates its food production and export capacity against scientific predictions of climate change impacts. With the federal government forecasting declines in the production of wheat, beef, dairy and sugar, Australia’s key export commodities may well be compromised. Calls to produce more food using new technologies are likely to generate significant environmental problems. Yet, a radical reconfiguration of Australian agriculture which incorporates alternative approaches, such as agro-ecology, is rarely considered by government and industry.

The environmental enigma : why do producers professing stewardship continue to practice poor natural resource management?

Despite a wide acceptance that primary producers in Australia subscribe to a stewardship ethic, land and water degradation remains an ongoing problem. Recent calculations suggest that the economic cost of Australia's environmental degradation is amounting to more than $A3.5 billion a year with an estimated cost of managing (not overcoming) problems of salinity, acidification, soil erosion totalling $A60 billion over the next decade. This paper argues that stewardship itself is an unsatisfactory concept when looking to landholders to respond to environmental problems, for rarely does the attitude of stewardship translate into behaviours of improving natural resource management practices on private land. Whilst there is some acceptance of the environmental problem among primary producers, a number of external constraints may also impede the uptake of conservation-orientated practices. In light of the prevailing accounts of poor adoption of sustainable practices a number of policy options are reviewed in this paper, including formal regional partnerships, regulatory frameworks and market-based measures. It is concluded that the contentious nature of some of these new opportunities for change will mean that any moves aimed at reversing environmental degradation in Australia will be slow.

Climate Change and the Resilience of Commodity Food Production in Australia

The current view of Australian state and national governments about the effects of climate change on agriculture is that farmers – through the adoption of mitigation and adaptation strategies – will remain resilient, and agricultural production will continue to expand. The assumption is that neoliberalism will provide the best ‘free market’ options for climate change mitigation and adaptation in farming. In contrast, we argue that neoliberalism will increase the move towards productivis (‘high-tech’) agriculture – the very system that has caused major environmental damage to the Australian continent. High-tech farming is highly dependent upon access to water and fossil fuels, both of which would appear to be the main limits to production in future decades. Productivist agriculture is a system highly reliant upon fertilizers and fuels that are derived from the petrochemical industry, and are currently increasing in cost as the price of oil increases.