Failure of amino acid homeostasis causes cell death following proteasome inhibition

The ubiquitin-proteasome system targets many cellular proteins for degradation and thereby controls most cellular processes. Although it is well established that proteasome inhibition is lethal, the underlying mechanism is unknown. Here, we show that proteasome inhibition results in a lethal amino acid shortage. In yeast, mammalian cells, and flies, the deleterious consequences of proteasome inhibition are rescued by amino acid supplementation. In all three systems, this rescuing effect occurs without noticeable changes in the levels of proteasome substrates. In mammalian cells, the amino acid scarcity resulting from proteasome inhibition is the signal that causes induction of both the integrated stress response and autophagy, in an unsuccessful attempt to replenish the pool of intracellular amino acids. These results reveal that cells can tolerate protein waste, but not the amino acid scarcity resulting from proteasome inhibition.

Laying equitable claims to rest : key concerns in estate litigation post death

Equitable claims now increasingly arise in Australian estate litigation, particularly in conjunction with family provision applications.

Exploring Australian intensive care physicians clinical judgement during donation after cardiac death : an exploratory qualitative study

BACKGROUND: Donation after Cardiac Death (DCD) is one possible solution to the world wide organ shortage. Intensive care physicians are central to DCD becoming successful since they are responsible for making the clinical judgements and decisions associated with DCD. Yet international evidence shows health care professionals have not embraced DCD and are often reluctant to consider it as an option for patients. PURPOSE: To explore intensive care physicians' clinical judgements when selecting a suitable DCD candidate. METHODS: Using interpretative exploratory methods six intensive care physicians were interviewed from three hospital sites in Australia. Following verbatim transcription, data was subjected to thematic analysis. FINDINGS: Three distinct themes emerged. Reducing harm and increasing benefit was a major focus of intensive care physicians during determination of DCD. There was an acceptance of DCD if there was clear evidence that donation was what the patient and family wanted. Characteristics of a defensible decision reflected the characteristics of sequencing, separation and isolation, timing, consensus and collaboration, trust and communication to ensure that judgements were robust and defensible. The final theme revealed the importance of minimising uncertainty and discomfort when predicting length of survival following withdrawal of life-sustaining treatment. CONCLUSION: DCD decisions are made within an environment of uncertainty due to the imprecision associated with predicting time of death. Lack of certainty contributed to the cautious and collaborative strategies used by intensive care physicians when dealing with patients, family members and colleagues around end-of-life decisions, initiation of withdrawal of life-sustaining treatment and the discussion about DCD. This study recommends that nationally consistent policies are urgently needed to increase the degree of certainty for intensive care staff concerning the DCD processes.

Exploring the re-criminalising of OHS breaches in the context of industrial death

Since the 1980s the calls for further criminalisation of organisational conduct causing harm to workers, the public and the environment have intensified in Australia, Canada and England and Wales.' One focal point of this movement has been the criminal law's response to organisations (and their personnel) failing to comply with occupational health and safety ('OHS') standards, particularly when physical harm (death and serious injury) has resulted from those breaches. Some governments have responded with proposals to enable manslaughter prosecutions to be initiated 'more effectively' against organisations causing the deaths of workers or, in some cases, members of the public (Archibald et al, 2004; Haines and Hall, 2004; Hall et al, 2004; Tombs and Whyte, 2003). In Australia governments have also increased monetary penalties for regulatory OHS offences, a few have introduced other contemporary organisational sanctions, and some have initiated OHS prosecutions more vigorously and with larger fines.

The seconds that separated life and death

WHEN the water in the living room of Steven and Sandra Matthews's home reached ankle deep on Monday, they began to discuss how to save their furniture...

Women who cheated death thank their saviours

"Two women who survived the Murphys Creek flood have thanked the passers-by who hauedl them from the maelstrom."

Child's body in tree adds to Lockyer Valley death toll

"Two more bodies, including a that of child discovered in a tree, were retrieved in the Lockyer Valley at the weekend, reinforcing the grisly complexity of the search for the missing."

Suicide, statistics and the coroner: A comparative study of death investigations

Australia has a significantly higher suicide rate than England. Rather than accepting that this ‘statistical fact’ is a direct reflection of some positivist truth, this paper begins with the premise that how suicide is counted depends upon what counts as suicide. This study involves semi-structured interviews with coroners both in Australia and England, as well as observations at inquests. Important differences between the two coronial systems include: first, quite different logics of operation; second, the burden of proof for reaching a finding of suicide is significantly higher in England; and third, the presence of family members at English inquests results in far greater pressure being brought to bear upon coroners. These combined factors result in a reduced likelihood of English coroners reaching a finding of suicide. The conclusions are twofold. First, this research supports existing criticisms of comparative suicide statistics. Second, this research adds theoretical weight to criticisms of positivist analyses of social phenomena.

Improving treatment for obese women with early stage cancer of the uterus : rationale and design of the levonorgestrel intrauterine device ±Metformin ±weight loss in endometrial cancer (feMME) trial

Purpose Endometrial adenocarcinoma (EC) is the most common gynaecologic cancer. Up to 90% of EC patients are obese which poses a health threat to patients post-treatment. Standard treatment for EC includes hysterectomy, although this has significant side effects for obese women at high risk of surgical complications and for women of childbearing age. This trial investigates the effectiveness of non-surgical or conservative treatment options for obese women with early stage EC. The primary aim is to determine the efficacy of: levonorgestrel intrauterine device (LNG-IUD); with or without metformin (an antidiabetic drug); and with or without a weight loss intervention to achieve a pathological complete response (pCR) in EC at six months from study treatment initiation. The secondary aim is to enhance understanding of the molecular processes and to predict a treatment response by investigating EC biomarkers. Methods An open label, three-armed, randomised, phase-II, multi-centre trial of LNG-IUD ± metformin ± weight loss intervention. 165 participants from 28 centres are randomly assigned in a 3:3:5 ratio to the treatment arms. Clinical, quality of life and health behavioural data will be collected at baseline, six weeks, three and six months. EC biomarkers will be assessed at baseline, three and six months. Conclusions There is limited prospective evidence for conservative treatment for EC. Trial results could benefit patients and reduce health system costs through a reduction in hospitalisations and through lower incidence of adverse events currently observed with standard treatment.

Making scenes : Reggae, punk, and death metal in 1990s Bali

In 1996, Emma Baulch went to live in Bali to do research on youth culture. Her chats with young people led her to an enormously popular regular outdoor show dominated by local reggae, punk, and death metal bands. In this rich ethnography, she takes readers inside each scene: hanging out in the death metal scene among unemployed university graduates clad in black T-shirts and ragged jeans; in the punk scene among young men sporting mohawks, leather jackets, and hefty jackboots; and among the remnants of the local reggae scene in Kuta Beach, the island’s most renowned tourist area. Baulch tracks how each music scene arrived and grew in Bali, looking at such influences as the global extreme metal underground, MTV Asia, and the internationalization of Indonesia’s music industry. Making Scenes is an exploration of the subtle politics of identity that took place within and among these scenes throughout the course of the 1990s. Participants in the different scenes often explained their interest in death metal, punk, or reggae in relation to broader ideas about what it meant to be Balinese, which reflected views about Bali’s tourism industry and the cultural dominance of Jakarta, Indonesia’s capital and largest city. Through dance, dress, claims to public spaces, and onstage performances, participants and enthusiasts reworked “Balinese-ness” by synthesizing global media, ideas of national belonging, and local identity politics. Making Scenes chronicles the creation of subcultures at a historical moment when media globalization and the gradual demise of the authoritarian Suharto regime coincided with revitalized, essentialist formulations of the Balinese self.

Epistemological lens : birth, death and ecology of documentary practices

This paper considers the epistemological life cycle of the camera lens in documentary practices. The 19th century industrial economies that manufactured and commercialised the camera lens have engendered political and economic contingencies on documentary practices to sustain a hegemonic and singular interpretive epistemology. Colonial documentary practices are considered from the viewpoint of manipulative hegemonic practices - all of which use the interpretive epistemology of the camera lens to capitalise a viewpoint which is singular and possesses the power to sustain its own status and economic privilege. I suggest that decolonising documentary practices can be nurtured in what Boaventura de Sousa Santos proposes as an 'ecology of knowledges' (Andreotti, Ahenakew, & Cooper 2011) - a way of including the epistemologies of cultures beyond the 'abyssal' (Santos), outside the limits of epistemological dominance. If an 'epistemicide' (Santos) of indigenous knowledges in the dominant limits has occurred then in an ecology of knowledges the limits become limitless and what were once invisible knowledges, come into their own ontological and epistemological being: as free agents and on their own terms. In an ecology of knowledges, ignorance and blindness may still exist but are not privileged. The decolonisation of documentary practices inevitably destabilises prevailing historicities and initiates ways for equal privilege to exist between multiple epistemologies.