Malta's 'push back' stand-off: what can Australia learn?

Malta has become the latest country to try to “push back” asylum seekers, implementing a policy similar to that being advocated by the Coalition as its “Real Solution” to the phenomenon of boats arriving on Australian shores.In policies reminiscent of Australia, the Maltese government is scrambling to appear tough on migration and depict the arrival of asylum seekers as a crisis that warrants a security response

The systemic response to topical Aldara treatment is mediated through direct TLR7 stimulation as Imiquimod enters the circulation

Topical application of Aldara cream, containing the Toll-like receptor 7/8 agonist Imiquimod, is a widely used mouse model for investigating the pathogenesis of psoriasis. We have previously used this model to study the effects of peripheral inflammation on the brain, and reported a brain-specific response characterised by increased transcription, infiltration of immune cells and anhedonic-like behavior. Here, we perform a more robust characterisation of the systemic response to Aldara application and find a potent but transient response in the periphery, followed by a prolonged response in the brain. Mass spectrometry analysis of plasma and brain samples identified significant levels of Imiquimod in both compartments at molar concentrations likely to evoke a biological response. Indeed, the association of Imiquimod with the brain correlated with increased Iba1 and GFAP staining, indicative of microglia and astrocyte reactivity. These results highlight the potency of this model and raise the question of how useful it is for interpreting the systemic response in psoriasis-like skin inflammation. In addition, the potential impact on the brain should be considered with regards to human use and may explain why fatigue, headaches and nervousness have been reported as side effects following prolonged Aldara use

Peripheral inflammation is associated with remote global gene expression changes in the brain

Background: Although the central nervous system (CNS) was once considered an immunologically privileged site, in recent years it has become increasingly evident that cross talk between the immune system and the CNS does occur. As a result, patients with chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease or psoriasis, are often further burdened with neuropsychiatric symptoms, such as depression, anxiety and fatigue. Despite the recent advances in our understanding of neuroimmune communication pathways, the precise effect of peripheral immune activation on neural circuitry remains unclear. Utilizing transcriptomics in a well-characterized murine model of systemic inflammation, we have started to investigate the molecular mechanisms by which inflammation originating in the periphery can induce transcriptional modulation in the brain.<p></p> Methods: Several different systemic and tissue-specific models of peripheral toll-like-receptor-(TLR)-driven (lipopolysaccharide (LPS), lipoteichoic acid and Imiquimod) and sterile (tumour necrosis factor (TNF) and 12-O-tetradecanoylphorbol-13-acetate (TPA)) inflammation were induced in C57BL/6 mice. Whole brain transcriptional profiles were assessed and compared 48 hours after intraperitoneal injection of lipopolysaccharide or vehicle, using Affymetrix GeneChip microarrays. Target gene induction, identified by microarray analysis, was validated independently using qPCR. Expression of the same panel of target genes was then investigated in a number of sterile and other TLR-dependent models of peripheral inflammation.<p></p> Results: Microarray analysis of whole brains collected 48 hr after LPS challenge revealed increased transcription of a range of interferon-stimulated genes (ISGs) in the brain. In addition to acute LPS challenge, ISGs were induced in the brain following both chronic LPS-induced systemic inflammation and Imiquimod-induced skin inflammation. Unique to the brain, this transcriptional response is indicative of peripherally triggered, interferon-mediated CNS inflammation. Similar models of sterile inflammation and lipoteichoic-acid-induced systemic inflammation did not share the capacity to trigger ISG induction in the brain.<p></p> Conclusions: These data highlight ISG induction in the brain as being a consequence of a TLR-induced type I interferon response. As considerable evidence links type I interferons to psychiatric disorders, we hypothesize that interferon production in the brain could represent an important mechanism, linking peripheral TLR-induced inflammation with behavioural changes.<p></p&gt

Using legislation to teach Indigenous cultural competence in an introductory law subject

Embedding Indigenous cultural competence into law curriculum at universities is an important project that recognises the place of Aboriginal and Torres Strait Islander peoples as the custodians of one of the oldest continuing cultural traditions in the world.1 It is a critical responsibility of higher education institutions, particularly law schools, to lead social change in this area for several reasons. First, it pays respect to Elders as the guardians of Indigenous knowledges and fosters collaboration between Aboriginal and Torres Strait Islander staff, students and communities. Second, incorporating Indigenous cultures, histories and contemporary social realities into law curriculum necessitates critical reflection on the role of the legal profession and the law in driving policies and practices of colonisation, many of them harmful, that continue to resonate widely in a contemporary setting. Third, producing law graduates who are culturally competent fulfills the overarching mission of law schools in Australia that are committed to the 'rule of law, and the promotion of the highest standards of ethical conduct, professional responsibility, and community service'.2 This mission ought to extend to being committed to enhancing cultural safety for staff and students, and to valuing the richness of cultural diversity. Finally, embedding cultural competence provides opportunities for students to benefit from authentic learning experiences that recognise and celebrate the unique nature of Indigenous knowledges and the strength and resilience of Aboriginal and Torres Strait Islander peoples

Robodeport or Surveillance Fantasy?:How automated is automatic visa cancellation in Australia?

Australia has been widely condemned for its harsh and comprehensive external border controls that seek to control the inward mobility of would-be asylum seekers through visa denial, interdiction and offshore detention. Less widely discussed is the fact that internal controls have been repeatedly ramped up over the past two decades. This includes the administrative removal of lawfully-present non-citizens following visa cancellation on character grounds under s501 of the Migration Act 1958 (Cth). Automatic visa cancellation was introduced in 2014 for non-citizens sentenced to a prison term of 12 months or more, or for certain offences, bypassing individualised decision-making and raising the spectre of a visa cancellation pipeline feeding a highly automated deportation machinery. In an age of increasingly automated forms of governance, a key question that arises is the role that has been played by automated systems in achieving what has been a seismic shift in practice, and the normative implications of any developments towards automation within the visa cancellation and removal systems. This paper outlines this shift towards automation in other systems of governance in Australia – most notably the notorious Robodebt scheme – before examining automation in Australia’s visa cancellation system. Documentary analysis of recent parliamentary inquiries, independent reports and government policy is used to piece together the development of inter-agency data exchange practices and automation over three specific periods - historical practice pre-2014, post-2014 to the present, and proposed future developments. We conclude that Australia’s s501 visa cancellation system is neither automated nor automatic. Rather, the 2014 law reform gave rise to a ‘surveillance fantasy’ with immense consequences for non-citizens, particularly those who face long days in immigration detention at the conclusion of their prison sentence. We show that while concerns about increasing automation are well-founded, systems based on less sophisticated forms of information handling and reliant on human decision-making nevertheless continue to raise age-old questions concerning efficiency, accuracy and fairness

Sustained exposure to systemic endotoxin triggers chemokine induction in the brain followed by a rapid influx of leukocytes

Background: Recent years have seen an explosion of research pertaining to biological psychiatry, yet despite subsequent advances in our understanding of neuroimmune communication pathways, how the brain senses and responds to peripheral inflammation remains poorly understood. A better understanding of these pathways may be important for generating novel therapeutics to treat many patients with chronic inflammatory diseases who also suffer from neuropsychiatric comorbidities. Here we have systematically assessed the leukocyte infiltrate to the brain following systemic endotoxin exposure to better understand this novel route of neuroimmune communication. Methods: Mice were injected intraperitoneally with LPS daily for 2, 5 or 7 consecutive days. We systematically interrogated the subsequent induction of chemokine transcription in the brain using TaqMan low-density arrays. A combination of flow cytometry and immunohistochemistry was then used to characterise the accompanying leukocyte infiltrate Result: Repeated LPS challenges resulted in prolonged activation of brain-resident microglia, coupled with an increased local transcription of numerous chemokines. After 2 days of administering LPS, there was a marked increase in the expression of the neutrophil chemoattractants CXCL1 and CXCL2; the monocyte chemoattractants CCL2, CCL5, CCL7 and CCL8; and the lymphocyte chemoattractants CXCL9, CXCL10 and CXCL16. In a number of cases, this response was sustained for several days. Chemokine induction was associated with a transient recruitment of neutrophils and monocytes to the brain, coupled with a sustained accumulation of macrophages, CD8+ T cells, NK cells and NKT cells. Strikingly, neutrophils, monocytes and T cells appeared to extravasate from the vasculature and/or CSF to infiltrate the brain parenchyma. Conclusions: Prolonged exposure to a peripheral inflammatory stimulus triggers the recruitment of myeloid cells and lymphocytes to the brain. By altering the inflammatory or metabolic milieu of the brain, this novel method of immune-to-brain communication may have profound implications for patients with chronic inflammatory diseases, potentially leading to neuropsychiatric comorbidities

Plain Tobacco Packaging: A Systematic Review

(From the Executive Summary): This systematic review outlines findings from 37 studies that provide evidence of the impacts of plain tobacco packaging. The review was conducted following the publication of the March 2011 White Paper Healthy Lives: Healthy People which set out a renewed Tobacco Control Plan for England. One of the key actions identified in the plan was to consult on possible options to reduce the promotional impact of tobacco packaging, including plain packaging. This systematic review was commissioned to provide a comprehensive overview of evidence on the impact of plain packaging in order to inform a public consultation on the issue

One Step Beyond: Is the Public Sector Ready to Let Go of Budgeting?

There have been numerous attempts at reforming public sector budgeting in recent years, with most of these attempting to improve efficiency and effectiveness by switching emphasis from inputs to outputs and outcomes. However, proponents of Beyond Budgeting claim the problems associated with traditional budgeting systems are such that the solution is not to reform budgeting, but to abandon it in its traditional form entirely, advocating the need for a more flexible approach based on the principals of devolved managerial responsibility and adaptive management process. Before attempting to implement such a fundamental change in approach it is necessary to determine firstly, whether the organisation is dissatisfied with the current budget system, secondly, the extent to which the organisation is currently working according to beyond budgeting principles or has the structures and systems capable of supporting the beyond budgeting philosophy, and finally, the extent to which the organisation would be in a position to satisfy the preconditions needed for the successful implementation of beyond budgeting. The focus of this study is to review the current position of a sample of Irish Local Authorities in respect of these three questions. The research targeted twenty two senior and front line managers in three different types of authority using data gathered in the field by means of a structured questionnaire and a series of semistructured interviews administered in tandem. The results suggest considerable dissatisfaction with the current budget process suggesting that it is time consuming , out of touch with reality and largely incremental , but indicate that the structures and systems currently in place in this area of the public sector are not yet conducive to the introduction of an approach based on Beyond Budgeting principals. The research indicates that the biggest obstacle to the introduction of these changes may be a lack of commitment to change and the unwillingness of management and in particular, the finance function, to loosen central control over the budget process

6-OHDA generated ROS induces DNA damage and p53- and PUMA-dependent cell death

<p>Abstract</p> <p>Background</p> <p>Parkinson's disease (PD) is characterized by the selective loss of dopaminergic neurons in the substantia nigra (SN), resulting in tremor, rigidity, and bradykinesia. Although the etiology is unknown, insight into the disease process comes from the dopamine (DA) derivative, 6-hydroxydopamine (6-OHDA), which produces PD-like symptoms. Studies show that 6-OHDA activates stress pathways, such as the unfolded protein response (UPR), triggers mitochondrial release of cytochrome-c, and activates caspases, such as caspase-3. Because the BH3-only protein, Puma (p53-upregulated mediator of apoptosis), is activated in response to UPR, it is thought to be a link between cell stress and apoptosis.</p> <p>Results</p> <p>To test the hypothesis that Puma serves such a role in 6-OHDA-mediated cell death, we compared the response of dopaminergic neurons from wild-type and <it>Puma</it>-null mice to 6-OHDA. Results indicate that Puma is required for 6-OHDA-induced cell death, in primary dissociated midbrain cultures as well as <it>in vivo</it>. In these cultures, 6-OHDA-induced DNA damage and p53 were required for 6-OHDA-induced cell death. In contrast, while 6-OHDA led to upregulation of UPR markers, loss of ATF3 did not protect against 6-OHDA.</p> <p>Conclusions</p> <p>Together, our results indicate that 6-OHDA-induced upregulation of <it>Puma </it>and cell death are independent of UPR. Instead, p53 and DNA damage repair pathways mediate 6-OHDA-induced toxicity.</p