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Macrophages are tissue resident innate phagocytic cells that take on contrasting phenotypes, or polarization states, in response to the changing combination of microbial and cytokine signals at sites of infection. During the opening stages of an infection, macrophages adopt the proinflammatory, highly antimicrobial M1 state, later shifting to an anti-inflammatory, pro-tissue repair M2 state as the infection resolves. The changes in gene expression underlying these transitions are primarily governed by nuclear factor kappaB (NF-kB), Janus kinase (JAK)/signal transducer and activation of transcription (STAT), and hypoxia-inducible factor 1 (HIF1) transcription factors, the activity of which must be carefully controlled to ensure an effective yet spatially and temporally restricted inflammatory response. While much of this control is provided by pathway-specific feedback loops, recent work has shown that the transcriptional co-regulators of the CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxy-terminal domain (CITED) family serve as common controllers for these pathways. In this review, we describe how CITED proteins regulate polarization-associated gene expression changes by controlling the ability of transcription factors to form chromatin complexes with the histone acetyltransferase, CBP/p300. We will also cover how differences in the interactions between CITED1 and 2 with CBP/p300 drive their contrasting effects on pro-inflammatory gene expression. [ABSTRACT FROM AUTHOR]

Bare v Independent Broad-Based Anti-Corruption Commission is a landmark in the history of Victoria's Charter of Human Rights and Responsibilities. The Court of Appeal's recent decision has significant implications for future litigation under the Charter. First, while not binding on this point, Bare considered in detail whether a breach of s 38(1) of the Charter by a public authority constitutes a jurisdictional error. Second, the Court adopted a cautious approach to the use of international law to construe the scope of Charter rights. This departs from previous Charter case law. Third, Bare demonstrates the Charter's power to have a normative influence on the behaviour of public authorities, by requiring them to give proper consideration to human rights. Finally, Bare illustrates how the Administrative Law Act 1978 (Vic) augments the Charter's power as a human rights instrument., CONTENTS I Introduction II Facts III Key Charter Issues on Appeal IV The Jurisdictional Error Issue A Background B Warren CJ's Reasoning C Tate JA and Santamaria JA's Reasoning D [...]

Macrophages serve as a first line of defense against microbial pathogens. Exposure to interferon-γ (IFNγ) increases interferonstimulated gene (ISG) expression in these cells, resulting in enhanced antimicrobial and proinflammatory activity. Although this response must be sufficiently vigorous to ensure the successful clearance of pathogens, it must also be carefully regulated to prevent tissue damage. This is controlled in part by CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2), a transcriptional coregulator that limits ISG expression by inhibiting STAT1 and IRF1. Here, we show that the closely related Cited1 is an ISG, which is expressed in a STAT1-dependent manner, and that IFNγ stimulates the nuclear accumulation of CITED1 protein. In contrast to CITED2, ectopic CITED1 enhanced the expression of a subset of ISGs, including Ccl2, Ifit3b, Isg15 and Oas2. This effect was reversed in a Cited1-null cell line produced by CRISPR-based genomic editing. Collectively, these data show that CITED1 maintains proinflammatory gene expression during periods of prolonged IFNγ exposure and suggest that there is an antagonistic relationship between CITED proteins in the regulation of macrophage inflammatory function. [ABSTRACT FROM AUTHOR]

This paper considers legal contestation in the UK as a source of useful reflections for AI policy. The government has published a 'National AI Strategy', but it is unclear how effective this will be given doubts about levels of public trust. One key concern is the UK's apparent 'side-lining' of the law. A series of events were convened to investigate critical legal perspectives on the issues, culminating in an expert workshop addressing five sectors. Participants discussed AI in the context of wider trends towards automated decision-making (ADM). A recent proliferation in legal actions is expected to continue. The discussions illuminated the various ways in which individual examples connect systematically to developments in governance and broader 'AI-related decision-making', particularly due to chronic problems with transparency and awareness. This provides a fresh and current insight into the perspectives of key groups advancing criticisms relevant to policy in this area. Policymakers' neglect of the law and legal processes is contributing to quality issues with recent practical ADM implementation in the UK. Strong signals are now required to switch back from the vicious cycle of increasing mistrust to an approach capable of generating public trust. Suggestions are summarised for consideration by policymakers. [ABSTRACT FROM AUTHOR]

The UK has recently adopted a policy of granting digital-only proof of immigration status for certain groups of migrants. More than 4.5 million individuals are reliant on this form of status and the number is growing. In this paper, we argue that this policy, as currently operationalised, is unlawful as a result of its discriminatory impact. If it remains unchanged, the roots of digital discrimination in immigration policy and administration will be allowed to spread, with potentially disastrous consequences. [ABSTRACT FROM AUTHOR]

Our review of the authorities establishes that the courts are recognising a clear presumption that the government ought to disclose the models it uses to make decisions. Broadly speaking, the government must disclose enough information to enable those potentially affected by a model to regulate their conduct accordingly and meaningfully challenge (and the courts to meaningfully assess) the lawfulness of government decisions. If the presumption otherwise requires the government to disclose a model, however, the courts will be very slow to allow administrative considerations to stand in the way.[75] In relation to confidentiality, the government must overcome several hurdles. [Extracted from the article]

If a teacher abuses a student, is the school authority liable in damages to the student? Over the past 20 years, courts in Australia and England have invariably treated this as a question of vicarious liability. In this article, I argue that this approach is wrong and disruptive of the principled development of the law of torts. In cases of institutional child abuse, breach of a non-delegable duty of care is the more appropriate ground of liability. The prevailing approach in Australia and England reflects a continuing confusion about and between these two quite distinct forms of liability. This confusion has meant that, in Australia, abuse victims have been denied compensation while, in England, the doctrine of vicarious liability has had to be seriously distorted in order to provide a remedy. [ABSTRACT FROM AUTHOR]

Bare v Independent Broad-Based Anti-Corruption Commission is a landmark in the history of Victoria's Charter of Human Rights and Responsibilities. The Court of Appeal's recent decision has significant implications for future litigation under the Charter. First, while not binding on this point, Bare considered in detail whether a breach of s 38(1) of the Charter by a public authority constitutes a jurisdictional error. Second, the Court adopted a cautious approach to the use of international law to construe the scope of Charter rights. This departs from previous Charter case law. Third, Bare demonstrates the Charter's power to have a normative influence on the behaviour of public authorities, by requiring them to give proper consideration to human rights. Finally, Bare illustrates how the Administrative Law Act 1978 (Vic) augments the Charter's power as a human rights instrument. [ABSTRACT FROM AUTHOR]