Perspectives on the effectiveness of the late night liquor trading lockout legislative provision

The effectiveness of ‘the lockout policy’ integrated within a broader police enforcement strategy to reduce alcohol-related harm, in and around late-night licensed premises, in major drinking precincts was examined. First response operational police (n= 280) recorded all alcohol and non alcohol-related incidents they attended in and around late-night liquor trading premises. A before and after study design was used, with police completing modified activity logs prior to and following the introduction of the lockout policy in two policing regions: Gold Coast (n = 12,801 incidents); Brisbane City/Fortitude Valley (n = 9,117 incidents). Qualitative information from key stakeholders (e.g., Police, Security Staff & Politicians n = 20) was also obtained. The number of alcohol-related offences requiring police attention was significantly reduced in some policing areas and for some types of offences (e.g., sex offences, street disturbances, traffic incidents. However, there was no variation for a number of other offence categories (e.g., assault). Interviews with licensees revealed that although all were initially opposed to the lockout policy, most perceived benefits from its introduction. This study was the first of its kind to comprehensively examine the impact of a lockout policy and provides supportive evidence for the effectiveness of the lockout policy as integrating positively with police enforcement to enhance public safety in some areas in and around late-night liquor trading premises.

Broadening of transgenic adenocarcinoma of the mouse prostate (TRAMP) model to represent late stage androgen depletion independent cancer

BACKGROUND The transgenic adenocarcinoma of the mouse prostate (TRAMP) model closely mimics PC-progression as it occurs in humans. However, the timing of disease incidence and progression (especially late stage) makes it logistically difficult to conduct experiments synchronously and economically. The development and characterization of androgen depletion independent (ADI) TRAMP sublines are reported. METHODS Sublines were derived from androgen-sensitive TRAMP-C1 and TRAMP-C2 cell lines by androgen deprivation in vitro and in vivo. Epithelial origin (cytokeratin) and expression of late stage biomarkers (E-cadherin and KAI-1) were evaluated using immunohistochemistry. Androgen receptor (AR) status was assessed through quantitative real time PCR, Western blotting, and immunohistochemistry. Coexpression of AR and E-cadherin was also evaluated. Clonogenicity and invasive potential were measured by soft agar and matrigel invasion assays. Proliferation/survival of sublines in response to androgen was assessed by WST-1 assay. In vivo growth of subcutaneous tumors was assessed in castrated and sham-castrated C57BL/6 mice. RESULTS The sublines were epithelial and displayed ADI in vitro and in vivo. Compared to the parental lines, these showed (1) significantly faster growth rates in vitro and in vivo independent of androgen depletion, (2) greater tumorigenic, and invasive potential in vitro. All showed substantial downregulation in expression levels of tumor suppressor, E-cadherin, and metastatis suppressor, KAI-1. Interestingly, the percentage of cells expressing AR with downregulated E-cadherin was higher in ADI cells, suggesting a possible interaction between the two pathways. CONCLUSIONS The TRAMP model now encompasses ADI sublines potentially representing different phenotypes with increased tumorigenicity and invasiveness.

Chronological age and age-related cognitive deficits are associated with an increase in multiple types of driving errors in late life

Objective: Older driver research has mostly focused on identifying that small proportion of older drivers who are unsafe. Little is known about how normal cognitive changes in aging affect driving in the wider population of adults who drive regularly. We evaluated the association of cognitive function and age, with driving errors. Method: A sample of 266 drivers aged 70 to 88 years were assessed on abilities that decline in normal aging (visual attention, processing speed, inhibition, reaction time, task switching) and the UFOV® which is a validated screening instrument for older drivers. Participants completed an on-road driving test. Generalized linear models were used to estimate the associations of cognitive factor with specific driving errors and number of errors in self-directed and instructor navigated conditions. Results: All errors types increased with chronological age. Reaction time was not associated with driving errors in multivariate analyses. A cognitive factor measuring Speeded Selective Attention and Switching was uniquely associated with the most errors types. The UFOV predicted blindspot errors and errors on dual carriageways. After adjusting for age, education and gender the cognitive factors explained 7% of variance in the total number of errors in the instructor navigated condition and 4% of variance in the self-navigated condition. Conclusion: We conclude that among older drivers errors increase with age and are associated with speeded selective attention particularly when that requires attending to the stimuli in the periphery of the visual field, task switching, errors inhibiting responses and visual discrimination. These abilities should be the target of cognitive training.

Visual acuity is not what it seems : on Ian Burn's 'Late' reflections

A whole tradition is said to be based on the hierarchical distinction between the perceptual and conceptual. In art, Niklas Luhmann argues, this schism is played out and repeated in conceptual art. This paper complicates this depiction by examining Ian Burn's last writings in which I argue the artist-writer reviews the challenge of minimal-conceptual art in terms of its perceptual pre-occupations. Burn revisits his own work and the legacy of minimal-conceptual by moving away from the kind of ideology critique he is best known for internationally in order to reassert the long overlooked visual-perceptual preoccupations of the conceptual in art.

The rest flies down the wind : complexities of late style in the work of Christina Stead

Examining the late style of a writer is like skirting around quicksand. End-of-career reflection can subvert long standing critical accounts; revisionist publishing histories or newly minted archival work can do likewise. And, as Nancy J. Troy suggests, an artist’s last thoughts are rarely planned as such (15). In the case of Christina Stead any consideration of late style is made more difficult because, chronologically speaking, her ‘late’ works were written some 20 years before her death in 1983. Thus chronology can be deceptive, as Nicholas Delbanco points out in Lastingness: The Art of Old Age. Stead’s last novel, I’m Dying Laughing The Humourist, was completed, at least in rough draft form in 1966, when Stead was 64, but friends and readers suggested many changes. The book was published posthumously in 1986. Stead’s work is receiving increasing critical attention so a discussion of her ‘late style’ is important, particularly given that her fiction seems to refuse so many attempts at category-making. This perspective reveals two interesting aspects of her late work: first her consistent engagement with the problems of age for women, and in particular women writers, and second, the consequence of a life-long attention to the representation of dialogic sound in her novels, a preoccupation that results in what can be termed an aural signature. My discussion refers to Edward Said’s and Nicholas Delbanco’s ideas about late style by way of a focus on selective biographical issues and Stead’s engagement with radical politics before moving to an examination of what can be called an aural signature in several novels. Her fiction demonstrates one of the agreed markers of late style: she was constantly looking forward and looking back through innovation in form and content.

Syntaxin 11 binds Vti1b and regulates late endosome to lysosome fusion in macrophages

Syntaxin 11 (Stx11) is a SNARE protein enriched in cells of the immune system. Loss or mutation of Stx11 results in familial hemophagocytic lymphohistiocytosis type-4 (FHL-4), an autosomal recessive disorder of immune dysregulation characterized by high levels of inflammatory cytokines along with defects in T-cell and natural killer cell function. We show here Stx11 is located on endosomalmembranes including late endosomes and lysosomes in macrophages. While Stx11 did not form a typical trans-SNARE complex, it did bind to the Q-SNARE Vti1b and was able to regulate the availability of Vti1b to form the Q-SNARE complexes Stx6/Stx7/Vtib and Stx7/Stx8/Vti1b. The mutant form of Stx11 sequestered Vti1b from forming the Q-SNARE complex that mediates late endosome to lysosome fusion. Depletion of Stx11 in activated macrophages leads to an accumulation of enlarged late endocytic compartments, increased trafficking to the cell surface and inhibition of late endosome to lysosome fusion. These phenotypes arerescued by the expression of an siRNA-resistant Stx11 construct in Stx11-depleted cells. Our results suggest that by regulating the availability of Vti1b, Stx11 regulates trafficking steps between late endosomes, lysosomes and the cell surface in macrophages.

Flightless, secreted through a late endosome/lysosome pathway, binds LPS and dampens cytokine secretion.

Flightless (Flii) is upregulated in response to wounding and has been shown to function in wound closure and scarring. In macrophages intracellular Flii negatively modulates TLR signalling and dampens cytokine production. We now show that Flii is constitutively secreted from macrophages and fibroblasts and is present in human plasma. Secretion from fibroblasts is upregulated in response to scratch wounding and LPS-activated macrophages also temporally upregulate their secretion of Flii. Using siRNA, wild-type and mutant proteins we show that Flii is secreted via a late endosomal/lysosomal pathway that is regulated by Rab7 and Stx11. Flii contains 11 leucine rich repeat (LRR) domains in its N-terminus that have nearly 50% similarity to those in the extracellular pathogen binding portion of Toll-like receptor 4 (TLR4). We show secreted Flii can also bind LPS and has the ability to alter macrophage activation. LPS activation of macrophages in Flii depleted conditioned media leads to enhanced macrophage activation and increased TNF secretion compared to cells activated in the presence of Flii. These results show secreted Flii binds to LPS and in doing so alters macrophage activation and cytokine secretion, suggesting that like the intracellular pool of Flii, secreted Flii also has the ability to alter inflammation.