Chancellery Research - Research Publications

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    Ocular and Systemic Factors Affecting Laser Speckle Flowgraphy Measurements in the Optic Nerve Head
    Turpin, A ; McKendrick, AM (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2021-01-01)
    Purpose: To investigate the ocular and systemic factors related to glaucoma and to be adjusted for interindividual comparison of ocular blood flow measurement results by laser speckle flowgraphy (LSFG) obtained from the optic nerve head (ONH) in normal Japanese individuals. Methods: A multicenter, prospective cross-sectional study was conducted. The ONH tissue-area and vessel-area mean blur rate (MT and MV) were evaluated using LSFG and ONH structural parameters using planimetric methods. Multivariate linear mixed-effects modeled regression analysis was used to identify the contributing factors to the MT and MV. The explanatory variables were age; gender; smoking history; body mass index; mean arterial pressure (MAP); heart rate; intraocular pressure; axial length (AL); disc, rim, cup, and β-peripapillary atrophy (β-PPA) areas; and central retinal artery and vein equivalents. Results: In total, 195 eyes of 126 healthy individuals with an average age of 48.1 years were included. Multivariate analysis showed that MAP and disc area had a negative (P < 0.001) correlation, whereas β-PPA area had a positive correlation with MT (P = 0.010). Age and AL had a negative correlation (P = 0.001 and P = 0.011, respectively), whereas cup area had a positive correlation (P = 0.012) with MV. Conclusions: Interindividual comparison of MT or MV must be adjusted for both systemic factors (blood pressure or age) and local ocular factors (AL and disc, cup, or β-PPA area). Translational Relevance: Our results provided reference data on the LSFG measurement and are important in comparing ocular blood flow between individuals using LSFG.
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    When proxy-driven learning is no better than random: The consequences of representational incompleteness.
    Zobel, J ; Vázquez-Abad, FJ ; Lin, P ; Gu, Q (Public Library of Science (PLoS), 2022)
    Machine learning is widely used for personalisation, that is, to tune systems with the aim of adapting their behaviour to the responses of humans. This tuning relies on quantified features that capture the human actions, and also on objective functions-that is, proxies - that are intended to represent desirable outcomes. However, a learning system's representation of the world can be incomplete or insufficiently rich, for example if users' decisions are based on properties of which the system is unaware. Moreover, the incompleteness of proxies can be argued to be an intrinsic property of computational systems, as they are based on literal representations of human actions rather than on the human actions themselves; this problem is distinct from the usual aspects of bias that are examined in machine learning literature. We use mathematical analysis and simulations of a reinforcement-learning case study to demonstrate that incompleteness of representation can, first, lead to learning that is no better than random; and second, means that the learning system can be inherently unaware that it is failing. This result has implications for the limits and applications of machine learning systems in human domains.
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    Affective enactments of class: attuning to events, practice, capacity
    Mulcahy, D ; Martinussen, M (ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD, 2022-05-06)
    Based on empirical research with working-class students studying in Australian universities, this article frames class as a structuring relation, but also as a series of affective events, through which we emphasise capacities. Putting the concept of class in conversation with two analytics of affect, we show how class is a relational site of struggle in which subjectivities and socio-material arrangements come together to produce emergent yet patterned effects. Lines of inquiry are opened up that go beyond the reproduction of inequalities, which tends to command attention in customary critical class analysis. Class struggle is enacted via events of an affective-discursive-material kind that constrain and capacitate. While working-class identifications are normatively devalued, working-class students hold on to them, enacting classed subjectivities affirmatively. We suggest that expanding class analysis to include affective capacities illuminates new dimensions of class struggle.
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    Friends tell it like it is: Therapy culture, postfeminism and friendships between women
    Martinussen, M ; Wetherell, M (SAGE PUBLICATIONS LTD, 2021-12-28)
    Feminist cultural studies researchers have produced a rich body of work showing how postfeminism and therapy cultures pervade a range of media. However, receiving less attention are questions of exactly how the neoliberal technologies of self implicated in these two cultural persuasions ‘land’, and are practised in everyday life. In this article, we forward an identity practice approach to understand the interrelated cultures of therapy and postfeminism using data from a qualitative investigation of women’s friendships in Aotearoa New Zealand. We are interested in how the cultural resources concerning postfeminism and the ‘psy complex’ are used flexibly within friendship interactions in concert with other identities, such as national identities and caring identities. Overall, aligning with previous feminist analyses of media artefacts, we find that as postfeminist and therapeutic subjectivity-making entwine with the moral orders of women’s friendships, women carry out their self-surveillance and self-transformation work collaboratively. Yet, remaining attentive to how women tailor cultural resources in their creative identity work leads us to a more hopeful reading. We suggest that the confidence gained by women through their therapised friendships should also be acknowledged for its nourishing qualities.
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    The balance of interleukin-12 and interleukin-23 determines the bias of MAIT1 versus MAIT17 responses during bacterial infection
    Wang, H ; Nelson, AG ; Wang, B ; Zhao, Z ; Lim, XY ; Shi, M ; Meehan, LJ ; Jia, X ; Kedzierska, K ; Meehan, BS ; Eckle, SBG ; Souter, MNT ; Pediongco, TJ ; Mak, JYW ; Fairlie, DP ; McCluskey, J ; Wang, Z ; Corbett, AJ ; Chen, Z (WILEY, 2022-06-02)
    Mucosal-associated invariant T (MAIT) cells are a major subset of innate-like T cells mediating protection against bacterial infection through recognition of microbial metabolites derived from riboflavin biosynthesis. Mouse MAIT cells egress from the thymus as two main subpopulations with distinct functions, namely, T-bet-expressing MAIT1 and RORγt-expressing MAIT17 cells. Previously, we reported that inducible T-cell costimulator and interleukin (IL)-23 provide essential signals for optimal MHC-related protein 1 (MR1)-dependent activation and expansion of MAIT17 cells in vivo. Here, in a model of tularemia, in which MAIT1 responses predominate, we demonstrate that IL-12 and IL-23 promote MAIT1 cell expansion during acute infection and that IL-12 is indispensable for MAIT1 phenotype and function. Furthermore, we showed that the bias toward MAIT1 or MAIT17 responses we observed during different bacterial infections was determined and modulated by the balance between IL-12 and IL-23 and that these responses could be recapitulated by cytokine coadministration with antigen. Our results indicate a potential for tailored immunotherapeutic interventions via MAIT cell manipulation.
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    Developing a Screening Tool for Areas of Abnormal Central Vision Using Visual Stimuli With Natural Scene Statistics
    Srinivasan, R ; Turpin, A ; McKendrick, AM (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2022-02-01)
    PURPOSE: Previous studies show that some visual field (VF) defects are detectable from visual search behavior; for example, when watching video. Here, we developed and tested a VF testing approach that measures the number of fixations to find targets on a background with spatial frequency content similar to natural scenes. METHODS: Twenty-one older controls and 20 people with glaucoma participated. Participants searched for a Gabor (6 c/°) that appeared in one of 25 possible locations within a 15° (visual angle) 1/f noise background (RMS contrast: 0.20). Procedure performance was assessed by calculating sensitivity and specificity for different combinations of control performance limits (p = 95%, 98%, 99%), number of target locations with fixations outside control performance limits (k = 0 to 25) and number of repeated target presentations (n = 1 to 20). RESULTS: Controls made a median of two to three fixations (twenty-fifth to seventy-fifth percentile: two to four) to locate the target depending on location. A VF was flagged "abnormal" when the number of fixations was greater than the p = 99% for k = 3 or more locations with n = 2 repeated presentations, giving 85% sensitivity and 95.2% specificity. The median test time for controls was 85.71 (twenty-fifth to seventy-fifth percentile: 66.49-113.53) seconds. CONCLUSION: Our prototype test demonstrated effective and efficient screening of abnormal areas in central vision. TRANSLATIONAL RELEVANCE: Visual search behavior can be used to detect central vision loss and may produce results that relate well to performance in natural visual environments.
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    Do Additional Testing Locations Improve the Detection of Macular Perimetric Defects in Glaucoma?
    Montesano, G ; McKendrick, AM ; Turpin, A ; Brusini, P ; Oddone, F ; Fogagnolo, P ; Perdicchi, A ; Johnson, CA ; Lanzetta, P ; Rossetti, LM ; Garway-Heath, DF ; Crabb, DP (ELSEVIER SCIENCE INC, 2021-11-18)
    PURPOSE: To evaluate the ability of additional central testing locations to improve detection of macular visual field (VF) defects in glaucoma. DESIGN: Prospective cross-sectional study. PARTICIPANTS: Four hundred forty healthy people and 499 patients with glaucomatous optic neuropathy (GON) were tested with a fundus tracked perimeter (CMP; CenterVue) using a 24-2 grid with 12 additional macular locations (24-2+). METHODS: Glaucomatous optic neuropathy was identified based on expert evaluation of optic nerve head photographs and OCT scans, independently of the VF. We defined macular defects as locations with measurements outside the 5% and 2% normative limits on total deviation (TD) and pattern deviation (PD) maps within the VF central 10°. Classification was based on the total number of affected macular locations (overall detection) or the largest number of affected macular locations connected in a contiguous cluster (cluster detection). Criteria based on the number of locations and cluster size were used to obtain equivalent specificity between the 24-2 grid and the 24-2+ grids, calculated using false detections in the healthy cohort. Partial areas under the receiver operating characteristic curve (pAUCs) were also compared at specificities of 95% or more. MAIN OUTCOME MEASURES: Matched specificity comparison of the ability to detect glaucomatous macular defects between the 24-2 and 24-2+ grids. RESULTS: At matched specificity, cluster detection identified more macular defects with the 24-2+ grid compared with the 24-2 grid. For example, the mean increase in percentage of detection was 8% (95% confidence interval [CI], 5%-11%) and 10% (95% CI, 7%-13%) for 5% TD and PD maps, respectively, and 5% (95% CI, 2%-7%) and 6% (95% CI, 4%-8%) for the 2% TD and PD maps, respectively. Good agreement was found between the 2 grids. The improvement measured by pAUCs was also significant but generally small. The percentage of eyes with macular defects ranged from about 30% to 50%. Test time for the 24-2+ grid was longer (21% increase) for both cohorts. Between 74% and 98% of defects missed by the 24-2 grid had at least 1 location with sensitivity of < 20 dB. CONCLUSIONS: Visual field examinations with additional macular locations can improve the detection of macular defects in GON modestly without loss of specificity when appropriate criteria are selected.
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    The Melbourne Safe Injecting Room Attracted People Most in Need of Its Service
    Van Den Boom, W ; Quiroga, MDM ; Fetene, DM ; Agius, PA ; Higgs, PG ; Maher, L ; Hickman, M ; Stoov, MA ; Dietze, PM (ELSEVIER SCIENCE INC, 2021-07-19)
    INTRODUCTION: In 2018, the first Medically Supervised Injecting Room in Melbourne, Australia was officially opened. This study assessed whether this facility attracted people who inject drugs, who were socially vulnerable, and who engaged in drug-related behaviors associated with increased morbidity and mortality risk. METHODS: This was a cross-sectional analysis of the frequency of Medically Supervised Injecting Room use during the first 18 months after opening (July 2018-December 2019) among 658 people who inject drugs participating in the Melbourne Injecting Drug User Cohort Study (SuperMIX). To examine the differences between no Medically Supervised Injecting Room use, infrequent use (<50% injections within the facility), and frequent use (≥50% of injections within the facility), RRRs were estimated using bivariate multinomial logistic regression analyses and postestimation Wald tests. Analyses were conducted in 2020. RESULTS: A total of 451 participants (68%) reported no Medically Supervised Injecting Room use, 142 (22%) reported infrequent use, and 65 (10%) reported frequent use. Participants who reported either infrequent or frequent use of the facility were more socially vulnerable (e.g., more often homeless) and more likely to report risky drug-related behaviors and poor health outcomes than those who reported no use. Participants who reported frequent use of the facility were also more likely to live close to the facility than those reporting infrequent use. CONCLUSIONS: The Melbourne Medically Supervised Injecting Room attracted socially marginalized people who inject drugs who are most at risk of harms related to injecting drug use and therefore who are most in need of the service. To determine the long-term impact use of this facility on key health outcomes such as overdose, future studies should consider the differences in vulnerability and risk behavior of people who inject drugs who use the Medically Supervised Injecting Room when examining the outcomes associated with the use of the facility.
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    Mouse models illuminate MAIT cell biology
    Wang, H ; Chen, Z ; McCluskey, J ; Corbett, AJ (PERGAMON-ELSEVIER SCIENCE LTD, 2021-02-01)
    The field of mucosal-associated invariant T cell (MAIT) biology has grown rapidly since the identification of the vitamin-B-based antigens recognised by these specialised T cells. Over the past few years, our understanding of the complexities of MAIT cell function has developed, as they find their place among the other better known cells of the immune system. Key questions relate to understanding when MAIT cells help, when they hinder or cause harm, and when they do not matter. Exploiting mouse strains that differ in MAIT cell numbers, leveraged by specific detection of MAIT cells using MR1-tetramers, it has now been shown that MAIT cells play important immune roles in settings that include bacterial and viral infections, autoimmune diseases and cancer. We have also learnt much about their development, modes of activation and response to commensal microbiota, and begun to try ways to manipulate MAIT cells to improve disease outcomes. Here we review recent studies that have assessed MAIT cells in models of disease.
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    Subjective measurement of the Stiles-Crawford effect with different field sizes
    Nilagiri, VK ; Suheimat, M ; Lambert, AJ ; Turpin, A ; Vohnsen, B ; Atchison, DA (OPTICAL SOC AMER, 2021-08-01)
    The Stiles-Crawford effect of the first kind (SCE) is the phenomenon in which light entering the eye near the center of the pupil appears brighter than light entering near the edge. Previous investigations have found an increase in the directionality (steepness) of the effect as the testing location moves from the center of the visual field to parafoveal positions, but the effect of central field size has not been considered. The influence of field size on the SCE was investigated using a uniaxial Maxwellian system in which stimulus presentation was controlled by an active-matrix liquid crystal display. SCE directionality increased as field size increased from 0.5° to 4.7° diameter, although this was noted in four mild myopes and not in two emmetropes. The change with field size was supported by a geometric optics absorption model.