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We aimed to compare measurements from three of the most widely used software packages in the literature and to generate conversion algorithms for measurement of the central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) between SIVA and IVAN and between SIVA and VAMPIRE. We analyzed 223 retinal photographs from 133 human participants using both SIVA, VAMPIRE and IVAN independently for computing CRAE and CRVE. Agreement between measurements was assessed using Bland-Altman plots and intra-class correlation coefficients. A conversion algorithm between measurements was carried out using linear regression, and validated using bootstrapping and root-mean-square error. The agreement between VAMPIRE and IVAN was poor to moderate: The mean difference was 20.2 µm (95% limits of agreement, LOA, -12.2-52.6 µm) for CRAE and 21.0 µm (95% LOA, -17.5-59.5 µm) for CRVE. The agreement between VAMPIRE and SIVA was also poor to moderate: the mean difference was 36.6 µm (95% LOA, -12.8-60.4 µm) for CRAE, and 40.3 µm (95% LOA, 5.6-75.0 µm) for CRVE. The agreement between IVAN and SIVA was good to excellent: the mean difference was 16.4 µm (95% LOA, -4.25-37.0 µm) for CRAE, and 19.3 µm (95% LOA, 0.09-38.6 µm) for CRVE. We propose an algorithm converting IVAN and VAMPIRE measurements into SIVA-estimated measurements, which could be used to homogenize sets of vessel measurements obtained with different software packages.

Objectives: To determine if lopinavir/ritonavir +/- hydroxychloroquine will reduce the proportion of participants who survive without requiring ventilatory support, 15 days after enrolment, in adult participants with non-critically ill SARS-CoV-2 infection. Trial design: ASCOT is an investigator-initiated, multi-centre, open-label, randomised controlled trial. Participants will have been hospitalised with confirmed COVID-19, and will be randomised 1:1:1:1 to receive lopinavir /ritonavir, hydroxychloroquine, both or neither drug in addition to standard of care management. Participants: Participants will be recruited from >80 hospitals across Australia and New Zealand, representing metropolitan and regional centres in both public and private sectors. Admitted patients will be eligible if aged ≥ 18 years, have confirmed SARS-CoV-2 by nucleic acid testing in the past 12 days and are expected to remain an inpatient for at least 48 hours from the time of randomisation. Potentially eligible participants will be excluded if admitted to intensive care or requiring high level respiratory support, are currently receiving study drugs or their use is contraindicated due to allergy, drug interaction or comorbidities (including baseline QTc prolongation of 470ms for women or 480ms for men), or death is anticipated imminently.

Background: Bromodomain and Extra-Terminal (BET) proteins are a highly conserved family of epigenetic 'readers' that recognise and bind acetylated lysine residues on histones and other proteins to modulate gene expression. BET proteins are enriched at enhancer regions regulating oncogenic transcription and inhibitors (BETi) displace BET proteins from chromatin leading to suppression of oncogenes (e.g. cMYC). BETi elicit a heterogeneous range of tumour cell responses including apoptosis, growth arrest, differentiation, and senescence. However, responses to single agent BETi are self-limited in vivo and drug resistance uniformly emerges in preclinical modelling. As BETinhibitors (BETi) are now being clinically evaluated in both haematological and solid malignancies, the focus is now shifting to the design of effective combination strategies for phase II studies. Aim(s): BETi have potent anti-inflammatory properties, including chromatinindependent downregulation of NFkB signalling. However, broader mechanisms of immunomodulation by BETi in the context of anti-tumour responses remain poorly defined. Having previously discovered NK- and T-cell immunostimulatory activity of an acetyllysine mimetic fragment (n-methylpyrrolidone), we sought to evaluate the immunomodulatory activity of the prototypical theinodiazapine BETi, JQ1. Method(s): Utilising the syngeneic model of transplanted Emu-Myc aggressive 'Burkitt-like' lymphoma we first compared the efficacy of JQ1 in wild-type (immunocompetent) and immunodeficient RAG1-/- or RAG2-/-cgamma-/-mice. To interrogate the functional interaction between JQ1 and the immune system, we profiled changes in tumour cell immunogenicity following drug exposure by flow cytometry. Result(s): We observed a 50% reduction in the survival advantage conveyed by JQ1 in mice deficient in T- and/or B-lymphocytes compared to immunocompetent controls. Notably, tumour-infiltrating lymphocytes (TILs) and peripheral blood T-cells from wild-type mice faili