Message Journal, Issue 5: COVID-19 SPECIAL ISSUE Capturing visual insights, thoughts and reflections on 2020/21 and beyond...

If there is a theme running through the Message Covid-19 special issue, it is one of caring. Of our own and others’ resilience and wellbeing, of friendship and community, of students, practitioners and their futures, of social justice, equality and of doing the right thing. The veins of designing with care run through the edition, wide and deep. It captures, not designers as heroes, but those with humble views, exposing the need to understand a diversity of perspectives when trying to comprehend the complexity that Covid-19 continues to generate. As graphic designers, illustrators and visual communicators, contributors have created, documented, written, visualised, reflected, shared, connected and co-created, designed for good causes and re-defined what it is to be a student, an academic and a designer during the pandemic. This poignant period in time has driven us, through isolation, towards new rules of living, and new ways of working; to see and map the world in a different light. A light that is uncertain, disjointed, and constantly being redefined. This Message issue captures responses from the graphic communication design community in their raw state, to allow contributors to communicate their experiences through both their written and visual voice. Thus, the reader can discern as much from the words as the design and visualisations. Through this issue a substantial number of contributions have focused on personal reflection, isolation, fear, anxiety and wellbeing, as well as reaching out to community, making connections and collaborating. This was not surprising in a world in which connection with others has often been remote, and where ‘normal’ social structures of support and care have been broken down. We also gain insight into those who are using graphic communication design to inspire and capture new ways of teaching and learning, developing themselves as designers, educators, and activists, responding to social justice and to do good; gaining greater insight into society, government actions and conspiracy. Introduction: Victoria Squire - Coping with Covid: Community, connection and collaboration: James Alexander & Carole Evans, Meg Davies, Matthew Frame, Chae Ho Lee, Alma Hoffmann, Holly K. Kaufman-Hill, Joshua Korenblat, Warren Lehrer, Christine Lhowe, Sara Nesteruk, Cat Normoyle & Jessica Teague, Kyuha Shim. - Coping with Covid: Isolation, wellbeing and hope: Sadia Abdisalam, Tom Ayling, Jessica Barness, Megan Culliford, Stephanie Cunningham, Sofija Gvozdeva, Hedzlynn Kamaruzzaman, Merle Karp, Erica V. P. Lewis, Kelly Salchow Macarthur, Steven McCarthy, Shelly Mayers, Elizabeth Shefrin, Angelica Sibrian, David Smart, Ane Thon Knutsen, Isobel Thomas, Darryl Westley. - Coping with Covid: Pedagogy, teaching and learning: Bernard J Canniffe, Subir Dey, Aaron Ganci, Elizabeth Herrmann, John Kilburn, Paul Nini, Emily Osborne, Gianni Sinni & Irene Sgarro, Dave Wood, Helena Gregory, Colin Raeburn & Jackie Malcolm. - Coping with Covid: Social justice, activism and doing good: Class Action Collective, Xinyi Li, Matt Soar, Junie Tang, Lisa Winstanley. - Coping with Covid: Society, control and conspiracy: Diana Bîrhală, Maria Borțoi, Patti Capaldi, Tânia A. Cardoso, Peter Gibbons, Bianca Milea, Rebecca Tegtmeyer, Danne Wo

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

A Bayesian reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial

Background Timing of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney injury and found neutral results for 90-day all-cause mortality. Probabilistic exploration of the trial endpoints may enable greater understanding of the trial findings. We aimed to perform a reanalysis using a Bayesian framework. Methods We performed a secondary analysis of all 2927 patients randomized in multi-national STARRT-AKI trial, performed at 168 centers in 15 countries. The primary endpoint, 90-day all-cause mortality, was evaluated using hierarchical Bayesian logistic regression. A spectrum of priors includes optimistic, neutral, and pessimistic priors, along with priors informed from earlier clinical trials. Secondary endpoints (KRT-free days and hospital-free days) were assessed using zero–one inflated beta regression. Results The posterior probability of benefit comparing an accelerated versus a standard KRT initiation strategy for the primary endpoint suggested no important difference, regardless of the prior used (absolute difference of 0.13% [95% credible interval [CrI] − 3.30%; 3.40%], − 0.39% [95% CrI − 3.46%; 3.00%], and 0.64% [95% CrI − 2.53%; 3.88%] for neutral, optimistic, and pessimistic priors, respectively). There was a very low probability that the effect size was equal or larger than a consensus-defined minimal clinically important difference. Patients allocated to the accelerated strategy had a lower number of KRT-free days (median absolute difference of − 3.55 days [95% CrI − 6.38; − 0.48]), with a probability that the accelerated strategy was associated with more KRT-free days of 0.008. Hospital-free days were similar between strategies, with the accelerated strategy having a median absolute difference of 0.48 more hospital-free days (95% CrI − 1.87; 2.72) compared with the standard strategy and the probability that the accelerated strategy had more hospital-free days was 0.66. Conclusions In a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation