User experiences of an American-adapted moderated online social media platform for first-episode psychosis: Qualitative analysis

Objectives The current study sought to qualitatively characterize the experiences of American users in a recent open trial of the Horyzons digital platform. Methods In total, 20 users on Horyzons USA completed semistructured interviews 12 weeks after their orientation to the platform and addressed questions related to (1) the platform, (2) their online therapist, and (3) the peer workers and community space. A hybrid inductive-deductive coding strategy was used to conduct a thematic analysis of the data (NCT04673851). Results The authors identified seven prominent themes that mapped onto the three components of self-determination theory. Features of the platform itself as well as inter- and intra-personal factors supported the autonomous use of Horyzons. Users also reflected that their perceived competence in social settings and in managing mental health was increased by the familiarity, privacy, and perceived safety of the platform and an emphasis on personalized therapeutic content. The behaviors or traits of online therapists as perceived by users and regular contact with peers and peer support specialists satisfied users’ need for relatedness and promoted confidence in social settings. Users also described aspects of Horyzons USA that challenged their satisfaction of autonomy, competence, and relatedness, highlighting potential areas for future iterations of the platform's content and interface. Conclusions Horyzons USA is a promising digital tool that provides young adults with psychosis with the means to access tailored therapy material on demand and a supportive digital community to aid in the recovery process

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

Horyzons USA : A moderated online social intervention for first episode psychosis

Aim We evaluated the feasibility and acceptability of Horyzons, an online social media platform designed to facilitate relationship development among, and introduce therapeutic content to, first-episode psychosis (FEP) clients. We also evaluated whether participation in the platform was related to reduced loneliness, improved social integration and increased psychological well-being. Methods Twenty-six participants diagnosed with a schizophrenia spectrum disorder were provided access to the moderated Horyzons platform for 12 weeks. During the intervention period, participants were encouraged to access therapeutic content and social components embedded within the site. Participants were recruited from three first-episode coordinated specialty care clinics in North Carolina and assessed at four time points: baseline, mid-treatment, post-treatment and 1-month follow-up. Results Findings indicated that Horyzons was both feasible and very well tolerated, with a 92.3% retention rate and 79.2% of participants actively engaged in the platform. The most commonly identified personal strengths selected by Horyzons users were creativity (61.5%), curiosity (42.3%) and courage (38.5%). Feedback from participants indicated Horyzons could be improved by the development of a smartphone application, expanding the size of the Horyzons community and facilitating private messages between users. Preliminary results with engaged participants showed the greatest improvements in psychosis-related symptoms, followed by self-reported experience of negative emotions, depressive symptoms and loneliness. Conclusions This open trial found that Horyzons is both feasible and acceptable to FEP persons early in the course of illness living in the United States

Correlates of loneliness among persons with psychotic disorders

Introduction Persons diagnosed with schizophrenia spectrum disorders (SSDs) often experience pervasive feelings of loneliness, which are considered a significant barrier to treatment and recovery. Aim As impaired social cognition may contribute to increased loneliness and less skillful social interactions, this study examines the relationships between loneliness and measures of social cognition and functional outcome from the Social Cognition Psychometric Evaluation (SCOPE) study. Methods This study evaluated the relationship between loneliness, social cognitive ability, and social functioning in the context of a large-scale psychometric investigation. We also explored the associations of select demographic characteristics and clinical variables on the endorsement of loneliness in persons diagnosed with a psychotic disorder. Results Seventy-four stable outpatients with SSDs and 58 healthy controls completed the UCLA Loneliness Scale in addition to the standard SCOPE battery. Our findings support prior research indicating persons diagnosed with a psychotic disorder experience greater levels of loneliness than normative groups. However, the results also indicate that self-reported loneliness is not associated with social cognitive abilities or functional outcome in psychosis. Regression analyses indicate that roughly half the variance in loneliness endorsed by persons with SSDs is accounted for by clinical variables, with loneliness most strongly associated with guilt and self-esteem. Conclusion These findings suggest that treatments aiming to reduce perceived social isolation in psychosis should incorporate techniques to bolster selfesteem, reduce guilt, and improve depressive symptoms

Paleoproterozoic orogenesis in the southeastern Gawler Craton, South Australia

Integrated structural, metamorphic and geochronological data demonstrate the existence of a contractional orogen preserved in the ca 1850 Ma Donington Suite batholith along the eastern margin of the Gawler Craton, South Australia. The earliest structures are a pervasive gneissic foliation developed in the Donington Suite and interleaved metasedimentary rocks. This has been overprinted by isoclinal and non-cylindrical folding, and zones of pervasive non-coaxial shear with north-directed transport, suggesting that deformation was the result of orogenic contraction. SHRIMP U - Pb zircon data indicate that a syn-contractional granitic dyke was emplaced at 1846 ± 4 Ma. Overprinting the contractional structures are a series of discrete, migmatitic high-strain zones that show a normal geometry with a component of oblique dextral shear. U - Pb zircon data from a weakly foliated microgranite in one such shear zone give an emplacement age of 1843 ± 5 Ma. Rare aluminous metasedimentary rocks in the belt preserve a granulite-grade assemblage of garnet + biotite + plagioclase + K-feldspar + silicate melt that formed at ∼600 MPa and ∼750°C. Peak metamorphic garnets are partially replaced by biotite + sillimanite+ cordierite assemblages suggesting post-thermal peak cooling and decompression, and are indicative of a clockwise P - T evolution. Chemical U - Th - Pb electron microprobe ages from monazites in retrograde biotite yield a minimum estimate for the timing of retrogression of ca 1830 Ma, indicating that decompression may be linked to the development of the broadly extensional shear zones and that the clockwise P - T path occurred during a single tectonothermal cycle. We define this ca 1850 Ma phase of crustal evolution in the eastern Gawler Craton as the Cornian Orogeny.A. Reid, M. Hand, E. Jagodzinski, D. Kelsey, N. Pearso

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease