Coproduction with peer support groups: A new approach to culturally responsive social services.

The disparity of access to suitable social services for people from culturally diverse backgrounds is receiving increased attention. Coproduction between service users and providers has the potential as an approach to improve the cultural responsiveness of social services. What remains unknown is how social service organizations can facilitate and support coproduction with people from culturally diverse backgrounds. This article examines how three disability support organizations in Australia worked with peer support groups run by people with disability and their families from Chinese background to improve the organizations' service provision. We collected qualitative data through observations of activities in the groups and semistructured interviews with group members and organization staff. We found that organizing peer support groups facilitated knowledge exchange between people from culturally diverse backgrounds and organizations to inform practice development. Five contributors to the knowledge exchange were as follows: (1) assigning staff responsibility for exchange and trust with the group; (2) encouraging the group to challenge practice and cultural norms; (3) identifying and supporting the capacity of peer facilitators; (4) fostering trust within the group; and (5) collaborating with other organizations. Cultural responsiveness means incorporating people's cultural preferences in support provision and addressing the negative influences of cultural norms on people.

'Nothing About Us Without Us': exploring benefits and challenges of peer support for people with disability in peer support organisations - protocol paper for a qualitative coproduction project.

INTRODUCTION: One in six people live with disability in Australia with higher levels of disability of people from diverse communities, such as those with culturally and linguistically diverse (CALD) backgrounds. In Australia, CALD refers to people from diverse ethnicity and cultures, nationalities, societal structures and religions that may or may not speak a language other than English. This study employs researchers with lived experience of disability and peer support to study the impact of peer support for people with disability, including people from CALD backgrounds, in two peer-led organisations in New South Wales (NSW) Australia. METHODS AND ANALYSIS: This study uses participatory action research and inclusive research design with researchers with lived experience, having lived experience of disability and a peer in the disability community, leading the research.Over three years, three different groups will be recruited through Community Disability Alliance Hunter (CDAH) and Diversity and Disability Alliance (DDAlliance): (1) peers with disability, (2) peer leaders with disability and (3) researchers with lived experience of disability and peer support. Data collection and creation methods include semistructured interviews, surveys and focus groups. Qualitative data will be analysed using thematic analysis through the lens of the researchers with lived experience. ETHICS AND DISSEMINATION: Ethical approval was granted by the University of Newcastle Human Research Ethics Committee (Approval No: H-2021-0088). Dissemination includes peer-reviewed publications, presentations at local, national and international conferences and written reports for user-led organisations, disability service providers, disability agencies and people with disability.

Treatment outcomes of stereotactic ablative body radiotherapy on oligometastases from colorectal cancer: early results of a single institution service evaluation.

Objective: Stereotactic ablative radiotherapy (SABR) has been suggested to be an effective non-invasive ablative therapy for oligometastases originated from colorectal cancer (CRC). This study aimed to report CRC oligometastases SABR treatment outcomes in terms of overall survival (OS), progression-free survival (PFS) and post-treatment toxicities. Methods: Treatment records of patients with CRC metachronous oligometastases who underwent SABR at a single institution between February 2015 and December 2018 were retrospectively reviewed. OS and PFS were calculated using Kaplan-Meier statistics and post-RT toxicity data was scored following CTCAE v. 4.0. Analysis of prognostic factors on OS and PFS was performed based on site of primary cancer, types of treatment to primary cancer, number of oligometastases, SABR treatment sites, intervals between treatment to primary cancer and SABR to oligometastases, biological equivalent dose, cumulative gross tumour volume and planning target volume. Results: 75 patients with 86 CRC metachronous oligometastases (including liver, lung, lymph nodes and bone) were included. The median age was 65.5 years (range 42.5-87.2) with a median follow-up of 23.8 months (range 3.1-46.5). The estimated median PFS was 14.6 months (95% CI 9.6-19.6). and estimated median OS was 33.3 months (95% CI 22.9-43.7). Majority of patients tolerated SABR well with the most common acute side-effects of Grade 1 fatigue. No Grade 3 or higher toxicities were reported at any time points.Only SABR treatment sites (p = 0.03) and cumulative volumes of planning target volume (p = 0.02) were found to be statistically significant independent predictors of PFS and OS respectively. Conclusion: This study showed modest PFS, OS, and post-treatment toxicity outcomes on SABR to metachronous oligometastases from CRC. It has highlighted that cumulative tumour volume may be a stronger prognostic factor of OS comparing to the number of metastases. Advances in knowledge: There are limited data published on the efficacy and post-treatment toxicity of CRC oligometastases SABR with adequate length of follow-up. Our retrospective study suggests that cumulative tumour volume may be a stronger prognostic factor of OS comparing to the number of oligometastases.

Regulation of innate and adaptive immune responses by MAP kinase phosphatase 5.

Mitogen-activated protein (MAP) kinases are essential regulators in immune responses, and their activities are modulated by kinases and phosphatases. MAP kinase phosphatase (MKP) is a family of dual-specificity phosphatases whose function is evolutionarily conserved. A number of mammalian MKPs have been identified so far, but their specific physiological functions in negative regulation of MAP kinases have not been genetically defined. Here we examine innate and adaptive immune responses in the absence of MKP5. JNK activity was selectively increased in Mkp5 (also known as Dusp10)-deficient mouse cells. Mkp5-deficient cells produced greatly enhanced levels of pro-inflammatory cytokines during innate immune responses and exhibited greater T-cell activation than their wild-type counterparts. However, Mkp5-deficient T cells proliferated poorly upon activation, which resulted in increased resistance to experimental autoimmune encephalomyelitis. By contrast, Mkp5-deficient CD4(+) and CD8(+) effector T cells produced significantly increased levels of cytokines compared with wild-type cells, which led to much more robust and rapidly fatal immune responses to secondary infection with lymphocytic choriomeningitis virus. Therefore, MKP5 has a principal function in both innate and adaptive immune responses, and represents a novel target for therapeutic intervention of immune diseases.

Murine B7-H3 is a negative regulator of T cells.

T cell activation is regulated by the innate immune system through positive and negative costimulatory molecules. B7-H3 is a novel B7-like molecule with a putative receptor on activated T cells. Human B7-H3 was first described as a positive costimulator, most potently inducing IFN-gamma production and cellular immunity. In this study we examined the expression and function of mouse B7-H3. B7-H3 is mostly expressed on professional APCs; its expression on dendritic cells appears to be up-regulated by LPS. In contrast to human B7-H3, we found that mouse B7-H3 protein inhibited T cell activation and effector cytokine production. An antagonistic mAb to B7-H3 enhanced T cell proliferation in vitro and led to exacerbated experimental autoimmune encephalomyelitis in vivo. Therefore, mouse B7-H3 serves as a negative regulator of T cell activation and function.

Transcriptional regulation of th2 differentiation by inducible costimulator.

Helper T (Th) cell differentiation is accompanied by complex transcriptional changes. Although costimulatory receptors are important in Th differentiation, the underlying mechanisms are poorly understood. Here we examine the transcriptional mechanisms by which ICOS regulates Th2 differentiation and selective IL-4 expression by effector T cells. We found impaired expression of c-Maf transcription factor functionally associated with the IL-4 defect in ICOS(-/-) cells. c-Maf expression in effector cells was regulated by IL-4 levels during Th differentiation. ICOS costimulation potentiated the T cell receptor (TcR)-mediated initial IL-4 production, possibly through the enhancement of NFATc1 expression. These data indicate that ICOS, by enhancing TcR signals at an early stage of T cell activation, regulates IL-4 transcription and T cell function in effector cells.

Inducible costimulator is essential for collagen-induced arthritis.

CD4(+) helper Th cells play a major role in the pathogenesis of rheumatoid arthritis. Th cell activation, differentiation, and immune function are regulated by costimulatory molecules. Inducible costimulator (ICOS) is a novel costimulatory receptor expressed on activated T cells. We, as well as others, recently demonstrated its importance in Th2 cytokine expression and Ab class switching by B cells. In this study, we examined the role of ICOS in rheumatoid arthritis using a collagen-induced arthritis model. We found that ICOS knockout mice on the DBA/1 background were completely resistant to collagen-induced arthritis and exhibited absence of joint tissue inflammation. These mice, when immunized with collagen, exhibited reduced anti-collagen IgM Ab's in the initial stage and IgG2a Ab's at the effector phase of collagen-induced arthritis. Furthermore, ICOS regulates the in vitro and in vivo expression of IL-17, a proinflammatory cytokine implicated in rheumatoid arthritis. These data indicate that ICOS is essential for collagen-induced arthritis and may suggest novel means for treating patients with rheumatoid arthritis.