Reporting on our recent book, The Solidarity Society, this article explores the way in which the design of welfare programmes interacts with and shapes the underlying quality of social relations between members of society—and, through this, public attitudes to welfare. Given that sustaining generous welfare over long timescales requires the support of electorates, this ‘relational’ dimension of welfare policy is crucial for the long‐term strategy of tackling poverty and inequality. The article looks in particular at the ‘welfare dilemmas’ that can arise from tensions between targeting and universalism and between need and entitlement, where the distributional and relational elements of welfare policy work against one another. We conclude that entrenching a generous welfare settlement will require strong elements of both universalism and reciprocity in the design of welfare.

About the reportThe Health Foundation is an independent charity committed to bringing about better health and health care for people in the UK.Health Data Research UK (HDR UK) is the UK's national institute for health data science. HDR UK's mission is to bring together the UK's health and care data to enable discoveries that improve people's lives by uniting, improving and using data as one national institute. HDR UK's Better Care programme aims to equip clinicians and patients in the UK with the best possible data-based information to make decisions about their care. 1 Over the past 2 years, as part of this wider programme, the Health Foundation and HDR UK have been working in partnership to deliver the Better Care Catalyst programme. This has funded three projects to develop data-driven tools that aim to improve health care decision making 2 and also supported three workstreams to set out the training, knowledge mobilisation and policy actions required to support data-driven learning and improvement in health care. This report is the final output of the Better Care Catalyst programme's policy and insights workstream, which researched the barriers and enablers for implementing learning health system approaches in the UK. It supports the wider Better Care programme and community by providing analysis and advice to further the use of data to improve health care services. It also identifies a range of opportunities and actions that policymakers and organisational and system leaders can take to advance the learning health systems agenda across the UK. 3

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Purpose/Objective(s): Androgen deprivation therapy (ADT) has been a clinical standard of care for the treatment of castration sensitive prostate cancer (CSPC). However, it is not curative, and ADT has significant systemic effects including hot flashes, osteoporosis, anemia, etc. We sought to identify agents that would inhibit AR signaling without causing these systemic effects. Histone deacetylase inhibitors (HDACis) are attractive agents because they impede AR signaling and DNA damage repair in PCa and show epigenetic modifications in prostate cancer (PCa) development and progression. This study demonstrated romidepsin as an alternative to ADT and the development of a romidepsin encapsulated CSPC PCa targeted nanoparticle for PCa cell killing and growth inhibition without the toxicity associated with free romidepsin or ADT. Materials/Methods: Three PCa cell lines, LNCaP, 22Rv1 and PC3 that express different androgen receptor (AR) levels were used for this study. Cell viability was tested by real-time cell analysis (RTCA), protein expression by western blot analysis, and quantification of γ-H2AX double stranded DNA (dsDNA) breaks by immunofluorescent microscopy. We developed a poly (D,L-lactide-co-glycolide) (PLGA) and 1, 2-Distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol (DSPE-PEG) polymer-lipid nanoparticle coated with vipivotide tetraxetan(PSMA-617) for prostate specific membrane antigen (PSMA) targeting. Nanoparticles were characterized by transmission electron microscope (TEM), dynamic light scattering (DLS) analysis, and nanoparticle tracking analysis (NTA). Romidepsin encapsulation efficiency was quantified by high-performance liquid chromatography(HPLC). Results: RTCA showed free romidepsin inhibited cell growth in all three PCa cell lines in a dose dependent manner. The addition of ADT exhibited an additive effect with low romidepsin doses, but did not significantly improve cell growth inhibition when combined with high doses of romidepsin. Western blot and γ-H2AX foci staining confirmed that romidepsin inhibited AR signaling and increased dsDNA damage, respectively. HPLC showed nanoparticle encapsulated romidepsin of 0.7%wt and TEM/DLS/NTA showed a size of 130 ±20nm. Furthermore, PSMA-617 coated nanoparticles exhibited enhanced uptake in LNCaP cells compared to non-coated nanoparticles. Conclusion: Our study showed that the romidepsin has a dual effect on inhibiting AR signaling as well as downregulating DNA damage repair genes. Additionally, we developed a PCa targeted nanoparticle for specific PCa delivery of romidepsin. PSMA-targeted, romidepsin-encapsulated nanoparticles would reduce the systemic effects of free romidepsin and a potential replacement for ADT. Citation Format: Wendi Ma, Daiki Hara, Yu-Ping Yang, Olivia Yolande Bosquet, Wei Zhang, Emre Dikici, Huayang Feng, Tim Horton, Wensi Tao, Jessi Hersh, Junwei Shi, Sylvia Daunert, Sapna Deo, Alan Pollack. Prostate cancer androgen receptor signaling inhibition via romidepsin encapsulated lipid-polymer hybrid nanoparticle with PSMA617 targeting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1996.