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Summary: The ability of tumors to establish a pro-tumorigenic microenvironment is an important point of investigation in the search for new therapeutics. Tumors form microenvironments in part by the “education” of immune cells attracted via chemotactic axes such as that of CCR5-CCL5. Further, CCR5 upregulation by cancer cells, coupled with its association with pro-tumorigenic features such as drug resistance and metastasis, has suggested CCR5 as a therapeutic target. However, with several conformational “pools” being reported, phenotypic investigations must be capable of unveiling conformational heterogeneity. Addressing this challenge, we performed super-resolution structured illumination microscopy (SIM) and single molecule partially TIRF-coupled HILO (PaTCH) microscopy of CCR5 in fixed cells. SIM data revealed a non-random spatial distribution of CCR5 assemblies, while Intensity-tracking of CCR5 assemblies from PaTCH images indicated dimeric sub-units independent of CCL5 perturbation. These biophysical methods can provide important insights into the structure and function of onco-immunogenic receptors and many other biomolecules.

Background: In response to COVID-19, alongside other service changes, North Central London and East Kent implemented prehospital video triage: this involved stroke and ambulance clinicians communicating over FaceTime (Apple Inc., Cupertino, CA, USA) to assess suspected stroke patients while still on scene. Objective: To evaluate the implementation, experience and impact of prehospital video triage in North Central London and East Kent. Design: A rapid mixed-methods service evaluation (July 2020 to September 2021) using the following methods. (1) Evidence reviews: scoping review (15 reviews included) and rapid systematic review (47 papers included) on prehospital video triage for stroke, covering usability (audio-visual and signal quality); acceptability (whether or not clinicians want to use it); impact (on outcomes, safety, experience and cost-effectiveness); and factors influencing implementation. (2) Clinician views of prehospital video triage in North Central London and East Kent, covering usability, acceptability, patient safety and implementation: qualitative analysis of interviews with ambulance and stroke clinicians (n = 27), observations (n = 12) and documents (n = 23); a survey of ambulance clinicians (n = 233). (3) Impact on safety and quality: analysis of local ambulance conveyance times (n = 1400; April to September 2020). Analysis of national stroke audit data on ambulance conveyance and stroke unit delivery of clinical interventions in North Central London, East Kent and the rest of England (n = 137,650; July 2018 to December 2020). Results: (1) Evidence: limited but growing, and sparse in UK settings. Prehospital video triage can be usable and acceptable, requiring clear network connection and audio-visual signal, clinician training and communication. Key knowledge gaps included impact on patient conveyance, patient outcomes and cost-effectiveness. (2) Clinician views. Usability – relied on stable Wi-Fi and audio-visual signals, and back-up processes for when signals failed. Clinicians described training as important for confidence in using prehospital video triage services, noting potential for ‘refresher’ courses and joint training events. Ambulance clinicians preferred more active training, as used in North Central London. Acceptability – most clinicians felt that prehospital video triage improved on previous processes and wanted it to continue or expand. Ambulance clinicians reported increased confidence in decisions. Stroke clinicians found doing assessments alongside their standard duties a source of pressure. Safety – clinical leaders monitored and managed potential patient safety issues; clinicians felt strongly that services were safe. Implementation – several factors enabled prehospital video triage at a system level (e.g. COVID-19) and more locally (e.g. facilitative governance, receptive clinicians). Clinical leaders reached across and beyond their organisations to engage clinicians, senior managers and the wider system. (3) Impact on safety and quality: we found no evidence of increased times from symptom onset to arrival at services or of stroke clinical interventions reducing in studied areas. We found several significant improvements relative to the rest of England (possibly resulting from other service changes). Limitations: We could not interview patients and carers. Ambulance data had no historic or regional comparators. Stroke audit data were not at patient level. Several safety issues were not collected routinely. Our survey used a convenience sample. Conclusions: Prehospital video triage was perceived as usable, acceptable and safe in both areas. Future research: Qualitative research with patients, carers and other stakeholders and quantitative analysis of patient-level data on care delivery, outcomes and cost-effectiveness, using national controls. Focus on sustainability and roll-out of services. Study registration: This study is registered as PROSPERO CRD42021254209. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 10, No. 26. See the NIHR Journals Library website for further project information.