UK Longitudinal Linkage Collaboration – and the challenges in creating a new Longitudinal Populations Studies linked data resource.

Objectives The UK Longitudinal Linkage Collaboration (UK LLC) is a new, unprecedented infrastructure enabling research into the COVID-19 pandemic. The UK LLC integrates data from >20 UK longitudinal studies with systematically linked health, administrative and environmental records to facilitate cross-disciplinary COVID-19 research for accredited UK based researchers. Approach Bringing together all of the key components that form the UK LLC was a huge challenge that may have only been possible in the midst of the pandemic. First, we collaborated with the Longitudinal Population Studies (LPS) to create and agree how data linkage, data provision and applications to access the UK LLC would work. In parallel, public contributors helped to create fair processing materials. Finally, we worked closely with NHS Digital and other key national data providers to organise approvals for all studies to be linked, and for the UK LLC to have delegated decision-making for research applications. Results We faced a myriad of challenges creating the UK LLC including: • Short timeframe and short-term funding structure – initial funding for six months with an 18-month extension. • Working across >20 different LPS and four nations with different structures for access, consent and data provision. • Lack of capacity at various points in the data pipeline due to the volume of COVID-19 research required and underway across the involved organisations. • Data processing complexities – split data method means no one can see the entire process therefore catching linkage errors requires working across four different organisations. • With such complex data flows it is challenging to find the balance with communications about data to the public – being accurate about what we are doing, but expressing the complexity in lay terms. Conclusion Creating the UK LLC required collaboration with LPS, data providers and researchers. An iterative approach to creating the data application and data provision pipelines was crucial in developing these processes. The UK LLC was built quickly, from initial funding in October 2020 to provisioning data to researchers in December 2021

The UK Longitudinal Linkage Collaboration: A trusted research environment for the longitudinal research community

Objectives Our Trusted Research Environment (TRE) provides a centralised infrastructure to pool Longitudinal Population Studies’ (LPS) data and systematically link participants’ routine health, administrative and environmental records. All data are held in a centralised research resource which is now certified by UK Statistics Authority as meeting the Digital Economy Act standard. Approach We have created an unprecedented infrastructure integrating data from interdisciplinary and pan-UK LPS linked to participants’ NHS England records with delegated access responsibilities. Integrated and curated data are made available for pooled analysis within a functionally anonymous DEA and ISO 27001 accredited TRE. We developed a bespoke governance and data curation framework with LPS data managers and Public/participant contributors. New data pipelines are being built with partners at ADRUK and the Office of National Statistics to link non-health records. Our design supports long-term sustainability, linkage accuracy and the ability to link data at both an individual and household level. Results This organisation is a collaboration of >24 LPS with ~280,000 participants. Participants' data are linked to NHS records and geo-coded environmental exposures. This resource is now accessible for public benefit research for bona fide UK researchers. Administrative data including tax, work and pensions, and education are being added to the resource. This data flow is enabled by: (1) a model where TTP processes participant identifiers for many different data owners; (2) creation of a novel longitudinal data pipeline, enabling linkage, data extraction and update of records over time; (3) an access framework where Linked Data Access Panel considers applications on behalf of data owners (e.g., the NHS), with review by a Public Panel and distributing applications to LPS for approval of appropriate data use. Conclusion Our organisation provides a strategic research-ready platform for longitudinal research. We are extending linkages of LPS participants to previously inaccessible datasets. The research resource is positioned to allow researchers to investigate cross-cutting themes such as understanding health and social inequalities, health-social-environmental interactions, and managing the COVID-19 recovery

The philanthropist next door

University campuses are peppered with buildings named for big benefactors, the people whose sizable gifts have helped propel higher education forward, often in tough economic times. But behind every major donor is a throng of everyday donors - alumni and community members, employees and retirees, families and clubs - whose contributions fuel our progress.Story by Mizzou Staff ; illustrations by Jacqui Oakley

Efficacy of LY303366 against Amphotericin B-Susceptible and -Resistant Aspergillus fumigatus in a Murine Model of Invasive Aspergillosis

LY303366 is a novel antifungal echinocandin with excellent in vitro activity against Aspergillus spp. We compared four doses (1, 2.5, 10, and 25 mg/kg of body weight) of LY303366 with amphotericin B (0.5 to 5 mg/kg) in a temporarily neutropenic murine model of invasive aspergillosis against an amphotericin B-susceptible (AF210) and an amphotericin B-resistant (AF65) Aspergillus fumigatus isolate based on in vivo response. Mice were immunosuppressed with cyclophosphamide (200 mg/kg) and infected 3 days later. Treatment started 18 h after infection and lasted for 10 days. LY303366 was given once daily intravenously for 10 days, and amphotericin B (at 0.5, 2, and 5 mg/kg) was given once daily intraperitoneally for 10 days, or only on days 1, 2, 4, and 7 (at 5 mg/kg). Kidneys and lungs from survivors were cultured on day 11. Control mice in both experiments had 90 to 100% mortality. Amphotericin B at 0.5 mg/kg and LY303366 at 1 mg/kg yielded 10 to 20% survival rates for mice infected with either AF210 or AF65. Amphotericin B at 2 and 5 (both regimens) mg/kg yielded a 70 to 100% survival rate for mice infected with AF210 but a 10 to 30% survival rate for mice infected with AF65 (P = 0.01 to 0.04 compared with AF210). Against AF210 and AF65, LY303366 at 2.5, 10, and 25 mg/kg produced a survival rate of 70 to 80%, which was as effective as amphotericin B for AF210, but superior to amphotericin B for AF65 (P < 0.03 to 0.0006). For AF65, LY303366 at 10 and 25 mg/kg/day was superior to amphotericin B at 2 and 5 mg/kg/day in reducing tissue colony counts (P = 0.01 to 0.003), and for AF210, amphotericin B at 5 mg/kg/day and at 5 mg/kg in four doses was more effective than all four regimens of LY303366 in reducing renal culture counts (P = 0.01 to 0.0001). The present study shows, for the first time, that in vivo resistance of A. fumigatus to amphotericin B exists, although this could not be detected by in vitro susceptibility assays. Furthermore, LY303366 appears to be effective against amphotericin B-susceptible and -resistant A. fumigatus infection in this model and should be further evaluated clinically