ABSTRACT
OBJECTIVES: The UK National Institute for Health Research (NIHR) training programmes were created to build and sustain research capacity in healthcare. Following the training programme 10-year strategic review, this qualitative study aimed to deepen understanding of facilitators and barriers for those progressing through NIHR-supported research careers. DESIGN: Semistructured qualitative study. DATA COLLECTION AND ANALYSIS: Telephone interviews conducted between May and August 2017 were digitally recorded, transcribed and analysed using Framework Approach. SETTING: UK National Health Service (NHS) Trusts, university medical schools, District General Hospitals, Integrated Academic Training Programme centres and Research Design Services across the North East, North West, South East and South West of England, London and the Midlands. PARTICIPANTS: Fourteen women and eight men, of whom, 14 were previous or current NIHR personal awardees (seven doctors and seven allied health professionals (AHPs) or nurses) and eight were managers (staff within clinical or university training-related roles). RESULTS: (1) NIHR awards were viewed as transformative for research careers; (2) however, there were perceptions of a biased 'playing field'. (3) Inequalities were perceived for AHPs and nurses, those outside of established research institutes and those in 'unfashionable' specialisms. (4) While support for NIHR awards contributed to a healthy research culture, (5) short-term awards were perceived as a barrier to continuing an independent research career. CONCLUSIONS: Participants perceived many strengths of the NIHR training programmes in terms of developing individual careers and research capacity. Areas in which improvement could enhance the ability to attract, develop and retain researcher were identified. Our findings are of relevance to schemes in other countries, where healthcare researchers experience similar challenges. Further work is needed to overcome barriers and ensure equity of access to, and success within, clinical research training schemes to sustain the research workforce needed to address future global health challenges.
Subject(s)
Physicians , State Medicine , Allied Health Personnel , Female , Humans , Male , Qualitative Research , Research PersonnelSubject(s)
Anti-Inflammatory Agents/therapeutic use , Cardiovascular Agents/therapeutic use , Cardiovascular Diseases/drug therapy , Colchicine/therapeutic use , Drug Repositioning , Inflammation Mediators/antagonists & inhibitors , Anti-Inflammatory Agents/adverse effects , Cardiovascular Agents/adverse effects , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/mortality , Cardiovascular Diseases/physiopathology , Colchicine/adverse effects , Humans , Inflammation Mediators/metabolismABSTRACT
The mosquito protein AEG12 is up-regulated in response to blood meals and flavivirus infection though its function remained elusive. Here, we determine the three-dimensional structure of AEG12 and describe the binding specificity of acyl-chain ligands within its large central hydrophobic cavity. We show that AEG12 displays hemolytic and cytolytic activity by selectively delivering unsaturated fatty acid cargoes into phosphatidylcholine-rich lipid bilayers. This property of AEG12 also enables it to inhibit replication of enveloped viruses such as Dengue and Zika viruses at low micromolar concentrations. Weaker inhibition was observed against more distantly related coronaviruses and lentivirus, while no inhibition was observed against the nonenveloped virus adeno-associated virus. Together, our results uncover the mechanistic understanding of AEG12 function and provide the necessary implications for its use as a broad-spectrum therapeutic against cellular and viral targets.