Infection with Ebola virus (EBOV) is responsible for haemorrhagic fever in humans with a high mortality rate. Combined efforts of prevention and therapeutic intervention are required to tackle highly variable RNA viruses, whose infections often lead to outbreaks. Here, we have screened the 2P2I3D chemical library using a nanoluc-based protein complementation assay (NPCA) and isolated two compounds disrupting the interaction of the EBOV protein fragment VP35IID with the N terminus of the dsRNA-binding proteins PKR and PACT, involved in IFN response and/or intrinsic immunity, respectively. The two compounds inhibited EBOV infection in cell culture as well as infection by measles virus (MV) independently of IFN induction. Consequently, we propose the compounds are antiviral by restoring intrinsic immunity driven by PACT. Given that PACT is highly conserved across mammals, we support further testing of the compounds in other species, as well as against further negative sense RNA viruses.

The Performance Assessment for California Teachers (PACT) is a high stakes summative assessment that was designed to measure pre-service teacher readiness. We examined the inter-rater reliability (IRR) of trained PACT evaluators who rated 19 candidates. As measured by Cohen’s weighted kappa, the overall IRR estimate was .17 (poor strength of agreement). IRR estimates ranged from -.29 (worse than expected by chance) to .54 (moderate strength of agreement); all were below the standard of .70 for consensus agreement. Follow up interviews of 10 evaluators revealed possible reasons we observed low IRR, such as departures from established PACT scoring protocol, and lack of, or inconsistent, use of a scoring aid document. Evaluators reported difficulties scoring the materials that candidates submitted, particularly the use of Academic Language. Cognitive Task Analysis (CTA) is suggested as a method to improve IRR in the PACT and other teacher performance assessments such as the edTPA.

It is widely recognized that public health interventions benefit from community engagement and leadership, yet there are challenges to evaluating complex, community-led interventions assuming hierarchies of evidence derived from laboratory experimentation and clinical trials. Particular challenges include, first, inconsistency of the intervention across sites; and second, absence of researcher control over the sampling frame and methodology. This report highlights these challenges as they played out in the evaluation of a community-organized health project in South London. The project aimed to benefit maternal mental health, health literacy and social capital, and especially to engage local populations known to have reduced contact with statutory services. We evaluated the project using two studies with different designs, sampling frames and methodologies. In one the sampling frame and methodology were under community control, permitting comparison of change in outcomes from before to after participation in the project. In the other, the sampling frame and methodology were under researcher control, permitting a case-control design. The two evaluations led to different results however: participants in the community-controlled study showed benefits, while participants in the researcher-controlled study did not. The principal conclusions are that while there are severe challenges to evaluating a community-led health intervention using a controlled design, measurement of pre-/post-participation changes in well-defined health outcomes should typically be a minimum evaluation requirement, and confidence in attributing causation of any positive changes to participation can be increased by use of interventions in the project and in the engagement process itself that have a credible theoretical and empirical basis.