Genetic and functional basis of the reduction effect in bacteriophage ΦX174.

The ΦX174 reduction effect describes a plasmid-based inhibitory phenomenon that mimics the superinfection inhibition found in wild phage populations. In this effect, when a portion of the ΦX174 genome - the 3' end of the pilot protein gene (H), the 5' end of the replication gene (A), and the H-A intergenic region - is present on a plasmid in the host cell, almost complete protection from phage infection occurs. Here we demonstrate that only the phage pilot protein H portion of the plasmid is sufficient for the observed inhibition, that protein synthesis is necessary for inhibition to occur, that inserting the entire H gene in the plasmid may also impart a blocking effect, and that partial to complete recovery from this inhibition is possible with minimal viral evolution.

Time to STEP UP: methods and findings from the development of guidance to help researchers design inclusive clinical trials.

Background: It is important to design clinical trials to include all those who may benefit from the intervention being tested. Several frameworks have been developed to help researchers think about the barriers to inclusion of particular under-served groups when designing a trial, but there is a lack of practical guidance on how to implement these frameworks. This paper describes the ACCESS project, the findings from each phase of the project and the guidance we developed (STEP UP) on how to design more inclusive trials.

Effective interventions to increase representation of under-served groups in randomised trials in UK and Ireland: a scoping literature review.

Background: Participants in clinical trials often do not reflect the populations that could benefit from the treatments being investigated. There are known barriers to trial participation for under-served groups, but limited evidence on strategies to alleviate these barriers to improve representation. This scoping review aimed to identify effective interventions and design features that improve the representation `of under-served groups in trials, focusing on the UK and Ireland.

A methodological review of randomised n-of-1 trials.

Background: n-of-1 trials are a type of crossover trial designed to optimise the evaluation of health technologies in individual patients. This trial design may be considered for the evaluation of health technologies in rare conditions where fewer patients are available to take part in research. This review describes the characteristics of randomised n-of-1 trials conducted over the span of 12 years, including how the n-of-1 design has been employed to study both rare and non-rare conditions.

Serious bacterial infection risk in recently immunized febrile infants in the emergency department.

Study Objectives: Fever following immunizations is a common presenting chiefcomplaint among infants. The 2021 American Academy of Pediatrics (AAP) febrile infant clinical practice guidelines exclude recently immunized (RI) infants. This is a challenge for clinicians in the management of the febrile RI young infant.