MRNIP limits ssDNA gaps during replication stress.

Replication repriming by the specialized primase-polymerase PRIMPOL ensures the continuity of DNA synthesis during replication stress. PRIMPOL activity generates residual post-replicative single-stranded nascent DNA gaps, which are linked with mutagenesis and chemosensitivity in BRCA1/2-deficient models, and which are suppressed by replication fork reversal mediated by the DNA translocases SMARCAL1 and ZRANB3. Here, we report that the MRE11 regulator MRNIP limits the prevalence of PRIMPOL and MRE11-dependent ssDNA gaps in cells in which fork reversal is perturbed either by treatment with the PARP inhibitor Olaparib, or by depletion of SMARCAL1 or ZRANB3. MRNIP-deficient cells are sensitive to PARP inhibition and accumulate PRIMPOL-dependent DNA damage, supportive of a pro-survival role for MRNIP linked to the regulation of gap prevalence. In MRNIP-deficient cells, post-replicative gap filling is driven in S-phase by UBC13-mediated template switching involving REV1 and the TLS polymerase Pol-ζ. Our findings represent the first report of modulation of post-replicative ssDNA gap dynamics by a direct MRE11 regulator.

The most effective way of delivering a train-the-trainers program: a systematic review.

INTRODUCTION: Previous literature has shown that multifaceted, interactive interventions may be the most effective way to train health and social care professionals. A Train-the-Trainer (TTT) model could incorporate all these components. We conducted a systematic review to determine the overall effectiveness and optimal delivery of TTT programs. METHODS: We searched 15 databases. Reference lists and online resources were also screened. Studies with an objective follow-up measure collected over 1 week after the intervention were included. The intervention had to be based on a TTT model for health and social care professionals. RESULTS: Eighteen studies met the inclusion criteria. TTT interventions varied greatly, ranging from didactic presentations to group discussions and role-plays. The heterogeneity of the studies and limited data prevented meta-analysis. A narrative review found that the TTT programs in 13 studies helped to increase knowledge, improve clinical behavior, or produce better patient outcomes. One study showed no effect. Three studies showed possible effect and one study showed that a CD-ROM training method was more effective than a TTT training method in improving participants' knowledge. Ratings of the studies' methodologies suggested moderate risk of bias, which limits interpretation of the results. DISCUSSION: There is evidence that using a blended learning approach to deliver TTT programs--combining different techniques such as interactive, multifaceted methods and accompanying learning materials--can help to effectively disseminate and implement guidelines and curricula to health and social care professionals. However, further research is needed to determine the optimum "blend" of techniques.

Using a Delphi process to develop an effective train-the-trainers program to train health and social care professionals throughout Europe.

Research has shown that developing a Train-the-Trainers (TTT) program is important if agencies are to implement guidelines, but the most effective way to deliver a TTT program remains unanswered. This article presents data from a 3-round Internet-based Delphi process, which was used to help develop consensus-based guidelines for a TTT programme to deliver to health and social care professionals throughout Europe a curriculum on traumatic stress. In Round 1, 74 experts rated the importance of statements relating to the TTT field and then reassessed their scores in the light of others' responses in subsequent rounds. Forty-one (67%) of 61 statements achieved consensus (defined as having a mean score >7 or < 3 on the 0-9 rating scales used and 70% of participants scoring 7 and above or 3 and below) for inclusion. Key TTT components included interactive and practical presentations, delivery to groups of 7-12 people over 2 days, external and local expert facilitation, course manuals, refresher courses, and supervision. The Delphi process allowed a consensus to be achieved in an area in which there are limitations in the current evidence.