Building bridges? An evaluation of the costs and effectiveness of the separated parents information programme (PIP)

The Separated Parent Information Programme (PIP) is the first nationally available parent education programme for parents involved in litigation over contact and residence in England. The programme is a Contact Activity, introduced by the Children and Adoption Act 2006 as an additional tool for courts to facilitate contact. PIP is a four hour group programme for parents referred by the court. Both parties, i.e. the applicant and respondent, are required to attend the programme, but former couples attend separate groups. The groups are designed to include both men and women. The aim of the programme is to encourage parents to focus on children’s needs and perspectives. The programme is delivered by trained providers from mediation, counselling or contact services backgrounds

Multiplexed activation in mammalian cells using a split-intein CRISPR/Cas12a based synthetic transcription factor

The adoption of CRISPR systems for the generation of synthetic transcription factors has greatly simplified the process for upregulating endogenous gene expression, with a plethora of applications in cell biology, bioproduction and cell reprogramming. The recently discovered CRISPR/Cas12a (Cas12a) systems offer extended potential, as Cas12a is capable of processing its own crRNA array, to provide multiple individual crRNAs for subsequent targeting from a single transcript. Here we show the application of dFnCas12a-VPR in mammalian cells, with the Francisella novicida Cas12a (FnCas12a) possessing a shorter PAM sequence than Acidaminococcus sp. (As) or Lachnospiraceae bacterium (Lb) variants, enabling denser targeting of genomic loci, while performing just as well or even better than the other variants. We observe that synergistic activation and multiplexing can be achieved using crRNA arrays but also show that crRNAs expressed towards the 5′ of 6-crRNA arrays show evidence of enhanced activity. This not only represents a more flexible tool for transcriptional modulation but further expands our understanding of the design capabilities and limitations when considering longer crRNA arrays for multiplexed targeting

Multiple Imputation When Rate of Change Is The Outcome of Interest

Little research has been devoted to multiple imputation (MI) of derived variables. We investigated various MI approaches for the outcome, rate of change, when the analysis model is a two-stage linear regression. Our simulations showed that competitive approaches depended on the missing data mechanism and presence of auxiliary terms