Neither Fear Nor Favour, Affection Or Ill Will: Modernisation of care proceedings and the use and value of independent social work expertise to senior judges

This is part two of an evaluation of the work of independent social work experts (ISWs) in care proceedings (stage I was published in April 2012). It takes forward findings from stage I exploring further the evidential base for views put to the Family Justice Review about the practice of courts. It examines the views, experiences and practices of a sample of senior judges in commissioning ISW assessments, placing these in the context of the timing, format and value of local authority assessments. Finally, judges’ views about the implications of the modernisation programme for use of ISWs are explored - in the light of a need for earlier completion of cases, without loss of quality in assessments, and with regard to issues of fairness, justice and transparency in judicial decision making. In the report each section is followed by a summary of findings reflecting the key issue for policy and practice. The study is based on interviews with 23 senior judges (20 DFJs, 3 Circuit Judges) in 20/43 county courts in England and Wales. Interviews were held between February and April 2013. They include representation from all circuits, and courts with small and high volume case loads (less than 115, 251 - 900 applications in 12 months). They hear applications from just over half of authorities in England (59%) and just over one third (36%) in Wales

MITF and c-Jun antagonism interconnects melanoma dedifferentiation with pro-inflammatory cytokine responsiveness and myeloid cell recruitment.

Inflammation promotes phenotypic plasticity in melanoma, a source of non-genetic heterogeneity, but the molecular framework is poorly understood. Here we use functional genomic approaches and identify a reciprocal antagonism between the melanocyte lineage transcription factor MITF and c-Jun, which interconnects inflammation-induced dedifferentiation with pro-inflammatory cytokine responsiveness of melanoma cells favouring myeloid cell recruitment. We show that pro-inflammatory cytokines such as TNF-α instigate gradual suppression of MITF expression through c-Jun. MITF itself binds to the c-Jun regulatory genomic region and its reduction increases c-Jun expression that in turn amplifies TNF-stimulated cytokine expression with further MITF suppression. This feed-forward mechanism turns poor peak-like transcriptional responses to TNF-α into progressive and persistent cytokine and chemokine induction. Consistently, inflammatory MITF(low)/c-Jun(high) syngeneic mouse melanomas recruit myeloid immune cells into the tumour microenvironment as recapitulated by their human counterparts. Our study suggests myeloid cell-directed therapies may be useful for MITF(low)/c-Jun(high) melanomas to counteract their growth-promoting and immunosuppressive functions