These results suggest that there are substantial variations in glycaemic control among people with Type 1 diabetes between the data sources and that there is room for improvement in all populations, especially in young adults.

Aims/hypothesis While the use of insulin pumps in paediatrics has expanded dramatically, there is still considerable variability among countries in the use of pump technology. The present study sought to describe differences in metabolic control and pump use in young people with type 1 diabetes using data collected in three multicentre registries. Methods Data for the years 2011 and 2012 from 54,410 children and adolescents were collected from the Prospective Diabetes n=26,198), T1D Exchange (T1DX; n=13,755) and the National Paediatric Diabetes Audit (NPDA; n=14,457). The modality of insulin delivery, based on age, sex and ethnic minority status, and the impact of pump use on HbA 1c levels were compared. differences in metabolic control exist across the three large transatlantic registries of paediatric patients with type 1 diabetes, which appears to be due in part to the frequency of insulin pump therapy. Results

Early cellular events associated with tumorigenesis often include loss of cell cycle checkpoints or alteration in growth signaling pathways. Identification of novel genes involved in cellular proliferation may lead to new classes of cancer therapeutics. By screening a tetracycline-inducible cDNA library in A549 cells for genes that interfere with proliferation, we have identified a fragment of UHRF1 (ubiquitin-like protein containing PHD and RING domains 1), a nuclear RING finger protein, that acts as a dominant negative effector of cell growth. Reduction of UHRF1 levels using an UHRF1-specific shRNA decreased growth rates in several tumor cell lines. In addition, treatment of A549 cells with agents that activated different cell cycle checkpoints resulted in down-regulation of UHRF1. The primary sequence of UHRF1 contains a PHD and a RING motif, both of which are structural hallmarks of ubiquitin E3 ligases. We have confirmed using an in vitro autoubiquitination assay that UHRF1 displays RING-dependent E3 ligase activity. Overexpression of a GFP-fused UHRF1 RING mutant that lacks ligase activity sensitizes cells to treatment with various chemotherapeutics. Taken together, our results suggest a general requirement for UHRF1 in tumor cell proliferation and implicate the RING domain of UHRF1 as a functional determinant of growth regulation.