Renal medullary carcinomas depend upon SMARCB1 loss and are sensitive to proteasome inhibition.

Renal medullary carcinoma (RMC) is a rare and deadly kidney cancer in patients of African descent with sickle cell trait. We have developed faithful patient-derived RMC models and using whole-genome sequencing, we identified loss-of-function intronic fusion events in one SMARCB1 allele with concurrent loss of the other allele. Biochemical and functional characterization of these models revealed that RMC requires the loss of SMARCB1 for survival. Through integration of RNAi and CRISPR-Cas9 loss-of-function genetic screens and a small-molecule screen, we found that the ubiquitin-proteasome system (UPS) was essential in RMC. Inhibition of the UPS caused a G2/M arrest due to constitutive accumulation of cyclin B1. These observations extend across cancers that harbor SMARCB1 loss, which also require expression of the E2 ubiquitin-conjugating enzyme, UBE2C. Our studies identify a synthetic lethal relationship between SMARCB1-deficient cancers and reliance on the UPS which provides the foundation for a mechanism-informed clinical trial with proteasome inhibitors.

An interprofessional learning experience for trainee general practitioners in an academic urban minor injuries unit with advanced nurse practitioners (Emergency).

BACKGROUND: There is a body of empirical literature indicating that interprofessional education (IPE) not only enriches students' understanding of their own discipline but of other disciplines. However, giving the on-going emphasis on the importance of IPE to healthcare processes and outcomes, on-going attention is needed to advancing the research evidence related to the emergency department setting. The aim of this qualitative descriptive study was to determine the clinical learning experiences of GPs who rotated through an academic urban minor injuries unit as part of their training, led by advanced nurse practitioners (emergency). METHODS: Data were drawn from semi-structured interviews of sixty to ninety minutes duration with 5 general practitioners (GPs) who completed the trainee rotation practicum in an academic urban minor injuries unit led by advanced nurse practitioners (ANPs) emergency. STUDY FINDINGS: The GPs indicated that their knowledge translation of minor injuries to practice was connected to their utilisation of algorithm rules and case management processes modelled by ANPs (emergency). The outcome of this process reported by GPs brought notable reductions to their referral of patients with minor injuries to emergency departments. CONCLUSION: Interprofessional learning in clinical practice with ANPs (emergency) was seen as a valuable role making model for the trainee GPs who are now employed in primary care.

Minor injury attendance times to the ED.

The Health Service Executive (HSE) highlights the need for effective patient throughput and management, whilst providing appropriate staffing and therapeutic interventions. It acknowledges that patient need is integral to the development of a nurse led service and advocates planning staffing levels to reflect arrival times of patients. An observational study of all patients who presented to the emergency department in July 2005 and February 2006 was undertaken (n=7768). The study identified 1577 patients suitable for treatment by the Advanced Nurse Practitioner (ANP) in these two months, which represents 20% of all patient attendances to the ED in this time period. A data collection tool was devised collectively by the ANPs to identify appropriate patients. The findings of the study revealed that 73% of patients suitable for the ANP service presented between the hours of 0800 and 2000, of which 54% attended between 0800 and 1600 h. Sunday emerged as the busiest day in July 2005 whereas Monday was found to be the busiest day in February 2006. Friday was found to be consistently busy for both months.