Scope of Work and Background. The NHS is facing a period of unprecedented change – probably the most complex and significant in its history. The role of managers and leaders during this transition period is critical. They will need to help create the conditions for the new system to succeed, balance a number of competing tensions and „chart a path‟ through both „for‟; and „with‟ their staff, ensuring deep engagement in order to improve the quality of services, retain financial control and meet the quality and productivity challenge. It is with this new phase of the NHS in mind, that the Institute for Innovation and Improvement has refreshed its award winning NHS Graduate Management Training Scheme in order to strengthen the development of emerging talent and leadership capacity to effectively lead and manage change through transition and into the future. We are refreshing the scheme ready for the 2011 intake in terms of: A new recruitment and assessment process that measures updated leadership behaviours based on the new NHS Leadership Framework, together with a greater emphasis on emotional intelligence and NHS values A new education tender stressing the need for leaders for improvement in the new NHS New competencies both technical and leadership (mapped against updated professional body and NHS needs and the new Leadership Framework) New work placement experiences to reflect the changing nature of the new NHS structures The Institute for Innovation and Improvement therefore invites providers of quality educational input to express an interest in the delivery of one, or a multiple of, education inputs for the 2011 intake to support the refreshed scheme and to contribute to the challenges facing the NHS.
Scope of Work and Background. Scope of the work is the establishment and characterization of in vitro models for the prediction of the renal proximal tubular (PT) toxicity of environmental and industrial chemicals in humans. Furthermore, the in vitro models should be applied for predicting the human PT toxicity of [redacted] ToxCast compounds with unknown nephrotoxicity in humans. A longer term goal is the regulatory acceptance of the in vitro models and a respective proposal to FDA should be submitted during the current funding period. The kidney is a major target organ for chemical-induced toxicity, both drugs and environmental chemicals, and injury to the renal PT is frequently observed (Choudhury and Ahmed, 2006; Gil et al., 2005; Jarup and Akesson, 2009; Xxxxxxxx, 2008; Tiong et al., 2014; Xxxxxx et al., 1979). This is due to the roles of the PT in clearing compounds from the bloodstream by active transport into the glomerular filtrate, in reabsorbing compounds from the glomerular filtrate and in compound metabolism (Lash et al., 2006; Lash et al., 2008; Xxxx et al., 1998; Xxxxxxxxx et al., 2013; Xxxxxxxxx et al., 2012). The ToxCast models have not covered nephrotoxicity yet due to a lack of in vitro models that can reliably predict nephrotoxicity, and in particular PT toxicity (a comprehensive overview over current renal in vitro models and their predictivity is provided in (Tiong et al., 2014)). Recently, the group of X. Xxxx (IBN) has established the first in vitro models for the prediction of renal PT toxicity in humans. These models employed human primary renal proximal tubular cells (HPTC) (Li et al., 2013) or pluripotent stem cell-derived HPTC-like cells (Li et al., 2014). Pre-validation was performed with a set of 41 compounds, which comprised drugs as well as environmental and industrial chemicals (Li et al., 2014; Li et al., 2013). All compounds had well-characterized effects on human kidneys and PT (listed in detail in (Li et al., 2014)). Endpoints of the in vitro models were expression of interleukin (IL)6 and IL8 determined by qPCR. It was demonstrated that use of these endpoints resulted in much higher predictivity than use of other commonly applied endpoints (Li et al., 2014). Computational analysis of the results by using machine learning methods further improved the predictivity (Su et al., 2014). The computational work was performed by the group of Lit Xxxx Xxx (BII). More recently, an in vitro model based on human induced pluripotent stem cell (iPS)-derived HPTC...
