Long-range Angular Correlations On The Near And Away Side In P-pb Collisions At √snn=5.02 Tev

7191/Mar294

On moving targets and magic bullets: Can the UK lead the way with responsible data linkage for health research?

AbstractPurposeTo provide an overview of essential elements of good governance of data linkage for health-related research, to consider lessons learned so far and to examine key factors currently impeding the delivery of good governance in this area. Given the considerable hurdles which must be overcome and the changing landscape of health research and data linkage, a principled, proportionate, risk-based approach to governance is advocated.DiscussionIn light of the considerable value of data linkage to health and well-being, the United Kingdom aspires to design and deliver good governance in health-related research. A string of projects have been asking: what does good governance look like in data linkage for health research? It is argued here that considerable progress can and must be made in order to develop the UK’s contribution to future health and wealth economies, particularly in light of mis-start initiatives such as care.data in NHS England. Discussion centres around lessons learned from previous successful health research initiatives, identifying those governance mechanisms which are essential to achieving good governance.ConclusionThis article suggests that a crucial element in any step-increase of research capability will be the adoption of adaptive governance models. These must recognise a range of approaches to delivering safe and effective data linkage, while remaining responsive to public and research user expectations and needs as these shift and change with time and experience. The targets are multiple and constantly moving. There is not – nor should we seek – a single magic bullet in delivering good governance in health research

Interaction of Shiga toxin from Escherichia coli with human intestinal epithelial cell lines and explants: Stx2 induces epithelial damage in organ culture

Shiga toxins (Stx) produced by Escherichia coli are associated with systemic complications such as haemolytic-uraemic syndrome. The mechanism of Stx translocation across the epithelial barrier is unknown as human intestinal epithelium lacks receptor Gb3. In this study, we have examined the interaction of purified Stx1 and 2 with Caco-2 (Gb3(+)) and T84 (Gb3(-)) cell lines, and determined the effects of Stx on human intestine using in vitro organ culture (IVOC). Stx exposure caused inhibition of protein synthesis and apoptosis in Caco-2 but not in T84 cells. However, both Stx1 and 2 were transported to the endoplasmic reticulum, and the Stx1 A-subunit was cleaved in a furin-dependent manner in both cell lines. Thus, a Gb3-independent retrograde transport route exists in T84 cells for Stx that does not induce cell damage. IVOC demonstrated increased epithelial cell extrusion in response to exposure to Stx2, but not Stx1, in both small intestine and colon. Pretreatment of Stx2 with Stx2-specific antibody abrogated this effect. Overlaying frozen sections with Stx showed lamina propria, but not epithelial, cell binding that paralleled Gb3 localization, and included endothelium and pericryptal myofibroblasts. This indicates that human intestinal epithelium may evince Stx2-induced damage in the absence of Gb3 receptors, by an as yet unrecognized mechanism