4 resultados para 1178
em WestminsterResearch - UK
Resumo:
The debate about the need to build social capital and to engage local communities in public policy has become a central issue in many advanced liberal societies and developing countries. In many countries new forms of governance have emerged out of a growing realisation that representative democracy by itself is no longer sufficient. One of the most significant public policy trends in the UK has been the involvement of community organisations and their members in the delivery of national policy, mediated through local systems of governance and management. One such policy area is urban regeneration. Central government now requires local authorities in England to set up Local Strategic Partnerships (LSPs) to bring together stakeholders who can prepare Community Strategies and deliver social and economic programmes which target areas of deprivation. This paper reviews the key institutional processes which must be addressed, such as representation, accountability and transformation.
Resumo:
Pre-publicity for the final volume of Harold Macmillan’s memoirs, At the End of the Day, stressed that it would provide the British side of the Cuban missile crisis for the first time. The Churchillian model chosen, changes required by the Cabinet Office and Macmillan’s desire to rebuke those political opponents who claimed that the crisis demonstrated a lack of British influence in Washington, however ensured a focus on his personal relationship with President Kennedy. His larding the text with contemporary observations from his diaries also skewed Macmillan’s account and, in particular, underplayed the significance of British moves at the United Nations in New York to secure a credible United Nations inspection regime and a US guarantee of the inviolability of Cuba. Careful reconstruction of Macmillan’s real-time experience of the Cuban missile crisis demonstrates the limitations of his own account of this event
Resumo:
Type 2 diabetes is a metabolic disease categorized primarily by reduced insulin sensitivity, β-cell dysfunction, and elevated hepatic glucose production. Treatments reducing hyperglycemia and the secondary complications that result from these dysfunctions are being sought after. Two distinct pathways encourage glucose transport activity in skeletal muscle, ie, the contraction-stimulated pathway reliant on Ca2+/5′-monophosphate-activated protein kinase (AMPK)-dependent mechanisms and an insulin-dependent pathway activated via upregulation of serine/threonine protein kinase Akt/PKB. Metformin is an established treatment for type 2 diabetes due to its ability to increase peripheral glucose uptake while reducing hepatic glucose production in an AMPK-dependent manner. Peripheral insulin action is reduced in type 2 diabetics whereas AMPK signaling remains largely intact. This paper firstly reviews AMPK and its role in glucose uptake and then focuses on a novel mechanism known to operate via an insulin-dependent pathway. Inositol hexakisphosphate (IP6) kinase 1 (IP6K1) produces a pyrophosphate group at the position of IP6 to generate a further inositol pyrophosphate, ie, diphosphoinositol pentakisphosphate (IP7). IP7 binds with Akt/PKB at its pleckstrin homology domain, preventing interaction with phosphatidylinositol 3,4,5-trisphosphate, and therefore reducing Akt/PKB membrane translocation and insulin-stimulated glucose uptake. Novel evidence suggesting a reduction in IP7 production via IP6K1 inhibition represents an exciting therapeutic avenue in the treatment of insulin resistance. Metformin-induced activation of AMPK is a key current intervention in the management of type 2 diabetes. However, this treatment does not seem to improve peripheral insulin resistance. In light of this evidence, we suggest that inhibition of IP6K1 may increase insulin sensitivity and provide a novel research direction in the treatment of insulin resistance.