A Framework for Citizen-Centred Social Statistics and Analysis (Working Paper 48)

Economic policy-making has long been more integrated than social policy-making in part because the statistics and much of the analysis that supports economic policy are based on a common conceptual framework – the system of national accounts. People interested in economic analysis and economic policy share a common language of communication, one that includes both concepts and numbers. This paper examines early attempts to develop a system of social statistics that would mirror the system of national accounts, particular the work on the development of social accounts that took place mainly in the 60s and 70s. It explores the reasons why these early initiatives failed but argues that the preconditions now exist to develop a new conceptual framework to support integrated social statistics – and hence a more coherent, effective social policy. Optimism is warranted for two reasons. First, we can make use of the radical transformation that has taken place in information technology both in processing data and in providing wide access to the knowledge that can flow from the data. Second, the conditions exist to begin to shift away from the straight jacket of government-centric social statistics, with its implicit assumption that governments must be the primary actors in finding solutions to social problems. By supporting the decision-making of all the players (particularly individual citizens) who affect social trends and outcomes, we can start to move beyond the sterile, ideological discussions that have dominated much social discourse in the past and begin to build social systems and structures that evolve, almost automatically, based on empirical evidence of ‘what works best for whom’. The paper describes a Canadian approach to developing a framework, or common language, to support the evolution of an integrated, citizen-centric system of social statistics and social analysis. This language supports the traditional social policy that we have today; nothing is lost. However, it also supports a quite different social policy world, one where individual citizens and families (not governments) are seen as the central players – a more empirically-driven world that we have referred to as the ‘enabling society’.

Interactions of Lipoprotein(a) with the Plasminogen System: Mechanisms and Pathophysiological Consequences

Elevated plasma concentrations of lipoprotein(a) (Lp(a)) are associated with increased risk of atherothrombotic disease. Lp(a) is a unique lipoprotein consisting of a low density lipoprotein-like moiety covalently linked to apolipoprotein(a) (apo(a)), a homologue of the fibrinolytic proenzyme plasminogen. Apo(a) is extremely heterogeneous in size with small isoforms being independently associated with increased cardiovascular risk. Several in vitro and in vivo studies have shown that Lp(a)/apo(a) can inhibit tissue-type plasminogen activator (tPA)-mediated plasminogen activation on fibrin surfaces, although the mechanism of inhibition by apo(a) remains controversial. Essential to fibrin clot lysis are a number of plasmin-dependent positive feedback reactions that enhance the efficiency of plasminogen activation, including the plasmin-mediated conversion of Glu1-plasminogen to Lys78-plasminogen. Additionally, abnormal fibrin clot structures have been associated with both an increased risk of cardiovascular disease and elevated Lp(a) levels. Similarly, oxidized phospholipids have been implicated in the development of cardiovascular disease, and are not only preferentially carried by Lp(a) in the plasma but have also been shown to covalently-modify both apo(a) and plasminogen. In this thesis, we built upon the understanding of the role of apo(a) in plasminogen activation on the fibrin/degraded fibrin surface by determining that: (i) apo(a) inhibits plasmin-mediated Glu1-plasminogen to Lys78-plasminogen conversion and identifying the critical domains in apo(a) responsible for this effect, (ii) apo(a) isoform size does not affect either the inhibition of tPA-mediated plasminogen activation or the inhibition of plasmin-mediated Glu1-plasminogen to Lys78-plasminogen conversion, (iii) apo(a) modifies fibrin clot structure to form more dense clots with thinner fibers and reduced permeability, modifications that enhance the ability of apo(a) to inhibit tPA-mediated plasminogen activation and (iv) the phosphorus content of apo(a) affects its ability to inhibit tPA-mediated plasminogen activation and the phosphorus content of plasminogen affects its ability to be activated by tPA. By understanding these individual reactions, each of which has the potential to affect the broader fibrin clot lysis process, we have expanded our understanding of the overall effect of Lp(a)/apo(a) in the inhibition of plasminogen activation on the fibrin/degraded fibrin surface and thus broadened our understanding of how Lp(a)/apo(a) may mediate the inhibition of thrombolysis in vivo.