Justin Larkin, MD

Abstract
Rationale, aims and objectives
The current health system in the United States is the result of a history of patchwork policy decisions and cultural assumptions that have led to persistent contradictions in practice, gaps in coverage, unsustainable costs, and inconsistent outcomes. In working toward a more efficient health system, understanding and applying complexity science concepts will allow for policy that better promotes desired outcomes and minimizes the effects of… Show more

Abstract
Rationale, aims and objectives
The current health system in the United States is the result of a history of patchwork policy decisions and cultural assumptions that have led to persistent contradictions in practice, gaps in coverage, unsustainable costs, and inconsistent outcomes. In working toward a more efficient health system, understanding and applying complexity science concepts will allow for policy that better promotes desired outcomes and minimizes the effects of unintended consequences.

Methods
This paper will consider three applied complexity science concepts in the context of the Patient Protection and Affordable Care Act (PPACA): developing a shared vision around reimbursement for value, creating an environment for emergence through simple rules, and embracing transformational leadership at all levels.

Results and conclusions
Transforming the US health system, or any other health system, will be neither easy nor quick. Applying complexity concepts to health reform efforts, however, will facilitate long-term change in all levels, leading to health systems that are more effective, efficient, and equitable. Show less

HtrA1, Ddr-2 and Mmp-13 are reliable biomarkers for osteoarthritis (OA), yet the exact mechanism for the upregulation of HtrA-1 is unknown. Some have shown that chondrocyte hypertrophy is associated with early indicators of inflammation including TGF- and the Receptor for Advanced Glycation End products (RAGE). To examine the correlation of inflammation with the expression of biomarkers in osteoarthritis, we performed right knee destabilization surgery on four week old wild type and RAGE… Show more

HtrA1, Ddr-2 and Mmp-13 are reliable biomarkers for osteoarthritis (OA), yet the exact mechanism for the upregulation of HtrA-1 is unknown. Some have shown that chondrocyte hypertrophy is associated with early indicators of inflammation including TGF- and the Receptor for Advanced Glycation End products (RAGE). To examine the correlation of inflammation with the expression of biomarkers in osteoarthritis, we performed right knee destabilization surgery on four week old wild type and RAGE knock-out (KO) mice. We assayed for HtrA-1, TGF-1, Mmp-13, and Ddr-2 in articular cartilage at 3, 7, 14 and 28 days post-surgery by immunohistochemistry on left and right knee joints. RAGE KO and wild type mice both showed staining for key OA biomarkers. However, RAGE KO mice were significantly protected against OA compared to controls. We observed a difference in the total number of chondrocytes and percentage of chondrocytes staining positive for OA biomarkers between RAGE KO and control mice. The percentage of cells staining for OA biomarkers correlated with severity of cartilage degradation. Our results indicate that the absence of RAGE did protect against the development of advanced OA. We conclude that HtrA-1 plays a role in lowering TGF-B1 expression in the process of making articular cartilage vulnerable to damage associated with OA progression. Show less