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1.  ECM stiffness primes the TGFβ pathway to promote chondrocyte differentiation 
Molecular Biology of the Cell  2012;23(18):3731-3742.
ECM stiffness enhances chondrocyte differentiation by priming cells for a potent response to TGFβ. ECM stiffness modifies the TGFβ pathway at multiple levels, including stiffness-sensitive induction of TGFβ1 expression, Smad3 phosphorylation, and synergistic activation of chondrocyte differentiation, by combining TGFβ and an inductive ECM stiffness.
Cells encounter physical cues such as extracellular matrix (ECM) stiffness in a microenvironment replete with biochemical cues. However, the mechanisms by which cells integrate physical and biochemical cues to guide cellular decision making are not well defined. Here we investigate mechanisms by which chondrocytes generate an integrated response to ECM stiffness and transforming growth factor β (TGFβ), a potent agonist of chondrocyte differentiation. Primary murine chondrocytes and ATDC5 cells grown on 0.5-MPa substrates deposit more proteoglycan and express more Sox9, Col2α1, and aggrecan mRNA relative to cells exposed to substrates of any other stiffness. The chondroinductive effect of this discrete stiffness, which falls within the range reported for articular cartilage, requires the stiffness-sensitive induction of TGFβ1. Smad3 phosphorylation, nuclear localization, and transcriptional activity are specifically increased in cells grown on 0.5-MPa substrates. ECM stiffness also primes cells for a synergistic response, such that the combination of ECM stiffness and exogenous TGFβ induces chondrocyte gene expression more robustly than either cue alone through a p38 mitogen-activated protein kinase–dependent mechanism. In this way, the ECM stiffness primes the TGFβ pathway to efficiently promote chondrocyte differentiation. This work reveals novel mechanisms by which cells integrate physical and biochemical cues to exert a coordinated response to their unique cellular microenvironment.
PMCID: PMC3442419  PMID: 22833566
2.  Transfusion related acute lung injury after transfusion of maternal blood: a case control study 
Spine  2010;35(23):E1322-E1327.
Study Design
This is a single center retrospective case control study of 7 Transfusion Related Acute Lung Injury (TRALI) cases and 28 controls in the pediatric spinal surgery population.
To determine the association between maternal transfusion and risk of TRALI in pediatric spinal surgery patients.
Summary of Background Data
Previous studies support a “two-hit” model for the pathogenesis of TRALI – activation and sequestration of neutrophils in the pulmonary vasculature followed by transfusion of a biologic response modifier such as anti-leukocyte antibodies. Maternal donation of blood products is a potential risk factor for TRALI due to the development of anti-leukocyte antibodies during pregnancy. Until now there have been no studies specifically addressing the risk of TRALI following maternal transfusions.
This is a retrospective case control study of 7 TRALI cases with 4 controls per case, matched by strata for volume of plasma transfused. All cases identified by the Transfusion Biology and Medicine Specialized Center of Clinically Oriented Research (SCCOR) with a TRALI diagnosis were eligible for inclusion. Electronic medical records and operative notes were reviewed to obtain demographic data, diagnosis, surgical approach and number of spine levels for each operation.
An increased prevalence of maternal blood transfusion was found among the TRALI cases compared to the control cases: 43% (3 of 7) versus 7% (2 of 28), p = 0.044. There were otherwise no statistical differences between the groups, including age, gender, surgical approach, number of spinal levels, or type of blood product transfused.
Pediatric patients undergoing spinal surgery may be at increased risk for the development of TRALI following the transfusion of maternal blood products. Accordingly, we recommend that directed donation of maternal blood products should be avoided in this population. This study also found that TRALI may be under-recognized and under-reported to the transfusion service.
PMCID: PMC2964398  PMID: 20938390
3.  Increasing the use of evidence in health policy: practice and views of policy makers and researchers 
Better communication is often suggested as fundamental to increasing the use of research evidence in policy, but little is known about how researchers and policy makers work together or about barriers to exchange. This study explored the views and practice of policy makers and researchers regarding the use of evidence in policy, including: (i) current use of research to inform policy; (ii) dissemination of and access to research findings for policy; (iii) communication and exchange between researchers and policy makers; and (iv) incentives for increasing the use of research in policy.
Separate but similar interview schedules were developed for policy makers and researchers. Senior policy makers from NSW Health and senior researchers from public health and health service research groups in NSW were invited to participate. Consenting participants were interviewed by an independent research company.
Thirty eight policy makers (79% response rate) and 41 researchers (82% response rate) completed interviews. Policy makers reported rarely using research to inform policy agendas or to evaluate the impact of policy; research was used more commonly to inform policy content. Most researchers reported that their research had informed local policy, mainly by increasing awareness of an issue. Policy makers reported difficulty in accessing useful research syntheses, and only a third of researchers reported developing targeted strategies to inform policy makers of their findings. Both policy makers and researchers wanted more exchange and saw this as important for increasing the use of research evidence in policy; however, both groups reported a high level of involvement by policy makers in research.
Policy makers and researchers recognise the potential of research to contribute to policy and are making significant attempts to integrate research into the policy process. These findings suggest four strategies to assist in increasing the use of research in policy: making research findings more accessible to policy makers; increasing opportunities for interaction between policy makers and researchers; addressing structural barriers such as research receptivity in policy agencies and a lack of incentives for academics to link with policy; and increasing the relevance of research to policy.
PMCID: PMC2739528  PMID: 19698186

Results 1-3 (3)