Adapting systems thinking and safety reporting in high-consequence industries to healthcare.

This chapter uses a systems approach to represent the healthcare sector and positions safety reporting programs as feedback mechanisms to reactively, proactively, and predictively improve the overall reliability and safety of care practices. Drawing from the aviation sector, benefits and limitations of different safety reporting systems are explored and challenges to adapting such systems into healthcare are presented. Examples of successful adaptation and implementation in healthcare demonstrate that while adaptation is possible and could yield impressive outcomes, such programs remain susceptible to the natural tendency of the healthcare system to remain siloed and internally competitive, rather than holistic and team-oriented. Thus, one could conclude that in order for safety reporting programs to be self-sustaining, the systemic disincentives need to be examined carefully and intentionally removed, replacing them with meaningful incentives to collaboration and maximization of patient safety outcomes.

Comparative analysis of mesenchymal stem cell and embryonic tendon progenitor cell response to embryonic tendon biochemical and mechanical factors.

INTRODUCTION: Advances in tendon engineering with mesenchymal stem cells (MSCs) are hindered by a need for cues to direct tenogenesis, and markers to assess tenogenic state. We examined the effects of factors involved in embryonic tendon development on adult MSCs, and compared MSC responses to that of embryonic tendon progenitor cells (TPCs), a model system of tenogenically differentiating cells. METHODS: Murine MSCs and TPCs subjected to cyclic tensile loading, transforming growth factor-ß2 (TGFß2), and fibroblast growth factor-4 (FGF4) in vitro were assessed for proliferation and mRNA levels of scleraxis, TGFß2, tenomodulin, collagen type I and elastin. RESULTS: Before treatment, scleraxis and elastin levels in MSCs were lower than in TPCs, while other tendon markers expressed at similar levels in MSCs as TPCs. TGFß2 alone and combined with loading were tenogenic based on increased scleraxis levels in both MSCs and TPCs. Loading alone had minimal effect. FGF4 downregulated tendon marker levels in MSCs but not in TPCs. Select tendon markers were not consistently upregulated with scleraxis, demonstrating the importance of characterizing a profile of markers. CONCLUSIONS: Similar responses as TPCs to specific treatments suggest MSCs have tenogenic potential. Potentially shared mechanisms of cell function between MSCs and TPCs should be investigated in longer term studies.

Embryonic mechanical and soluble cues regulate tendon progenitor cell gene expression as a function of developmental stage and anatomical origin.

Stem cell-based engineering strategies for tendons have yet to yield a normal functional tissue, due in part to a need for tenogenic factors. Additionally, the ability to evaluate differentiation has been challenged by a lack of markers for differentiation. We propose to inform tendon regeneration with developmental cues involved in normal tissue formation and with phenotypic markers that are characteristic of differentiating tendon progenitor cells (TPCs). Mechanical forces, fibroblast growth factor (FGF)-4 and transforming growth factor (TGF)-ß2 are implicated in embryonic tendon development, yet the isolated effects of these factors on differentiating TPCs are unknown. Additionally, developmental mechanisms vary between limb and axial tendons, suggesting the respective cell types are programmed to respond uniquely to exogenous factors. To characterize developmental cues and benchmarks for differentiation toward limb vs. axial phenotypes, we dynamically loaded and treated TPCs with growth factors and assessed gene expression profiles as a function of developmental stage and anatomical origin. Based on scleraxis expression, TGFß2 was tenogenic for TPCs at all stages, while loading was for late-stage cells only, and FGF4 had no effect despite regulation of other genes. When factors were combined, TGFß2 continued to be tenogenic, while FGF4 appeared anti-tenogenic. Various treatments elicited distinct responses by axial vs. limb TPCs of specific stages. These results identified tenogenic factors, suggest tendon engineering strategies should be customized for tissues by anatomical origin, and provide stage-specific gene expression profiles of limb and axial TPCs as benchmarks with which to monitor tenogenic differentiation of stem cells.

Elastogenic protein expression of a highly elastic murine spinal ligament: the ligamentum flavum.

Spinal ligaments, such as the ligamentum flavum (LF), are prone to degeneration and iatrogenic injury that can lead to back pain and nerve dysfunction. Repair and regeneration strategies for these tissues are lacking, perhaps due to limited understanding of spinal ligament formation, the elaboration of its elastic fibers, maturation and homeostasis. Using immunohistochemistry and histology, we investigated murine LF elastogenesis and tissue formation from embryonic to mature postnatal stages. We characterized the spatiotemporal distribution of the key elastogenic proteins tropoelastin, fibrillin-1, fibulin-4 and lysyl oxidase. We found that elastogenesis begins in utero with the microfibril constituent fibrillin-1 staining intensely just before birth. Elastic fibers were first detected histologically at postnatal day (P) 7, the earliest stage at which tropoelastin and fibulin-4 stained intensely. From P7 to P28, elastic fibers grew in diameter and became straighter along the axis. The growth of elastic fibers coincided with intense staining of tropoelastin and fibulin-4 staining, possibly supporting a chaperone role for fibulin-4. These expression patterns correlated with reported skeletal and behavioral changes during murine development. This immunohistochemical characterization of elastogenesis of the LF will be useful for future studies investigating mechanisms for elastogenesis and developing new strategies for treatment or regeneration of spinal ligaments and other highly elastic tissues.

Building geographic information system capacity in local health departments: lessons from a North Carolina project.

State government, university, and local health department (LHD) partners collaborated to build the geographic information system (GIS) capacity of 5 LHDs in North Carolina. Project elements included procuring hardware and software, conducting individualized and group training, developing data layers, guiding the project development process, coordinating participation in technical conferences, providing ongoing project consultation, and evaluating project milestones. The project provided health department personnel with the skills and resources required to use sophisticated information management systems, particularly those that address spatial dimensions of public health practice. This capacity-building project helped LHDs incorporate GIS technology into daily operations, resulting in improved time and cost efficiency. Keys to success included (1) methods training rooted in problems specific to the LHD, (2) required project identification by LHD staff with associated timelines for development, (3) ongoing technical support as staff returned to home offices after training, (4) subgrants to LHDs to ease hardware and software resource constraints, (5) networks of relationships among LHDs and other professional GIS users, and (6) senior LHD leadership who supported the professional development activities being undertaken by staff.