Evaluation of Factors that Modulate Cellular Adipogenesis for Breast Tissue Engineering Strategies

It is estimated that this year more than 200,000 women in the United States will be diagnosed with breast cancer. Treatment for most occurrences of breast cancer will often include surgical removal of the tumorigenic tissue, resulting in a soft tissue defect within the subcutaneous tissue of the skin. Post-surgical reconstruction methods are often sought by patients to restore the aesthetic function of the breast via cellular or non-cellular methods; however, because of complications associated with currently used methods for breast reconstruction, researchers are investigating tissue engineering methods to produce viable autologous adipose tissue for breast reconstruction. Previous research in our laboratory has focused on the development of an injectable composite system for breast reconstruction that uses injectable microcarrier beads as support scaffolds for cellular growth. In vitro and in vivo studies of this system have shown that the polymeric microcarriers not only support cellular attachment, but also facilitate proliferation and differentiation of adipose cells, and yield biocompatible tissue response in an in vivo host. Successful clinical implementation of this system, like many other adipose tissue engineering methods, has been limited by an inability to engineer adipose tissue of sustained volume long-term. It is hypothesized that more optimal in vitro culturing methods for adipose cells could yield populations of fat cells capable of differentiating to adipocytes and retaining their capacity for lipid-filing over time. The goal of this work, therefore, was to evaluate specific factors that influence adipose cell differentiation in an attempt to create a more successful injectable composite system for breast reconstruction. While adipogenesis is influenced by many factors, for this work, we investigated two specific areas: 1) the influence of adipose cell-mammary epithelial cell interactions and 2) the influence of fatty acids on adipose cell differentiation in vitro. A series of conditioned media studies were first performed to determine how adipogenesis of primary adipose cells from bovine, murine, and human tissue samples was influenced by mammary epithelial cell-conditioned media. Depending on the source of conditioned media and the species of adipose cell, adipose cell differentiation was either positively or negatively influenced by the conditioned media as evidenced by increased or decreased triglyceride production and lipid accumulation in the two-dimensional cultures. Characterization of the components of the conditioned media samples showed that mammary epithelial cell-conditioned media contains measurable quantities of factors that influence adipogenesis. To investigate the influence of fatty acids on adipose cell differentiation, a series of studies were performed to identify an optimal concentration of fatty acid and an optimal culture time for supplementing adipose cells with a fatty acid that would stimulate fatty acid uptake and subsequent lipid filling of the cells. Exogenous fatty acids in cell culture medium were found to influence adipogenesis. Microcarrier beads containing fatty acids were then manufactured and used in three-dimensional cell culture experiments to determine if microcarrier beads could be used for fatty acid delivery while simultaneously supporting adipose cell growth and differentiation. Results of the studies performed in this work suggest that fatty acids as well as specific factors produced by mammary epithelial cells will influence adipogenesis, suggesting that these factors may be used to enhance the in vitro culturing of adipose cells for the injectable composite system. Methods to more optimally culture the adipose cells in vitro could be used to identify strategies that could then reduce the concerns of tissue resorption and volume-reduction that have limited the success of breast tissue engineering strategies clinically. Ideally, the incorporation of fatty acids and/or cellular components into the injectable composite would allow immediate delivery of a cellular implant without the need for in vitro cultivation

ComprehensiveCare and the Failed Implementation of an Electronic Health Records System

Administrator Jennifer Stanton attempts to adopt an Electronic Health Records system at ComprehensiveCare, a multispecialty healthcare practice. Consultants from the vendor provide guidance to the organization, but do not provide that guidance in a way that the non-technical administrator understands. The project experiences escalation of commitment as the administrator attempts to budget for a project that requires unforeseen infrastructure investments. Customizations undertaken at the behest of the managing partner, Dr. Francine Harris, make using the system slow. This interruption in workflow incites user resistance, derailing the benefits that ComprehensiveCare expects to gain from the adoption. The owner-physicians on the board of directors must decide whether to require Jennifer to pull the plug on the system. This is the first case in a series of three cases concerning ComprehensiveCare’s adoption of Electronic Health Records. This case challenges readers to examine escalation of commitment in a real-life context and appreciate that while each decision could make sense on its own, in totality, the project is clearly out of control. Readers must then decide whether to abandon the system by “pulling the plug” or to undergo a rebranding plan to save the investments. This case provides a context that would be relevant in a graduate-level IS management course, an undergraduate fundamentals course, or a project management course

ComprehensiveCare and the Stalled Adoption of an Electronic Health Records System: IT Governance and Employee Succession

ComprehensiveCare, a multi-specialty healthcare organization, struggles to implement Electronic Health Records. The first adoption failed outright because the customizations made the system unusable. The second attempted adoption has not officially failed yet, but the system fails to live up to the expectations. It lingers on the edge of usefulness: staff members cannot use it in real-time for most things, but the interfaces to the equipment prove helpful. Temporary staff members enter information from the day’s work after-hours, which wastes productivity. In this adoption, IT decides what customizations can be made. In addition, the IT department provides all training for staff members. IT gains the unfortunate moniker of the “no-help desk” because IT chooses to keep the system as close to the default vendor configurations as possible. This creates a system that does not work well with ComprehensiveCare’s processes. William, the administrator, and the board of directors must now decide how to manage and leverage IT assets to complete the implementation. This is the final case in a series of three cases following ComprehensiveCare’s adoption of Electronic Health Records. It covers the decision-making necessary for ComprehensiveCare to correct the adoption that is lingering in disuse. This is the final set of decisions required before the adoption ultimately succeeds. This case provides a context that would be most relevant in a graduate level IS management course, an undergraduate fundamentals course, or a project management course

ComprehensiveCare and the Re-Adoption of an Electronic Health Records System: Preparing for a Successful Adoption after a Failed Attempt

After a prior failed adoption, ComprehensiveCare plans for a second attempt in adopting Electronic Health Records. The owner-physicians on the board of directors have replaced the administrator due in part to the missteps of the prior adoption. William Shoemaker, the new administrator, must grapple with several important decisions to provide the highest likelihood of success for adopting the large-scale system. He must decide how the organization should choose the new system, the extent to which the system should be customized to their organization’s idiosyncrasies, who should be responsible for tactical decisions in the customizations that are planned, what role consultants should play for their small to medium enterprise, how training should be accomplished, and finally how the implementation should be scheduled. This is the second case in a series of three cases concerning ComprehensiveCare’s adoption of Electronic Health Records. This case challenges readers to make decisions based on the organizational context. Part two, provided in the teaching notes, updates readers on decisions made by the board and provides readers the opportunity to think critically about the potential ramifications of those decisions. This case provides a context that would be most relevant in a graduate level IS management course, an undergraduate fundamentals course, or a project management course

Perceived Organizational Readiness Study on EHR Implementation

Electronic Health Record (EHR) systems represent an opportunity to improve the delivery of health care. However, lowimplementation rates inhibit the ability of EHR to fulfill the promise of the information systems. One possible reason whyimplementation rates remain low is the high degree of customization required by clinical workers to fit the informationsystems to the organization. This work is unlikely to occur when such potential users believe the organization to be illpreparedfor the system. The present study reports on a multiple case qualitative study examining how individualstakeholders perceive their organization’s readiness

Virginia Beach offshore sediment study

This investigation was initiated from discussions among members of the Minerals Management Service-Virginia Task Force in an effort to locate a nearby and offshore source of beach-quality sand for the resort strip at Virginia Beach. Because of the increasing difficulty of relying upon land-based material, attention has been focused on investigating offshore sources. Previous work (Kimball and others, 1991) suggests an offshore deposit of beach-quality sands is located on a shoal between 3 and 8 km east of Sandbridge. Planned vibracoring on this shoal during the fall of 1993 should establish the viability of the sand occurrence. Although material from this site could . be used to nourish the resort strip, the dredging and transportation costs for an offshore resource would be decreased if another source could be located closer to the strip