We have developed a methodology for allocating operating room capacity to specialties. Our methodology consists of a finite-horizon mixed integer programming (MIP) model which determines a weekly operating room allocation template that minimizes inpatients' cost measured as their length of stay. A number of patient type priority (e.g., emergency over non-emergency patient) and clinical constraints (e.g., maximum number of hours allocated to each specialty, surgeon and staff availability) are included in the formulation. The optimal solution from the analytical model is inputted into a simulation model that captures some of the randomness of the processes (e.g., surgery time, demand, arrival time, and no-show rate of the outpatients) and non-linearities (e.g., the MIP assumes proportional allocation of demand satisfaction (output) with room allocation (input)). The simulation model outputs the average length of stay for each specialty and the room utilization. On a case example of a Los Angeles County Hospital, we show how the hospital length of stay pertaining to surgery can be reduced.
In leukemia patients, resistance to drug treatment develops while the malignant cells can interact with and derive support from their microenvironment, such as bone marrow stroma. To model this process, lymphoblastic leukemia cells from BCR/ABL transgenic mice were treated with the farnesyltransferase inhibitor (FTI) SCH66336 while in coculture with primary mouse embryonic fibroblasts. Coculture with fibroblasts allowed the outgrowth of a subpopulation of drug-resistant lymphoblasts that expressed N-cadherin, a cell-cell adhesion protein that normally is only expressed on specific cell types, including hematopoietic stem cells and fibroblasts. N-cadherin expression promoted increased adhesion of the lymphoblasts to the fibroblasts. Importantly, de novo expression of N-cadherin in parental nonexpressing lymphoblasts using lentiviral transduction increased the ability of the cells to survive FTI treatment. We conclude that FTI drug treatment of Bcr/Abl-positive lymphoblastic leukemia cells that are in contact with a defined microenvironment induces the selective survival of a more primitive subpopulation of leukemia cells that expresses N-cadherin. Experimental drug treatment of cancer cells in model systems that include a microenvironment may reveal novel molecules that contribute to drug resistance and may aid in the design of specific therapies to eradicate more primitive cells.
SummaryPerivascular mural cells including vascular smooth cells (VSMCs) and pericytes are integral components of the vascular system. In the central nervous system (CNS), pericytes are also known as the guardian of the blood-brain barrier, blood-spinal cord barrier and blood-retinal barrier, and play key roles in maintaining cerebrovascular and neuronal functions. However, the functional difference between CNS and peripheral pericytes has not been resolved at the genetic and molecular levels. Hence, the generation of reliable CNS pericyte-specific models and genetic tools remains very challenging. Here, we report a new CNS pericyte marker in mice. This cation-transporting ATPase 13A5 (Atp13a5) marker is highly specific to the pericytes in brain, spinal cord and retina. We generated a transgenic model with a knock-in tdTomato reporter and Cre recombinase. The tdTomato reporter reliably labels the CNS pericytes, but not found in any other CNS cell types including closely related VSMCs, or in peripheral organs. More importantly, Atp13a5 is turned on at embryonic day E15, suggesting brain pericytes are shaped by the developing neural environment. We hope that the new tools will allow us to further explore the heterogeneity of pericytes and achieve a better understanding of CNS pericytes in health and diseases.
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