Benchmarking en el sector público : aportes y propuestas de implementación para la provincia de Buenos Aires (original) (raw)
British Journal of Haematology, 2008
Although interferon α (IFN-α) is able to induce haematological remission in 60–80% of patients with chronic myeloid leukaemia (CML) in early chronic phase, major cytogenetic remissions are only achievable in 30–40%. Recent clinical data suggest that the addition of granulocyte–macrophage colony-stimulating factor (GM-CSF) to IFN-α therapy can significantly improve the cytogenetic response in some patients, although the mechanism remains unknown. We hypothesized that the combination of GM-CSF and IFN-α induces the differentiation of dendritic cells, which subsequently stimulates a specific anti-leukaemic response. Monocytes from CML patients were cultured in GM-CSF and interleukin (IL)-4 (GM/IL-4)or in GM-CSF and IFN-α (GM/IFN-α). After 7 d, the number of cells exhibiting typical antigen-presenting cell (APC) morphology was equal in both groups, and fluorescence in situ hybridization (FISH) analysis confirmed that the APCs generated with GM/IFN-α were of leukaemic origin. Phenotypically, both sets of APCs expressed typical surface markers; however, CD86, CD83, CD11c, HLA-ABC and HLA-DR expression was significantly higher in the GM/IFN-α APCs, whereas CD1a expression was significantly lower. In mixed lymphocyte reactions (MLR), GM/IFN-α APCs stimulated the proliferation of allogeneic T cells significantly better than GM/IL-4 APCs. However, both groups of APCs stimulated autologous T-cell proliferation equally. Finally, we assessed the ability of GM/IFN-α APCs to induce a leukaemia-specific cytotoxic T-cell response. Some samples generated cytotoxic T lymphocytes (CTLs) that specifically lysed bcr-abl-positive target cells. These data show that the combination of GM-CSF and IFN-α, when used in vitro, induces the differentiation of malignant APCs with potent T-cell stimulatory capacity. Although there is no in vivo evidence to support these findings, it is possible that, when administered to CML patients, GM-CSF in combination with IFN-α results in the generation of highly stimulatory leukaemic APCs.
Dynamic evolutionary optimisation: an analysis of frequency and magnitude of change
2009
Abstract In this paper, we rigorously analyse how the magnitude and frequency of change may affect the performance of the algorithm (1+ 1) EA dyn on a set of artificially designed pseudo-Boolean functions, given a simple but well-defined dynamic framework. We demonstrate some counter-intuitive scenarios that allow us to gain a better understanding of how the dynamics of a function may affect the runtime of an algorithm.