Most patients relapse after high-dose chemotherapy (HDCT) with autologous stem-cell transplantation (ASCT) for metastatic breast cancer. Further chemotherapy immediately after hematopoietic recovery from ASCT is not given for fear of irreversibly damaging the newly engrafted stem cells. In a pilot chemoprotection trial, autologous CD34+ cells from patients with metastatic breast cancer were exposed to a replication-incompetent retroviral vector carrying MDR-1 cDNA and then reinfused after HDCT. Immediately on recovery, patients received multiple courses of escalating dose paclitaxel. All of the 10 patients tolerated reinfusion of modified cells without any toxicity and had myeloid engraftment within 12 days (range, 11-14). The bone marrow cells of three patients contained vector MDR-1-positive cells only at the time of the first course of posttransplant paclitaxel, indicating that the MDR-1 vector-modified cells had only short-term engrafting potential. A total of 83 courses of paclitaxel were administered starting at a median of 30 (range, 21-32) days from ASCT. The median dose of paclitaxel was 225 mg/m2 and the median interval between paclitaxel cycles of therapy was 21 (range, 20-41) days. Five of the six CR patients were able to receive all of the 12 courses of paclitaxel. Three patients who had achieved less than a complete response to the HDCT (2 patients) and partial response (1 patient) were converted to complete clinical responses during the 12 cycles of paclitaxel. No delayed toxicity or bone marrow failure was noted in these patients with a median follow-up of 2 years from ASCT. This is the first study of chemotherapy immediately after transplantation with autologous CD34+ cells. These data indicate that paclitaxel can be safely administered immediately after ASCT without any delayed toxicities. Paclitaxel given immediately after ASCT can further improve the response to pretransplant chemotherapy in patients with advanced breast cancer. 相似文献
The feasibility of achieving both universal application of nonthoracotomy leads and low (< or = 15 J) defibrillation energy requirements by optimizing lead system configuration for use with low-output (<30 J) biphasic shock pulse generators was examined. Sixteen patients (mean age 62 +/- 8 years and mean left ventricular ejection fraction of 38 +/- 15%) were included in the study. All patients had either experienced syncope with induced ventricular tachycardia (n = 4) or had documented sustained ventricular tachycardia (n = 7) or ventricular fibrillation (n = 5). Defibrillation threshold testing was performed in 2 stages on different days in these patients. In the first stage, 2 defibrillation catheter electrodes were positioned in the right ventricle and superior vena cava with an axillary cutaneous patch. Fifteen-joule, 10- and 5-J biphasic shocks were delivered across 3 different electrode configurations-right ventricle to superior vena cava, right ventricle to axillary patch, right ventricle to a combination of superior vena cava and axillary patch. In the second stage, an 80-ml can electrode was added subcutaneously in a pectoral location to the previous leads. Configurations compared were the right ventricle to pectoral can, and right ventricle to an "array"-combining superior vena cava, can, and axillary patch leads. The defibrillation threshold was determined using a step-down method. In stage 1, mean defibrillation threshold for the right ventricle to axillary patch (12.7 +/- 5.9 J) and right ventricle to superior vena cava plus axillary patch (9.8 +/- 5.2 J) configurations was lower than the right ventricle to superior vena cava configuration (14.2 +/- 6.4 J, p <0.05). In stage 2, the defibrillation was higher for the right ventricle to pectoral can (9.2 +/- 5.1 J) configuration compared with the right ventricle to the array (5.6 +/- 3.6 J, p < or =0.05). The right ventricle to array had the lowest defibrillation threshold, whereas the right ventricle to pectoral can was the best dual electrode system. Low-energy endocardial defibrillation (< or =10 J) was feasible in 72% of tested patients with > 1 electrode configuration at 10 J, whereas only 53% of successful patients could be reverted at >1 electrode configuration at 5 J (p <0.05). Reduction in maximum pulse generator output to < or =25 J using these electrode configurations with bidirectional shocks is feasible and maintains an adequate safety margin. 相似文献
Identifying those nodes that play a critical role within a network is of great importance. Many applications such as gossip spreading, disease spreading, news dispersion, identifying prominent individuals in a social network, etc. may take advantage of this knowledge in a complex network. The basic concept is generally to identify the nodes with the highest criticality in a network. As a result, the centrality principle has been studied extensively and in great detail, focusing on creating a consistent and accurate location of nodes within a network in terms of their importance. Both single centrality measures and group centrality measures, although, have their certain drawbacks. Other solutions to this problem include the game-theoretic Shapley Value (SV) calculations measuring the effect of a collection of nodes in complex networks via dynamic network data propagation process. Our novel proposed algorithm aims to find the most significant communities in a graph with community structure and then employs the SV-based games to find the most influential node from each community. A Susceptible-Infected-Recovered (SIR) model has been employed to distinctly determine each powerful node's capacity to spread. The results of the SIR simulation have also been used to show the contrast between the spreading capacity of nodes found through our proposed algorithm and that of nodes found using SV-algorithm and centrality measures alone.
The omega ratio, a performance measure, is the ratio of the expected upside deviation of return to the expected downside deviation of return from a predetermined threshold described by an investor. It has been exhibited that the omega ratio optimization is equivalent to a linear program under a mild condition and thus easily tractable. But the omega ratio optimization fails to hedge against many other risks involved in portfolio return that may adversely affect the interests of a risk‐averse investor. On the other hand, there are widely accepted mean‐risk models for portfolio selection that seek to maximize mean return and minimize the associated risk but in general fail to maximize the relative performance ratio around the threshold return. In this paper, we aim to propose a model called ‘extended omega ratio optimization’ that combines the features of the omega ratio optimization model and mean‐risk models. The proposed model introduces constraint on a general risk function in the omega ratio optimization model in such a way that the resultant model remains linear and thus tractable. Our empirical experience with real data from S&P BSE sensex index shows that the optimal portfolios from the extended omega ratio optimization model(s) improved over the optimal portfolios from the omega ratio optimization in having less associated risk and over the optimal portfolios from the corresponding mean‐risk model(s) in having a high value omega ratio. 相似文献
In the present study, simultaneous reactive dyeing and easy care finishing of cotton with a non-formaldehyde and environment-friendly compound (citric acid [CA]) was successfully optimised using a statistical model. An optimised recipe was formulated based on the half factorial central composite design and numerical optimisation solution by Design-Expert 6.0 software. The optimised conditions were investigated for the concentration of CA, catalyst, reactive dye, alkali and urea. Evaluation of the recipe was made with respect to K/S, percent fixation of reactive dye, dry crease recovery angle and tensile strength. The simultaneous dyeing and finishing using theoretical optimised recipe was carried out and performance of the sample was compared with the sample using conventional two-step dyeing and finishing process. 相似文献
d. c. -Conductivity measurements have been made as a function of temperature (80–330 K) on bulk amorphous samples of GexSe1?x (0.1 ? x ?0.7), in order to identify the conduction mechanism and to observe the effect of selenium -doping on the d. c.-conductivity of germanium. It is found that for samples with a low concentration of selenium (0. 5? x ? 0. 7 ), conduction in the high temperature region (330-180 K) is due to thermally assisted tunneling of electrons in the localized states at the conduction band edge, and in the low temperature region (80–190 K), conduction takes place through variable range hopping in the localized states near the Fermi level. The addition of selenium is found to increase the amorphicity of the samples. In the samples with a relatively high content of selenium (0.1 ? x ? 0.4), conduction in the entire temperature range of investigation is due to the thermally assisted tunneling of holes in the localized states at the valence band edge. 相似文献
In order to optimize defibrillation electrode systems for ventricular defibrillation thresholds (DFTs), a Finite Element Torso model was built from fast CT scans of a patient who had large cardiac dimensions (upper bound of normal) but no heart disease. Clinically used defibrillation electrode configurations, i.e. Superior Vena Cava (SVC) to Right Ventricle (RV) (SVC-RV), left pectoral Can to RV (Can-RV) and Can + SVC-RV, were analyzed. The DFTs were calculated based on 95% ventricular mass having voltage gradient > 5 V/cm and these results were also compared with clinical data. The low voltage gradient regions with voltage gradient < 5 V/cm were identified and the effect of electrode dimension and location on DFTs were also investigated for each system. A good correlation between the model results and the clinical data supports the use of Finite Element Analysis of a human torso model for optimization of defibrillation electrode systems. This correlation also indicates that the critical mass hypothesis is the primary mechanism of defibrillation. Both the FEA results and the clinical data show that Can + SVC-RV system offers the lowest voltage DFTs when compared with SVC-RV and Can-RV systems. Analysis of the effect of RV, SVC and Can electrode dimensions and locations can have an important impact on defibrillation lead designs. 相似文献