High-dose busulfan, melphalan, thiotepa and peripheral blood stem cell infusion for the treatment of metastatic breast cancer

The purpose of this study was to determine the outcome of patients with metastatic breast cancer treated with high-dose busulfan (Bu), melphalan (Mel) and thiotepa (TT) followed by peripheral blood stem cell (PBSC) infusion. Fifty-one patients with chemotherapy refractory (n = 32) or responsive (n = 19) metastatic breast cancer received Bu (12 mg/kg), Mel (100 mg/m2) and TT (500 mg/m2) followed by PBSC collected after chemotherapy and growth factor (n = 43) or growth factor alone (n = 8). The 100 day treatment-related mortality was 8% including one death from cytomegalovirus pneumonia, one from aspiration pneumonia and two from regimen-related toxicity (RRT). Seven of 28 refractory (25%) and 5/7 (71%) responsive patients with evaluable disease achieved a complete response of all measurable disease or all soft tissue disease with at least improvement in bone lesions (PR*). Fifteen of 51 patients (29%) are alive and progression-free a median of 423 days (range 353-934) after treatment, 5/32 (16%) with refractory disease and 10/19 (53%) with responsive disease. The probabilities of progression-free survival (PFS) at 1.5 years for the patients with refractory (n = 32) and responsive (n = 19) disease were 0.24 and 0.53, respectively. These preliminary data suggest that high-dose Bu/Mel/TT has significant activity in patients with advanced breast cancer and may be superior to some previously published regimens.     

Epitope specificity of CD44 for monoclonal antibody-dependent facilitation of marrow engraftment in a canine model

Primary graft rejection after marrow transplantation occurs more frequently in patients receiving HLA-haploidentical compared with HLA-identical sibling transplants. Both human and experimental animal data suggest that the cells responsible for this phenomenon are either host natural killer (NK) cells, T cells, or both. To investigate the mechanisms of graft rejection, we have developed a canine model of marrow transplantation, which uses DLA-nonidentical unrelated donors in the absence of postgrafting immunosuppression. In this model most animals rejected their marrow grafts after a preparative regimen of 9.2 Gy total body irradiation (TBI). However, engraftment of DLA-nonidentical marrow can be facilitated when the recipients are pretreated with monoclonal antibody (MoAb) S5, which recognizes CD44. In this report, we extended these observations by first cloning the canine CD44 and, next, mapping the epitope recognized by S5, which was located in a region conserved among human and canine CD44 and was distinct from the hyaluronan binding domain. However, in vitro binding of S5 caused a conformational change in CD44, which allowed increased hyaluronan binding. Then, we reexamined the in vivo model of marrow transplantation and compared results with MoAb S5 to those with two other anti-CD44 MoAbs, IM7 and S3. Only MoAb S5 significantly increased the engraftment rate of DLA-nonidentical unrelated marrow, whereas the two other anti-CD44 MoAbs were ineffective. The enhanced in vivo effect was not related to differences in the MoAbs' avidities, since both S5 and IM7 had equivalent binding to CD44, but most likely related to the specific epitope that S5 recognizes. Thus, this study shows that the effect of the anti-CD44 MoAb S5 in facilitating engraftment is epitope specific and if one is to use an anti-CD44 to facilitate engraftment of marrow in humans, one cannot assume that any anti-CD44 would work.     

Two studies of the long-term follow-up of minimal therapist contact treatments of vascular and tension headache.

Tension and vascular headache patients, initially treated with biofeedback and/or relaxation training in either a minimal therapist contact protocol (3 visits) or an intensive individual protocol (10 or 16 visits) were followed-up prospectively for 2 years. In the first study, for the first 6 months of follow-up, half of all patients continued to keep headache diaries and were seen monthly and the other half had only minimal contact. The results at 1-year follow-up, based on 4 weeks of daily headache diaries, revealed equally good maintenance from both treatment protocols and from both follow-up conditions. In Study 2, we found that patients remained improved over pretreatment baseline levels at the 2-year follow-up regardless of initial treatment intensity. Approximately three quarters of vascular patients who were initially improved at posttreatment remained improved at 2 years. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Antipneumococcal activities of levofloxacin and clarithromycin as determined by agar dilution, microdilution, E-test, and disk diffusion methodologies

The activities of levofloxacin and clarithromycin against 199 penicillin- and macrolide-susceptible and -resistant pneumococci were tested by agar and microdilution methods in air and by disk diffusion and E-test methods in air and CO2. For levofloxacin, >/=99. 0% of strains were susceptible at /=17 mm, regardless of incubation in air or CO2. Although zone sizes were smaller and E-test MICs were higher for clarithromycin in CO2 than those in air, category differences were minor, and susceptibility rates for clarithromycin were similar to those obtained by agar and microdilution in air (range, 76.9 to 80.9% by all methods). For clarithromycin, adjustment of breakpoints based upon distribution of results resulted in susceptibility rates which were similar by all methods (75.8 to 76.9% susceptible, 0 to 1.5% intermediate, 22.6 to 23.1% resistant). Minor discrepancies were obtained with levofloxacin for one strain (0.5%) by microdilution and two strains (1.0%) by disk diffusion in CO2. For clarithromycin, minor discrepancies were found in three strains (1.5%) by microdilution, seven strains (3.5%) by agar dilution, four strains (2.0%) by E-test in air, six strains (3.0%) by disk diffusion in air, and five strains (2.5%) by disk diffusion in CO2. Major discrepancies occurred with levofloxacin in one strain (0.5%) by microdilution but were not found with clarithromycin. Very major discrepancies were not seen with levofloxacin, but occurred with clarithromycin in five strains (2.5%) by microdilution, three strains (1.5%) by agar dilution, two strains (1.0%) by E-test in air, eight strains (4.0%) by disk diffusion in air, and one strain (0.5%) by disk diffusion in CO2.     

Matching with don't-cares and a small number of mismatches

In matching with don't-cares and k mismatches we are given a pattern of length m and a text of length n, both of which may contain don't-cares (a symbol that matches all symbols), and the goal is to find all locations in the text that match the pattern with at most k mismatches, where k is a parameter. We present new algorithms that solve this problem using a combination of convolutions and a dynamic programming procedure. We give randomized and deterministic solutions that run in time O(nk²logm) and O(nk³logm), respectively, and are faster than the most efficient extant methods for small values of k. Our deterministic algorithm is the first to obtain an O(polylog(k)⋅nlogm) running time.     

Superfast densification of nanocrystalline oxide powders by spark plasma sintering

Spark plasma sintering (SPS) is a newly discovered old technique which recently has been used for superfast densification of ceramic powders. Simultaneous application of pulsed high dc current densities and load is the necessary condition for rapid and full densification of ceramic powders by SPS. Commercial nanocrystalline magnesium oxide (nc-MgO) and yttrium aluminum garnet (nc-YAG) powders were densified to optical transparency using spark plasma sintering at distinctly different homologous temperatures (0.3 T _m for nc-MgO and 0.7 T _m for nc-YAG). The observed microstructure, density and grain size evolutions versus the SPS temperature were analyzed. The enhanced densification of the nc-MgO powder at the present SPS conditions was related to plastic deformation followed by diffusion processes. Densification of nc-YAG powder was described by the formation of viscous layer at the particle surfaces and corresponding densification by grain rotation and diffusion through the liquid phase. Densification by normal grain growth takes place at higher relative densities, regardless of the material.     

Effect of grain size on elastic modulus and hardness of nanocrystalline ZrO2-3 wt% Y2O3 ceramic

Dense nanocrystalline ZrO₂-3 wt% Y₂O₃ ceramics with grain sizes ranging between 23 to 130 nm were tested by ultrasonic pulse echo and Vickers hardness. The elastic modulus and hardness results were corrected for the residual porosity and the phase content. The corrected elastic moduli exhibited continuous decrease with decrease in the grain size. In contrast, no correlation was found between the corrected hardness and grain size. The percolative composite model was used to describe the changes in the elastic moduli in terms of percolation of the elastic wave through the intercrystalline phase at the percolation threshold. The absence of correlation with the hardness results was explained due to the other energy absorbing mechanisms such as microcracking beneath the indenter.     

Electric field effects during spark plasma sintering of ceramic nanoparticles

The effects of the applied electric field during the spark plasma sintering of ceramic nanoparticles were examined at various stages of the process. It was assumed that local intensification of the electric field arises due to the nanoscale structural features. Enhanced surface conductivity is expected in the nanoparticles during the heating, which otherwise are electrically non-conducting as a bulk. Percolation of the electric current at “optimal” electrical conductivity is obtained by fractal dimension. The defective nanoparticle surfaces experience charging–discharge cycles which lead to local breakdown and to plasma formation due to the ionized surface molecules. High local temperatures which evolved in a nonlinear fashion at the particle surfaces lead to enhanced sintering and densification kinetics, consistent with the flash sintering phenomenon. The contribution of the pondermotive force to the enhancement of the diffusion kinetics is discussed. Temperature windows for enhanced densification kinetics via plastic deformation or plasma-assisted processes are estimated for MgO, Al₂O₃, and YAG.     

Parameter estimation and screening of solar cells

The aggregation (sorting) of the individual solar cells into an array is commonly based on a single operating point on the current-voltage (I-V) characteristic curve. an alternative approach for cell performance prediction and cell screening is provided by modelling the cell using an equivalent electrical circuit, in which the parameters involved are related to the physical phenomena in the device. These analytical models may be represented by a double exponential I-V characteristic with seven parameters, by a double exponential model with five parameters or by a single exponential equation with four or five parameters. In this article we address issues concerning methodologies for the determination of solar cell parameters based on measured data points of the I-V characteristic, and introduce a procedure for screening solar cells for arrays. We show that common curve-fitting techniques, e.g. least-squares, may produce many combinations of parameter values while maintaining a good fit between the fitted and measured I-V characteristics of the cell. Therefore, techniques relying on curve-fitting criteria alone cannot be used directly for cell parameterization. We propose a consistent procedure that takes into account the entire set of parameter values for a batch of cells. This procedure is based on a definition of a mean cell representing the batch, and takes into account the relative contribution of each parameter to the overall goodness of fit. the procedure is demonstrated on a batch of 50 silicon cells for Space Station Freedom.     

Densification of nanocrystalline Y2O3 ceramic powder by spark plasma sintering

Nanocrystalline Y₂O₃ powders with 18 nm crystallite size were sintered using spark plasma sintering (SPS) at different conditions between 1100 and 1600 °C. Dense specimens were fabricated at 100 MPa and 1400 °C for 5 min duration. A maximum in density was observed at 1400 °C. The grain size continuously increased with the SPS temperature into the micrometer size range. The maximum in density arises from competition between densification and grain growth. Retarded densification above 1400 °C is associated with enhanced grain growth that resulted in residual pores within the grains. Analysis of the grain growth kinetics resulted in activation energy of 150 kJ mol^?1 and associated diffusion coefficients higher by 10³ than expected for Y³⁺ grain boundary diffusion. The enhanced diffusion may be explained by combined surface diffusion and particle coarsening during the heating up with grain boundary diffusion at the SPS temperature.