Survival and predictors of disability in Turkish MS patients. Turkish Multiple Sclerosis Study Group (TUMSSG)

OBJECTIVE: To examine the natural history, survival, and prognostic factors in a sample of Turkish MS patients. METHOD: This multicenter study included 1,259 definite MS patients diagnosed according to the criteria of Poser et al. Actuarial analysis of selected disability levels of 3, 6, 8, and 10 achieved with the Expanded Disability Status Scale (EDSS); a multivariate Cox regression analysis for prognostic factors related to time to reach EDSS > or = 6; and Pearson's correlation coefficient for individual factors were performed. RESULTS: The survival (+/- SE) at 15 years from onset was 94.6 +/- 2.9%, and at 25 years was 89.0 +/- 5.8%. The disability reached by 15 years was EDSS > or = 3 in 66.4%, EDSS > or = 6 in 41.2%, EDSS > or = 8 in 10.5%, and EDSS = 10 in 5.4%. The most significant unfavorable prognostic factors were progressive course (relative risk [RR], 3.73; CI, 2.71 to 5.13) and sphincter symptoms at onset (RR, 1.86; CI, 1.23 to 2.82), followed by male sex, motor symptoms at onset, and a high attack frequency within the first 5 years. Primary progressive disease was correlated positively with male sex (r = 0.0895, p = 0.001), older age (r = 0.1807, p = 0.000), and motor (r = 0.1433, p = 0.000) or sphincter symptoms (r = 0.1001, p = 0.000) at onset, unlike relapsing-remitting and secondary progressive disease. CONCLUSIONS: Although a slightly better prognosis is observed in the Turkish MS population, early prognostic factors are similar to most of the previous Western series. Primary progressive disease, mostly seen in older men with motor and sphincter involvement at onset, has a worse prognosis and may represent a distinct behavioral variant of MS.     

Comparative evaluation of macrodilution and alamar colorimetric microdilution broth methods for antifungal susceptibility testing of yeast isolates

A comparative evaluation of the macrodilution method and the Alamar colorimetric method for the susceptibility testing of amphotericin B, fluconazole, and flucytosine was conducted with 134 pathogenic yeasts. The clinical isolates included 28 Candida albicans, 17 Candida tropicalis, 15 Candida parapsilosis, 12 Candida krusei, 10 Candida lusitaniae, 9 Candida guilliermondii, 18 Torulopsis glabrata, and 25 Cryptococcus neoformans isolates. The macrodilution method was performed and interpreted according to the recommendations of the National Committee for Clinical Laboratory Standards (document M27-P), and the Alamar colorimetric method was performed according to the manufacturer's instructions. For the Alamar colorimetric method, MICs were determined at 24 and 48 h of incubation for Candida species and T. glabrata and at 48 and 72 h of incubation for C. neoformans. The overall agreement within +/- 1 dilution for Candida species and T. glabrata against the three antifungal agents was generally good, with the values for amphotericin B, fluconazole, and flucytosine being 85.3, 77.9, and 86.2%, respectively, at the 24-h readings and 69.3, 65.2, and 97.2%, respectively, at the 48-h readings. Most disagreement was noted with fluconazole against C. tropicalis and T. glabrata. Our studies indicate that determination of MICs at 24 h by the Alamar colorimetric method is a valid alternate method for testing amphotericin B, fluconazole, and flucytosine against Candida species but not for testing fluconazole against C. tropicalis and T. glabrata. For flucytosine, much better agreement can be demonstrated against Candida species and T. glabrata at the 48-h readings by the Alamar method. Excellent agreement within +/- dilution can also be observed for amphotericin B, fluconazole, and flucytosine (80, 96, and 96%, respectively) against c. neoformans when the MICs were determined at 72 h by the Alamar method.     

Mechanism of Work-hardening for Austenitic Manganese Steel under Non-severe Impact Loading Conditions

The effect of C,Mn and heat-treatment onwork-hardening of austenitic Mn steel and thework-hardening mechanism have been investigatedunder non-severe impact loading condition.Theresults show that the ability of work-hardening in-creases with the increase of C and aging tempera-ture but decreases with Mn.The work-hardeningwith high austenitic stability results mainly fromdislocations,and that with low austenitic stabilityresults mainly from combined effects of strain-in-duced martensite and high density of dislocationsunder non-severe impact loading conditions.Thewear resistance of medium manganese steel (Mn7)is 1.64-2.46 times that of Hadfield steel (Mnl3).     

Granulocyte colony-stimulating factor (G-CSF) dose-dependent efficacy in peripheral blood stem cell mobilization in patients who had failed initial mobilization with chemotherapy and G-CSF

For 10 consecutive patients in our unit who did not show a significant rise in blood progenitor cells within 14 days following chemotherapy and G-CSF, we increased the G-CSF dose from 5 to 10 microg/kg/day (n = 9) or from 10 to 15 microg/kg/day (n = 1). As a result, there were significant increases in total yield as well as yield per apheresis of mononuclear cells, CD34+ cells and CFU-GM (P < 0.025, <0.01 and <0.005, respectively). After G-CSF dose escalation, six of the 10 patients had sufficient CD34+ cells for performing transplantation. These results demonstrate a dose-dependent response of progenitor cell mobilization by G-CSF when used in combination with chemotherapy. Moreover, increasing the dose of G-CSF as late as the third week of mobilization may still provide sufficient cell yield even with patients who did not show a significant mobilization with conventional doses of G-CSF.     

A concept of cooperative equilibrium for dynamic games

The paper proposes an equilibrium solution concept for dynamic games where players can communicate with one another, but cannot make contractual agreements. In such games, unlike the static problems without contracting possibilities, the cooperation between players is possible due to the fact that the realization of negotiated agreements can be enforced by suitably-defined strategies. The definition presented combines dynamic programming, the theory of bargaining and the notion of enforceable agreements to produce a class of cooperative solutions defined in the form of memory Nash equilibria satisfying the principle of optimality along the equilibrium trajectory. The choice of a particular solution in this class depends on players' expected actions in case of disagreement, and on an adopted negotiation scheme formalized in the form of a bargaining model. Possible formulations of disagreement policies and bargaining models are discussed in some detail.     

Antiovarian antibodies and their effect on the outcome of assisted reproduction

PURPOSE: To compare the presence in levels of antiovarian antibodies (AOAb) in the pre- and postovulatory stage from serum of infertile patients undergoing intrauterine insemination (IUI) or in vitro fertilization (IVF) with outcome of the procedures. RESULTS: Serum from 36 women undergoing IUI, 36 women undergoing IVF and 25 fertile, healthy controls were assayed for the presence of AOAb by a commercially available ELISA kit. AOAb was positive in 59.7% of infertile women, while none of the fertile controls were positive for AOAb. The levels of these antibodies increased as the patient age and the number of treatment attempts increased. Though the presence of AOAb did not affect oocyte recovery rate, it resulted in decreased fertilization rate, cleavage rate, and pregnancy rate in infertile women. CONCLUSIONS: Our studies suggest that AOAb may be a cause of infertility and presence of these antibodies could have adverse effects on the outcome of assisted reproductive techniques.     

Mobility of holes in p-type silicon determined by the self-consistent method

The mobility of majority carriers is calculated in p-type silicon in the impurity concentration range from 10¹⁶ to 10²⁰ cm^?3. Taking into account the complexity of the band structure of holes and using the self-consistent model development earlier for electrons, the value of the Fermi energy and the screening length is determined. The following scattering types are considered: scattering by acoustical phonons, scattering by non-polar optical phonon and scattering by ionized impurities. The influence of interband transition of heavy and light holes on the total relaxation time is analysed. It is shown that it does not lead to essential changes in mobility. The obtained results are compared with experimental results and satisfactory agreement is found.     

A TAT-streptavidin fusion protein directs uptake of biotinylated cargo into mammalian cells

The HIV-1 TAT peptide has been used extensively for directing the intracellular delivery of an assortment of cargo, including DNA, liposomes and macromolecules. For protein delivery, a variety of TAT-fusion proteins have been described which link the TAT coding sequence to the protein coding sequence of interest. Streptavidin represents a potentially useful TAT-fusion protein because it could be used to deliver a wide array of biotinylated cargo. Here we have characterized a TAT-streptavidin (TAT-SA) fusion protein, which retains the ability to bind biotinylated cargo while directing their efficient cellular uptake. Fluorescence activated cell sorting (FACS) analysis and confocal microscopy characterization showed that TAT-SA is internalized by Jurkat T-cells and NIH 3T3 cells alone and when complexed to phycoerythrin, whereas the native streptavidin is not. Additionally, biotinylated alkaline phosphatase is successfully internalized and retains its activity when complexed to TAT-SA and incubated with Jurkat T-cells. Confocal microscopy suggested, however, that internalized TAT-SA and TAT-SA complexes were largely compartmentalized in vesicular compartments, rather than freely diffusing in the cytoplasmic compartment. To effect cytoplasmic delivery, the endosomal releasing polymer, poly(propylacrylic acid) (PPAA), was biotinylated and complexed to TAT-SA. Endosomal release and cytoplasmic delivery of fluorescently labeled TAT-SA complexes with PPAA was shown by the diffuse distribution of fluorescent protein in the cytoplasm. Taken together, these results demonstrate that TAT-SA can be used to direct intracellular delivery of large biotinylated cargo to intracellular compartments and that biotinylated PPAA can direct cytoplasmic delivery where desired.     

Modelling of heat and moisture transport during drying black grapes

In this work, heat and moisture transport occurred during drying of black grapes in a laboratory dryer were investigated. In the experiments, the air was passed through the chamber at a variety of flow rates (0.5, 0.75, 1.0 and 1.25 m s^?1) and temperatures (40, 50, 60 and 70 °C). Thermal and moisture diffusivities were determined. The possibility of expressing the moisture removal from the grapes was searched with the fourteen one‐layer drying models selected from the literature. Among all the models, the Page model was found the best for explaining the experimental results. The effects of the drying temperature and air velocity on the constants and coefficients of Page model and diffusivities were also investigated by multiple combinations of the different equations as the linear, power, logarithmic, exponential, polynomial, inverse polynomial and Arrhenius type by non‐ linear regression analyses. Models obtained were also analysed statistically using t‐test, RMSE, MBE and χ².