Methods of Reduction of Unevenness of the Transfer Characteristic of the Shaper of Analog Counting of Digital Synthesizers of Signals with Uniform Sampling

Digital methods of decrease of nonuniformity of the transmitting characteristic of the shaper of analog counting of digital synthesizers of signals with the uniform sampling are offered. The second method can be used also for decrease of noise of digital-to-analog transformation. Decrease in nonuniformity of the transmitting characteristic of the shaper of analog counting leads to increase in probability of the exact detection and allowing ability of radar stations

Go-activation endures following the presentation of a stop-signal: evidence from startle

It has been proposed that, in a stop-signal task (SST), independent go- and stop-processes “race” to control behavior. If the go-process wins, an overt response is produced, whereas, if the stop-process wins, the response is withheld. One prediction that follows from this proposal is that, if the activation associated with one process is enhanced, it is more likely to win the race. We looked to determine whether these initiation and inhibition processes (and thus response outcomes) could be manipulated by using a startling acoustic stimulus (SAS), which has been shown to provide additional response activation. In the present study, participants were to respond to a visual go-stimulus; however, if a subsequent stop-signal appeared, they were to inhibit the response. The stop-signal was presented at a delay corresponding to a probability of responding of 0.4 (determined from a baseline block of trials). On stop-trials, a SAS was presented either simultaneously with the go-signal or stop-signal or 100, 150, or 200 ms following the stop-signal. Results showed that presenting a SAS during stop-trials led to an increase in probability of responding when presented with or following the stop-signal. The latency of SAS responses at the stop-signal + 150 ms and stop-signal + 200 ms probe times suggests that they would have been voluntarily inhibited but instead were involuntarily initiated by the SAS. Thus results demonstrate that go-activation endures even 200 ms following a stop-signal and remains accessible well after the response has been inhibited, providing evidence against a winner-take-all race between independent go- and stop-processes. NEW & NOTEWORTHY In this study, a startling acoustic stimulus (SAS) was used to determine whether response outcome could be manipulated in a stop-signal task. Results revealed that presenting a SAS during stop-signal trials led to an increase in probability of responding even when presented 200 ms following the stop-signal. The latency of SAS responses indicates that go-activation remains accessible and modifiable well after the response is voluntarily inhibited, providing evidence against an irrevocable commitment to inhibition.

Results and Cost Effectiveness of "on-Demand" Plerixafor Added to Chemotherapy and Granulocyte Colony-Stimulating Factor for Peripheral Blood Stem Cell Mobilization in Multiple Myeloma

The failure of peripheral blood stem cell (PBSC) mobilization and harvest is a critical issue for multiple myeloma (MM) patients undergoing high-dose chemotherapy. Plerixafor (PLX) is an effective mobilizing agent; however, its use for every MM patient undergoing high-dose chemotherapy has led to a notable increase in costs. We designed a highly specific and sensitive algorithm for identifying patients likely to fail PBSC mobilization after chemotherapy and G-CSF (Blood Transfusion 2013.11:94). The use of this algorithm thereby allows selective administration of PLX to patients predicted to fail mobilization after chemotherapy and G-CSF (on-demand PLX) and may reduce failure rate of PBSC mobilization while limiting cost. We performed a multicenter phase II prospective study of on-demand PLX used according to our algorithm for patients with lymphoma or MM, who were mobilized by cyclophosphamide and G-CSF. The study was powered to demonstrate a reduction in mobilization failure from 14% to 7% for the entire population of treated patients. Here, we report the final results for MM patients. The inclusion criteria for MM patients were as follows: diagnosis of symptomatic MM, age 18-70 yr, achievement of any response after first-line treatment administered for 4-8 months, first mobilization attempt, cardiac and pulmonary function adequate for high-dose chemotherapy. Mobilization schedule was cyclophosphamide (CTX, 4 g/m2) and G-CSF (5-10 mcg/Kg), PLX (240 mcg/Kg) was administered only to patients selected by the algorithm. Estimation of costs was performed according to a previously reported study (BJH 2014, 164, 113). There were 111 patients with MM who underwent treatment. Successful CD34+ cell mobilization (>20×109 cells/mL in PB) was achieved for 97.2% (108/111) of patients, and failure of mobilization occurred in the remaining 3 (2.8%); minimal apheretic harvest success (>2.0×106 CD34+ cells/Kg) was achieved for 97.2% (108/111); and optimal harvest success (=/>4.0×106 CD34+ cells/Kg) was achieved for 84.6% (94/111). On-demand PLX was needed for 8.2% of patients (9/111). After autologous hematopoietic transplantation, neutrophil (N) engraftment (N>0.5x109 cells/L) was reached at day +11.8 (range day +8 to +24). We compared these prospective results with the mobilization results obtained retrospectively in a control group of 183 MM patients who received the same mobilization schedule without PLX. After the two groups were adjusted for unbalanced factors, multivariable logistic regression analysis revealed that on-demand PLX treatment according to the algorithm led to significant increases in the probabilities of achieving a successful minimal apheretic harvest (p=0.006; hazard ratio [HR] 5.624, 95% confidence interval [CI] 1.168-19.548) and optimal harvest (p=0.02; HR 2.121, 95% CI 1.118-4.025). The mean cost increase for the first mobilization in the PLX-on-demand prospective study, in respect to control group, was 615 €/patient. The incremental cost-effectiveness ratio (ICER) was calculated as: (cost1-cost2)/(result1-result2). ICER was 47 €/1% increase in probability of a minimal apheretic harvest while it was 68 €/1% increase in probability of an optimal apheretic harvest. In conclusion, the final analysis of our study found that on-demand PLX for MM patients, which was added to the mobilization schedule of CTX (4 g/m2) + G-CSF (5-10 mcg/Kg), allowed a successful harvest from the first mobilization treatment in > 97% of patients, with 85% of patients achieving a harvest sufficient for two rounds of high-dose chemotherapy. These results indicate that on-demand PLX added to mobilization chemotherapy is a significant improvement over the same type of mobilization chemotherapy without PLX. The limited use of PLX in this study allowed for a favorable incremental cost-effectiveness ratio of this expensive agent. On-demand PLX used according to a validated algorithm in addition to CTX plus G-CSF may be considered a new standard for PBSC mobilization and harvest in patients with MM. Table 1.Failure of CD34+ Mobilization in PB Failure of Minimal Harvest Failure of Optimal Harvest Cost per PatientICER (Minimal Harvest)ICER (Optimal Harvest)PLX on Demand (n 111)2.8%2.8%15.4%3,969 €47 €/ 1% increase in probability of a Minimal Harvest68 €/ 1% increase in probability of an Optimal HarvestControl Cohort (n 183)7.6%15.8%24.4%3,354 €P (adjusted for comparisons)NS0.0060.02 Disclosures Milone: Sanofi: Consultancy. Martino:Sanofi: Consultancy. Olivieri:Sanofi: Consultancy.