Complexification methods of interval forecast estimates in the problems on short-term prediction

Вирішено завдання удосконалення методичної бази системи підтримки прийняття рішень у процесi короткострокового прогнозування показникiв організаційно-технічних систем шляхом розробки нових i адаптації існуючих методiв комплексування, здатних врахувати інтервальну невизначеність прогнозних оцінок. Актуальнiсть даного завдання обумовлена необхідністю врахування невизначеності первинної інформації, викликаної проявом НI-чинникiв. Проведений аналіз передумов i особливостей формалiзації невизначеності первинних даних в інтервальнiй формi, виявлені переваги iнтервального аналiзу для вирішення задачi комплексування інтервальних прогнозних оцінок. Викладено короткі відомості про базовий математичний апарат: iнтервальну арифметику та інтервальний аналiз. Вдосконалено методи комплексування прогнозних оцінок шляхом синтезу iнтервальних розширень, отриманих вiдповiдно до парадигми інтервального аналізу. В результатi досліджень встановлено, що введення аналiтичної функцiї переваг дозволило синтезувати модель комплексування в досить загальному виглядi, шляхом об'єднання в єдинiй формi класiв гiбридних i селективних моделей для генерації консолідованих прогнозiв на основi інтервальних прогнозних оцiнок. Це дозволяє отримувати комплексовані прогнози на основi інтервальних прогнозних оцінок, тим самим забезпечувати точність консолідованого короткострокового прогнозу. Проведено критичний аналіз запропонованих методiв i розроблено рекомендацiї щодо їх практичного використання. Сформульовано рекомендації щодо параметричного налаштування аналітичної функції переваг. На прикладi показано адаптивні властивості інтервальної моделі комплексування

Reduced number and function of peripheral dendritic cells in coeliac disease.

Dendritic cells (DC) play a pivotal role in shaping the immune response in both physiological and pathological conditions. In peripheral blood at least two subsets, the myeloid and plasmacytoid, have been described as having different T stimulatory functions and a variable degree of maturation. Certainly, antigen presentation plays a crucial role in the pathogenesis of coeliac disease and circulating immune cells are thought to reflect the state of immune response within the gut. Therefore,we aimed to investigate the quantitative and phenotypical modifications of peripheral bloodDC, together with their functional properties, in this pathological condition. Blood samples from 11 untreated patients before and after a course of gluten-free diet, 27 treated patients and 14 controls underwent flow-cytometric analysis, while immunomagnetically sorted DC from the CD patients and eight human leucocyte antigen (HLA)-DQ2/8+ bone marrow donors were used to evaluate maturation status through the CD83 expression, cytokine profile for interleukin (IL)-6, IL-10, IL-12 and interferon (IFN)-a by enzyme-linked immunosorbent assay (ELISA), and functional properties by mixed leucocyte reaction before and after pulsing with digested gliadin. We found that in both untreated and treated patients, a significant reduction of the entire DC population, mainly the plasmacytoid subset, in comparison to healthy controls was observed. In active disease, an impaired allogenic lymphocyte reaction and a significant reduction of IFN-a production, paralleled by the presence of a more immature status, were also demonstrated. All the latter modifications have been reverted by pulsing DC with digested gliadin

Bone marrow stem cell damage after three different chemotherapy regimens for advanced Hodgkin's lymphoma

The aim of this study was to evaluate the apoptotic damage to bone marrow cells caused by three chemotherapy regimens for advanced Hodgkin's lymphoma, ABVD, COPPEBVCAD and BEACOPP, which were randomly administered in the HD 2000 GISL trial. Bone marrow mononuclear cells (BMMCs) stained with anti-CD34 antibody and Annexin V, were evaluated by flow cytometry before starting chemotherapy, 30 days after completing chemotherapy and after 6 months. Results are expressed as the percentages of BMMCs positive to anti-CD34, to Annexin V or to both. Fourteen patients treated with ABVD, 11 with COPPEBVCAD and 13 with BEACOPP were evaluated before and 30 days after treatment. Late assessments were made in 6, 7 and 8 of them, respectively. No differences were found among the pretherapeutic flow cytometry findings in relation to the staging characteristics (marrow involvement included). All the regimens increased the apoptotic fraction of the whole mononuclear bone marrow cells (COPPEBVCAD did so significantly) and increased the CD34+ compartment (with significant early differences after ABVD and BEACOPP, tending to late persistence for ABVD, only). All the regimens increased the apoptotic CD34+ cells within the whole BMMC population (significantly after BEACOPP), although with a general trend to decrease in their percentage within the CD34+ compartment over time, even after the most dose-dense regimens. Based on the variations induced in the apoptotic fraction of all mononuclear and CD34+ cells, ABVD was the least toxic regimen and COPPEBVCAD the most toxic one

Gemcitabine and Oxaliplatin in the Treatment of Patients with Immunotherapy-Resistant Advanced Renal Cell Carcinoma: Final Results of a Single-Institution Phase II Study

BACKGROUND. Currently, there is no standard treatment for patients with advanced renal cell carcinoma (RCC) who do not experience a response to first-line immunotherapy. In the current Phase II study, the authors explored the antitumor activity of a combination of gemcitabine and oxaliplatin (L-OHP) in this setting. METHODS. Forty-two patients with RCC who had progressive disease following immunotherapy received gemcitabine (1000 mg/m2 intravenously on Days 1 and 8 every 21 days) and L-OHP (90 mg/m2 intravenously on Day 1 every 21 days) for a minimum of 2 cycles before responses were evaluated. Responses to treatment and toxicity were recorded according to the Response Evaluation Criteria in Solid Tumors and the National Cancer Institute Common Toxicity Criteria, respectively. RESULTS. No complete responses were recorded; however, 6 patients experienced a partial response (14.28%; 95% confidence interval, 5.43-28.5%), 11 patients (26.19%) had temporary stable disease as a best response, and the remaining 25 patients (59.52%) experienced progression despite receiving treatment. The median time to disease progression was 2.5 months (mean, 3.86 months; range, 1.5-11.0 months), whereas the median overall survival was 9.5 months (mean, 10.46 months; range, 4.0-22.5 months). With regard to toxicity, treatment generally was well tolerated, with only one episode of Grade 4 toxicity and expected episodes of Grade 3 toxicity, including myelosuppression and neuropathy. CONCLUSIONS. The current results suggest that the combination of gemcitabine and L-OHP possesses a certain level of activity and an acceptable toxicity profile in patients with immunotherapy-resistant advanced RCC

\u201cWeekly docetaxel and gemcitabine as first line treatment for metastatic breast cancer: results of a multicenter phase II study\u201d

Objectives: We conducted a multicenter phase II study to evaluate the clinical effi cacy, toxicity, and dose intensity of a new weekly schedule of docetaxel and gemcitabine as fi rst-line treatment of metastatic breast cancer patients. Methods: We enrolled 58 patients, 52% of whom had received a previous anthracycline-containing chemotherapy. The treatment schedule was: docetaxel 35 mg/m 2 and gemcitabine 800 mg/m 2 i.v. on days 1, 8,15 every 28 days. Results: All patients were assessable for toxicity and 56 for effi cacy. Overall response rate was 64.3% with 16.1% of complete responses and 48.2% of partial responses. Median survival was 22.10 months (95% CI: 15.53\u201328.67) and median time to tumor progression was 13.6 months (95% CI: 10.71\u201316.49). The most common hematological toxicity was neutropenia (no febrile neutropenia), which occurred in 28 patients (48.3%) but grade 3\u20134 in only 8 patients (14%). Alopecia, the most common nonhematological toxicity, occurred in 20 (34.5%) patients, but only 5 patients (8.6%) experienced grade 3 alopecia. Conclusion: The activity of docetaxel and gemcitabine in metastatic breast cancer is confirmed. The promising results of the employed schedule,in agreement with other published studies, need to be further confirmed within a phase III study