Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): And randomised, phase 3, open-label, multicentre study

Background: Bortezomib with dexamethasone is a standard treatment option for relapsed or refractory multiple myeloma. Carfilzomib with dexamethasone has shown promising activity in patients in this disease setting. The aim of this study was to compare the combination of carfilzomib and dexamethasone with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Methods: In this randomised, phase 3, open-label, multicentre study, patients with relapsed or refractory multiple myeloma who had one to three previous treatments were randomly assigned (1:1) using a blocked randomisation scheme (block size of four) to receive carfilzomib with dexamethasone (carfilzomib group) or bortezomib with dexamethasone (bortezomib group). Randomisation was stratified by previous proteasome inhibitor therapy, previous lines of treatment, International Staging System stage, and planned route of bortezomib administration if randomly assigned to bortezomib with dexamethasone. Patients received treatment until progression with carfilzomib (20 mg/m2 on days 1 and 2 of cycle 1; 56 mg/m2 thereafter; 30 min intravenous infusion) and dexamethasone (20 mg oral or intravenous infusion) or bortezomib (1·3 mg/m2; intravenous bolus or subcutaneous injection) and dexamethasone (20 mg oral or intravenous infusion). The primary endpoint was progression-free survival in the intention-to-treat population. All participants who received at least one dose of study drug were included in the safety analyses. The study is ongoing but not enrolling participants; results for the interim analysis of the primary endpoint are presented. The trial is registered at ClinicalTrials.gov, number NCT01568866. Findings: Between June 20, 2012, and June 30, 2014, 929 patients were randomly assigned (464 to the carfilzomib group; 465 to the bortezomib group). Median follow-up was 11·9 months (IQR 9·3-16·1) in the carfilzomib group and 11·1 months (8·2-14·3) in the bortezomib group. Median progression-free survival was 18·7 months (95% CI 15·6-not estimable) in the carfilzomib group versus 9·4 months (8·4-10·4) in the bortezomib group at a preplanned interim analysis (hazard ratio [HR] 0·53 [95% CI 0·44-0·65]; p<0·0001). On-study death due to adverse events occurred in 18 (4%) of 464 patients in the carfilzomib group and in 16 (3%) of 465 patients in the bortezomib group. Serious adverse events were reported in 224 (48%) of 463 patients in the carfilzomib group and in 162 (36%) of 456 patients in the bortezomib group. The most frequent grade 3 or higher adverse events were anaemia (67 [14%] of 463 patients in the carfilzomib group vs 45 [10%] of 456 patients in the bortezomib group), hypertension (41 [9%] vs 12 [3%]), thrombocytopenia (39 [8%] vs 43 [9%]), and pneumonia (32 [7%] vs 36 [8%]). Interpretation: For patients with relapsed or refractory multiple myeloma, carfilzomib with dexamethasone could be considered in cases in which bortezomib with dexamethasone is a potential treatment option. Funding: Onyx Pharmaceuticals, Inc., an Amgen subsidiary

Using the satellite GPS system for monitoring work parameters of vehicles and machines in agriculture

W opracowaniu przedstawiono ocenę satelitarnego systemu monitorowania parametrów eksploatacyjnych pracy pojazdów oraz wykorzystania jego możliwości do wspomagania procesu zarządzania i poprawy funkcjonowania gospodarstwa. Przeprowadzono również ocenę porównawczą raportów zarejestrowanych przez system monitoringu GPS z wykazem kart pracowniczych oraz faktur.The study presents the evaluation of a satellite system for monitoring operating parameters of vehicles and using its potential to support farm management process and improvement in functioning. Moreover, the researchers have completed comparative analysis of reports registered by GPS monitoring system with a list of work records and invoices

Application of the GPS monitoring system in effective management of agricultural vehicles operation

W opracowaniu przestawiono przeprowadzone analizy zużycia paliwa oraz oceniono wielkość ponoszonych kosztów w okresie 4 zimowych miesięcy pracy dwóch ciągników rolniczych JCB Fastrac 3190 i 3220. Badaniom podlegała weryfikacja danych zapisanych w raportach systemu monitoringu GPS z danymi księgowymi otrzymanymi od pracowników administracyjnych gospodarstwa usługowego. Zasadność wykorzystania systemu monitoringu w gospodarstwie potwierdzono na podstawie wykonanej analizy finansowej zysków i strat, w której obliczono koszty użytkowania ciągników oraz sumaryczne koszty pracy obciążające gospodarstwo.The study presents the conducted analyses of fuel consumption and evaluates the amount of costs, which were incurred by two tractors JCB Fastrac 3190 i 3220 during 4 winter months. The study consisted in verification of data reported by the GPS monitoring system in comparison with accounting data received from administrative employees of a service farm. Validity of using the monitoring system on the farm was confirmed based on financial analysis of profits and loses which was carried out, within which, the costs of using tractors and the total costs of the work charging the farm were calculated

Investigation of apples sensitivity to bruising at impact loading

W pracy zaprezentowano wyniki badań wpływu obciążeń o charakterze udarowym na wrażliwość jabłek na stłuczenia przy zmiennych wartościach wysokości zrzutu i ilości uderzeń. Wyznaczono wartości impulsów sił, pola powierzchni styku oraz nacisków powierzchniowych w funkcji wysokości i ilości stłuczeń. Wykonano dokumentację fotograficzną, która posłużyła do przeprowadzenia komputerowej analizy obrazów w celu wyznaczenia objętości zniszczonej tkanki oraz przedstawienia oceny jakościowej wrażliwości jabłek na stłuczenia. Pomiary przy obciążeniach udarowych przeprowadzono za pomocą aparatury firmy Tekscan na specjalnie zbudowanym stanowisku badawczym, którego działanie oparte było na zasadzie wahadła. Analiza zmian objętości deformacji w funkcji sił chwilowych podczas uderzenia wykazała, że przy wzroście obciążenia z 57 N do 106 N następuje gwałtowny wzrost wartości objętości z 363 do 6233 mm3. Analiza nacisków powierzchniowych potwierdziła występowanie maksymalnych wartości dla pierwszych uderzeń jabłek, największą zaś wartość wynoszącą 0,256 MPa uzyskano dla wysokości zrzutu równej 250 mm. Niezależnie od wysokości zrzutu, po dziesięciu uderzeniach naciski powierzchniowe stabilizują się na poziomie 0,160 MPa. Stwierdzono, że badane jabłka wykazują dużą wrażliwość pod wpływem obciążeń o charakterze udarowym. Oszacowano wysokość zrzutu około 30 mm, którą można uznać za wartość niewywołującą odkształceń o charakterze plastycznym.The paper presents results of research on the influence of impact loading on sensitivity of apples to bruising at variable values of the drop height and the number of impacts. Values of power impulses, contact surface area and surface pressure as the function of height and the number of bruises were determined. Photographic documentation was prepared, which served for carrying out a computer analysis of images in order to determine the volume of the damaged tissue and for presenting the assessment of quality sensitivity of apples to impact. Measurements at impact loading were carried out with the use of Tekscan apparatus on a specially constructed research stand, whose operation was based on the pendulum principle. Analysis of volume changes of deformation as the function of temporary powers during impact proved that at the increase of loading from 57 N to 106 N a violent increase of the volume value from 363 do 6233 mm3 took place. Analysis of surface pressures confirmed occurrence of maximum values for first impact to apples, whereas the highest value of 2.256 MPa was obtained for the drop height amounting to 250 mm. Independently from the drop height, after ten impacts, surface pressures stabilize at the level 0.160 MPa. It was determined that the investigated apples prove high sensitivity under the influence of impact loading. The drop height was estimated to be 30 mm, which may be recognized as the value, which does not cause plastic deformations

Agent based power system management - concept of congestion management

Congestion management is one of the technical challenges in the power system. Privatization and market liberalization lead to stressed operating conditions in existing and future power systems. Additionally, the increasing complexity of the power system results in an increased need for information on the actual grid condition and intelligent control methods. Unfortunately, measurement data from each node is not in the distribution level. Introduction of decentralized control methods allows overcoming the limitations associated with centralized control, like failure of main controller. In this paper, a concept of congestion management using a multi-agent system is presented. In this approach, control processes are realized by active power adjustments based on Power Transfer Distribution Factor methodology. Depending on localization of congested line, appropriate agent initiates the whole redispatch procedure