5 research outputs found

    A study of the rotating-stall inception in high-speed compressors

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    Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 1994.Includes bibliographical references (leaves 41-42).by Michail Tryfonidis.M.S

    Robust adaptive control modeling of human arm movements subject to altered gravity and mechanical loads

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    Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 1999.Includes bibliographical references (leaves 159-164).It has been observed that during orbital spaceflight the absence of gravitation related sensory inputs causes incongruence between the expected and the actual sensory feedback resulting from voluntary movements. This incongruence results in a reinterpretation or neglect of gravity-induced sensory input signals. Over time, new internal models develop, gradually compensating for the loss of spatial reference. The study of adaptation of goal-directed movements is the main focus of this thesis. The hypothesis is that during the adaptive learning process the neural connections behave in ways that can be described by an adaptive control method. The investigation presented in this thesis includes two different sets of experiments. A series of dart throwing experiments took place onboard the space station Mir. Experiments also took place at the Biomechanics lab at MIT, where the subjects performed a series of continuous trajectory tracking movements while a planar robotic manipulandum exerted external torques on the subjects' moving arms. The experimental hypothesis for both experiments is that during the first few trials the subjects will perform poorly trying to follow a prescribed trajectory, or trying to hit a target. A theoretical framework is developed that is a modification of the sliding control method used in robotics. The new control framework is an attempt to explain the adaptive behavior of the subjects. Numerical simulations of the proposed framework are compared with experimental results and predictions from competitive models. The proposed control methodology extends the results of the sliding mode theory to human motor control. The resulting adaptive control model of the motor system is robust to external dynamics, even those of negative gain, uses only position and velocity feedback, and achieves bounded steady-state error without explicit knowledge of the system's nonlinearities. In addition, the experimental and modeling results demonstrate that visuomotor learning is important not only for error correction through internal model adaptation on ground or in microgravity, but also for the minimization of the total mean-square error in the presence of random variability. Thus human intelligent decision displays certain attributes that seem to conform to Bayesian statistical games.by Michail Tryfonidis.Ph.D

    Liquid biopsy-based clinical research in early breast cancer: The EORTC 90091-10093 Treat CTC trial

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    There is increasing evidence that breast cancer evolves over time under the selection pressure of systemic treatment. Today, treatment decisions in early breast cancer are based on primary tumour characteristics without considering the disease evolution. Chemoresistant micrometastatic disease is poorly characterised and thus it is not used in current clinical practice as a tool to personalise treatment approaches. The detection of chemoresistant circulating tumour cells (CTCs) has been shown to be associated with worse prognosis in early breast cancer. The ongoing Treat CTC trial is the first international, liquid biopsy-based trial evaluating the concept of targeting chemoresistant minimal residual disease: detection of CTCs following adjuvant chemotherapy (adjuvant cohort) or neoadjuvant chemotherapy in patients who did not achieve pathological complete response (neoadjuvant cohort). This article presents the rational and design of this trial and the results of the pilot phase after 350 patients have been screened and provides insights that might provide information for future trials using the liquid biopsy approach as a tool towards precision medicine (NCT01548677).SCOPUS: re.jinfo:eu-repo/semantics/publishe

    Niraparib for Advanced Breast Cancer with Germline and Mutations: the EORTC 1307-BCG/BIG5-13/TESARO PR-30-50-10-C BRAVO Study.

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    To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadPurpose: To investigate the activity of niraparib in patients with germline-mutated BRCA1/2 (gBRCAm) advanced breast cancer. Patients and methods: BRAVO was a randomized, open-label phase III trial. Eligible patients had gBRCAm and HER2-negative advanced breast cancer previously treated with ≤2 prior lines of chemotherapy for advanced breast cancer or had relapsed within 12 months of adjuvant chemotherapy, and were randomized 2:1 between niraparib and physician's choice chemotherapy (PC; monotherapy with eribulin, capecitabine, vinorelbine, or gemcitabine). Patients with hormone receptor-positive tumors had to have received ≥1 line of endocrine therapy and progressed during this treatment in the metastatic setting or relapsed within 1 year of (neo)adjuvant treatment. The primary endpoint was centrally assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), PFS by local assessment (local-PFS), objective response rate (ORR), and safety. Results: After the pre-planned interim analysis, recruitment was halted on the basis of futility, noting a high degree of discordance between local and central PFS assessment in the PC arm that resulted in informative censoring. At the final analysis (median follow-up, 19.9 months), median centrally assessed PFS was 4.1 months in the niraparib arm (n = 141) versus 3.1 months in the PC arm [n = 74; hazard ratio (HR), 0.96; 95% confidence interval (CI), 0.65-1.44; P = 0.86]. HRs for OS and local-PFS were 0.95 (95% CI, 0.63-1.42) and 0.65 (95% CI, 0.46-0.93), respectively. ORR was 35% (95% CI, 26-45) with niraparib and 31% (95% CI, 19-46) in the PC arm. Conclusions: Informative censoring in the control arm prevented accurate assessment of the trial hypothesis, although there was clear evidence of niraparib's activity in this patient population.TESARO United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI
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