MPC fault-tolerant flight control case study: Flight 1862

We demonstrate that the fatal crash of El Al Flight 1862 might have been avoided by using MPC-based fault-tolerant control. Simulation on a detailed nonlinear model shows that it is possible to reconfigure the controller so that the aircraft is flown successfully down to ground level, without entering the condition in which it was lost. We use a reference-model based approach, in which an MPC controller attempts to restore the original functionality of the pilot’s controls. For the purposes of simulation, we emulate the pilot by another MPC controller, running at a lower sampling rate. We assume in this paper that an FDI function delivers information about actuator damage, and about changes to aerodynamic coefficients in the failed condition

Primal-Dual Enumeration for Multiparametric Linear Programming

Optimal control problems for constrained linear systems with a linear cost can be posed as multiparametric linear programs (pLPs) and solved explicitly offline. Several algorithms have recently been proposed in the literature that solve these pLPs in a fairly efficient manner, all of which have as a base operation the computation and removal of redundant constraints. For many problems, it is this redundancy elimination that requires the vast majority of the computation time. This paper introduces a new solution technique for multiparametric linear programs based on the primal–dual paradigm. The proposed approach reposes the problem as the vertex enumeration of a linearly transformed polytope and then simultaneously computes both its vertex and halfspace representations. Exploitation of the halfspace representation allows, for smaller problems, a very significant reduction in the number of redundancy elimination operations required, resulting in many cases in a much faster algorithm

Equality Set Projection: A new algorithm for the projection of polytopes in halfspace representation

In this paper we introduce a new algorithm called Equality Set Projection (ESP) for computing the orthogonal projection of bounded, convex polytopes. Our solution addresses the case where the input polytope is represented as the intersection of a finite number of halfplanes and its projection is given in an irredundant halfspace form. Unlike many existing approaches, the key advantage offered by ESP is its output sensitivity, i.e., its complexity is a function of the number of facets in the projection of the polytope. This feature makes it particularly suited for many problems of theoretical and practical importance in which the number of vertices far exceeds the number of facets. Further, it is shown that for non-degenerate polytopes of fixed size (dimension and number of facets) the complexity is linear in the number of facets in the projection. Numerical results are presented that demonstrate that high dimensional polytopes can be projected efficiently

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

Clinical course and outcome of SARS-CoV-2 infection in multiple sclerosis patients treated with disease-modifying therapies — the Polish experience

Introduction. The aim of this study was to report the course and outcome of SARS-CoV-2 infection in multiple sclerosis (MS) patients treated with disease-modifying therapies (DMTs) in Poland. A major concern for neurologists worldwide is the course and outcome of SARS-CoV-2 infection in patients with MS treated with different DMTs. Although initial studies do not suggest an unfavourable course of infection in this group of patients, the data is limited.Materials and methods. This study included 396 MS patients treated with DMTs and confirmed SARS-CoV-2 infection from 28 Polish MS centres. Information concerning patient demographics, comorbidities, clinical course of MS, current DMT use, as well as symptoms of SARS-CoV-2 infection, need for pharmacotherapy, oxygen therapy, and/or hospitalisation, and short-term outcomes was collected up to 30 January 2021. Additional data about COVID-19 cases in the general population in Poland was obtained from official reports of the Polish Ministry of Health.Results. There were 114 males (28.8%) and 282 females (71.2%). The median age was 39 years (IQR 13). The great majority of patients with MS exhibited relapsing-remitting course (372 patients; 93.9%). The median EDSS was 2 (SD 1.38), and the mean disease duration was 8.95 (IQR 8) years. Most of the MS patients were treated with dimethyl fumarate (164; 41.41%). Other DMTs were less frequently used: interferon beta (82; 20.70%), glatiramer acetate (42; 10.60%), natalizumab (35;8.84%), teriflunomide (25; 6.31%), ocrelizumab (20; 5.05%), fingolimod (16; 4.04), cladribine (5; 1.26%), mitoxantrone (3; 0.76%), ozanimod (3; 0.76%), and alemtuzumab (1; 0.25%). The overall hospitalisation rate due to COVID-19 in the cohort was 6.81% (27 patients). Only one patient (0.3%) died due to SARS-CoV-2 infection, and three (0.76%) patients were treated with mechanical ventilation; 106 (26.8%) patients had at least one comorbid condition. There were no significant differences in the severity of SARS-CoV-2 infection regarding patient age, duration of the disease, degree of disability (EDSS), lymphocyte count, or type of DMT used.Conclusions and clinical implications. Most MS patients included in this study had a favourable course of SARS-CoV-2 infection. The hospitalisation rate and the mortality rate were not higher in the MS cohort compared to the general Polish population. Continued multicentre data collection is needed to increase the understanding of SARS-CoV-2 infection impact on the course of MS in patients treated with DMTs

Performance evaluation of multiplexed model predictive control for a large airliner in nominal and contingency scenarios

Model predictive control allows systematic han- dling of physical and operational constraints through the use of constrained optimisation. It has also been shown to successfully exploit plant redundancy to maintain a level of control in scenarios when faults are present. Unfortunately, the computa- tional complexity of each individual iteration of the algorithm to solve the optimisation problem scales cubically with the number of plant inputs, so the computational demands are high for large MIMO plants. Multiplexed MPC only calculates changes in a subset of the plant inputs at each sampling instant, thus reducing the complexity of the optimisation. This paper demonstrates the application of multiplexed model predictive control to a large transport airliner in a nominal and a contingency scenario. The performance is compared to that obtained with a conventional synchronous model predictive controller, designed using an equivalent cost function.This work was supported by Engineering and Physical Sciences Research Council grant number EP/G030308/1.The 2012 American Control Conference, June 27-29, Montreal, Canada