This paper presents a planning and execution architecture suited for the initial planning, the execution and the on-board repair of a plan for a multi-robot mission. The team as a whole must ...accomplish its mission while dealing with online events such as robots breaking down, new objectives for the team, late actions and intermittent communications. We have chosen a “plan then repair” approach where an initial plan is computed offline and updated online whenever disruptive events happen. We have defined an hybrid planner that mixes Partial Order Planning (POP) with a Hierarchical Task Network (HTN)-based modelling of actions. This planner, called HiPOP for Hierarchical Partial-Order Planner, computes plans with temporal flexibility (thus easing its execution) and abstract actions (thus easing the repair process). It uses a symbolic representation of the world and has been extended with geometrical reasoning to adapt to multi-robots missions. Plans are executed in a distributed way: each robot is responsible of executing its own actions, and to propagate delays in its local plan, taking benefit from the temporal flexibility of the plan. When an inconsistency or a failure arises, a distributed repair algorithm based on HiPOP is used to repair the plan, by iteratively removing actions in the plan in order to amend the global plan. This repair is done onboard one of the robot of the team, and takes care of partial communication. The whole architecture has been evaluated through several benchmarks, statistical simulations, and field experiments involving 8 robots.
•Imaging biomarkers with high effect sizes are needed for clinical trials in AMN.•Spine imaging studies are scarce.•Multiparametric brain and spine imaging better characterizes the disease.
...Progressive myelopathy causes severe handicap in men with adrenomyeloneuropathy (AMN), an X-linked disorder due to ABCD1 pathogenic variants. At present, treatments are symptomatic but disease-modifying therapies are under evaluation. Given the small effect size of clinical scales in AMN, biomarkers with higher effect size are needed. Here we used high-resolution magnetic resonance techniques to identify non-invasive in vivo biomarkers of the brain and spine with high effect sizes.
We performed a multiparametric imaging and spectroscopy study in 23 male patients with AMN (age: 44 ± 11) and 23 male controls (age: 43 ± 11) of similar age and body-mass index. We combined (i) macrostructural analyses of the spine, using cross-sectional area (CSA) and magnetization transfer ratio (MTR), (ii) microstructural analyses of the spine and the brain, using diffusion tensor and the newly developed fixel-based analysis, and (iii) advanced metabolic analyses of the spine using metabolite cycling coupled to a semi-LASER sequences.
Macrostructural alterations (decrease in CSA and MTR) were observed in patients at all spinal cord levels studied (C1-T2 for CSA and C1-C5 for MTR) (p < 0.001). Microstructural alterations were observed in the spine and brain on diffusion tensor and fixel-based metrics though the latter showed higher effect sizes. Metabolic alterations were observed in patients as a decreased total N-acetylaspartate/myo-inositol ratio (p < 0.001). Overall, MTR showed the highest effect size.
This cross-sectional study supports the use of multiparametric techniques that elucidate the structural, microstructural and metabolic alterations in AMN. These outcome measures should be tested longitudinally and in clinical trials.
Realizing long-term autonomous missions involving teams of heterogeneous robots is a challenge. It requires mechanisms to make robots react to disturbances or failures that will arise during the ...mission, while trying to successfully achieve the mission in cooperation. This paper presents HiDDeN, a distributed deliberative architecture that manages the execution of a hierarchical plan. This plan has initially been computed offline, ensuring some military operational constraints of the mission. Each robot’s supervisor then executes its own part of the plan, and reacts to failures using a hierarchical repair approach. This hierarchical repair has been designed with the sake of ensuring operational constraints, while reducing the need of communication between robots, as communication may be intermittent or even nonexistent when the robots operate in completely separate environments. HiDDeN’s robustness and scalability is evaluated with simulations. Experiments with an autonomous helicopter and an autonomous underwater vehicle have been realized and are presented as the defining point of our contribution.
Abstract Cerebral adrenoleukodystrophy (CALD) is an X-linked rapidly progressive demyelinating disease leading to death usually within a few years. The standard of care is hematopoietic stem cell ...transplantation (HSCT), but many men are not eligible due to age, absence of a matched donor, or lesions of the corticospinal tracts (CST). Based on the ADVANCE study showing that leriglitazone decreases the occurrence of CALD, we treated 13 adult CALD patients (19-67 years of age) either not eligible to HSCT (n= 8) or awaiting HSCT (n= 5). Patients were monitored every 3 months with standardized neurological scores, plasma biomarkers and brain MRI comprising lesion volumetrics and diffusion tensor imaging. The disease stabilized clinically and radiologically in 10 patients with up to 2 years of follow-up. Five patients presented with gadolinium enhancing CST lesions that all turned gadolinium negative and, remarkably, regressed in four patients. Plasma neurofilament light chain levels stabilized in all 10 patients and correlated with lesion load. The two patients who continued to deteriorate were over 60 years of age with prominent cognitive impairment. One patient rapidly died from Covid19. These results suggest that leriglitazone can arrest disease progression in adults with early-stage CALD and may be an alternative treatment to HSCT.
Performing a complex autonomous mission with a multi-robot system requires to integrate several deliberative approaches to perform task allocation, optimization, and execution control. Implementing ...such a deliberative architecture is a complex task: it requires the developer to master the decision algorithms themselves (e.g., automated planning models), to have a good knowledge of the involved robotic platforms, and to think about how these elements will be assembled as a system architecture. We propose a framework to help designing such deliberative architectures. The framework relies on the concept of a hierarchical structure of actors, each actor managing goals with specific planning or optimization approaches, and delegating sub-goals to other actors.
Realizing long-term autonomous missions involving teams of heterogeneous robots is a challenge. It requires mechanisms to make robots react to disturbances or failures that will arise during the ...mission, while trying to successfully achieve the mission in cooperation. This paper presents HiDDeN, a distributed deliberative architecture that manages the execution of a hierarchical plan. This plan has initially been computed offline, ensuring some military operational constraints of the mission. Each robot’s supervisor then executes its own part of the plan, and reacts to failures using a hierarchical repair approach. This hierarchical repair has been designed with the sake of ensuring operational constraints, while reducing the need of communication between robots, as communication may be intermittent or even nonexistent when the robots operate in completely separate environments. HiDDeN’s robustness and scalability is evaluated with simulations. Experiments with an autonomous helicopter and an autonomous underwater vehicle have been realized and are presented as the defining point of our contribution.
Adult patients with adrenoleukodystrophy have a poor prognosis owing to development of adrenomyeloneuropathy. Additionally, a large proportion of patients with adrenomyeloneuropathy develop ...life-threatening progressive cerebral adrenoleukodystrophy. Leriglitazone is a novel selective peroxisome proliferator-activated receptor gamma agonist that regulates expression of key genes that contribute to neuroinflammatory and neurodegenerative processes implicated in adrenoleukodystrophy disease progression. We aimed to assess the effect of leriglitazone on clinical, imaging, and biochemical markers of disease progression in adults with adrenomyeloneuropathy.
ADVANCE was a 96-week, randomised, double-blind, placebo-controlled, phase 2–3 trial done at ten hospitals in France, Germany, Hungary, Italy, the Netherlands, Spain, the UK, and the USA. Ambulatory men aged 18–65 years with adrenomyeloneuropathy without gadolinium enhancing lesions suggestive of progressive cerebral adrenoleukodystrophy were randomly assigned (2:1 without stratification) to receive daily oral suspensions of leriglitazone (150 mg starting dose; between baseline and week 12, doses were increased or decreased to achieve plasma concentrations of 200 μg·h/mL SD 20%) or placebo by means of an interactive response system and a computer-generated sequence. Investigators and patients were masked to group assignment. The primary efficacy endpoint was change from baseline in the Six-Minute Walk Test distance at week 96, analysed in the full-analysis set by means of a mixed model for repeated measures with restricted maximum likelihood and baseline value as a covariate. Adverse events were also assessed in the full-analysis set. This study was registered with ClinicalTrials.gov, NCT03231878; the primary study is complete; patients had the option to continue treatment in an open-label extension, which is ongoing.
Between Dec 8, 2017, and Oct 16, 2018, of 136 patients screened, 116 were randomly assigned; 62 81% of 77 patients receiving leriglitazone and 34 87% of 39 receiving placebo completed treatment. There was no between-group difference in the primary endpoint (mean SD change from baseline leriglitazone: –27·7 41·4 m; placebo: –30·3 60·5 m; least-squares mean difference –1·2 m; 95% CI –22·6 to 20·2; p=0·91). The most common treatment emergent adverse events in both the leriglitazone and placebo groups were weight gain (54 70% of 77 vs nine 23% of 39 patients, respectively) and peripheral oedema (49 64% of 77 vs seven 18% of 39). There were no deaths. Serious treatment-emergent adverse events occurred in 14 (18%) of 77 patients receiving leriglitazone and ten (26%) of 39 patients receiving placebo. The most common serious treatment emergent adverse event, clinically progressive cerebral adrenoleukodystrophy, occurred in six 5% of 116 patients, all of whom were in the placebo group.
The primary endpoint was not met, but leriglitazone was generally well tolerated and rates of adverse events were in line with the expected safety profile for this drug class. The finding that cerebral adrenoleukodystrophy, a life-threatening event for patients with adrenomyeloneuropathy, occurred only in patients in the placebo group supports further investigation of whether leriglitazone might slow the progression of cerebral adrenoleukodystrophy.
Minoryx Therapeutics.
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