International Consensus Recommendations for the Treatment of Pediatric NMDAR Antibody Encephalitis.

OBJECTIVE: To create an international consensus treatment recommendation for pediatric NMDA receptor antibody encephalitis (NMDARE). METHODS: After selection of a panel of 27 experts with representation from all continents, a 2-step Delphi method was adopted to develop consensus on relevant treatment regimens and statements, along with key definitions in pediatric NMDARE (disease severity, failure to improve, and relapse). Finally, an online face-to-face meeting was held to reach consensus (defined as ≥75% agreement). RESULTS: Corticosteroids are recommended in all children with NMDARE (pulsed IV preferred), with additional IV immunoglobulin or plasma exchange in severe patients. Prolonged first-line immunotherapy can be offered for up to 3-12 months (oral corticosteroids or monthly IV corticosteroids/immunoglobulin), dependent on disease severity. Second-line treatments are recommended for cases refractory to first-line therapies (rituximab preferred over cyclophosphamide) and should be considered about 2 weeks after first-line initiation. Further immunotherapies for refractory disease 1-3 months after second-line initiation include another second-line treatment (such as cyclophosphamide) and escalation to tocilizumab. Maintenance immune suppression beyond 6 months (such as rituximab redosing or mycophenolate mofetil) is generally not required, except for patients with a more severe course or prolonged impairments and hospitalization. For patients with relapsing disease, second-line and prolonged maintenance therapy should be considered. The treatment of NMDARE following herpes simplex encephalitis should be similar to idiopathic NMDARE. Broad guidance is provided for the total treatment duration (first line, second line, and maintenance), which is dictated by the severity and clinical course (i.e., median 3, 9 and 18 months in the best, average, and worst responders, respectively). Recommendations on the timing of oncologic searches are provided. CONCLUSION: These international consensus recommendations for the management of pediatric NMDARE aim to standardize the treatment and provide practical guidance for clinicians, rather than absolute rules. A similar recommendation could be applicable to adult patients

Joint Goal and Strategy Inference across Heterogeneous Demonstrators via Reward Network Distillation

Reinforcement learning (RL) has achieved tremendous success as a general framework for learning how to make decisions. However, this success relies on the interactive hand-tuning of a reward function by RL experts. On the other hand, inverse reinforcement learning (IRL) seeks to learn a reward function from readily-obtained human demonstrations. Yet, IRL suffers from two major limitations: 1) reward ambiguity - there are an infinite number of possible reward functions that could explain an expert's demonstration and 2) heterogeneity - human experts adopt varying strategies and preferences, which makes learning from multiple demonstrators difficult due to the common assumption that demonstrators seeks to maximize the same reward. In this work, we propose a method to jointly infer a task goal and humans' strategic preferences via network distillation. This approach enables us to distill a robust task reward (addressing reward ambiguity) and to model each strategy's objective (handling heterogeneity). We demonstrate our algorithm can better recover task reward and strategy rewards and imitate the strategies in two simulated tasks and a real-world table tennis task.Comment: In Proceedings of the 2020 ACM/IEEE In-ternational Conference on Human-Robot Interaction (HRI '20), March 23 to 26, 2020, Cambridge, United Kingdom.ACM, New York, NY, USA, 10 page

International Consensus Recommendations for the Treatment of Pediatric NMDAR Antibody Encephalitis

To create an international consensus treatment recommendation for pediatric NMDA receptor antibody encephalitis (NMDARE).After selection of a panel of 27 experts with representation from all continents, a 2-step Delphi method was adopted to develop consensus on relevant treatment regimens and statements, along with key definitions in pediatric NMDARE (disease severity, failure to improve, and relapse). Finally, an online face-to-face meeting was held to reach consensus (defined as ?75% agreement).Corticosteroids are recommended in all children with NMDARE (pulsed IV preferred), with additional IV immunoglobulin or plasma exchange in severe patients. Prolonged first-line immunotherapy can be offered for up to 3-12 months (oral corticosteroids or monthly IV corticosteroids/immunoglobulin), dependent on disease severity. Second-line treatments are recommended for cases refractory to first-line therapies (rituximab preferred over cyclophosphamide) and should be considered about 2 weeks after first-line initiation. Further immunotherapies for refractory disease 1-3 months after second-line initiation include another second-line treatment (such as cyclophosphamide) and escalation to tocilizumab. Maintenance immune suppression beyond 6 months (such as rituximab redosing or mycophenolate mofetil) is generally not required, except for patients with a more severe course or prolonged impairments and hospitalization. For patients with relapsing disease, second-line and prolonged maintenance therapy should be considered. The treatment of NMDARE following herpes simplex encephalitis should be similar to idiopathic NMDARE. Broad guidance is provided for the total treatment duration (first line, second line, and maintenance), which is dictated by the severity and clinical course (i.e., median 3, 9 and 18 months in the best, average, and worst responders, respectively). Recommendations on the timing of oncologic searches are provided.These international consensus recommendations for the management of pediatric NMDARE aim to standardize the treatment and provide practical guidance for clinicians, rather than absolute rules. A similar recommendation could be applicable to adult patients.Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology

Acute flaccid myelitis:cause, diagnosis, and management

Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of MM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for MM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host-virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population

Treatment of MOG-IgG-associated disorder with rituximab: An international study of 121 patients

OBJECTIVE: To assess the effect of anti-CD20 B-cell depletion with rituximab (RTX) on relapse rates in myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD). METHODS: Retrospective review of RTX-treated MOGAD patients from 29 centres in 13 countries. The primary outcome measure was change in relapse rate after starting rituximab (Poisson regression model). RESULTS: Data on 121 patients were analysed, including 30 (24.8%) children. Twenty/121 (16.5%) were treated after one attack, of whom 14/20 (70.0%) remained relapse-free after median (IQR) 11.2 (6.3-14.1) months. The remainder (101/121, 83.5%) were treated after two or more attacks, of whom 53/101 (52.5%) remained relapse-free after median 12.1 (6.3-24.9) months. In this 'relapsing group', relapse rate declined by 37% (95%CI=19-52%, p<0.001) overall, 63% (95%CI=35-79%, p = 0.001) when RTX was used first line (n = 47), and 26% (95%CI=2-44%, p = 0.038) when used after other steroid-sparing immunotherapies (n = 54). Predicted 1-year and 2-year relapse-free survival was 79% and 55% for first-line RTX therapy, and 38% and 18% for second-/third-line therapy. Circulating CD19+B-cells were suppressed to <1% of total circulating lymphocyte population at the time of 45/57 (78.9%) relapses. CONCLUSION: RTX reduced relapse rates in MOGAD. However, many patients continued to relapse despite apparent B-cell depletion. Prospective controlled studies are needed to validate these results

A systematic review of attitudes, anxiety, acceptance, and trust towards social robots

As social robots become more common, there is a need to understand how people perceive and interact with such technology. This systematic review seeks to estimate people’s attitudes toward, trust in, anxiety associated with, and acceptance of social robots; as well as factors that are associated with these beliefs. Ninety-seven studies were identified with a combined sample of over 13,000 participants and a standardized score was computed for each in order to represent the valence (positive, negative, or neutral) and magnitude (on a scale from 1 to − 1) of people’s beliefs about robots. Potential moderating factors such as the robots’ domain of application and design, the type of exposure to the robot, and the characteristics of potential users were also investigated. The findings suggest that people generally have positive attitudes towards social robots and are willing to interact with them. This finding may challenge some of the existing doubt surrounding the adoption of robotics in social domains of application but more research is needed to fully understand the factors that influence attitudes

Incremental Scheduling with Upper and Lowerbound Temporospatial Constraints

Responding quickly and efficiently to dynamic disturbances is a crucial challenge in domains such as manufacturing, aerial and underwater vehicle tasking, and health care. In many cases, accurately capturing the complicated dependencies between tasks in these environments requires the use of upper and lowerbound temporal constraints (i.e, deadlines and wait constraints). However, optimally scheduling tasks related by upper and lowerbound temporal constraints is known to be NP-Hard.3 While exact solution techniques exist to efficiently schedule resources, these techniques are computationally intractable for problems of interest with fifty or more tasks and five agents. Furthermore, techniques that seek to improve scalability often attempt to distribute the scheduling problem amongst the agents, where each agent generates its own schedule.5 However, when agents must share unary-access resources (e.g., a spatial location that can be occupied by only one agent at a time), these techniques lose their advantage because the problems do not naturally lend themselves to decomposition. As a result, many techniques work by first finding an initial, though possibly infeasible, schedule through solving a relaxed version of the problem, and then repairing the schedule to resolve any constraint violations.National Science Foundation (U.S.). Graduate Research Fellowship Program (Grant 2388357