Functional Compensation of Gait Deficits with Minimal Actuation

Mobility is a basic human need, and the ability to walk plays a key role. Unfortunately, this ability is severely limited for people with lower extremity impairments. While many still have the ability to walk in spite of muscular or neurological deficits, the effort required for walking, as well as the fear of falling, are often so dominant that bipedal locomotion is largely abandoned in everyday life. The vision of this work is to help mobilize these people in everyday life by intelligently redistributing the kinetic energy available from their residual muscle function, to enable safe and functional motion. In the present work, the following hypotheses were investigated: A modular, computer-controlled orthotic system provides functional support in mobility activities of daily life for people with lower limb impairments, without applying net positive power from external energy sources. Users will integrate such a system into their activities of daily life. By adding an energy-storing hip module, the user group for such a system can be extended to more severely affected people, who cannot benefit from a solution that only controls the knee joint. Energy recuperation at the hip joint will improve their ability to walk. A modular, computer-controlled orthotic system that brings a portion of these individuals closer to this vision is presented and evaluated. The development of the system was based on the assumption that, even without motor support, external energy sources or complex control algorithms, a high level of functionality can be achieved to support activities of daily life. Depending on their severity of muscular deficits, subjects were either stabilized solely by an orthosis with a computer-controlled knee joint, or if necessary additionally supported by a hip module. The goal of the fitting was to efficiently use the kinetic energy provided by the user, while ensuring the user is always the highest level control entity of the system. This can be achieved with a system behavior that is predictable for the user in every situation. Differences between individual users pose a major challenge in this regard. This includes both the different physiological conditions of the users, and the operating conditions for the support system, which depend on the daily habits of the individual users. Both aspects were considered in this work. Since the most important function of an orthotic knee joint is stabilization in stance phase, an adaptive damper was incorporated to control the knee joint. Hip musculature and hip motion play an essential role in forward propulsion during walking. Therefore, the possibility for elastic energy recuperation was provided by the hip joint, to ensure beneficial use of energy coming from the remaining musculature or from compensatory movements. Both components were evaluated with human subjects in clinical studies. In the case of the knee joint, an extended in-home use study was conducted, focused on the use of the system in everyday life, as well as the loads that occurred during this use. It was shown that the system was well accepted and used intensively by all subjects. The loads observed justify the robust design of the system. The control of the knee joint was perceived as intuitive, and seven out of eight users wanted to use the device in everyday life, even after the study. For the system that includes an additional hip joint, the focus was on determining energy storage characteristics, to ensure optimal energy recuperation for the user. For this purpose, data from several subjects using various systems with different energy storage properties were analyzed. Results showed significant adaptability by the test subjects. After a short familiarization phase, movement sequences were already adjusted to the different system properties, to ensure optimal use of the energy storage provided. For the hip joint control, good results were achieved with a simple control paradigm, in which the hip behaved like a spring with a variable neutral position. However, all users reported that the prototype hip joint used in the study was perceived as too large and heavy, and therefore not suitable for use in everyday life. In the course of the studies it was shown that through dissipative movement control of the knee joint by an adaptive damper, a significant improvement in function and an everyday benefit for the users could be achieved. The described knee joint system is now commercially available. The high adaptability of the subjects to different characteristics of the hip support system, as well as the functionality that could be achieved with a simple spring behavior, reveal potential for a simplified version of this system. Taking these findings into account for further development of the orthotic hip joint, it should also be possible in the future to provide high-quality functional care to people with severely limited hip function

Patient Motion Using a Computerized Leg Brace in Everyday Locomotion Tasks

Exoskeletal systems are becoming a rehabilitation standard of care for persons with lower limb paralysis. As muscular dysfunctions affect a heterogeneous patient group, each individual develops their own strategy to negotiate everyday locomotion challenges. This paper introduces a microprocessor controlled orthotic system that passively supports people with lower limb paralyses in their everyday locomotion tasks while incorporating the user as the highest control entity. A clinical study with seven patients with a range of leg pareses investigated the functionality and usage of the system while capturing the mechanical stress on the device. Data from the knee joint was recorded in locomotion tasks including level walking, ramp, and stair negotiation. For all patients, the measurements demonstrate that the motion for level walking was close to the motion of healthy individuals. In other tasks, variations between the patients were large with respect to motion kinematics, power, and torque requirements. As the control concept supported individualized motion patterns, patients perceived the system functionality as intuitive. The mechanically most demanding task was stair descent with a peak torque of 1.47 Nm/kg and peak dissipative power up to 2.67 W/kg. Intra-subject variability makes prediction of movements and loads challenging

Energy Recuperation at the Hip Joint for Paraplegic Walking: Interaction Between Patient and Supportive Device

For patients with lower limb paralysis, wearable robotic systems are becoming increasingly important for regaining mobility. The actuation of these systems is challenging because of the necessity to deliver high power within very limited space. However, not all patients need full support, as many patients have residual muscle function that can be applied for locomotion. This work introduces a microprocessor-controlled leg (hip-knee-ankle-foot) orthosis (mpLeg) with energy recuperation capabilities at the hip joint. The system redistributes motion energy generated by the patient during walking. In stance phase of walking, energy is stored in an elastic element at the hip joint. This energy can be released by computer control later in the gait phase, to support swing phase motion. This work aims at investigating the influence of the elastic element in the orthotic hip joint on a patient’s motion. Experiments conducted with a patient suffering from incomplete paraplegia demonstrated that the motion pattern during walking improved with activated energy recuperation. This observation was made over a wide range of system parameters. The patient used the energy recuperation capabilities of the mpLeg with up to 4.1 J recuperated energy per step, which resulted in a more natural swing phase motion during walking. Therefore energy recuperation at the hip joint is a feasible technology for future supportive devices

Activities with a Microprocessor-Controlled Leg Brace for Patients with Lower Limb Paralysis: A Series of Case Studies

Lower limb paralysis often leads to depreciation in mobility of the affected individuals. Computer-controlled leg brace systems open up new possibilities for these patients, by improving the safety of mobility tasks in everyday life, especially when walking on uneven terrain, inclined surfaces, steps and stairs. This paper introduces such a system. To investigate the use of device functionalities in the patient’s everyday environment, the knee joint of the brace was configured to store data of various sensors, measuring motion with a high temporal resolution over several weeks of home use. Results from a clinical trial including 8 patients with different pathologies show that the system was used by the patients for more than 10 hours per day on average, taking more than 2,100 steps per day. Maximum use time was more than 20.24 hours with 12,609 steps per day. An implemented yielding function to support walking down slopes or stairs was used by all patients. This function can also catch the user in case of stumbling, which on average happened 3 times per day. Seven out of eight patients reported improvements in quality and safety of many activities in daily life using the novel system, compared to their previous device

Recurrent FOXK1 :: GRHL and GPS2 :: GRHL fusions in trichogerminoma

International audienceWe report 21 cases of trichogerminoma harbouring previously undescribed FOXK1::GRHL1/2 or GPS2::GRHL1/2/3 in-frame fusion transcripts. Microscopic examination of a preliminary set of five cases revealed well-delimitated tumours located in the dermis with frequent extension to the subcutaneous tissue. Tumours presented a massive and nodular architecture and consisted of a proliferation of basaloid cells. A biphasic pattern sometime resulting in tumour cell nests ('cell balls') was present. Immunohistochemistry demonstrated the expression of cytokeratins (CKs) 15, 17, and PHLDA1. In addition, numerous CK20-positive Merkel cells were detected. RNA sequencing (RNA-seq) revealed a FOXK1::GRHL1 chimeric transcript in three cases and a FOXK1::GRHL2 fusion in two cases. In a second series for validation (n = 88), FOXK1::GRHL1/2 fusion transcripts were detected by RT-qPCR or FISH in an additional 12 trichogerminomas and not in any other follicular tumour entities or basal cell carcinoma cases (n = 66). Additional RNA-seq analysis in trichogerminoma cases without detected FOXK1::GRHL1/2 rearrangements revealed GPS2::GRHL1 fusion transcripts in two cases, GPS2::GRHL2 in one case, and GPS2::GRHL3 fusion transcript in one case. Therefore, our study strongly suggests that GRHL1/2/3 gene rearrangements might represent the oncogenic driver in trichogerminoma, a subset of follicular tumours characterized by immature features and numerous Merkel cells

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

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