A Novel Gait Event Detection Algorithm Using a Thigh-Worn Inertial Measurement Unit and Joint Angle Information.

This paper describes the development and evaluation of a novel, threshold-based gait event detection algorithm utilizing only one thigh inertial measurement unit (IMU) and unilateral, sagittal plane hip and knee joint angles. The algorithm was designed to detect heel strike (HS) and toe off (TO) gait events, with the eventual goal of detection in a real-time exoskeletal control system. The data used in the development and evaluation of the algorithm were obtained from two gait databases, each containing synchronized IMU and ground reaction force (GRF) data. All database subjects were healthy individuals walking in either a level-ground, urban environment or a treadmill lab environment. Inertial measurements used were three-dimensional thigh accelerations and three-dimensional thigh angular velocities. Parameters for the TO algorithm were identified on a per-subject basis. The GRF data were utilized to validate the algorithm's timing accuracy and quantify the fidelity of the algorithm, measured by the F1-Score. Across all participants, the algorithm reported a mean timing error of -41±20 ms with an F1-Score of 0.988 for HS. For TO, the algorithm reported a mean timing error of -1.4±21 ms with an F1-Score of 0.991. The results of this evaluation suggest that this algorithm is a promising solution to inertial based gait event detection; however, further refinement and real-time evaluation are required for use in exoskeletal control.

An Anthropometrically Parameterized Assistive Lower Limb Exoskeleton.

This paper presents an innovative design methodology for development of lower limb exoskeletons with the fabrication and experimental evaluation of prototype hardware. The proposed design approach is specifically conceived to be suitable for the pediatric population and uses additive manufacturing and a model parameterized in terms of subject anthropometrics to give a person-specific custom fit. The methodology is applied to create computer-aided design models using average anthropometrics of children 6-11 years old and using anthropometrics of an individual measured by the researchers. This demonstrates that the approach can scale to subject weight and height. A prototype exoskeleton is fabricated, which can actuate the hip and knee joints without restricting hip abduction-adduction motion. In order to test usability of the device and evaluate walking assistance, user effort is quantified in an assisted condition where the subject walks on a level treadmill with the exoskeleton powered. This is compared to an unassisted condition with the exoskeleton unpowered and a baseline condition with the subject not wearing the exoskeleton. Comparing assisted to baseline conditions, torque magnitudes increased at the hip and knee, mechanical energy generated increased at the hip but decreased at the knee, and muscle activations increased in the Vastus Lateralis but decreased in the Biceps Femoris. While the preliminary evidence for walking assistance is not entirely convincing for the tested conditions, the presented design methodology itself is promising as it has been successfully validated through the creation of computer-aided design models for children and fabrication of a serviceable exoskeleton prototype.

Bacterial community comparisons by taxonomy-supervised analysis independent of sequence alignment and clustering.

High-throughput sequencing of 16S rRNA genes has increased our understanding of microbial community structure, but now even higher-throughput methods to the Illumina scale allow the creation of much larger datasets with more samples and orders-of-magnitude more sequences that swamp current analytic methods. We developed a method capable of handling these larger datasets on the basis of assignment of sequences into an existing taxonomy using a supervised learning approach (taxonomy-supervised analysis). We compared this method with a commonly used clustering approach based on sequence similarity (taxonomy-unsupervised analysis). We sampled 211 different bacterial communities from various habitats and obtained ∼1.3 million 16S rRNA sequences spanning the V4 hypervariable region by pyrosequencing. Both methodologies gave similar ecological conclusions in that ß-diversity measures calculated by using these two types of matrices were significantly correlated to each other, as were the ordination configurations and hierarchical clustering dendrograms. In addition, our taxonomy-supervised analyses were also highly correlated with phylogenetic methods, such as UniFrac. The taxonomy-supervised analysis has the advantages that it is not limited by the exhaustive computation required for the alignment and clustering necessary for the taxonomy-unsupervised analysis, is more tolerant of sequencing errors, and allows comparisons when sequences are from different regions of the 16S rRNA gene. With the tremendous expansion in 16S rRNA data acquisition underway, the taxonomy-supervised approach offers the potential to provide more rapid and extensive community comparisons across habitats and samples.

Hybrid Zero Dynamics Control for Gait Guidance of a Novel Adjustable Pediatric Lower-Limb Exoskeleton.

Exoskeleton technology has undergone significant developments for the adult population but is still lacking for the pediatric population. This paper presents the design of a hip-knee exoskeleton for children 6 to 11 years old with gait abnormalities. The actuators are housed in an adjustable exoskeleton frame where the thigh part can adjust in length and the hip cradle can adjust in the medial-lateral and posterior-anterior directions concurrently. Proper control of exoskeletons to follow nominal healthy gait patterns in a time-invariant manner is important for ease of use and user acceptance. In this paper, a hybrid zero dynamics (HZD) controller was designed for gait guidance by defining the zero dynamics manifold to resemble healthy gait patterns. HZD control utilizes a time-invariant feedback controller to create dynamically stable gaits in robotic systems with hybrid models containing both discrete and continuous dynamics. The effectiveness of the controller on the novel pediatric exoskeleton was demonstrated via simulation. The presented preliminary results suggest that HZD control provides a viable method to control the pediatric exoskeleton for gait guidance.

Laying the foundation for a Genomic Rosetta Stone: creating information hubs through the use of consensus identifiers.

Given the growing wealth of downstream information, the integration of molecular and non-molecular data on a given organism has become a major challenge. For micro-organisms, this information now includes a growing collection of sequenced genes and complete genomes, and for communities of organisms it includes metagenomes. Integration of the data is facilitated by the existence of authoritative, community-recognized, consensus identifiers that may form the heart of so-called information knuckles. The Genomic Standards Consortium (GSC) is building a mapping of identifiers across a group of federated databases with the aim to improve navigation across these resources and to enable the integration of their information in the near future. In particular, this is possible because of the existence of INSDC Genome Project Identifiers (GPIDs) and accession numbers, and the ability of the community to define new consensus identifiers such as the culture identifiers used in the StrainInfo.net bioportal. Here we outline (1) the general design of the Genomic Rosetta Stone project, (2) introduce example linkages between key databases (that cover information about genomes, 16S rRNA gene sequences, and microbial biological resource centers), and (3) make an open call for participation in this project providing a vision for its future use.

FES Coupled With A Powered Exoskeleton For Cooperative Muscle Contribution In Persons With Paraplegia.

This paper describes the effects of a novel functional electrical stimulation (FES) system which has been integrated in a powered exoskeleton to provide up to 10 channels of stimulation to users with paraplegia via surface electrodes. Experimental data collected from three users with spinal cord injury (SCI) indicate the system reduced the exoskeleton motor torques necessary to perform sit-to-stand transitions in the exoskeleton. All subjects exhibited reduced muscle spasticity immediately after walking in the exoskeleton with FES. Additionally, one subject with stretch-reflex spasms exhibited increased joint excursion and reduced exoskeleton motor torques required to achieve over-ground gait when FES was incorporated.

5-Fluorouracil chemotherapy upregulates cytokines and alters hippocampal dendritic complexity in aged mice.

5-Fluorouracil (5-Fu) is commonly used chemotherapy drug, but it can lead to the impairment of cognitive function. The pathogenesis of this injury is unknown but may involve modifications to dendritic structure and/or alterations in dendritic spine density and morphology. Dendritic spines are sites of excitatory synaptic transmission and changes in spine structure and dendrite morphology are thought to represent a morphological correlate of altered brain functions associated with hippocampal dependent learning and memory. A total of 28 one-year-old C57BL6/J male mice were used in this study; 14 mice received 5-Fu treatment and 14 were given saline injections. One month post treatment, 14 cytokines were measured at the same time Golgi samples were taken. 8 analytes were significantly elevated in mice treated with 5-Fu. 5-Fu significantly compromised the dendritic architecture and reduced spine density throughout the hippocampal tri-synaptic network. The present data provide the evidence that 5-Fu has deleterious effects on mature neurons associated with hippocampal learning and memory.

Mobility Outcomes Following Five Training Sessions with a Powered Exoskeleton.

BACKGROUND: Loss of legged mobility due to spinal cord injury (SCI) is associated with multiple physiological and psychological impacts. Powered exoskeletons offer the possibility of regained mobility and reversal or prevention of the secondary effects associated with immobility. OBJECTIVE: This study was conducted to evaluate mobility outcomes for individuals with SCI after 5 gait-training sessions with a powered exoskeleton, with a primary goal of characterizing the ease of learning and usability of the system. METHODS: Sixteen subjects with SCI were enrolled in a pilot clinical trial at Shepherd Center, Atlanta, Georgia, with injury levels ranging from C5 complete to L1 incomplete. An investigational Indego exoskeleton research kit was evaluated for ease of use and efficacy in providing legged mobility. Outcome measures of the study included the 10-meter walk test (10 MWT) and the 6-minute walk test (6 MWT) as well as measures of independence including donning and doffing times and the ability to walk on various surfaces. RESULTS: At the end of 5 sessions (1.5 hours per session), average walking speed was 0.22 m/s for persons with C5-6 motor complete tetraplegia, 0.26 m/s for T1-8 motor complete paraplegia, and 0.45 m/s for T9-L1 paraplegia. Distances covered in 6 minutes averaged 64 meters for those with C5-6, 74 meters for T1-8, and 121 meters for T9-L1. Additionally, all participants were able to walk on both indoor and outdoor surfaces. CONCLUSIONS: Results after only 5 sessions suggest that persons with tetraplegia and paraplegia learn to use the Indego exoskeleton quickly and can manage a variety of surfaces. Walking speeds and distances achieved also indicate that some individuals with paraplegia can quickly become limited community ambulators using this system.

Fenofibrate Attenuates Neutrophilic Inflammation in Airway Epithelia: Potential Drug Repurposing for Cystic Fibrosis.

A hallmark of cystic fibrosis (CF) lung disease is neutrophilic airway inflammation. Elevated neutrophil counts have been associated with decreased forced expiratory volume in 1 second and poor clinical measures in patients with CF. Interleukin 8 (IL-8), epithelial neutrophil activating protein 78 (ENA-78), tumor necrosis factor alpha (TNF-α), granulocyte macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF) contribute to neutrophil activation and disease pathogenesis in the airways of patients with CF. Drugs that modify the production of these chemokines in the airways could potentially benefit CF patients. Thus, we determined the effects of fenofibrate on their production in cell populations obtained from the airways. Human small airway epithelial cells and CF bronchial epithelial cells were treated with IL-1ß to induce inflammation. We cotreated the cells with fenofibrate at concentrations ranging from 10 to 50 µM to determine if this drug could attenuate the inflammation. IL-8, ENA-78, TNF-α, GM-CSF, and G-CSF production were measured from the cell culture supernates by ELISA. ANOVA statistical testing was conducted using SPSS 17.0. IL-1ß increased the production of each of the chemokines by several fold. Fenofibrate reduced IL-1ß induced production of each of these neutrophilic chemokines at the concentrations used. IL-1ß increases the production of neutrophilic chemokines in airway epithelial cells. Cotreatment with fenofibrate blunts these processes. Fenofibrate should be explored as a therapeutic option to modulate the abundant neutrophilic inflammation observed in CF.

A preliminary assessment of legged mobility provided by a lower limb exoskeleton for persons with paraplegia.

This paper presents an assessment of a lower limb exoskeleton for providing legged mobility to people with paraplegia. In particular, the paper presents a single-subject case study comparing legged locomotion using the exoskeleton to locomotion using knee-ankle-foot orthoses (KAFOs) on a subject with a T10 motor and sensory complete injury. The assessment utilizes three assessment instruments to characterize legged mobility, which are the timed up-and-go test, the Ten-Meter Walk Test (10 MWT), and the Six-Minute Walk Test (6 MWT), which collectively assess the subject's ability to stand, walk, turn, and sit. The exertion associated with each assessment instrument was assessed using the Physiological Cost Index. Results indicate that the subject was able to perform the respective assessment instruments 25%, 70%, and 80% faster with the exoskeleton relative to the KAFOs for the timed up-and-go test, the 10 MWT, and the 6 MWT, respectively. Measurements of exertion indicate that the exoskeleton requires 1.6, 5.2, and 3.2 times less exertion than the KAFOs for each respective assessment instrument. The results indicate that the enhancement in speed and reduction in exertion are more significant during walking than during gait transitions.

A Method for the Autonomous Control of Lower Limb Exo-skeletons for Persons with Paraplegia.

Efforts have recently been reported by several research groups on the development of computer-controlled lower limb orthoses to enable legged locomotion in persons with paraplegia. Such systems must employ a control framework that provides essential movements to the paraplegic user (i.e., sitting, standing, and walking), and ideally enable the user to autonomously command these various movements in a safe, reliable, and intuitive manner. This paper describes a control method that enables a paraplegic user to perform sitting, standing, and walking movements, which are commanded based on postural information measured by the device. The proposed user interface and control structure was implemented on a powered lower limb orthosis, and the system was tested on a paraplegic subject with a T10 complete injury. Experimental data is presented that indicates the ability of the proposed control architecture to provide appropriate user-initiated control of sitting, standing, and walking. The authors also provide a link to a video that qualitatively demonstrates the user's ability to independently control basic movements via the proposed control method.

Performance evaluation of a lower limb exoskeleton for stair ascent and descent with paraplegia.

This paper describes the application of a powered lower limb exoskeleton to aid paraplegic individuals in stair ascent and descent. A brief description of the exoskeleton hardware is provided along with an explanation of the control methodology implemented to allow stair ascent and descent. Tests were performed with a paraplegic individual (T10 complete injury level) and data is presented from multiple trials, including the hip and knee joint torque and power required to perform this functionality. Joint torque and power requirements are summarized, including peak hip and knee joint torque requirements of 0.75 Nm/kg and 0.87 Nm/kg, respectively, and peak hip and knee joint power requirements of approximately 0.65 W/kg and 0.85 W/kg, respectively.

Preliminary assessment of the efficacy of supplementing knee extension capability in a lower limb exoskeleton with FES.

The authors describe a cooperative controller that combines the knee joint actuation of an externally powered lower limb exoskeleton with the torque and power contribution from the electrically stimulated quadriceps muscle group. The efficacy of combining these efforts is experimentally validated with a series of weighted leg lift maneuvers. Measurements from these experiments indicate that the control approach effectively combines the respective efforts of the motor and muscle, such that good control performance is achieved, with substantial torque and energy contributions from both the biological and non-biological actuators.

Enhancing stance phase propulsion during level walking by combining FES with a powered exoskeleton for persons with paraplegia.

This paper describes the design and implementation of a cooperative controller that combines functional electrical stimulation (FES) with a powered lower limb exoskeleton to provide enhanced hip extension during the stance phase of walking in persons with paraplegia. The controller utilizes two sources of actuation: the electric motors of the powered exoskeleton and the user's machine (FSM), a set of FES. It consists of a finite-state machine (FSM), a set of proportional-derivative (PD) controllers for the exoskeleton and a cycle-to-cycle adaptive controller for muscle stimulation. Level ground walking is conducted on a single subject with complete T10 paraplegia. Results show a 34% reduction in electrical power requirements at the hip joints during the stance phase of the gait cycle with the cooperative controller compared to using electric motors alone.

Preliminary evaluation of a powered lower limb orthosis to aid walking in paraplegic individuals.

This paper describes a powered lower-limb orthosis that is intended to provide gait assistance to spinal cord injured (SCI) individuals by providing assistive torques at both hip and knee joints. The orthosis has a mass of 12 kg and is capable of providing maximum joint torques of 40 Nm with hip and knee joint ranges of motion from 105° flexion to 30° extension and 105° flexion to 10° hyperextension, respectively. A custom distributed embedded system controls the orthosis with power being provided by a lithium polymer battery which provides power for one hour of continuous walking. In order to demonstrate the ability of the orthosis to assist walking, the orthosis was experimentally implemented on a paraplegic subject with a T10 complete injury. Data collected during walking indicates a high degree of step-to-step repeatability of hip and knee trajectories (as enforced by the orthosis) and an average walking speed of 0.8 km/hr. The electrical power required at each hip and knee joint during gait was approximately 25 and 27 W, respectively, contributing to the 117 W overall electrical power required by the device during walking. A video of walking corresponding to the aforementioned data is included in the supplemental material.

Control and implementation of a powered lower limb orthosis to aid walking in paraplegic individuals.

This paper describes a powered lower-limb orthosis that is intended to provide gait assistance to spinal cord injured (SCI) individuals by providing assistive torques at both hip and knee joints, along with a user interface and control structure that enables control of the powered orthosis via upper-body influence. The orthosis and control structure was experimentally implemented on a paraplegic subject (T10 complete) in order to provide a preliminary characterization of its capability to provide basic walking. Data and video is presented from these initial trials, which indicates that the orthosis and controller are able to effectively provide walking within parallel bars at an average speed of 0.8 km/hr.

A Powered Lower Limb Orthosis for Providing Legged Mobility in Paraplegic Individuals.

This paper presents preliminary results on the development of a powered lower limb orthosis intended to provide legged mobility (with the use of a stability aid, such as forearm crutches) to paraplegic individuals. The orthosis contains electric motors at both hip and both knee joints, which in conjunction with ankle-foot orthoses, provides appropriate joint kinematics for legged locomotion. The paper describes the orthosis and the nature of the controller that enables the SCI patient to command the device, and presents data from preliminary trials that indicate the efficacy of the orthosis and controller in providing legged mobility.

Feasibility of a hybrid-FES system for gait restoration in paraplegics.

This paper proposes a new configuration for a hybrid-FES gait restoration system, and presents a combination of simulation and experiment that support the feasibility of the proposed approach. Gait simulation results are presented that indicate the majority of load bearing and the majority of power for gait is provided by the legs (i.e., quadriceps muscle stimulation). Based on these simulations, experiments on healthy subjects indicate that the gait restoration approach should be capable of providing long periods of locomotion unimpeded by quadriceps muscle fatigue.