Stem-like exhausted CD8 T cells in pleural effusions predict improved survival in non-small cell lung cancer (NSCLC) and mesothelioma.

Background: Anti-tumor CD8 T cells are important for immunity but can become 'exhausted' and hence ineffective. Tumor-infiltrating exhausted CD8 T cells include less differentiated stem-like exhausted T (Tex) cells and terminally exhausted T (Tex) cells. Both subsets have been proposed as prognostic biomarkers in cancer patients.

A usability study on the inGAIT-VSO: effects of a variable-stiffness ankle-foot orthosis on the walking performance of children with cerebral palsy.

Background: Ankle-foot orthoses (AFOs) are commonly used by children with cerebral palsy (CP), but traditional solutions are unable to address the heterogeneity and evolving needs amongst children with CP. One key limitation lies in the inability of current passive devices to customize the torque-angle relationship, which is essential to adapt the support to the specific individual needs. Powered alternatives can provide customized behavior, but often face challenges with reliability, weight, and cost.

Experiment-free exoskeleton assistance via learning in simulation.

Exoskeletons have enormous potential to improve human locomotive performance. However, their development and broad dissemination are limited by the requirement for lengthy human tests and handcrafted control laws. Here we show an experiment-free method to learn a versatile control policy in simulation.

Reliability and minimal detectable change of stiffness and other mechanical properties of the ankle joint in standing and walking.

Background: Ankle joint stiffness and viscosity are fundamental mechanical descriptions that govern the movement of the body and impact an individual's walking ability. Hence, these internal properties of a joint have been increasingly used to evaluate the effects of pathology (e.g.

Comparison of Two Design Principles of Unpowered Ankle-Foot Orthoses for Supporting Push-Off: A Case Study.

Ankle propulsion is essential for efficient human walking. In recent years, several working principles have been investigated and applied to ankle-foot orthoses (AFOs) to enhance the work of the plantarflexor muscles and achieve proper propulsion during gait. Comparing the performance and effectiveness of different designs is difficult because researchers do not have a standardized set of criteria and procedures to follow.

Design of a Quasi-Passive Ankle-Foot Orthosis with Customizable, Variable Stiffness.

Most commercial ankle-foot orthoses (AFOs) are passive structures that cannot modulate stiffness to assist with a diverse range of activities, such as stairs and ramps. It is sometimes possible to change the stiffness of passive AFOs through reassembly or benchtop adjustment, but they cannot change stiffness during use. Passive AFOs are also limited in their ankle mechanics and cannot replicate a biomimetic, nonlinear torque-angle relationship.

User preference optimization for control of ankle exoskeletons using sample efficient active learning.

One challenge to achieving widespread success of augmentative exoskeletons is accurately adjusting the controller to provide cooperative assistance with their wearer. Often, the controller parameters are "tuned" to optimize a physiological or biomechanical objective. However, these approaches are resource intensive, while typically only enabling optimization of a single objective.

Data-Driven Variable Impedance Control of a Powered Knee-Ankle Prosthesis for Adaptive Speed and Incline Walking.

Most impedance-based walking controllers for powered knee-ankle prostheses use a finite state machine with dozens of user-specific parameters that require manual tuning by technical experts. These parameters are only appropriate near the task (., walking speed and incline) at which they were tuned, necessitating many different parameter sets for variable-task walking.

Real-Time Gait Phase and Task Estimation for Controlling a Powered Ankle Exoskeleton on Extremely Uneven Terrain.

Positive biomechanical outcomes have been reported with lower-limb exoskeletons in laboratory settings, but these devices have difficulty delivering appropriate assistance in synchrony with human gait as the task or rate of phase progression change in real-world environments. This paper presents a controller for an ankle exoskeleton that uses a data-driven kinematic model to continuously estimate the phase, phase rate, stride length, and ground incline states during locomotion, which enables the real-time adaptation of torque assistance to match human torques observed in a multi-activity database of 10 able-bodied subjects. We demonstrate in live experiments with a new cohort of 10 able-bodied participants that the controller yields phase estimates comparable to the state of the art, while also estimating task variables with similar accuracy to recent machine learning approaches.

Agreement Level of Inflammatory Bowel Disease Symptom Reports between Children and Their Parents.

Purpose: Children with inflammatory bowel disease (IBD) frequently undergo clinical assessments, involving triadic communication between clinician, parent, and child. During such encounters parents are traditionally the main communicator of information on their child's IBD, including subjective symptom reports. The level of agreement between children and their parents for IBD symptoms is poorly understood, and this study aimed to examine this factor.

Enhancing Voluntary Motion with Modular, Backdrivable, Powered Hip and Knee Orthoses.

Mobility disabilities are prominent in society with wide-ranging deficits, motivating modular, partial-assist, lower-limb exoskeletons for this heterogeneous population. This paper introduces the Modular Backdrivable Lower-limb Unloading Exoskeleton (M-BLUE), which implements high torque, low mechanical impedance actuators on commercial orthoses with sheet metal modifications to produce a variety of hip- and/or knee-assisting configurations. Benchtop system identification verifies the desirable backdrive properties of the actuator, and allows for torque prediction within ±0.

A morphological study of schizophrenia with magnetic resonance imaging, advanced analytics, and machine learning.

We have performed a morphological analysis of patients with schizophrenia and compared them with healthy controls. Our analysis includes the use of publicly available automated extraction tools to assess regional cortical thickness (inclusive of within region cortical thickness variability) from structural magnetic resonance imaging (MRI), to characterize group-wise abnormalities associated with schizophrenia based on a publicly available dataset. We have also performed a correlation analysis between the automatically extracted biomarkers and a variety of patient clinical variables available.

Designing Custom Mechanics in Running-Specific Prosthetic Feet via Shape Optimization.

Objective: Running-specific prosthetic feet are curved cantilever springs, distinguished from ordinary prosthetic feet by their size, shape, and greater ability to store and return elastic potential energy. Finite element analyses show how modifications to prosthesis shape alter the multidimensional and nonlinear mechanics, but designers seeking to prescribe custom mechanics are limited by the complex constraints and high dimensionality of possible geometries.

Methods: We introduce two simple formulations for describing foot mechanics, and use them with a custom spline-based shape optimization to generate new prosthetic foot shapes given desired endpoint mechanics.

Analysis of the Bayesian Gait-State Estimation Problem for Lower-Limb Wearable Robot Sensor Configurations.

Many exoskeletons today are primarily tested in controlled, steady-state laboratory conditions that are unrealistic representations of their real-world usage in which walking conditions (.., speed, slope, and stride length) change constantly.

Comprehensive genomic and tumour immune profiling reveals potential therapeutic targets in malignant pleural mesothelioma.

Background: Malignant pleural mesothelioma (MPM) has a poor overall survival with few treatment options. Whole genome sequencing (WGS) combined with the immune features of MPM offers the prospect of identifying changes that could inform future clinical trials.

Methods: We analysed somatic mutations from 229 MPM samples, including previously published data and 58 samples that had undergone WGS within this study.

The role of user preference in the customized control of robotic exoskeletons.

User preference is a promising objective for the control of robotic exoskeletons because it may capture the multifactorial nature of exoskeleton use. However, to use it, we must first understand its characteristics in the context of exoskeleton control. Here, we systematically measured the control preferences of individuals wearing bilateral ankle exoskeletons during walking.

Phase-Variable Control of a Powered Knee-Ankle Prosthesis over Continuously Varying Speeds and Inclines.

Most controllers for lower-limb robotic prostheses require individually tuned parameter sets for every combination of speed and incline that the device is designed for. Because ambulation occurs over a continuum of speeds and inclines, this design paradigm requires tuning of a potentially prohibitively large number of parameters. This limitation motivates an alternative control framework that enables walking over a range of speeds and inclines while requiring only a limited number of tunable parameters.

Can humans perceive the metabolic benefit provided by augmentative exoskeletons?

Background: The purpose of augmentative exoskeletons is to help people exceed the limitations of their human bodies, but this cannot be realized unless people choose to use these exciting technologies. Although human walking efficiency has been highly optimized over generations, exoskeletons have been able to consistently improve this efficiency by 10-15%. However, despite these measurable improvements, exoskeletons today remain confined to the laboratory.

How Does Ankle Mechanical Stiffness Change as a Function of Muscle Activation in Standing and During the Late Stance of Walking?

Objective: Ankle joint stiffness is known to be modulated by co-contraction of the ankle muscles; however, it is unclear to what extent changes in agonist muscle activation alone affect ankle joint stiffness. This study tested the effects of varying levels of ankle muscle activation on ankle joint mechanical stiffness in standing and during the late stance phase of walking.

Methods: Dorsiflexion perturbations were applied at various levels of ankle muscle activation via a robotic platform in standing and walking conditions.

Understanding patient preference in prosthetic ankle stiffness.

Background: User preference has the potential to facilitate the design, control, and prescription of prostheses, but we do not yet understand which physiological factors drive preference, or if preference is associated with clinical benefits.

Methods: Subjects with unilateral below-knee amputation walked on a custom variable-stiffness prosthetic ankle and manipulated a dial to determine their preferred prosthetic ankle stiffness at three walking speeds. We evaluated anthropomorphic, metabolic, biomechanical, and performance-based descriptors at stiffness levels surrounding each subject's preferred stiffness.

Characterization and clinical implications of ankle impedance during walking in chronic stroke.

Individuals post-stroke experience persisting gait deficits due to altered joint mechanics, known clinically as spasticity, hypertonia, and paresis. In engineering, these concepts are described as stiffness and damping, or collectively as joint mechanical impedance, when considered with limb inertia. Typical clinical assessments of these properties are obtained while the patient is at rest using qualitative measures, and the link between the assessments and functional outcomes and mobility is unclear.

A passive mechanism for decoupling energy storage and return in ankle-foot prostheses: A case study in recycling collision energy.

Individuals with lower limb amputation experience reduced ankle push-off work in the absence of functional muscles spanning the joint, leading to decreased walking performance. Conventional energy storage and return (ESR) prostheses partially compensate by storing mechanical energy during midstance and returning this energy during the terminal stance phase of gait. These prostheses can provide approximately 30% of the push-off work performed by a healthy ankle-foot during walking.

Hold-out validation for the assessment of stability and reliability of multivariable regression demonstrated with magnetic resonance imaging of patients with schizophrenia.

Neuroscience studies are very often tasked with identifying measurable differences between two groups of subjects, typically one group with a pathological condition and one group representing control subjects. It is often expected that the measurements acquired for comparing groups are also affected by a variety of additional patient characteristics such as sex, age, and comorbidities. Multivariable regression (MVR) is a statistical analysis technique commonly employed in neuroscience studies to "control for" or "adjust for" secondary effects (such as sex, age, and comorbidities) in order to ensure that the main study findings are focused on actual differences between the groups of interest associated with the condition under investigation.

Validation of Methods for Estimation of Knee Joint Mechanical Impedance During Locomotion Using a Torque-Controllable Knee Exoskeleton.

The mechanical impedance of the joints of the leg governs the body's response to external disturbances, and its regulation is essential for the completion of tasks of daily life. However, it is still unclear how this quantity is regulated at the knee during dynamic tasks. In this work, we introduce a method to estimate the mechanical impedance of spring-mass systems using a torque-controllable exoskeleton with the intention of extending these methods to characterize the mechanical impedance of the human knee during locomotion.

Systematic Review of Self-Management Assessment Tools for Children With Inflammatory Bowel Disease.

The relapsing pattern of illness and diverse management strategies for children with inflammatory bowel disease (IBD) may inhibit their opportunities to develop self-management skills. Interventions focused on the development of these skills require population-specific outcome measures. We provide a comprehensive overview of self-management skills assessment tools that are available for children with IBD that target processes and behaviors outlined as beneficial for the development of these skills.