Design of a Passive Ankle Prosthesis with Energy Return That Increases with Increasing Walking Velocity

Patients who undergo a transtibial (below the knee) amputation are often met with a difficult decision: selection of a prosthesis. Limitations of currently available prostheses motivate work on a new solution, the EaSY Walk, a passive device that mimics two key aspects of the natural ankle: non-linear rotational stiffness through implementation of a stiffening flexure mechanism and rotational work output that varies as a function of walking velocity to propel the user forward. To achieve the latter, a strategy to convert the maximum available translational energy acquired from deflection along the leg into rotational energy about the ankle joint through coupling of these two degrees of freedom is used. This strategy utilizes maxima/minima of known ankle profiles to control timing of critical device functions as well as the quantity of energy input from leg deflection. In doing so, both consistent operation of the device and maximal energy output at a given walking velocity are theoretically obtained. Optimizing for both aforementioned ankle criteria, 25.1% of the work of the average natural ankle was achieved for 15 mm of leg deflection, less deflection than is exhibited by many shock absorbing pylon prostheses. After fabricating and testing the optimized design using a repeatable robot trajectory, the device was found to convert 26.6% of input translational work as rotational work, accounting for 63.1% of modeled rotational work. Through human subject testing, the device was found to function inconsistently due to the large impact loadings associated with human gait. In order to achieve proper functionality with human gait, design modifications to the energy storage and release devices are recommended

Design of a Passive Ankle Prosthesis With Energy Return That Increases With Increasing Walking Velocity

An estimated 623,000 individuals are living with a major lower leg amputation in the United States [1]. Of these amputations, 78% were due to peripheral vascular disease (PVD) and 45% were due to PVD in individuals with type I or II diabetes [2]. With diabetes and PVD incidence levels on the rise [1] and those in a depressed socio-economic situation more susceptible to develop type II diabetes [3], the demand for affordable, high quality ankle prostheses has never been higher. Prostheses currently available on the market include both passive and active devices, neither of which fully satisfies user requirements. Passive prostheses, the more commonly prescribed style, are economically priced but lack the powered push-off observed in a natural ankle [4] due to the absence of an actuator. As a result, passive prostheses cause a multitude of quality of life detriments to the end user including asymmetrical gait (for unilateral amputees), slower self-selected walking speeds, higher metabolic cost per distance traveled and increased pain in the residual limb [5–6]. Conversely, active devices can nearly match the functionality and powered push-off of a natural ankle [7] but are cost prohibitive. Among active devices, one of the most successful models is the BiOM. Initially developed at MIT, the BiOM uses an actuator in series with a spring to achieve near natural ankle behavior. In 2013, two years after the product’s official launch, the device cost approximately $50,000 and had only sold about 1,000 units [7]. The limitations of currently available ankle prostheses motivates work on a new solution, the EaSY-Walk (Early Stance Y-deflection), a passive ankle device that mimics several key aspects of a natural ankle joint, especially nonlinear rotational stiffness and rotational work output (powered push-off) that increases with walking velocity while remaining relatively inexpensive

Cell type-specific transcriptomics of esophageal adenocarcinoma as a scalable alternative for single cell transcriptomics

Single-cell transcriptomics have revolutionized our understanding of the cell composition of tumors and allowed us to identify new subtypes of cells. Despite rapid technological advancements, single-cell analysis remains resource-intense hampering the scalability that is required to profile a sufficient number of samples for clinical associations. Therefore, more scalable approaches are needed to understand the contribution of individual cell types to the development and treatment response of solid tumors such as esophageal adenocarcinoma where comprehensive genomic studies have only led to a small number of targeted therapies. Due to the limited treatment options and late diagnosis, esophageal adenocarcinoma has a poor prognosis. Understanding the interaction between and dysfunction of individual cell populations provides an opportunity for the development of new interventions. In an attempt to address the technological and clinical needs, we developed a protocol for the separation of esophageal carcinoma tissue into leukocytes (CD45+), epithelial cells (EpCAM+), and fibroblasts (two out of PDGFR alpha, CD90, anti-fibroblast) by fluorescence-activated cell sorting and subsequent RNA sequencing. We confirm successful separation of the three cell populations by mapping their transcriptomic profiles to reference cell lineage expression data. Gene-level analysis further supports the isolation of individual cell populations with high expression of CD3, CD4, CD8, CD19, and CD20 for leukocytes, CDH1 and MUC1 for epithelial cells, and FAP, SMA, COL1A1, and COL3A1 for fibroblasts. As a proof of concept, we profiled tumor samples of nine patients and explored expression differences in the three cell populations between tumor and normal tissue. Interestingly, we found that angiogenesis-related genes were upregulated in fibroblasts isolated from tumors compared with normal tissue. Overall, we suggest our protocol as a complementary and more scalable approach compared with single-cell RNA sequencing to investigate associations between clinical parameters and transcriptomic alterations of specific cell populations in esophageal adenocarcinoma