Vibrational Feedback Training System for Use with SEMG Controlled Powered Prostheses

Loss of limb results in loss of function and a partial loss of freedom. A powered prosthetic device can partially assist an individual with everyday tasks and therefore return some level of independence. Powered upper limb prostheses are often controlled by the user generating surface electromyographic (SEMG) signals. The goal of this thesis is to develop a virtual environment in which a user can control a virtual hand to safely grasp representations of everyday objects using EMG signals from his/her forearm muscles, and experience visual and vibrotactile feedback relevant to the grasping force in the process. This can then be used to train potential wearers of real EMG controlled prostheses, with or without vibrotactile feedback. To test this system an experiment was designed and executed involving ten subjects, twelve objects, and three feedback conditions. The tested feedback conditions were visual, vibrotactile, and both visual and vibrotactile. In each experimental exercise the subject attempted to grasp a virtual object on the screen using the virtual hand controlled by EMG electrodes placed on his/her forearm. Two metrics were used: score, and time to task completion, where score measured grasp dexterity. It was hypothesized that with the introduction of vibrotactile feedback, dexterity, and therefore score, would improve and time to task completion would decrease. Results showed that time to task completion increased, and score did not improve with vibrotactile feedback. Details on the developed system, the experiment, and the results are presented in this thesis.

Interactions of Lipoprotein(a) with the Plasminogen System: Mechanisms and Pathophysiological Consequences

Elevated plasma concentrations of lipoprotein(a) (Lp(a)) are associated with increased risk of atherothrombotic disease. Lp(a) is a unique lipoprotein consisting of a low density lipoprotein-like moiety covalently linked to apolipoprotein(a) (apo(a)), a homologue of the fibrinolytic proenzyme plasminogen. Apo(a) is extremely heterogeneous in size with small isoforms being independently associated with increased cardiovascular risk. Several in vitro and in vivo studies have shown that Lp(a)/apo(a) can inhibit tissue-type plasminogen activator (tPA)-mediated plasminogen activation on fibrin surfaces, although the mechanism of inhibition by apo(a) remains controversial. Essential to fibrin clot lysis are a number of plasmin-dependent positive feedback reactions that enhance the efficiency of plasminogen activation, including the plasmin-mediated conversion of Glu1-plasminogen to Lys78-plasminogen. Additionally, abnormal fibrin clot structures have been associated with both an increased risk of cardiovascular disease and elevated Lp(a) levels. Similarly, oxidized phospholipids have been implicated in the development of cardiovascular disease, and are not only preferentially carried by Lp(a) in the plasma but have also been shown to covalently-modify both apo(a) and plasminogen. In this thesis, we built upon the understanding of the role of apo(a) in plasminogen activation on the fibrin/degraded fibrin surface by determining that: (i) apo(a) inhibits plasmin-mediated Glu1-plasminogen to Lys78-plasminogen conversion and identifying the critical domains in apo(a) responsible for this effect, (ii) apo(a) isoform size does not affect either the inhibition of tPA-mediated plasminogen activation or the inhibition of plasmin-mediated Glu1-plasminogen to Lys78-plasminogen conversion, (iii) apo(a) modifies fibrin clot structure to form more dense clots with thinner fibers and reduced permeability, modifications that enhance the ability of apo(a) to inhibit tPA-mediated plasminogen activation and (iv) the phosphorus content of apo(a) affects its ability to inhibit tPA-mediated plasminogen activation and the phosphorus content of plasminogen affects its ability to be activated by tPA. By understanding these individual reactions, each of which has the potential to affect the broader fibrin clot lysis process, we have expanded our understanding of the overall effect of Lp(a)/apo(a) in the inhibition of plasminogen activation on the fibrin/degraded fibrin surface and thus broadened our understanding of how Lp(a)/apo(a) may mediate the inhibition of thrombolysis in vivo.