A real-time comparison between direct control, sequential pattern recognition control and simultaneous pattern recognition control using a Fitts’ law style assessment procedure

Background: Pattern recognition (PR) based strategies for the control of myoelectric upper limb prostheses are generally evaluated through offline classification accuracy, which is an admittedly useful metric, but insufficient to discuss functional performance in real time. Existing functional tests are extensive to set up and most fail to provide a challenging, objective framework to assess the strategy performance in real time. Methods: Nine able-bodied and two amputee subjects gave informed consent and participated in the local Institutional Review Board approved study. We designed a two-dimensional target acquisition task, based on the principles of Fitts' law for human motor control. Subjects were prompted to steer a cursor from the screen center of into a series of subsequently appearing targets of different difficulties. Three cursor control systems were tested, corresponding to three electromyography-based prosthetic control strategies: 1) amplitude-based direct control (the clinical standard of care), 2) sequential PR control, and 3) simultaneous PR control, allowing for a concurrent activation of two degrees of freedom (DOF). We computed throughput (bits/second), path efficiency (%), reaction time (second), and overshoot (%)) and used general linear models to assess significant differences between the strategies for each metric. Results: We validated the proposed methodology by achieving very high coefficients of determination for Fitts' law. Both PR strategies significantly outperformed direct control in two-DOF targets and were more intuitive to operate. In one-DOF targets, the simultaneous approach was the least precise. The direct control was efficient in one-DOF targets but cumbersome to operate in two-DOF targets through a switch-depended sequential cursor control. Conclusions: We designed a test, capable of comprehensively describing prosthetic control strategies in real time. When implemented on control subjects, the test was able to capture statistically significant differences (p < 0.05) in control strategies when considering throughputs, path efficiencies and reaction times. Of particular note, we found statistically significant (p < 0.01) improvements in throughputs and path efficiencies with simultaneous PR when compared to direct control or sequential PR. Amputees could readily achieve the task; however a limited number of subjects was tested and a statistical analysis was not performed with that population

Evaluating Nutraceuticals for Selective Toxicity Toward Leukemia Stem Cells

Targeting leukemia stem cells (LSCs) is critical to improving the poor outcome of acute myeloid leukemia (AML) patients. Nutraceuticals (i.e., food derived bioactive compounds) provide a wealthy resource for novel anti-cancer, and specifically anti-AML drug discovery. With the advent of novel LSC cell lines, preliminary screening of these compounds against LSC-like cells can be achieved rapidly. To identify potential novel anti-LSC therapeutics, we created and screened a unique library consisting of 288 nutraceuticals in an MTS assay against TEX leukemia cells, a surrogate LSC line and K562, a control cell line which does not possess LSC activity. Here, we identified diosmetin, a flavonoid found in citrus fruits and various green plants, as a novel anti- LSC agent (EC50: 6.0 ± 1.7μM). To confirm its activity, diosmetin (10μM) reduced clonogenic growth of primary AML cells (n = 4) with no effect on normal CD34 positive bone marrow derived stem cells (n = 3) observed in colony forming cell assays. A dose-response and time course analysis performed via the Annexin/PI assay and flow cytometry revealed that diosmetin induced apoptosis, as evidenced by the accumulation of ANN+/PI- cells. Apoptosis was further confirmed by a subG1 peak after performing cell cycle analysis. Utilizing the Database for Annotation, Visualization and Integrated Discovery (DAVID) tool, we determined that the estrogen receptor (ER) was a potential molecular target for diosmetin’s anti-leukemia activity. To assess the role of estrogen receptors, we measured ERα and ERβ protein levels in diosmetin sensitive and insensitive cell lines. Interestingly, diosmetin sensitive cell lines display significantly elevated ERβ protein levels compared to diosmetin insensitive cells. However, this pattern was not observed for ERα. Similar results were observed through quantitative PCR measures, as TEX cells displayed levels of ESR2 (ERβ) mRNA, with no observed levels of ESR1 (ERα) mRNA levels. The opposite results were observed in K562 cells. Through ER reporter assays, it was demonstrated that diosmetin acts as a partial agonist in ERβ reporter cells, increasing luciferase activity with increasing doses of diosmetin in ERβ reporter cells. Moreover, we find that caspase 8 but not caspase 9 is elevated following diosmetin treatment, consistent with the extrinsic pathway of apoptosis and our observed increased in TNF-α, similar to previous reports highlighting the link between ERβ agonists and cancer cell death. In summary, these studies highlight that estrogen receptors, specifically ERβ, is a novel LSC therapeutic target, and the potential role of nutraceuticals as promising compounds for future drug discovery endeavours

Rehabilitative Soft Exoskeleton for Rodents

Robotic exoskeletons provide programmable, consistent and controllable active therapeutic assistance to patients with neurological disorders. Here we introduce a prototype and preliminary experimental evaluation of a rehabilitative gait exoskeleton that enables compliant yet effective manipulation of the fragile limbs of rats. To assist the displacements of the lower limbs without impeding natural gait movements, we designed and fabricated soft pneumatic actuators (SPAs). The exoskeleton integrates two customizable SPAs that are attached to a limb. This configuration enables a 1 N force load, a range of motion exceeding 80 mm in the major axis, and speed of actuation reaching two gait cycles/s. Preliminary experiments in rats with spinal cord injury validated the basic features of the exoskeleton. We propose strategies to improve the performance of the robot and discuss the potential of SPAs for the design of other wearable interfaces

Hybrid peripheral-spinal neuroprosthesis for refined motor execution after paralysis

Spinal cord injury (SCI) disrupts the communication between the brain and the spinal circuits responsible for movement, thereby causing severe motor deficits. Current strategies to restore function to paralyzed limbs have separately investigated electrical stimulation of the spinal cord or of the peripheral neuromuscular system. Various neuromodulation strategies, for instance electrical epidural stimulation (EES) of the spinal cord, reactivate spinal circuits below the lesion and enable the generation of locomotor activity. EES targets muscle synergies rather than specific muscles or joints, and can therefore be limited by low selectivity. Accessing distal muscles individually is key to restore refined movement. Peripheral nerve stimulation (PNS) offers this possibility by selectively recruiting fibers innervating distinct muscles. Here, I developed a hybrid electrical stimulation paradigm, concomitantly targeting the spinal cord and the peripheral nerves for a global activation of coordinated multi-joint leg movements and a selective activation of distal muscles respectively. This approach combines two highly complementary stimulation paradigms into one refined neuroprosthetic system that could improve functional restoration after paralysis. The first part of this work addressed the validation of intraneural electrodes for selective and stable PNS. Albeit highly promising, incomplete characterization of long-term usability and biocompatibility has so far restricted their widespread use. To bridge this gap, I conducted a longitudinal assessment and comprehensively characterized their functional properties in light of their bio-integration in rats. Results showed that i) stimulation thresholds increased moderately during one month after implantation and then stabilized, ii) these changes correlated with progressive implant encapsulation, and iii) selectivity in muscle recruitment was retained in spite of the encapsulation, permitting precise control over ankle kinematics in anesthetized experiments. Overall, these results demonstrated the potential for long-term usability of intraneural implants. In the second part of this work, I developed and characterized a hybrid PNS-EES paradigm that concomitantly stimulated the spinal cord and the sciatic nerves in rat models of severe SCI, and validated it in a pilot study with a human SCI. I showed that i) muscle recruitment obtained by EES and PNS was highly complementary, ii) PNS enabled controllable adjustments in leg movements during locomotion, and iii) the hybrid PNS-EES paradigm permitted refined movements that increased functionality during locomotion in rats and a human pilot subject. This thesis provides evidence about the long-term functionality of intraneural implants and demonstrates their potential for stable interfacing with peripheral nerves. The hybrid PNS-EES paradigm reveals how the complementarity of both strategies effectively improved functional outcomes for paralyzed lower limbs. These findings open promising perspectives for the development of hybrid neuroprosthetic systems to restore functional and refined movements to paralyzed limbs

A neurostimulation system for central nervous stimulation (cns) and peripheral nervous stimulation (pns)

The present disclosure relates to a neuromodulation and/or neurostimulation system comprising at least the following components: at least one sensing unit, at least control unit, at least one stimulation unit, at least one Central Nervous System (CNS) stimulation module, at least one Peripheral Nervous System (PNS) stimulation module,wherein at least one of the components of the neuromodulation and/or neurostimulation system is implantable

A Real Time Performance Assessment of Simultaneous Pattern Recognition Control for Multi-functional Upper Limb Prostheses

A natural and intuitive operation of multifunctional upper limb prostheses involves the concurrent activation of multiple degrees of freedom in a proportional way. Several approaches to simultaneous and proportional control strategies have been investigated; provided outcome measures however were offline accuracy or error rates and lacked the functional component of a preclinical assessment. This study evaluated a simultaneous proportional pattern recognition control strategy with two parallel classifiers in a two-dimensional Fitts' law style test and compared it to a sequential pattern recognition approach. The proposed test allowed for a complete evaluation through different performance metrics such as throughput (TP, bits/sec), path efficiency (PE, %), completion rate (%), overshoot (%) and reaction time (sec). We found that the simultaneous approach presented with numerous advantages with respect to the sequential alternative through significantly higher TP and PE for combined-motion targets (p<0.001) and significantly less overshooting in both combined and discrete targets (p<0.01). For discrete motions, the TP was significantly lower for the simultaneous approach (p<0.001) but PE was similar. There was no difference in either completion rate or reaction time. These results support the potential of simultaneous pattern recognition for the control of multifunctional prostheses and underline the usefulness of a simple functional test in a preclinical framework

Open Access

A real-time comparison between direct control, sequential pattern recognition control and simultaneous pattern recognition control using a Fitts ’ law style assessment procedur

Intentions pédagogiques et perceptions d’un dispositif de formation médiatisée : analyse de réception médiatique d’un MOOC à visée professionnalisante

Cette étude porte sur la perception des intentions pédagogiques et médiatiques d’un MOOC destiné à des professionnels de la santé et de ses effets sur différentes dimensions de l’apprentissage. Conçu dans une perspective réflexive, ce MOOC présente la particularité de s’appuyer notamment sur des capsules vidéo narratives. Les résultats obtenus à travers l’analyse des données issues de trois questionnaires successifs adressés aux participants du MOOC ont permis d’éprouver un instrument d’analyse destiné à décrire et à étudier la convergence entre intentions pédagogiques et perceptions des apprenants, mais également de mettre en avant le potentiel des vidéos narratives à des fins réflexives et relationnelles.This study focuses on the perception of the media and the pedagogical intentions of a MOOC intended for health professionals and its effects on various dimensions of learning. Designed from a reflective perspective, this MOOC is unusual in that it is based on short narrative videos. The results obtained by analyzing data from three successive questionnaires sent to MOOC participants made it possible to test an analysis tool designed to describe and study how closely the learners’ perceptions correspond with the pedagogical intentions, and to highlight the potential of narrative videos for reflective and relational purposes

Development of complex pedagogical competencies and reflexivity in clinical teachers via distance learning: a mixed methods study

ABSTRACTClinical reasoning is the cornerstone to healthcare practice and teaching it appropriately is of utmost importance. Yet there is little formal training for clinical supervisors in supervising this reasoning process. Distance education provides interesting opportunities for continuous professional development of healthcare professionals. This mixed methods study aimed at gaining in-depth understanding about whether and how clinical teachers can develop complex pedagogical competencies through participation in a Massive Open Online Course on the supervision of clinical reasoning (MOOC SCR). Participants self-assed their clinical supervision skills before and after partaking in the MOOC SCR through the Maastricht Clinical Teachers Questionnaire. Item scores and the distribution of response proportions before and after participation were compared using paired t-tests and McNemar’s tests respectively. In parallel, the evolution of a subset of MOOC participants’ pedagogical practice and posture was explored via semi-structured interviews throughout and beyond their MOOC participation using simulated and personal situational recalls. The verbatim were analysed with standard thematic analysis. Quantitative and qualitative findings converged and their integration demonstrated that partaking in the MOOC SCR promoted the development of complex pedagogical competencies and reflexivity with the participants. This was quantitatively evidenced by significantly higher self-assessed supervision skills and corresponding attitudes after completing the MOOC. The qualitative data provided rich descriptions of how this progression in pedagogical practice and posture occurred in the field and how it was shaped by participants’ interaction with the MOOC’s content and their motivations to progress. Our findings provide evidence for the development of pedagogical skills and corresponding attitudes for the supervision of clinical reasoning through participation in the MOOC SCR and contribute to the literature body on the opportunities that distance learning provides for the development of pedagogical competencies. The extent to which the pedagogical underpinnings of the MOOC contributed to these developments remains to be determined