Distributed Sensing and Stimulation Systems Towards Sense of Touch Restoration in Prosthetics

Modern prostheses aim at restoring the functional and aesthetic characteristics of the lost limb. To foster prosthesis embodiment and functionality, it is necessary to restitute both volitional control and sensory feedback. Contemporary feedback interfaces presented in research use few sensors and stimulation units to feedback at most two discrete feedback variables (e.g. grasping force and aperture), whereas the human sense of touch relies on a distributed network of mechanoreceptors providing high-fidelity spatial information. To provide this type of feedback in prosthetics, it is necessary to sense tactile information from artificial skin placed on the prosthesis and transmit tactile feedback above the amputation in order to map the interaction between the prosthesis and the environment. This thesis proposes the integration of distributed sensing systems (e-skin) to acquire tactile sensation, and non-invasive multichannel electrotactile feedback and virtual reality to deliver high-bandwidth information to the user. Its core focus addresses the development and testing of close-loop sensory feedback human-machine interface, based on the latest distributed sensing and stimulation techniques for restoring the sense of touch in prosthetics. To this end, the thesis is comprised of two introductory chapters that describe the state of art in the field, the objectives and the used methodology and contributions; as well as three studies distributed over stimulation system level and sensing system level. The first study presents the development of close-loop compensatory tracking system to evaluate the usability and effectiveness of electrotactile sensory feedback in enabling real-time close-loop control in prosthetics. It examines and compares the subject\u2019s adaptive performance and tolerance to random latencies while performing the dynamic control task (i.e. position control) and simultaneously receiving either visual feedback or electrotactile feedback for communicating the momentary tracking error. Moreover, it reported the minimum time delay needed for an abrupt impairment of users\u2019 performance. The experimental results have shown that electrotactile feedback performance is less prone to changes with longer delays. However, visual feedback drops faster than electrotactile with increased time delays. This is a good indication for the effectiveness of electrotactile feedback in enabling close- loop control in prosthetics, since some delays are inevitable. The second study describes the development of a novel non-invasive compact multichannel interface for electrotactile feedback, containing 24 pads electrode matrix, with fully programmable stimulation unit, that investigates the ability of able-bodied human subjects to localize the electrotactile stimulus delivered through the electrode matrix. Furthermore, it designed a novel dual parameter -modulation (interleaved frequency and intensity) and compared it to conventional stimulation (same frequency for all pads). In addition and for the first time, it compared the electrotactile stimulation to mechanical stimulation. More, it exposes the integration of virtual prosthesis with the developed system in order to achieve better user experience and object manipulation through mapping the acquired real-time collected tactile data and feedback it simultaneously to the user. The experimental results demonstrated that the proposed interleaved coding substantially improved the spatial localization compared to same-frequency stimulation. Furthermore, it showed that same-frequency stimulation was equivalent to mechanical stimulation, whereas the performance with dual-parameter modulation was significantly better. The third study presents the realization of a novel, flexible, screen- printed e-skin based on P(VDF-TrFE) piezoelectric polymers, that would cover the fingertips and the palm of the prosthetic hand (particularly the Michelangelo hand by Ottobock) and an assistive sensorized glove for stroke patients. Moreover, it developed a new validation methodology to examine the sensors behavior while being solicited. The characterization results showed compatibility between the expected (modeled) behavior of the electrical response of each sensor to measured mechanical (normal) force at the skin surface, which in turn proved the combination of both fabrication and assembly processes was successful. This paves the way to define a practical, simplified and reproducible characterization protocol for e-skin patches In conclusion, by adopting innovative methodologies in sensing and stimulation systems, this thesis advances the overall development of close-loop sensory feedback human-machine interface used for restoration of sense of touch in prosthetics. Moreover, this research could lead to high-bandwidth high-fidelity transmission of tactile information for modern dexterous prostheses that could ameliorate the end user experience and facilitate it acceptance in the daily life

Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in nonbreast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Validation of Screen-Printed Electronic Skin Based on Piezoelectric Polymer Sensors

This paper proposes a validation method of the fabrication technology of a screen-printed electronic skin based on polyvinylidene fluoride-trifluoroethylene P(VDF-TrFE) piezoelectric polymer sensors. This required researchers to insure, through non-direct sensor characterization, that printed sensors were working as expected. For that, we adapted an existing model to non-destructively extract sensor behavior in pure compression (i.e., the d33 piezocoefficient) by indentation tests over the skin surface. Different skin patches, designed to sensorize a glove and a prosthetic hand (11 skin patches, 104 sensors), have been tested. Reproducibility of the sensor response and its dependence upon sensor position on the fabrication substrate were examined, highlighting the drawbacks of employing large A3-sized substrates. The average value of d33 for all sensors was measured at incremental preloads (1–3 N). A systematic decrease has been checked for patches located at positions not affected by substrate shrinkage. In turn, sensor reproducibility and d33 adherence to literature values validated the e-skin fabrication technology. To extend the predictable behavior to all skin patches and thus increase the number of working sensors, the size of the fabrication substrate is to be decreased in future skin fabrication. The tests also demonstrated the efficiency of the proposed method to characterize embedded sensors which are no more accessible for direct validation

Synthesis, Optical, and Geometrical Approaches of New Natural Fatty Acids’ Esters/Schiff Base Liquid Crystals

Schiff base liquid crystals, known as [4-(hexyloxy)phenylimino)methyl]phenyl palmitate (IA), [4-(hexyloxy)phenylimino)methyl]phenyl oleate (IIA) and [4-(hexyloxy)phenylimino)methyl]phenyl linoleate (IIIA), were synthesized from palmitic, oleic, and linoleic natural fatty acids. The prepared compounds have been investigated for their thermal and optical behavior as well as phase formation using differential scanning calorimetry (DSC) and polarized optical microscopy (POM). Molecular structures of all studied compounds were confirmed via elemental analysis, FT-IR, 1H NMR, and 13C NMR. Smectic phase is the observed mesophase for all compounds; however, their type and range depend upon the terminal alkanoate chains attached to the phenyl ring. Computational calculations, Density functional theory (DFT), energy difference of the frontier molecular orbital (FMOs), as well as the thermodynamic parameters of different molecular configurations isomers were discussed. It was found that the mesophase behavior and the geometrical characteristics were affected by the degree of unsaturation of fatty terminal chains. Furthermore, the geometrical structure of the CH=N linkage plays an important role in the thermal stability and optical transition temperature

Distributed sensing and stimulation systems for sense of touch restoration in prosthetics

Modern prostheses aim at restoring the functional and aesthetic characteristics of the lost limb. To foster prosthesis embodiment and functionality, it is necessary to re-establish both volitional control and sensory feedback. Contemporary feedback interfaces presented in research use few sensors and stimulation units to feedback at most two discrete feedback variables (e.g., grasping force and aperture), whereas the human sense of touch relies on a distributed network of mechanoreceptors providing high-fidelity spatial information. To provide this type of feedback in prosthetics, it is necessary to sense tactile information from artificial skin placed on the prosthesis and transmit tactile feedback above the amputation in order to map the interaction between the prosthesis and the environment. This paper will provide a perspective on the use of distributed sensing and electrical stimulation systems for the restoration of the sense of touch in prosthetics. \ua9 2017 IEEE

A systematic review on functional electrical stimulation based rehabilitation systems for upper limb post-stroke recovery

Background: Stroke is one of the most common neurological conditions that often leads to upper limb motor impairments, significantly affecting individuals' quality of life. Rehabilitation strategies are crucial in facilitating post-stroke recovery and improving functional independence. Functional Electrical Stimulation (FES) systems have emerged as promising upper limb rehabilitation tools, offering innovative neuromuscular reeducation approaches.Objective: The main objective of this paper is to provide a comprehensive systematic review of the start-of-the-art functional electrical stimulation (FES) systems for upper limb neurorehabilitation in post-stroke therapy. More specifically, this paper aims to review different types of FES systems, their feasibility testing, or randomized control trials (RCT) studies.Methods: The FES systems classification is based on the involvement of patient feedback within the FES control, which mainly includes "Open-Loop FES Systems" (manually controlled) and "Closed-Loop FES Systems" (brain-computer interface-BCI and electromyography-EMG controlled). Thus, valuable insights are presented into the technological advantages and effectiveness of Manual FES, EEG-FES, and EMG-FES systems.Results and discussion: The review analyzed 25 studies and found that the use of FES-based rehabilitation systems resulted in favorable outcomes for the stroke recovery of upper limb functional movements, as measured by the FMA (Fugl-Meyer Assessment) (Manually controlled FES: mean difference = 5.6, 95% CI (3.77, 7.5), P < 0.001; BCI-controlled FES: mean difference = 5.37, 95% CI (4.2, 6.6), P < 0.001; EMG-controlled FES: mean difference = 14.14, 95% CI (11.72, 16.6), P < 0.001) and ARAT (Action Research Arm Test) (EMG-controlled FES: mean difference = 11.9, 95% CI (8.8, 14.9), P < 0.001) scores. Furthermore, the shortcomings, clinical considerations, comparison to non-FES systems, design improvements, and possible future implications are also discussed for improving stroke rehabilitation systems and advancing post-stroke recovery. Thus, summarizing the existing literature, this review paper can help researchers identify areas for further investigation. This can lead to formulating research questions and developing new studies aimed at improving FES systems and their outcomes in upper limb rehabilitation

Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

Breast cancer; Genes; LociCàncer de mama; Gens; LociCáncer de mama; Genes; LociGenome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer