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  • Patterns of lower limb muscular activity and joint moments during directional efforts using a static dynamometer
    BMC Biomed. Eng. (IF 0) Pub Date : 2020-01-08
    Mathieu Lalumiere; Cloé Villeneuve; Cassandra Bellavance; Michel Goyette; Daniel Bourbonnais

    Strength and coordination of lower muscle groups typically identified in healthy subjects are two prerequisites to performing functional activities. These physical qualities can be impaired following a neurological insult. A static dynamometer apparatus that measures lower limb joint moments during directional efforts at the foot was developed to recruit different patterns of muscular activity. The objectives of the present study were to 1) validate joint moments estimated by the apparatus, and 2) to characterize lower limb joint moments and muscular activity patterns of healthy subjects during progressive static efforts. Subjects were seated in a semi-reclined position with one foot attached to a force platform interfaced with a laboratory computer. Forces and moments exerted under the foot were computed using inverse dynamics, allowing for the estimation of lower limb joint moments. To achieve the study’s first objective, joint moments were validated by comparing moments of various magnitudes of force applied by turnbuckles on an instrumented leg equipped with strain gauges with those estimated by the apparatus. Concurrent validity and agreement were assessed using Pearson correlation coefficients and Bland and Altman analysis, respectively. For the second objective, joint moments and muscular activity were characterized for five healthy subjects while exerting progressive effort in eight sagittal directions. Lower limb joint moments were estimated during directional efforts using inverse dynamics. Muscular activity of eight muscles of the lower limb was recorded using surface electrodes and further analyzed using normalized root mean square data. The joint moments estimated with the instrumented leg were correlated (r > 0.999) with those measured by the dynamometer. Limits of agreement ranged between 8.5 and 19.2% of the average joint moment calculated by both devices. During progressive efforts on the apparatus, joint moments and patterns of muscular activity were specific to the direction of effort. Patterns of muscular activity in four directions were similar to activation patterns reported in the literature for specific portions of gait cycle. This apparatus provides valid joint moments exerted at the lower limbs. It is suggested that this methodology be used to recruit muscular activity patterns impaired in neurological populations.

  • Developing preclinical models of neuroblastoma: driving therapeutic testing
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-12-20
    Kimberly J. Ornell; Jeannine M. Coburn

    Despite advances in cancer therapeutics, particularly in the area of immuno-oncology, successful treatment of neuroblastoma (NB) remains a challenge. NB is the most common cancer in infants under 1 year of age, and accounts for approximately 10% of all pediatric cancers. Currently, children with high-risk NB exhibit a survival rate of 40–50%. The heterogeneous nature of NB makes development of effective therapeutic strategies challenging. Many preclinical models attempt to mimic the tumor phenotype and tumor microenvironment. In vivo mouse models, in the form of genetic, syngeneic, and xenograft mice, are advantageous as they replicated the complex tumor-stroma interactions and represent the gold standard for preclinical therapeutic testing. Traditional in vitro models, while high throughput, exhibit many limitations. The emergence of new tissue engineered models has the potential to bridge the gap between in vitro and in vivo models for therapeutic testing. Therapeutics continue to evolve from traditional cytotoxic chemotherapies to biologically targeted therapies. These therapeutics act on both the tumor cells and other cells within the tumor microenvironment, making development of preclinical models that accurately reflect tumor heterogeneity more important than ever. In this review, we will discuss current in vitro and in vivo preclinical testing models, and their potential applications to therapeutic development.

  • Correction to: Osteogenic potential of heterogeneous and CD271-enriched mesenchymal stromal cells cultured on apatite-wollastonite 3D scaffolds
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-12-11
    Sylvia Müller; Lyndsey Nicholson; Naif Al Harbi; Elena Mancuso; Elena Jones; Anne Dickinson; Xiao Nong Wang; Kenneth Dalgarno

    In the original publication of this article [1] the figures and captions were linked incorrectly. In this correction article the figures & captions are correctly published.

  • Exploring physiological signals on people with Duchenne muscular dystrophy for an active trunk support: a case study
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-12-09
    Stergios Verros; Laura Peeters; Arjen Bergsma; Edsko E. G. Hekman; Gijsbertus J. Verkerke; Bart F. J. M. Koopman

    Arm support devices are available to support people with Duchenne muscular dystrophy (DMD), but active trunk support devices are lacking. An active trunk support device can potentially extend the reach of the arm and stabilize the unstable trunk of people with DMD. In a previous study, we showed that healthy people were able to control an active trunk support using four different control interfaces (based on joystick, force on feet, force on sternum and surface electromyography). All four control interfaces had different advantages and disadvantages. The aim of this study was to explore which of the four inputs is detectably used by people with DMD to control an active trunk support. The results were subject-dependent in both experiments. In the active experiment, the joystick was the most promising control interface. Regarding the static experiment, surface electromyography and force on feet worked for two out of the three subjects. To our knowledge, this is the first time that people with DMD have engaged in a control task using signals other than those related to their arm muscles. According to our findings, the control interfaces have to be customised to every DMD subject.

  • The problem with skeletal muscle series elasticity
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-12-03
    Walter Herzog

    Muscles contain contractile and (visco-) elastic passive components. At the latest since Hill’s classic works in the 1930s, it has been known that these elastic components affect the length and rate of change in length of the contractile component, and thus the active force capability of dynamically working muscles. In an attempt to elucidate functional properties of these muscle elastic components, scientists have introduced the notion of “series” and “parallel” elasticity. Unfortunately, this has led to much confusion and erroneous interpretations of results when the mechanical definitions of parallel and series elasticity were violated. In this review, I will focus on muscle series elasticity, by first providing the mechanical definition for series elasticity, and then provide theoretical and experimental examples of the concept of series elasticity. Of particular importance is the treatment of aponeuroses. Aponeuroses are not in series with the tendon of a muscle nor the muscle’s contractile elements. The implicit and explicit treatment of aponeuroses as series elastic elements in muscle has led to incorrect conclusions about aponeuroses stiffness and Young’s modulus, and has contributed to vast overestimations of the storage and release of mechanical energy in cyclic muscle contractions. Series elasticity is a defined mechanical concept that needs to be treated carefully when applied to skeletal muscle mechanics. Measuring aponeuroses mechanical properties in a muscle, and its possible contribution to the storage and release of mechanical energy is not trivial, and to my best knowledge, has not been (correctly) done yet.

  • Models of tendon development and injury
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-11-29
    Sophia K. Theodossiou; Nathan R. Schiele

    Tendons link muscle to bone and transfer forces necessary for normal movement. Tendon injuries can be debilitating and their intrinsic healing potential is limited. These challenges have motivated the development of model systems to study the factors that regulate tendon formation and tendon injury. Recent advances in understanding of embryonic and postnatal tendon formation have inspired approaches that aimed to mimic key aspects of tendon development. Model systems have also been developed to explore factors that regulate tendon injury and healing. We highlight current model systems that explore developmentally inspired cellular, mechanical, and biochemical factors in tendon formation and tenogenic stem cell differentiation. Next, we discuss in vivo, in vitro, ex vivo, and computational models of tendon injury that examine how mechanical loading and biochemical factors contribute to tendon pathologies and healing. These tendon development and injury models show promise for identifying the factors guiding tendon formation and tendon pathologies, and will ultimately improve regenerative tissue engineering strategies and clinical outcomes.

  • BMC Biomedical Engineering: a home for all biomedical engineering research
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-01-30
    Alexandros Houssein; Alan Kawarai Lefor; Antonio Veloso; Zhi Yang; Jong Chul Ye; Dimitrios I. Zeugolis; Sang Yup Lee

    This editorial accompanies the launch of BMC Biomedical Engineering, a new open access, peer-reviewed journal within the BMC series, which seeks to publish articles on all aspects of biomedical engineering. As one of the first engineering journals within the BMC series portfolio, it will support and complement existing biomedical communities, but at the same time, it will provide an open access home for engineering research. By publishing original research, methodology, database, software and review articles, BMC Biomedical Engineering will disseminate quality research, with a focus on studies that further the understanding of human disease and that contribute towards the improvement of human health.

  • Robotic and laparoscopic surgery of the pancreas: an historical review
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-01-30
    Alan Kawarai Lefor

    Surgery of the pancreas is a relatively new field, with operative series appearing only in the last 50 years. Surgery of the pancreas is technically challenging. The entire field of general surgery changed radically in 1987 with the introduction of the laparoscopic cholecystectomy. Minimally Invasive surgical techniques rapidly became utilized worldwide for gallbladder surgery and were then adapted to other abdominal operations. These techniques are used regularly for surgery of the pancreas including distal pancreatectomy and pancreatoduodenectomy. The progression from open surgery to laparoscopy to robotic surgery has occurred for many operations including adrenalectomy, thyroidectomy, colon resection, prostatectomy, gastrectomy and others. Data to show a benefit to the patient are scarce for robotic surgery, although both laparoscopic and robotic surgery of the pancreas have been shown not to be inferior with regard to major operative and oncologic outcomes. While there were serious concerns when laparoscopy was first used in patients with malignancies, robotic surgery has been used in many benign and malignant conditions with no obvious deterioration of outcomes. Robotic surgery for malignancies of the pancreas is well accepted and expanding to more centers. The importance of centers of excellence, surgeon experience supported by a codified mastery-based training program and international registries is widely accepted. Robotic pancreatic surgery is associated with slightly decreased blood loss and decreased length of stay compared to open surgery. Major oncologic outcomes appear to have been preserved, with some studies showing higher rates of R0 resection and tumor-free margins. Patients with lesions of the pancreas should find a surgeon they trust and do not need to be concerned with the operative approach used for their resection. The step-wise approach that has characterized the growth in robotic surgery of the pancreas, in contradistinction to the frenzy that accompanied the introduction of laparoscopic cholecystectomy, has allowed the identification of areas for improvement, many of which lie at the junction of engineering and medical practice. Refinements in robotic surgery depend on a partnership between engineers and clinicians.

  • An upper body garment with integrated sensors for people with neurological disorders – early development and evaluation
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-01-30
    Margit Alt Murphy; Filip Bergquist; Bengt Hagström; Niina Hernández; Dongni Johansson; Fredrik Ohlsson; Leif Sandsjö; Jan Wipenmyr; Kristina Malmgren

    In neurology and rehabilitation the primary interest for using wearables is to supplement traditional patient assessment and monitoring in hospital settings with continuous data collection at home and in community settings. The aim of this project was to develop a novel wearable garment with integrated sensors designed for continuous monitoring of physiological and movement related variables to evaluate progression, tailor treatments and improve diagnosis in epilepsy, Parkinson’s disease and stroke. In this paper the early development and evaluation of a prototype designed to monitor movements and heart rate is described. An iterative development process and evaluation of an upper body garment with integrated sensors included: identification of user needs, specification of technical and garment requirements, garment development and production as well as evaluation of garment design, functionality and usability. The project is a multidisciplinary collaboration with experts from medical, engineering, textile, and material science within the wearITmed consortium. The work was organized in regular meetings, task groups and hands-on workshops. User needs were identified using results from a mixed-methods systematic review, a focus group study and expert groups. Usability was evaluated in 19 individuals (13 controls, 6 patients with Parkinson’s disease) using semi-structured interviews and qualitative content analysis. The garment was well accepted by the users regarding design and comfort, although the users were cautious about the technology and suggested improvements. All electronic components passed a washability test. The most robust data was obtained from accelerometer and gyroscope sensors while the electrodes for heart rate registration were sensitive to motion artefacts. The algorithm development within the wearITmed consortium has shown promising results. The prototype was accepted by the users. Technical improvements are needed, but preliminary data indicate that the garment has potential to be used as a tool for diagnosis and treatment selection and could provide added value for monitoring seizures in epilepsy, fluctuations in PD and activity levels in stroke. Future work aims to improve the prototype further, develop algorithms, and evaluate the functionality and usability in targeted patient groups. The potential of incorporating blood pressure and heart-rate variability monitoring will also be explored.

  • Fully convolutional architecture vs sliding-window CNN for corneal endothelium cell segmentation
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-01-30
    Juan P. Vigueras-Guillén; Busra Sari; Stanley F. Goes; Hans G. Lemij; Jeroen van Rooij; Koenraad A. Vermeer; Lucas J. van Vliet

    Corneal endothelium (CE) images provide valuable clinical information regarding the health state of the cornea. Computation of the clinical morphometric parameters requires the segmentation of endothelial cell images. Current techniques to image the endothelium in vivo deliver low quality images, which makes automatic segmentation a complicated task. Here, we present two convolutional neural networks (CNN) to segment CE images: a global fully convolutional approach based on U-net, and a local sliding-window network (SW-net). We propose to use probabilistic labels instead of binary, we evaluate a preprocessing method to enhance the contrast of images, and we introduce a postprocessing method based on Fourier analysis and watershed to convert the CNN output images into the final cell segmentation. Both methods are applied to 50 images acquired with an SP-1P Topcon specular microscope. Estimates are compared against a manual delineation made by a trained observer. U-net (AUC=0.9938) yields slightly sharper, clearer images than SW-net (AUC=0.9921). After postprocessing, U-net obtains a DICE=0.981 and a MHD=0.22 (modified Hausdorff distance), whereas SW-net yields a DICE=0.978 and a MHD=0.30. U-net generates a wrong cell segmentation in only 0.48% of the cells, versus 0.92% for the SW-net. U-net achieves statistically significant better precision and accuracy than both, Topcon and SW-net, for the estimates of three clinical parameters: cell density (ECD), polymegethism (CV), and pleomorphism (HEX). The mean relative error in U-net for the parameters is 0.4% in ECD, 2.8% in CV, and 1.3% in HEX. The computation time to segment an image and estimate the parameters is barely a few seconds. Both methods presented here provide a statistically significant improvement over the state of the art. U-net has reached the smallest error rate. We suggest a segmentation refinement based on our previous work to further improve the performance.

  • Battling adhesions: from understanding to prevention
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-02-27
    Héctor Capella-Monsonís; Stephen Kearns; Jack Kelly; Dimitrios I. Zeugolis

    Adhesions represent a major burden in clinical practice, particularly following abdominal, intrauterine, pericardial and tendon surgical procedures. Adhesions are initiated by a disruption in the epithelial or mesothelial layer of tissue, which leads to fibrin adhesion sites due to the downregulation of fibrinolytic activity and an increase in fibrin deposition. Hence, the metabolic events involved in tissue healing, coagulation, inflammation, fibrinolysis and angiogenesis play a pivotal role in adhesion formation. Understanding these events, their interactions and their influence on the development of post-surgical adhesion is crucial for the development of effective therapies to prevent them. Mechanical barriers, antiadhesive agents and combination thereof are customarily used in the battle against adhesions. Although these systems seem to be effective at reducing adhesions in clinical procedures, their prevention remains still elusive, imposing the need for new antiadhesive strategies.

  • Spiropyran as a potential molecular diagnostic tool for double-stranded RNA detection
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-03-18
    Ahsan Ausaf Ali; Minjeong Kang; Raisa Kharbash; Yoosik Kim

    Long double-stranded RNAs (dsRNAs) are duplex RNAs that can induce immune response when present in mammalian cells. These RNAs are historically associated with viral replication, but recent evidence suggests that human cells naturally encode endogenous dsRNAs that can regulate antiviral machineries in cellular contexts beyond immune response. In this study, we use photochromic organic compound spiropyran to profile and quantitate dsRNA expression. We show that the open form of spiropyran, merocyanine, can intercalate between RNA base pairs, which leads to protonation and alteration in the spectral property of the compound. By quantifying the spectral change, we can detect and quantify dsRNA expression level, both synthetic and cellular. We further demonstrate that spiropyrans can be used as a molecular diagnostic tool to profile endogenously expressed dsRNAs. Particularly, we show that spiropyrans can robustly detect elevated dsRNA levels when colorectal cancer cells are treated with 5-aza-2′-deoxycytidine, an FDA-approved DNA-demethylating agent used for chemotherapy, thus demonstrating the use of spiropyran for predicting responsiveness to the drug treatment. As dsRNAs are signature of virus and accumulation of dsRNAs is implicated in various degenerative disease, our work establishes potential application of spiropyrans as a simple spectral tool to diagnose human disease based on dsRNA expression.

  • Assessment of frailty: a survey of quantitative and clinical methods
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-03-18
    Yasmeen Naz Panhwar; Fazel Naghdy; Golshah Naghdy; David Stirling; Janette Potter

    Frailty assessment is a critical approach in assessing the health status of older people. The clinical tools deployed by geriatricians to assess frailty can be grouped into two categories; using a questionnaire-based method or analyzing the physical performance of the subject. In performance analysis, the time taken by a subject to complete a physical task such as walking over a specific distance, typically three meters, is measured. The questionnaire-based method is subjective, and the time-based performance analysis does not necessarily identify the kinematic characteristics of motion and their root causes. However, kinematic characteristics are crucial in measuring the degree of frailty. The studies reviewed in this paper indicate that the quantitative analysis of activity of daily living, balance and gait are significant methods for assessing frailty in older people. Kinematic parameters (such as gait speed) and sensor-derived parameters are also strong markers of frailty. Seventeen gait parameters are found to be sensitive for discriminating various frailty levels. Gait velocity is the most significant parameter. Short term monitoring of daily activities is a more significant method for frailty assessment than is long term monitoring and can be implemented easily using clinical tests such as sit to stand or stand to sit. The risk of fall can be considered an outcome of frailty. Frailty is a multi-dimensional phenomenon that is defined by various domains; physical, social, psychological and environmental. The physical domain has proven to be essential in the objective determination of the degree of frailty in older people. The deployment of inertial sensor in clinical tests is an effective method for the objective assessment of frailty.

  • Compressed sensing MRI: a review from signal processing perspective
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-03-29
    Jong Chul Ye

    Magnetic resonance imaging (MRI) is an inherently slow imaging modality, since it acquires multi-dimensional k-space data through 1-D free induction decay or echo signals. This often limits the use of MRI, especially for high resolution or dynamic imaging. Accordingly, many investigators has developed various acceleration techniques to allow fast MR imaging. For the last two decades, one of the most important breakthroughs in this direction is the introduction of compressed sensing (CS) that allows accurate reconstruction from sparsely sampled k-space data. The recent FDA approval of compressed sensing products for clinical scans clearly reflect the maturity of this technology. Therefore, this paper reviews the basic idea of CS and how this technology have been evolved for various MR imaging problems.

  • Image improvement in linear-array photoacoustic imaging using high resolution coherence factor weighting technique
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-04-05
    Moein Mozaffarzadeh; Bahador Makkiabadi; Maryam Basij; Mohammad Mehrmohammadi

    In Photoacoustic imaging (PAI), the most prevalent beamforming algorithm is delay-and-sum (DAS) due to its simple implementation. However, it results in a low quality image affected by the high level of sidelobes. Coherence factor (CF) can be used to address the sidelobes in the reconstructed images by DAS, but the resolution improvement is not good enough, compared to the high resolution beamformers such as minimum variance (MV). In this paper, it is proposed to use high-resolution-CF (HRCF) weighting technique in which MV is used instead of the existing DAS in the formula of the conventional CF. The higher performance of HRCF is proved numerically and experimentally. The quantitative results obtained with the simulations show that at the depth of 40 mm, in comparison with DAS+CF and MV+CF, HRCF improves the full-width-half-maximum of about 91% and 15% and the signal-to-noise ratio about 40% and 14%, respectively. Proposed method provides a high resolution along with a low level of sidelobes for PAI.

  • Analysis of a poly(ε-decalactone)/silver nanowire composite as an electrically conducting neural interface biomaterial
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-04-15
    Katarzyna Krukiewicz; Jorge Fernandez; Małgorzata Skorupa; Daria Więcławska; Anup Poudel; Jose-Ramon Sarasua; Leo R. Quinlan; Manus J. P. Biggs

    Advancement in polymer technologies, facilitated predominantly through chemical engineering approaches or through the identification and utilization of novel renewable resources, has been a steady focus of biomaterials research for the past 50 years. Aliphatic polyesters have been exploited in numerous biomedical applications including the formulation of soft-tissue sutures, bone fixation devices, cardiovascular stents etc. Biomimetic ‘soft’ polymer formulations are of interest in the design of biological interfaces and specifically, in the development of implantable neuroelectrode systems intended to interface with neural tissues. Critically, soft polymer formulations have been shown to address the challenges associated with the disregulation of mechanotransductive processes and micro-motion induced inflammation at the electrode/tissue interface. In this study, a polyester-based poly(ε-decalactone)/silver nanowire (EDL:Ag) composite was investigated as a novel electrically active biomaterial with neural applications. Neural interfaces were formulated through spin coating of a polymer/nanowire formulation onto the surface of a Pt electrode to form a biocompatible EDL matrix supported by a percolated network of silver nanowires. As-formed EDL:Ag composites were characterized by means of infrared spectroscopy, scanning electron microscopy and electrochemical methods, with their cytocompatibility assessed using primary cultures of a mixed neural population obtained from the ventral mesencephalon of Sprague-Dawley rat embryos. Electrochemical characterization of various EDL:Ag composites indicated EDL:Ag 10:1 as the most favourable formulation, exhibiting high charge storage capacity (8.7 ± 1.0 mC/cm2), charge injection capacity (84.3 ± 1.4 μC/cm2) and low impedance at 1 kHz (194 ± 28 Ω), outperforming both pristine EDL and bare Pt electrodes. The in vitro biological evaluation showed that EDL:Ag supported significant neuron viability in culture and to promote neurite outgrowth, which had the average length of 2300 ± 6 μm following 14 days in culture, 60% longer than pristine EDL and 120% longer than bare Pt control substrates. EDL:Ag nanocomposites are shown to serve as robust neural interface materials, possessing favourable electrochemical characteristics together with high neural cytocompatibility.

  • A biomechanical test model for evaluating osseous and osteochondral tissue adhesives
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-05-07
    Philip Procter; Michael Pujari-Palmer; Gry Hulsart-Billström; David Wenner; Gerard Insley; Sune Larsson; Håkan Engqvist

    Currently there are no standard models with which to evaluate the biomechanical performance of calcified tissue adhesives, in vivo. We present, herein, a pre-clinical murine distal femoral bone model for evaluating tissue adhesives intended for use in both osseous and osteochondral tissue reconstruction. Cylindrical cores (diameter (Ø) 2 mm (mm) × 2 mm depth), containing both cancellous and cortical bone, were fractured out from the distal femur and then reattached using one of two tissue adhesives. The adhesiveness of fibrin glue (Tisseeltm), and a novel, biocompatible, calcium phosphate-based tissue adhesive (OsStictm) were evaluated by pullout testing, in which glued cores were extracted and the peak force at failure recorded. The results show that Tisseel weakly bonded the metaphyseal bone cores, while OsStic produced > 30-fold higher mean peak forces at failure (7.64 Newtons (N) vs. 0.21 N). The failure modes were consistently disparate, with Tisseel failing gradually, while OsStic failed abruptly, as would be expected with a calcium-based material. Imaging of the bone/adhesive interface with microcomputed tomography revealed that, for OsStic, failure occurred more often within cancellous bone (75% of tested samples) rather than at the adhesive interface. Despite the challenges associated with biomechanical testing in small rodent models the preclinical ex-vivo test model presented herein is both sensitive and accurate. It enabled differences in tissue adhesive strength to be quantified even for very small osseous fragments (<Ø4mm). Importantly, this model can easily be scaled to larger animals and adapted to fracture fragment fixation in human bone. The present model is also compatible with other long-term in vivo evaluation methods (i.e. in vivo imaging, histological analysis, etc.).

  • Robots in laparoscopic surgery: current and future status
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-05-29
    Kenji Kawashima; Takahiro Kanno; Kotaro Tadano

    In this paper, we focus on robots used for laparoscopic surgery, which is one of the most active areas for research and development of surgical robots. We introduce research and development of laparoscope-holder robots, master-slave robots and hand-held robotic forceps. Then, we discuss future directions for surgical robots. For robot hardware, snake like flexible mechanisms for single-port access surgery (SPA) and NOTES (Natural Orifice Transluminal Endoscopic Surgery) and applications of soft robotics are actively used. On the software side, research such as automation of surgical procedures using machine learning is one of the hot topics.

  • Iterative Bayesian denoising based on variance stabilization using Contourlet Transform with Sharp Frequency Localization: application to EFTEM images
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-06-13
    Soumia Sid Ahmed; Zoubeida Messali; Larbi Boubchir; Ahmed Bouridane; Sergio Marco; Cédric Messaoudi

    Due to the presence of high noise level in tomographic series of energy filtered transmission electron microscopy (EFTEM) images, alignment and 3D reconstruction steps become so difficult. To improve the alignment process which will in turn allow a more accurate and better three dimensional tomography reconstructions, a preprocessing step should be applied to the EFTEM data series. Experiments with real EFTEM data series at low SNR, show the feasibility and the accuracy of the proposed denoising approach being competitive with the best existing methods for Poisson image denoising. The effectiveness of the proposed denoising approach is thanks to the use of a nonparametric Bayesian estimation in the Contourlet Transform with Sharp Frequency Localization Domain (CTSD) and variance stabilizing transformation (VST). Furthermore, the optimal inverse Anscome transformation to obtain the final estimate of the denoised images, has allowed an accurate tomography reconstruction. The proposed approach provides qualitative information on the 3D distribution of individual chemical elements on the considered sample.

  • Osteogenic potential of heterogeneous and CD271-enriched mesenchymal stromal cells cultured on apatite-wollastonite 3D scaffolds
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-06-19
    Sylvia Müller; Lyndsey Nicholson; Naif Al Harbi; Elena Mancuso; Elena Jones; Anne Dickinson; Xiao Nong Wang; Kenneth Dalgarno

    Mesenchymal stromal cells (MSCs) are widely used in clinical trials for bone repair and regeneration. Despite previous evidence showing a prominent osteogenic potential of 2D cultured CD271 enriched MSCs, the osteogenic potential of CD271 enriched cells cultured on 3D scaffold is unknown. Apatite-wollastonite glass ceramic (A-W) is an osteoconductive biomaterial shown to be compatible with MSCs. This is the first study comparing the attachment, growth kinetics, and osteogenic potential of two MSC populations, namely heterogeneous plastic adherence MSCs (PA-MSCs) and CD271-enriched MSCs (CD271-MSCs), when cultured on A-W 3D scaffold. The paired MSC populations were assessed for their attachment, growth kinetics and ALP activity using confocal and scanning electron microscopy and the quantifications of DNA contents and p-nitrophenyl (pNP) production respectively. While the PA-MSCs and CD271-MSCs had similar expansion and tri-lineage differentiation capacity during standard 2D culture, they showed different proliferation kinetics when seeded on the A-W scaffolds. PA-MSCs displayed a well-spread attachment with more elongated morphology compared to CD271-MSCs, signifying a different level of interaction between the cell populations and the scaffold surface. Following scaffold seeding PA-MSCs fully integrated into the scaffold surface and showed a stronger propensity for osteogenic differentiation as indicated by higher ALP activity than CD271-MSCs. Furthermore, A-W scaffold seeded uncultured non-enriched bone marrow mononuclear cells also demonstrated a higher proliferation rate and greater ALP activity compared to their CD271-enriched counterpart. Our findings suggest that CD271-positive enrichment of a population is not beneficial for osteogenesis when the cells are seeded on A-W scaffold. Furthermore, unselected heterogeneous MSCs or BM-MNCs are more promising for A-W scaffold based bone regeneration. This leads to a conclusion of broader clinical relevance for tissue engineering: on the basis of our observations here the osteogenic potential observed in 2D cell culture should not be considered indicative of likely performance in a 3D scaffold based system, even when one of the cell populations is effectively a subset of the other.

  • A high content, phenotypic ‘scar-in-a-jar’ assay for rapid quantification of collagen fibrillogenesis using disease-derived pulmonary fibroblasts
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-06-28
    Robert B. Good; Jessica D. Eley; Elaine Gower; Genevieve Butt; Andrew D. Blanchard; Andrew J. Fisher; Carmel B. Nanthakumar

    Excessive extracellular matrix (ECM) deposition is a hallmark feature in fibrosis and tissue remodelling diseases. Typically, mesenchymal cells will produce collagens under standard 2D cell culture conditions, however these do not assemble into fibrils. Existing assays for measuring ECM production are often low throughput and not disease relevant. Here we describe a robust, high content, pseudo-3D phenotypic assay to quantify mature fibrillar collagen deposition which is both physiologically relevant and amenable to high throughput compound screening. Using pulmonary fibroblasts derived from patients with idiopathic pulmonary fibrosis (IPF), we developed the ‘scar-in-a-jar’ assay into a medium-throughput phenotypic assay to robustly quantify collagen type I deposition and other extracellular matrix (ECM) proteins over 72 h. This assay utilises macromolecular crowding to induce an excluded volume effect and enhance enzyme activity, which in combination with TGF-β1 stimulation significantly accelerates ECM production. Collagen type I is upregulated approximately 5-fold with a negligible effect on cell number. We demonstrate the robustness of the assay achieving a Z prime of approximately 0.5, and % coefficient of variance (CV) of < 5 for the assay controls SB-525334 (ALK5 inhibitor) and CZ415 (mTOR inhibitor). This assay has been used to confirm the potency of a number of potential anti-fibrotic agents. Active compounds from the ‘scar-in-a-jar’ assay can be further validated for other markers of ECM deposition and fibroblast activation such as collagen type IV and α-smooth muscle actin exhibiting a 4-fold and 3-fold assay window respectively. In conclusion, we have developed ‘scar -in-a-jar is’ into a robust disease-relevant medium-throughput in vitro assay to accurately quantify ECM deposition. This assay may enable iterative compound profiling for IPF and other fibroproliferative and tissue remodelling diseases.

  • Overcoming the limitations of locally administered oncolytic virotherapy
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-07-01
    JinWoo Hong; Chae-Ok Yun

    Adenovirus (Ad) has been most extensively evaluated gene transfer vector in clinical trials due to facile production in high viral titer, highly efficient transduction, and proven safety record. Similarly, an oncolytic Ad, which replicates selectively in cancer cells through genetic modifications, is actively being evaluated in various phases of clinical trials as a promising next generation therapeutic against cancer. Most of these trials with oncolytic Ads to date have employed intratumoral injection as the standard administration route. Although these locally administered oncolytic Ads have shown promising outcomes, the therapeutic efficacy is not yet optimal due to poor intratumoral virion retention, nonspecific shedding of virion to normal organs, variable infection efficacy due to heterogeneity of tumor cells, adverse antiviral immune response, and short biological activity of oncolytic viruses in situ. These inherent problems associated with locally administered Ad also holds true for other oncolytic viral vectors. Thus, this review will aim to discuss various nanomaterial-based delivery strategies to improve the intratumoral administration efficacy of oncolytic Ad as well as other types of oncolytic viruses.

  • Skin substitutes are more potent than dermal or epidermal substitutes in stimulating endothelial cell sprouting
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-07-17
    Hanneke N. Monsuur; Ester M. Weijers; Susan Gibbs; Lenie J. van den Broek

    Therapy resistant ulcers are wounds that remain open for a long time period and often arise from chronic venous disease, prolonged pressure or diabetes. For healing of chronic wounds, revitalization of the inert wound bed, which is achieved by angiogenic sprouting of new blood vessels is of great importance. An alternative treatment option to conventional therapies is the use of skin substitutes: dermal (DS), epidermal (ES) or bi-layered skin substitutes (SS). The aim of this study was to determine the mode of action of an autologous SS, ES and DS with regards to endothelial cell proliferation, migration and angiogenic sprouting into a fibrin hydrogel. SS consists of a fully differentiated epidermis expanding over the acellular donor dermis (AD) which has become repopulated with fibroblasts. DS is the same construct as SS but without the epidermis and ES is the same construct as SS but without the fibroblasts. As a control, AD was used throughout. It was found that the bi-layered SS was the most potent substitute in inducing migration and sprouting of endothelial cells. The cross talk between dermis and epidermis resulted in the strongest induction of sprouting via VEGF and uPAR. ES stimulated sprouting more than DS again via VEGF and uPAR. The slight induction of sprouting mediated by DS was not mediated by VEGF, but was in part stimulated through uPAR. This in vitro study supports our clinical observations that a bi-layered SS is a strong stimulator of angiogenesis and therefore has the potential to revitalize an inert wound bed.

  • Perfusion culture maintained with an air-liquid interface to stimulate epithelial cell organization in renal organoids in vitro
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-07-23
    Sachiko Sekiya; Tetsutaro Kikuchi; Tatsuya Shimizu

    Organoids derived from induced pluripotent stem (iPS) or embryonic stem (ES) cells have been evaluated as in vitro models of development and disease. However, maintaining these cells under long-term static culture conditions is difficult because of nutrition shortages and waste accumulation. To overcome these issues, perfusion culture systems are required for organoid technology. A system with a stable microenvironment, nutrient availability, and waste removal will accelerate organoid generation. The aim of this study was to develop a novel perfusion system for renal organoids by maintaining the air-liquid interface with a device fabricated using a 3D printer. Our results revealed slow flow at the organoid cultivation area based on microbead movement on the membrane, which depended on the perfusion rate under the membrane. Moreover, the perfused culture medium below the organoids via a porous membrane diffused throughout the organoids, maintaining the air-liquid interface. The diffusion rates within organoids were increased according to the flow rate of the culture medium under the membrane. The perfused culture medium also stimulated cytoskeletal and basement membrane re-organization associated with promotion tubular formation under 2.5 μL/min flow culture. In contrast, tubules in organoids were diminished at a flow rate of 10 μL/min. Our liquid-air interface perfusion system accelerated organization of the renal organoids. These results suggest that suitable perfusion conditions can accelerate organization of epithelial cells and tissues in renal organoids in vitro.

  • Telemetry-controlled simultaneous stimulation-and-recording device (SRD) to study interhemispheric cortical circuits in rat primary somatosensory (SI) cortex
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-08-08
    John T. Ramshur; Bashir I. Morshed; Amy L. de Jongh Curry; Robert S. Waters

    A growing need exists for neuroscience platforms that can perform simultaneous chronic recording and stimulation of neural tissue in animal models in a telemetry-controlled fashion with signal processing for analysis of the chronic recording data and external triggering capability. We describe the system design, testing, evaluation, and implementation of a wireless simultaneous stimulation-and-recording device (SRD) for modulating cortical circuits in physiologically identified sites in primary somatosensory (SI) cortex in awake-behaving and freely-moving rats. The SRD was developed using low-cost electronic components and open-source software. The function of the SRD was assessed by bench and in-vivo testing. The SRD recorded spontaneous spiking and bursting neuronal activity, evoked responses to programmed intracortical microstimulation (ICMS) delivered internally by the SRD, and evoked responses to external peripheral forelimb stimulation. The SRD is capable of wireless stimulation and recording on a predetermined schedule or can be wirelessly synchronized with external input as would be required in behavioral testing prior to, during, and following ICMS.

  • Treadmill training augmented with real-time visualisation feedback and function electrical stimulation for gait rehabilitation after stroke: a feasibility study
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-08-22
    Chanwit Phongamwong; Philip Rowe; Karen Chase; Andrew Kerr; Lindsay Millar

    Stroke rehabilitation often uses the motor relearning concept that require patients to perform active practice of skill-specific training and to receive feedback. Treadmill training augmented with real-time visualisation feedback and functional electrical stimulation may have a beneficial synergistic effect on motor recovery. This study aims to determine the feasibility of this kind of enhanced treadmill training for gait rehabilitation among patients after stroke. A system for dynamic visualisation of lower-limb movement based on 3-dimentional motion capture and a computer timed functional electrical stimulation system was developed. Participants received up to 20-min enhanced treadmill training instead of their over-ground gait training once or twice a week for 6 weeks at Coathill hospital, Lanarkshire, United Kingdom. Number of training sessions attended, and training duration were used to assess feasibility. Ankle kinematics in the sagittal plane of walking with and without functional electrical stimulation support of the pre-tibial muscles were also compared and used to confirm the functional electrical stimulation was triggered at the targeted time. Six patients after stroke participated in the study. The majority of participants were male (5/6) with a age range from 30 to 84 years and 4/6 had left hemiplegia. All participants suffered from brain infarction and were at least 3 months after stroke. Number of training sessions attended ranged from 5 to 12. The duration of training sessions ranged from 11 to 20 min. No serious adverse events were reported. The computerised functional electrical stimulation to the pre-tibial muscles was able to reduce plantarflexion angle during the swing phase with statistical significance (p = 0.015 at 80%; p = 0.008 at 90 and 100% of the gait cycle). It is safe and feasible to use treadmill gait training augmented with real-time visual feedback and computer-controlled functional electrical stimulation with patients after stroke in routine clinical practice. NCT03348215. Registered 20 November 2017.

  • User perspective and higher cognitive task-loads influence movement and performance in immersive training environments
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-08-30
    Juan Trelles Trabucco; Andrea Rottigni; Marco Cavallo; Daniel Bailey; James Patton; G. Elisabeta Marai

    In virtual reality (VR) applications such as games, virtual training, and interactive neurorehabilitation, one can employ either the first-person user perspective or the third-person perspective to perceive the virtual environment; however, applications rarely offer both perspectives for the same task. We used a targeted-reaching task in a large-scale virtual reality environment (N=30 healthy volunteers) to evaluate the effects of user perspective on the head and upper extremity movements, and on user performance. We further evaluated how different cognitive challenges would modulate these effects. Finally, we obtained the user-reported engagement level under the different perspectives. We found that first-person perspective resulted in larger head movements (3.52±1.3m) than the third-person perspective (2.41±0.7m). First-person perspective also resulted in more upper-extremity movement (30.08±7.28m compared to 26.66±4.86m) and longer completion times (61.3±16.4s compared to 53±10.4s) for more challenging tasks such as the “flipped mode”, in which moving one arm causes the opposite virtual arm to move. We observed no significant effect of user perspective alone on the success rate. Subjects reported experiencing roughly the same level of engagement in both first-person and third-person perspectives (F(1.58)=0.9,P=.445). User perspective and its interaction with higher-cognitive load tasks influences the extent of movement and user performance in a virtual theater environment, and may influence the choice of the interface type (first or third person) in immersive training depending on the user conditions and exercise requirements.

  • Human motor decoding from neural signals: a review
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-09-03
    Wing-kin Tam; Tong Wu; Qi Zhao; Edward Keefer; Zhi Yang

    Many people suffer from movement disability due to amputation or neurological diseases. Fortunately, with modern neurotechnology now it is possible to intercept motor control signals at various points along the neural transduction pathway and use that to drive external devices for communication or control. Here we will review the latest developments in human motor decoding. We reviewed the various strategies to decode motor intention from human and their respective advantages and challenges. Neural control signals can be intercepted at various points in the neural signal transduction pathway, including the brain (electroencephalography, electrocorticography, intracortical recordings), the nerves (peripheral nerve recordings) and the muscles (electromyography). We systematically discussed the sites of signal acquisition, available neural features, signal processing techniques and decoding algorithms in each of these potential interception points. Examples of applications and the current state-of-the-art performance were also reviewed. Although great strides have been made in human motor decoding, we are still far away from achieving naturalistic and dexterous control like our native limbs. Concerted efforts from material scientists, electrical engineers, and healthcare professionals are needed to further advance the field and make the technology widely available in clinical use.

  • Detection of stretch reflex onset based on empirical mode decomposition and modified sample entropy
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-09-26
    Mingjia Du; Baohua Hu; Feiyun Xiao; Ming Wu; Zongjun Zhu; Yong Wang

    Accurate spasticity assessment provides an objective evaluation index for the rehabilitation treatment of patients with spasticity, and the key is detecting stretch reflex onset. The surface electromyogram of patients with spasticity is prone to false peaks, and its data length is unstable. These conditions decrease signal differences before and after stretch reflex onset. Therefore, a method for detecting stretch reflex onset based on empirical mode decomposition denoising and modified sample entropy recognition is proposed in this study. The empirical mode decomposition algorithm is better than the wavelet threshold algorithm in denoising surface electromyogram signal. Without adding Gaussian white noise to the electromyogram signal, the stretch reflex onset recognition rate of the electromyogram signal before and after empirical mode decomposition denoising was increased by 56%. In particular, the recognition rate of stretch reflex onset under the optimal parameter of the modified sample entropy can reach up to 100% and the average recognition rate is 93%. The empirical mode decomposition algorithm can eliminate the baseline activity of the surface electromyogram signal before stretch reflex onset and effectively remove noise from the signal. The identification of stretch reflex onset using combined empirical mode decomposition and modified sample entropy is better than that via modified sample entropy alone, and stretch reflex onset can be accurately determined.

  • Lights, camera, path splitter: a new approach for truly simultaneous dual optical mapping of the heart with a single camera
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-09-27
    Rafael Jaimes; Damon McCullough; Bryan Siegel; Luther Swift; James Hiebert; Daniel McInerney; Nikki Gillum Posnack

    Optical mapping of transmembrane voltage and intracellular calcium is a powerful tool for investigating cardiac physiology and pathophysiology. However, simultaneous dual mapping of two fluorescent probes remains technically challenging. We introduce a novel, easy-to-use approach that requires a path splitter, single camera and excitation light to simultaneously acquire voltage and calcium signals from whole heart preparations, which can be applied to other physiological models – including neurons and isolated cardiomyocytes. Complementary probes were selected that could be excited with a single wavelength light source. Langendorff-perfused hearts (rat, swine) were stained and imaged using a sCMOS camera outfitted with an optical path splitter to simultaneously acquire two emission fields at high spatial and temporal resolution. Voltage (RH237) and calcium (Rhod2) signals were acquired concurrently on a single sensor, resulting in two 384 × 256 images at 814 frames per second. At this frame rate, the signal-to-noise ratio was 47 (RH237) and 85 (Rhod2). Imaging experiments were performed on small rodent hearts, as well as larger pig hearts with sufficient optical signals. In separate experiments, each dye was used independently to assess crosstalk and demonstrate signal specificity. Additionally, the effect of ryanodine on myocardial calcium transients was validated – with no measurable effect on the amplitude of optical action potentials. To demonstrate spatial resolution, ventricular tachycardia was induced –resulting in the novel finding that spatially discordant calcium alternans can be present in different regions of the heart, even when electrical alternans remain concordant. The described system excels in providing a wide field of view and high spatiotemporal resolution for a variety of cardiac preparations. We report the first multiparametric mapping system that simultaneously acquires calcium and voltage signals from cardiac preparations, using a path splitter, single camera and excitation light. This approach eliminates the need for multiple cameras, excitation light patterning or frame interleaving. These features can aid in the adoption of dual mapping technology by the broader cardiovascular research community, and decrease the barrier of entry into panoramic heart imaging, as it reduces the number of required cameras.

  • Technical feasibility of constant-load and high-intensity interval training for cardiopulmonary conditioning using a re-engineered dynamic leg press
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-10-03
    Farouk Chrif; Tobias Nef; Kenneth J Hunt

    Leg-press devices are one of the most widely used training tools for musculoskeletal strengthening of the lower-limbs, and have demonstrated important cardiopulmonary benefits for healthy and patient populations. Further engineering development was done on a dynamic leg-press for work-rate estimation by integrating force and motion sensors, power calculation and a visual feedback system for volitional work-rate control. This study aimed to assess the feasibility of the enhanced dynamic leg press for cardiopulmonary exercise training in constant-load training and high-intensity interval training. Five healthy participants aged 31.0±3.9 years (mean ± standard deviation) performed two cardiopulmonary training sessions: constant-load training and high-intensity interval training. Participants carried out the training sessions at a work rate that corresponds to their first ventilatory threshold for constant-load training, and their second ventilatory threshold for high-intensity interval training. All participants tolerated both training protocols, and could complete the training sessions with no complications. Substantial cardiopulmonary responses were observed. The difference between mean oxygen uptake and target oxygen uptake was 0.07±0.34 L/min (103 ±17%) during constant-load training, and 0.35±0.66 L/min (113 ±27%) during high-intensity interval training. The difference between mean heart rate and target heart rate was −7±19 bpm (94 ±15%) during constant-load training, and 4.2±16 bpm (103 ±12%) during high-intensity interval training. The enhanced dynamic leg press was found to be feasible for cardiopulmonary exercise training, and for exercise prescription for different training programmes based on the ventilatory thresholds.

  • An automatic nuclei segmentation method based on deep convolutional neural networks for histopathology images
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-10-17
    Hwejin Jung; Bilal Lodhi; Jaewoo Kang

    Since nuclei segmentation in histopathology images can provide key information for identifying the presence or stage of a disease, the images need to be assessed carefully. However, color variation in histopathology images, and various structures of nuclei are two major obstacles in accurately segmenting and analyzing histopathology images. Several machine learning methods heavily rely on hand-crafted features which have limitations due to manual thresholding. To obtain robust results, deep learning based methods have been proposed. Deep convolutional neural networks (DCNN) used for automatically extracting features from raw image data have been proven to achieve great performance. Inspired by such achievements, we propose a nuclei segmentation method based on DCNNs. To normalize the color of histopathology images, we use a deep convolutional Gaussian mixture color normalization model which is able to cluster pixels while considering the structures of nuclei. To segment nuclei, we use Mask R-CNN which achieves state-of-the-art object segmentation performance in the field of computer vision. In addition, we perform multiple inference as a post-processing step to boost segmentation performance. We evaluate our segmentation method on two different datasets. The first dataset consists of histopathology images of various organ while the other consists histopathology images of the same organ. Performance of our segmentation method is measured in various experimental setups at the object-level and the pixel-level. In addition, we compare the performance of our method with that of existing state-of-the-art methods. The experimental results show that our nuclei segmentation method outperforms the existing methods. We propose a nuclei segmentation method based on DCNNs for histopathology images. The proposed method which uses Mask R-CNN with color normalization and multiple inference post-processing provides robust nuclei segmentation results. Our method also can facilitate downstream nuclei morphological analyses as it provides high-quality features extracted from histopathology images.

  • In vitro tissue-engineered adipose constructs for modeling disease
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-10-29
    Connor S. Murphy; Lucy Liaw; Michaela R. Reagan

    Adipose tissue is a vital tissue in mammals that functions to insulate our bodies, regulate our internal thermostat, protect our organs, store energy (and burn energy, in the case of beige and brown fat), and provide endocrine signals to other organs in the body. Tissue engineering of adipose and other soft tissues may prove essential for people who have lost this tissue from trauma or disease. In this review, we discuss the applications of tissue-engineered adipose tissue specifically for disease modeling applications. We provide a basic background to adipose depots and describe three-dimensional (3D) in vitro adipose models for obesity, diabetes, and cancer research applications. The approaches to engineering 3D adipose models are diverse in terms of scaffold type (hydrogel-based, silk-based and scaffold-free), species of origin (H. sapiens and M. musculus) and cell types used, which allows researchers to choose a model that best fits their application, whether it is optimization of adipocyte differentiation or studying the interaction of adipocytes and other cell types like endothelial cells. In vitro 3D adipose tissue models support discoveries into the mechanisms of adipose-related diseases and thus support the development of novel anti-cancer or anti-obesity/diabetes therapies.

  • Determination of physiological parameters for endogenous glucose production in individuals using diurnal data
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-11-15
    Mariël F. van Stee; Shaji Krishnan; Albert K. Groen; Albert A. de Graaf

    Triple tracer meal experiments used to investigate organ glucose-insulin dynamics, such as endogenous glucose production (EGP) of the liver are labor intensive and expensive. A procedure was developed to obtain individual liver related parameters to describe EGP dynamics without the need for tracers. The development used an existing formula describing the EGP dynamics comprising 4 parameters defined from glucose, insulin and C-peptide dynamics arising from triple meal studies. The method employs a set of partial differential equations in order to estimate the parameters for EGP dynamics. Tracer-derived and simulated data sets were used to develop and test the procedure. The predicted EGP dynamics showed an overall mean R2 of 0.91. In summary, a method was developed for predicting the hepatic EGP dynamics for healthy, pre-diabetic, and type 2 diabetic individuals without applying tracer experiments.

  • A portable assist-as-need upper-extremity hybrid exoskeleton for FES-induced muscle fatigue reduction in stroke rehabilitation
    BMC Biomed. Eng. (IF 0) Pub Date : 2019-11-19
    Ashley Stewart; Christopher Pretty; Xiaoqi Chen

    Hybrid exoskeletons are a recent development which combine Functional Electrical Stimulation with actuators to improve both the mental and physical rehabilitation of stroke patients. Hybrid exoskeletons have been shown capable of reducing the weight of the actuator and improving movement precision compared to Functional Electrical Stimulation alone. However little attention has been given towards the ability of hybrid exoskeletons to reduce and manage Functional Electrical Stimulation induced fatigue or towards adapting to user ability. This work details the construction and testing of a novel assist-as-need upper-extremity hybrid exoskeleton which uses model-based Functional Electrical Stimulation control to delay Functional Electrical Stimulation induced muscle fatigue. The hybrid control is compared with Functional Electrical Stimulation only control on a healthy subject. The hybrid system produced 24° less average angle error and 13.2° less Root Mean Square Error, than Functional Electrical Stimulation on its own and showed a reduction in Functional Electrical Stimulation induced fatigue. As far as the authors are aware, this is the study which provides evidence of the advantages of hybrid exoskeletons compared to use of Functional Electrical Stimulation on its own with regards to the delay of Functional Electrical Stimulation induced muscle fatigue.

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上海纽约大学William Glover