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by Keyword: Trial

Blanco-Fernandez, B, Ibanez-Fonesca, A, Orbanic, D, Ximenes-Carballo, C, Perez-Amodio, S, Rodriguez-Cabello, JC, Engel, E, (2023). Elastin-like Recombinamer Hydrogels as Platforms for Breast Cancer Modeling Biomacromolecules 24, 4408-4418

The involvement of the extracellular matrix (ECM) in tumor progression has motivated the development of biomaterials mimicking the tumor ECM to develop more predictive cancer models. Particularly, polypeptides based on elastin could be an interesting approach to mimic the ECM due to their tunable properties. Here, we demonstrated that elastin-like recombinamer (ELR) hydrogels can be suitable biomaterials to develop breast cancer models. This hydrogel was formed by two ELR polypeptides, one containing sequences biodegradable by matrix metalloproteinase and cyclooctyne and the other carrying arginylglycylaspartic acid and azide groups to allow cell adhesion, biodegradability, and suitable stiffness through "click-chemistry" cross-linking. Our findings show that breast cancer or nontumorigenic breast cells showed high viability and cell proliferation for up to 7 days. MCF7 and MCF10A formed spheroids whereas MDA-MB-231 formed cell networks, with the expression of ECM and high drug resistance in all cases, evidencing that ELR hydrogels are a promising biomaterial for breast cancer modeling.

JTD Keywords: clinical-trials, collagen i, discovery, mcf-7 cells, phenotype, progression, spheroids, translation, tumor microenvironment, Extracellular-matrix


Bartova, S, Madrid-Gambin, F, Fernandez, L, Carayol, J, Meugnier, E, Segrestin, B, Delage, P, Vionnet, N, Boizot, A, Laville, M, Vidal, H, Marco, S, Hager, J, Moco, S, (2022). Grape polyphenols decrease circulating branched chain amino acids in overfed adults Front Nutr 9, 998044

Introduction and aimsDietary polyphenols have long been associated with health benefits, including the prevention of obesity and related chronic diseases. Overfeeding was shown to rapidly induce weight gain and fat mass, associated with mild insulin resistance in humans, and thus represents a suitable model of the metabolic complications resulting from obesity. We studied the effects of a polyphenol-rich grape extract supplementation on the plasma metabolome during an overfeeding intervention in adults, in two randomized parallel controlled clinical trials.MethodsBlood plasma samples from 40 normal weight to overweight male adults, submitted to a 31-day overfeeding (additional 50% of energy requirement by a high calorie-high fructose diet), given either 2 g/day grape polyphenol extract or a placebo at 0, 15, 21, and 31 days were analyzed (Lyon study). Samples from a similarly designed trial on females (20 subjects) were collected in parallel (Lausanne study). Nuclear magnetic resonance (NMR)-based metabolomics was conducted to characterize metabolome changes induced by overfeeding and associated effects from polyphenol supplementation. The clinical trials are registered under the numbers NCT02145780 and NCT02225457 atResultsChanges in plasma levels of many metabolic markers, including branched chain amino acids (BCAA), ketone bodies and glucose in both placebo as well as upon polyphenol intervention were identified in the Lyon study. Polyphenol supplementation counterbalanced levels of BCAA found to be induced by overfeeding. These results were further corroborated in the Lausanne female study.ConclusionAdministration of grape polyphenol-rich extract over 1 month period was associated with a protective metabolic effect against overfeeding in adults.

JTD Keywords: branched chain amino acids, grape polyphenols, human trials, metabolism, metabolomics, nmr, obesity, Branched chain amino acids, Grape polyphenols, Human trials, Metabolism, Metabolomics, Nmr, Obesity, Overfeeding


Monteil, V, Eaton, B, Postnikova, E, Murphy, M, Braunsfeld, B, Crozier, I, Kricek, F, Niederhofer, J, Schwarzbock, A, Breid, H, Devignot, S, Klingstrom, J, Thalin, C, Kellner, MJ, Christ, W, Havervall, S, Mereiter, S, Knapp, S, Jimenez, AS, Bugajska-Schretter, A, Dohnal, A, Ruf, C, Gugenberger, R, Hagelkruys, A, Montserrat, N, Kozieradzki, I, Ali, OH, Stadlmann, J, Holbrook, MR, Schmaljohn, C, Oostenbrink, C, Shoemaker, RH, Mirazimi, A, Wirnsberger, G, Penninger, JM, (2022). Clinical grade ACE2 as a universal agent to block SARS-CoV-2 variants Embo Molecular Medicine 14, e15230

The recent emergence of multiple SARS-CoV-2 variants has caused considerable concern due to both reduced vaccine efficacy and escape from neutralizing antibody therapeutics. It is, therefore, paramount to develop therapeutic strategies that inhibit all known and future SARS-CoV-2 variants. Here, we report that all SARS-CoV-2 variants analyzed, including variants of concern (VOC) Alpha, Beta, Gamma, Delta, and Omicron, exhibit enhanced binding affinity to clinical grade and phase 2 tested recombinant human soluble ACE2 (APN01). Importantly, soluble ACE2 neutralized infection of VeroE6 cells and human lung epithelial cells by all current VOC strains with markedly enhanced potency when compared to reference SARS-CoV-2 isolates. Effective inhibition of infections with SARS-CoV-2 variants was validated and confirmed in two independent laboratories. These data show that SARS-CoV-2 variants that have emerged around the world, including current VOC and several variants of interest, can be inhibited by soluble ACE2, providing proof of principle of a pan-SARS-CoV-2 therapeutic.

JTD Keywords: clinical trial, covid-19, treatment, Clinical trial, Converting enzyme 2, Covid-19, Spike, Treatment, Vaccine


Chattopadhyay, P, Magdanz, V, Hernandez-Melia, M, Borchert, KBL, Schwarz, D, Simmchen, J, (2022). Size-Dependent Inhibition of Sperm Motility by Copper Particles as a Path toward Male Contraception Advanced Nanobiomed Research 2, 2100152

Effective inhibition of sperm motility using a spermicide can be a promising approach in developing non-invasive male contraceptive agents. Copper is known to have contraceptive properties and has been used clinically for decades as intrauterine contraceptive devices (IUDs) for contraception in females. Beyond that, the spermicidal use of copper is not explored much further, even though its use can also subdue the harmful effects caused by the hormonal female contraceptive agents on the environment. Herein, the size, concentration, and time-dependent in vitro inhibition of bovine spermatozoa by copper microparticles are studied. The effectivity in inhibiting sperm motility is correlated with the amount of Cu2+ ions released by the particles during incubation. The copper particles cause direct suppression of sperm motility and viability upon incubation and thereby show potential as sperm-inhibiting, hormone-free candidate for male contraception. In addition, biocompatibility tests using a cervical cell line help optimizing the size and concentration of the copper particles for the best spermicidal action while avoiding toxicity to the surrounding tissue.

JTD Keywords: Bovine spermatozoa, Clinical-trial, Copper, Human-spermatozoa, Ions, Male contraception, Metallic copper, Microparticles, Progestins, Sperm motility, Sperm viability, Spermicide, Viability


Mura, A, Maier, M, Ballester, BR, Costa, JD, Lopez-Luque, J, Gelineau, A, Mandigout, S, Ghatan, PH, Fiorillo, R, Antenucci, F, Coolen, T, Chivite, I, Callen, A, Landais, H, Gomez, OI, Melero, C, Brandi, S, Domenech, M, Daviet, JC, Zucca, R, Verschure, PFMJ, (2022). Bringing rehabilitation home with an e-health platform to treat stroke patients: study protocol of a randomized clinical trial (RGS@home) Trials 23, 518

Background: There is a pressing need for scalable healthcare solutions and a shift in the rehabilitation paradigm from hospitals to homes to tackle the increase in stroke incidence while reducing the practical and economic burden for patients, hospitals, and society. Digital health technologies can contribute to addressing this challenge; however, little is known about their effectiveness in at-home settings. In response, we have designed the RGS@home study to investigate the effectiveness, acceptance, and cost of a deep tech solution called the Rehabilitation Gaming System (RGS). RGS is a cloud-based system for delivering Al-enhanced rehabilitation using virtual reality, motion capture, and wearables that can be used in the hospital and at home. The core principles of the brain theory-based RGS intervention are to deliver rehabilitation exercises in the form of embodied, goal-oriented, and task-specific action.; Methods: The RGS@home study is a randomized longitudinal clinical trial designed to assess whether the combination of the RGS intervention with standard care is superior to standard care alone for the functional recovery of stroke patients at the hospital and at home. The study is conducted in collaboration with hospitals in Spain, Sweden, and France and includes inpatients and outpatients at subacute and chronic stages post-stroke. The intervention duration is 3 months with assessment at baseline and after 3, 6, and 12 months. The impact of RGS is evaluated in terms of quality of life measurements, usability, and acceptance using standardized clinical scales, together with health economic analysis. So far, one-third of the patients expected to participate in the study have been recruited (N = 90, mean age 60, days after stroke >= 30 days). The trial will end in July 2023.; Discussion: We predict an improvement in the patients' recovery, high acceptance, and reduced costs due to a soft landing from the clinic to home rehabilitation. In addition, the data provided will allow us to assess whether the prescription of therapy at home can counteract deterioration and improve quality of life while also identifying new standards for online and remote assessment, diagnostics, and intervention across European hospitals.

JTD Keywords: deep tech, e-health, home treatment, motor recovery, randomized clinical trial, stroke, upper extremities, virtual reality, Deep tech, E-health, Functional recovery, Home treatment, Motor recovery, Randomized clinical trial, Stroke, Upper extremities, Virtual reality, Wearables


English, C, Ceravolo, MG, Dorsch, S, Drummond, A, Gandhi, DBC, Green, JH, Schelfaut, B, Verschure, P, Urimubenshi, G, Savitz, S, (2022). Telehealth for rehabilitation and recovery after stroke: State of the evidence and future directions International Journal Of Stroke 17, 487-493

Aims: The aim of this rapid review and opinion paper is to present the state of the current evidence and present future directions for telehealth research and clinical service delivery for stroke rehabilitation. Methods: We conducted a rapid review of published trials in the field. We searched Medline using key terms related to stroke rehabilitation and telehealth or virtual care. We also searched clinical trial registers to identify key ongoing trials. Results: The evidence for telehealth to deliver stroke rehabilitation interventions is not strong and is predominantly based on small trials prone to Type 2 error. To move the field forward, we need to progress to trials of implementation that include measures of adoption and reach, as well as effectiveness. We also need to understand which outcome measures can be reliably measured remotely, and/or develop new ones. We present tools to assist with the deployment of telehealth for rehabilitation after stroke. Conclusion: The current, and likely long-term, pandemic means that we cannot wait for stronger evidence before implementing telehealth. As a research and clinical community, we owe it to people living with stroke internationally to investigate the best possible telehealth solutions for providing the highest quality rehabilitation.

JTD Keywords: rehabilitation, telehealth, Care, Feasibility, Rehabilitation, Telehealth, Trial, Virtual care


McGill, K, Sackley, C, Godwin, J, Gavaghan, D, Ali, M, Ballester, BR, Brady, MC, (2022). Using the Barthel Index and modified Rankin Scale as Outcome Measures for Stroke Rehabilitation Trials; A Comparison of Minimum Sample Size Requirements Journal Of Stroke & Cerebrovascular Diseases 31, 106229

Underpowered trials risk inaccurate results. Recruitment to stroke rehabilitation randomised controlled trials (RCTs) is often a challenge. Statistical simulations offer an important opportunity to explore the adequacy of sample sizes in the context of specific outcome measures. We aimed to examine and compare the adequacy of stroke rehabilitation RCT sample sizes using the Barthel Index (BI) or modified Rankin Scale (mRS) as primary outcomes.We conducted computer simulations using typical experimental event rates (EER) and control event rates (CER) based on individual participant data (IPD) from stroke rehabilitation RCTs. Event rates are the proportion of participants who experienced clinically relevant improvements in the RCT experimental and control groups. We examined minimum sample size requirements and estimated the number of participants required to achieve a number needed to treat within clinically acceptable boundaries for the BI and mRS.We secured 2350 IPD (18 RCTs). For a 90% chance of statistical accuracy on the BI a rehabilitation RCT would require 273 participants per randomised group. Accurate interpretation of effect sizes would require 1000s of participants per group. Simulations for the mRS were not possible as a clinically relevant improvement was not detected when using this outcome measure.Stroke rehabilitation RCTs with large sample sizes are required for accurate interpretation of effect sizes based on the BI. The mRS lacked sensitivity to detect change and thus may be unsuitable as a primary outcome in stroke rehabilitation trials.Copyright © 2021 Elsevier Inc. All rights reserved.

JTD Keywords:  , barthel index, design, increasing value, modified rankin scale, randomised controlled trials, recruitment, reducing waste, reliability, sample size calculations, simulations, stroke rehabilitation, Adult, Article, Barthel index, Calculation, Computer simulation, Controlled study, Effect size, Female, Human, Human experiment, Major clinical study, Male, Modified rankin scale, Numbers needed to treat, Outcome assessment, Randomised controlled trials, Randomized controlled trial, Randomized controlled-trials, Rankin scale, Recruitment, Rehabilitation, Sample size, Sample size calculations, Simulations, Stroke rehabilitation


Rial-Hermida, MI, Rey-Rico, A, Blanco-Fernandez, B, Carballo-Pedrares, N, Byrne, EM, Mano, JF, (2021). Recent Progress on Polysaccharide-Based Hydrogels for Controlled Delivery of Therapeutic Biomolecules Acs Biomaterials Science & Engineering 7, 4102-4127

A plethora of applications using polysaccharides have been developed in recent years due to their availability as well as their frequent nontoxicity and biodegradability. These polymers are usually obtained from renewable sources or are byproducts of industrial processes, thus, their use is collaborative in waste management and shows promise for an enhanced sustainable circular economy. Regarding the development of novel delivery systems for biotherapeutics, the potential of polysaccharides is attractive for the previously mentioned properties and also for the possibility of chemical modification of their structures, their ability to form matrixes of diverse architectures and mechanical properties, as well as for their ability to maintain bioactivity following incorporation of the biomolecules into the matrix. Biotherapeutics, such as proteins, growth factors, gene vectors, enzymes, hormones, DNA/RNA, and antibodies are currently in use as major therapeutics in a wide range of pathologies. In the present review, we summarize recent progress in the development of polysaccharide-based hydrogels of diverse nature, alone or in combination with other polymers or drug delivery systems, which have been implemented in the delivery of biotherapeutics in the pharmaceutical and biomedical fields. © 2021 American Chemical Society.

JTD Keywords: biodegradable dextran hydrogels, biotherapeutics, bone morphogenetic protein-2, carrageenan-based hydrogels, chitosan-based hydrogels, controlled delivery, controlled-release, cross-linked hydrogels, growth-factor delivery, hydrogels, in-vitro characterization, polysaccharides, self-healing hydrogel, stimuli-responsiveness, tissue engineering, Antibodies, Bioactivity, Biodegradability, Biomedical fields, Biomolecules, Biotherapeutics, Chemical modification, Circular economy, Controlled delivery, Controlled drug delivery, Delivery systems, Drug delivery system, Functional polymers, Hyaluronic-acid hydrogels, Hydrogels, Industrial processs, Polysaccharides, Recent progress, Renewable sources, Stimuli-responsiveness, Targeted drug delivery, Tissue engineering, Waste management


Ojosnegros, S, Seriola, A, Godeau, AL, Veiga, A, (2021). Embryo implantation in the laboratory: an update on current techniques Human Reproduction Update 27, 501-530

BACKGROUND: The embryo implantation process is crucial for the correct establishment and progress of pregnancy. During implantation, the blastocyst trophectoderm cells attach to the epithelium of the endometrium, triggering intense cell-to-cell crosstalk that leads to trophoblast outgrowth, invasion of the endometrial tissue, and formation of the placenta. However, this process, which is vital for embryo and foetal development in utero, is still elusive to experimentation because of its inaccessibility. Experimental implantation is cumbersome and impractical in adult animal models and is inconceivable in humans. OBJECTIVE AND RATIONALE: A number of custom experimental solutions have been proposed to recreate different stages of the implantation process in vitro, by combining a human embryo (or a human embryo surrogate) and endometrial cells (or a surrogate for the endometrial tissue). In vitro models allow rapid high-throughput interrogation of embryos and cells, and efficient screening of molecules, such as cytokines, drugs, or transcription factors, that control embryo implantation and the receptivity of the endometrium. However, the broad selection of available in vitro systems makes it complicated to decide which system best fits the needs of a specific experiment or scientific question. To orient the reader, this review will explore the experimental options proposed in the literature, and classify them into amenable categories based on the embryo/cell pairs employed. The goal is to give an overview of the tools available to study the complex process of human embryo implantation, and explain the differences between them, including the advantages and disadvantages of each system. SEARCH METHODS: We performed a comprehensive review of the literature to come up with different categories that mimic the different stages of embryo implantation in vitro, ranging from initial blastocyst apposition to later stages of trophoblast invasion or gastrulation. We will also review recent breakthrough advances on stem cells and organoids, assembling embryo-like structures and endometrial tissues. OUTCOMES: We highlight the most relevant systems and describe the most significant experiments. We focus on in vitro systems that have contributed to the study of human reproduction by discovering molecules that control implantation, including hormones, signalling molecules, transcription factors and cytokines. WIDER IMPLICATIONS: The momentum of this field is growing thanks to the use of stem cells to build embryo-like structures and endometrial tissues, and the use of bioengineering to extend the life of embryos in culture. We propose to merge bioengineering methods derived from the fields of stem cells and reproduction to develop new systems covering a wider window of the implantation process.

JTD Keywords: in vitro models, blastocyst, blastocyst-like structures, early-pregnancy, endometrial cells, epidermal-growth-factor, gene-expression, implantation, in vitro models, in-vitro model, indian hedgehog, organoids, receptivity, self-organization, spheroids, trophoblast, trophoblast invasion, uterine receptivity, Blastocyst, Blastocyst-like structures, Early-pregnancy, Endometrial cells, Endometrial stromal cells, Epidermal-growth-factor, Gene-expression, Implantation, In vitro models, In-vitro model, Indian hedgehog, Organoids, Receptivity, Self-organization, Spheroids, Trophoblast, Trophoblast invasion, Uterine receptivity


Burgués, J, Esclapez, MD, Doñate, S, Pastor, L, Marco, S, (2021). Aerial mapping of odorous gases in a wastewater treatment plant using a small drone Remote Sensing 13, 1757

Wastewater treatment plants (WWTPs) are sources of greenhouse gases, hazardous air pollutants and offensive odors. These emissions can have negative repercussions in and around the plant, degrading the quality of life of surrounding neighborhoods, damaging the environment, and reducing employee’s overall job satisfaction. Current monitoring methodologies based on fixed gas detectors and sporadic olfactometric measurements (human panels) do not allow for an accurate spatial representation of such emissions. In this paper we use a small drone equipped with an array of electrochemical and metal oxide (MOX) sensors for mapping odorous gases in a mid-sized WWTP. An innovative sampling system based on two (10 m long) flexible tubes hanging from the drone allowed near-source sampling from a safe distance with negligible influence from the downwash of the drone’s propellers. The proposed platform is very convenient for monitoring hard-toreach emission sources, such as the plant’s deodorization chimney, which turned out to be responsible for the strongest odor emissions. The geo-localized measurements visualized in the form of a two-dimensional (2D) gas concentration map revealed the main emission hotspots where abatement solutions were needed. A principal component analysis (PCA) of the multivariate sensor signals suggests that the proposed system can also be used to trace which emission source is responsible for a certain measurement.

JTD Keywords: air pollution, environmental monitoring, gas sensors, industrial emissions, mapping, odour, uav, Air pollution, Drone, Environmental monitoring, Gas sensors, Industrial emissions, Mapping, Odour, Sensors, Uav


Monteil, V, Dyczynski, M, Lauschke, VM, Kwon, H, Wirnsberger, G, Youhanna, S, Zhang, HB, Slutsky, AS, del Pozo, CH, Horn, M, Montserrat, N, Penninger, JM, Mirazimi, A, (2021). Human soluble ACE2 improves the effect of remdesivir in SARS-CoV-2 infection Embo Molecular Medicine 13, e13426

© 2020 The Authors. Published under the terms of the CC BY 4.0 license There is a critical need for safe and effective drugs for COVID-19. Only remdesivir has received authorization for COVID-19 and has been shown to improve outcomes but not decrease mortality. However, the dose of remdesivir is limited by hepatic and kidney toxicity. ACE2 is the critical cell surface receptor for SARS-CoV-2. Here, we investigated additive effect of combination therapy using remdesivir with recombinant soluble ACE2 (high/low dose) on Vero E6 and kidney organoids, targeting two different modalities of SARS-CoV-2 life cycle: cell entry via its receptor ACE2 and intracellular viral RNA replication. This combination treatment markedly improved their therapeutic windows against SARS-CoV-2 in both models. By using single amino-acid resolution screening in haploid ES cells, we report a singular critical pathway required for remdesivir toxicity, namely, Adenylate Kinase 2. The data provided here demonstrate that combining two therapeutic modalities with different targets, common strategy in HIV treatment, exhibit strong additive effects at sub-toxic concentrations. Our data lay the groundwork for the study of combinatorial regimens in future COVID-19 clinical trials.

JTD Keywords: clinical trial, combination therapy, covid-19, Clinical trial, Combination therapy, Covid-19, Treatment


Burgués, Javier, Marco, Santiago, (2020). Environmental chemical sensing using small drones: A review Science of The Total Environment 748, 141172

Recent advances in miniaturization of chemical instrumentation and in low-cost small drones are catalyzing exponential growth in the use of such platforms for environmental chemical sensing applications. The versatility of chemically sensitive drones is reflected by their rapid adoption in scientific, industrial, and regulatory domains, such as in atmospheric research studies, industrial emission monitoring, and in enforcement of environmental regulations. As a result of this interdisciplinarity, progress to date has been reported across a broad spread of scientific and non-scientific databases, including scientific journals, press releases, company websites, and field reports. The aim of this paper is to assemble all of these pieces of information into a comprehensive, structured and updated review of the field of chemical sensing using small drones. We exhaustively review current and emerging applications of this technology, as well as sensing platforms and algorithms developed by research groups and companies for tasks such as gas concentration mapping, source localization, and flux estimation. We conclude with a discussion of the most pressing technological and regulatory limitations in current practice, and how these could be addressed by future research.

JTD Keywords: Unmanned aircraft systems, Remotely piloted aircraft systems, Chemical sensors, Gas sensors, Environmental monitoring, Industrial emission monitoring


Beiert, T., Tiyerili, V., Knappe, V., Effelsberg, V., Linhart, M., Stöckigt, F., Klein, S., Schierwagen, R., Trebicka, J., Nickenig, G., Schrickel, J. W., Andrié, R. P., (2017). Relaxin reduces susceptibility to post-infarct atrial fibrillation in mice due to anti-fibrotic and anti-inflammatory properties Biochemical and Biophysical Research Communications , 490, (3), 643-649

Background Relaxin-2 (RLX) is a peptide hormone that exerts beneficial anti-fibrotic and anti-inflammatory effects in diverse models of cardiovascular disease. The goal of this study was to determine the effects of RLX treatment on the susceptibility to atrial fibrillation (AF) after myocardial infarction (MI). Methods Mice with cryoinfarction of the left anterior ventricular wall were treated for two weeks with either RLX (75 μg/kg/d) or vehicle (sodium acetate) delivered via subcutaneously implanted osmotic minipumps. Results RLX treatment significantly attenuated the increase in AF-inducibility following cryoinfarction and reduced the mean duration of AF episodes. Furthermore, epicardial mapping of both atria revealed an increase in conduction velocity. In addition to an attenuation of atrial hypertrophy, chronic application of RLX reduced atrial fibrosis, which was linked to a significant reduction in atrial mRNA expression of connective tissue growth factor. Transcript levels of the pro-inflammatory cytokines interleukin-6 and interleukin-1β were reduced in RLX treated mice, but macrophage infiltration into atrial myocardium was similar in the vehicle and RLX treated groups. Conclusion Treatment with RLX in mice after MI reduces susceptibility to AF due to anti-inflammatory and anti-fibrotic properties. Because to these favorable actions, RLX may become a new therapeutic option in the treatment of AF, even when complicating MI.

JTD Keywords: Atrial fibrillation, Atrial fibrosis, Myocardial infarction, Relaxin-2


Giraldo, B. F., Chaparro, J. A., Caminal, P., Benito, S., (2013). Characterization of the respiratory pattern variability of patients with different pressure support levels Engineering in Medicine and Biology Society (EMBC) 35th Annual International Conference of the IEEE , IEEE (Osaka, Japan) , 3849-3852

One of the most challenging problems in intensive care is still the process of discontinuing mechanical ventilation, called weaning process. Both an unnecessary delay in the discontinuation process and a weaning trial that is undertaken too early are undesirable. In this study, we analyzed respiratory pattern variability using the respiratory volume signal of patients submitted to two different levels of pressure support ventilation (PSV), prior to withdrawal of the mechanical ventilation. In order to characterize the respiratory pattern, we analyzed the following time series: inspiratory time, expiratory time, breath duration, tidal volume, fractional inspiratory time, mean inspiratory flow and rapid shallow breathing. Several autoregressive modeling techniques were considered: autoregressive models (AR), autoregressive moving average models (ARMA), and autoregressive models with exogenous input (ARX). The following classification methods were used: logistic regression (LR), linear discriminant analysis (LDA) and support vector machines (SVM). 20 patients on weaning trials from mechanical ventilation were analyzed. The patients, submitted to two different levels of PSV, were classified as low PSV and high PSV. The variability of the respiratory patterns of these patients were analyzed. The most relevant parameters were extracted using the classifiers methods. The best results were obtained with the interquartile range and the final prediction errors of AR, ARMA and ARX models. An accuracy of 95% (93% sensitivity and 90% specificity) was obtained when the interquartile range of the expiratory time and the breath duration time series were used a LDA model. All classifiers showed a good compromise between sensitivity and specificity.

JTD Keywords: autoregressive moving average processes, feature extraction, medical signal processing, patient care, pneumodynamics, signal classification, support vector machines, time series, ARX, autoregressive modeling techniques, autoregressive models with exogenous input, autoregressive moving average model, breath duration time series, classification method, classifier method, discontinuing mechanical ventilation, expiratory time, feature extraction, final prediction errors, fractional inspiratory time, intensive care, interquartile range, linear discriminant analysis, logistic regression analysis, mean inspiratory flow, patient respiratory volume signal, pressure support level, pressure support ventilation, rapid shallow breathing, respiratory pattern variability characterization, support vector machines, tidal volume, weaning trial, Analytical models, Autoregressive processes, Biological system modeling, Estimation, Support vector machines, Time series analysis, Ventilation


Juanola-Feliu, E., Colomer-Farrarons, J., Miribel-Català , P., Samitier, J., Valls-Pasola, J., (2012). Market challenges facing academic research in commercializing nano-enabled implantable devices for in-vivo biomedical analysis Technovation , 32, (3-4), 193-204

This article reports on the research and development of a cutting-edge biomedical device for continuous in-vivo glucose monitoring. This entirely public-funded process of technological innovation has been conducted at the University of Barcelona within a context of converging technologies involving the fields of medicine, physics, chemistry, biology, telecommunications, electronics and energy. The authors examine the value chain and the market challenges faced by in-vivo implantable biomedical devices based on nanotechnologies. In so doing, they trace the process from the point of applied research to the final integration and commercialization of the product, when the social rate of return from academic research can be estimated. Using a case-study approach, the paper also examines the high-tech activities involved in the development of this nano-enabled device and describes the technology and innovation management process within the value chain conducted in a University-Hospital-Industry-Administration-Citizens framework. Here, nanotechnology is seen to represent a new industrial revolution, boosting the biomedical devices market. Nanosensors may well provide the tools required for investigating biological processes at the cellular level in vivo when embedded into medical devices of small dimensions, using biocompatible materials, and requiring reliable and targeted biosensors, high speed data transfer, safely stored data, and even energy autonomy.

JTD Keywords: Biomedical device, Diabetes, Innovation management, Nanobiosensor, Nanotechnology, Research commercialization, Technology transfer, Academic research, Applied research, Barcelona, Biocompatible materials, Biological process, Biomedical analysis, Biomedical devices, Cellular levels, Converging technologies, Glucose monitoring, High-speed data transfer, Implantable biomedical devices, Implantable devices, In-vivo, Industrial revolutions, Innovation management, Medical Devices, Nanobiosensor, Rate of return, Research and development, Technological innovation, Value chains, Biological materials, Biomedical engineering, Biosensors, Commerce, Data transfer, Earnings, Engineering education, Glucose, Implants (surgical), Industrial research, Innovation, Medical problems, Nanosensors, Nanotechnology, Technology transfer, Equipment


Giraldo, B.F., Gaspar, B.W., Caminal, P., Benito, S., (2012). Analysis of roots in ARMA model for the classification of patients on weaning trials Engineering in Medicine and Biology Society (EMBC) 34th Annual International Conference of the IEEE , IEEE (San Diego, USA) , 698-701

One objective of mechanical ventilation is the recovery of spontaneous breathing as soon as possible. Remove the mechanical ventilation is sometimes more difficult that maintain it. This paper proposes the study of respiratory flow signal of patients on weaning trials process by autoregressive moving average model (ARMA), through the location of poles and zeros of the model. A total of 151 patients under extubation process (T-tube test) were analyzed: 91 patients with successful weaning (GS), 39 patients that failed to maintain spontaneous breathing and were reconnected (GF), and 21 patients extubated after the test but before 48 hours were reintubated (GR). The optimal model was obtained with order 8, and statistical significant differences were obtained considering the values of angles of the first four poles and the first zero. The best classification was obtained between GF and GR, with an accuracy of 75.3% on the mean value of the angle of the first pole.

JTD Keywords: Analytical models, Biological system modeling, Computational modeling, Estimation, Hospitals, Poles and zeros, Ventilation, Autoregressive moving average processes, Patient care, Patient monitoring, Pneumodynamics, Poles and zeros, Ventilation, ARMA model, T-tube test, Autoregressive moving average model, Extubation process, Mechanical ventilation, Optimal model, Patient classification, Respiratory flow signal, Roots, Spontaneous breathing, Weaning trials


Amigo, L. E., Fernandez, Q., Giralt, X., Casals, A., Amat, J., (2012). Study of patient-orthosis interaction forces in rehabilitation therapies IEEE Conference Publications 4th IEEE RAS & EMBS International Conference on Biomedical Robotics and Biomechatronics (BioRob) , IEEE (Roma, Italy) , 1098-1103

The design of mechanical joints that kinematically behave as their biological counterparts is a challenge that if not addressed properly can cause inadequate forces transmission between robot and patient. This paper studies the interaction forces in rehabilitation therapies of the elbow joint. To measure the effect of orthosis-patient misalignments, a force sensor with a novel distributed architecture has been designed and used for this study. A test-bed based on an industrial robot acting as a virtual exoskeleton that emulates the action of a therapist has been developed and the interaction forces analyzed.

JTD Keywords: Force, Force measurement, Force sensors, Joints, Medical treatment, Robot sensing systems, Force sensors, Medical robotics, Patient rehabilitation, Biological counterparts, Distributed architecture, Elbow joint, Force sensor, Inadequate forces transmission, Industrial robot, Mechanical joints design, Orthosis-patient misalignments, Patient-orthosis interaction forces, Rehabilitation therapies, Robot, Test-bed, Virtual exoskeleton


Correa, L. S., Laciar, E., Mut, V., Giraldo, B. F., Torres, A., (2010). Multi-parameter analysis of ECG and Respiratory Flow signals to identify success of patients on weaning trials Engineering in Medicine and Biology Society (EMBC) 32nd Annual International Conference of the IEEE , IEEE (Buenos Aires, Argentina) -----, 6070-6073

Statistical analysis, power spectral density, and Lempel Ziv complexity, are used in a multi-parameter approach to analyze four temporal series obtained from the Electrocardiographic and Respiratory Flow signals of 126 patients on weaning trials. In which, 88 patients belong to successful group (SG), and 38 patients belong to failure group (FG), i.e. failed to maintain spontaneous breathing during trial. It was found that mean values of cardiac inter-beat and breath durations give higher values for SG than for FG; Kurtosis coefficient of the spectrum of the rapid shallow breathing index is higher for FG; also Lempel Ziv complexity mean values associated with the respiratory flow signal are bigger for FG. Patients were then classified with a pattern recognition neural network, obtaining 80% of correct classifications (81.6% for FG and 79.5% for SG).

JTD Keywords: Electrocardiography, Medical signal processing, Neural nets, Pattern recognition, Pneumodynamics, Signal classification, Statistical analysis, ECG, Kurtosis coefficient, Lempel Ziv complexity, Breath durations, Cardiac interbeat durations, Electrocardiography, Multiparameter analysis, Pattern recognition neural network, Power spectral density, Respiratory flow signals, Signal classification, Spontaneous breathing, Statistical analysis, Weaning trials


Farre, R., Navajas, D., (2009). Quality control: A necessary, but sometimes overlooked, tool for improving respiratory medicine European Respiratory Journal 33, (4), 722-723

The importance of quality control in both general and respiratory medicine has increased in parallel with the complexity of healthcare provision. Only a few decades ago, the respiratory physician and/or scientist had a very limited number of diagnostic and therapeutic tools available and, moreover, medical practice was based almost exclusively on the personal interaction between doctor and patient. Consequently, at that time the quality of the respiratory healthcare depended entirely on the professional competence of the doctor. Although nowadays the relationship between physician and patient undoubtedly still lies at the heart of respiratory medical practice, the quality of the medical service received by the patient also depends on many other participants in a complex healthcare network: various medical specialists, lung function technicians, nurses, respiratory therapists, social workers and administrative staff. Accordingly, several quality control programmes are applied in order to avoid, or at least to reduce, errors in diagnosis, improper performance of procedures, errors in medication, and failure to supervise or monitor care or recognise complications associated with treatment

JTD Keywords: Airway pressure devices, Clinical-trial, Standardization, Spirometry, Lung, Home, Ventilators, Publication, Performance, Technology