Publications by authors named "Pedro Vieira"

82 Publications

Salvage Surgery after Organ-Preservation - Simply Another Piece of the Puzzle.

Dis Colon Rectum 2021 Feb 18. Epub 2021 Feb 18.

Champalimaud Foundation, Lisbon, Portugal Angelita & Joaquim Gama Institute, Sao Paulo - Brazil University of São Paulo School of Medicine, Colorectal Surgery Division, Sao Paulo - Brazil Ludwig Institute for Cancer Research São Paulo Branch, Sao Paulo - Brazil.

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http://dx.doi.org/10.1097/DCR.0000000000002003DOI Listing
February 2021

Are lesion features reproducible between F-FDG PET/CT images when acquired on analog or digital PET/CT scanners?

Eur Radiol 2020 Oct 30. Epub 2020 Oct 30.

Nuclear Medicine - Radiopharmacology, Champalimaud Centre for the Unknown, Champalimaud Foundation, Av. Brasília, 1400-038, Lisbon, Portugal.

Objectives: To compare lesion features extracted from F-FDG PET/CT images acquired on analog and digital scanners, on consecutive imaging data from the same subjects.

Methods: Whole-body F-FDG PET/CT images from 55 oncological patients were acquired twice after a single F-FDG injection, with a digital and an analog PET/CT scanner, alternately. Twenty-nine subjects were examined first on the digital, and 26 first on the analog equipment. Image reconstruction was performed using manufacturer standard clinical protocols and protocols that fulfilled EARL1 specifications. Twenty-five features based on lesion standardized uptake value (SUV) and geometry were assessed. To compare these features, intraclass correlation coefficient (ICC), relative difference (RD), absolute value of RD (|RD|), and repeatability coefficient (RC) were used.

Results: In total, 323 F-FDG avid lesions were identified. High agreement (ICC > 0.75) was obtained for most of the lesion features pulled out from both scanners' imaging data, especially when reconstruction protocols fulfilled EARL1 specifications. For EARL1 reconstruction images, the features frequently used in clinics, SUV, SUV, SUV, metabolic tumor volume, and total lesion glycolysis, reached an ICC of 0.92, 0.95, 0.87, 0.98, and 0.98, and a median RD (digital-analog) of 3%, 5%, 4%, - 3% and 1%, respectively. Using standard reconstruction protocols, the ICC were 0.84, 0.93, 0.80, 0.98, and 0.98, and the RD were 20%, 11%, 13%, - 7%, and 7%, respectively.

Conclusion: Under controlled acquisition and reconstruction parameters, most of the features studied can be used for research and clinical work. This is especially important for multicenter studies and patient follow-ups.

Key Points: • Using manufacturer standard clinical reconstruction protocols, lesions SUV was significantly higher when using the digital scanner, especially the SUV that was approximately 20% higher. • High agreement was obtained for the majority of the lesion features when using reconstruction protocols that fulfilled EARL1 specifications. • Longitudinal patient studies can be performed interchangeably between digital and analog scanners when both fulfill EARL1 specifications.
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http://dx.doi.org/10.1007/s00330-020-07390-8DOI Listing
October 2020

tACS entrains neural activity while somatosensory input is blocked.

PLoS Biol 2020 10 1;18(10):e3000834. Epub 2020 Oct 1.

Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.

Transcranial alternating current stimulation (tACS) modulates brain activity by passing electrical current through electrodes that are attached to the scalp. Because it is safe and noninvasive, tACS holds great promise as a tool for basic research and clinical treatment. However, little is known about how tACS ultimately influences neural activity. One hypothesis is that tACS affects neural responses directly, by producing electrical fields that interact with the brain's endogenous electrical activity. By controlling the shape and location of these electric fields, one could target brain regions associated with particular behaviors or symptoms. However, an alternative hypothesis is that tACS affects neural activity indirectly, via peripheral sensory afferents. In particular, it has often been hypothesized that tACS acts on sensory fibers in the skin, which in turn provide rhythmic input to central neurons. In this case, there would be little possibility of targeted brain stimulation, as the regions modulated by tACS would depend entirely on the somatosensory pathways originating in the skin around the stimulating electrodes. Here, we directly test these competing hypotheses by recording single-unit activity in the hippocampus and visual cortex of alert monkeys receiving tACS. We find that tACS entrains neuronal activity in both regions, so that cells fire synchronously with the stimulation. Blocking somatosensory input with a topical anesthetic does not significantly alter these neural entrainment effects. These data are therefore consistent with the direct stimulation hypothesis and suggest that peripheral somatosensory stimulation is not required for tACS to entrain neurons.
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http://dx.doi.org/10.1371/journal.pbio.3000834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553316PMC
October 2020

BAGS: An automated Barcode, Audit & Grade System for DNA barcode reference libraries.

Mol Ecol Resour 2021 Feb 28;21(2):573-583. Epub 2020 Oct 28.

Department of Biology, CBMA - Centre of Molecular and Environmental Biology, University of Minho, Braga, Portugal.

Biodiversity studies greatly benefit from molecular tools, such as DNA metabarcoding, which provides an effective identification tool in biomonitoring and conservation programmes. The accuracy of species-level assignment, and consequent taxonomic coverage, relies on comprehensive DNA barcode reference libraries. The role of these libraries is to support species identification, but accidental errors in the generation of the barcodes may compromise their accuracy. Here, we present an R-based application, Barcode, Audit & Grade System (BAGS) (https://github.com/tadeu95/BAGS), that performs automated auditing and annotation of cytochrome c oxidase subunit I (COI) sequences libraries, for a given taxonomic group of animals, available in the Barcode of Life Data System (BOLD). This is followed by implementing a qualitative ranking system that assigns one of five grades (A to E) to each species in the reference library, according to the attributes of the data and congruency of species names with sequences clustered in barcode index numbers (BINs). Our goal is to allow researchers to obtain the most useful and reliable data, highlighting and segregating records according to their congruency. Different tests were performed to perceive its usefulness and limitations. BAGS fulfils a significant gap in the current landscape of DNA barcoding research tools by quickly screening reference libraries to gauge the congruence status of data and facilitate the triage of ambiguous data for posterior review. Thereby, BAGS has the potential to become a valuable addition in forthcoming DNA metabarcoding studies, in the long term contributing to globally improve the quality and reliability of the public reference libraries.
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http://dx.doi.org/10.1111/1755-0998.13262DOI Listing
February 2021

Status and prospects of marine NIS detection and monitoring through (e)DNA metabarcoding.

Sci Total Environ 2021 Jan 18;751:141729. Epub 2020 Aug 18.

Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal; Institute of Science and Innovation for Bio-Sustainability (IB-S), University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.

In coastal ecosystems, non-indigenous species (NIS) are recognized as a major threat to biodiversity, ecosystem functioning and socio-economic activities. Here we present a systematic review on the use of metabarcoding for NIS surveillance in marine and coastal ecosystems, through the analysis of 42 publications. Metabarcoding has been mainly applied to environmental DNA (eDNA) from water samples, but also to DNA extracted from bulk organismal samples. DNA extraction kits have been widely used and the 18S rRNA and the COI genes the most employed markers, but less than half of the studies targeted more than one marker loci. The Illumina MiSeq platform has been used in >50% of the publications. Current weaknesses include potential occurrence of false negatives due to the primer-biased or faulty DNA amplification and the incompleteness of reference libraries. This is particularly concerning in the case of NIS surveillance, where proficiency in species level detection is critical. Until these weaknesses are resolved, ideally NIS metabarcoding should be supported by complementary approaches, such as morphological analysis or more targeted molecular approaches (e.g. qPCR, ddPCR). Even so, metabarcoding has already proved to be a highly sensitive tool to detect small organisms or undifferentiated life stages across a wide taxonomic range. In addition, it also seems to be very effective in ballast water management and to improve the spatial and temporal sampling frequency of NIS surveillance in marine and coastal ecosystems. Although specific protocols may be required for species-specific NIS detection, for general monitoring it would be vital to settle on a standard protocol able to generate comparable results among surveillance campaigns and regions of the globe, seeking the best approach for detecting the broadest range of species, while minimizing the chances of a false positive or negative detection.
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http://dx.doi.org/10.1016/j.scitotenv.2020.141729DOI Listing
January 2021

Preliminary Assays towards Melanoma Cells Using Phototherapy with Gold-Based Nanomaterials.

Nanomaterials (Basel) 2020 Aug 5;10(8). Epub 2020 Aug 5.

Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal.

Cancer like melanoma is a complex disease, for which standard therapies have significant adverse side effects that in most cases are ineffective and highly unspecific. Thus, a new paradigm has come with the need of achieving alternative (less invasive) and effective therapies. In this work, biocompatible gold nanoparticles (GNPs) coated with hyaluronic acid and oleic acid were prepared and characterized in terms of size, morphology and cytotoxicity in the presence of , and two cell lines, the keratinocytes (healthy skin cells, HaCat) and the melanoma cells (B16F10). Results showed that these GNPs absorb within the near-infrared region (750-1400 nm), in the optical therapeutic window (from 650 to 1300 nm), in contrast to other commercial gold nanoparticles, which enables light to penetrate into deep skin layers. A laser emitting in this region was applied and its effect also analyzed. The coated GNPs showed a spherical morphology with a mean size of 297 nm without cytotoxic effects towards yeast and tested cell lines. Nevertheless, after laser irradiation, a reduction of 20% in B16F10 cell line viability was observed. In summary, this work appears to be a promising strategy for the treatment of non-metastatic melanoma or other superficial tumors.
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http://dx.doi.org/10.3390/nano10081536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466595PMC
August 2020

Salvage Surgery With Organ Preservation for Patients With Local Regrowth After Watch and Wait: Is It Still Possible?

Dis Colon Rectum 2020 08;63(8):1053-1062

Champalimaud Foundation, Lisbon, Portugal.

Background: Patients with rectal cancer who achieve complete clinical response after neoadjuvant chemoradiation have been managed nonoperatively. Thirty percent of these patients may develop a local regrowth, and salvage resection with radical surgery is usually recommended. However, selected patients could be offered additional organ preservation by local excision. We hypothesized that patients with baseline T2 who underwent neoadjuvant therapy (for the specific purpose of achieving a complete clinical response) were more likely to harbor recurrent disease at an earlier stage and amenable to organ preservation strategies (local excision) when compared with T3/T4 (undergoing neoadjuvant chemoradiation for oncologic reasons).

Objective: The purpose of this study was to compare patients with local regrowth requiring salvage resection according to their baseline stage.

Design: This was a retrospective review of consecutive patients with nonmetastatic distal rectal cancer undergoing neoadjuvant chemoradiation.

Settings: The study included 2 independent tertiary centers with institutional watch-and-wait organ preservation programs.

Patients: Consecutive patients with distal rectal cancer (cT2-4N1-2M0) managed by watch and wait and local regrowth from 2 institutions were included.

Main Outcomes Measures: Final pathologic features and surgical and oncologic outcomes were compared according to baseline staging.

Results: A total of 73 of 257 patients experienced local regrowth. cT2 presented similar to ypT, ypN, R0, and abdominal perineal resection rates (p > 0.05) at the time of salvage when compared with cT3 to cT4. Patients with cT2 at baseline were more likely to undergo an organ preservation procedure for salvage (56.2% vs 26.5%; p = 0.03). Overall and disease-free survival after salvage were similar between groups irrespective of the type of surgery for the regrowth.

Limitations: Retrospective study, small sample size, and possible inaccurate baseline staging.

Conclusions: Although patients with baseline cT2 rectal cancer had similar pathologic stage at the time of recurrence, these patients were more likely to continue an organ preservation pathway after local regrowth through transanal local excision when compared with cT3 to cT4. Despite differences in the use of radical salvage resection, there were no differences in oncologic outcomes. See Video Abstract at http://links.lww.com/DCR/B254. CIRUGÍA DE RESCATE CON PRESERVACIÓN DE ORGANO PARA PACIENTES CON RECIDIVA LOCAL LUEGO DE WATCH & WAIT: ¿SIGUE SIENDO POSIBLE?: Los pacientes con cáncer rectal que logran una respuesta clínica completa luego de la quimiorradiación neoadyuvante han sido tratados de forma no quirúrgica. El treinta por ciento de estos pacientes pueden desarrollar un nuevo crecimiento local y generalmente se recomienda la resección de rescate con cirugía radical. Sin embargo, en pacientes seleccionados se podría ofrecer la posibilidad de preservación de órgano mediante escisión local. Se formuló la hipótesis de que los pacientes con estadio clinico inicial T2 y sometidos a terapia neoadyuvante (con el propósito específico de lograr una respuesta clínica completa) tenían más probabilidades de presentar una recurrencia local en una etapa más temprana y suceptibles de estrategias de preservación de órgano (escisión local) en comparación con T3 / T4 (sometidos a nCRT por razones oncológicas).Comparar los pacientes con recidiva local que requirieron cirugia de rescate de acuerdo con su estadio inicial.Revisión retrospectiva de pacientes consecutivos con cáncer de recto distal no metastásico sometidos a quimiorradiación neoadyuvante.Dos centros terciarios independientes con programas institucionales de preservación de órgano - Watch & Wait.Pacientes consecutivos con cáncer rectal distal (cT2-4N1-2M0) manejados por Watch & Wait y recidiva local.Las características patológicas finales, los resultados quirúrgicos y oncológicos se compararon de acuerdo con la estadificación inicial.Un total de 73 de 257 pacientes presentaron recidiva local. cT2 presentaron similares ypT, ypN, R0 y tasas de resección abdominoperineal (p>0,05) en el momento del rescate en comparación con cT3-4.Los pacientes con cT2 de base tuvieron más probabilidades de someterse a un procedimiento de preservación de órgano durante el rescate (56,2% frente a 26,5%; p = 0,03). Supervivencia general y DFS después del rescate fueron similares entre los grupos, independientemente del tipo de cirugía para la recidiva.Estudio retrospectivo, tamaño de muestra pequeño, la posible estadificación basal inexacta.Aunque los pacientes con cáncer rectal cT2 de base presentaron estadio patologico similar en el momento de la recidiva, estos pacientes tuvieron más probabilidades de continuar una vía de preservación de órgano luego de una recidiva local a través de la escisión local transanal en comparación con cT3-4. A pesar de las diferencias en el uso de la resección radical de rescate, no hubo diferencias en los resultados oncológicos. Consulte Video Resumen en http://links.lww.com/DCR/B254.
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http://dx.doi.org/10.1097/DCR.0000000000001707DOI Listing
August 2020

Late Primary Palatoplasty in Skeletally Mature Patients: Obstacles and Outcomes.

J Craniofac Surg 2020 Sep;31(6):1544-1546

Institute of Plastic and Craniofacial Surgery, SOBRAPAR Hospital, Campinas.

Background: As the performance of late primary palatoplasty for skeletally mature patients remains controversial, there is little data available regarding speech outcomes for this patient population. The purpose of this study therefore is to identify and evaluate the impact of speech outcomes following late palate repair on skeletally mature patients.

Methods: A retrospective study was performed on 19 consecutive skeletally mature patients who underwent late primary palate repair between 2010 and 2018. Speech assessment was performed preoperatively, between 3 and 6 months postoperatively, and then after 6 months postoperatively. Levels for hypernasality, oral pressure, and audible nasal air emission were scored and recorded.Patients were stratified by age, gender, presence of postoperative fistula, and Veau cleft type, in order to determine the impact of each variable on final speech outcomes. The Kruskal-Wallis test was used to compare the preoperative speech assessment with the postoperative speech outcomes, and the Mann-Whitney test was used to analyze the impact of the above variables on final speech outcomes.

Results: Our data showed overall postoperative speech improvement for all tested variables. Patients without postoperative fistula presented better results in oral pressure than those patients with postoperative fistula (P < 0.05). None of the other tested variables presented a significant negative impact on speech outcomes.

Conclusion: Late primary palatoplasty significantly improves speech outcomes for skeletally mature patients. Fistula has a negative impact on oral pressure.
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http://dx.doi.org/10.1097/SCS.0000000000006390DOI Listing
September 2020

Crescent-Like Lesions as an Early Signature of Nephropathy in a Rat Model of Prediabetes Induced by a Hypercaloric Diet.

Nutrients 2020 Mar 25;12(4). Epub 2020 Mar 25.

Institute of Pharmacology & Experimental Therapeutics, & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.

Diabetic nephropathy (DN) is a major microvascular complication of diabetes. Obesity and hyperlipidemia, fueled by unhealthy food habits, are risk factors to glomerular filtration rate (GFR) decline and DN progression. Several studies recommend that diabetic patients should be screened early (in prediabetes) for kidney disease, in order to prevent advanced stages, for whom the current interventions are clearly inefficient. This ambition greatly depends on the existence of accurate early biomarkers and novel molecular targets, which only may arise with a more thorough knowledge of disease pathophysiology. We used a rat model of prediabetes induced by 23 weeks of high-sugar/high-fat (HSuHF) diet to characterize the phenotype of early renal dysfunction and injury. When compared with the control animals, HSuHF-treated rats displayed a metabolic phenotype compatible with obese prediabetes, displaying impaired glucose tolerance and insulin sensitivity, along with hypertriglyceridemia, and lipid peroxidation. Despite unchanged creatinine levels, the prediabetic animals presented glomerular crescent-like lesions, accompanied by increased kidney Oil-Red-O staining, triglycerides content and mRNA expression of IL-6 and iNOS. This model of HSuHF-induced prediabetes can be a useful tool to study early features of DN, namely crescent-like lesions, an early signature that deserves in-depth elucidation.
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http://dx.doi.org/10.3390/nu12040881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230605PMC
March 2020

Flux Tube S-Matrix Bootstrap.

Phys Rev Lett 2019 Nov;123(22):221602

Perimeter Institute for Theoretical Physics, 31 Caroline Street N Waterloo, Ontario N2L 2Y5, Canada and Instituto de Física Teórica, UNESP, ICTP South American Institute for Fundamental Research, Rua Dr Bento Teobaldo Ferraz 271, 01140-070 São Paulo, Brazil.

We bootstrap the S matrix of massless particles in unitary, relativistic two dimensional quantum field theories. We find that the low energy expansion of such S matrices is strongly constrained by the existence of a UV completion. In the context of flux tube (FT) physics, this allows us to constrain several terms in the S matrix low energy expansion or-equivalently-on Wilson coefficients of several irrelevant operators showing up in the FT effective action. These bounds have direct implications for other physical quantities; for instance, they allow us to further bound the ground state energy as well as the level splitting of degenerate energy levels of large FTs. We find that the S matrices living at the boundary of the allowed space exhibit an intricate pattern of resonances with one sharper resonance whose quantum numbers, mass, and width are precisely those of the world-sheet axion proposed by Athenodorou, Bringoltz, and Teper and Dubovsky, Flauger, and Gorbenko. The general method proposed here should be extendable to massless S matrices in higher dimensions and should lead to new quantitative bounds on irrelevant operators in theories of Goldstones and, also, in gauge and gravity theories.
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http://dx.doi.org/10.1103/PhysRevLett.123.221602DOI Listing
November 2019

Reply to Khatoun et al.: Speculation about brain stimulation must be constrained by observation.

Proc Natl Acad Sci U S A 2019 11 15;116(45):22440-22441. Epub 2019 Oct 15.

Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada;

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http://dx.doi.org/10.1073/pnas.1914483116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842577PMC
November 2019

Waldenström Macroglobulinemia and Cerebral Venous Thrombosis: From Diagnosis to Complication.

Case Rep Med 2019 14;2019:9581605. Epub 2019 Jul 14.

Department of Internal Medicine, Centro Hospitalar da Cova da Beira E.P.E., Covilhã 6200-251, Portugal.

Waldenström macroglobulinemia (WM) is a type of non-Hodgkin lymphoma in which cancer cells produce large amounts of an abnormal protein that can cause hyperviscosity syndrome (HVS). A 43-year-old woman with WM, who developed seizures, had a head computed tomography scan that showed signs of cerebral venous thrombosis (CVT). Nevertheless, the value of immunoglobulin M was lower than 50 g/L, and evaluation of serum viscosity was not performed. Moreover, there was no history of bleeding, and the eye funduscopy was normal. These findings lead to think of causes of CVT other than HVS in a patient with WM.
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http://dx.doi.org/10.1155/2019/9581605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6664570PMC
July 2019

Predictors of Speech Outcome in Posterior Pharyngeal Fat Graft Surgery for Velopharyngeal Insufficiency Management.

J Craniofac Surg 2020 Jan/Feb;31(1):41-45

Institute of Plastic and Craniofacial Surgery, SOBRAPAR Hospital, Campinas, Brazil.

Background: The identification of variables potentially correlated with speech outcome, following posterior pharyngeal fat grafting for treatment of velopharyngeal insufficiency (VPI), can provide useful information to guide decision-making and preoperative counseling. This study assessed the predictors of speech outcome after posterior pharyngeal fat grafting for VPI management.

Methods: One hundred and sixty-seven consecutive patients with repaired cleft palate and VPI who underwent posterior pharyngeal fat grafting were retrospectively enrolled. Perceptual speech and nasendoscopic parameters were randomly rated by 3 blinded evaluators. Speech outcome was stratified based on previously published criteria. Bivariate and multivariate analyses were performed to identify independent predictors of 15-month postoperative speech outcomes.

Results: Large velopharyngeal gap, higher number of previous palatal surgical procedures, and referral pattern (ie, patients who underwent primary palatoplasty elsewhere) were independently negative (for all, P < 0.05) predictors of speech outcome, whereas small velopharyngeal gap size was positively (P < 0.05) correlated with this outcome. Age, sex, race, Veau hierarchy, syndromic diagnosis, Angle classification of malocclusion, type of primary palatoplasty, body mass index, obstructive sleep apnea-related scores, surgical period, donor site, grafted volume, recipient site-related complications, and preoperative status (velopharyngeal closure pattern, hypernasality, audible nasal emissions, and intraoral pressure) were not associated (for all, P > 0.05) with speech outcomes.

Conclusion: Posterior pharyngeal fat grafting improves speech function in patients with VPI, whereas gap size, number of previous palatal surgeries, and referral pattern affect the speech outcome.
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http://dx.doi.org/10.1097/SCS.0000000000005802DOI Listing
April 2020

Bootstrapping QCD Using Pion Scattering Amplitudes.

Phys Rev Lett 2019 Jun;122(24):241604

Instituto de Física Teórica, UNESP, ICTP South American Institute for Fundamental Research, Rua Dr Bento Teobaldo Ferraz 271, 01140-070, São Paulo, Brazil and Perimeter Institute for Theoretical Physics, 31 Caroline St N Waterloo, Ontario N2L 2Y5, Canada.

We consider the S-matrix bootstrap of four-dimensional scattering amplitudes with O(3) symmetry and no bound states. We explore the allowed space of scattering lengths which parametrize the interaction strength at threshold of the various scattering channels. Next we consider an application of this formalism to pion physics. A signature of pions is that they are derivatively coupled leading to (chiral) zeros in their scattering amplitudes. In this work we explore the multidimensional space of chiral zeros positions, scattering length values, and resonance mass values. Interestingly, we encounter lakes, peninsulas, and kinks depending on which sections of this intricate multidimensional space we consider. We discuss the remarkable location where QCD seems to lie in these plots, based on various experimental and theoretical expectations.
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http://dx.doi.org/10.1103/PhysRevLett.122.241604DOI Listing
June 2019

Automatic detection of small bowel tumors in wireless capsule endoscopy images using ensemble learning.

Med Phys 2020 Jan 11;47(1):52-63. Epub 2019 Nov 11.

CMEMS-UMinho Research Unit, University of Minho, Guimarães, Portugal.

Purpose: Wireless Capsule Endoscopy (WCE) is a minimally invasive diagnosis tool for lesion detection in the gastrointestinal tract, reaching places where conventional endoscopy is unable to. However, the significant amount of acquired data leads to difficulties in the diagnosis by the physicians; which can be eased with computer assistance. This paper addresses a method for the automatic detection of tumors in WCE by using a two-step based procedure: region of interest selection and classification.

Methods: The first step aims to separate abnormal from normal tissue by using automatic segmentation based on a Gaussian Mixture Model (GMM). A modified version of the Anderson method for convergence acceleration of the expectation-maximization (EM) algorithm is proposed. The proposed features for both segmentation and classification are based on the CIELab color space, as a way of bypassing lightness variations, where the L component is discarded. Tissue variability among subjects, light inhomogeneities and even intensity differences among different devices can be overcome by using simultaneously features from both regions. In the second step, an ensemble system with partition of the training data with a new training scheme is proposed. At this stage, the gating network is trained after the experts have been trained decoupling the joint maximization of both modules. The partition module is also used at the test step, leading the incoming data to the most likely expert allowing incremental adaptation by preserving data diversity.

Results: This algorithm outperforms others based on texture features selected from Wavelets and Curvelets transforms, classified by a regular support vector machine (SVM) in more than 5%.

Conclusions: This work shows that simpler features can outperform more elaborate ones if appropriately designed. In the current case, luminance was discarded to cope with saturated tissue, facilitating the color perception. Ensemble systems remain an open research field. In the current case, changes in both topology and training strategy have led to significant performance improvements. A system with this level of performance can be used in current clinical practice.
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http://dx.doi.org/10.1002/mp.13709DOI Listing
January 2020

Tailored Posterior Pharyngeal Fat Grafting Outcomes in Velopharyngeal Insufficiency Managed According to a Simplified Algorithm.

Ann Plast Surg 2019 08;83(2):172-179

From the Institute of Plastic and Craniofacial Surgery, SOBRAPAR Hospital, Campinas, São Paulo, Brazil.

Background: This study aimed to evaluate the outcomes of posterior pharyngeal fat grafting for the management of velopharyngeal insufficiency using a simplified therapeutic algorithm and a tailored surgical technique.

Methods: This was a prospective study of consecutive nonsyndromic patients with repaired cleft palate and velopharyngeal insufficiency who were stratified according to a simplified algorithm (minimally scarred palate, transverse orientation of levator veli palatini, and pinhole-to-small velopharyngeal gaps) and who underwent tailored posterior pharyngeal fat grafting. The patients were screened for obstructive sleep apnea before and after surgery. Three blinded evaluators randomly rated perceptual speech (hypernasality, audible nasal emission, and intraoral pressure) and nasoendoscopic (velopharyngeal active gap size) characteristics using audio and video recordings. Successful speech outcome was defined as normal or borderline sufficient velopharyngeal function at 15 months after surgery.

Results: All included patients (n = 96) presented with a preoperative and postoperative low risk of obstructive sleep apnea. At 15 months after surgery, hypernasality (0.26 ± 0.53), audible nasal emissions (0.29 ± 0.48), intraoral pressure (0.1 ± 0.31), and velopharyngeal closure size (1.86 ± 0.34) were significantly decreased (all, P < 0.05) compared with the corresponding preoperative measurements (hypernasality, 2.17 ± 0.75; audible nasal emissions, 1.89 ± 0.82; intraoral pressure, 0.85 ± 0.35; and velopharyngeal closure size, 0.2 ± 0.49). In total, 84 (87.5%) patients showed successful speech outcomes.

Conclusions: Tailored posterior pharyngeal fat grafting is an effective and safe surgical strategy for the management of velopharyngeal insufficiency in a selected cohort of patients with repaired cleft palate.
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http://dx.doi.org/10.1097/SAP.0000000000001930DOI Listing
August 2019

Probing deep tissues with laser-induced thermotherapy using near-infrared light.

Lasers Med Sci 2020 Feb 17;35(1):43-49. Epub 2019 May 17.

Department of Physics, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, Monte da Caparica, Portugal.

Optically tunable gold nanoparticles have been widely used in research with near-infrared light as a means to enhance laser-induced thermal therapy since it capitalizes on nanoparticles' plasmonic heating properties. There have been several studies published on numerical models replicating this therapy in such conditions. However, there are several limitations on some of the models which can render the model unfaithful to therapy simulations. In this paper, two techniques of simulating laser-induced thermal therapy with a high-absorbing localized region of interest inside a phantom are compared. To validate these models, we conducted an experiment of an agar-agar phantom with an inclusion reproducing it with both models. The phantom was optically characterized by absorption and total attenuation. The first model is based on the macroperspective solution of the radiative transfer equation given by the diffusion equation, which is then coupled with the Pennes bioheat equation to obtain the temperature. The second is a Monte Carlo model that considers a stochastic solution of the same equation and is also considered as input to the Pennes bioheat transfer equation which is then computed. The Monte Carlo is in good agreement with the experimental data having an average percentage difference of 4.5% and a correlation factor of 0.98, while the diffusion method comparison with experimental data is 61% and 0.95 respectively. The optical characterization of the phantom and its inclusion were also validated indirectly since the Monte Carlo, which used those parameters, was also validated. While knowing the temperature in all points inside a body during photothermal therapy is important, one has to be mindful of the model which fits the conditions and properties. There are several reasons to justify the discrepancy of the diffusion method: low-scattering conditions, absorption, and reduced scattering are comparable. The error bars that are normally associated when characterizing an optical phantom can justify also a part of that uncertainty. For low-size tumors in depth, one may have to increase the light dosage in photothermal therapies to have a more effective treatment.
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http://dx.doi.org/10.1007/s10103-019-02768-7DOI Listing
February 2020

Salvage surgery for local regrowths in Watch & Wait - Are we harming our patients by deferring the surgery?

Eur J Surg Oncol 2019 Sep 13;45(9):1559-1566. Epub 2019 Apr 13.

Colorectal Surgery - Champalimaud Foundation, Lisbon, Portugal. Electronic address:

Background: Rectal cancer surgery conveys significant morbidity/mortality, long-term functional impairment and urinary & sexual dysfunction, especially if associated with neoadjuvant chemoradiotherapy (ChRT). Watch & Wait (W&W) is gaining momentum as an option for patients with clinical complete response (cCR) after ChRT. Approximately 30% will develop a local regrowth (RG) and need deferred surgery. Our study aimed to assess the short-term clinical outcomes after surgery for regrowths.

Patients And Methods: Consecutive rectal cancer patients from a tertiary institution who underwent neoadjuvant ChRT, between January 2013 and October 2018, were identified from a prospectively maintained database. Patients with RG under W&W surveillance were operated - regrowth deferred surgery (RDS) group - and compared to those with persistent disease after ChRT who did undergo surgery - non-deferred surgery (NDS) group.

Results: Total of 124 patients received neoadjuvant treatment: 46 (37%) underwent surgery for persistent disease; 78 (63%) with cCR entered W&W. Twenty three developed RG and underwent surgery, while 55 remain under surveillance. RDS group had lower tumors than NDS group (2.3 cm ± 2 vs 4.5 cm ± 3, p = 0.002). All RG underwent minimally invasive surgery (MIS). Anastomotic leaks, 30-day morbidity, reintervention and readmission rates were similar. Pathology features and 3-year oncological outcomes were identical between groups.

Conclusion: Patients with initial cCR and local regrowth may be safely managed by deferred surgery. Short-term outcomes suggest equivalent results to patients with incomplete clinical response and immediate radical surgery. Delayed MIS appears to have no negative impact on oncological outcomes.
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http://dx.doi.org/10.1016/j.ejso.2019.04.006DOI Listing
September 2019

Automatic Segmentation and Detection of Small Bowel Angioectasias in WCE Images.

Ann Biomed Eng 2019 Jun 27;47(6):1446-1462. Epub 2019 Mar 27.

CMEMS-Uminho Research Unit, University of Minho, Guimarães, Portugal.

Angioectasias are lesions that occur in the blood vessels of the bowel and are the cause of more than 8% of all gastrointestinal bleeding episodes. They are usually classified as bleeding related lesions, however current state-of-the-art bleeding detection algorithms present low sensitivity in the detection of these lesions. This paper proposes a methodology for the automatic detection of angioectasias in wireless capsule endoscopy (WCE) videos. This method relies on the automatic selection of a region of interest, selected by using an image segmentation module based on the Maximum a Posteriori (MAP) approach where a new accelerated version of the Expectation-Maximization (EM) algorithm is also proposed. Spatial context information is modeled in the prior probability density function by using Markov Random Fields with the inclusion of a weighted boundary function. Higher order statistics computed in the CIELab color space with the luminance component removed and intensity normalization of high reflectance regions, showed to be effective features regarding angioectasia detection. The proposed method outperforms some current state of the art algorithms, achieving sensitivity and specificity values of more than 96% in a database containing 800 WCE frames labeled by two gastroenterologists.
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http://dx.doi.org/10.1007/s10439-019-02248-7DOI Listing
June 2019

Transcranial alternating current stimulation entrains single-neuron activity in the primate brain.

Proc Natl Acad Sci U S A 2019 03 4;116(12):5747-5755. Epub 2019 Mar 4.

Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada;

Spike timing is thought to play a critical role in neural computation and communication. Methods for adjusting spike timing are therefore of great interest to researchers and clinicians alike. Transcranial electrical stimulation (tES) is a noninvasive technique that uses weak electric fields to manipulate brain activity. Early results have suggested that this technique can improve subjects' behavioral performance on a wide range of tasks and ameliorate some clinical conditions. Nevertheless, considerable skepticism remains about its efficacy, especially because the electric fields reaching the brain during tES are small, whereas the likelihood of indirect effects is large. Our understanding of its effects in humans is largely based on extrapolations from simple model systems and indirect measures of neural activity. As a result, fundamental questions remain about whether and how tES can influence neuronal activity in the human brain. Here, we demonstrate that tES, as typically applied to humans, affects the firing patterns of individual neurons in alert nonhuman primates, which are the best available animal model for the human brain. Specifically, tES consistently influences the timing, but not the rate, of spiking activity within the targeted brain region. Such effects are frequency- and location-specific and can reach deep brain structures; control experiments show that they cannot be explained by sensory stimulation or other indirect influences. These data thus provide a strong mechanistic rationale for the use of tES in humans and will help guide the development of future tES applications.
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http://dx.doi.org/10.1073/pnas.1815958116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431188PMC
March 2019

Deep segregation in the open ocean: Macaronesia as an evolutionary hotspot for low dispersal marine invertebrates.

Mol Ecol 2019 04 13;28(7):1784-1800. Epub 2019 Apr 13.

Departamento de Biologia and CESAM - Centro de Estudos do Ambiente e do Mar, Universidade de Aveiro, Aveiro, Portugal.

Diversification and speciation of terrestrial organisms are anticipated in oceanic islands such as Macaronesia, a group of Atlantic islands that have remained unconnected to continental landmasses. Hitherto, the diversification of marine organisms in oceanic islands, especially those with low vagility, has received little direct empirical analysis using molecular markers. Here, we focus on such a case study, through applying a multilocus molecular approach to investigate the diversity and evolution of a group that lacks a planktonic larval stage, the isopod genus Dynamene, in Macaronesia and Northeast Atlantic. Sequences of two mitochondrial (cytochrome c oxidase subunit I and 16S rRNA) and two nuclear (18S rRNA and 28S rRNA) loci were obtained from specimens of Dynamene edwardsi (Lucas, 1849), Dynamene magnitorata Holdich, 1968 and Dynamene bidentata (Adams, 1800) collected along the Northeast Atlantic and Macaronesia. Although no major phylogeographic structure was detected in D. bidentata and D. magnitorata, from five to nine deeply divergent lineages were evident within D. edwardsi. The divergent lineages displayed genetic distances comparable to those found among established species of peracarids. D. edwardsi exhibits a long, rich and complex phylogeographic history in Macaronesia, where the geodynamics of the islands possibly associated with founder effects and subsequent lack of gene flow among populations confounds patterns based on geographic proximity of targeted populations. Our findings collectively suggest a much larger role of oceanic islands in the diversification of marine invertebrates than previously anticipated. The work provides insights into the origins and dynamics of ongoing geographic segregation and associated deep divergence among sister evolutionary lineages in Macaronesia.
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http://dx.doi.org/10.1111/mec.15052DOI Listing
April 2019

Handling Handles: Nonplanar Integrability in N=4 Supersymmetric Yang-Mills Theory.

Phys Rev Lett 2018 Dec;121(23):231602

Instituto de Física Teórica, UNESP, ICTP South American Institute for Fundamental Research, Rua Dr Bento Teobaldo Ferraz 271, 01140-070, São Paulo, Brazil.

We propose an integrability setup for the computation of correlation functions of gauge-invariant operators in N=4 supersymmetric Yang-Mills theory at higher orders in the large N_{c} genus expansion and at any order in the 't Hooft coupling g_{YM}^{2}N_{c}. In this multistep proposal, one polygonizes the string world sheet in all possible ways, hexagonalizes all resulting polygons, and sprinkles mirror particles over all hexagon junctions to obtain the full correlator. We test our integrability-based conjecture against a nonplanar four-point correlator of large 1/2 Bogomol'nyi-Prasad-Sommerfield operators at one and two loops.
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http://dx.doi.org/10.1103/PhysRevLett.121.231602DOI Listing
December 2018

Serious Complications After Le Fort III Distraction Osteogenesis in Syndromic Craniosynostosis: Evolution of Preventive and Therapeutic Strategies.

J Craniofac Surg 2018 Sep;29(6):1397-1401

Institute of Plastic and Craniofacial Surgery, SOBRAPAR Hospital.

Background: There is a paucity of studies that report complication rates following a subcranial Le Fort III advancement using distraction osteogenesis. The purpose of this study was to identify and describe serious postoperative complications following Le Fort III advancement with distraction osteogenesis, and provide strategies to assist in the resolution of these complications.

Methods: An observational retrospective study was performed on consecutive patients with Apert, Crouzon, or Pfeiffer syndromes (n = 16) who underwent Le Fort III advancement using distraction osteogenesis between 2008 and 2017. Serious complications were defined as frontal bone loss, cerebrospinal fluid leak, meningitis, seizures, or major blood loss (ie, massive transfusion within the first postoperative day).

Results: Three (18.7%) patients presented serious complications, namely cerebrospinal fluid leak (n = 1; 6.2%), seizures (n = 1; 6.2%) due to a halo-type device trans-pin intracranial migration, and major blood loss (n = 1; 6.2%). Adopting well-delineated interventions, all of these complications were resolved without fatality.

Conclusion: A Le Fort III advancement has a significant morbidity rate, with 3 of our patients (18.7%) in this study presenting serious complications. Appropriate management reduced this morbidity, and all complications were resolved without fatality.
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http://dx.doi.org/10.1097/SCS.0000000000004770DOI Listing
September 2018

Development and clinical application of Vertebral Metrics: using a stereo vision system to assess the spine.

Med Biol Eng Comput 2018 Aug 20;56(8):1435-1446. Epub 2018 Jan 20.

Departamento de Física, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, Monte da Caparica, 2829-516, Caparica, Portugal.

The biomechanical changes in the spinal column are considered to be the main responsible for rachialgia. Although radiological techniques use ionizing radiation, they are the most applied tools to assess the biomechanics of the spine. To face this problem, non-invasive techniques must be developed. Vertebral Metrics is an ionizing radiation-free instrument designed to detect the 3D position of each vertebrae in a standing position. Using a stereo vision system combined with low intensity UV light, recognition is achieved with software capable of distinguishing fluorescent marks. The fluorescent marks are the skin projection of the vertex of the spinal processes. This paper presents a major development of Vertebral Metrics and its evaluation. It performs a scan in less than 45 s with a resolution on the order of 1 mm, in each spatial direction, therefore, allowing an accurate analysis of the spine. The instrument was applied to patients without associated pathology. Statistically significant differences between consecutive scans were not found. A positive correlation between the 3D positions of each vertebra and the homologous position of the other vertebrae was observed. Using Vertebral Metrics, innovative results can be obtained. It can be used in areas such as orthopedics, neurosurgery, and rehabilitation. Graphical abstract ᅟ.
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http://dx.doi.org/10.1007/s11517-018-1789-0DOI Listing
August 2018

Automatic T1 bladder tumor detection by using wavelet analysis in cystoscopy images.

Phys Med Biol 2018 02 2;63(3):035031. Epub 2018 Feb 2.

CMEMS-UMinho Research Unit, University of Minho, Guimarães, Portugal.

Correct classification of cystoscopy images depends on the interpreter's experience. Bladder cancer is a common lesion that can only be confirmed by biopsying the tissue, therefore, the automatic identification of tumors plays a significant role in early stage diagnosis and its accuracy. To our best knowledge, the use of white light cystoscopy images for bladder tumor diagnosis has not been reported so far. In this paper, a texture analysis based approach is proposed for bladder tumor diagnosis presuming that tumors change in tissue texture. As is well accepted by the scientific community, texture information is more present in the medium to high frequency range which can be selected by using a discrete wavelet transform (DWT). Tumor enhancement can be improved by using automatic segmentation, since a mixing with normal tissue is avoided under ideal conditions. The segmentation module proposed in this paper takes advantage of the wavelet decomposition tree to discard poor texture information in such a way that both steps of the proposed algorithm segmentation and classification share the same focus on texture. Multilayer perceptron and a support vector machine with a stratified ten-fold cross-validation procedure were used for classification purposes by using the hue-saturation-value (HSV), red-green-blue, and CIELab color spaces. Performances of 91% in sensitivity and 92.9% in specificity were obtained regarding HSV color by using both preprocessing and classification steps based on the DWT. The proposed method can achieve good performance on identifying bladder tumor frames. These promising results open the path towards a deeper study regarding the applicability of this algorithm in computer aided diagnosis.
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http://dx.doi.org/10.1088/1361-6560/aaa3afDOI Listing
February 2018

Brain extraction in partial volumes T2*@7T by using a quasi-anatomic segmentation with bias field correction.

J Neurosci Methods 2018 02 15;295:129-138. Epub 2017 Dec 15.

CMEMS-UMinho Research Unit, University of Minho, Guimarães, Portugal.

Background: Poor brain extraction in Magnetic Resonance Imaging (MRI) has negative consequences in several types of brain post-extraction such as tissue segmentation and related statistical measures or pattern recognition algorithms. Current state of the art algorithms for brain extraction work on weighted T1 and T2, being not adequate for non-whole brain images such as the case of T2*FLASH@7T partial volumes.

New Method: This paper proposes two new methods that work directly in T2*FLASH@7T partial volumes. The first is an improvement of the semi-automatic threshold-with-morphology approach adapted to incomplete volumes. The second method uses an improved version of a current implementation of the fuzzy c-means algorithm with bias correction for brain segmentation.

Results: Under high inhomogeneity conditions the performance of the first method degrades, requiring user intervention which is unacceptable. The second method performed well for all volumes, being entirely automatic.

Comparison With Existing Methods: State of the art algorithms for brain extraction are mainly semi-automatic, requiring a correct initialization by the user and knowledge of the software. These methods can't deal with partial volumes and/or need information from atlas which is not available in T2*FLASH@7T. Also, combined volumes suffer from manipulations such as re-sampling which deteriorates significantly voxel intensity structures making segmentation tasks difficult. The proposed method can overcome all these difficulties, reaching good results for brain extraction using only T2*FLASH@7T volumes.

Conclusions: The development of this work will lead to an improvement of automatic brain lesions segmentation in T2*FLASH@7T volumes, becoming more important when lesions such as cortical Multiple-Sclerosis need to be detected.
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http://dx.doi.org/10.1016/j.jneumeth.2017.12.006DOI Listing
February 2018

Using cystoscopy to segment bladder tumors with a multivariate approach in different color spaces.

Annu Int Conf IEEE Eng Med Biol Soc 2017 Jul;2017:656-659

Nowadays the diagnosis of bladder lesions relies upon cystoscopy examination and depends on the interpreter's experience. State of the art of bladder tumor identification are based on 3D reconstruction, using CT images (Virtual Cystoscopy) or images where the structures are exalted with the use of pigmentation, but none uses white light cystoscopy images. An initial attempt to automatically identify tumoral tissue was already developed by the authors and this paper will develop this idea. Traditional cystoscopy images processing has a huge potential to improve early tumor detection and allows a more effective treatment. In this paper is described a multivariate approach to do segmentation of bladder cystoscopy images, that will be used to automatically detect and improve physician diagnose. Each region can be assumed as a normal distribution with specific parameters, leading to the assumption that the distribution of intensities is a Gaussian Mixture Model (GMM). Region of high grade and low grade tumors, usually appears with higher intensity than normal regions. This paper proposes a Maximum a Posteriori (MAP) approach based on pixel intensities read simultaneously in different color channels from RGB, HSV and CIELab color spaces. The Expectation-Maximization (EM) algorithm is used to estimate the best multivariate GMM parameters. Experimental results show that the proposed method does bladder tumor segmentation into two classes in a more efficient way in RGB even in cases where the tumor shape is not well defined. Results also show that the elimination of component L from CIELab color space does not allow definition of the tumor shape.
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http://dx.doi.org/10.1109/EMBC.2017.8036910DOI Listing
July 2017

Serious games for upper limb rehabilitation: a systematic review.

Disabil Rehabil Assist Technol 2018 01 30;13(1):95-100. Epub 2017 Mar 30.

a Department of Physics , Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa , Portugal.

The aim of this research is to carry out a systematic review of the use of technological gaming platforms with serious games in the upper limb rehabilitation of patients with neuromotor disorders. Through a systematic review, the first two authors defined the inclusion criteria and extracted the data, resulting in 38 studies collected from B-On, PubMed and Medline. Ninety-two per cent of the selected articles were published since 2010. This review documents 35 different gaming platforms types. Twenty-one of the 38 articles included in this review conducted a clinical trial and of those only eight report improvements in the target population following the use of the games and platforms. This review concludes that a new paradigm is emerging in the rehabilitation field, characterized by the systematic use of technological gaming platforms with serious games in/for rehabilitation. The use of this approach seems to be beneficial. However, to facilitate the full integration of these platforms, it is necessary to conduct more research in this area, explore new approaches and carry out in-depth clinical studies into the benefits of these platforms. Implications for rehabilitation This review states that the use serious games and gaming platforms for upper limb rehabilitation are starting a new paradigm in the rehabilitation. For a full integration of this technologies in the rehabilitation field more studies are needed.
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http://dx.doi.org/10.1080/17483107.2017.1290702DOI Listing
January 2018

An adapted double threshold protocol for spastic muscles.

Annu Int Conf IEEE Eng Med Biol Soc 2016 Aug;2016:3630-3633

The onset of muscle contraction has been an important element in the understanding of human motor control system as well as in the development of medical devices. This task is problematic in the study of spasticity using surface Electromyography (sEMG). In fact, spasticity is characterized by involuntary muscle contractions that can be seen as both, a non-stationary background if they are weak or a severe non-stationary EMG signal if they are strong. In other hand, these sEMG signals present a very low signal to noise ratio, beyond the added noise that contaminates this signal. The double threshold protocol presumes non-stationary muscle activation under a stationary environment which does not accommodate non-stationary background conditions. Apart from that the Shewhart protocol which makes part of the Double Threshold Protocol (DTP) presumes an initial segment containing only noise which can't be guaranteed under spastic conditions. These are the main causes of failures of state of the art approaches when applied to sEMG spastic muscles. This paper proposes dealing with these constraints by adapting the first threshold to the noise conditions via Signal to Noise Ratio (SNR) estimation, which depends on the severity of the disease. The main idea is tuning the first threshold to low SNR conditions since it is where the DTP most degrades. This tuning is done in sEMG artificially contaminated at different SNRs where the multiple of standard deviation is heuristically determined based on experimentation. Noise is estimated in low energy segments instead of in an initial segment that can be contaminated by involuntary muscle contractions. The proposed algorithm was tested in sEMG signals from the Biceps Braquialis of 13 healthy individuals and in 9315 signals recorded in 23 subjects with spasticity. Improvements of more than 23% were obtained when compared with the classical DTP in moderate to severe spasticity.
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http://dx.doi.org/10.1109/EMBC.2016.7591514DOI Listing
August 2016