Introducing non-linear analysis into sustained speech characterization to improve sleep apnea detection

The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-642-25020-0_28Proceedings of 5th International Conference on Nonlinear Speech Processing, NOLISP 2011, Las Palmas de Gran Canaria (Spain)We present a novel approach for detecting severe obstructive sleep apnea (OSA) cases by introducing non-linear analysis into sustained speech characterization. The proposed scheme was designed for providing additional information into our baseline system, built on top of state-of-the-art cepstral domain modeling techniques, aiming to improve accuracy rates. This new information is lightly correlated with our previous MFCC modeling of sustained speech and uncorrelated with the information in our continuous speech modeling scheme. Tests have been performed to evaluate the improvement for our detection task, based on sustained speech as well as combined with a continuous speech classifier, resulting in a 10% relative reduction in classification for the first and a 33% relative reduction for the fused scheme. Results encourage us to consider the existence of non-linear effects on OSA patients’ voices, and to think about tools which could be used to improve short-time analysis.The activities described in this paper were funded by the Spanish Ministry of Science and Innovation as part of the TEC2009-14719-C02-02 (PriorSpeech) project

Characterization of the bacteriocins and the PrtR regulator in a plant-associated Pseudomonas strain

The emergence of antibiotic resistant bacterial strains demands the development of new antimicrobial agents. In the last decades, bacteriocins have gained significant interest due to their potential application as biopreservatives in the food industry and as therapeutic agents in medicine. Recent studies project the use of these antimicrobials in agriculture as biocontrol agents. The characterization of bacteriocins and their genetic regulation, however, have been scarcely studied in plant-associated bacteria. In this report, an in-silico and proteomic analysis was performed to identify the bacteriocins produced by Pseudomonas fluorescens SF4c. More than one functional bacteriocin was detected in this strain (S-type bacteriocins and phage-tail-like bacteriocins [tailocins]). It is known that the regulator PrtR represses bacteriocin production in P. aeruginosa under normal condition. However, the mechanism for tailocin regulation remains unknown in plant-associated pseudomonads. In this work, an orthologue of the prtR of P. aeruginosa was identified in the SF4c-tailocin cluster and a prtR null mutant constructed. The expression and production of tailocins was abolished in this mutant; thus evidencing that, unlike P. aeruginosa, PrtR is a positive regulator of tailocins expression in P. fluorescens.Fil: Fernandez, Maricruz. Universidad Nacional de Rio Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones Agrobiotecnológicas - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Agrobiotecnológicas; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Ciencias Naturales; ArgentinaFil: Godino, Agustina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Ciencias Naturales; ArgentinaFil: Principe, Analia. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Ciencias Naturales; ArgentinaFil: López Ramírez, Viviana. Universidad Nacional de Rio Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones Agrobiotecnológicas - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Agrobiotecnológicas; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Ciencias Naturales; ArgentinaFil: Quesada, José Miguel. Consejo Superior de Investigaciones Científicas. Estación Experimental del Zaidín; EspañaFil: Rigo, Virginia. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Ciencias Naturales; ArgentinaFil: Espinosa-Urgel, Manuel. Consejo Superior de Investigaciones Científicas. Estación Experimental del Zaidín; EspañaFil: Morales, Gustavo Marcelo. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; ArgentinaFil: Fischer, Sonia Elizabeth. Universidad Nacional de Rio Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones Agrobiotecnológicas - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Agrobiotecnológicas; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Ciencias Naturales; Argentin

Diseño de un cuestionario para evaluar conocimientos didáctico-matemáticos sobre razonamiento algebraico elemental

La promoció del pensament algebraic en alumnes de primària requereix implementar accions formatives específiques per als professors, la qual cosa al seu torn implica elaborar instruments d'avaluació de l'estat dels seus coneixements didàctic - matemàtics sobre el tema. En aquest treball presentem resultats de l'estudi realitzat per a la construcció d'un qüestionari d'avaluació dels coneixements didàctic - matemàtics d'estudiants de magisteri sobre raonament algebraic elemental. Descrivim les categories de coneixements algebraics tingudes en compte (estructures, funcions i modelització) i les categories de coneixements didàctics (facetes epistèmica, cognitiva, instruccional i ecològica). Així mateix es descriuen i analitzen les tasques incloses en el qüestionari informant de la validesa de contingut del mateix.Promoting algebraic thinking in elementary school pupils requires implementing specific training activities for teachers, which in turn involves developing tools to assess their didactic-mathematical knowledge about this subject. In this paper we present results of a study aimed to build a questionnaire for assessing the didactic-mathematic knowledge of prospective primary teachers on elementary algebraic reasoning. We describe the categories of algebraic knowledge (structures, functions and modeling), as well as the categories of didactical knowledge (epistemic, cognitive, instructional and ecological facets) taken into account. We also describe and analyze the tasks included in the questionnaire reporting its content validity.La promoción del pensamiento algebraico en alumnos de primaria requiere implementar acciones formativas específicas para los profesores, lo que a su vez implica elaborar instrumentos de evaluación del estado de sus conocimientos didáctico - matemáticos sobre el tema. En este trabajo presentamos resultados del estudio realizado para la construcción de un cuestionario de evaluación de los conocimientos didáctico - matemáticos de estudiantes de magisterio sobre razonamiento algebraico elemental. Describimos las categorías de conocimientos algebraicos tenidas en cuenta (estructuras, funciones y modelización) y las categorías de conocimientos didácticos (facetas epistémica, cognitiva, instruccional y ecológica). Así mismo se describen y analizan las tareas incluidas en el cuestionario informando de la validez de contenido del mismo

Deconstructing Weight Management Interventions for Young Adults: Looking Inside the Black Box of the EARLY Consortium Trials.

ObjectiveThe goal of the present study was to deconstruct the 17 treatment arms used in the Early Adult Reduction of weight through LifestYle (EARLY) weight management trials.MethodsIntervention materials were coded to reflect behavioral domains and behavior change techniques (BCTs) within those domains planned for each treatment arm. The analytical hierarchy process was employed to determine an emphasis profile of domains in each intervention.ResultsThe intervention arms used BCTs from all of the 16 domains, with an average of 29.3 BCTs per intervention arm. All 12 of the interventions included BCTs from the six domains of Goals and Planning, Feedback and Monitoring, Social Support, Shaping Knowledge, Natural Consequences, and Comparison of Outcomes; 11 of the 12 interventions shared 15 BCTs in common across those six domains.ConclusionsWeight management interventions are complex. The shared set of BCTs used in the EARLY trials may represent a core intervention that could be studied to determine the required emphases of BCTs and whether additional BCTs add to or detract from efficacy. Deconstructing interventions will aid in reproducibility and understanding of active ingredients

Ventricular arrhythmias in patients with functional mitral regurgitation and implantable cardiac devices: implications of mitral valve repair with Mitraclip

Background: Limited information has been reported regarding the impact of percutaneous mitral valve repair (PMVR) on ventricular arrhythmic (VA) burden. The aim of this study was to address the incidence of VA and appropriate antitachycardia implantable cardiac defibrillator (ICD) therapies before and after PMVR. Methods: We retrospectively analyzed all consecutive patients with heart failure with reduce left ventricular ejection fraction (LVEF), functional mitral regurgitation (FMR) grade 3+ or 4+ and an active ICD or cardiac resynchronizer who underwent PMVR in any of the eleven recruiting centers. Only patients with complete available device VA monitoring from one-year before to one year after PMVR were included. Baseline clinical and echocardiographic characteristics were collected before PMVR and at 12-months follow-up. Results: Ninety-three patients (68.2+/-10.9 years old, male 88.2%) were enrolled. PMVR was successfully performed in all patients and device success at discharge was 91.4%. At 12-month follow-up, we observed a significant reduction in mitral regurgitation severity, NT-proBNP and prevalence of severe pulmonary hypertension and severe kidney disease. Patients also referred a significant improvement in NYHA functional class and showed a non-significant trend to reserve left ventricular remodeling. After PMVR a significant decrease in the incidence of non-sustained ventricular tachycardia (VT) (5.0+/-17.8 vs. 2.7+/-13.5, P=0.002), sustained VT or ventricular fibrillation (0.9+/-2.5 vs. 0.5+/-2.9, P=0.012) and ICD antitachycardia therapies (2.5+/-12.0 vs. 0.9+/-5.0, P=0.033) were observed. Conclusions: PMVR was related to a reduction in arrhythmic burden and ICD therapies in our cohort

Response to Novel Drugs before and after Allogeneic Stem Cell Transplantation in Patients with Relapsed Multiple Myeloma

Multiple myeloma (MM) remains as an incurable disease and, although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative approach, most patients ultimately relapse, and their treatment remains challenging. Because allo-HSCT can modify not only the biology of the disease, but also the immune system and the microenvironment, it can potentially enhance the response to rescue therapies. Information on the efficacy and safety of novel drugs in patients relapsing after allo-HSCT is lacking, however. The objectives of this study were to evaluate the efficacy and toxicity of rescue therapies in patients with MM who relapsed after allo-HSCT, as well as to compare their efficacy before and after allo-HSCT. This retrospective multicenter study included 126 consecutive patients with MM who underwent allo-HSCT between 2000 and 2013 at 8 Spanish centers. All patients engrafted. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was 47%, and nonrelapse mortality within the first 100 days post-transplantation was 13%. After a median follow-up of 92 months, overall survival (OS) was 51% at 2 years and 43% at 5 years. The median progression-free survival after allo-HSCT was 7 months, whereas the median OS after relapse was 33 months. Patients relapsing in the first 6 months after transplantation had a dismal prognosis compared with those who relapsed later (median OS, 11 months versus 120 months; P <.001). The absence of chronic GVHD was associated with reduced OS after relapse (hazard ratio, 3.44; P <.001). Most patients responded to rescue therapies, including proteasome inhibitors (PIs; 62%) and immunomodulatory drugs (IMiDs; 77%), with a good toxicity profile. An in-depth evaluation, including the type and intensity of PI- and IMiD-based combinations used before and after allo-HSCT, showed that the overall response rate and duration of response after allo-HSCT were similar to those seen in the pretransplantation period. Patients with MM who relapse after allo-HSCT should be considered candidates for therapy with new drugs, which can achieve similar response rates with similar durability as seen in the pretransplantation period. This pattern does not follow the usual course of the disease outside the transplantation setting, where response rates and time to progression decreases with each consecutive line of treatment

Repurposing the Open Global Health Library for the discovery of novel Mpro destabilizers with scope as broad-spectrum antivirals

The SARS coronavirus 2 (SARS-CoV-2) epidemic remains globally active. The emergence of new variants of interest and variants of concern (VoCs), which are potentially more vaccine-resistant and less sensitive to existing treatments, is evident due to their high prevalence. The prospective spread of such variants and other coronaviruses with epidemic potential demands preparedness that can be met by developing fast-track workflows to find new candidates that target viral proteins with a clear in vitro and in vivo phenotype. Mpro (or 3CLpro) is directly involved in the viral replication cycle and the production and function of viral polyproteins, which makes it an ideal target. The biological relevance of Mpro is highly conserved among betacoronaviruses like HCoV-OC43 and SARS-CoV-2, which makes the identification of new chemical scaffolds targeting them a good starting point for designing broad-spectrum antivirals. We report an optimized methodology based on orthogonal cell-free assays to identify small molecules that inhibit the binding pockets of both SARS-CoV-2-Mpro and HCoV-OC43-Mpro; this blockade correlates with antiviral activities in HCoV-OC43 cellular models. By using such a fast-tracking approach against the Open Global Health Library (Merck KGaA), we have found evidence of the antiviral activity of compound OGHL98. In silico studies dissecting intermolecular interactions between OGHL98 and both proteases and comprising docking and molecular dynamics simulations (MDSs) concluded that the binding mode was primarily governed by conserved H-bonds with their C-terminal amino acids and that the rational design of OGHL98 has potential against VoCs proteases resistant to current therapeutics.The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. DG-P’s laboratory and research have been funded by the European Commission—Next Generation EU (regulation EU 2020/2094) through CSIC’s Global Health Platform (PTI Salud Global), the Instituto de Salud Carlos III Subdirección General de Redes y Centros de Investigación Cooperativa-Red de Investigación Cooperativa en Enfermedades Tropicales (RICET: RD16/0027/ 0014), and the MCIN/AEI/10.13039/501100011033, and by the grants PID2019-109623RB-I00, MCIN/AEI/10.13039/ 501100011033, and FEDER Una manera de hacer Europa (2016- 79957-R), and PID2022-142971OB-I00, MCIN/AEI/10.13039/501100011033/FEDER, UE, and by the Junta de Andalucía (BIO- 199). DR’s research has been funded by the Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT), grant number 1220656, and the Agencia Nacional de Investigación y Desarrollo (ANID), grant number COVID0199.Peer reviewe

A2 Noradrenergic Lesions Prevent Renal Sympathoinhibition Induced by Hypernatremia in Rats

Renal vasodilation and sympathoinhibition are recognized responses induced by hypernatremia, but the central neural pathways underlying such responses are not yet entirely understood. Several findings suggest that A2 noradrenergic neurons, which are found in the nucleus of the solitary tract (NTS), play a role in the pathways that contribute to body fluid homeostasis and cardiovascular regulation. The purpose of this study was to determine the effects of selective lesions of A2 neurons on the renal vasodilation and sympathoinhibition induced by hypertonic saline (HS) infusion. Male Wistar rats (280–350 g) received an injection into the NTS of anti-dopamine-beta-hydroxylase-saporin (A2 lesion; 6.3 ng in 60 nl; n = 6) or free saporin (sham; 1.3 ng in 60 nl; n = 7). Two weeks later, the rats were anesthetized (urethane 1.2 g⋅kg−1 b.wt., i.v.) and the blood pressure, renal blood flow (RBF), renal vascular conductance (RVC) and renal sympathetic nerve activity (RSNA) were recorded. In sham rats, the HS infusion (3 M NaCl, 1.8 ml⋅kg−1 b.wt., i.v.) induced transient hypertension (peak at 10 min after HS; 9±2.7 mmHg) and increases in the RBF and RVC (141±7.9% and 140±7.9% of baseline at 60 min after HS, respectively). HS infusion also decreased the RSNA (−45±5.0% at 10 min after HS) throughout the experimental period. In the A2-lesioned rats, the HS infusion induced transient hypertension (6±1.4 mmHg at 10 min after HS), as well as increased RBF and RVC (133±5.2% and 134±6.9% of baseline at 60 min after HS, respectively). However, in these rats, the HS failed to reduce the RSNA (115±3.1% at 10 min after HS). The extent of the catecholaminergic lesions was confirmed by immunocytochemistry. These results suggest that A2 noradrenergic neurons are components of the neural pathways regulating the composition of the extracellular fluid compartment and are selectively involved in hypernatremia-induced sympathoinhibition

Ion-Transfer Voltammetric Behavior of Propranolol at Nanoscale Liquid-Liquid Interface Arrays

In this work, the ion-transfer voltammetric detection of the protonated β-blocker propranolol was explored at arrays of nanoscale interfaces between two immiscible electrolyte solutions (ITIES). Silicon nitride nanoporous membranes with 400 pores in a hexagonal arrangement, with either 50 or 17 nm radius pores, were used to form regular arrays of nanoITIES. It was found that the aqueous-to-organic ion-transfer current continuously increased steadily rather than reaching a limiting current plateau after the ion-transfer wave; the slope of this limiting current region was concentration dependent and associated with the high ion flux at the nanointerfaces. Electrochemical data were examined in terms of an independent nanointerface approach and an equivalent microdisc approach, supported by finite element simulation. In comparison to the larger interface configuration (50 nm radius), the array of 17 nm radius nanoITIES exhibited a 6.5-times higher current density for propranolol detection due to the enhanced ion flux arising from the convergent diffusion to smaller electrochemical interfaces. Both nanoITIES arrays achieved the equivalent limits of detection, 0.8 μM, using cyclic voltammetry. Additionally, the effect of scan rate on the charging and faradaic currents at these nanoITIES arrays, as well as their stability over time, was investigated. The results demonstrate that arrays of nanoscale liquid–liquid interfaces can be applied to study electrochemical drug transfer, and provide the basis for the development of miniaturized and integrated detection platforms for drug analysis