Optimal control strategies to tailor antivirals for acute infectious diseases in the host

Several mathematical models in SARS-CoV-2 have shown how target-cell model can help to understand the spread of the virus in the host and how potential candidates of antiviral treatments can help to control the virus. Concepts as equilibrium and stability show to be crucial to qualitative determine the best alternatives to schedule drugs, according to effectivity in inhibiting the virus infection and replication rates. Important biological events such as rebounds of the infections (when antivirals are incorrectly interrupted) can also be explained by means of a dynamic study of the target-cell model. In this work a full characterization of the dynamical behavior of the target-cell models under control actions is made and, based on this characterization, the optimal fixeddose antiviral schedule that produces the smallest amount of dead cells (without viral load rebounds) is computed. Several simulation results - performed by considering real patient data - show the potential benefits of both, the model characterization and the control strategy.Fil: Perez, Mara Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Abuin, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Actis, Marcelo Jesús. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Ingeniería Química; ArgentinaFil: Ferramosca, Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Università Degli Studi Di Bergamo; ItaliaFil: Hernandez Vargas, Esteban Abelardo. Universidad Nacional Autónoma de México; MéxicoFil: González, Alejandro Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentin

The Personal Wellbeing among Community-Dwelling Older Adults in Spain and Associated Factors

Objective: The conceptual framework of Quality of Life (QoL) allows approaching the knowledge of the living conditions of people in order to help establishing policies for QoL improvement. This study is aimed at examining the assessment made by older adults on their personal wellbeing and the satisfaction with life and the associated factors. A summary of the psychometric properties of the measurement instrument was also presented. Method: The data came from the Ageing in Spain Longitudinal Study, Pilot Survey (ELES-PS), carried out in 2011 among people 50 years old or more living in family housing in Spain. The Personal Wellbeing Index (PWI), as a multidimensional measure of QoL, was used to evaluate the subjective wellbeing. Personal, social and residential characteristics were considered as independent variables. Descriptive statistical analysis, ANOVA, correlation, factor and regression analyses were applied. Results and conclusions: The PWI had good psychometric properties and showed the convergent validity with satisfaction with life as a whole (SWLW). Unidimensional structure of the scale was also demonstrated. PWI and SWLW total scores reached 74.5%SM and 77.1%SM, respectively. The best rated life domains were the satisfaction with relationships, safety and feeling part of the community. The SWLW observed significant differences in gender categories while PWI within age and social status. Both scales were associated with marital status, educational level, household size, current activity status and social status. The regression model of the PWI explained 34.2% of the variance through factors on socio-demographic and economic resources, psychosocial, health/functioning, family and social networks, leisure and residential environment. Based on these results, it would be desirable to deepen on this line from a longitudinal perspective to detect the influence of the changing conditions of the aged people in their personal well-being and life satisfaction.This research was funded by the Spanish Ministry of Science and Innovation (National R&D&I Plan: ref. CSO2009-08645-E/SOCI, CSO2009-06638-E/SOCI, CSO2009-06637-E/SOCI), by the Fundación Obra Social Cajamadrid and by the Basque Government, and supported by the Ageing Process Research Unit INGEMA-CSIC, for carrying out the ELES Project Pilot Survey. Another grant from the Spanish Ministry of Science and Innovation (National R&D&I Plan: ref. CSO2011-30210-C02-01) was endorsed for the analysis. Authors would like to thank the editor and the anonymous reviewer/s for their helpful comments during the development of this paper

Distribution and impact on quality of life of the pain modalities assessed by the King's Parkinson's disease pain scale

In Parkinson's disease, pain is a prevalent and complex symptom of diverse origin. King's Parkinson's disease pain scale, assesses different pain syndromes, thus allowing exploration of its differential prevalence and influence on the health-related quality of life of patients. Post hoc study 178 patients and 83 matched controls participating in the King's Parkinson's disease pain scale validation study were used. For determining the respective distribution, King's Parkinson's disease pain scale items and domains scores = 0 meant absence and ≥1 presence of the symptom. The regular scores were used for the other analyses. Health-related quality of lifewas evaluated with EQ-5D-3L and PDQ-8 questionnaires. Parkinson's disease patients experienced more pain modalities than controls. In patients, Pain around joints (King's Parkinson's disease pain scale item 1) and Pain while turning in bed (item 8) were the most prevalent types of pain, whereas Burning mouth syndrome (item 11) and Pain due to grinding teeth (item 10) showed the lowest frequency. The total number of experienced pain modalities closely correlated with the PDQ-8 index, but not with other variables. For all pain types except Pain around joints (item 1) and pain related to Periodic leg movements/RLS (item 7), patients with pain had significantly worse health-related quality of life. The influence of pain, as a whole, on the health-related quality of life was not remarkable after adjustment by other variables. When the particular types of pain were considered, adjusted by sex, age, and Parkinson's disease duration, pain determinants were different for EQ-5D-3L and PDQ-8. King's Parkinson's disease pain scale allows exploring the distribution of the diverse syndromic pain occurring in Parkinson's disease and its association with health-related quality of life.The study was funded by a Parkinson’s UK innovation grant, and adopted to the UK National Institute for Health Research (NIHR) national portfolio of studies and supported by NIHR Mental Health Biomedical Research Center and Dementia Unit at South London and Maudsley NHS Foundation Trust and King’s College London.S

Analysis of four scales for global severity evaluation in Parkinson’s disease

Global evaluations of Parkinson?s disease (PD) severity are available, but their concordance and accuracy have not been previously tested. The present international, cross-sectional study was aimed at determining the agreement level among four global scales for PD (Hoehn and Yahr, HY; Clinical Global Impression of Severity, CGIS; Clinical Impression of Severity Index, CISI-PD; and Patient Global Impression of Severity, PGIS) and identifying which of them better correlates with itemized PD assessments. Assessments included additional scales for evaluation of the movement impairment, disability, affective disorders, and quality of life. Spearman correlation coefficients, weighted and generalized kappa, and Kendall?s concordance coefficient were used. Four hundred thirty three PD patients, 66% in HY stages 2 or 3, mean disease duration 8.8 years, were analyzed. Correlation between the global scales ranged from 0.60 (HY with PGIS) to 0.91 (CGIS with CISI-PD). Kendall?s coefficient of concordance resulted 0.76 (P<0.0001). HY and CISI-PD showed the highest association with age, disease duration, and levodopa-equivalent daily dose, and CISI-PD with measures of PD manifestations, disability, and quality of life. PGIS and CISI-PD correlated similarly with anxiety and depression scores. The lowest agreement in classifying patients as mild, moderate, or severe was observed between PGIS and HY or CISI-PD (58%) and the highest between CGIS and CISI-PD (84.3%). The four PD global severity scales agree moderately to strongly among them; clinician-based ratings estimate PD severity, as established by other measures, better than PGIS; and the CISI-PD showed the highest association with measures of impairment, disability, and quality of life.Fil: Martinez Martin, Pablo. Universidad Carlos III de Madrid. Instituto de Salud; EspañaFil: Rojo Abuin, José Manuel. Consejo Superior de Investigaciones Cientificas. Centro de Ciencias Humanas y Sociales. Instituto de Historia.; EspañaFil: Rodríguez Violante, Mayela. Instituto Nacional de Neurología y Neurocirugía; MéxicoFil: Serrano Dueñas, Marcos. Pontificia Universidad Católica del Ecuador; EcuadorFil: Garreto, Nélida Susana. Universidad de Buenos Aires. Facultad de Medicina. Centro Universitario de Neurologia "dr. Jose Maria Ramos Mejia".; ArgentinaFil: Martínez Castrillo, Juan Carlos. Instituto Ramón y Cajal de Investigación Sanitaria; EspañaFil: Campos Arillo, Víctor. Hospital Xanit International; EspañaFil: Fernández, William. Universidad Nacional de Colombia; ColombiaFil: Chaná Cuevas, Pedro. Universidad de Santiago de Chile. Facultad de Humanidades. Instituto de Ciencias Biomédicas.; ChileFil: Arakaki, Tomoko. Universidad de Buenos Aires. Facultad de Medicina. Centro Universitario de Neurologia "dr. Jose Maria Ramos Mejia".; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Alvarez, Mario Gustavo. Centro Internacional de Restauración Neurológica ; CubaFil: Pedroso Ibañez, Ivonne. Centro Internacional de Restauración Neurológica ; CubaFil: Rodríguez Blázquez , Carmen. Universidad Carlos III de Madrid. Instituto de Salud; EspañaFil: Ray Chaudhuri , Kallol. National Parkinson Foundation International Centre of Excellence; Reino UnidoFil: Merello, Marcelo Jorge. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Búsqueda de empleo activo y mejora de la empleabilidad en el Grado en Educación Social

El desarrollo de este trabajo tiene como objetivo mejorar la tasa de empleabilidad de los egresados en el Grado en Educación Social de la Universidad Complutense de Madrid, así como la búsqueda de empleo activo, al proporcionar diferentes recursos y estrategias y crear redes y espacios de diálogo con las asociaciones profesionales del sector. Parte de la necesidad del fomento de la inserción laboral y el emprendimiento entre los estudiantes, el desarrollo de la orientación laboral como una herramienta básica para el estudio y el análisis del fortalecimiento del empleo para educadores sociales y la búsqueda activa del mismo. Igualmente, se apoya en postulados y paradigmas como el de educación para el bien común y sostenible, en un marco de educación permanente, humanista y con vocación para la transformación social

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Artificial pancreas under stable pulsatile MPC: Improving the closed-loop performance

This work presents a pulsatile Zone Model Predictive Control (pZMPC) for the control of blood glucose concentration (BGC) in patients with Type 1 Diabetes Mellitus (T1DM). The main novelties of the algorithm – in contrast to other existing strategies – are: (i) it controls the patient glycemia by injecting short duration insulin boluses for both, the basal and bolus infusions, in an unified manner, (ii) it performs the predictions and estimations (critical to anticipate both, hypo and hyperglycemia) based on a physiological individualized long-term model, (iii) it employs disturbance observers to compensate plant-model mismatches, (iv) it ensures, under standard assumptions, closed-loop stability, and (v) it can be used – under minor modifications – as an optimal basal–bolus calculator to emulate conventional therapies. Because of the latter characteristic, a significantly better performance is achieved, not only in terms of classical indexes (time in the normoglycemia zone, avoidance of hypoglycemia in the short term, avoidance of hyperglycemia in the long term) but also in terms of its applicability (use of the pump or injections). Such a performance is tested in a cohort of in-silico patients from the FDA-accepted UVA/Padova simulation platform, considering the most challenging scenarios.Fil: Abuin, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Rivadeneira, P.S.. Universidad Nacional de Colombia. Sede Medellin; ColombiaFil: Ferramosca, Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Tecnológica Nacional. Facultad Regional Reconquista; ArgentinaFil: González, Alejandro Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentin

Impulsive MPC schemes for biomedical processes: Application to type 1 diabetes

During the last decades, dynamic systems considering short-duration inputs have been extensively studied, mainly in the field of biomedical research (being the problem of administration of pills or injections in chronic disease treatments a typical example). Mathematically, inputs are modeled as a sequence of impulses, whose amplitude and frequency must be selected by appropriated control laws. In this chapter, advanced estimation/control schemes are developed for such kind of hybrid systems. In a first stage, the equilibrium of impulsive systems is studied, showing that the formal concept of equilibrium (of continuous or discrete-time systems) is no longer valid and, so, a more general definition (accounting for orbits instead of points) is needed. Then, in a second stage, and based on the aforementioned characterization, two underlying discrete-time systems are proposed to describe the state evolution just before and after the impulsive times. Finally, in a third stage, an impulsive zone model predictive control is formulated by means of the use of artificial/intermediary variables that ensures feasibility for any change of the target zone and provides an enlarged domain of attraction. To complement the model predictive control formulation, an enhanced Kalman observer is designed, able to adequately estimate the state even in cases when some of the system inputs are unknown. To assess the proposed controller, the problem of the glucose regulation in type 1 diabetes patients under challenging conditions is tackled. The example includes parameters variation, non-Gaussian sensor noise, unknown disturbances (i.e., meal intakes), and input constraints. The simulations are performed in a virtual type 1 diabetes mellitus patient extracted from the metabolic UVA/Padova metabolic simulator, and the obtained results show to be promising form both theoretical and practical points of view.Fil: Rivadeneira Paz, Pablo Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina. Universidad Nacional de Colombia; ColombiaFil: Godoy, José Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Sereno Mesa, Juan Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina. Universidad Nacional de Colombia; ColombiaFil: Abuin, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Ferramosca, Antonio. Universidad Tecnológica Nacional. Facultad Regional Reconquista; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: González, Alejandro Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentin

Dynamical characterization of antiviral effects in COVID-19

Mathematical models describing SARS-CoV-2 dynamics and the corresponding immune responses in patients with COVID-19 can be critical to evaluate possible clinical outcomes of antiviral treatments. In this work, based on the concept of virus spreadability in the host, antiviral effectiveness thresholds are determined to establish whether or not a treatment will be able to clear the infection. In addition, the virus dynamic in the host – including the time-to-peak and the final monotonically decreasing behavior – is characterized as a function of the time to treatment initiation. Simulation results, based on nine patient data, show the potential clinical benefits of a treatment classification according to patient critical parameters. This study is aimed at paving the way for the different antivirals being developed to tackle SARS-CoV-2.Fil: Abuin, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Anderson, Alejandro Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Ferramosca, Antonio. University of Bergamo; ItaliaFil: Hernandez Vargas, Esteban Abelardo. Universidad Nacional Autónoma de México; MéxicoFil: González, Alejandro Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentin