Genetic and Swarm Algorithms for Optimizing the Control of Building HVAC Systems Using Real Data: A Comparative Study.

Buildings consume a considerable amount of electrical energy, the Heating, Ventilation, and Air Conditioning (HVAC) system being the most demanding. Saving energy and maintaining comfort still challenge scientists as they conflict. The control of HVAC systems can be improved by modeling their behavior, which is nonlinear, complex, and dynamic and works in uncertain contexts. Scientific literature shows that Soft Computing techniques require fewer computing resources but at the expense of some controlled accuracy loss. Metaheuristics-search-based algorithms show positive results, although further research will be necessary to resolve new challenging multi-objective optimization problems. This article compares the performance of selected genetic and swarmintelligence- based algorithms with the aim of discerning their capabilities in the field of smart buildings. MOGA, NSGA-II/III, OMOPSO, SMPSO, and Random Search, as benchmarking, are compared in hypervolume, generational distance, ε-indicator, and execution time. Real data from the Building Management System of Teatro Real de Madrid have been used to train a data model used for the multiple objective calculations. The novelty brought by the analysis of the different proposed dynamic optimization algorithms in the transient time of an HVAC system also includes the addition, to the conventional optimization objectives of comfort and energy efficiency, of the coefficient of performance, and of the rate of change in ambient temperature, aiming to extend the equipment lifecycle and minimize the overshooting effect when passing to the steady state. The optimization works impressively well in energy savings, although the results must be balanced with other real considerations, such as realistic constraints on chillers’ operational capacity. The intuitive visualization of the performance of the two families of algorithms in a real multi-HVAC system increases the novelty of this proposal.post-print888 K

Autonomic Management Architecture for Multi-HVAC Systems in Smart Buildings.

This article proposes a self-managing architecture for multi-HVAC systems in buildings, based on the “Autonomous Cycle of Data Analysis Tasks” concept. A multi-HVAC system can be plainly seen as a set of HVAC subsystems, made up of heat pumps, chillers, cooling towers or boilers, among others. Our approach is used for improving the energy consumption, as well as to maintain the indoor comfort, and maximize the equipment performance, by means of identifying and selecting of a possible multi-HVAC system operational mode. The multi-HVAC system operational modes are the different combinations of the HVAC subsystems. The proposed architecture relies on a set of data analysis tasks that exploit the data gathered from the system and the environment to autonomously manage the multi-HVAC system. Some of these tasks analyze the data to obtain the optimal operational mode in a given moment, while others control the active HVAC subsystems. The proposed model is based on standard standard HVAC mathematical models, that are adapted on the fly to the contextual data sensed from the environment. Finally, two case studies, one with heterogeneous and another with homogeneous HVAC equipment, show the generality of the proposed autonomous management architecture for multi-HVAC systems.post-print4413 K

Autonomic management of a building's multi-HVAC system start-up

Most studies about the control, automation, optimization and supervision of building HVAC systems concentrate on the steady-state regime, i.e., when the equipment is already working at its setpoints. The originality of the current work consists of proposing the optimization of building multi-HVAC systems from start-up until they reach the setpoint, making the transition to steady state-based strategies smooth. The proposed approach works on the transient regime of multi-HVAC systems optimizing contradictory objectives, such as the desired comfort and energy costs, based on the "Autonomic Cycle of Data Analysis Tasks" concept. In this case, the autonomic cycle is composed of two data analysis tasks: one for determining if the system is going towards the defined operational setpoint, and if that is not the case, another task for reconfiguring the operational mode of the multi-HVAC system to redirect it. The first task uses machine learning techniques to build detection and prediction models, and the second task defines a reconfiguration model using multiobjective evolutionary algorithms. This proposal is proven in a real case study that characterizes a particular multi-HVAC system and its operational setpoints. The performance obtained from the experiments in diverse situations is impressive since there is a high level of conformity for the multi-HVAC system to reach the setpoint and deliver the operation to the steady-state smoothly, avoiding overshooting and other non-desirable transitional effects.European CommissionJunta de Comunidades de Castilla-La ManchaMinisterio de Ciencia e Innovació

CPEB4 Increases Expression of PFKFB3 to Induce Glycolysis and Activate Mouse and Human Hepatic Stellate Cells, Promoting Liver Fibrosis

BACKGROUND & AIMS: We investigated mechanisms of hepatic stellate cell (HSC) activation, which contributes to liver fibrogenesis. We aimed to determine whether activated HSCs increase glycolysis, which is regulated by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3), and whether this pathway might serve as a therapeutic target. METHODS: We performed studies with primary mouse HSCs, human LX2 HSCs, human cirrhotic liver tissues, rats and mice with liver fibrosis (due to bile duct ligation [BDL] or administration of carbon tetrachlo- ride), and CPEB4-knockout mice. Glycolysis was inhibited in cells and mice by administration of a small molecule antagonist of PFKFB3 (3-[3-pyridinyl]-1-[4-pyridinyl]-2- propen-1-one [3PO]). Cells were transfected with small interfering RNAs that knock down PFKFB3 or CPEB4. RESULTS: Up-regulation of PFKFB3 protein and increased glycolysis were early and sustained events during HSC activation and accompanied by increased expression of markers of fibrogenesis; incubation of HSCs with 3PO or knockdown of PFKFB3 reduced their activation and prolif- eration. Mice with liver fibrosis after BDL had increased hepatic PFKFB3; injection of 3PO immediately after the surgery prevented HSC activation and reduced the severity of liver fibrosis compared with mice given vehicle. Levels of PFKFB3 protein were increased in fibrotic liver tissues from patients compared with non-fibrotic liver. Up-regulation of PFKFB3 in activated HSCs did not occur via increased transcription, but instead via binding of CPEB4 to cyto- plasmic polyadenylation elements within the 3'-untranslated regions of PFKFB3 messenger RNA. Knockdown of CPEB4 in LX2 HSCs prevented PFKFB3 overexpression and cell acti- vation. Livers from CPEB4-knockout had decreased PFKFB3 and fibrosis after BDL or administration of carbon tetra- chloride compared with wild-type mice. CONCLUSIONS: Fibrotic liver tissues from patients and rodents (mice and rats) have increased levels of PFKFB3 and glycolysis, which are essential for activation of HSCs. Increased expression of PFKFB3 is mediated by binding of CPEB4 to its untranslated messenger RNA. Inhibition or knockdown of CPEB4 or PFKFB3 prevents HSC activation and fibrogenesis in livers of mice

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Genetic and Swarm Algorithms for Optimizing the Control of Building HVAC Systems Using Real Data: A Comparative Study

Buildings consume a considerable amount of electrical energy, the Heating, Ventilation, and Air Conditioning (HVAC) system being the most demanding. Saving energy and maintaining comfort still challenge scientists as they conflict. The control of HVAC systems can be improved by modeling their behavior, which is nonlinear, complex, and dynamic and works in uncertain contexts. Scientific literature shows that Soft Computing techniques require fewer computing resources but at the expense of some controlled accuracy loss. Metaheuristics-search-based algorithms show positive results, although further research will be necessary to resolve new challenging multi-objective optimization problems. This article compares the performance of selected genetic and swarm-intelligence-based algorithms with the aim of discerning their capabilities in the field of smart buildings. MOGA, NSGA-II/III, OMOPSO, SMPSO, and Random Search, as benchmarking, are compared in hypervolume, generational distance, ε-indicator, and execution time. Real data from the Building Management System of Teatro Real de Madrid have been used to train a data model used for the multiple objective calculations. The novelty brought by the analysis of the different proposed dynamic optimization algorithms in the transient time of an HVAC system also includes the addition, to the conventional optimization objectives of comfort and energy efficiency, of the coefficient of performance, and of the rate of change in ambient temperature, aiming to extend the equipment lifecycle and minimize the overshooting effect when passing to the steady state. The optimization works impressively well in energy savings, although the results must be balanced with other real considerations, such as realistic constraints on chillers’ operational capacity. The intuitive visualization of the performance of the two families of algorithms in a real multi-HVAC system increases the novelty of this proposal

Repositioning tolcapone as a potent inhibitor of transthyretin amyloidogenesis and associated cellular toxicity

Transthyretin (TTR) is a plasma homotetrameric protein implicated in fatal systemic amyloidoses. TTR tetramer dissociation precedes pathological TTR aggregation. Native state stabilizers are promising drugs to treat TTR amyloidoses. Here we repurpose tolcapone, an FDA-approved molecule for Parkinson's disease, as a potent TTR aggregation inhibitor. Tolcapone binds specifically to TTR in human plasma, stabilizes the native tetramer in vivo in mice and humans and inhibits TTR cytotoxicity. Crystal structures of tolcapone bound to wild-type TTR and to the V122I cardiomyopathy-associated variant show that it docks better into the TTR T4 pocket than tafamidis, so far the only drug on the market to treat TTR amyloidoses. These data indicate that tolcapone, already in clinical trials for familial amyloid polyneuropathy, is a strong candidate for therapeutic intervention in these diseases, including those affecting the central nervous system, for which no small-molecule therapy exists.Fil: Sant’Anna, Ricardo. Universitat Autonoma de Barcelona; EspañaFil: Gallego, Pablo. Universitat Autonoma de Barcelona; EspañaFil: Robinson, Lei Z.. The Scripps Research Institute; Estados UnidosFil: Pereira Henriques, Alda. Universidad de Porto; PortugalFil: Ferreira, Nelson. Universidad de Porto; PortugalFil: Pinheiro, Francisca. Universitat Autonoma de Barcelona; EspañaFil: Esperante, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad de Barcelona; EspañaFil: Pallares, Irantzu. Universitat Autonoma de Barcelona; EspañaFil: Huertas, Oscar. SOM-Biotech; EspañaFil: Almeida, Maria Rosario. Universidad de Porto; PortugalFil: Reixach, Natalia. The Scripps Research Institute; Estados UnidosFil: Insa, Raul. SOM-Biotech; EspañaFil: Velazquez Campoy, Adrian. Fundación ARAID; España. Universidad de Zaragoza; España. Instituto de Investigación Sanitaria de Aragón; EspañaFil: Reverter, David. Universitat Autonoma de Barcelona; EspañaFil: Reig, Nuria. SOM-Biotech; EspañaFil: Ventura, Salvador. Universitat Autonoma de Barcelona; Españ

A phase II randomized, multicenter, open-label trial of continuing adjuvant temozolomide beyond 6 cycles in patients with glioblastoma (GEINO 14-01).

Standard treatment for glioblastoma is radiation with concomitant and adjuvant temozolomide for 6 cycles, although the optimal number of cycles of adjuvant temozolomide has long been a subject of debate. We performed a phase II randomized trial investigating whether extending adjuvant temozolomide for more than 6 cycles improved outcome. Glioblastoma patients treated at 20 Spanish hospitals who had not progressed after 6 cycles of adjuvant temozolomide were centrally randomized to stop (control arm) or continue (experimental arm) temozolomide up to a total of 12 cycles at the same doses they were receiving in cycle 6. Patients were stratified by MGMT methylation and measurable disease. The primary endpoint was differences in 6-month progression-free survival (PFS). Secondary endpoints were PFS, overall survival (OS), and safety (Clinicaltrials.gov NCT02209948). From August 2014 to November 2018, 166 patients were screened, 7 of whom were ineligible. Seventy-nine patients were included in the stop arm and 80 in the experimental arm. All patients were included in the analyses of outcomes and of safety. There were no differences in 6-month PFS (control 55.7%; experimental 61.3%), PFS, or OS between arms. MGMT methylation and absence of measurable disease were independent factors of better outcome. Patients in the experimental arm had more lymphopenia (P  Continuing temozolomide after 6 adjuvant cycles is associated with greater toxicity but confers no additional benefit in 6-month PFS. 1. Extending adjuvant temozolomide to 12 cycles did not improve 6-month PFS.2. Extending adjuvant temozolomide did not improve PFS or OS in any patient subset.3. Extending adjuvant temozolomide was linked to increased toxicities

­Tenemos correo!

Se usa el correo para animar a la lectura a los alumnos de Primaria. Es una forma de variar la presentación de las lecturas haciendo que resulten más atractivas para el alumnado. Estos reciben unas cartas muy especiales, se trata de unas lecturas secuenciadas que se presentan de diferentes formas y que inducen a los alumnos a participar en juegos de lectura, ya que en cada carta se les presenta una incógnita que tienen que resolver. Con esta actividad se mejora su actitud hacia la lectura, mejoran la entonación, el ritmo de la lectura en voz alta, la comprensión lectora y la expresión escrita. Además, esta actividad también repercute en un aumento del número de visitas de la biblioteca para buscar información. Se realizan actividades como escribir las respuestas a las cartas, elaborar cuestionarios, realizar dibujos y actividades de expresión plástica como murales, convertirse en espías y tener que buscar información en la biblioteca, en internet para resolver los jeroglíficos, juegos de palabras o adivinanzas. Adjunta ejemplos del material elaborado para el desarrollo de las actividades.Madrid (Comunidad Autónoma). Consejería de Educación. Dirección General de Ordenación AcadémicaMadridMadrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; General Ricardos 179 - 28025 Madrid; Tel. + 34915250893ES