System dynamics modelling in systems biology and applications in pharmacology

El modelado matemático de sistemas biológicos complejos es uno de los temas clave en la Biología de Sistemas y varios métodos computacionales basados ​​en la simulación computarizada han sido aplicados hasta ahora para determinar el comportamiento de los sistemas no lineales. La Dinamica de Sistemas es una metodología de modelado intuitivo basada en el razonamiento cualitativo por el cual un modelo conceptual se puede describir como un conjunto de relaciones de causa y efecto entre las variables de un sistema. A partir de esta estructura, es posible obtener un conjunto de ecuaciones dinámicas que describan cuantitativamente el comportamiento del sistema. Centrándose en los sistemas farmacológicos, el modelado compartimental a menudo se utiliza para resolver un amplio espectro de problemas relacionados con la distribución de materiales en los sistemas vivos en la investigación, el diagnóstico y la terapia en todo el cuerpo, los órganos y los niveles celulares. En este artículo presentamos la metodología de modelado de Dinámica del Sistema y su aplicación al modelado de un modelo compartimental farmacocinético-farmacodinámico del efecto de profundidad anestésica en pacientes sometidos a intervenciones quirúrgicas, derivando un modelo de simulación en el entorno de simulación orientada a objetos OpenModelica. La Dinamica de Sistemas se puede ver como una herramienta educativa poderosa y fácil de usar y en la enseñanza de Biología de Sistemas.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Phase diagram of an extended Agassi model

Background: The Agassi model is an extension of the Lipkin-Meshkov-Glick model that incorporates the pairing interaction. It is a schematic model that describes the interplay between particle-hole and pair correlations. It was proposed in the 1960's by D. Agassi as a model to simulate the properties of the quadrupole plus pairing model. Purpose: The aim of this work is to extend a previous study by Davis and Heiss generalizing the Agassi model and analyze in detail the phase diagram of the model as well as the different regions with coexistence of several phases. Method: We solve the model Hamiltonian through the Hartree-Fock-Bogoliubov (HFB) approximation, introducing two variational parameters that play the role of order parameters. We also compare the HFB calculations with the exact ones. Results: We obtain the phase diagram of the model and classify the order of the different quantum phase transitions appearing in the diagram. The phase diagram presents broad regions where several phases, up to three, coexist. Moreover, there is also a line and a point where four and five phases are degenerated, respectively. Conclusions: The phase diagram of the extended Agassi model presents a rich variety of phases. Phase coexistence is present in extended areas of the parameter space. The model could be an important tool for benchmarking novel many-body approximations.Comment: Accepted for publication in PR

An extended Agassi model: algebraic structure, phase diagram, and large size limit

The Agassi model is a schematic two-level model that involves pairing and monopole-monopole interactions. It is, therefore, an extension of the well known Lipkin-Meshkov-Glick (LMG) model. In this paper we review the algebraic formulation of an extension of the Agassi model as well as its bosonic realization through the Schwinger representation. Moreover, a mean-field approximation for the model is presented and its phase diagram discussed. Finally, a $1/j$ analysis, with $j$ proportional to the degeneracy of each level, is worked out to obtain the thermodynamic limit of the ground state energy and some order parameters from the exact Hamiltonian diagonalization for finite$-j$.Comment: Accepted in Physica Scripta. Focus on SSNET 201

Second order SUSY transformations with `complex energies'

Second order supersymmetry transformations which involve a pair of complex conjugate factorization energies and lead to real non-singular potentials are analyzed. The generation of complex potentials with real spectra is also studied. The theory is applied to the free particle, one-soliton well and one-dimensional harmonic oscillator.Comment: 11 pages, 2 figures, submitted on 23 August 2002 to Phys. Lett.

PCL/POSS Nanocomposites: Effect of POSS Derivative and Preparation Method on Morphology and Properties

The incorporation of polyhedral oligomeric silsesquioxanes (POSS) molecules as nanoparticles into polymers can provide improved physico-chemical properties. The enhancement depends on the extent of dispersion of the nanofiller, which is determined by the compatibility with the polymer that is by the POSS type, and the processing method. In this study, poly(epsilon-caprolactone)/POSS derivatives nanocomposites (PCL/POSS) were obtained via solution-casting and melt compounding. Two amino-derivatives containing different alkyl substituents, and ditelechelic POSS-containing hybrid PCL masterbatch were used as nanofillers. The effect of preparation method, POSS content and type on the morphology, thermal, mechanical, and surface properties of nanocomposites were studied. Morphological analysis evidenced the formation of POSS crystalline aggregates, self-assembled POSS molecules of submicrometer size dispersed in the polymer matrix. The best dispersion was achieved using the ditelechelic POSS-containing hybrid PCL masterbatch, and comparing the two amino-POSS derivatives, the one with longer alkyl chain of substituents exhibited better degree of dispersion independent of preparation method. DSC analysis showed the role of POSS derivatives as nucleating agents for PCL. The incorporation of POSS derivatives into the PCL matrix improved thermal stability. The preparation method, POSS type and content had influence on mechanical properties of nanocomposites. POSS nanoparticles enhanced the surface hydrophobicity of PCL.This research was funded by the Basque Government (SAIOTEK 2012 S-PE12UN006) and the University of the Basque Country (UFI11/56)

Model and neural control of the depth of anesthesia during surgery

At present, the experimentation of anesthetic drugs on patients requires a regulation protocol, and the response of each patient to several doses of entry drug must be well known. Therefore, the development of pharmacological dose control systems is a promising field of research in anesthesiology. In this paper it has been developed a non-linear compartmental pharmacokinetic-pharmacodynamical model which describes the anesthesia depth effect on a sufficiently reliable way over a set of patients with the depth effect quantified by the Bi-Spectral Index. Afterwards, an Artificial Neural Network (ANN) predictive controller has been designed based on the depth of anesthesia model so as to keep the patient on the optimum condition while he undergoes surgical treatment. For the purpose of quantifying the efficiency of the neural predictive controller, a classical proportional-integral-derivative controller has also been developed to compare both strategies. Results show the superior performance of predictive neural controller during Bi- Spectral Index reference tracking.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

The incremental effect of Dark personality over the Big Five in workplace bullying: Evidence from perpetrators and targets

The current study analyzes the relationship between workplace bullying (self-reported experience of being a target and perpetration of bullying behaviors), Big Five and Dark Tetrad personality traits. The sample comprised 613 employees (54% female) from different Spanish organizations. Hierarchical regression analyses showed that neuroticism and Machiavellianism were positively related to being a target to bullying-related behaviors, whereas narcissism was negatively related. In the case of perpetrators, narcissism and sadism were positively, and agreeableness negatively related to workplace bullying behaviors. We conclude that personality traits are different in targets and perpetrators and should always be considered when investigating workplace bullying

Occupational factors associated with health-related quality of life in nursing professionals: a multi-centre study

Background: Nursing professionals are exposed to stressful situations arising from the work context that may affect health-related quality of life (HRQoL). The objective of this study was to analyse the relationship between sociodemographic and work-related variables regarding HRQoL in nursing professionals. Methods: A multi-centre, cross-sectional descriptive design was used. The participants consisted 1521 nurses working in healthcare centres, in both primary care and hospital care, in the eight provinces of the Andalusian Public Health System (APHS), Spain. Sociodemographic and work-related variables were analysed: Compassion fatigue, compassion satisfaction and burnout were measured using the professional quality of life questionnaire (ProQOL), and HRQoL was measured using the SF-12 health questionnaire. Results: Compassion fatigue, burnou, and, to a lesser extent, compassion satisfaction significantly influence the physical and mental components of HRQoL. The simple regression analysis showed that burnout and compassion fatigue were significantly associated with the mental component of HRQoL. Gender influenced the mental component of HRQoL. The rest of the sociodemographic and work-related variables were not significantly related to HRQoL. Conclusion: Work-related stress and repeated contact with situations of suffering influence HRQoL. Health systems must implement programmes to increase the emotional well-being of workers

Evaluación de la función adrenal en perros

En 30 perros sanos, hemos estudiado los niveles de cortisol plasmático antes y después de la administración de hormona adrenocórticotropa (ACTH sintético, vía i.m.) y de dexametasona (dosis de 0,01 y 0,02 mg/Kg p.v., vía i.v.), Las pruebas se iniciaron siempre antes de las 10 horas de la mañana y las determinaciones de cortisol plasmático se evaluaron mediante técnicas de RIA. En nuestras condiciones de trabajo, hemos encontrado unos niveles basales de cortisol cuyo rango va de 0,17 a 7,95 ug/ dl. Se ha observado que, en perros sin sintomatología adrenal y con perfiles hematológicos y bioquímicos normales, la prueba de estimulación con ACTH exógeno, a las dos horas de su administración, es capaz de discriminar como animales sanos el 76,7% de los individuos (23 animales), dando falsos resultados positivos en el 10% (3 animales) y una estimulación baja en el U)% (4 animales). La prueba con dexametasona (0,01 mg/Kg p.v.), a las 8 horas de su aplicación, sólo es capaz de ejercer efecto inhibitorio en el 40% de los casos (12 individuos); pero cuando se incrementa la dosis al doble (dexametasona 0,02 mg/Kg p.v.) se 49 obtienen los mejores resultados de toda la experiencia porque se produce el efecto supresor esperado en el 96,7% de los individuos (29 animales).Thirty healty dogs uiere evaluated for plasma cortisol values before and after adrenocorticotrophic hormone (ACm, administered i.m.) and low dose dexamethasone (0.01 and 0.02 mglKgp.v. administered i.u.). The assays started always before 10 hour A.M.} and cortisol plasma concentrations were determined by RIA. In our laboratory we have obserued the normal baseline morning cortisol concentration was between 0.17 and 7.95 ¡..tgldl. ACTH-estimulation test wasfound abnormal bypereponse in 10% (J animals), anormallow stimulation in 11.1% (a dogs) and a expected byperreponse in 76.7% (23) ofthe normal dogs.Dexamethasone-screening test (0.01 mg/Kgp.v.) bring us supressed effect in 40% (12 animals). But wefound the best reliable results when screening test was applied with 0.02 mg/Kgp.v. dexamethasone dose. the suppressed especting effect wasfound in 06. 7% (29 dogs)