Enhancing dendritic cell immunotherapy for melanoma using a simple mathematical model

ABSTRACT Background: The immunotherapy using dendritic cells (DCs) against different varieties of cancer is an approach that has been previously explored which induces a specific immune response. This work presents a mathematical model of DCs immunotherapy for melanoma in mice based on work by Experimental Immunotherapy Laboratory of the Medicine Faculty in the Universidad Autonoma de Mexico (UNAM). Method: The model is a five delay differential equation (DDEs) which represents a simplified view of the immunotherapy mechanisms. The mathematical model takes into account the interactions between tumor cells, dendritic cells, naive cytotoxic T lymphocytes cells (inactivated cytotoxic cells), effector cells (cytotoxic T activated cytotoxic cells) and transforming growth factor β cytokine (TGF − β). The model is validated comparing the computer simulation results with biological trial results of the immunotherapy developed by the research group of UNAM. Results: The results of the growth of tumor cells obtained by the control immunotherapy simulation show a similar amount of tumor cell population than the biological data of the control immunotherapy. Moreover, comparing the increase of tumor cells obtained from the immunotherapy simulation and the biological data of the immunotherapy applied by the UNAM researchers obtained errors of approximately 10 %. This allowed us to use the model as a framework to test hypothetical treatments. The numerical simulations suggest that by using more doses of DCs and changing the infusion time, the tumor growth decays compared with the current immunotherapy. In addition, a local sensitivity analysis is performed; the results show that the delay in time “τ ”, the maximal growth rate of tumor “r” and the maximal efficiency of tumor cytotoxic cells rate “aT” are the most sensitive model parameters. Conclusion: By using this mathematical model it is possible to simulate the growth of the tumor cells with or without immunotherapy using the infusion protocol of the UNAM researchers, to obtain a good approximation of the biological trials data. It is worth mentioning that by manipulating the different parameters of the model the effectiveness of the immunotherapy may increase. This last suggests that different protocols could be implemented by the Immunotherapy Laboratory of UNAM in order to improve their results

Monitoring of the arterial pressure in effort. dominant, not dominant arm or both?

Objetivo: evaluar la diferencia de los valores de Presión arterial (PA) entre ambos brazos, medida simultáneamente, durante una prueba de esfuerzo. Diseño del estudio: estudio transversal. Series de casos. Nivel de evidencia: 3 Material y Métodos: La población se compone de 225 deportistas sanos que realizaron una prueba de esfuerzo en nuestro centro. 128 hombres y 97 mujeres. Edad: 17± 5,5 años. Resultados: La PA tanto sistólica como diastólica no difiere significativamente entre ambos miembros superiores. No obstante, hemos encontrado casos de variabilidad individual donde la PA predomina en un brazo durante el reposo y en el otro brazo durante el máximo esfuerzo. Los valores de TA son independientes del brazo dominante. Conclusiones: La posibilidad que el brazo donde predomina la PA de Reposo no coincida durante el máximo esfuerzo, hace necesario, en nuestra opinión, que se mida la PA en ambos miembros superiores durante la prueba de esfuerzoObjective: To evaluate different blood pressure readings between both arms. Study design: cross-sectional study. Case series. Level of evidence: 3. Methods: a population of 225 healthy athletes underwent stress tests in our center: 128 males and 97 females. Age range: 17 +/- 5.5 years. Results: no significant differences in systolic or diastolic blood pressure readings were found between the right or left arm. We did, however, find cases where blood pressure is higher in one arm while resting and in the other arm during maximal exercise. Blood pressure readings were not associated with the dominant arm. Conclusions: The possibility that the arm in which there is a predominant rest blood pressure does not coincide during maximum stress, makes it necessary, according to our judgment, to measure blood pressure in both upper limbs during stress test

Management of inflammation in dry eye disease: Recommendations from a European panel of experts

Introduction: Early initiation of anti-inflammatory therapies is recommended for dry eye disease (DED) to break the vicious cycle of pathophysiology. However, there is limited guidance on how to implement topical ciclosporin (CsA) and corticosteroid treatment into clinical practice. This expert-led consensus provides practical guidance on the management of DED, including when and how to use topical CsA. Methods: A steering committee (SC) of seven European DED experts developed a questionnaire to gain information on the unmet needs and management of DED in clinical practice. Consensus statements on four key areas (disease severity and progression; patient management; efficacy, safety and tolerability of CsA; and patient education) were generated based on the responses. The SC and an expanded expert panel of 22 members used a nine-point scale (1 = strongly disagree; 9 = strongly agree) to rate statements; a consensus was reached if ≥75% of experts scored a statement ≥7. Results: A stepwise approach to DED management is required in patients presenting with moderate corneal staining. Early topical CsA initiation, alone or with corticosteroids, should be considered in patients with clinical risk factors for severe DED. Patient education is required before and during treatment to manage expectations regarding efficacy and tolerability in order to optimise adherence. Follow-up visits are required, ideally at Month 1 and every 3 months thereafter. Topical CsA may be continued indefinitely, especially when surgery is required. Conclusion: This consensus fills some of the knowledge gaps in previous recommendations regarding the use of topical corticosteroids and CsA in patients with DED

Long-time discrete particle effects versus kinetic theory in the self-consistent single-wave model

The influence of the finite number N of particles coupled to a monochromatic wave in a collisionless plasma is investigated. For growth as well as damping of the wave, discrete particle numerical simulations show an N-dependent long time behavior resulting from the dynamics of individual particles. This behavior differs from the one due to the numerical errors incurred by Vlasov approaches. Trapping oscillations are crucial to long time dynamics, as the wave oscillations are controlled by the particle distribution inhomogeneities and the pulsating separatrix crossings drive the relaxation towards thermal equilibrium.Comment: 11 pages incl. 13 figs. Phys. Rev. E, in pres

On scattering off the extreme Reissner-Nordstr\"om black hole in N=2 supergravity

The scattering amplitudes for the perturbed fields of the N=2 supergravity about the extreme Reissner-Nordstr\"om black hole is examined. Owing to the fact that the extreme hole is a BPS state of the theory and preserves an unbroken global supersymmetry(N=1), the scattering amplitudes of the component fields should be related to each other. In this paper, we derive the formula of the transformation of the scattering amplitudes.Comment: 9 pages, revtex, no figures, a few typing errors correcte

Modelización y estimación del riesgo para la salud de la vivienda urbana empleando redes neuronales artificiales

El presente proyecto se enmarca en una línea de investigación relacionada con la aplicación de técnicas de aprendizaje automático, especialmente las redes neuronales artificiales, a la resolución de problemas de las ciencias sociales. El grupo de investigación nuclea a investigadores de la UTN y IIGHI-Conicet, y tiene como uno de sus logros la creación de un software y un modelo computacional que implementa la metodología de estimación del riesgo para la salud de la vivienda urbana desde el enfoque de la vulnerabilidad social, propuesta por el IIGHI-CONICET. Este software denominado RVS (por sus siglas de Riesgo, Vivienda y Salud) se ha desarrollado de basado en redes neuronales artificiales que emula una red conceptual de relación de factores sociales, económicos y demográficos que no se ajusta a los modelos clásicos. Los demógrafos del IIGHI suponen el dominio de problema como complejo y no lineal; indican además que aún no existen mediciones precisas de causa y efecto para el mismo, por lo que su tratamiento por ecuaciones matemáticas no es posible. Se han utilizando cinco redes de tipo perceptron multicapa trabajando en forma conjunta para calcular un índice de riesgo que permitiría a las autoridades de salud dirigir más acertadamente los fondos disponibles, en la medida que la metodología sea confirmada por trabajo de campo, tarea que está en marcha en algunos países de América Latina.Eje: Agentes y sistemas inteligentesRed de Universidades con Carreras en Informática (RedUNCI

Modelo computacional empleando redes neuronales artificiales para la estimación del riesgo para la salud de la vivienda urbana

En este paper se describe brevemente la modelización del riesgo de la vivienda para la salud empleando un método elaborado por el instituto IIGHI-CONICET. A su vez, se creó un modelo informático-computacional que implementa este modelo conceptual. Como resultado de este proyecto, se diseñó e implemento un software denominado RVS (por sus siglas de Riesgo, Vivienda y Salud). Se comenta en este paper las bases de ambos modelos, como así también conclusiones parciales y los próximos pasos previstos en ese sentido.Eje: Agentes y sistemas inteligentesRed de Universidades con Carreras en Informática (RedUNCI

Modelo computacional empleando redes neuronales artificiales para la estimación del riesgo para la salud de la vivienda urbana

En este paper se describe brevemente la modelización del riesgo de la vivienda para la salud empleando un método elaborado por el instituto IIGHI-CONICET. A su vez, se creó un modelo informático-computacional que implementa este modelo conceptual. Como resultado de este proyecto, se diseñó e implemento un software denominado RVS (por sus siglas de Riesgo, Vivienda y Salud). Se comenta en este paper las bases de ambos modelos, como así también conclusiones parciales y los próximos pasos previstos en ese sentido.Eje: Agentes y sistemas inteligentesRed de Universidades con Carreras en Informática (RedUNCI