Cell culture-derived flu vaccine: Present and future

Producción CientíficaThe benefit of influenza vaccines is difficult to estimate due to the complexity of accurately assessing the burden of influenza. To improve the efficacy of influenza vaccines, vaccine manufacturers have developed quadrivalent influenza vaccine (QIV) formulations for seasonal vaccination by including both influenza B lineages. Three parallel approaches for producing influenza vaccines are attracting the interest of many vaccine manufacturing companies. The first and oldest is the conventional egg-derived influenza vaccine, which is used by the current licensed influenza vaccines. The second approach is a cell culture-derived influenza vaccine, and the third and most recent is synthetic vaccines. Here, we analyze the difficulties with vaccines production in eggs and compare this to cell culture-derived influenza vaccines and discuss the future of cell culture-derived QIVs.Keywords: Influenza vaccine, cell culture-derived, quadrivalent

Frontiers and political agregations in Celtiberia: data for a debate

Proyecto de investigación “Entre la paz y la guerra: alianzas, confederaciones y diplomacia en el Occidente mediterráneo (siglos III-I a.C.)” (Ref. HAR2011-27782), Plan Nacional I+D+I, Ministerio de Economía y Competitividad, Gobierno de España. Grupo de Investigación Occidens UIB-UAM (www.occidens.es).En el contexto de la II Guerra Púnica (218-206 a.C. para la península Ibérica) y el proceso de expansión romana en Celtiberia (ca. 195-133 a.C.), nuestro objetivo se centra en poner en valor la dimensión espacial, territorial, de las dinámicas históricas, delimitando su papel en la generación de identidades en el mundo celtibérico. Planteamos, en primer lugar, un análisis diacrónico y una contextualización geopolítica de las referencias a coaliciones militares en el interior peninsular, destacando las alianzas defensivas formadas en la década de los años 90 del siglo II a.C. para tratar de contener el avance romano en la línea del Tajo, así como otros ejemplos de coaliciones conocidas para las guerras celtibéricas de mediados de siglo. Estudiamos también, seguidamente, la estructura interna de las póleis celtibéricas, subrayando su composición mixta (oppidum-ager), y reconstruyendo algunos datos sobre la gestión local de los recintos defensivos y de los límites de los territorios. Finalmente, analizamos los tres niveles político-militares identificables en el mundo celtibérico y su correlato territorial. Partiendo del concepto básico de civitas (en terminología latina), se discute la naturaleza suprapolítica y/o étnica de los populi, para analizar finalmente los mecanismos de generación de grandes alianzas y coaliciones, cuya perpetuación en el tiempo habría propiciado también la aparición de elementos identitarios regionales.In the context of the Second Punic War (218-206 BC for the Iberian Peninsula) and the process of Roman expansion in Celtiberia (ca. 195-133 BC), we underline the importance of the territorial, spatial dimension of the historical dynamics, defining its role in the generation of identities in the Celtiberian world. We propose, firstly, a diachronic analysis and a geopolitical contextualization of references to military coalitions in the inner Iberian Peninsula, paying special attention to the defensive alliances formed in the early 90s of the 2nd century BC trying to contain the Roman advance on the line of the river Tagus. We consider also other examples of coalitions during the central decades of the 2nd century. Later on, we deal with the internal structure of the Celtiberian póleis, stressing its mixed composition (oppidum-ager), and reconstructing some data on the local management of the defensive structures and the limits of the territories. Finally, we analyze the three political-military layers that can be identified in the Celtiberian world and its territorial correlate. Starting from the basic concept of civitas (in Latin terminology), the suprapolitical and / or ethnic nature of the populi is discussed, to analyze, finally, the mechanisms of generation of large alliances and coalitions, whose perpetuation in time have also led to the emergence of elements of regional identity

Análisis del rastreo visual necesario para la evaluación de retinografías mediante Eye Tracker

La evaluación retiniana es una de las pruebas más importantes dentro del proceso de exploración del sistema visual. Además de encontrar hallazgos asociados a patología ocular (DMAE, glaucoma, desprendimientos de retina, etc), permite detectar gran cantidad de patologías sistémicas (hipertensión, diabetes, esclerosis múltiple, etc). La retinografía es una técnica que destaca sobre el resto (oftalmoscopía o exploración con lámpara de hendidura) porque permite ver un campo retiniano mucho mayor, reduciendo el tiempo de exploración, resultando más cómodo para el paciente, y permite comparar entre varias imágenes. Por ello, los profesionales de la salud visual, para el correcto ejercicio de su profesión deben dominar el rastreo visual de la retina in vivo o la retinografía. Esto debería realizarse de manera protocolizada, con el fin de aumentar la eficacia y eficiencia de la exploración. Una herramienta útil para evaluar cómo se realiza este rastreo es la tecnología Eye Tracker. Con ello se pretende valorar en este trabajo si alumnos y profesionales de la salud visual realizan de manera ordenada y sistematizada el rastreo visual. Gracias a los datos recogidos por el Eye Tracker se observa que el proceso de rastreo no es independiente de quien lo realiza, es decir, no se realiza de manera protocolizada y en muchos casos no se exploran todas las estructuras retinianas. Como conclusión se extrae que con una correcta enseñanza -en la que se puede incluir la utilización de la tecnología Eye Tracker-, los futuros ópticos-optometristas formados en la Universidad de Valladolid, podrían incrementar su habilidad para realizar un rastreo visual completo y efectivo sobre una retinografía, afianzando así esta competencia imprescindible, lo que acarrearía mejoras en la atención y screening de los pacientes.Retinal evaluation is one of the most important tests within the eye exam. In addition, pathology signs findings associated with ocular pathologies (AMD, glaucoma, retinal detachment, etc) allows us to detect many systemic pathologies, (such as hypertension, diabetes, multiple sclerosis, etc.) Retinography is a technique that stands out above the rest (ophthalmoscopy or slit-lamp examination) because it enables us to see a much larger retinal field, reducing the scanning time, making it more comfortable for the patient and compare between different images. Therefore, visual health professionals, must training on this technique for the correct exercise of their profession. This should be done in a protocolized way, in order to increase the screening efficiency. A useful tool to evaluate how a retinography has visualized is the Eye Tracker technology. With this document, it pretends to value whether students and professionals Optometrist are performing the procedure with an orderly and systematized method or not. Thanks to the data collected by the Eye Tracking tool, we can observe that the retinography visualization is professional dependent, which means that it is not done in a protocolized way, sometimes, any areas were not explored. We can conclude that with a correct training, which could include the use of Eye Tracker technology, the future optometrists formed in the University of Valladolid, could improve their ability to perform a complete and effective visual tracking on a retinography, improving this essential skill, which would lead to important improvements in the assess and screening of the patients.Grado en Óptica y Optometrí

Practical Characterization of Cell-Electrode Electrical Models in Bio-Impedance Assays

This paper presents the fitting process followed to adjust the parameters of the electrical model associated to a cell-electrode system in Electrical Cell-substrate Impedance Spectroscopy (ECIS) technique, to the experimental results from cell-culture assays. A new parameter matching procedure is proposed, under the basis of both, mismatching between electrodes and time-evolution observed in the system response, as consequence of electrode fabrication processes and electrochemical performance of electrode-solution interface, respectively. The obtained results agree with experimental performance, and enable the evaluation of the cell number in a culture, by using the electrical measurements observed at the oscillation parameters in the test circuits employed.Ministerio de Economía y Competitividad TEC2013-46242-C3-1-

Sensing Cell-Culture Assays with Low-Cost Circuitry

An alternative approach for cell-culture end-point protocols is proposed herein. This new technique is suitable for real-time remote sensing. It is based on Electrical Cell-substrate Impedance Spectroscopy (ECIS) and employs the Oscillation-Based Test (OBT) method. Simple and straightforward circuit blocks form the basis of the proposed measurement system. Oscillation parameters – frequency and amplitude – constitute the outcome, directly correlated with the culture status. A user can remotely track the evolution of cell cultures in real time over the complete experiment through a web tool continuously displaying the acquired data. Experiments carried out with commercial electrodes and a well-established cell line (AA8) are described, obtaining the cell number in real time from growth assays. The electrodes have been electrically characterized along the design flow in order to predict the system performance and the sensitivity curves. Curves for 1-week cell growth are reported. The obtained experimental results validate the proposed OBT for cell-culture characterization. Furthermore, the proposed electrode model provides a good approximation for the cell number and the time evolution of the studied cultures.España, Feder TEC2013-46242-C3-1-

An Empirical-Mathematical Approach for Calibration and Fitting Cell-Electrode Electrical Models in Bioimpedance Tests

This paper proposes a new yet efficient method allowing a significant improvement in the on-line analysis of biological cell growing and evolution. The procedure is based on an empirical-mathematical approach for calibration and fitting of any cell-electrode electrical model. It is valid and can be extrapolated for any type of cellular line used in electrical cell-substrate impedance spectroscopy (ECIS) tests. Parameters of the bioimpedance model, acquired from ECIS experiments, vary for each cell line, which makes obtaining results difficult and—to some extent-renders them inaccurate. We propose a fitting method based on the cell line initial characterization,and carry out subsequent experiments with the same line to approach the percentage of well filling and the cell density (or cell number in the well). To perform our calibration technique, the so-called oscillation-based test (OBT) approach is employed for each cell density. Calibration results are validated by performing other experiments with different concentrations on the same cell line with the same measurement technique. Accordingly, a bioimpedance electrical model of each cell line is determined, which is valid for any further experiment and leading to a more precise electrical model of the electrode-cell system. Furthermore, the model parameters calculated can be also used by any other measurement techniques. Promising experimental outcomes for three different cell-lines have been achieved, supporting the usefulness of this technique

Remote Cell Growth Sensing Using Self-Sustained Bio-Oscillations

A smart sensor system for cell culture real-time supervision is proposed, allowing for a significant reduction in human effort applied to this type of assay. The approach converts the cell culture under test into a suitable “biological” oscillator. The system enables the remote acquisition and management of the “biological” oscillation signals through a secure web interface. The indirectly observed biological properties are cell growth and cell number, which are straightforwardly related to the measured bio-oscillation signal parameters, i.e., frequency and amplitude. The sensor extracts the information without complex circuitry for acquisition and measurement, taking advantage of the microcontroller features. A discrete prototype for sensing and remote monitoring is presented along with the experimental results obtained from the performed measurements, achieving the expected performance and outcomes

Robust Federated Learning for execution time-based device model identification under label-flipping attack

The computing device deployment explosion experienced in recent years, motivated by the advances of technologies such as Internet-of-Things (IoT) and 5G, has led to a global scenario with increasing cybersecurity risks and threats. Among them, device spoofing and impersonation cyberattacks stand out due to their impact and, usually, low complexity required to be launched. To solve this issue, several solutions have emerged to identify device models and types based on the combination of behavioral fingerprinting and Machine/Deep Learning (ML/DL) techniques. However, these solutions are not appropriate for scenarios where data privacy and protection are a must, as they require data centralization for processing. In this context, newer approaches such as Federated Learning (FL) have not been fully explored yet, especially when malicious clients are present in the scenario setup. The present work analyzes and compares the device model identification performance of a centralized DL model with an FL one while using execution time-based events. For experimental purposes, a dataset containing execution-time features of 55 Raspberry Pis belonging to four different models has been collected and published. Using this dataset, the proposed solution achieved 0.9999 accuracy in both setups, centralized and federated, showing no performance decrease while preserving data privacy. Later, the impact of a label-flipping attack during the federated model training is evaluated using several aggregation mechanisms as countermeasures. Zeno and coordinate-wise median aggregation show the best performance, although their performance greatly degrades when the percentage of fully malicious clients (all training samples poisoned) grows over 50%