Setting up a C-arm for its use as a tomograph

The work included in this thesis is framed on one of the lines of research carried out by the Biomedical Imaging and Instrumentation group from the Bioengineering and Aerospace Department of Universidad Carlos III de Madrid working jointly with the Gregorio Marañón Hospital. Its goal is to design and develop a new generation of Radiology Systems, valid for clinical and veterinary applications, through the research and development of innovative technologies in advanced image processing oriented to increase image quality, to reduce dose and to incorporate tomography capabilities. The latter will allow bringing tomography to situations in which a CT system is not allowable, due to cost issues or when the patient cannot be moved (for instance, during surgery or ICU). It may also be relevant to reduce the radiation dose delivered to the patient, if we can obtain a tomographic image from fewer projections than using a CT. In that context, this thesis deals with incorporating tomography capabilities in a system originally design for planar images: the SIREMOBIL C-arm developed by SIEMENS. The system consists of an X-ray generator and a detector mounted in an arc-shaped wheeled base that allows a great variety of movements. The use of this C-arm for tomography presents several difficulties: (1) the detector is an image intensifier which is an analog detector with image distortions, (2) the system may have mechanical strains changing the relative positions of the source and detector, and (3) the movements of source-detector pair may differ from a circular path. To obtain good quality images, it is necessary to design a new acquisition protocol that solves the effects of these non-idealities including an exhaustive calibration of the system, not needed when it is used for planar imaging. First a calibration algorithm has been adapted to the system under study. Besides the mechanical calibration of the source and detector relative positions, it is necessary to obtain the angular position of the complete system. This work presents the effects of errors in the angle estimation and describes the implementation of a positioning system that obtains the angular position with the required precision for a tomographic reconstruction. A digital detector has also been incorporated to the system to solve the drawbacks of the image intensifier together with the development of a software tool to transform the data acquired into in the appropriate format for the reconstruction software. Evaluation of the proposed acquisition protocol on phantoms and rodent data show the feasibility of the proposal. Part of this project has generated a scientific publication and was presented as an oral communication at the Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB). Finally, it should be noted that the work of this thesis has a clear application in industry, since it is part of a proof of concept of the new generation of C-arm systems which will be commercialized worldwide by the company SEDECAL.El trabajo presentado en esta tesis forma parte de una línea de investigación llevada a cabo por el Grupo de Instrumentación e imagen Médica del departamento de Bioingeniería y Aeroespaciales de la Universidad Carlos III de Madrid en colaboración con el Hospital Gregorio Marañón. Tiene por objetivo el diseño y desarrollo de una nueva generación de sistemas radiológicos, con aplicación tanto en clínica como en veterinaria, a través de la investigación y el desarrollo de las nuevas tecnologías orientadas a la mejora de la calidad de la imagen, con el fin de reducir la dosis recibida por el paciente e incorporar capacidades tomográficas. Esta última característica permitiría el uso de la tomografía en situaciones en las que no es posible utilizar un sistema TAC, ya sea por razones económicas o porque el paciente no puede ser desplazado (por ejemplo, durante una cirugía o porque se encuentra en la UCI). Otro punto relevante sería la reducción de la dosis de radiación recibida por el paciente, al poder obtener imágenes tomográficas usando menos proyecciones que utilizando un TAC. En este contexto, esta tesis trata de incorporar capacidades tomográficas a un sistema originalmente diseñado para obtener imágenes planas, en particular, el arco en C SIREMOBIL desarrollado por SIEMENS. Este sistema consta de una fuente de rayos X y un detector montados sobre una base con forma de arco que permite una gran variedad de movimientos. El uso de este arco en C como tomógrafo presenta varias dificultades: (1) el detector es un intensificador de imagen, que es un detector analógico que presenta distorsiones en la imagen, (2) el sistema puede presentar deformaciones mecánicas que resultan en el cambio de la posición relativa de la fuente y el detector, y (3) los movimientos del conjunto fuente-detector pueden diferir de una trayectoria circular. Para obtener imágenes de buena calidad, es necesario diseñar un nuevo protocolo de adquisición que solucione los efectos de estas deficiencias incluyendo una calibración exhaustiva del sistema, no necesaria cuando es usado para obtener imágenes planas. IX En primer lugar, se ha adaptado un algoritmo de calibración al sistema en estudio. Además de la calibración mecánica de la posición relativa de la fuente y del detector, es necesario obtener la posición angular del sistema en su conjunto. Este trabajo presenta los efectos de errores en la estimación de la posición angular y describe la implementación de un sistema de posicionamiento que obtiene la posición angular con la precisión necesaria para llevar a cabo una reconstrucción tomográfica. Un detector digital ha sido también incorporado al sistema para solucionar los inconvenientes derivados del intensificador de imagen. Además, se ha desarrollado un software que permite adaptar los datos adquiridos al formato utilizado por el software de reconstrucción. Resultados de la evaluación del protocolo de adquisición propuesto en un maniquí de calibración y en un roedor muestran la viabilidad de la propuesta. Parte de este proyecto ha generado una publicación científica que ha sido presentada como comunicación oral en el Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB). Finalmente, cabe destacar que el trabajo de esta tesis tiene una clara aplicación industrial, ya que forma parte de una prueba de concepto de la nueva generación de sistemas de arco en C que comercializará la empresa SEDECAL en todo el mundo.Ingeniería Biomédic

Novel Horizons in Postbiotics: Lactobacillaceae Extracellular Vesicles and Their Applications in Health and Disease

Lactobacillus probiotics contained in dietary supplements or functional foods are wellknown for their beneficial properties exerted on host health and diverse pathological situations. Their capacity to improve inflammatory bowel disease (IBD) and regulate the immune system is especially remarkable. Although bacteria–host interactions have been thought to occur directly, the key role that extracellular vesicles (EVs) derived from probiotics play on this point is being unveiled. EVs are lipid bilayer-enclosed particles that carry a wide range of cargo compounds and act in different signalling pathways. Notably, these EVs have been recently proposed as a safe alternative to the utilisation of live bacteria since they can avoid the possible risks that probiotics may entail in vulnerable cases such as immunocompromised patients. Therefore, this review aims to give an updated overview of the existing knowledge about EVs from different Lactobacillus strains, their mechanisms and effects in host health and different pathological conditions. All of the information collected suggests that EVs could be considered as potential tools for the development of future novel therapeutic approaches.Junta de Andalucia CTS 164 PY20_01157Instituto de Salud Carlos III European Commission PI19/01058 European Commissio

Validation of the attitudinal scale of open educational practices in university teachers

The relevance of Open Educational Resources (OER) in the Latin American university context requires an instrument that measures the conceptual, procedural, and attitudinal aspects that teachers consider having in their open educational practices. The purpose of this research is to describe the process of design and validation of the Attitudinal Scale of Open Educational Practices (ASOEP) Scale. Consequently, the methodological approach corresponds to a descriptive, transectional, instrumental design that has three components: scale design, evaluation by expert judgment and validation with the pilot application. The pilot test was applied to a random sample with 123 teachers at a university in Colombia. The results from the validation of the content had the participation of five international experts who were classified according to coefficient K in the range between (k: .80 and k: 1.00). From the pilot application, the ASOEP Scale presented a general reliability of (?: .943)

Percepção de qualidade de vida e autonomia pessoal em crianças e adolescentes com TDAH: revisão sistemática.

Abstract: Attention deficit hyperactivity disorder (ADHD) encompasses a pattern of complex and heterogeneous symptoms. It has a neurobiological origin and produces alterations in the executive functions, being very characteristic the inability to focus the attention on the daily actions, regulate the level of activity and inhibit the motor and/or cognitive behavior. The disorder affects the development of the child and causes an alteration in the perception of the quality of life and personal autonomy. The performance of daily activities in the different levels of complexity they require is hampered by the presence of ADHD. There are evidence-based interventions for symptom reduction, although no treatment has been found to directly improve the performance of daily life activities or affect the well-being of children with ADHD and their families.Resumen: El Trastorno por Déficit de Atención con Hiperactividad (TDAH) comprende un patrón de síntomas complejos y heterogéneos. Tiene un origen neurobiológico y produce alteraciones en las funciones ejecutivas, siendo muy característica la incapacidad para centrar atención en las acciones cotidianas, regular el nivel de actividad e inhibir el comportamiento motriz y/o cognitivo. El trastorno impacta en el desarrollo del menor y provoca una alteración en la percepción de la calidad de vida y en la autonomía personal. El desempeño de las actividades diarias en los distintos niveles de la complejidad que requieren, está obstaculizado por la presencia del TDAH. Existen intervenciones basadas en evidencia para la reducción de los síntomas aunque no se ha encontrado tratamiento que mejore directamente la ejecución de las actividades de la vida diaria ni que incida en el bienestar de los niños con TDAH y de sus familia

Introducing life cycle thinking to define best available techniques for products: Application to the anchovy canning industry

This study presents a method based on life cycle assessment to reduce and simplify the decision-making process and to identify the best available techniques of a product. This procedure facilitates the selection of a technical alternative from an environmental point of view and the reduction of emission levels and the consumption of energy and primary resources. This method comprises the following four steps: (i) the identification of the current techniques of a specific product, (ii) the application of a life cycle assessment to determine the hot spots, (iii) the proposal of the best available techniques and (iv) the development of a best available techniques reference document (step not implemented in our case study). The Cantabrian anchovy canning industry is selected as a case study due to the importance of this sector from economic, social and touristic points of view. An entire life cycle assessment of one can of anchovies in extra virgin olive oil is conducted. The results indicated that the hot spots of the life cycle were the production of aluminium cans (for packaging) and extra virgin olive oil and the management of the packaging waste. According to these results, the study proposes several improvements, such as packaging recycling and several best available techniques for the canned anchovy product.The authors thank the Ministry of Economy and Competitiveness of the Spanish Government for their financial support via the project GeSAC-Conserva: Sustainable Management of the Cantabrian Anchovies (CTM2013-43539-R) and to Julia Celaya for her technical support. Jara Laso thanks the Ministry of Economy and Competitiveness of Spanish Government for their financial support via the research fellowship BES2014-069368. Pere Fullana y Alba Bala thanks the UNESCO Chair in Life Cycle and Climate Change

Incorporating linear programing and life cycle thinking into environmental sustainability decision-making: a case study on anchovy canning industry

Life cycle assessment (LCA) is a powerful tool to support environmental informed decisions among product and process alternatives. LCA results reflect the process stage contributions to several environmental impacts, which should be made mutually comparable to help in the decision-making process. Aggregated environmental indexes enable the translation of this set of metrics into a one final score, by defining the attached weights to impacts. Weighting values reflect the corresponding relevance assigned to each environmental impact. Current weighing schemes are based on pre-articulation of preferences, without considering the specific features of the system under study. This paper presents a methodology that combines LCA methodology and linear programming optimisation to determine the environmental improvement actions that conduct to a more sustainable production. LCA was applied using the environmental sustainability assessment methodology to obtain two main indexes: natural resources (NR) and environmental burdens (EB). Normalised indexes were optimised to determine the optimal joint of weighting factors that lead to an optimised global Environmental Sustainability Index. The proposed methodology was applied to a food sector, in particular, to the anchovy canning industry in Cantabria Region (Northern Spain). By maximising the objective function composed of NR and EB variables, it is possible to find the optimal joint of weights that identify the best environmental sustainable options. This study proves that LCA can be applied in combination with linear programing tools as a part of the decision-making process in the development of more sustainable processes and products.Authors thank to Ministry of Economy and Competitiveness of Spanish Government for the financial support through the project GeSAC-Conserva (CTM2013-43539-R). Jara Laso also thanks to the Ministry of Economy and Competitiveness of Spanish Government for the financial support through the research fellowship BES-2014-069368

Molecular Determinants of Kv1.3 Potassium Channels-induced Proliferation

Producción CientíficaChanges in voltage-dependent potassium channels (Kv channels) associate to proliferation in many cell types, including transfected HEK293 cells. In this system Kv1.5 overexpression decreases proliferation, whereas Kv1.3 expression increases it independently of K+ fluxes. To identify Kv1.3 domains involved in a proliferation-associated signaling mechanism(s), we constructed chimeric Kv1.3-Kv1.5 channels and point-mutant Kv1.3 channels, which were expressed as GFP- or cherry-fusion proteins. We studied their trafficking and functional expression, combining immunocytochemical and electrophysiological methods, and their impact on cell proliferation. We found that the C terminus is necessary for Kv1.3-induced proliferation. We distinguished two residues (Tyr-447 and Ser-459) whose mutation to alanine abolished proliferation. The insertion into Kv1.5 of a sequence comprising these two residues increased proliferation rate. Moreover, Kv1.3 voltage-dependent transitions from closed to open conformation induced MEK-ERK1/2-dependent Tyr-447 phosphorylation. We conclude that the mechanisms for Kv1.3-induced proliferation involve the accessibility of key docking sites at the C terminus. For one of these sites (Tyr-447) we demonstrated the contribution of MEK/ERK-dependent phosphorylation, which is regulated by voltage-induced conformational changes.Ministerio de Economía y Competitividad (MINECO), Instituto de Salud Carlos III y Programa Estatal de Investigación , Fundación Ramón Areces y Consejería de Sanidad de la Junta de Castilla y León

Combined application of Life Cycle Assessment and linear programming to evaluate food waste-to-food strategies: Seeking for answers in the nexus approach

The great concern regarding food loss (FL) has been studied previously, but in an isolated way, disregarding interdependencies with other areas. This paper aims to go a step further by proposing a new procedure to assess different waste management alternatives based on the nexus approach by means of an integrated Water-Energy-Food-Climate Nexus Index (WEFCNI). The environmental profile of the waste management techniques is determined using Life Cycle Assessment (LCA) which, in combination with Linear Programming (LP), explores the optimal aggregation of weighting factors that lead to an aggregated nexus index. The management of residues from the anchovy canning industry in Cantabria (Spain) has been used as a case study, considering the three current applied alternatives: (i) valorisation of FL as animal feed in aquaculture (food waste-to-food approach), (ii) incineration of FL with energy recovery, and (iii) landfilling with biogas recovery. The last two considered the use of energy recovered to produce a new aquaculture product (food waste-to-energy-to-food scenarios). The results indicate that incineration is the best performing scenario when the nutritional energy provided by the valorisation alternative is not high enough and the valorisation technology presents the highest water consumption. Therefore, a minimisation in the consumption of natural resources is suggested in order to improve the application of circular economy within the sector. The use of the nexus index as an environmental management tool is extendable to any food system with the aim of facilitating the decision-making process in the development of more sustainable products.The authors thank the Ministry of Economy and Competitiveness of the Spanish Government for its financial support via the project GeSAC-Conserva: Sustainable Management of the Cantabrian Anchovies (CTM2013-43539-R) and to Julia Celaya for her technical support. Jara Laso thanks the Ministry of Economy and Competitiveness of Spanish Government for its financial support via the research fellowship BES-2014-069368. Pere Fullana and Alba Bala thank the UNESCO Chair in Life Cycle and Climate Change. Ian Vázquez-Rowe thanks the Pontificia Universidad Católica del Perú for financing the Walaya Project

MUC1 aptamer-capped mesoporous silica nanoparticles for controlled drug delivery and radio-imaging applications

[EN] Mucin 1 (MUC1) is a cell surface protein overexpressed in breast cancer. Mesoporous silica nanoparticles (MSNs) loaded with safranin O, functionalized with aminopropyl groups and gated with the negatively charged MUC1 aptamer have been prepared (S1-apMUC1) for specific targeting and cargo release in tumoral versus non-tumoral cells. Confocal microscopy studies showed that the S1-apMUC1 nanoparticles were internalized in MDA-MB-231 breast cancer cells that overexpress MUC1 receptor with subsequent pore opening and cargo release. Interestingly, the MCF-10-A non-tumorigenic breast epithelial cell line that do not overexpress MUC1, showed reduced (S1-apMUC1) internalization. Negligible internalization was also found for S1-ap nanoparticles that contained a scrambled DNA sequence as gatekeeper. S2-apMUC1 nanoparticles (similar to S1-apMUC1 but loaded with doxorubicin) internalized in MDA-MB-231 cells and induced a remarkable reduction in cell viability. Moreover, S1-apMUC1 nanoparticles radio-labeled with Tc-99m (S1-apMUC1-Tc) showed a remarkable tumor targeting in in vivo studies with MDA-MB-231 tumor-bearing Balb/c mice. (C) 2017 Elsevier Inc. All rights reserved.Financial support from the Spanish Government and FEDER funds (Project MAT2015-64139-C4-1) and the Generalitat Valenciana (Project PROMETEOII/2014/047) is gratefully acknowledged.Pascual, L.; Cerqueira, C.; García-Fernández, A.; De Luis-Fernández, B.; Soares, E.; Souza, M.; Missailidis, S.... (2017). MUC1 aptamer-capped mesoporous silica nanoparticles for controlled drug delivery and radio-imaging applications. Nanomedicine Nanotechnology Biology and Medicine. 13(8):2495-2505. https://doi.org/10.1016/j.nano.2017.08.006S2495250513