Resumen El cáncer es una enfermedad genética compleja con opciones terapéuticas limitadas, debido a la heterogeneidad tumoral y a la aparición de multirresistencia a los fármacos. La vía metabólica de los esfingolípidos (SL) se caracteriza por ser capaz de integrar diferentes tipos de señales de estrés celular y definir la supervivencia celular. Por lo tanto, sugerimos estudiar las perturbaciones en la vía de los esfingolípidos (SLP) causadas por fármacos quimioterapéuticos utilizando un enfoque de biología de sistemas y evaluar su funcionalidad como sensor de respuesta a fármacos. Usamos un sensor de esfingomielina-BODIPY (SMBOD) para estudiar el metabolismo de SL mediante citometría de flujo e imágenes de células vivas en diferentes modelos de cáncer. Para decodificar la complejidad de la ruta, implementamos modelos de mezcla gaussianos, modelos de ecuaciones diferenciales ordinarias, algoritmos de clasificación no supervisados y un modelo de lógica difusa para evaluar su utilidad como sensor de respuesta a la quimioterapia. Nuestros resultados muestran que los fármacos quimioterapéuticos perturban la SLP de diferentes formas y de una manera específica de la línea celular. Además, encontramos que pocas características de fluorescencia de SM-BOD predicen la quimiosensibilidad con alta precisión. Finalmente, encontramos que la composición relativa de especies de SL parece contribuir a la citotoxicidad resultante de muchos tratamientos. Este informe ofrece un marco conceptual y matemático para desarrollar modelos matemáticos personalizados para predecir y mejorar la terapia del cáncer.

Resumo O câncer é uma doença genética complexa com opções terapêuticas limitadas, devido à heterogeneidade tumoral e ao aparecimento de multirresistência aos fármacos. A via metabólica dos esfingolipídeos (SP) é caracterizada por ser capaz de integrar diferentes tipos de sinais de estresse celular e definir a sobrevivência celular. Portanto, sugerimos estudar as perturbações na rota dos esfingolipídeos (SP) causadas por fármacos quimioterápicos usando uma abordagem de biologia de sistemas e avaliar sua funcionalidade como sensor de resposta a fármacos. Usamos um sensor de esfingomielina-BODIPY (SM-BOD) para estudar o metabolismo do SP por citometria de fluxo e imagens de células vivas em diferentes modelos de câncer. Para decodificar a complexidade do caminho, implementamos modelos de mistura gaussiana, modelos de equações diferenciais ordinárias, algoritmos de classificação não supervisionados e um modelo de lógica difusa para avaliar sua utilidade como sensor de resposta à quimioterapia. Nossos resultados mostram que os fármacos quimioterápicos perturbam a rota dos SP de diferentes maneiras e de maneira específica da linhagem celular. Além disso, descobrimos que poucas características de fluorescência do SM-BOD predizem a quimiossensibilidade com alta precisão. Finalmente, descobrimos que a composição relativa de espécies de SP parece contribuir para a citotoxicidade resultante de muitos tratamentos. Este relatório oferece uma estrutura conceitual e matemática para o desenvolvimento de modelos matemáticos personalizados para prever e melhorar a terapia do câncer.

Abstract Cancer is a complex genetic disease with reduced treatment alternatives due to tumor heterogeneity and drug multiresistance emergence. The sphingolipid (SL) metabolic pathway integrates different responses of cellular stress signals and defines cell survival. Therefore, we suggest studying the perturbations on the sphingolipid pathway (SLP) caused by chemotherapeutic drugs using a systems biology approach to evaluate its functionality as a drug response sensor. We used a sphingomyelin-BODIPY (SM-BOD) sensor to study SL metabolism by flow cytometry and live cell imaging in different cancer models. To decode pathway complexity, we implemented Gussian mixture models, ordinary differential equations models, unsupervised classification algorithms and a fuzzy logic approach to assess its utility as a chemotherapy response sensor. Our results show that chemotherapeutic drugs perturb the SLP in different ways in a cell line-specific manner. In addition, we found that few SM-BOD fluorescence features predict chemosensitivity with high accuracy. Finally, we found that the relative species composition of SL appears to contribute to the resulting cytotoxicity of many treatments. This report offers a conceptual and mathematical framework for developing personalized mathematical models to predict and improve cancer therapy.

Resumen Introducción: La disciplina científica de la bioinformática tiene el potencial de generar aplicaciones innovadoras para las sociedades humanas. Costa Rica, pequeña en tamaño y población en comparación con otros países de América Latina, ha ido adoptando la disciplina de manera progresiva. El reconocer los avances permite determinar hacia dónde puede dirigirse el país en este campo, así como su contribución a la región latinoamericana. Objetivo: En este manuscrito se reporta evidencia de la evolución de la bioinformática en Costa Rica, para identificar debilidades y fortalezas que permitan definir acciones a futuro. Métodos: Se realizaron búsquedas en bases de datos de publicaciones científicas y repositorios de secuencias, así como información de actividades de capacitación, redes, infraestructura, páginas web y fuentes de financiamiento. Resultados: Se observan avances importantes desde el 2010, incluyendo un aumento en oportunidades de entrenamiento y número de publicaciones, aportes significativos a las bases de datos de secuencias y conexiones por medio de redes. Sin embargo, ciertas áreas, como la masa crítica y la financiación requieren más desarrollo. La comunidad científica y sus patrocinadores deben promover la investigación basada en bioinformática, invertir en la formación de estudiantes de posgrado, aumentar la formación de profesionales, crear oportunidades laborales para carreras en bioinformática y promover colaboraciones internacionales a través de redes. Conclusiones: Se sugiere que para experimentar los beneficios de las aplicaciones de la bioinformática se deben fortalecer tres aspectos clave: la comunidad científica, la infraestructura de investigación y las oportunidades de financiamiento. El impacto de tal inversión sería el desarrollo de proyectos ambiciosos pero factibles y colaboraciones extendidas dentro de la región latinoamericana. Esto permitiría realizar contribuciones significativas para abordar los desafíos globales y la aplicación de nuevos enfoques de investigación, innovación y transferencia de conocimiento para el desarrollo de la economía, dentro de un marco de ética de la investigación.

Abstract Introduction: The scientific discipline of bioinformatics has the potential to generate innovative applications for human societies. Costa Rica, small in size and population compared to other Latin American countries, has been progressively adopting the discipline. Recognizing progress makes it possible to determine where the country can go in this field, as well as its contribution to the Latin American region. Objective: This manuscript reports evidence of the evolution of bioinformatics in Costa Rica, to identify weaknesses and strengths allowing future actions plans. Methods: We searched databases of scientific publications and sequence repositories, as well as information on training activities, networks, infrastructure, web pages and funding sources. Results: Important advances have been observed since 2010, such as increases in training opportunities and the number of publications, significant contributions to the sequence databases and connections through networks. However, areas such as critical mass and financing require further development. The scientific community and its sponsors should promote bioinformatics-based research, invest in graduate student training, increase professional training, create career opportunities in bioinformatics, and promote international collaborations through networks. Conclusions: It is suggested that in order to experience the benefits of bioinformatics applications, three key aspects must be strengthened: the scientific community, the research infrastructure, and funding opportunities. The impact of such investment would be the development of ambitious but feasible projects and extended collaborations within the Latin American region and abroad. This would allow significant contributions to address global challenges and the implementation of new approaches to research, innovation and knowledge transfer for the development of the economy, within an ethics of research framework.

Abstract: The pandemic forced the elderly to establish strict quarantines. But that measure of care prevented them from performing a daily self-care exercise: the urban walk. Based on this dilemma, the following research confirms how the city becomes hostile to the elderly, turning into an environment of “non-care.”

Resumen: La pandemia forzó a los adultos mayores a establecer estrictas cuarentenas. Pero esa medida de cuidado les impidió realizar un ejercicio diario de autocuidado: la caminata urbana. En base a esa disyuntiva, la siguiente investigación confirma cómo la ciudad se vuelve hostil a la tercera edad, convirtiéndose en un entorno del «no-cuidado».

Abstract: - Most empirical research on spatial patterns of intra-urban residential mobility has been based on the study of the inflow and outflow recorded in various spatial units. This approach does not allow for the definition of migratory areas by the origin, destination and intensity of residential mobility. Here the spatial types and structure of residential mobility in the communes of the Santiago Metropolitan Region (RMS) are studied using individual data on changes of residence between communes. Combining the application of spatial analysis methods and the analysis of geosocial networks has demonstrated: a) the complex and fairly well-integrated nature of the network of residential movements; b) the major influence of geographical proximity on changes of residence; and c) notable territorial differences in the effects of changes of residence on socio-spatial diversification. As a whole, the functional and spatial structure of residential mobility is consistent with the processes of expansion and physical, social and functional fragmentation of the RMS.

Resumen: - La mayor parte de la investigación empírica sobre los patrones espaciales de movilidad residencial intraurbana se ha llevado a cabo a partir del estudio de los balances de entradas y salidas registradas en diversas unidades espaciales. Esta aproximación no permite delimitar áreas migratorias definidas según el origen, destino e intensidad de la movilidad residencial. Aquí se estudian los tipos espaciales de la movilidad residencial y su estructura en las comunas de la Región Metropolitana de Santiago (RMS) utilizando datos individuales del cambio de residencia entre comunas. La aplicación combinada de métodos de análisis espacial y de análisis de redes geosociales, ha puesto de manifiesto: a) el carácter complejo y bastante integrado de la red de movimientos residenciales; b) la gran influencia de la proximidad geográfica en los cambios de residencia y c) los efectos de los cambios de residencia en la diversificación socioespacial presentan notables diferencias territoriales. En conjunto, la estructura funcional y espacial de la movilidad residencial es coherente con los procesos de expansión y fragmentación física, social y funcional de la RMS.

Abstract: Walking is a sustainable and healthy transport mode, which should be promoted through urban planning and design. In this context, the objective of this research is to identify and characterise the elements of the urban landscape which promote walking and, contrarily, the elements which inhibit walking in six peri-central neighbourhoods in Santiago, based on the perception of walkers. With this aim, 120 walking interviews were realised during September, October and November 2018 with residents, allowing for a detailed record of the self-declared perception of pedestrians about their urban mobility environments. Results show that elements which promote walking are the presence of wide sidewalks, trees and mixed use. In contrast, factors that inhibit walking are narrow sidewalks, intersections, and especially motorized traffic and vehicular noise. Finally, based on the results, recommendations are proposed for the planning and design of streets that promote walking.

Resumen: Caminar es un modo de transporte sustentable y saludable, que debería ser promovido mediante la planificación y el diseño urbano. En este contexto, la presente investigación tiene como objetivo identificar los elementos del paisaje urbano que, desde la percepción del caminante, facilitan la caminata y, en contraste, los elementos que la inhiben, dentro de seis barrios pericentrales del Gran Santiago. Con este fin, se realizaron 120 walking interviews (entrevistas caminando in situ) con residentes durante septiembre, octubre y noviembre de 2018, permitiendo un detallado registro de la percepción auto-declarada de los peatones sobre sus entornos de movilidad peatonal. Los resultados muestran que elementos que promueven la caminata son la presencia de veredas anchas, árboles y uso de suelo mixto. En contraste, elementos que inhiben la caminata son veredas angostas y en mal estado, los cruces y, en especial, el tráfico motorizado y el ruido vehicular. Finalmente, en base a los resultados, se proponen recomendaciones para una planificación y un diseño de calles que promuevan la caminata.

Abstract Over the 1997-2002 period, residential migrations among Chilean cities with more than 50,000 inhabitants maintained the intensity they had had ten years earlier which contrasts with the decrease in this type of mobility in smaller cities during the same period under review. Through the modeling and implementation of network analysis methods to the bilateral migratory flows between cities -collected through census microdata- it is revealed that interurban residential mobility is highly polarized, stable and compatible with a remarkable dynamic of changes in the direction and magnitude of flows. The spatial organization of interurban migrations has different levels and scales, whose hierarchy and ways of integration are strongly associated with the configuration of urban networks, that is, the spatial distribution of cities, population and specialization of economic activities. Although the material from the period under review shows a slight decrease in the destinations for residential mobility, there are no signs of an intense and widespread decentralization process.

Resumen Durante el quinquenio 1997-2002, las migraciones residenciales entre las ciudades chilenas mayores de 50.000 habitantes mantuvieron la intensidad que tenían diez años antes frente al descenso de este tipo de movilidad que, en el mismo período, se registró entre las ciudades de tamaño inferior a este umbral. Mediante el modelado y la aplicación de métodos de análisis de redes a los flujos migratorios bilaterales entre ciudades -obtenidos a partir de microdatos censales-, se ha constatado que los movimientos residenciales interurbanos presentan una estructura muy polarizada y estable, pero compatible con una notable dinámica de cambios en la dirección y magnitud de los flujos. La organización espacial de las migraciones interurbanas comprende varios niveles y escalas, cuya jerarquía y articulación se asocian fuertemente a la configuración de la red urbana, es decir, a la distribución espacial de las ciudades, de la población y de la especialización de las actividades económicas. En el período y materia investigados, ha decrecido ligeramente la concentración de los destinos de la movilidad residencial, pero no se observa un proceso de descentralización intenso y generalizado.

Background: With approximately 66% of the population overweight and nearly 90% with sedentary lifestyles, obesity has become a major public health problem in Chile. Thus, in the last fifteen years health policies have promoted active lifestyles. An interesting initiative in this context is the CicloRecreoVia program, which closes a set of public streets on Sunday mornings, allowing people to carry out PA in streets free of vehicles. Aim: To characterize PA and mobility patterns of participants of the CicloRecreoVía program in Santiago. Material and Methods: 401 participants of five circuits of the CicloRecreoVia surveyed on the type, frequency and durantion of the PA carried out, their daily mobility habits, motivations for attending the CicloRecreoVia, self-perceived health condition, among other aspects. Results: Participants spent 113 minutes in the CicloRecreoVia, 77% declared walking or bicycling at least 10 minutes per day and 56.7% traveled actively (bicycling or walking) at least four times per week. Finally, 69.1% perceived their health condition “better” or “much better” than one year ago. In addition, it was noted that CicloRecreoVías attracted different type of participants depending on their location in the city. Conclusions: In line with previous studies, most users achieve about 75% of the weekly PA recommended by attending the CicloRecreoVía, and the main motivations to attend the program were to make PA, to be outdoor and to socialize. As a result, the CicloRecreoVía has the potential to become an effective public nationwide health policy to combat obesity.

Resumen En las ciudades contemporáneas el espacio construido y el social se encuentran en un proceso constante de transformación. En este contexto, el barrio es una unidad cuya función es reunir a la comunidad y a sus prácticas, al mismo tiempo que opera como vínculo entre el espacio privado de la vivienda y la metrópolis. El rol del barrio en la construcción de la comunidad cobra especial relevancia en los barrios vulnerables. En Chile después de años de políticas viviendistas que privilegiaban la construcción de casas, se ha cambiado el foco hacia el mejoramiento de los barrios con intervenciones integrales multisectoriales. En este contexto, el objetivo del presente artículo es evaluar la relación entre las estructuras del espacio físico y las estructuras de sociabilidad en habitantes de barrios vulnerables en proceso de consolidación en Santiago, específicamente, a través del estudio de dos casos emblemáticos de la comuna de El Bosque. La hipótesis general es que el espacio físico y la configuración actual de muchos de los barrios con estas características de vulnerabilidad so-cioterritorial actúan como una estructura estructurante de relaciones sociales que es capaz de inhibir la difusión de la sociabilidad y favorecer el aislamiento metropolitano.

Abstract The built and social urban space in contemporary cities are in a continuous transformation process. In this context, neighbourhoods have a double function that gathers community values while operates as link between the homes and the metropolis. The neighbourhood's role in the building of the community is especially relevant in vulnerable neighbourhoods. In Chile, after years of housing public policies that privileged the construction of houses, the focus has changed towards neighbourhood improvement with multi-sectorial integral interventions. In this context, the objective of the present paper is to evaluate the relationship between the physical space and the sociability structures of inhabitants from vulnerable neighbourhoods in the process of consolidation in Santiago de Chile, through the analysis of two cases in the municipality of El Bosque. The general hypothesis is that the physic space and the configuration of many vulnerable neighbourhoods, work as a structure-that-structures social relation, capable of inhibiting sociability and favouring urban isolation.

Resumo Nas cidades contemporâneas o espaço construído e o espaço social estão num constante processo de transformação. Neste contexto, o bairro é uma unidade com uma dupla função que congrega a comunidade e a suas práticas, ao mesmo tempo que opera como um vinculo entre o espaço privado da habitação e a metrópoles. O papel da vizinhança na construção da comunidade é particularmente importante em bairros vulneráveis. No Chile, após anos de políticas pro habitação, favorecendo a construção de casas, o foco tem sido mudado para a melhoria dos bairros com intervenções multisectoriais abrangentes. Neste contexto, o objetivo deste texto é avaliar a relação entre as estruturas de espaço físico e as estruturas de sociabilidade em habitantes dos bairros vulneráveis em processo de consolidação em Santiago. A hipótese geral é que o espaço físico e a configuração atual de muitos bairros e, especificamente nos bairros vulneráveis, atua como uma estrutura - estruturando as relações sociais e capaz de inibir a difusão de sociabilidade e favorecer o isolamento metropolitano.

Abstract Aims To put together a registry of the location of all existing outdoor gyms (OGs) in Santiago, Chile, and establish a profile of the users of these gyms. Methods All OGs in Santiago located in public spaces were identified and geo-referenced, and an accessibility analysis of them was carried out. A total of 1,023 users of OGs were surveyed (71% men, average age 31.5 years old, SD =16.6), about the frequency of use of OGs, amount of time spent using them, transportation habits, motivation for usage, and their perceptions regarding their own health, among other questions. In addition, each person's neck circumference was measured. Results There are 1,981 OGs in the city squares, sidewalks and parks, mostly located in poorest areas of the city. Most OG users live less than one kilometer away from an OG. Discussion In line with international studies, this research demonstrates that OGs have positive collateral effects, as they not only contribute to users to increase their physical activity, but also because they attract people with sedentary lifestyles to make physical activity. This, in turn, might contribute to make urban areas more livable and safer, for they bring new "eyes to the street" and permit to use cities' under-occupied public spaces. Conclusion The proliferation of outdoor gyms should be regarded as an opportunity for public health policies aimed at tackling the obesity problem and increasing the physical activity of people.

Stated choice methods were used to measure the effect of different types of incentives (direct and indirect subsidies, changes in building regulations and others) in the willingness to build denser and socially integrated residential projects by real estate firms in the vicinity of metro and bus rapid transit (BRT) stations. A sample of 52 professionals, from building companies and real estate firms, was asked to evaluate a series of urban scenarios under various incentive schemes; in each case they had to choose whether they would be willing to start a conventional residential project (i.e. for buyers belonging to the same socio- economic group) or a socially integrated one (i.e. mixing buyers from different groups). Results show that an aggregate level, only 16% of respondents would be interested in starting new residential projects at those locations. However, the availability of incentives could have a significant impact in the willingness to initiate higher density projects around the stations and also, but to a lesser degree, in the willingness to initiate socially mixed residential projects.

Usando técnicas de preferencias declaradas se buscó dimensionar el efecto de incentivos de distinto tipo (subsidios directos e indirectos, cambios normativos y otros), en la disposición a densificar e integrar socialmente a través de proyectos residenciales en las inmediaciones de estaciones de metro y corredores de transporte público. Un total de 52 profesionales, de empresas constructoras e inmobiliarias, debieron evaluar una serie de escenarios urbanos considerando la existencia de distintos tipos de incentivos y elegir, sucesivamente, en cuáles estarían dispuestos a iniciar proyectos residenciales convencionales (dirigidos a un mismo grupo socioeconómico), o socialmente integrados (que incorporaran grupos de distinto nivel socioeconómico). Los resultados muestran que, a nivel agregado, sólo 16% de los encuestados estaría interesado en iniciar proyectos residenciales alrededor de las estaciones analizadas. Sin embargo, la aplicación de incentivos podría aumentar en forma significativa la disposición a iniciar obras de densificación y también, aunque en menor grado, a construir conjuntos residenciales socialmente mixtos.

Background: Sense of orientation in hospitals can be tricky considering the large extension of buildings and the inadequate signage. Aim: To report some of the findings of a larger research project on wayfinding and patient navigation in Chilean hospitals. Material and Methods: Five hundred nine hospital users waiting for attention in three hospitals were contacted and asked to answer a survey that lasted 10 minutes, about wayfinding and sense of orientation within the hospital. Results: Users declared to have a good opinion of existing signage in the three hospitals analyzed as well as their architectural organization in terms of their capacity to orient people. However, the vast majority of users asked for directions to navigate within the hospital to staff and medical personnel. Conclusions: Patient navigation problems are imposing a great “hidden” cost to hospitals management due to missed appointments.

This article examines wayfinding behavior in an extended parking lot belonging to one of the largest shopping malls in Santiago, Chile. About 500 people were followed while going to the mall and returning from it, and their trajectories were mapped and analyzed. The results indicate that inbound paths were, in average, 10% shorter that outbound paths, and that people stopped three times more frequently when leaving the mall than when accessing it. It is argued that these results are in line with previous research on the subject, which stress the importance of environmental information in shaping people`s behavior.

Como componente estructural de la realidad urbana, la calle suele tomarse como un hecho dado y hasta cierto punto, obvio. La reflexión sobre las primeras normativas que regularon su naturaleza da pistas sobre los destinos y roles que, en nuestra realidad contemporánea, la calle puede asumir.