In silico drug prescription for targeting cancer patient heterogeneity and prediction of clinical outcome

In silico drug prescription tools for precision cancer medicine can match molecular alterations with tailored candidate treatments. These methodologies require large and well-annotated datasets to systematically evaluate their performance, but this is currently constrained by the lack of complete patient clinicopathological data. Moreover, in silico drug prescription performance could be improved by integrating additional tumour information layers like intra-tumour heterogeneity (ITH) which has been related to drug response and tumour progression. PanDrugs is an in silico drug prescription method which prioritizes anticancer drugs combining both biological and clinical evidence. We have systematically evaluated PanDrugs in the Genomic Data Commons repository (GDC). Our results showed that PanDrugs is able to establish an a priori stratification of cancer patients treated with Epidermal Growth Factor Receptor (EGFR) inhibitors. Patients labelled as responders according to PanDrugs predictions showed a significantly increased overall survival (OS) compared to non-responders. PanDrugs was also able to suggest alternative tailored treatments for non-responder patients. Additionally, PanDrugs usefulness was assessed considering spatial and temporal ITH in cancer patients and showed that ITH can be approached therapeutically proposing drugs or combinations potentially capable of targeting the clonal diversity. In summary, this study is a proof of concept where PanDrugs predictions have been correlated to OS and can be useful to manage ITH in patients while increasing therapeutic options and demonstrating its clinical utilityThis work was supported by the Instituto de Salud Carlos III (ISCIII); Marie-Curie Career Integration Grant (CIG334361); and Paradifference Foundatio

Design of universal multicoset sampling patterns for compressed sensing of multiband sparse signals

Many problems in digital communications involve wideband radio signals. As the most recent example, the impressive advances in Cognitive Radio systems make even more necessary the development of sampling schemes for wideband radio signals with spectral holes. This is equivalent to considering a sparse multiband signal in the framework of Compressive Sampling theory. Starting from previous results on multicoset sampling and recent advances in compressive sampling, we analyze the matrix involved in the corresponding reconstruction equation and define a new method for the design of universal multicoset codes, that is, codes guaranteeing perfect reconstruction of the sparse multiband signal

Role of Mesenchymal Stromal Cells as Therapeutic Agents: Potential Mechanisms of Action and Implications in Their Clinical Use

Due to the great therapeutic interest that involves the translation of mesenchymal stromal cells (MSCs) into clinical practice, they have been widely studied as innovative drugs, in order to treat multiple pathologies. MSC-based cell therapy involves the administration of MSCs either locally or systemically into the receptor body where they can traffic and migrate towards the affected tissue and participate in the process of healing. The therapeutic effects of MSCs compromise of different mechanisms such as the functional integration of differentiated MSCs into diseased host tissue after transplantation, their paracrine support, and their impact on the regulation of both the innate and the acquired immune system. Here, we establish and provide recent advances about the principal mechanisms of action through which MSCs can perform their activity and effect as a therapeutic tool. The purpose of this review is to examine and discuss the MSCs capacity of migration, their paracrine effect, as well as MSC-mediated modifications on immune cell responses.This work was supported by the Fundación Mutua Madrileña (project FMM-AP17196-2019) and by the Ministerio de Economía, Industria y Competitividad (FEDER funds, project RTC-2016-5451-1)

Food Safety Risk Management

It is a principal aim of governments to assure the safety of societies in all sectors. In the food field, safety has been dealt with for a long time by making decisions in an empirical manner. Recently, risk management has been appointed as the formal scientific-based approach to address food safety issue

Satisfaction with life, victimization, and perception of insecurity in Morelos

Objetivo. Examinar la influencia que ejercen la victimización, la percepción de inseguridad y los cambios en las rutinas en la satisfacción con la vida. Material y métodos. Participaron 7 535 sujetos (50.2% hombres) de entre 12 y 60 años, seleccionados a partir de un muestreo estratificado proporcional. Se calculó un análisis multivariado de la varianza (Manova) y un análisis de regresión logística politómica. Resultados. Se observaron diferencias significativas en victimización, percepción de inseguridad y restricciones en actividades cotidianas en función del grado de satisfacción con la vida. Además, las medidas de protección, la percepción de inseguridad y las restricciones en actividades cotidianas se relacionaron con la satisfacción con la vida. Conclusiones. Un bajo nivel de satisfacción con la vida se asoció con haber sido víctima, con la percepción de inseguridad en espacios públicos y con la adopción de medidas de protección física y control de la información.Objective. To examines the influence of victimization, perceived insecurity and restrictions on daily routines in life satisfaction. Materials and methods. Participants were 7 535 (50.2% men) aged between 12 and 60, selected from a proportional stratified sampling. MANOVA and polytomous logistic regression model were calculated. Results. We found significant differences in victimization, perceived insecurity and restrictions on daily routines in relation with life satisfaction levels. Also, physical protective measures, control of personal information, perception of insecurity in public areas and restrictions on daily routines were related to lower levels of satisfaction with life. Conclusions. Lowest levels of satisfaction with life were associated with victimization, perception of insecurity in public areas, and restrictions on daily routines.Departamento de Educación y Psicología SocialFacultad de Psicología, Universidad Autónoma del Estado de MorelosVersión del edito

Contextos de socialización y consumo de drogas ilegales en adolescentes escolarizados

El objetivo del presente estudio fue contrastar un modelo explicativo del consumo de drogas ilegales en adolescentes escolarizados, considerando variables personales (autoestima académica, autoestima social y sintomatología depresiva), familiares (funcionamiento familiar, comunicación familiar madre y padre), escolares (expectativa académica) y sociales (integración y participación comunitaria). La muestra estuvo conformada por 1.285 adolescentes de ambos sexos con edades comprendidas entre los 12 y 20 años de edad, procedentes de cuatro centros educativos localizados en Monterrey (México). Se realizó un modelo de ecuaciones estructurales que explicó el 20% de la varianza y se exploró el efecto moderador del género. Los resultados muestran una relación significativa y positiva entre el contexto comunitario y el consumo de drogas ilegales a través de la autoestima social, en el caso de los chicos. Igualmente, se encontró una relación indirecta y positiva entre el contexto familiar y el consumo de drogas, a través de la autoestima social, la autoestima escolar y las expectativas académicas. Además, el contexto familiar mostró una relación negativa con las sintomatología depresiva y esta, a su vez, con el consumo de drogas. ABSTRACT The aim of this study was to test an explanatory model about illegal drug use among schooled adolescents. Different types of variables were used, including personal variables (academic self-esteem, social selfesteem and depressive symptoms), family variables (family functioning, father-mother communication), school variables (academic expectations), and social variables (community integration and participation). A sample of 1,285 adolescents, both males and females, aged between 12 and 20 years old, from four different schools in Monterrey, Mexico, was used. A structural equation model was used, explaining 20% of variance. The moderating effect of gender was explored. Results show a significant positive relationship between community context and illegal drugs use, mediated by social self-esteem only for boys. Likewise, a positive indirect relationship was found between the family context and drug use, mediated by social self-esteem, school self-esteem and academic expectations. Moreover, the family context showed a negative relationship with depressive symptoms, which in turn were related to drug use

Design of a case management model for people with chronic disease (Heart Failure and COPD). Phase I: modeling and identification of the main components of the intervention through their actors: patients and professionals (DELTA-ICE-PRO Study

Background Chronic diseases account for nearly 60% of deaths around the world. The extent of this silent epidemic has not met determined responses in governments, policies or professionals in order to transform old Health Care Systems, configured for acute diseases. There is a large list of research about alternative models for people with chronic conditions, many of them with an advanced practice nurse as a key provider, as case management. But some methodological concerns raise, above all, the design of the intervention (intensity, frequency, components, etc). Methods/Design Objectives: General: To develop the first and second phases (theorization and modeling) for designing a multifaceted case-management intervention in people with chronic conditions (COPD and heart failure) and their caregivers. Specific aims: 1) To identify key events in people living with chronic disease and their relation with the Health Care System, from their point of view. 2) To know the coping mechanisms developed by patients and their caregivers along the story with the disease. 3) To know the information processing and its utilization in their interactions with health care providers. 4) To detect potential unmet needs and the ways deployed by patients and their caregivers to resolve them. 5) To obtain a description from patients and caregivers, about their itineraries along the Health Care System, in terms of continuity, accessibility and comprehensiveness of care. 6) To build up a list of promising case-management interventions in patients with Heart Failure and COPD with this information in order to frame it into theoretical models for its reproducibility and conceptualization. 7) To undergo this list to expert judgment to assess its feasibility and pertinence in the Andalusian Health Care. Design: Qualitative research with two phases: For the first five objectives, a qualitative technique with biographic stories will be developed and, for the remaining objectives, an expert consensus through Delphi technique, on the possible interventions yielded from the first phase. The study will be developed in the provinces of Almería, Málaga and Granada in the Southern Spain, from patients included in the Andalusian Health Care Service database with the diagnosis of COPD or Heart Failure, with the collaboration of case manager nurses and general practitioners for the assessment of their suitability to inclusion criteria. Patients and caregivers will be interviewed in their homes or their Health Centers, with their family or their case manager nurse as mediator. Discussion First of a series of studies intended to design a case-management service for people with heart failure and COPD, in the Andalusian Health Care System, where case management has been implemented since 2002. Accordingly with the steps of a theoretical model for complex interventions, in this study, theorization and intervention modeling phases will be developed.This research was carried out with the support of one research grant, awarded by the Regional Health Ministry of Andalusia (Exp. 0222/2008

Percepção da insegurança, vitimização e as limitações na vida diária baseada no ciclo vital, em Morelos, México

Palabras claves: fuente, Tesauro de política criminal latinoamericana - ILANUDLos estudios sobre percepción de inseguridad, victimización y restricciones en la vida cotidiana en países con altos índices de criminalidad son escasos. Objetivo: examinar la percepción de inseguridad, victimización y variaciones de las rutinas en función de la edad. Método: se ha realizado una adaptación de la Encuesta Nacional sobre Victimización y Percepción de Inseguridad (ENVIPE). Participaron 8.170 sujetos de ambos sexos (49,9 % mujeres y 50,1 % hombres), de entre 12 y 75 años, residentes en el Estado de Morelos, seleccionados a partir de un muestreo probabilístico estratifi cado y proporcional. Respecto a la edad, se establecieron los siguientes intervalos en función de las distintas etapas del ciclo vital: [12-17 años] 24 %, [18-20 años] 8 %, [21-30 años] 14 %, [31 y 40 años] 14 %, [41 y 60 años] 20 % y [61 o más años] 20 %. Resultados: indicaron diferencias significativas en la percepción de inseguridad, victimización y restricciones en las actividades cotidianas en función de la edad. Los adolescentes informaron de mayor percepción de inseguridad y de menos restricciones en su vida cotidiana. También, los adolescentes y los mayores de 61 años presentaron una menor victimización. Conclusión: los adolescentes constituyen el grupo de mayor vulnerabilidad para la victimización, perciben mayor inseguridad y realizan menos cambios en sus rutinas para protegerse de la delincuencia. Finalmente, se discuten los resultados.Studies on the perception of insecurity, victimization and restrictions in daily life in countries with high crime rates are scarce. Objective: examining the awareness of insecurity and victimization, and the routine variations taking place according to age. Method: an adaptation has been made of the National Survey on Victimization and Perception of Insecurity (ENVIPE). A total of 8,170 subjects of both sexes (49.9% women and 50.1% men), between 12 and 75 years old, residents in the State of Morelos, selected from a stratified and proportional probabilistic sampling. Regarding age, the following intervals were established depending on the different stages of the life cycle: [12-17 years] 24%, [18-20 years] 8%, [21-30 years] 14%, [31 and 40 years] 14%, [41 and 60 years] 20% and [61 or above] 20%. Results: Significant differences in the perception of insecurity, victimization and restrictions in daily activities based on age were shown. Adolescents reported greater insight with respect to insecurity and fewer restrictions in their daily lives. Also, adolescents and those over 61 years of age presented lower victimization. Conclusion: adolescents are the most vulnerable group for victimization; they perceive higher uncertainty and generally introduce fewer changes in their routines to protect themselves from crime. Finally, the results are discussed.Os estudos sobre a percepção da insegurança, vitimização e as limitações na vida diária nos países com índices elevados de criminalidade são escassos. Objetivo: examinar a percepção da insegurança, vitimização e as variações das rotinas baseadas na idade. Método: uma adaptação da Escola Nacional sobre Vitimização e Percepção de Insegurança (ENVIPE) foi realizada. 8.170 sujeitos de ambos os sexos participaram (49.9% mulheres e 50.1% homens), entre e 75 anos, residentes no estado de Morelos, selecionados de uma amostra probabilística estratificada e proporcional. Com respeito à idade, os seguintes intervalos baseados nos diferentes estágios do ciclo vital forma estabelecidos: [12- 17 anos] 24%, [18-20 anos] 8%, [21-30 anos] 14%, [31 e 40 anos] 14%, [41 e 60 anos] 20% e [61 ou mais anos] 20%. Resultados: indicaram diferenças significativas na percepção de insegurança, vitimização e as limitações nas atividades diárias baseadas na idade. Os adolescentes informaram uma maior percepção de insegurança e de menos limitações em sua vida diária. Também, os adolescentes e maiores de 61 anos apresentaram uma vitimização menor. Conclusão: os adolescentes constituem o grupo de maior vulnerabilidade para a vitimização, percebem maior insegurança e fazem menos mudanças em suas rotinas para proteger-se da delinquência. Finalmente, os resultados são discutidos.Departamento de Educación y Psicología SocialVersión del edito

Teorias sobre o início da violência filio-parental desdea perspectiva parental: um estudo exploratório

Objetivo.Conocer las teorías implícitas que utilizan los padres víctimas de la violencia de sus hijos para explicar su inicio. Método.Se ha llevado a cabo un estudio cualitativo exploratorio siguiendo el método propuesto por la Teoría Fundamentada. La información fue obtenida a partir de seis grupos de discusión guiados por entrevistas semiestructuradas y analizada mediante ATLAS.ti 5.0. En total, participaron 42 progenitores víctimas de violencia filio-parental (VFP;18 padres y 24 madres) seleccionados por muestreo intencional teórico de dos contextos: un centro de reforma de menores y un centro privado especializado en terapia de violencia intrafamiliar. Resultados. Los progenitores mantienen tres teorías para explicar el inicio de la VFP: (a) la teoría del alumno ausente, que alude al absentismo escolar como predictor de la conducta violenta; (b) la teoría del alumno consumidor, en la que el consumo de sustancias (alcohol, cannabis y cocaína) sería el factor antecedente; y (c) la teoría de la acumulación de la tensión, en la que se plantea la presencia de unos factores previos que contribuirían a incrementar el malestar (¿rabia¿) que antecedería el consumo abusivo de drogas y, posteriormente, la violencia hacia los padres. Conclusión. Los progenitores señalan que la VFP coincide con el comienzo de la etapa de educación secundaria. Un aspecto común a las tres teorías emergentes es que son factores distales y relacionados con el entorno que rodea a los adolescentes los principales desencadenantes de la VFP, quedando al margen variables relacionadas con la dinámica familiar.Escopo. Conhecer as teorias implícitas que utilizam os pais vitimas da violência de seus filhos para explicar seu início. Metodologia. Foi feito um estudo qualitativo exploratório seguindo a metodologia proposta pela Teoria Fundamentada. A informação foi obtida a partir de seis grupos de discussão guiados por entrevistas semiestruturadas e analisadas mediante ATLAS.ti 5.0. Em total, participaram 42 pais vitimas de violência filio-parental (VPF; 18 homens e 24 mulheres) selecionadas por amostragem intencional teórica de dois contextos: um centro de reforma de menores e um centro privado especializado em terapia de violência intrafamiliar. Resultados. Os pais mantêm três teorias para explicar o inicio da VFP: (a) a teoria do estudante ausente, que alude ao absentismo escolar como preditor da conduta violenta; (b) a teoria do estudante consumidor, na que o consumo de sustâncias (álcool, cannabis c cocaína) é o fator antecedente; e (c) a teoria da acumulação da tensão, na que se propõe a presença de uns fatores prévios que contribuem ao incremento do desconforto (¿raiva¿) que supostamente antecede o consumo abusivo de drogas e, posteriormente, à violência contra os pais. Conclusão. Os pais assinalam que a VFP coincide com o começo da etapa da educação secundaria. Um aspeto comum às três teorias emergentes é que são fatores distais e relacionados com o entorno que rodea aos adolescentes os principais desencadeantes da VPF, deixando de fora variáveis relacionadas com a dinâmica familiar.Objective. To explore the implicit theories that parents victims of violence from their children (VFP) to explain the onset. Method. An exploratory qualitative study was done following the method proposed by the Grounded Theory. Information was obtained from six Focus Groups guided by semi-structured interviews and analyzed using ATLAS.ti 5.0. A total of 42 parents, victims of violence-towards-parents (VTP; 18 fathers and 24 mothers) participated and were selected by theoretical intentional sampling purposive sampling from two contexts: one juvenile reform center and a private family therapy center. Results. Parents have three theories to explain the onset of VFP: (a) the theory of the absent student, referred to truancy as a predictor of violent behavior; (b) addict student theory, in which substance abuse (alcohol, cannabis and cocaine) works as the antecedent factor; and (c) the theory of the accumulation of stress, in which the presence of previous factors contribute to increased discomfort (¿rage¿) that would precede the drug abuse and later violence toward parents. Conclusion. Parents report that the VFP begins in the first stage of secondary education. A common aspect of the three emerging theories is that VFP is triggered by some distal factors related to the environment surrounding adolescent, leaving aside variables related to family dynamics.Departamento de Educación y Psicología SocialDepartamento de Ciencias Sociales, Pontificia Universidad Javeriana de CaliVersión del edito