Mathematical modeling of collagen turnover in biological tissue

The final publication is available at Springer via http://dx.doi.org/10.1007/s00285-012-0613-yWe present a theoretical and computational model for collagen turnover in soft biological tissues. Driven by alterations in the mechanical environment, collagen fiber bundles may undergo important chronic changes, characterized primarily by alterations in collagen synthesis and degradation rates. In particular, hypertension triggers an increase in tropocollagen synthesis and a decrease in collagen degradation, which lead to the well-documented overall increase in collagen content. These changes are the result of a cascade of events, initiated mainly by the endothelial and smooth muscle cells. Here, we represent these events collectively in terms of two internal variables, the concentration of growth factor TGF-$\beta$ and tissue inhibitors of metalloproteinases TIMP. The upregulation of TGF-$\beta$ increases the collagen density. The upregulation of TIMP also increases the collagen density through decreasing matrix metalloproteinase MMP. We establish a mathematical theory for mechanically-induced collagen turnover and introduce a computational algorithm for its robust and efficient solution. We demonstrate that our model can accurately predict the experimentally observed collagen increase in response to hypertension reported in literature. Ultimately, the model can serve as a valuable tool to predict the chronic adaptation of collagen content to restore the homeostatic equilibrium state in vessels with arbitrary micro-structure and geometry.Peer ReviewedPostprint (author's final draft

Rationale of the association between Mediterranean diet and the risk of frailty in older adults and systematic review and meta-analysis

Frailty is a geriatric syndrome whose frequency is increasing in parallel with population aging and is of great interest due to its dire consequences: increased disability, hospitalizations, falls and fractures, institutionalization, and mortality. Frailty is multifactorial but nutritional factors, which are modifiable, play a crucial role in its pathogenesis. Epidemiologic evidence supports that high-quality dietary patterns can prevent, delay or even reverse the occurrence of frailty. In order to add new knowledge bridging the gap as the main purpose of the present article we performed a comprehensive review of the rationale behind the association of MedDiet with frailty and a systematic review and meta-analysis updating the latest ones published in 2018 specifically examining the relationship of Mediterranean diet (MedDiet) and incident frailty. Adding the updated information, our results confirmed a robust association of a higher adherence to MedDiet with reduced incident frailty. Key components of the MedDiet, i.e., abundant consumption of vegetables and fruit as well as the use of olive oil as the main source of fat, all of which have been associated with a lower incidence of frailty, may help explain the observed benefit. Future well-designed and sufficiently large intervention studies are needed to confirm the encouraging findings of the current observational evidence. Meanwhile, based on the existing evidence, the promotion of MedDiet, a high-quality dietary pattern, adapted to the conditions and traditions of each region, and considering lifelong and person-tailored strategies, is an open opportunity to reduced incident frailty. This could also help counteract the worrying trend towards the spread of unhealthy eating and lifestyle models such as those of Western diets that greatly contribute to the genesis of chronic non-communicable diseases and disabilit

Strategies for annotation and curation of translational databases: the eTUMOUR project

The eTUMOUR (eT) multi-centre project gathered in vivo and ex vivo magnetic resonance (MR) data, as well as transcriptomic and clinical information from brain tumour patients, with the purpose of improving the diagnostic and prognostic evaluation of future patients. In order to carry this out, among other work, a database—the eTDB—was developed. In addition to complex permission rules and software and management quality control (QC), it was necessary to develop anonymization, processing and data visualization tools for the data uploaded. It was also necessary to develop sophisticated curation strategies that involved on one hand, dedicated fields for QC-generated meta-data and specialized queries and global permissions for senior curators and on the other, to establish a set of metrics to quantify its contents. The indispensable dataset (ID), completeness and pairedness indices were set. The database contains 1317 cases created as a result of the eT project and 304 from a previous project, INTERPRET. The number of cases fulfilling the ID was 656. Completeness and pairedness were heterogeneous, depending on the data type involved

No Excess Mortality up to 10 Years in Early Stages of Breast Cancer in Women Adherent to Oral Endocrine Therapy: A Probabilistic Graphical Modeling Approach

Breast cancer (BC) is globally the most frequent cancer in women. Adherence to endocrine therapy (ET) in hormone-receptor-positive BC patients is active and voluntary for the first five years after diagnosis. This study examines the impact of adherence to ET on 10-year excess mortality (EM) in patients diagnosed with Stages I to III BC (N = 2297). Since sample size is an issue for estimating age- and stage-specific survival indicators, we developed a method, ComSynSurData, for generating a large synthetic dataset (SynD) through probabilistic graphical modeling of the original cohort. We derived population-based survival indicators using a Bayesian relative survival model fitted to the SynD. Our modeling showed that hormone-receptor-positive BC patients diagnosed beyond 49 years of age at Stage I or beyond 59 years at Stage II do not have 10-year EM if they follow the prescribed ET regimen. This result calls for developing interventions to promote adherence to ET in patients with hormone receptor-positive BC and in turn improving cancer survival. The presented methodology here demonstrates the potential use of probabilistic graphical modeling for generating reliable synthetic datasets for validating population-based survival indicators when sample size is an issue

Major Adverse Cardiovascular Events in Coronary Type 2 Diabetic Patients: Identification of Associated Factors Using Electronic Health Records and Natural Language Processing

Patients with Type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) are at high risk of developing major adverse cardiovascular events (MACE). This is a multicenter, retrospective, and observational study performed in Spain aimed to characterize these patients in a real-world setting. Unstructured data from the Electronic Health Records were extracted by EHRead (R), a technology based on Natural Language Processing and machine learning. The association between new MACE and the variables of interest were investigated by univariable and multivariable analyses. From a source population of 2,184,662 patients, we identified 4072 adults diagnosed with T2DM and CAD (62.2% male, mean age 70 +/- 11). The main comorbidities observed included arterial hypertension, hyperlipidemia, and obesity, with metformin and statins being the treatments most frequently prescribed. MACE development was associated with multivessel (Hazard Ratio (HR) = 2.49) and single coronary vessel disease (HR = 1.71), transient ischemic attack (HR = 2.01), heart failure (HR = 1.32), insulin treatment (HR = 1.40), and percutaneous coronary intervention (PCI) (HR = 2.27), whilst statins (HR = 0.73) were associated with a lower risk of MACE occurrence. In conclusion, we found six risk factors associated with the development of MACE which were related with cardiovascular diseases and T2DM severity, and treatment with statins was identified as a protective factor for new MACE in this study

Excess mortality among breast cancer patients in early stages in Tarragona and Gerona

Objetivo: analizar la supervivencia poblacional del cáncer de mama (CM) en estadios precoces, estimando la tendencia temporal del exceso de mortalidad (EM) a largo plazo en periodos anuales y quinquenales, y determinando, si es posible, una proporción de pacientes que puedan considerarse curadas. Método: Se incluyó la cohorte de pacientes diagnosticadas de CM en estadios I y II antes de los 60 anos de edad en Gerona y Tarragona (N = 2453). Se calcularon la supervivencia observada (SO) y la supervivencia relativa (SR) al CM hasta los 20 aaños de seguimiento. Para valorar el EM se estimó la SR a intervalos anuales (SRI) y quinquenales (SR5). Los resultados se presentan por grupos de edad (≤49 y 50-59), estadio (I/II) y periodo de diagnóstico (1985-1994 y 1995-2004). Resultados: en el estadio I, la SO y la SR fueron mayores en 1995-2004 que en 1985-1994: 3,5% a los 15 años de seguimiento y 4,5% a los 20 años. La SO superó el 80% en el estadio I y se mantuvo inferior al 70% en el estadio II. Sin embargo, el EM a largo plazo no desapareció (SRI <1) independientemente del grupo de edad, el estadio y el periodo de diagnóstico. A los 15 años de seguimiento, el EM a 5 años osciló entre el 1-5% en el estadio I (SR5 ≥0,95) y el 5-10% en el estadio II. Conclusiones: En nuestra cohorte, a los 15 años de seguimiento se detectó que el EM anual no desapareció y el quinquenal fue del 1-10%. Por ello, no se pudo determinar una proporción de curación del CM durante el periodo de estudio

WebSurvCa: web-based estimation of death and survival probabilities in a cohort

La supervivencia relativa se ha utilizado habitualmente como medida de la evolución temporal del exceso de riesgo de mortalidad en cohortes de pacientes diagnosticados de cáncer, teniendo en cuenta la mortalidad de una población de referencia. Una vez estimado el exceso de riesgo de mortalidad pueden calcularse tres probabilidades acumuladas a un tiempo T: 1) la probabilidad de fallecer asociada a la causa de diagnóstico inicial (enfermedad en estudio), 2) la probabilidad de fallecer asociada a otras causas, y 3) la probabilidad de supervivencia absoluta en la cohorte a un tiempo T. Este trabajo presenta la aplicación WebSurvCa (https://shiny.snpstats.net/WebSurvCa/), mediante la cual los registros de cáncer de base hospitalaria y poblacional, y los registros de otras enfermedades, estiman dichas probabilidades en sus cohortes seleccionando como población de referencia la mortalidad de la comunidad autónoma que consideren

TFG 2013/2014

Amb aquesta publicació, EINA, Centre universitari de Disseny i Art adscrit a la Universitat Autònoma de Barcelona, dóna a conèixer el recull dels Treballs de Fi de Grau presentats durant el curs 2013-2014. Voldríem que un recull com aquest donés una idea més precisa de la tasca que es realitza a EINA per tal de formar nous dissenyadors amb capacitat de respondre professionalment i intel·lectualment a les necessitats i exigències de la nostra societat. El treball formatiu s’orienta a oferir resultats que responguin tant a paràmetres de rigor acadèmic i capacitat d’anàlisi del context com a l’experimentació i la creació de nous llenguatges, tot fomentant el potencial innovador del disseny.Con esta publicación, EINA, Centro universitario de diseño y arte adscrito a la Universidad Autónoma de Barcelona, da a conocer la recopilación de los Trabajos de Fin de Grado presentados durante el curso 2013-2014. Querríamos que una recopilación como ésta diera una idea más precisa del trabajo que se realiza en EINA para formar nuevos diseñadores con capacidad de responder profesional e intelectualmente a las necesidades y exigencias de nuestra sociedad. El trabajo formativo se orienta a ofrecer resultados que respondan tanto a parámetros de rigor académico y capacidad de análisis, como a la experimentación y la creación de nuevos lenguajes, al tiempo que se fomenta el potencial innovador del diseño.With this publication, EINA, University School of Design and Art, affiliated to the Autonomous University of Barcelona, brings to the public eye the Final Degree Projects presented during the 2013-2014 academic year. Our hope is that this volume might offer a more precise idea of the task performed by EINA in training new designers, able to speak both professionally and intellectually to the needs and demands of our society. The educational task is oriented towards results that might respond to the parameters of academic rigour and the capacity for contextual analysis, as well as to considerations of experimentation and the creation of new languages, all the while reinforcing design’s innovative potential

Desalination in Spain and the Role of Solar Photovoltaic Energy

Water scarcity will increase in the world in the coming decades due to climate change, especially in areas that currently already have water scarcity, such as the Mediterranean area. In these areas, to guarantee water resources, systems’ sustainability is necessary to improve demand management and the development of non-conventional resources, such as treated wastewater reuse or seawater desalination. These non-conventional resources are highly energy-consuming; so, reducing energy costs is a key element in developing their use in different sectors, including agriculture. Combining photovoltaic solar energy with seawater desalination by reverse osmosis will reduce the cost of producing water to below 0.36 EUR/m3; so, this resource can be attractive for agriculture, as demonstrated in this work. The arrangement of bifacial solar modules in horizontal single-axis tracking systems increases the energy amount generated from the sun in one hour or more, improving the facility’s efficiency and reducing the desalinated water cost. The greater distance between the solar module lines, with a ground coverage ratio (GCR) = 0.3, makes for a better environmental integration of the facility and allows the development of agrovoltaic strategies, such as native flora planting and pollinator colonization

Mathematical modeling of collagen turnover in biological tissue

The final publication is available at Springer via http://dx.doi.org/10.1007/s00285-012-0613-yWe present a theoretical and computational model for collagen turnover in soft biological tissues. Driven by alterations in the mechanical environment, collagen fiber bundles may undergo important chronic changes, characterized primarily by alterations in collagen synthesis and degradation rates. In particular, hypertension triggers an increase in tropocollagen synthesis and a decrease in collagen degradation, which lead to the well-documented overall increase in collagen content. These changes are the result of a cascade of events, initiated mainly by the endothelial and smooth muscle cells. Here, we represent these events collectively in terms of two internal variables, the concentration of growth factor TGF-$\beta$ and tissue inhibitors of metalloproteinases TIMP. The upregulation of TGF-$\beta$ increases the collagen density. The upregulation of TIMP also increases the collagen density through decreasing matrix metalloproteinase MMP. We establish a mathematical theory for mechanically-induced collagen turnover and introduce a computational algorithm for its robust and efficient solution. We demonstrate that our model can accurately predict the experimentally observed collagen increase in response to hypertension reported in literature. Ultimately, the model can serve as a valuable tool to predict the chronic adaptation of collagen content to restore the homeostatic equilibrium state in vessels with arbitrary micro-structure and geometry.Peer Reviewe