Patient-specific Boolean models of signalling networks guide personalised treatments

Prostate cancer is the second most occurring cancer in men worldwide. To better understand the mechanisms of tumorigenesis and possible treatment responses, we developed a mathematical model of prostate cancer which considers the major signalling pathways known to be deregulated. We personalised this Boolean model to molecular data to reflect the heterogeneity and specific response to perturbations of cancer patients. 488 prostate samples were used to build patient-specific models and compared to available clinical data. Additionally, eight prostate cell-line-specific models were built to validate our approach with dose-response data of several drugs. The effects of single and combined drugs were tested in these models under different growth conditions. We identified 15 actionable points of interventions in one cell-line-specific model whose inactivation hinders tumorigenesis. To validate these results, we tested nine small molecule inhibitors of five of those putative targets and found a dose-dependent effect on four of them, notably those targeting HSP90 and PI3K. These results highlight the predictive power of our personalised Boolean models and illustrate how they can be used for precision oncology.This work has been partially supported by the European Commission under the PrECISE project (H2020-PHC-668858), the INFORE project (H2020-ICT-825070) and the PerMedCoE (H2020-ICT-951773)Peer Reviewed"Article signat per 12 autors/es: Arnau Montagud, Jonas Béal, Luis Tobalina, Pauline Traynard, Vigneshwari Subramanian, Bence Szalai, Róbert Alföldi, László Puskás, Alfonso Valencia, Emmanuel Barillot, Julio Saez-Rodriguez, Laurence Calzone"Postprint (author's final draft

Differences in areal bone mineral density between metabolically healthy and unhealthy overweight/obese children: the role of physical activity and cardiorespiratory fitness

Objectives: To examine whether areal bone mineral density (aBMD) differs between metabolically healthy (MHO) and unhealthy (MUO) overweight/obese children and to examine the role of moderate-to-vigorous physical activity (MVPA) and cardiorespiratory fitness (CRF) in this association. Methods: A cross-sectional study was developed in 188 overweight/obese children (10.4 ± 1.2 years) from the ActiveBrains and EFIGRO studies. Participants were classified as MHO or MUO based on Jolliffe and Janssen’s metabolic syndrome cut-off points for triglycerides, glucose, high-density cholesterol and blood pressure. MVPA and CRF were assessed by accelerometry and the 20-m shuttle run test, respectively. Body composition was measured by dual-energy X-ray absorptiometry. Results: In model 1 (adjusted for sex, years from peak high velocity, stature and lean mass), MHO children had significantly higher aBMD in total body less head (Cohen’s d effect size, ES = 0.34), trunk (ES = 0.43) and pelvis (ES = 0.33) than MUO children. These differences were attenuated once MVPA was added to model 1 (model 2), and most of them disappeared once CRF was added to the model 1 (model 3). Conclusions: This novel research shows that MHO children have greater aBMD than their MUO peers. Furthermore, both MVPA and more importantly CRF seem to partially explain these findings.This study has been partially funded by the University of Granada, UGR Research and Knowledge Transfer Fund (PPIT) 2016, Excellence Actions Programme: Units of Scientific Excellence; Scientific Unit of Excellence on Exercise and Health (UCEES), and by the Regional Government of Andalusia, Regional Ministry of Economy, Knowledge, Enterprises and University and European Regional Development Fund (ERDF), ref. SOMM17/6107/UGR. The ActiveBrains study was funded by the Spanish Ministry of Economy and Competitiveness (Reference DEP2013-47540, DEP2016-79512-R, and DEP2017-91544-EXP). The EFIGRO study was funded by the Spanish Ministry of Health, 'Fondo de Investigación Sanitaria del Instituto de Salud Carlos III' (PI13/01335), 'Fondos Estructurales de la Unión Europea (FEDER), Una manera de hacer Europa,' and by the University of the Basque Country (GIU14/21). L.G.-M. is supported by 'La Caixa' Foundation within the Junior Leader fellowship programme (ID 100010434); M.M. is supported by the Spanish Ministry of Education, Culture and Sport (FPU14/03329) and EST17/00210; L.A. is supported by the Education Department of the Government of the Basque Country (PRE_2016_1_0057, PRE_2017_2_0224 and PRE_2018_2_0057); J.M.-G. and J.H.M. are supported by the Spanish Ministry of Education, Culture and Sport (FPU14/06837 and FPU15/02645, respectively)

Associations of dietary energy density with body composition and cardiometabolic risk in children with overweight and obesity: role of energy density calculations, under-reporting energy intake and physical activity

This study examined (1) the association of dietary energy density from solid (EDS) and solid plus liquids (EDSL) with adiposity and cardiometabolic risk factors (CRF) in children with overweight and obesity, (2) the effect of under-reporting on the mentioned associations and (3) whether the association between ED and body composition and CRF is influenced by levels of physical activity. In a cross-sectional design, 208 overweight and obese children (8-12-year-old; 111 boys) completed two non-consecutive 24 h recalls. ED was calculated using two different approaches: EDS and EDSL. Under-reporters were determined with the Goldberg method. Body composition, anthropometry and fasting blood sample measurements were performed. Moderate to vigorous physical activity (MVPA) was registered with accelerometers (7-d-register). Linear regressions were performed to evaluate the association of ED with the previously mentioned variables. Neither EDS nor EDSL were associated with body composition or CRF. However, when under-reporters were excluded, EDS was positively associated with BMI (P=0 019), body fat percentage (P=0 005), abdominal fat (P=0 008) and fat mass index (P=0 018), while EDSL was positively associated with body fat percentage (P=0 008) and fat mass index (P=0 026). When stratifying the group according to physical activity recommendations, the aforementioned associations were only maintained for non-compliers. Cluster analysis showed that the low-ED and high-MVPA group presented the healthiest profile for all adiposity and CRF. These findings could partly explain inconsistencies in literature, as we found that different ED calculations entail distinct results. Physical activity levels and excluding under-reporters greatly influence the associations between ED and adiposity in children with overweight and obesity.The research leading to these results has received funding from la Caixa Foundation and Triptolemos Foundation, the Ministry of Health (FIS PI081297), the Research Network on Preventative Activities and Health Promotion (RD06/0018/ 0038), the Henning and Johan Throne-Holst Foundation (F. B. O.), the Spanish Ministry of Education, Culture and Sport (FPU14/03329 to M. M.), the Spanish Ministry of Economy and Competitiveness (DEP2013-47540 and DEP2016-78377-R; BES-2014-068829 to C. C.-S.), Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III (PI13/01335), Fondos Estructurales de la Union Europea (FEDER), Una manera de hacer Europa, the Spanish Ministry of Science and Innovation (RYC-2011-09011 to F. B. O.), the University of Granada, Plan Propio de Investigacion 2016, Excellence Actions: Units of Excellence, Unit of Excellence on Exercise and Health (UCEES), Programa de Captacion de Talento - UGR Fellows (L. G.-M.), the SAMID III network, RETICS (PN I +D+ I 2017-2021). This study has been partially funded by the University of Granada, Plan Propio de Investigacion 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES), and by the Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades and European Regional Development Fund (ERDF), reference SOMM17/6107/UGR. ISCIII-Sub-Directorate General for Research Assessment and Promotion, the European Regional Development Fund (RD16/ 0022), the EXERNET Research Network on Exercise and Health in Special Populations (DEP2005-00046/ACTI), and the University of the Basque Country (GIU14/21). J. M.-G. is supported by the Spanish Ministry of Education, Culture and Sport (FPU14/06837). J. H. M. is supported by the Spanish Ministry of Education, Culture and Sport (FPU15/02645)

Programa de coordinación en el Máster Universitario en Física y Tecnología de los Láseres

Memoria ID-042. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2010-2011.El proyecto ha pretendido desarrollar un programa integral de coordinación en la titulación de Máster en Física y Tecnología de los Láseres. Desde que se implantó el máster en el curso 2006-07 se han llevado a cabo tareas de coordinación de forma continua con el objeto de subsanar problemas detectados. Durante la ejecución de este proyecto se ha intentado sistematizar el proceso de coordinación y documentar las actuaciones realizadas

Actividades para la captación de estudiantes para el Máster en Física y Tecnología de los Láseres

Memoria ID-212. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2013-2014

Elaboración de un archivo fotográfico de fenómenos ópticos y experiencias sencillas con luz. Edición de informe didáctico

Memoria ID-0199. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2014-2015

Actividades para la captación de estudiantes para el Máster en Física y Tecnología de los Láseres

Memoria ID-0306. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2014-2015

Promoción de la titulación de Máster Universitario en Física y Tecnología de los Láseres

Memoria ID12-0215. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2012-2013

LA REFORMA REGIONAL EN FRANCIA.

SUMMARY: I. INTRODUCTION. - II. IMMEDIATE BACKGROUND. - III. THE LAW OF 1982. - IV. SINGULARITY OF THE FRENCH REFORM. - V. CONCLUSION.SUMARIO: I. INTRODUCCIÓN. — II. ANTECEDENTES INMEDIATOS. — III. LA LEY DE 1982. — IV. SINGULARIDAD DE LA REFORMA FRANCESA. — V. CONCLUSIÓN