The SASSCAL contribution to climate observation, climate data management and data rescue in Southern Africa

A major task of the newly established "Southern African Science Service Centre for Climate Change and Adaptive Land Management" (SASSCAL; www.sasscal.org) and its partners is to provide science-based environmental information and knowledge which includes the provision of consistent and reliable climate data for Southern Africa. Hence, SASSCAL, in close cooperation with the national weather authorities of Angola, Botswana, Germany and Zambia as well as partner institutions in Namibia and South Africa, supports the extension of the regional meteorological observation network and the improvement of the climate archives at national level. With the ongoing rehabilitation of existing weather stations and the new installation of fully automated weather stations (AWS), altogether 105 AWS currently provide a set of climate variables at 15, 30 and 60 min intervals respectively. These records are made available through the SASSCAL WeatherNet, an online platform providing near-real time data as well as various statistics and graphics, all in open access. This effort is complemented by the harmonization and improvement of climate data management concepts at the national weather authorities, capacity building activities and an extension of the data bases with historical climate data which are still available from different sources. These activities are performed through cooperation between regional and German institutions and will provide important information for climate service related activities

Structure and Stability of an Amorphous Metal

Using molecular dynamics simulations, with a realistic many-body embedded-atom potential, and a novel method to characterize local order, we study the structure of pure nickel during the rapid quench of the liquid and in the resulting glass. In contrast with previous simulations with pair potentials, we find more crystalline order and fewer icosahedra for slower quenching rates, resulting in a glass less stable against crystallization. It is shown that there is not a specific amorphous structure, only the arrest of the transition from liquid to crystal, resulting in small crystalline clusters immersed in an amorphous matrix with the same structure of the liquid.Comment: 4 pages, 4 ps figs., to appear in Phys. Rev. Let

Development of lifetime comorbidity in the world health organization world mental health surveys

CONTEXT: Although numerous studies have examined the role of latent variables in the structure of comorbidity among mental disorders, none has examined their role in the development of comorbidity. OBJECTIVE: To study the role of latent variables in the development of comorbidity among 18 lifetime DSM-IV disorders in the World Health Organization World Mental Health Surveys. DESIGN: Nationally or regionally representative community surveys. SETTING: Fourteen countries. PARTICIPANTS: A total of 21 229 survey respondents. MAIN OUTCOME MEASURES: First onset of 18 lifetime DSM-IV anxiety, mood, behavior, and substance disorders assessed retrospectively in the World Health Organization Composite International Diagnostic Interview. RESULTS: Separate internalizing (anxiety and mood disorders) and externalizing (behavior and substance disorders) factors were found in exploratory factor analysis of lifetime disorders. Consistently significant positive time-lagged associations were found in survival analyses for virtually all temporally primary lifetime disorders predicting subsequent onset of other disorders. Within-domain (ie, internalizing or externalizing) associations were generally stronger than between-domain associations. Most time-lagged associations were explained by a model that assumed the existence of mediating latent internalizing and externalizing variables. Specific phobia and obsessive-compulsive disorder (internalizing) and hyperactivity and oppositional defiant disorders (externalizing) were the most important predictors. A small number of residual associations remained significant after controlling the latent variables. CONCLUSIONS: The good fit of the latent variable model suggests that common causal pathways account for most of the comorbidity among the disorders considered herein. These common pathways should be the focus of future research on the development of comorbidity, although several important pairwise associations that cannot be accounted for by latent variables also exist that warrant further focused study

The potential of marginal coastal nursery habitats for the conservation of a culturally important Caribbean marine species

Aim: Identifying the potential of marginal habitats for species conservation is of key importance when their core high-quality habitats are under substantial disturbances and threats. However, there is currently a knowledge gap on how useful marine marginal habitats may be for conserving endangered marine species. Here, we investigate the potential of groundwater-fed coastal areas for the conservation of the queen conch, an economically and culturally important marine gastropod. Location: The inlet of Xel-Ha, typical of groundwater-fed coastal areas widely distributed along the Yucatan Peninsula coast in Mexico and partially protected by a network of marine protected areas. Methods: We tracked 66 queen conchs (Lobatus gigas) using acoustic telemetry over a period of 3.5 years. We investigated for ontogenetic niche shift using a network analysis and by modelling their growth. Results: The queen conchs exhibited the same ontogenetic niche shift required to complete their life cycle in this marginal habitat as they do in offshore core habitats. A total of 33 individuals departed the inlet and migrated from shallow groundwater-affected nursery grounds to deeper marine habitats more suitable for breeding aggregation. Main conclusions: As the broad-scale movement behaviour of queen conch in this inlet is similar to that observed on the overfished core habitats, our findings suggest that groundwater-fed coastal areas should be included in conservation planning for an effective management of this species within a network of marine protected areas

Cross-national differences in the prevalence and correlates of burden among older family caregivers in the World Health Organization World Mental Health (WMH) Surveys

Background Current trends in population aging affect both recipients and providers of informal family caregiving, as the pool of family caregivers is shrinking while demand is increasing. Epidemiological research has not yet examined the implications of these trends for burdens experienced by aging family caregivers. Method Cross-sectional community surveys in 20 countries asked 13 892 respondents aged 50+ years about the objective (time, financial) and subjective (distress, embarrassment) burdens they experience in providing care to first-degree relatives with 12 broadly defined serious physical and mental conditions. Differential burden was examined by country income category, kinship status and type of condition. Results Among the 26.9-42.5% respondents in high-, upper-middle-, and low-/lower-middle-income countries reporting serious relative health conditions, 35.7-42.5% reported burden. Of those, 25.2-29.0% spent time and 13.5-19.4% money, while 24.4-30.6% felt distress and 6.4-21.7% embarrassment. Mean caregiving hours per week in those giving any time were 16.6-23.6 (169.9-205.8 h/week per 100 people aged 50+ years). Burden in low-/lower-middle-income countries was 2- to 3-fold higher than in higher-income countries, with any financial burden averaging 14.3% of median family income in high-, 17.7% in upper-middle-, and 39.8% in low-/lower-middle-income countries. Higher burden was reported by women than men and for conditions of spouses and children than parents or siblings. Conclusions Uncompensated family caregiving is an important societal asset that offsets rising formal healthcare costs. However, the substantial burdens experienced by aging caregivers across multiple family health conditions and geographic regions threaten the continued integrity of their caregiving capacity. Initiatives supporting older family caregivers are consequently needed, especially in low-/lower-middle-income countrie

Including information about co-morbidity in estimates of disease burden: results from the World Health Organization World Mental Health Surveys

Background The methodology commonly used to estimate disease burden, featuring ratings of severity of individual conditions, has been criticized for ignoring co-morbidity. A methodology that addresses this problem is proposed and illustrated here with data from the World Health Organization World Mental Health Surveys. Although the analysis is based on self-reports about one's own conditions in a community survey, the logic applies equally well to analysis of hypothetical vignettes describing co-morbid condition profiles. Method Face-to-face interviews in 13 countries (six developing, nine developed; n=31 067; response rate=69.6%) assessed 10 classes of chronic physical and nine of mental conditions. A visual analog scale (VAS) was used to assess overall perceived health. Multiple regression analysis with interactions for co-morbidity was used to estimate associations of conditions with VAS. Simulation was used to estimate condition-specific effects. Results The best-fitting model included condition main effects and interactions of types by numbers of conditions. Neurological conditions, insomnia and major depression were rated most severe. Adjustment for co-morbidity reduced condition-specific estimates with substantial between-condition variation (0.24-0.70 ratios of condition-specific estimates with and without adjustment for co-morbidity). The societal-level burden rankings were quite different from the individual-level rankings, with the highest societal-level rankings associated with conditions having high prevalence rather than high individual-level severity. Conclusions Plausible estimates of disorder-specific effects on VAS can be obtained using methods that adjust for co-morbidity. These adjustments substantially influence condition-specific rating

A dashboard-based system for supporting diabetes care

[EN] Objective To describe the development, as part of the European Union MOSAIC (Models and Simulation Techniques for Discovering Diabetes Influence Factors) project, of a dashboard-based system for the management of type 2 diabetes and assess its impact on clinical practice. Methods The MOSAIC dashboard system is based on predictive modeling, longitudinal data analytics, and the reuse and integration of data from hospitals and public health repositories. Data are merged into an i2b2 data warehouse, which feeds a set of advanced temporal analytic models, including temporal abstractions, care-flow mining, drug exposure pattern detection, and risk-prediction models for type 2 diabetes complications. The dashboard has 2 components, designed for (1) clinical decision support during follow-up consultations and (2) outcome assessment on populations of interest. To assess the impact of the clinical decision support component, a pre-post study was conducted considering visit duration, number of screening examinations, and lifestyle interventions. A pilot sample of 700 Italian patients was investigated. Judgments on the outcome assessment component were obtained via focus groups with clinicians and health care managers. Results The use of the decision support component in clinical activities produced a reduction in visit duration (P¿¿¿.01) and an increase in the number of screening exams for complications (P¿<¿.01). We also observed a relevant, although nonstatistically significant, increase in the proportion of patients receiving lifestyle interventions (from 69% to 77%). Regarding the outcome assessment component, focus groups highlighted the system¿s capability of identifying and understanding the characteristics of patient subgroups treated at the center. Conclusion Our study demonstrates that decision support tools based on the integration of multiple-source data and visual and predictive analytics do improve the management of a chronic disease such as type 2 diabetes by enacting a successful implementation of the learning health care system cycle.This work was supported by the European Union in the Seventh Framework Programme, grant number 600914.Dagliati, A.; Sacchi, L.; Tibollo, V.; Cogni, G.; Teliti, M.; Martinez-Millana, A.; Traver Salcedo, V.... (2018). A dashboard-based system for supporting diabetes care. Journal of the American Medical Informatics Association. 25(5):538-547. https://doi.org/10.1093/jamia/ocx159S538547255Sim, I., Gorman, P., Greenes, R. A., Haynes, R. B., Kaplan, B., Lehmann, H., & Tang, P. C. (2001). Clinical Decision Support Systems for the Practice of Evidence-based Medicine. Journal of the American Medical Informatics Association, 8(6), 527-534. doi:10.1136/jamia.2001.0080527Palmer, A. J., Roze, S., Valentine, W. J., Minshall, M. E., Foos, V., Lurati, F. M., … Spinas, G. A. (2004). The CORE Diabetes Model: Projecting Long-term Clinical Outcomes, Costs and Costeffectiveness of Interventions in Diabetes Mellitus (Types 1 and 2) to Support Clinical and Reimbursement Decision-making. Current Medical Research and Opinion, 20(sup1), S5-S26. doi:10.1185/030079904x1980O’Connor, P. J., Bodkin, N. L., Fradkin, J., Glasgow, R. E., Greenfield, S., Gregg, E., … Wysham, C. H. (2011). Diabetes Performance Measures: Current Status and Future Directions. Diabetes Care, 34(7), 1651-1659. doi:10.2337/dc11-0735Donsa, K., Beck, P., Höll, B., Mader, J. K., Schaupp, L., Plank, J., … Pieber, T. R. (2016). Impact of errors in paper-based and computerized diabetes management with decision support for hospitalized patients with type 2 diabetes. A post-hoc analysis of a before and after study. International Journal of Medical Informatics, 90, 58-67. doi:10.1016/j.ijmedinf.2016.03.007Sáenz, A., Brito, M., Morón, I., Torralba, A., García-Sanz, E., & Redondo, J. (2012). Development and Validation of a Computer Application to Aid the Physician’s Decision-Making Process at the Start of and during Treatment with Insulin in Type 2 Diabetes: A Randomized and Controlled Trial. Journal of Diabetes Science and Technology, 6(3), 581-588. doi:10.1177/193229681200600313Ampudia-Blasco, F. J., Benhamou, P. Y., Charpentier, G., Consoli, A., Diamant, M., Gallwitz, B., … Stoevelaar, H. (2015). A Decision Support Tool for Appropriate Glucose-Lowering Therapy in Patients with Type 2 Diabetes. Diabetes Technology & Therapeutics, 17(3), 194-202. doi:10.1089/dia.2014.0260Lim, S., Kang, S. M., Shin, H., Lee, H. J., Won Yoon, J., Yu, S. H., … Jang, H. C. (2011). Improved Glycemic Control Without Hypoglycemia in Elderly Diabetic Patients Using the Ubiquitous Healthcare Service, a New Medical Information System. Diabetes Care, 34(2), 308-313. doi:10.2337/dc10-1447Lipton, J. A., Barendse, R. J., Akkerhuis, K. M., Schinkel, A. F. L., & Simoons, M. L. (2010). Evaluation of a Clinical Decision Support System for Glucose Control. Critical Pathways in Cardiology: A Journal of Evidence-Based Medicine, 9(3), 140-147. doi:10.1097/hpc.0b013e3181e7d7caNeubauer, K. M., Mader, J. K., Höll, B., Aberer, F., Donsa, K., Augustin, T., … Pieber, T. R. (2015). Standardized Glycemic Management with a Computerized Workflow and Decision Support System for Hospitalized Patients with Type 2 Diabetes on Different Wards. Diabetes Technology & Therapeutics, 17(10), 685-692. doi:10.1089/dia.2015.0027Rodbard, D., & Vigersky, R. A. (2011). Design of a Decision Support System to Help Clinicians Manage Glycemia in Patients with Type 2 Diabetes Mellitus. Journal of Diabetes Science and Technology, 5(2), 402-411. doi:10.1177/193229681100500230Augstein, P., Vogt, L., Kohnert, K.-D., Heinke, P., & Salzsieder, E. (2010). Translation of Personalized Decision Support into Routine Diabetes Care. Journal of Diabetes Science and Technology, 4(6), 1532-1539. doi:10.1177/193229681000400631Reza, A. W., & Eswaran, C. (2009). A Decision Support System for Automatic Screening of Non-proliferative Diabetic Retinopathy. Journal of Medical Systems, 35(1), 17-24. doi:10.1007/s10916-009-9337-yKumar, S. J. J., & Madheswaran, M. (2012). An Improved Medical Decision Support System to Identify the Diabetic Retinopathy Using Fundus Images. Journal of Medical Systems, 36(6), 3573-3581. doi:10.1007/s10916-012-9833-3Cho, B. H., Yu, H., Kim, K.-W., Kim, T. H., Kim, I. Y., & Kim, S. I. (2008). Application of irregular and unbalanced data to predict diabetic nephropathy using visualization and feature selection methods. Artificial Intelligence in Medicine, 42(1), 37-53. doi:10.1016/j.artmed.2007.09.005Cleveringa, F. G. W., Gorter, K. J., van den Donk, M., & Rutten, G. E. H. M. (2008). Combined Task Delegation, Computerized Decision Support, and Feedback Improve Cardiovascular Risk for Type 2 Diabetic Patients: A cluster randomized trial in primary care. Diabetes Care, 31(12), 2273-2275. doi:10.2337/dc08-0312Haussler, B., Fischer, G. C., Meyer, S., & Sturm, D. (2007). Risk assessment in diabetes management: how do general practitioners estimate risks due to diabetes? Quality and Safety in Health Care, 16(3), 208-212. doi:10.1136/qshc.2006.019539Heselmans, A., Van de Velde, S., Ramaekers, D., Vander Stichele, R., & Aertgeerts, B. (2013). Feasibility and impact of an evidence-based electronic decision support system for diabetes care in family medicine: protocol for a cluster randomized controlled trial. Implementation Science, 8(1). doi:10.1186/1748-5908-8-83Koopman, R. J., Kochendorfer, K. M., Moore, J. L., Mehr, D. R., Wakefield, D. S., Yadamsuren, B., … Belden, J. L. (2011). A Diabetes Dashboard and Physician Efficiency and Accuracy in Accessing Data Needed for High-Quality Diabetes Care. The Annals of Family Medicine, 9(5), 398-405. doi:10.1370/afm.1286Den Ouden, H., Vos, R. C., Reidsma, C., & Rutten, G. E. (2015). Shared decision making in type 2 diabetes with a support decision tool that takes into account clinical factors, the intensity of treatment and patient preferences: design of a cluster randomised (OPTIMAL) trial. BMC Family Practice, 16(1). doi:10.1186/s12875-015-0230-0Holbrook, A., Thabane, L., Keshavjee, K., Dolovich, L., Bernstein, B., … Chan, D. (2009). Individualized electronic decision support and reminders to improve diabetes care in the community: COMPETE II randomized trial. Canadian Medical Association Journal, 181(1-2), 37-44. doi:10.1503/cmaj.081272O’Reilly, D., Holbrook, A., Blackhouse, G., Troyan, S., & Goeree, R. (2012). Cost-effectiveness of a shared computerized decision support system for diabetes linked to electronic medical records. Journal of the American Medical Informatics Association, 19(3), 341-345. doi:10.1136/amiajnl-2011-000371Parker, R. F., Mohamed, A. Z., Hassoun, S. A., Miles, S., & Fernando, D. J. S. (2014). The Effect of Using a Shared Electronic Health Record on Quality of Care in People With Type 2 Diabetes. Journal of Diabetes Science and Technology, 8(5), 1064-1065. doi:10.1177/1932296814536880Caban, J. J., & Gotz, D. (2015). Visual analytics in healthcare - opportunities and research challenges. Journal of the American Medical Informatics Association, 22(2), 260-262. doi:10.1093/jamia/ocv006Mick, J. (2011). Data-Driven Decision Making. JONA: The Journal of Nursing Administration, 41(10), 391-393. doi:10.1097/nna.0b013e31822edb8cBatley, N. J., Osman, H. O., Kazzi, A. A., & Musallam, K. M. (2011). Implementation of an Emergency Department Computer System: Design Features That Users Value. The Journal of Emergency Medicine, 41(6), 693-700. doi:10.1016/j.jemermed.2010.05.014Sprague, A. E., Dunn, S. I., Fell, D. B., Harrold, J., Walker, M. C., Kelly, S., & Smith, G. N. (2013). Measuring Quality in Maternal-Newborn Care: Developing a Clinical Dashboard. Journal of Obstetrics and Gynaecology Canada, 35(1), 29-38. doi:10.1016/s1701-2163(15)31045-8WILBANKS, B. A., & LANGFORD, P. A. (2014). A Review of Dashboards for Data Analytics in Nursing. CIN: Computers, Informatics, Nursing, 32(11), 545-549. doi:10.1097/cin.0000000000000106Hartzler, A. L., Izard, J. P., Dalkin, B. L., Mikles, S. P., & Gore, J. L. (2015). Design and feasibility of integrating personalized PRO dashboards into prostate cancer care. Journal of the American Medical Informatics Association, 23(1), 38-47. doi:10.1093/jamia/ocv101Dixon, B. E., Jabour, A. M., Phillips, E. O., & Marrero, D. G. (2014). An informatics approach to medication adherence assessment and improvement using clinical, billing, and patient-entered data. Journal of the American Medical Informatics Association, 21(3), 517-521. doi:10.1136/amiajnl-2013-001959Murphy, S. N., Weber, G., Mendis, M., Gainer, V., Chueh, H. C., Churchill, S., & Kohane, I. (2010). Serving the enterprise and beyond with informatics for integrating biology and the bedside (i2b2). Journal of the American Medical Informatics Association, 17(2), 124-130. doi:10.1136/jamia.2009.000893Shahar, Y., & Musen, M. A. (1996). Knowledge-based temporal abstraction in clinical domains. Artificial Intelligence in Medicine, 8(3), 267-298. doi:10.1016/0933-3657(95)00036-4Sacchi, L., Capozzi, D., Bellazzi, R., & Larizza, C. (2015). JTSA: An open source framework for time series abstractions. Computer Methods and Programs in Biomedicine, 121(3), 175-188. doi:10.1016/j.cmpb.2015.05.006Dagliati, A., Sacchi, L., Zambelli, A., Tibollo, V., Pavesi, L., Holmes, J. H., & Bellazzi, R. (2017). Temporal electronic phenotyping by mining careflows of breast cancer patients. Journal of Biomedical Informatics, 66, 136-147. doi:10.1016/j.jbi.2016.12.012Hripcsak, G., & Albers, D. J. (2013). Next-generation phenotyping of electronic health records. Journal of the American Medical Informatics Association, 20(1), 117-121. doi:10.1136/amiajnl-2012-001145Bijlsma, M. J., Janssen, F., & Hak, E. (2015). Estimating time-varying drug adherence using electronic records: extending the proportion of days covered (PDC) method. Pharmacoepidemiology and Drug Safety, 25(3), 325-332. doi:10.1002/pds.3935Robusto, F., Lepore, V., D’Ettorre, A., Lucisano, G., De Berardis, G., Bisceglia, L., … Nicolucci, A. (2016). The Drug Derived Complexity Index (DDCI) Predicts Mortality, Unplanned Hospitalization and Hospital Readmissions at the Population Level. PLOS ONE, 11(2), e0149203. doi:10.1371/journal.pone.0149203De Berardis, G., D’Ettorre, A., Graziano, G., Lucisano, G., Pellegrini, F., Cammarota, S., … Nicolucci, A. (2012). The burden of hospitalization related to diabetes mellitus: A population-based study. Nutrition, Metabolism and Cardiovascular Diseases, 22(7), 605-612. doi:10.1016/j.numecd.2010.10.016Van Gemert-Pijnen, J. E., Nijland, N., van Limburg, M., Ossebaard, H. C., Kelders, S. M., Eysenbach, G., & Seydel, E. R. (2011). A Holistic Framework to Improve the Uptake and Impact of eHealth Technologies. Journal of Medical Internet Research, 13(4), e111. doi:10.2196/jmir.1672Shahar, Y. (1997). A framework for knowledge-based temporal abstraction. Artificial Intelligence, 90(1-2), 79-133. doi:10.1016/s0004-3702(96)00025-2Tenenbaum, J. D., Avillach, P., Benham-Hutchins, M., Breitenstein, M. K., Crowgey, E. L., Hoffman, M. A., … Freimuth, R. R. (2016). An informatics research agenda to support precision medicine: seven key areas. Journal of the American Medical Informatics Association, 23(4), 791-795. doi:10.1093/jamia/ocv213Bottomly, D., McWeeney, S. K., & Wilmot, B. (2015). HitWalker2: visual analytics for precision medicine and beyond. Bioinformatics, 32(8), 1253-1255. doi:10.1093/bioinformatics/btv739Fabris, C., Facchinetti, A., Fico, G., Sambo, F., Arredondo, M. T., & Cobelli, C. (2015). Parsimonious Description of Glucose Variability in Type 2 Diabetes by Sparse Principal Component Analysis. Journal of Diabetes Science and Technology, 10(1), 119-124. doi:10.1177/1932296815596173Hassenzahl, M., Wiklund-Engblom, A., Bengs, A., Hägglund, S., & Diefenbach, S. (2015). Experience-Oriented and Product-Oriented Evaluation: Psychological Need Fulfillment, Positive Affect, and Product Perception. International Journal of Human-Computer Interaction, 31(8), 530-544. doi:10.1080/10447318.2015.106466

Design and Bolometer Characterization of the SPT-3G First-year Focal Plane

During the austral summer of 2016-17, the third-generation camera, SPT-3G, was installed on the South Pole Telescope, increasing the detector count in the focal plane by an order of magnitude relative to the previous generation. Designed to map the polarization of the cosmic microwave background, SPT-3G contains ten 6-in-hexagonal modules of detectors, each with 269 trichroic and dual-polarization pixels, read out using 68x frequency-domain multiplexing. Here we discuss design, assembly, and layout of the modules, as well as early performance characterization of the first-year array, including yield and detector properties.Comment: Conference proceeding for Low Temperature Detectors 2017. Accepted for publication: 27 August 201

Extracellular vesicles-based biomarkers represent a promising liquid biopsy in endometrial cancer

Tumor-derived extracellular vesicles (EVs) are secreted in large amounts into biological fluids of cancer patients. The analysis of EVs cargoes has been associated with patient´s outcome and response to therapy. However, current technologies for EVs isolation are tedious and low cost-e cient for routine clinical implementation. To explore the clinical value of circulating EVs analysis we attempted a proof-of-concept in endometrial cancer (EC) with ExoGAG, an easy to use and highly e cient new technology to enrich EVs. Technical performance was first evaluated using EVs secreted by Hec1A cells. Then, the clinical value of this strategy was questioned by analyzing the levels of two well-known tissue biomarkers in EC, L1 cell adhesion molecule (L1CAM) and Annexin A2 (ANXA2), in EVs purified from plasma in a cohort of 41 EC patients and 20 healthy controls. The results demonstrated the specific content of ANXA2 in the purified EVs fraction, with an accurate sensitivity and specificity for EC diagnosis. Importantly, high ANXA2 levels in circulating EVs were associated with high risk of recurrence and non-endometrioid histology suggesting a potential value as a prognostic biomarker in EC. These results also confirmed ExoGAG technology as a robust technique for the clinical implementation of circulating EVs analysesThis research was funded by Instituto de Salud Carlos III, grant PI17/01919, co-financed by the European Regional Development Fund (FEDER), and by Fundación Científica de la Asociación Española Contra el Cáncer (AECC), Grupos Clínicos Coordinados 2018. Carolina Herrero is supported by a predoctoral i-PFIS fellowship from Instituto de Salud Carlos III (IFI17/00047); Laura Muinelo is supported by Asociación Española Contra el Cáncer (AECC)