LIMNOCLIBER: a transect of high-resolution lacustrine records of climate and environmental variability in Spain since the Last Glacial Maximum

1 Poster with 6 Fig., 1 Tabl.The LIMNOCLIBER project represents a multidisciplinary, international effort to recover, for the first time, long paleoenvironmental and paleoclimate records from relatively deep lakes in Spain. New records from the Iberian Peninsula during the last decade have changed our views on Holocene history from a generally benign climate punctuated by dry mid Holocene period and an amelioration afterwards, to a complex fluctuation of arid and humid periods. Lateglacial reconstructions have also shown large variability and a multifaceted regional pattern in the Iberian Peninsula. The fact that the maximum extent of mountain glaciers occurred much earlier than the global LGM, also underlines the differences in timing of the main climatic events in Southwestern Europe. To resolve the contradictory interpretations of available records and to reconstruct the effective moisture history of the region since the Last Global Glacial Maximum (LGM), long, high resolution, well-dated records from hydrologically-sensitive regions in Spain are needed. Although deep lakes are not common in Spain, numerous, relatively deep (up to 20 m), karstic lakes with carbonate-rich sediments occur in the Iberian Range and the Pyrenees, and deep terminal-moraine lakes occur in the mountains of northern and western Spain.The LIMNOCLIBER project is funded by the Spanish government (ref: REN 2003-09130-C02-02/CLI).Peer reviewe

Oxygen and Hydrogen Isotopic Signatures of Large Atmospheric Ice Conglomerations

18 páginas, 5 figuras, 4 tablas.Specific studies about the stable isotope composition (18O/16O and D/H) of atmospheric icy conglomerations are still scarce. The present work offers, for the first time, a very detailed analysis of oxygen and hydrogen isotopic signatures of unusually large ice conglomerations, or “megacryometeors”, that fell to the ground in Spain during January 2000. The hydrochemical analysis is based on the bulk isotopic composition and systematic selective sampling (deuterium isotopic mapping) of eleven selected specimens. δ18O and δD (V-SMOW) of all samples fall into the Meteoric Water Line matching well with typical tropospheric values. The distribution of the samples on Craig's line suggests either a variation in condensation temperature and/or different residual fractions of water vapour (Rayleigh processes). Three of the largest megacryometeors exhibited unequivocally distinctive negative values (δ18O = −17.2%0 and δD = −127 %0 V-SMOW), (δ18O = −15.6%0 and δD = −112%0 V-SMOW) and (δ18O = −14.4%0 and δD = −100%0 V-SMOW), suggesting an atmospheric origin typical of the upper troposphere. Theoretical calculations indicate that the vertical trajectory of growth was lower than 3.2 km. During the period in which the fall of megacryometeors occurred, anomalous atmospheric conditions were observed to exist: a substantial lowering of the tropopause with a deep layer of saturated air below, ozone depression and strong wind shear. Moreover, these large ice conglomerations occurred during non-thunderstorm conditions, suggesting an alternative process of ice growth was responsible for their formation.This work was supported by the Spanish Council for Scientific Research.Peer reviewe

Desarrollo de Negocios 2 - GD27 - 202100

Descripción: En la actualidad, los empresarios e inversionistas necesitan invertir en negocios que sean viables, rentables, sostenibles, innovadores y escalables. Para ello necesitan una verificación a través de un documento que sea sintético, fácil de leer, sustentado a través de datos y cifras. Para ello el alumno realizará un proyecto de investigación orientado a otorgar una respuesta sólida, argumentada y coherente al reto empresarial identificado. El reto empresarial es entonces definido como una oportunidad de mejora dentro de una organización, así como también el desarrollo de un plan para la toma de oportunidades para la organización. El estudiante será capaz de compartir información útil para la resolución de situaciones de negocios y de participar activamente en la consecución de una meta común al equipo de trabajo. Propósito: Curso de especialidad, de carácter teórico práctico, dirigido a los estudiantes del décimo ciclo, que busca desarrollar las competencias generales de la universidad de Pensamiento innovador y razonamiento cuantitativo y la competencia específica de la carrera Investigación e Innovación, todas a un nivel 3. Según los Lineamientos de Carga hábil del alumno de pregrado EPE por lo estipulado por SUNEDU: https://sica.upc.edu.pe/sites/sica.upc.edu.pe/files/MAT-PYL- 02%20V03%20LINEAMIENTOS%20DE%20CARGA%20ACAD%C3%89MICA%20EN%20PREGRADO% 20EPE%20(2) 1Los alumnos de Pregrado EPE con código de admisión 2016 en adelante que no acrediten haber iniciado estudios en el sistema de educación superior antes del año 2016, o no acrediten haber cursado un mínimo de cinco años en dicho sistema, deberán elaborar y aprobar un trabajo de investigación conducente a la obtención del grado académico de bachiller (en forma posterior a la aprobación por parte del alumno de los créditos obligatorios y electivos respectivos contemplados en el Plan de Estudios)que se considera parte de la malla curricular del programa académico cursado por el alumno. La elaboración de dicho trabajo de investigación será adicional al alcance de nuestro curso Desarrollo de Negocios 2

Immune checkpoint inhibitors-associated thrombosis in patients with lung cancer and melanoma: a study of the Spanish society of medical oncology (SEOM) thrombosis and cancer group.

Immune Checkpoint Inhibitors (ICI) can be associated with thrombotic events, both venous and arterial (VTE/AT). However, there is a paucity of information regarding patients in routine clinical practice. Retrospective, multicenter study promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Patients with melanoma and lung cancer who initiated ICI between 01/01/2015 and 31/12/2019 were recruited. Minimum follow-up was 6 months (unless it was not possible because of death). The primary objective was to calculate the incidence of ICI-associated VTE/AT and the secondary objectives included to analyze its impact on survival and to identify predictor variables for VTE/AT. 665 patients with lung cancer were enrolled. The incidence of VTE/AT during follow-up was 8.4%. Median overall survival (OS) was lower in the VTE/AT group (12 months 95% CI 4.84-19.16 vs. 19 months 95% CI 16.11-21.9; p = 0.0049). Neutrophil/lymphocyte ratio (NLR) and anemia upon initiation of IT, as well as a history of thrombosis between cancer diagnosis and the start of ICI, were predictive variables for developing of VTE/AT (p  ICI increases the risk of VTE/AT in patients with lung cancer and melanoma, which impact OS

Management of infliximab refractory immune checkpoint inhibitor gastrointestinal toxicity: a multicenter case series

Background Immune checkpoint inhibitor (ICI) gastrointestinal toxicity (gastritis, enteritis, colitis) is a major cause of morbidity and treatment-related death. Guidelines agree steroid-refractory cases warrant infliximab, however best management of infliximab-refractory ICI gastrointestinal toxicity (IRIGItox) is unknown.Methods We conducted an international multicenter retrospective case series. IRIGItox was defined as failure of symptom resolution ≤grade 1 (Common Terminology Criteria for Adverse Events V.5.0) following ≥2 infliximab doses or failure of symptom resolution ≤grade 2 after one dose. Data were extracted regarding demographics, steroid use, response to treatment, and survival outcomes. Toxicity was graded at symptom onset and time of infliximab failure. Efficacy of infliximab refractory therapy was assessed by symptom resolution, time to resolution and steroid wean duration. Survival outcomes were examined based on immunosuppressive therapy received.Results 78 patients were identified: median age 60 years; 56% men; majority melanoma (N=70, 90%); 60 (77%) received anti-cytotoxic T-lymphocyte-associated protein 4 alone or in combination with anti-programmed cell death protein-1 and most had colitis (N=74, 95%). 106 post-infliximab treatments were given: 31 calcineurin inhibitors (CNIs); 27 antimetabolites (mycophenolate, azathioprine); 16 non-systemic immunomodulatory agents (eg, mesalazine or budesonide); 15 vedolizumab; 5 other biologics (anti-interleukin-12/23, 16, Janus kinase inhibitors) and 7 interventional procedures (including colectomy); 5 did not receive post-infliximab therapy. Symptom resolution was achieved in most (N=23/31, 74%) patients treated with CNIs; 12/27 (44%) with antimetabolites; 7/16 (44%) with non-systemic immunomodulation, 8/15 (53%) with vedolizumab and 5/7 (71%) with interventional procedures. No non-vedolizumab biologics resulted in toxicity resolution. CNIs had the shortest time to symptom resolution (12 days) and steroid wean (43 days); however, were associated with poorer event-free survival (6.3 months) and overall survival (26.8 months) than other agents. Conversely, vedolizumab had the longest time to toxicity resolution and steroid wean, 66 and 124 days, but most favorable survival data: EFS 24.5 months; median OS not reached. Six death occurred (three due to IRIGItox or management of toxicity; three with persisting IRIGItox and progressive disease).Conclusions IRIGItox causes major morbidity and mortality. Management is heterogeneous. CNIs appear most likely to result in toxicity resolution in the shortest time period, however, are associated with poorer oncological outcomes in contrast to vedolizumab

El parque de Yuncos como espacio educativo y recreativo

Resumen basado en el del proyecto. Premiado en la convocatoria: Premios para proyectos de innovación concluidos durante el curso 2006-2007, en los centros educativos no universitarios sostenidos con fondos públicos de la Comunidad Autónoma de Castilla-La Mancha (Orden 30-01-2008, de la Consejería de Educación y Ciencia de la Junta de Comunidades de Castilla-La Mancha. Resolución de 15-05-2009, de la Viceconsejería de Educación)El proyecto desarrolla una serie de actividades de enseñanza y aprendizaje en el campo de la educación ambiental basadas en el principio de la investigación recreativa. Las actividades se realizan en un parque municipal. Programadas por profesores del Instituto y del Colegio Público, en colaboración con el Ayuntamiento del municipio, dirigidas a alumnos de Primaria, e impartidas por alumnos de Secundaria, que intervienen como monitores. Los objetivos básicos que se persiguen son: mejorar la comunicación educativa entre centros de Primaria y de Secundaria, mediante el diseño compartido de actividades de enseñanza y aprendizaje, integrando conocimientos, planteamientos y experiencias docentes diferentes. Se persigue así una cooperación real y eficaz entre un Colegio y un Instituto de un mismo municipio, a partir de la colaboración en tareas comunes. Colaboración, a la que se suma el Ayuntamiento, facilitando aspectos logísticos y espacios necesarios para llevar a cabo las actividades programadas. En segundo lugar, incorporar al alumnado de secundaria en el proceso educativo como docente, impartiendo y adaptando actividades dirigidas a alumnos de niveles inferiores, como estrategia para lograr aprendizajes significativos y funcionales. El tercer objetivo es abordar la educación ambiental, explorando actividades con metodologías educativas basadas en el principio de la investigación recreativa con el objetivo de favorecer la adquisición de valores y conductas de respeto al medio ambiente. La metodología de trabajo se basa en el principio educativo de aprender a aprender, favoreciendo estrategias de aprendizaje a través del descubrimiento y de la interacción y facilitando la consecución de aprendizajes funcionales. La organización de las tareas se plantea a partir de un aprendizaje en grupos, que favorece las relaciones entre iguales y la superación de conflictos mediante el diálogo y la cooperación.Castilla La ManchaConsejería de Educación, Ciencia y Cultura. Viceconsejería de Educación y Cultura. Servicio de Documentación; Bulevar del Río Alberche, s. n. - 1 Planta; 45071 Toledo; Tel. +34925286045; Fax +34925247410; [email protected]

A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study

© 2023Background: The benefit of pharmacogenetic testing before starting drug therapy has been well documented for several single gene–drug combinations. However, the clinical utility of a pre-emptive genotyping strategy using a pharmacogenetic panel has not been rigorously assessed. Methods: We conducted an open-label, multicentre, controlled, cluster-randomised, crossover implementation study of a 12-gene pharmacogenetic panel in 18 hospitals, nine community health centres, and 28 community pharmacies in seven European countries (Austria, Greece, Italy, the Netherlands, Slovenia, Spain, and the UK). Patients aged 18 years or older receiving a first prescription for a drug clinically recommended in the guidelines of the Dutch Pharmacogenetics Working Group (ie, the index drug) as part of routine care were eligible for inclusion. Exclusion criteria included previous genetic testing for a gene relevant to the index drug, a planned duration of treatment of less than 7 consecutive days, and severe renal or liver insufficiency. All patients gave written informed consent before taking part in the study. Participants were genotyped for 50 germline variants in 12 genes, and those with an actionable variant (ie, a drug–gene interaction test result for which the Dutch Pharmacogenetics Working Group [DPWG] recommended a change to standard-of-care drug treatment) were treated according to DPWG recommendations. Patients in the control group received standard treatment. To prepare clinicians for pre-emptive pharmacogenetic testing, local teams were educated during a site-initiation visit and online educational material was made available. The primary outcome was the occurrence of clinically relevant adverse drug reactions within the 12-week follow-up period. Analyses were irrespective of patient adherence to the DPWG guidelines. The primary analysis was done using a gatekeeping analysis, in which outcomes in people with an actionable drug–gene interaction in the study group versus the control group were compared, and only if the difference was statistically significant was an analysis done that included all of the patients in the study. Outcomes were compared between the study and control groups, both for patients with an actionable drug–gene interaction test result (ie, a result for which the DPWG recommended a change to standard-of-care drug treatment) and for all patients who received at least one dose of index drug. The safety analysis included all participants who received at least one dose of a study drug. This study is registered with ClinicalTrials.gov, NCT03093818 and is closed to new participants. Findings: Between March 7, 2017, and June 30, 2020, 41 696 patients were assessed for eligibility and 6944 (51·4 % female, 48·6% male; 97·7% self-reported European, Mediterranean, or Middle Eastern ethnicity) were enrolled and assigned to receive genotype-guided drug treatment (n=3342) or standard care (n=3602). 99 patients (52 [1·6%] of the study group and 47 [1·3%] of the control group) withdrew consent after group assignment. 652 participants (367 [11·0%] in the study group and 285 [7·9%] in the control group) were lost to follow-up. In patients with an actionable test result for the index drug (n=1558), a clinically relevant adverse drug reaction occurred in 152 (21·0%) of 725 patients in the study group and 231 (27·7%) of 833 patients in the control group (odds ratio [OR] 0·70 [95% CI 0·54–0·91]; p=0·0075), whereas for all patients, the incidence was 628 (21·5%) of 2923 patients in the study group and 934 (28·6%) of 3270 patients in the control group (OR 0·70 [95% CI 0·61–0·79]; p <0·0001). Interpretation: Genotype-guided treatment using a 12-gene pharmacogenetic panel significantly reduced the incidence of clinically relevant adverse drug reactions and was feasible across diverse European health-care system organisations and settings. Large-scale implementation could help to make drug therapy increasingly safe. Funding: European Union Horizon 2020