Vulnerability and resilience of high-mountain pine forests of the Gredos range (Ávila, Spanish Central System): two thousand years of socio-ecological dynamics

RESUMEN: En este trabajo se presenta el análisis palinológico de la turbera de Pozo de la Nieve, localizada en el Parque Natural del Valle de Iruelas (Ávila), un área de alto valor sociocultural dentro de la Sierra de Gredos (Sistema Central). Con el objetivo de relacionar los cambios en el paisaje con la explotación de los recursos naturales y eventos climáticos, en primer lugar se han realizado 7 dataciones radiocarbónicas que sitúan el inicio del registro sedimentario ca. 240 cal BC. Los datos polínicos indican la existencia de un denso pinar altimontano dominado por Pinus sylvestris/nigra desde la Segunda Edad de Hierro hasta el periodo islámico. A partir del periodo cristiano las actividades antrópicas se intensifican, especialmente la ganadería en la Edad Contemporánea, lo cual conlleva la progresiva desaparición del pinar de alta montaña y el desarrollo de pastizales mediante el manejo del fuego, situación que culmina con el desarrollo del paisaje actual dominado por piornales pirófilos.ABSTRACT: We present the palynological study of Pozo de la Nieve peat bog, located in a very valuable socio-cultural placement within the Iruelas Valley Natural Park (Gredos range, Iberian Central System). We have focused in relating landscape changes to natural resources management and climatic events. Firstly, we carried out seven radiocarbon dates suggesting the origin of this record ca. 240 cal BC. The palynological data show the existence of dense high-mountain pine woodlands dominated by Pinus sylvestris/nigra from the Late Iron Age to the Muslim period. Later, from the Christian period, anthropogenic activities have intensified, especially livestock grazing in the Contemporary Age. Its consequences are the progressive disappearance of highmountain pine forests and the extension of grasslands by means of fire, which has shaped current landscape dominated by broom communities.Este trabajo ha sido financiado por el proyecto Desirè-HAR2013-43701-P (Plan Nacional I+D+I, Ministerio de Economía y Competitividad de España). Sebastián Pérez Díaz está financiado por el Programa Estatal de Promoción del Talento y su Empleabilidad en I+D+i en la modalidad Juan de la Cierva-Incorporación. Mónica Ruiz Alonso está financiada por el Programa Estatal de Promoción del Talento y su Empleabilidad en I+D+i en la modalidad Juan de la Cierva-Formación

Coordinación entre asignaturas mediante un proyecto transversal

[ES] Se describe una novedosa experiencia de coordinación de las asignaturas del primer semestre del primer curso del Grado en Diseño y Tecnologías Creativas de la Universitat Politècnica de València en la que los estudiantes realizan de forma cooperativa, organizados en equipos de tres alumnos y bajo la supervisión, orientación y el apoyo del cuerpo docente, un proyecto que integra las distintas inteligencias, conocimientos y habilidades que han adquirido en dichas asignaturas. Como guía y soporte para el desarrollo de la tarea, se proporciona un conjunto de documentos que recogen, en apartados específicos y de forma pautada, las distintas fases que se han de ir cubriendo para culminar con éxito el proyecto. Este conjunto de documentos establece una clara planificación temporal y sirve para que el cuerpo docente pueda valorar, en cada fase del desarrollo, la viabilidad del proyecto, su conformidad con el enunciado inicial, la adecuación a los plazos indicados y la idoneidad de los resultados atendiendo a dinámicas de trabajo en equipo. Gracias a esta herramienta de aprendizaje, los alumnos perciben las distintas asignaturas como fuentes de soluciones prácticas para abordar el reto planteado y su autoestima y autoconfianza crecen al superarlo, al constatar la inmediata aplicabilidad del aprendizaje.[EN] A novel syllabus coordination strategy is described, in which all the subjects from the first semester of the Degree in Design and Creative Technologies (GDTC) of the Polytechnic University of Valencia end up fused on a Problem-Based Learning experience during the last weeks of the semester, where students work cooperatively, in teams of three students, on a single project that integrates the different intelligences, knowledge and skills they have acquired in the four subjects, with the guidance and support of the teaching staff. A set of documents has been developed as a guide for students, detailing the different phases that they must cover to successfully complete the project and the partial results they should deliver on every deadline. These documents establish a clear temporal planning and facilitates the assessment, at each stage of the development, of the project's viability, its compliance with the initial specifications, the fulfilment of the deadlines and the suitability of the results according to correct teamwork dynamics. As a result, students now perceive our subjects as sources of solutions to address a close and motivating challenge that they still do not know how to solve, and their self-esteem and selfconfidence grow as they overcome it.Giner Martínez, F.; Hermida Pérez, A.; Luelmo Jareño, JMD.; Martínez Lance, M.; Moreno Ribelles, E.; Piris Ruano, FJ.; Ramón-Marqués, N. (2020). Coordinación entre asignaturas mediante un proyecto transversal. En IN-RED 2020: VI Congreso de Innovación Educativa y Docencia en Red. Editorial Universitat Politècnica de València. 170-183. https://doi.org/10.4995/INRED2020.2020.1195017018

The Effect of Using Pazopanib With Food vs. Fasted on Pharmacokinetics, Patient Safety, and Preference (DIET Study)

Pazopanib is taken fasted in a fixed oral daily dose of 800 mg. We hypothesized that ingesting pazopanib with food may improve patients' comfort and reduce gastrointestinal (GI) adverse events. Therefore, we investigated the bioequivalent dose of pazopanib when taken with food compared with 800 mg pazopanib taken fasted. In addition, we investigated the differences in GI toxicity, patient satisfaction, and patient's preference for either intake. The intake of 600 mg pazopanib with food resulted in a bioequivalent exposure and was preferred over a standard pazopanib dose without food. No differences were seen in GI toxicities under both intake regimens. Patients seem to be more positive about their feelings about side effects and satisfaction with their therapy when pazopanib was taken with food. Forty-one of the patients (68%) preferred the intake with a continental breakfast

High mortality during tuberculosis treatment does not indicate long diagnostic delays in Vietnam: a cohort study

<p>Abstract</p> <p>Background</p> <p>Delay in tuberculosis diagnosis and treatment initiation may increase disease severity and mortality. In evaluations of tuberculosis control programmes high fatality rates during tuberculosis treatment, are used as an indicator of long delays in low HIV-prevalence settings. However, data for this presumed association between delay and fatality are lacking. We assessed the association between diagnostic delay and mortality of new smear-positive pulmonary tuberculosis patients in Vietnam.</p> <p>Methods</p> <p>Follow-up of a patient cohort included in a survey of diagnostic delay in 70 randomly selected districts. Data on diagnosis and treatment were extracted from routine registers. Patients who had died during the course of treatment were compared to those with reported cure, completed treatment or failure (survivors).</p> <p>Results</p> <p>Complete data were available for 1881/2093 (89.9%) patients, of whom 82 (4.4%) had died. Fatality was 4.5% for patients with ≤ 4 weeks delay, 5.0% for 5- ≤ 8 weeks delay (aOR 1.11, 95%CI 0.67–1.84) and 3.2% for > 9 weeks delay (aOR 0.69, 95%CI 0.37–1.30). Fatality tended to decline with increasing delay but this was not significant. Fatality was not associated with median diagnostic delay at district level (Spearman's rho = -0.08, P = 0.5).</p> <p>Conclusion</p> <p>Diagnostic delay is not associated with treatment mortality in Vietnam at individual nor district level, suggesting that high case fatality should not be used as an indicator of long diagnostic delay in national tuberculosis programmes.</p

Palaeoecological data indicates land-use changes across Europe linked to spatial heterogeneity in mortality during the Black Death pandemic

Historical accounts of the mortality outcomes of the Black Death plague pandemic are variable across Europe, with much higher death tolls suggested in some areas than others. Here the authors use a 'big data palaeoecology' approach to show that land use change following the pandemic was spatially variable across Europe, confirming heterogeneous responses with empirical data.The Black Death (1347-1352 ce) is the most renowned pandemic in human history, believed by many to have killed half of Europe's population. However, despite advances in ancient DNA research that conclusively identified the pandemic's causative agent (bacterium Yersinia pestis), our knowledge of the Black Death remains limited, based primarily on qualitative remarks in medieval written sources available for some areas of Western Europe. Here, we remedy this situation by applying a pioneering new approach, 'big data palaeoecology', which, starting from palynological data, evaluates the scale of the Black Death's mortality on a regional scale across Europe. We collected pollen data on landscape change from 261 radiocarbon-dated coring sites (lakes and wetlands) located across 19 modern-day European countries. We used two independent methods of analysis to evaluate whether the changes we see in the landscape at the time of the Black Death agree with the hypothesis that a large portion of the population, upwards of half, died within a few years in the 21 historical regions we studied. While we can confirm that the Black Death had a devastating impact in some regions, we found that it had negligible or no impact in others. These inter-regional differences in the Black Death's mortality across Europe demonstrate the significance of cultural, ecological, economic, societal and climatic factors that mediated the dissemination and impact of the disease. The complex interplay of these factors, along with the historical ecology of plague, should be a focus of future research on historical pandemics

Circulating TP53 mutations are associated with early tumor progression and poor survival in pancreatic cancer patients treated with FOLFIRINOX

Background: Biomarkers predicting treatment response may be used to stratify pancreatic ductal adenocarcinoma (PDAC) patients for therapy. The aim of this study was to identify circulating tumor DNA (ctDNA) mutations that associate with tumor progression during FOLFIRINOX chemotherapy, and overall survival (OS). Methods: Circulating cell-free DNA was analyzed with a 57 gene next-generation sequencing panel using plasma samples of 48 PDAC patients of all disease stages. Patients received FOLFIRINOX as initial treatment. Chemotherapy response was determined on CT scans as disease control (n = 30) or progressive disease (n = 18) within eight cycles of FOLFIRINOX, based on RECIST 1.1 criteria. Results: Detection of a TP53 ctDNA mutation before start of FOLFIRINOX [odds ratio (OR) 10.51, 95% confidence interval (CI) 1.40-79.14] and the presence of a homozygous TP53 Pro72Arg germline variant (OR 6.98, 95% CI 1.31-37.30) were predictors of early tumor progression during FOLFIRINOX in multivariable analysis. Five patients presented with the combination of a TP53 ctDNA mutation before start of FOLFIRINOX and the homozygous Pro72Arg variant. All five patients showed progression during FOLFIRINOX. The combination of the TP53 mutation and TP53 germline variant was associated with shorter survival (median OS 4.4 months, 95% CI 2.6-6.2 months) compared with patients without any TP53 alterations (median OS 13.0 months, 95% CI 8.6-17.4 months). Conclusion: The combination of a TP53 ctDNA mutation before start of FOLFIRINOX and a homozygous TP53 Pro72Arg variant is a promising biomarker, associated with early tumor progression during FOLFIRINOX and poor OS. The results of this exploratory study need to be validated in an independent cohort.Surgical oncolog

Serum miR-373-3p and miR-194-5p are associated with early tumor progression during FOLFIRINOX treatment in pancreatic cancer patients: a prospective multicenter study

In this study, we explored the predictive value of serum microRNA (miRNA) expression for early tumor progression during FOLFIRINOX chemotherapy and its association with overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). A total of 132 PDAC patients of all disease stages were included in this study, of whom 25% showed progressive disease during FOLFIRINOX according to the RECIST criteria. MiRNA expression was analyzed in serum collected before the start and after one cycle of chemotherapy. In the discovery cohort (n = 12), a 352-miRNA RT-qPCR panel was used. In the validation cohorts (total n = 120), miRNA expression was detected using individual RT-qPCR miRNA primers. Before the start of FOLFIRINOX, serum miR-373-3p expression was higher in patients with progressive disease compared to patients with disease control after FOLFIRINOX (Log2 fold difference (FD) 0.88, p = 0.006). MiR-194-5p expression after one cycle of FOLFIRINOX was lower in patients with progressive disease (Log2 FD -0.29, p = 0.044). Both miRNAs were predictors of early tumor progression in a multivariable model including disease stage and baseline CA19-9 level (miR-373-3p odds ratio (OR) 3.99, 95% CI 1.10-14.49; miR-194-5p OR 0.91, 95% CI 0.83-0.99). MiR-373-3p and miR-194-5p did not show an association with OS after adjustment for disease stage, baseline CA19-9, and chemotherapy response. In conclusion, high serum miR-373-3p before the start and low serum miR-194-5p after one cycle are associated with early tumor progression during FOLFIRINOX.Surgical oncolog

Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1): A multicenter stepped-wedge cluster randomized controlled trial

Background: Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. Methods/design: PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. Discussion: The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. Trial registration: ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018

Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1):a multicenter stepped-wedge cluster randomized controlled trial

Background: Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. Methods/design: PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. Discussion: The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. Trial registration: ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018