Palaeoenvironmental History of the Gredos Range (Spanish Central System, Avila) in Visigothic Times: The Impact of the Justinianic Plague (AD 541–543)

This paper evaluates the possible impact of the early medieval pandemic known as the “Justinianic plague” as one of the factors that shaped the mountain ecosystems in the Spanish Central System of the Iberian Peninsula. For this purpose, we focus on two high-resolution, radiocarbon-dated natural pollen records from the Gredos Range (Avila). These cores frame the information they offer within the general picture of the socio-political and environmental transformations of Late Antiquity. Along these three centuries, between c. AD 400 and AD 720, the palynological sequence allows us to recognize eight short phases (on a ten-year and even five-year scale) through which the forest formations traversed. This analysis has made it possible to identify olive and chestnut tree arboriculture since the beginning of the studied interval, as well as to characterize the fluctuation in the thinning processes of the high montane pine forests, due to slash-and-burn practices to open pastures, especially from the permanent occupation of the piedmont in Visigothic times (c. AD 450). The sequence also shows a significant decrease in the anthropic signal during a short period (c. AD 540-545) that can be disassociated from the early effects of the Late Antique Little Ice Age (c. AD 450-660) and which is possibly more related to the plague, as evidenced by the subsequent recovery of anthropic pressure on the pine forest and the extension of the olive and chestnut grove in the 6th and 7th centuries AD.El presente trabajo evalúa la posible influencia de la pandemia altomedieval conocida como «plaga de Justiniano» como uno de los factores que contribuyeron a configurar los ecosistemas de montaña enclavados en el Sistema Central de la península ibérica. Para ello, el artículo se centra en dos registros polínicos naturales de alta resolución y bien datados mediante radiocarbono, obtenidos en la Sierra de Gredos (Ávila), y enmarca la información que ofrecen en el cuadro general de las dinámicas sociopolíticas y ambientales de la Antigüedad Tardía. En el intervalo de tres siglos, entre c. 400 y 720 A. D., la secuencia palinológica permite reconocer ocho fases breves (de escala decenal e incluso quinquenal) que marcaron las transformaciones del paisaje. Este análisis ha posibilitado identificar la implantación de la arboricultura de olivo y castaño desde el inicio del intervalo estudiado, así como caracterizar la fluctuación en los procesos de clareo de los pinares altimontanos, por la incidencia de talas y rozas con fuego para abrir pastizales, especialmente desde la ocupación permanente del piedemonte en época visigoda (c. 450 A. D.). La secuencia analizada muestra un significativo aminoramiento de la señal antrópica durante un breve intervalo (c. 540-545 A. D.) que cabe desvincular de los efectos tempranos de la Pequeña Edad de Hielo tardoantigua (c. 450-660 A. D.) y resulta más plausible relacionar con la plaga, como avala la subsiguiente recuperación de la presión antrópica sobre el pinar y la extensión del olivar y el castañar en los siglos VI y VII A. D.- Introducción - Zona de estudio - Consideraciones metodológicas - Historia de la vegetación e impacto humano (400-720 A.D.) - Conclusiones, variabilidad climática y efectos de la pandemia (541-543 A.D.

La peste negra bajomedieval (1348-1351 AD) en el valle del Tiétar (sierra de Gredos, Ávila): aspectos económicos y paleoambientales

En el presente trabajo se evalúan los efectos de la peste negra bajomedieval (1348–1351 AD) sobre los bosques y las actividades agroforestales de un valle intramontano de la Meseta sur española, a partir de análisis polínicos de alta resolución. Para comprender mejor los efectos de aquella pandemia se analiza la secuencia paleoambiental de cinco turberas, a lo largo de un amplio recorrido cronológico entre los siglos XII y XIV. Este análisis demuestra que la peste provocó una desaceleración de las actividades agropecuarias –agricultura, arboricultura, ganadería– y la consiguiente recuperación de las masas forestales, salvo en las zonas de montaña donde un menor control de los pasos ganaderos incidió en cierta degradación del bosque.1 Introducción 2 Área de estudio y metodología 2.1 El valle del Tiétar en la provincia de Ávila 2.2 Registros polínicos fósiles 3 Resultados y discusión 3.1 Antes de la pandemia (1200–1348 AD) 3.2 La epidemia de peste negra en la sierra de Gredos (1348–1351 AD) 3.3 Recuperación tras la pandemia (1351–1400 AD) 4 Conclusione

Evaluating standards of care in psoriatic arthritis of the QUANTUM project (qualitative initiative to improve outcomes): results of an accreditation project in Spain

In Spain, the QUANTUM project has been promoted to reduce variability in clinical practice and improve the care and quality of life of people with psoriatic arthritis (PsA) by accrediting PsA units throughout the Spanish national health system. To present the results of this approach which sought to ensure an optimum level of quality for patients with PsA. Descriptive analysis of the self-assessments that the PsA units have carried out assessing their degree of compliance with the quality standards established in the QUANTUM project grouped into four blocks: shortening time to diagnosis; optimizing disease management; improving multidisciplinary collaboration; and improving patient monitoring. A total of 41 PsA units were self-evaluated. They met 64.1% of the defined quality standards. Optimize disease management obtained a higher level of standards compliance (72%) and improve multidisciplinary collaboration the lesser (63.9%). Accessibility to the treatments available for PsA in all hospitals was guaranteed (100%). Appropriate diagnostic equipment is available (97.6%). Compliance with specific quality standards leads to detect actions that should be implemented: quality of life assessment (9.8%), locomotor system assessment (12.2%), physical examination data record (14.6%), periodic cardiovascular risk assessment (17.1%). The QUANTUM project results make it possible to visualise how to care for patients with PsA is being developed in Spain. Problems identified in recent multinational reports are also identified in Spain

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

Overview and future perspectives on tumor-targeted positron emission tomography and fluorescence imaging of pancreatic cancer in the era of neoadjuvant therapy

Simple Summary Patients diagnosed with pancreatic cancer have a poor prognosis at time of diagnosis, with a 5-year survival rate of merely 10%. The only treatment with curative intent is surgical resection of the tumor and adjacent tumor-containing lymph nodes. To improve surgical outcome and survival, additional (imaging) tools are needed that support complete surgical tumor resection. Firstly, more accurate monitoring of tumor response to neoadjuvant treatment and subsequent determination of resectability is needed. Secondly, an imaging tool is needed for intraoperative guidance allowing accurate identification, delineation, and complete resection of the tumor and suspected lymph nodes. Therefore, both tumor-targeted PET/CT before surgery and real time fluorescence-guidance during surgery could be helpful to improve patient outcome. This review focusses on literature considering tumor-targeted PET/CT and near-infrared fluorescence (NIRF) imaging. Several tumor-targeted agents are under clinical evaluation, and several other promising agents are currently tested preclinically, both with promising results. Their additional diagnostic value and feasibility for future implementation in standard clinical care of PDAC has yet to be established in phase III clinical trials. Background: Despite recent advances in the multimodal treatment of pancreatic ductal adenocarcinoma (PDAC), overall survival remains poor with a 5-year cumulative survival of approximately 10%. Neoadjuvant (chemo- and/or radio-) therapy is increasingly incorporated in treatment strategies for patients with (borderline) resectable and locally advanced disease. Neoadjuvant therapy aims to improve radical resection rates by reducing tumor mass and (partial) encasement of important vascular structures, as well as eradicating occult micrometastases. Results from recent multicenter clinical trials evaluating this approach demonstrate prolonged survival and increased complete surgical resection rates (R0). Currently, tumor response to neoadjuvant therapy is monitored using computed tomography (CT) following the RECIST 1.1 criteria. Accurate assessment of neoadjuvant treatment response and tumor resectability is considered a major challenge, as current conventional imaging modalities provide limited accuracy and specificity for discrimination between necrosis, fibrosis, and remaining vital tumor tissue. As a consequence, resections with tumor-positive margins and subsequent early locoregional tumor recurrences are observed in a substantial number of patients following surgical resection with curative intent. Of these patients, up to 80% are diagnosed with recurrent disease after a median disease-free interval of merely 8 months. These numbers underline the urgent need to improve imaging modalities for more accurate assessment of therapy response and subsequent re-staging of disease, thereby aiming to optimize individual patient's treatment strategy. In cases of curative intent resection, additional intra-operative real-time guidance could aid surgeons during complex procedures and potentially reduce the rate of incomplete resections and early (locoregional) tumor recurrences. In recent years intraoperative imaging in cancer has made a shift towards tumor-specific molecular targeting. Several important molecular targets have been identified that show overexpression in PDAC, for example: CA19.9, CEA, EGFR, VEGFR/VEGF-A, uPA/uPAR, and various integrins.Tumor-targeted PET/CT combined with intraoperative fluorescence imaging, could provide valuable information for tumor detection and staging, therapy response evaluation with re-staging of disease and intraoperative guidance during surgical resection of PDAC. Methods: A literature search in the PubMed database and (inter)national trial registers was conducted, focusing on studies published over the last 15 years. Data and information of eligible articles regarding PET/CT as well as fluorescence imaging in PDAC were reviewed. Areas covered: This review covers the current strategies, obstacles, challenges, and developments in targeted tumor imaging, focusing on the feasibility and value of PET/CT and fluorescence imaging for integration in the work-up and treatment of PDAC. An overview is given of identified targets and their characteristics, as well as the available literature of conducted and ongoing clinical and preclinical trials evaluating PDAC-targeted nuclear and fluorescent tracers.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

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

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