Increased plasma neurofilament light chain levels in patients with type-1 diabetes with impaired awareness of hypoglycemia

Altres ajuts: This work was financially supported by a grant from the SPANISH DIABETES SOCIETY.Impaired awareness of hypoglycemia (IAH) is a common complication in patients with type-1 diabetes (T1D). IAH is a major risk factor for severe hypoglycemic events, leading to adverse clinical consequences and cerebral damage. Non-invasive, cost-effective, and logistically efficient biomarkers for this condition have not been validated. Here, we propose plasma neurofilament light chain (NfL) levels as a biomarker of neuroaxonal damage in patients with T1D-IAH. 54 patients were included into the study (18 T1D-IAH, 18 T1D with normal awareness of hypoglycemia (NAH) and 18 healthy controls). We measured plasma NfL levels and studied cerebral gray matter alterations on MRI. We found that NfL levels were increased in patients with T1D-IAH compared with patients with T1D-NAH and healthy controls. Importantly, increased NfL levels correlated with reduced cerebral gray matter volume and increased IAH severity in patients with T1D-IAH. Overall, our findings identify plasma NfL levels as a potential biomarker of cerebral damage in this population, motivating further confirmatory studies with potential implications in clinical trials

FERO: Finding Extreme Relativistic Objects. I. Statistics of Relativistic Fe Kalpha lines in Radio-Quiet Type 1 AGN

Accretion models predict that fluorescence lines broadened by relativistic effects should arise from reflection of X-ray emission onto the inner region of the accretion disc surrounding the central black hole of active galactic nuclei (AGN). The theory behind the origin of relativistic lines is well established, and observational evidence from a moderate number of sources seems to support the existence of these lines. The aim of this work is to establish the fraction of AGN with relativistic Fe Kalpha lines, and study possible correlations with source physical properties. An XMM-Newton collection of 149 radio-quiet Type 1 AGN has been systematically and uniformly analyzed in order to search for significant evidence of a relativistically broadened Fe Kalpha line. To enable statistical studies, an almost complete, flux-limited subsample of 31 sources has been defined. The 2-10 keV spectra of the FERO sources have been compared with a complex model including most of the physical components observed in the X-ray spectra of Seyfert galaxies: a power law primary continuum modified by non-relativistic Compton reflection and warm absorption, plus a series of narrow Fe line reflection features. The observed fraction of sources in the flux-limited sample that show significant evidence of a relativistic Fe Kalpha line is 36%. The average line Equivalent Width (EW) is of the order of 100 eV, while the average disc inclination angle is 28+/-5 deg and the average power-law index of the radial disc emissivity law is 2.4+/-0.4. The spin value is well constrained only in 2 cases (MCG-6-30-15 and MRK509), and in the rest of the cases, whenever a constraint can be placed, it always implies the rejection of the static black hole solution. The Fe Kalpha line EW does not correlate with disc parameters or with system physical properties, such as black hole mass, accretion rate and hard X-ray luminosity.Comment: 22 pages, 7 figures. Accepted for publication in A&

Actividades de aprendizaje activo para una evaluación sostenible en el ámbito universitario

Desde que se inició la pandemia del COVID19, la docencia de nuestras asignaturas ha pasado por diversos modelos (virtual, híbrido y de nuevo presencial) de manera muy abrupta. Esto nos ha llevado a realizar una tarea continua de adaptación y detectar la necesidad de disponer de nuevas estrategias para conseguir una tutorización y evaluación continua del estudiantado que sea sostenible para el profesorado y, a su vez, útil para el estudiantado. Aunque existen múltiples herramientas en las plataformas de aprendizaje que utiliza el profesorado, se necesita integrar las actividades en una metodología conjunta que garantice el aprendizaje activo y autónomo, que fomente la metacognición en el alumnado, y asegure que reciben realimentaciones pertinentes a lo largo del curso. En este trabajo, analizamos qué actividades de aprendizaje activo pueden ser adecuadas para el alumnado y el profesorado. En lo que se refiere al estudiantado analizamos si le ha ayudado a reflexionar sobre su aprendizaje, el aprendizaje en sí, su implicación y su motivación. Para el profesorado, si percibe que estas actividades cumplen con su objetivo de aprendizaje, y además si la carga de trabajo relacionada con la evaluación es sostenible. Los resultados obtenidos de este estudio son relevantes para la comunidad educativa, ya que nos servirán para seleccionar las actividades de aprendizaje activo que cumplan con las dos premisas antes señaladas, que nos lleven a optimizar el trabajo del profesorado y a obtener una mayor satisfacción del estudiantado, mejorando o al menos manteniendo el aprendizaje.Since the COVID19 pandemic began, the teaching of our subjects has gone through different models (virtual, hybrid and again face-to-face) in a very abrupt manner. This has led us to carry out a continuous task of adaptation and to detect the need for new strategies to achieve continuous tutoring and assessment of students that is sustainable for the teaching staff and, at the same time, useful for the students. Although there are multiple tools in the learning platforms used by teachers, there is a need to integrate the activities into a joint methodology that guarantees active and autonomous learning, encourages metacognition in students, and ensures that they receive relevant feedback throughout the course. In this paper, we analyse which active learning activities are satisfactory for students and teachers. For the students, we analyse whether it has helped them to reflect on their learning, the learning itself, their involvement, and their motivation. For the teaching staff, whether they perceive these activities as fulfilling their learning objective, and whether the workload related to assessment will be less in the future. The results obtained from this study are relevant for the educational community, as they will help us to select active learning activities that comply with the two aforementioned premises, which will lead us to optimise the work of the teaching staff and to obtain greater student satisfaction, improving or at least maintaining learning.Este trabajo está financiado por UV-SFPIE_PID-1642016 y UV-SFPIE_PID-1642041 del Servei de Formació Permanent i Innovació Educativa de la UV

Assessing the role of the TREM2 p.R47H variant as a risk factor for Alzheimer's disease and frontotemporal dementia

4 páginas, 1 figura, a tabla. Los autores pertenecen a The dementia genetic Spanish consortium (DEGESCO).A non-synonymous genetic rare variant, rs75932628-T (p.R47H), in the TREM2 gene has recently been reported to be a strong genetic risk factor for Alzheimer's disease (AD). Also, rare recessive mutations have been associated with frontotemporal dementia (FTD). We aimed to investigate the role of p.R47H variant in AD and FTD through a multi-center study comprising 3,172 AD and 682 FTD patients and 2,169 healthy controls from Spain. We found that 0.6% of AD cases carried this variant compared to 0.1% of controls (odds ratio [OR]=4.12, 95% confidence interval [CI]: 1.21-14.00, P=0.014). A meta-analysis comprising 32,598 subjects from four previous studies demonstrated the large effect of the p.R47H variant in AD risk (OR=4.11, 95% CI: 2.99-5.68, P=5.27x10-18). We did not find an association between p.R47H and age of onset of AD or family history of dementia. Finally, none of the FTD patients harbored this genetic variant. These data strongly support the important role of p.R47H in AD risk and suggest that this rare genetic variant is not related to FTD.This study was supported by grants from Instituto de Salud Carlos III (PI12/01311 and 12/00013), grants from the Ministry of Science (SAF2010-15558, SAF2009-10434), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, Spain), Consolider (CSD2010-00045), and the Department of Health of the Government of Navarra (refs. 13085 and 3/2008). CR held during the period 2009-2013 a “Torres Quevedo” fellowship from the Spanish Ministry of Science and Technology, co-financed by the European Social Fund. Fundació ACE researchers are indebted to Trinitat Port-Carbó and her family who are supporting Fundació ACE scientific programs.Peer reviewe

Obscured Activity: AGN, Quasars, Starbursts and ULIGs observed by the Infrared Space Observatory

Some of the most active galaxies in the Universe are obscured by large quantities of dust and emit a substantial fraction of their bolometric luminosity in the infrared. Observations of these infrared luminous galaxies with the Infrared Space Observatory (ISO) have provided a relatively unabsorbed view to the sources fuelling this active emission. The improved sensitivity, spatial resolution and spectroscopic capability of ISO over its predecessor Infrared Astronomical Satellite (IRAS), has enabled significant advances in the understanding of the infrared properties of active galaxies. ISO surveyed a wide range of active galaxies which, in the context of this review, includes those powered by intense bursts of star-formation as well as those containing a dominant active galactic nucleus (AGN). Mid infrared imaging resolved for the first time the dust enshrouded nuclei in many nearby galaxies, while a new era in infrared spectroscopy was opened by probing a wealth of atomic, ionic and molecular lines as well as broad band features in the mid and far infrared. This was particularly useful since it resulted in the understanding of the power production, excitation and fuelling mechanisms in the nuclei of active galaxies including the intriguing but so far elusive ultraluminous infrared galaxies. Detailed studies of various classes of AGN and quasars greatly improved our understanding of the unification scenario. Far-infrared imaging and photometry also revealed the presence of a new very cold dust component in galaxies and furthered our knowledge of the far-infrared properties of faint starbursts, ULIGs and quasars. We summarise almost nine years of key results based upon ISO data spanning the full range of luminosity and type of active galaxies.Comment: Accepted for publication in 'ISO science legacy - a compact review of ISO major achievements', Space Science Reviews - dedicated ISO issue. To be published by Springer in 2005. 62 pages (low resolution figures version). Higher resolution PDFs available from http://users.physics.uoc.gr/~vassilis/papers/VermaA.pdf or http://www.iso.vilspa.esa.es/science/SSR/Verma.pd

Teaching precision farming and entrepreneurship for European students: Sparkle online course

Within the framework of the European project named ‘SPARKLE’, an online course was created after studying educational needs on precision agriculture (PA), state of the art of technologies and a prospective study of the commercial sector. Five educational and research institutions, high-tech farms and enterprises specializing in technology transfer created the syllabus of the course and the platform contents. The course was designed to provide 30 h of student dedication, via online presentations, documents and videos for each topic. A free pilot course started in April 2020 and 385 students from Italy, Portugal, Greece & Spain enrolled. To trace performance and acquisition of competences, questionnaires were completed by students for each topic and a final overall test. Students’ opinions about the course were also registered using anonymous polls, and results evaluated, to be able to enhance the Sparkle course for subsequent editions. Students also took part in a business model competition, to solve real challenges proposed by farms, related to the use of these technologies

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks : The GR@ACE project

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele