Simultaneous gain and phase profile determination on an interferometric BOTDA

24th International Conference on Optical Fibre Sensors, 96343Y, Curitiba, Brazil, September 28, 2015.Up to now, complex (phase and intensity) measurements in Brillouin Optical Time-Domain Analysis (BOTDA) systems required complex phase modulation methods and high-bandwidth (multi-GHz) detection. In this work, we propose a novel technique that is able to retrieve simultaneously both gain/loss and phase characteristics of the Brillouin interaction by just introducing a Sagnac Interferometer (SI) 011 a standard BOTDA sensing scheme. The technique is described analytically and demonstrated experimentally. With this technique, a reliability increase is produced since redundant measurements can be performed.European CommissionMinisterio de Economía y CompetitividadUniversidad de AlcaláComunidad de MadridGeneralitat Valencian

Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical Trial

PD1 expression in CD4+ and CD8+ T cells is increased after treatment in multiple myeloma patients with persistent disease. The GEM-Pembresid trial analyzed the efficacy and safety of pembrolizumab as consolidation in patients achieving at least very good partial response but with persistent measurable disease after first- or second-line treatment. Moreover, the characteristics of the immune system were investigated to identify potential biomarkers of response to pembrolizumab. One out of the 17 evaluable patients showed a decrease in the amount of M-protein, although a potential late effect of high-dose melphalan could not be ruled out. Fourteen adverse events were considered related to pembrolizumab, two of which (G3 diarrhea and G2 pneumonitis) prompted treatment discontinuation and all resolving without sequelae. Interestingly, pembrolizumab induced a decrease in the percentage of NK cells at cycle 3, due to the reduction of the circulating and adaptive subsets (0.615 vs. 0.43, p = 0.007; 1.12 vs. 0.86, p = 0.02). In the early progressors, a significantly lower expression of PD1 in CD8+ effector memory T cells (MFI 1327 vs. 926, p = 0.03) was observed. In conclusion, pembrolizumab used as consolidation monotherapy shows an acceptable toxicity profile but did not improve responses in this MM patient population. The trial was registered at clinicaltrials.gov with identifier NCT02636010 and with EUDRACT number 2015-003359-23.This study was funded by Fundación Ramón Areces (FRA 16/003). T.P. is supported by a grant from the AECC (INVES18043PAIN). This study received financial support from Merck Sharp & Dohme of Spain, a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USA

Cost-effectiveness analysis of a multiple health behaviour change intervention in people aged between 45 and 75 years: a cluster randomized controlled trial in primary care (EIRA study)

Background: Multiple health behaviour change (MHBC) interventions that promote healthy lifestyles may be an efficient approach in the prevention or treatment of chronic diseases in primary care. This study aims to evaluate the cost-utility and cost-effectiveness of the health promotion EIRA intervention in terms of MHBC and cardiovascular reduction. Methods: An economic evaluation alongside a 12-month cluster-randomised (1:1) controlled trial conducted between 2017 and 2018 in 25 primary healthcare centres from seven Spanish regions. The study took societal and healthcare provider perspectives. Patients included were between 45 and 75 years old and had any two of these three behaviours: smoking, insufficient physical activity or low adherence to Mediterranean dietary pattern. Intervention duration was 12 months and combined three action levels (individual, group and community). MHBC, defined as a change in at least two health risk behaviours, and cardiovascular risk (expressed in % points) were the outcomes used to calculate incremental cost-effectiveness ratios (ICER). Quality-adjusted life-years (QALYs) were estimated and used to calculate incremental cost-utility ratios (ICUR). Missing data was imputed and bootstrapping with 1000 replications was used to handle uncertainty in the modelling results. Results: The study included 3062 participants. Intervention costs were €295 higher than usual care costs. Five per-cent additional patients in the intervention group did a MHBC compared to usual care patients. Differences in QALYS or cardiovascular risk between-group were close to 0 (- 0.01 and 0.04 respectively). The ICER was €5598 per extra health behaviour change in one patient and €6926 per one-point reduction in cardiovascular risk from a societal perspective. The cost-utility analysis showed that the intervention increased costs and has no effect, in terms of QALYs, compared to usual care from a societal perspective. Cost-utility planes showed high uncertainty surrounding the ICUR. Sensitivity analysis showed results in line with the main analysis. Conclusion: The efficiency of EIRA intervention cannot be fully established and its recommendation should be conditioned by results on medium-long term effects. Trial registration: Clinicaltrials.gov NCT03136211. Registered 02 May 2017 – Retrospectively registered © 2021, The Author(s)

Development of an activity disease score in patients with uveitis (UVEDAI)

To develop a disease activity index for patients with uveitis (UVEDAI) encompassing the relevant domains of disease activity considered important among experts in this field. The steps for designing UVEDAI were: (a) Defining the construct and establishing the domains through a formal judgment of experts, (b) A two-round Delphi study with a panel of 15 experts to determine the relevant items, (c) Selection of items: A logistic regression model was developed that set ocular inflammatory activity as the dependent variable. The construct "uveitis inflammatory activity" was defined as any intraocular inflammation that included external structures (cornea) in addition to uvea. Seven domains and 15 items were identified: best-corrected visual acuity, inflammation of the anterior chamber (anterior chamber cells, hypopyon, the presence of fibrin, active posterior keratic precipitates and iris nodules), intraocular pressure, inflammation of the vitreous cavity (vitreous haze, snowballs and snowbanks), central macular edema, inflammation of the posterior pole (the presence and number of choroidal/retinal lesions, vascular inflammation and papillitis), and global assessment from both (patient and physician). From all the variables studied in the multivariate model, anterior chamber cell grade, vitreous haze, central macular edema, inflammatory vessel sheathing, papillitis, choroidal/retinal lesions and patient evaluation were included in UVEDAI. UVEDAI is an index designed to assess the global ocular inflammatory activity in patients with uveitis. It might prove worthwhile to motorize the activity of this extraarticular manifestation of some rheumatic diseases

Predicting long-term disease control in transplant-ineligible patients with multiple myeloma: impact of an MGUS-like signature

Disease control at 5 years would be a desirable endpoint for elderly multiple myeloma (MM) patients, but biomarkers predicting this are not defined. Therefore, to gain further insights in this endpoint, a population of 498 newly diagnosed transplant-ineligible patients enrolled in two Spanish trials (GEM2005MAS65 and GEM2010MAS65), has been analyzed. Among the 435 patients included in this post-hoc study, 18.6% remained alive and progression free after 5 years of treatment initiation. In these patients, overall survival (OS) rate at 10 years was 60.8% as compared with 11.8% for those progressing within the first 5 years. Hemoglobin (Hb) = 12 g/dl (OR 2.74, p = 0.001) and MGUS-like profile (OR 4.18, p = 0.005) were the two baseline variables associated with long-term disease-free survival. Upon including depth of response (and MRD), Hb = 12 g/dl (OR 2.27) and MGUS-like signature (OR 7.48) retained their predictive value along with MRD negativity (OR 5.18). This study shows that despite the use of novel agents, the probability of disease control at 5 years is still restricted to a small fraction (18.6%) of elderly MM patients. Since this endpoint is associated with higher rates of OS, this study provides important information about diagnostic and post-treatment biomarkers helpful in predicting the likelihood of disease control at 5 years

Pembrolizumab as consolidation strategy in patients with multiple myeloma: Results of the GEM-Pembresid clinical trial

PD1 expression in CD4+ and CD8+ T cells is increased after treatment in multiple myeloma patients with persistent disease. The GEM-Pembresid trial analyzed the efficacy and safety of pembrolizumab as consolidation in patients achieving at least very good partial response but with persistent measurable disease after first- or second-line treatment. Moreover, the characteristics of the immune system were investigated to identify potential biomarkers of response to pembrolizumab. One out of the 17 evaluable patients showed a decrease in the amount of M-protein, although a potential late effect of high-dose melphalan could not be ruled out. Fourteen adverse events were considered related to pembrolizumab, two of which (G3 diarrhea and G2 pneumonitis) prompted treatment discontinuation and all resolving without sequelae. Interestingly, pembrolizumab induced a decrease in the percentage of NK cells at cycle 3, due to the reduction of the circulating and adaptive subsets (0.615 vs. 0.43, p = 0.007; 1.12 vs. 0.86, p = 0.02). In the early progressors, a significantly lower expression of PD1 in CD8+ effector memory T cells (MFI 1327 vs. 926, p = 0.03) was observed. In conclusion, pembrolizumab used as consolidation monotherapy shows an acceptable toxicity profile but did not improve responses in this MM patient population. The trial was registered at clinicaltrials.gov with identifier NCT02636010 and with EUDRACT number 2015-003359-23

Use of interactive response devices for the improvement of teaching in the degrees of the Faculty of Sciences

La implantación de los nuevos Grados dentro del EEES supone un nuevo enfoque metodológico, pero sobre todo evaluador. El profesor debe esforzarse en ser capaz de valorar no sólo el nivel de conocimientos del alumnado sobre los contenidos, ya que la sociedad actual demanda un perfil de los egresados más completo basado en la formación por competencias. La adquisición de ambas facetas por parte del alumnado se basa principalmente en actividades presenciales y metodologías docentes aplicadas en el desarrollo de las asignaturas, tanto en grupo reducido como en grupo completo. Por tanto, cualquier herramienta adicional que ayude al docente a facilitar esta doble tarea es bien recibida, pues permitirá evaluar el rendimiento académico global del alumnado. Recientemente la Facultad de Ciencias ha puesto en marcha una experiencia piloto mediante la cual un nutrido grupo de profesores ha incorporado en su docencia un sistema de mandos inalámbricos de respuesta. Actualmente, la Facultad de Ciencias dispone de un total de 82 mandos inalámbricos de respuesta y tres antenas receptoras. Esta nueva tecnología ha permitido al docente realizar, de forma interactiva, preguntas colectivas al alumnado y recoger las respuestas individuales de forma inmediata. Los resultados obtenidos en este proyecto nos permiten ser muy optimistas con el uso de esta herramienta y nos animan a continuar en la misma línea. El profesorado participante se ha mostrado dispuesto a continuar empleando esta TIC en su docencia, tratando de abarcar más asignaturas, diversificar el tipo de pruebas, y emplear los mandos de respuesta en grupo completo, cuando el número de alumnos lo permita. La puesta en común de los resultados revela que, de forma general, este tipo de sistemas de respuesta incrementa el nivel de atención del alumnado, ya que se les demanda de forma continuada su participación activa durante la sesión. Se potencia la retención de conceptos, al suministrar en el acto la respuesta correcta a cada pregunta realizada. Permite también al profesorado conocer el nivel previo de conocimientos sobre la materia a impartir, ya que se puede realizar este tipo de preguntas al comienzo de la sesión y enfocar entonces su atención en las debilidades manifestadas. Asimismo se puede testar el grado de adquisición de dichos conocimientos, realizando este tipo de cuestionarios después de la sesión. Además, el tratamiento posterior de los resultados, de forma individualizada, permite gestionar de forma ágil el nivel de conocimientos y adquisición de competencias en lo que es un sistema de evaluación continua, tan necesario en los nuevos enfoques metodológicos nacidos de la implantación del EEES. Por último destacar que el profesorado participante ha considerado que se trata de una herramienta de gran utilidad para la consecución del objetivo de excelencia en la docencia, que además es eficaz y de fácil manejo, y entiende que no debe ser una actividad puntual, sino un proceso transformador en la actividad docente e interacción alumno-profesor, configurándose como una herramienta habitual en los sistemas de enseñanza-aprendizaje.Implementation of the new degrees in the EHEA involve a new methodological approach, but above all evaluation. The teacher should strive to be able to assess not only the level of knowledge of the students on the content, as the current society demands a profile of the most complete graduates based on training by competencies. The acquisition of both facets by students is based mainly on face-to-face activities and teaching methodologies applied in the development of the subjects, both in small group and in whole group. Therefore, any additional tool that helps the teacher to facilitate this double task is well received, since it will allow to evaluate the overall academic performance of the students. Recently the Faculty of Sciences has launched a pilot experience through which a large group of teachers has incorporated into their teaching a system of interactive response devices. Currently, the Faculty of Sciences has a total of 82 wireless response controllers and three receiving antennas. This new technology has enabled the teacher to interact interactively with the students and collect the individual answers immediately. The results obtained in this project allow us to be very optimistic with the use of this tool and encourage us to continue in the same line. The participating teachers have been willing to continue using this ICT in their teaching, trying to cover more subjects, diversify the type of tests, and use the full group response commands, when the number of students allows. The sharing of results reveals that, in a general way, this type of response systems increases the level of attention of the students, since they are continuously demanded their active participation during the session. The retention of concepts is strengthened by providing the correct answer to every question asked. It also allows the faculty to know the previous level of knowledge about the subject to be taught, since this type of questions can be asked at the beginning of the session and then focus their attention on the weaknesses manifested. It is also possible to test the degree of acquisition of this knowledge, performing this type of questionnaire after the session. In addition, the subsequent treatment of the results, in an individualized way, allows to manage in an agile way the level of knowledge and acquisition of competences in what is a system of continuous evaluation, so necessary in the new methodological approaches born from the implantation of the EHEA. Finally, it should be pointed out that the participating teachers have considered that this is a very useful tool for achieving the objective of excellence in teaching, which is also efficient and easy to use and understands that it should not be a specific activity, but a transforming process in the teaching activity and student-teacher interaction, being configured as a habitual tool in the teaching-learning systems

Immune status of high-risk smoldering multiple myeloma patients and its therapeutic modulation under LenDex: a longitudinal analysis

Persistence of chemoresistant minimal residual disease (MRD) plasma cells (PCs) is associated with inferior survival in multiple myeloma (MM). Thus, characterization of the minor MRD subclone may represent a unique model to understand chemoresistance, but to our knowledge, the phenotypic and genetic features of the MRD subclone have never been investigated. Here, we compared the antigenic profile of MRD vs diagnostic clonal PCs in 40 elderly MM patients enrolled in the GEM2010MAS65 study and showed that the MRD subclone is enriched in cells overexpressing integrins (CD11a/CD11c/CD29/CD49d/CD49e), chemokine receptors (CXCR4), and adhesion molecules (CD44/CD54). Genetic profiling of MRD vs diagnostic PCs was performed in 12 patients; 3 of them showed identical copy number alterations (CNAs), in another 3 cases, MRD clonal PCs displayed all genetic alterations detected at diagnosis plus additional CNAs that emerged at the MRD stage, whereas in the remaining 6 patients, there were CNAs present at diagnosis that were undetectable in MRD clonal PCs, but also a selected number of genetic alterations that became apparent only at the MRD stage. The MRD subclone showed significant downregulation of genes related to protein processing in endoplasmic reticulum, as well as novel deregulated genes such as ALCAM that is prognostically relevant in MM and may identify chemoresistant PCs in vitro. Altogether, our results suggest that therapy-induced clonal selection could be already present at the MRD stage, where chemoresistant PCs show a singular phenotypic signature that may result from the persistence of clones with different genetic and gene expression profiles. This trial was registered at www.clinicaltrials.gov as #NCT01237249

Fisiología de la nutrición y del estrés en las primeras fases de vida del pulpo común (Octopus vulgaris). Resultados del proyecto OCTOPHYS

El cultivo del pulpo común (Oclopus vulgaris) está severamente limitado por las altas mortalidades que se producen durante su cultivo larvano, aunque en la actualidad, las causas especfficas de tan alta mortalidad siguen siendo desconocidas. Este proyecto pretende adquirir conocimientos básicos sobre la biología y fisiologia de las paralarvas a través de un enfoque multidisciplinarque incluye aspectos innovadores relacionados con la fisiologia de la nutrición y el estrés. Los objetivos propuestos están basados en un fuerte input zootécnico y prevén el uso de herramientas biométricas, bioquímicas, enzimáticas, moleculares y proteómicas, con el fin último de optimizar la condición y supervivencia de las paralarvas. Incluyen asimismo la búsqueda y selección de biomarcadores capaces de detectar y cuantíñcar el estrés nutricional.The culture oflhe common octopus (Octopus vulgaris) is hindered by high mortalities encountered during its paralarval rearing, allhough at present, Ihe specific causes forlhe high mortalities observed remain unidentified. This project aims at galhering a beller understanding of Ihe basic biology and physiology ofthe paralarvae, through a multidisciplinary and integrated approach, which includes Ihe study oflhe physiology 01 nutrition and!he evaluation 01Ihe stress condition. The objectives proposed are basad on a strong zootechnical input and foresee Ihe use of biometric, biochemical, enzymatic, molecular biology and proteomic tools, pointing towards the ultimate optimisation of Ihe paralarval condition and survival. They also include Ihe study ofthe nutritionally-derived stress and Ihe selection ofbiomarkers capable of its detection and quantification