AIP and MEN1 mutations and AIP immunohistochemistry in pituitary adenomas in a tertiary referral center.

Background: Pituitary adenomas have a high disease burden due to tumor growth/ invasion and disordered hormonal secretion. Germline mutations in genes such as MEN1 and AIP are associated with early onset of aggressive pituitary adenomas that can be resistant to medical therapy. Aims: We performed a retrospective screening study using published risk criteria to assess the frequency of AIP and MEN1 mutations in pituitary adenoma patients in a tertiary referral center. Methods: Pituitary adenoma patients with pediatric/adolescent onset, macroadenomas occurring ≤30 years of age, familial isolated pituitary adenoma (FIPA) kindreds and acromegaly or prolactinoma cases that were uncontrolled by medical therapy were studied genetically. We also assessed whether immunohistochemical staining for AIP (AIP-IHC) in somatotropinomas was associated with somatostatin analogs (SSA) response. Results: Fifty-five patients met the study criteria and underwent genetic screening for AIP/MEN1 mutations. No mutations were identified and large deletions/duplications were ruled out using MLPA. In a cohort of sporadic somatotropinomas, low AIP-IHC tumors were significantly larger (P = 0.002) and were more frequently sparsely granulated (P = 0.046) than high AIP-IHC tumors. No significant relationship between AIP-IHC and SSA responses was seen. Conclusions: Germline mutations in AIP/MEN1 in pituitary adenoma patients are rare and the use of general risk criteria did not identify cases in a large tertiary-referral setting. In acromegaly, low AIP-IHC was related to larger tumor size and more frequent sparsely granulated subtype but no relationship with SSA responsiveness was seen. The genetics of pituitary adenomas remains largely unexplained and AIP screening criteria could be significantly refined to focus on large, aggressive tumors in young patients

Comparison of Clustering Algorithms for Learning Analytics with Educational Datasets

Learning Analytics is becoming a key tool for the analysis and improvement of digital education processes, and its potential benefit grows with the size of the student cohorts generating data. In the context of Open Education, the potentially massive student cohorts and the global audience represent a great opportunity for significant analyses and breakthroughs in the field of learning analytics. However, these potentially huge datasets require proper analysis techniques, and different algorithms, tools and approaches may perform better in this specific context. In this work, we compare different clustering algorithms using an educational dataset. We start by identifying the most relevant algorithms in Learning Analytics and benchmark them to determine, according to internal validation and stability measurements, which algorithms perform better. We analyzed seven algorithms, and determined that K-means and PAM were the best performers among partition algorithms, and DIANA was the best performer among hierarchical algorithms

Retrieval and assessment of CO2 uptake by Mediterranean ecosystems using remote sensing and meteorological data

El IPCC (Intergovernmental Panel onClimateChange) apunta que, sin una reducción de las emisiones antropogénicas de gases de efecto invernadero, la temperatura media del planeta aumentaría y el sistema climático mundial experimentaría durante el siglo XXI cambios muy probablemente mayores a los ya observados durante el siglo XX. Los ecosistemas terrestres desarrollan un papel fundamental en el ciclo del carbono a través de la fotosíntesis, la respiración, combustión de biomasa y la descomposición. La energía es fijada mediante fotosíntesis y es directamente empleada por la vegetación para su crecimiento produciendo materia orgánica que será posteriormente consumida por microorganismos y resto de seres vivos de manera directa o indirecta. La producción primaria bruta (GPP), i.e., el carbono fijado por la vegetación a través de la fotosíntesis, se puede estimar utilizando el modelo clásico de Monteith. Según el mismo, la GPP viene dada por el producto de tres variables: la radiación incidente fotosintéticamente activa (PAR), la fracción de PAR absorbida por la cubierta vegetal (fAPAR) y la eficiencia en el uso de la radiación (LUE). En el trabajo de tesis realizado se ha tratado la problemática de la obtención de estimaciones diarias de GPP para España. Esto involucra la investigación y mejora de las variables que componen el modelo de Monteith. Para ello se han adaptado, mejorado y desarrollado nuevas metodologías para la obtención de la LUE, la PAR y la fAPAR. Para la obtención de la PAR se han aplicado dos metodologías complementarias: (i) La primera estima la radiación a partir de datos de estación de otras variables meteorológicas (como temperatura y precipitación) mediante la construcción de diversos modelos (redes neuronales, procesos regresión mediante kernels,…), y obtiene los mapas a partir de la espacialización de dichas variables puntuales. (ii) La segunda obtiene el PAR a partir de las imágenes de irradiancia del satélite MSG (Meteosat Segunda Generación), e incorpora además un remuestreo de dichas imágenes y una corrección topográfica (por elevación). Para la obtención fAPAR se han aplicado algoritmos operacionales avalados y se han post-procesado para la corrección de huecos y ruido en las series temporales para aumentar la consistencia de las mismas. Finalmente, para la obtención de la LUE se han empleado cartografías híbridas del tipo de cubierta vegetal adaptadas al área de estudio, se han aplicado estimadores a partir de variables meteorológicas (coeficientes de estrés hídrico y por bajas temperaturas) y se ha evaluado el potencial de índices espectrales a partir de datos de satélite como el índice de reflectividad fotoquímico (PRI) u otros índices espectrales sensibles al contenido en agua de la cubierta. Finalmente los resultados de las estimaciones de GPP se han validado de forma directa sobre datos de estaciones terrestres (torres Eddy covariance) y de forma indirecta por comparación con otros productos de satélite (productos de la NASA obtenidos mediante MODIS y Copernicus DMP). Adicionalmente se ha realizado un análisis del potencial explicativo de las variables de entrada para de esta forma observar patrones espaciales relacionados con la relevancia de su variabilidad temporal en las estimaciones del modelo optimizado en el trabajo de tesis.Photosynthesis is a process by which carbon and energy enter ecosystems. The knowledge of where,when, and how carbon dioxide (CO2) is exchanged between terrestrial ecosystems and atmosphere is crucial to close the Earth's carbon budget and predict feedbacks in a likely warming climate. Gross photosynthesis (uptake of CO2) by vegetation is responsible for the gross primary production (GPP) of the ecosystem. Normally GPP refers to the sum of the photosynthesis by all leaves measured at the ecosystem scale. John Monteith proposed in 1972 a simple approach that has become the paradigm for understanding GPP. It considers GPP as proportional to the incident short wave radiation (PAR), the fractional absorption of that flux (fAPAR) and the radiation use conversion efficiency, also known as light-use efficiency (LUE). This simple equation involves a great deal of biological and biophysical complexity. Photosynthesis requires that the plant replace the water that inevitably escapes from its leaves when CO2 is taken up from the atmosphere. Plants also require a supply of nutrients. Physiological and developmental mechanisms operate to adjust the GPP to the availability of resources. Thus, different types of stresses can affect the efficiency. The different terms in Monteith's equation are emphasized by different scientists. Crop physiologists focus on the PAR term, which explains the seasonal growth of crops and year-to-year variation in yield. Early work within the remote sensing community focused on the fAPAR term, which is linked to canopy structure and condition (i.e. to green biomass). It has a clear seasonal evolution in deciduous species and shows limited variability in evergreen forest ecosystems. The fAPAR is a common biophysical product derived from different remote sensing missions through the inversion of radiative transfer models or from empirical relations with vegetation indices. More recently the strong influence of the LUE term on productivity --particularly in strongly seasonal and nutrient-limited and/or water stressed vegetation canopies-- has been recognized. Variation in LUE is significant over shorter time scales when water or temperature stress develop. The LUE has been shown to vary spatially between biomes, ecosystems, and plant species, and to vary temporally during the growing season, due to environmental and physiological limitations. LUE responds more rapidly than fAPAR to different environmental factors related to the energy balance, water availability and nutrient levels. For operational applications, LUE can be expressed as the product of a LUEmax (maximum light-use efficiency), which depends on cover type, and different terms accounting for the reduction in efficiency due to different types of stress. The computation of these terms frequently requires meteorological data, which are seldom available at the needed spatial and temporal scales. The Monteith's approach provides the theoretical basis for most production efficiency models (PEMs), also known as light-use-efficiency (LUE) models: the MODIS-GPP model describes the global terrestrial photosynthesis at 1 km spatial scale and various time steps; the parametric model C-Fix has been applied to estimate forest GPP in several European countries and the modified C-Fix also takes into account the short-term water stress, a typical feature of the hot and dry Mediterranean summer. These models use remotely sensed data as well as meteorological data. In most PEMs, fAPAR is the only satellite-derived variable and, as such, it provides the link between ecosystem function and structure. Validation of satellite-derived GPP products is problematic. The development of eddy covariance (EC) as a method for quantifying the carbon, water, and energy balance over so-called "flux sites" has provided observational data to test and calibrate models; but the EC towers measure net CO2 exchange. GPP is obtained from these measurements after correcting them for respiratory losses (about half). The density of sampling is never enough to get regional or continental scale GPP. This is the domain of models. The modeling approaches also have specific limitations concerning: (i) the uncertainties of vegetation indices due to the presence of soil background mainly in sparse areas, and due to cloud and aerosol contamination problems, (ii) errors in the re-analysis of meteorological data, and (iii) difficulty constraining the light-use-efficiency term. The quality assessment of GPP products is rather complicated by the fact that GPP cannot be measured directly on a geographically relevant scale. In this Thesis, a model to estimate GPP for Mediterranean ecosystems at regional scale is proposed. The three terms in Monteith's equation have been obtained following procedures optimized for the study area, Spain (excluding Canary Islands). The "optimized model" is driven by meteorological and satellite data (MODIS/TERRA and SEVIRI/MSG). Considering the peculiarities of the study area, i.e., the diversity of the vegetation type dynamics and its spatial heterogeneity, the algorithm has been developed to run at a daily time step (to capture the dynamics even in agro-ecosystems) and 1 km spatial resolution (to assure that the spatial resolution of the remote sensing estimates is comparable to the footprint of ground estimates). Thus, the inputs of the model have been retrieved at these temporal and spatial resolutions. The daily GPP product obtained as explained above is difficult to validate due to the lack of ground GPP data. Nevertheless, GPP estimations from several eddy covariance (EC) towers have been used. These towers belong to the European Fluxes Database Cluster (http://www.europe-fluxdata.eu). By chance, these EC towers are mainly located in the semi-arid areas, which are more difficult to model due to their larger soil background effects. Thus, this direct validation of the GPP product serves to establish its upper uncertainty level. Moreover, an indirect validation, by means of an inter-comparison with two other operational products (from MODIS and Copernicus), is carried out. The results have been highly satisfactory and promising. A further analysis of the percentage of variance associated with each input of the Monteith's equation clearly evidences the role of the water stress in the inter-annual variation of GPP in Mediterranean ecosystems

La feligresía de La Carolina de las nuevas poblaciones de Sierra Morena: análisis y estudio socio espacial del territorio (1781-1819)

Las Nuevas Poblaciones de Sierra Morena y Andalucía creadas a partir de 1767, bajo el reinado de Carlos III de Borbón, cuentan con una amplia historiografía que ha permitido el estudio en profundidad de este espacio geográfico durante las últimas décadas. A través del presente trabajo, hemos podido profundizar en dicho acontecimiento histórico, el porqué de la creación de las nuevas poblaciones, y también, el papel de los colonos, los verdaderos protagonistas de tal empresa. Además, todo el trabajo se complementa con la información geográfica obtenida a partir de la cartografía del siglo XVIII, aportando una serie de análisis espaciales llevados a cabo con Sistemas de Información Geográfica (SIG), dotando de una visión diferente al proceso de creación y consolidación de las Nuevas Poblaciones, teniendo como caso principal la capital de dichas poblaciones: La Carolina

PDbm: People detection benchmark repository

This paper is a postprint of a paper submitted to and accepted for publication in Electronics Letters and is subject to Institution of Engineering and Technology Copyright. The copy of record is available at IET Digital Library and IEEE XploreFollowing the approach of the change detection challenge, in order to facilitate the evaluation of new algorithms for people detection, a people detection benchmarking repository is presented. It includes realistic sequences, people detection ground truth and an evaluation framework. It will be updated based on received feedback, and will maintain a comprehensive ranking of submitted methods for years to come

Humoral response (IgG) of goats experimentally infected with Fasciola hepatica against cysteine proteinases of adult fluke

The use of cysteine proteinases from Fasciola hepatica adult flukes for the serodiagnosis of caprine fasciolosis by means of an indirect ELISA test was studied. Two proteolytic fractions from adult fluke homogenates, with apparent molecular weights of 28 and 34 kDa (P28 and P34 respectively), were characterised as cysteine proteinases using azocasein assays and gelatin gel analysis. Both P28 and P34 fractions were electroluted and used as antigens in two different indirect ELISA tests. Serum IgG levels against P28 and P34 in goats given an experimental primary infection with 200 metacercariae or in goats given two experimental infections with 200 metacercariae were determined and compared with those observed in an uninfected control group. ELISA tests using both cysteine proteases showed a rapid and consistent detection of specific IgG in all experimentally infected goats. The IgG response to P28 was the first to be detected as early as 2–3 weeks post-infection and remained elevated throughout the experiment. The response to P34 was detected later (4–6 wpi) and disappeared in some animals at 18 wpi, while flukes were still present in the bile ducts. No significant differences were observed between the anti-P28 and anti-P34 IgG responses between animals receiving a primary or a challenge infection. The results of our study, although preliminary, are promising since the P28 ELISA described here may be a reliable method for the immunodiagnosis of F. hepatica infection in goats

La valoración de la prueba neurocientífica en el proceso penal español: la P300

Debido al gran desarrollo que han sufrido las nuevas tecnologías nos encontramos ante la necesidad de incluirlas en el proceso penal. Esta situación ha supuesto que se tengan que analizar los derechos y garantías que se pueden ver vulnerados a la hora de aplicarse. El trabajo se ha centrado principalmente en la P300 y la opinión que tiene la doctrina y los tribunales sobre su uso tanto en la fase de instrucción como en el juicio oral.<br /

Distribution of Foxp3+ T cells in the liver and hepatic lymph nodes of goats and sheep experimentally infected with Fasciola hepatica

Foxp3 regulatory T cells (Tregs) are now considered to play a key role in modulation of immune responses during parasitic helminth infections. Immunomodulation is a key factor in Fasciola hepatica infection; however, the distribution and role of Foxp3+ Tregs cells have not been investigated in F. hepatica infected ruminants. The aim of this study was to evaluate the presence of Foxp3+ Tregs in the liver and hepatic lymph nodes from experimentally infected sheep and goats during acute and chronic stages of infection. Three groups of goats (n = 6) and three groups of sheep (n = 6) were used in this study. Goats in groups 1–2 and sheep in groups 4–5 were orally infected with metacercarie of ovine origin. Groups 1 and 4 were killed during the acute stage of the infection, at nine days post infection (dpi); groups 2 and 5 were killed during the chronic stage, at 15 and19 weeks post infection respectively (wpi). Groups 3 (goats) and 6 (sheep) were left as uninfected controls. Fluke burdens and liver damage were assessed and the avidin–biotin–complex method was used for the immunohistochemical study. At nine dpi in acute hepatic lesions, the number of both Foxp3+ and CD3+ T lymphocytes increased significantly in goats and sheep. In the chronic stages of infection (15–19 wpi), the number of Foxp3+ and CD3+ T lymphocytes were also significantly increased with respect to control livers, particularly in portal spaces with severely enlarged bile ducts (response to adult flukes) while the increase was lower in granulomas, chronic tracts and smaller portal spaces (response to tissue damage). Foxp3+ Tregs were increased in the cortex of hepatic lymph nodes of sheep (chronic infection) and goats (acute and chronic infection). The estimated proportion of T cells which were Foxp3+ was significantly increased in the large bile ducts and hepatic lymph node cortex of chronically infected goats but not sheep. This first report of the expansion of Foxp3+ Tregs in acute and chronic hepatic lesions in ruminants suggests that these cells may be involved in both parasite survival and modulation of hepatic damage. Future studies should be focused on the investigation of parasite molecules and cytokines involved in this process

On-line remaining useful life estimation of power connectors focused on predictive maintenance

Connections are critical elements in power systems, exhibiting higher failure probability. Power connectors are considered secondary simple devices in power systems despite their key role, since a failure in one such element can lead to major issues. Thus, it is of vital interest to develop predictive maintenance approaches to minimize these issues. This paper proposes an on-line method to determine the remaining useful life (RUL) of power connectors. It is based on a simple and accurate model of the degradation with time of the electrical resistance of the connector, which only has two parameters, whose values are identified from on-line acquired data (voltage drop across the connector, electric current and temperature). The accuracy of the model presented in this paper is compared with the widely applied autoregressive integrated moving average model (ARIMA), showing enhanced performance. Next, a criterion to determine the RUL is proposed, which is based on the inflection point of the expression describing the electrical resistance degradation. This strategy allows determination of when the connector must be replaced, thus easing predictive maintenance tasks. Experimental results from seven connectors show the potential and viability of the suggested method, which can be applied to many other devices.This research was partially funded by Ministerio de Ciencia, Innovación y Universidades de España, grant number RTC-2017-6297-3 and by the Generalitat de Catalunya, grant number 2017 SGR 967.Peer ReviewedPostprint (author's final draft