Biomarkers of basal cell carcinoma resistance to methyl-aminolevulinate photodynamic therapy

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Methyl-aminolevulinate photodynamic therapy (MAL-PDT) is an excellent option for the treatment of basal cell carcinoma (BCC). However, up to 25% of cases are resistant to this treatment modality. Objective The aim of this study was to identify potential biomarkers of BCC response to MAL-PDT. Material and methods Clinical, histological, and immunohistochemical (p53, Ki-67, CD-31, COX2, β-catenin, EGFR, and survivin) variables were analyzed in a retrospective study of consecutive BCC patients treated with MAL-PDT at the San Jorge Hospital, Huesca, Spain between January 2006 and December 2015. To deepen on these markers, the effects on p53 and cyclin D1 expression, in vitro response to MAL-PDT of 2 murine BCC cell lines (ASZ and BSZ), was also evaluated. Results The retrospective study examined the response to MAL-PDT of 390 BCCs from 182 patients. The overall clinical response rate was 82.8%, with a mean follow-up time of 35.96 months (SD = 23.46). Immunohistochemistry revealed positive p53 in 84.6% of responders but only 15.4% of nonresponsive tumors (p = 0.011). Tumors with increased peripheral palisading of basal cell islands to immunostaining β-catenin responded poorly to PDT (p = 0.01). In line with our findings in patients, in vitro studies revealed a better response to PDT in the p53-positive ASZ cell line than the p53-negative BSZ cell line (p<0.01). Multivariate analysis revealed that the following variables were significantly associated with response to PDT: age, nBCC, presence of peritumoral inflammatory infiltrate, and p53 immunopositivity. Patients with positive p53 immunostaining were 68.54 times more likely to achieve cure than p53-negative patients (CI95% 2.94–159.8) Conclusion Our finding suggest that certain clinicopathological and immunohistochemical variables, particularly p53 expression, may serve as indicators of BCC response to MAL-PDT, and thus facilitate the selection of patients who are most likely to benefit from this therapyThis project received support from the Instituto de Salud Carlos III and Fondos Feder Europeos, MINECO (FIS PI15/00974). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

Performance of likelihood ratios considering bounds on the probability of observing misleading evidence

This is a pre-copyedited, author-produced version of an article accepted for publication in Law, Probability & Risk following peer review. The version of record Jose Juan Lucena-Molina, Daniel Ramos-Castro, Joaquin Gonzalez-Rodriguez; Performance of likelihood ratios considering bounds on the probability of observing misleading evidence. Law, Probability and Risk 2015; 14 (3): 175-192 is available online at: http://dx.doi.org/10.1093/lpr/mgu022In this article, we introduce a new tool, namely 'Limit Tippett Plots', to assess the performance of likelihood ratios in evidence evaluation including theoretical bounds on the probability of observing misleading evidence. To do that, we first review previous work about such bounds. Then we derive 'Limit Tippett Plots' that complements Tippett plots with information about the limits on the probability of observing misleading evidence, which are taken as a reference. Thus, a much richer way to measure performance of likelihood ratios is given. Finally, we present an experimental example in forensic automatic speaker recognition following the protocols of the Acoustics Laboratory of Guardia Civil, where it can be seen that 'Limit Tippett Plots' help to detect problems in the calculation of likelihood ratios

Contribución al estudio de la prescripción y la caducidad

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Derecho, Departamento de Derecho Procesal, leída en 1983.Depto. de Derecho Procesal y Derecho PenalFac. de DerechoTRUEProQuestpu

Hybrid power-heat microgrid solution using hydrogen as an energy vector for residential houses in Spain. A case study

In order to favor a transition to a renewable energy economy, it is necessary to study the possible permeation of renewable energy sources not only in the electric grid or industrial scale, but also in the small householding scale. One of the most interesting technologies available for this purpose is solar energy, since it is a mature technology that can be easily installed in every rooftop. Thus, a techno-economic assessment was carried out to evaluate the installation of a solar-based power-heat hybrid microgrid considering the use of hydrogen as an energy vector in a typical residential house in Spain. Lead-acid batteries plus the photovoltaic and solar thermal energy installation are complemented with a hydrogen system composed of an electrolyzer, two metal hydride bottles, and a fuel cell. A simulation tool has been generated using experimental models developed and validated with real equipment for each one of the electric microgrid component. Three operating modes were tested making use of this tool to better manage the energy consumed/produced and optimize the economic output of the facility. The results show that setting up a hydrogen-based microgrid in a residential house is unviable today, mainly due to the high cost of hydrogen generation and consumption equipment. If only solar energy is considered, the microgrid inversion (12.500 €) is recovered in ten years. On the other hand, selling the electricity output has almost no repercussions considering current electrical rates in Spain. Finally, while using an optimization algorithm to manage energy use, battery life-spam, and economic benefit slightly increase. However, this profit may not be enough to justify the use of a more complex control system. The results of this research will help users, renewable energy companies, investigators, and policymakers to better understand the different factors influencing the spread of renewable smart grids in households and propose solutions to address these.Junta de Andalucía - Consejería de Conocimiento, Investigación y Universidad PY18-RE-002

Fatiga digital en estudiantes universitarios como consecuencia de la enseñanza online durante la pandemia Covid-19

The continued use of videoconferencing systems to carry out the teaching-learning process in higher education institutions during the Covid-19 pandemic has had a negative impact on university students' learning, causing digital fatigue. This fatigue mainly affects eyesight, emotional, motivational and social status. The aim of this study was to determine the degree of digital fatigue derived from prolonged exposure to videoconferencing systems among university students. For this purpose, a cross-sectional study design was applied based on the distribution of an online survey. A total of 613 university students aged 18-35 years (M = 21.54, SD = 3.85) participated in the study. The results obtained revealed that: 1) the degree of prevalence of digital fatigue among university students was medium-high; 2) socio-demographic variables linked to being female, studying in the Arts and Humanities, spending more time in front of an electronic device and connecting via a laptop were indicators of a higher rate of digital fatigue; 3) gender and high hours consumption were predictors of visual fatigue, social fatigue, motivational fatigue and emotional fatigue; 4) visual fatigue, motivational fatigue and emotional fatigue, together with the field of study knowledge, had a significant influence on overall fatigue. Finally, the future lines of research of this work are discussed, highlighting the richness of the data obtained to advance knowledge about digital fatigue and its influence on university learning.El uso continuo de los sistemas de videoconferencia para llevar a cabo el proceso de enseñanza-aprendizaje en las instituciones de educación superior, durante la pandemia derivada de la Covid-19, ha influido negativamente en el aprendizaje de los estudiantes universitarios, provocando fatiga digital. Esta fatiga afecta principalmente a la vista, estado emocional, motivacional y social. El objetivo de este trabajo fue determinar el grado de fatiga digital derivada de la exposición prolongada a sistemas de videoconferencia de los estudiantes universitarios. Para ello, se aplicó un diseño de estudio transversal a partir de la distribución de una encuesta en línea. En el estudio participaron un total de 613 estudiantes universitarios, con edades comprendidas entre los 18 y 35 años (M = 21,54; DT = 3,85). Los resultados obtenidos revelaron que: 1) el grado de prevalencia de la fatiga digital en los estudiantes universitarios fue medio-alto; 2) las variables sociodemográficas vinculadas a ser mujer, cursar estudios de la rama de Artes y Humanidades, pasar más tiempo frente a un dispositivo electrónico y conectarse a través de un ordenador portátil fueron indicadores de una mayor tasa de fatiga digital; 3) el sexo y el consumo elevado de horas fueron variables predictores de la fatiga visual, fatiga social, fatiga motivacional y fatiga emocional; 4) la fatiga visual, fatiga motivacional y fatiga emocional, junto a la rama de conocimiento de los estudios cursados, influyeron de forma significativa en la fatiga general. Finalmente, se discuten las futuras líneas de investigación de este trabajo, destacando la riqueza de los datos obtenidos para avanzar en el conocimiento sobre la fatiga digital y su influencia en el aprendizaje universitario

Technical-economic potential of PV systems on Colombian residential sector

Solar energy is the second most applied variable renewable source worldwide, after the wind. In 2014, its world installed capacity was around 177 GW. During the past years, the yearly new capacity of photovoltaic (PV) solar yearly new capacity has exceeded new wind projects, highlighting this new solar power trend. This study aims to estimate technical and economic potential of the solar PV in the Colombian residential sector taking into account characteristics such as socio-economic stratum, household electric power consumption, tariffs by utility and capital cost. Technical-economic simulation tools were integrated into a geographical information system (‘GIS’) to permit a spatial analysis. Results shows solar generation potential and its annual penetration potential for all socioeconomic strata within all Colombian municipalities up to 2030. The current technical potential is around 9.1 GWp (13.10 TWh/year), while the economic potential will be 3.2 GWp by 2030.The authors would like to express their gratitude to the Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (National Scientific and Technological Development Council – CNPQ), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior ((Brazilian Federal Agency for the Improvement of Higher Education-CAPES) and NETEP - European-Brazilian Network on Energy Planning, a project supported by a Marie Curie International Research Staff Exchange Scheme Fellowship within the 7th European Union Framework Programme (PIRSES-GA-2013-612263), for the essential support given for this work to be carried out

Drug properties and host factors contribute to biochemical presentation of drug-induced liver injury: a prediction model from a machine learning approach

Drug-induced liver injury (DILI) presentation varies biochemically and histologically. Certain drugs present quite consistent injury patterns, i.e., DILI signatures. In contrast, others are manifested as broader types of liver injury. The variety of DILI presentations by a single drug suggests that both drugs and host factors may contribute to the phenotype. However, factors determining the DILI types have not been yet elucidated. Identifying such factors may help to accurately predict the injury types based on drugs and host information and assist the clinical diagnosis of DILI. Using prospective DILI registry datasets, we sought to explore and validate the associations of biochemical injury types at the time of DILI recognition with comprehensive information on drug properties and host factors. Random forest models identified a set of drug properties and host factors that differentiate hepatocellular from cholestatic damage with reasonable accuracy (69-84%). A simplified logistic regression model developed for practical use, consisting of patient’s age, drug’s lipoaffinity, and hybridization ratio, achieved a fair prediction (68%-74%), but suggested potential clinical usability, computing the likelihood of liver injury type based on two properties of drugs taken by a patient and patient’s age. In summary, considering both drug and host factors in evaluating DILI risk and phenotypes open an avenue for future DILI research and aid in the refinement of causality assessment.The present study has been supported by grants of Instituto de Salud Carlos III cofounded by Fondo Europeo de Desarrollo Regional – FEDER (contract numbers: PI 18/01804; PT20/00127) and Agencia Española del Medicamento. Plataforma ISCiii de Investigación Clínica and CIBERehd are funded by Instituto de Salud Carlos III. IAA holds a Sara Borrell research contract from the National Health System, Instituto de Salud Carlos III (CD20/00083)

Public Resource usage in Health Systems: A Data Envelopment Analysis of the Efficiency of Regional Health Systems in Spain

The efficiency in the management of public re sources is on of the main pillars of the welfare state. The objective of this work is to analyze the efficiency of the public resources that regional governments invest in health systems. To this end, Data Envelopment Analysis (DEA) is applied which enable researchers and managers to obtain measurements of efficiency of the analyzed re gions, and proposing corrective steps to achieve ef ficiency for non-efficient regions. Results show that not every health systems present technical efficiency, nor scale efficiencyMinisterio de Economía y Competitividad TIN2009-14378-C02-01Junta de Andalucía TIC-805

Effects of Extending Milk Replacer Feeding during the Fattening Period on the Behaviour and Welfare of Lambs: A Preliminary Study

There is a lack of information on the behavioural and welfare effects of sustaining artificial milk feeding in fattening lambs. Therefore, the present work aimed to study the effects of prolonged artificial milk feeding during fattening with a high concentrate diet on the behaviour of lambs. The behaviour of 16 non castrated male lambs of the Manchega sheep breed (eight lambs were in the group that were fed daily a bottle of milk, and the other eight were in the weaned group) was recorded with four fixed cameras just before bottle feeding (~8:30 a.m.) of the unweaned group till four hours later, every day for 7 weeks. The solid diet (pelleted concentrate plus cereal straw) and housing conditions were the same in both groups. Solid feeds were offered ad libitum. There were no differences between groups in time spent eating nor in drinking, playing, scratching and oral activity behaviours (p > 0.05), but resting episodes were longer in weaned lambs (p < 0.05). Weaned lambs presented a higher frequency of self-grooming behaviour (p < 0.05), while the unweaned group performed a higher frequency of interaction behaviour (p < 0.05). In conclusion, the behaviours of lambs that were fed daily a bottle of milk during the fattening period did not substantially differ from the weaned individuals