Cost/efficacy analysis of preferred Spanish AIDS study group regimens and the dual therapy with LPV/r+3TC for initial ART in HIV infected adults.

INTRODUCTION: The National AIDS Plan and the Spanish AIDS study group (GESIDA) panel of experts propose 'preferred regimens' of antiretroviral treatment (ART) as initial therapy in HIV-infected patients for 2013 [1]. All these regimens are triple therapy regimens. The Gardel Study assessed the efficacy and safety of a dual therapy (DT) combination of lopinavir/ritonavir (LPV/r) 400/100 mg BID+ lamivudine (3TC) 150 mg BID [2]. The objective of this study is to evaluate the costs and efficiency of initiating treatment with the GESIDA 'preferred regimens' and DT. MATERIALS AND METHODS: Economic assessment of costs and efficiency (cost/efficacy) through decision tree analysis models. Efficacy was defined as the probability of having viral load <50 copies/mL at week 48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regime was defined as the costs of ART and its consequences (adverse effects, changes of ART regime and drug resistance tests) during the first 48 weeks. The payer perspective (Spanish National Health System) was applied considering only differential direct costs: ART (official prizes), management of adverse effects, resistance tests, and determination of HLA B*5701. The setting is Spain and the costs are those of 2013. A sensitivity deterministic analysis was conducted, building three scenarios for each regime: base, most favourable and most unfavourable cases. RESULTS: In the base case scenario, the cost of initiating treatment ranges from 5138 euros for DT, to 12,059 euros for tenofovir DF/emtricitabine (TDF/FTC)+raltegravir (RAL). The efficacy ranges between 0.66 for abacavir (ABC)/3TC+LPV/r and ABC/3TC+atazanavir (ATV)/r, and 0.88 for DT. Efficiency, in terms of cost/efficacy, varies between 5817 and 13,930 euros per responder at 48 weeks, for DT and TDF/FTC+RAL respectively. DT is the most efficient regimen in the most favourable (5503 euros per responder) and most unfavourable (6169 euros per responder) scenarios. CONCLUSIONS: Considering the ART official Spanish prizes, the most efficient regimen was DT, followed by the triple therapy with non-nucleoside containing regimens. The sensitivity analysis confirms the robustness of these findings

Functional characterization of highly processive protein-primed DNA polymerases from phages Nf and GA-1, endowed with a potent strand displacement capacity

This paper shows that the protein-primed DNA polymerases encoded by bacteriophages Nf and GA-1, unlike other DNA polymerases, do not require unwinding or processivity factors for efficient synthesis of full-length terminal protein (TP)-DNA. Analysis of their polymerization activity shows that both DNA polymerases base their replication efficiency on a high processivity and on the capacity to couple polymerization to strand displacement. Both enzymes are endowed with a proofreading activity that acts coordinately with the polymerization one to edit polymerization errors. Additionally, Nf double-stranded DNA binding protein (DBP) greatly stimulated the in vitro formation of the TP-dAMP initiation complex by decreasing the K(m) value for dATP of the Nf DNA polymerase by >20-fold. Whereas Nf DNA polymerase, as the φ29 enzyme, is able to use its homologous TP as well as DNA as primer, GA-1 DNA polymerase appears to have evolved to use its corresponding TP as the only primer of DNA synthesis. Such exceptional behaviour is discussed in the light of the recently solved structure of the DNA polymerase/TP complex of the related bacteriophage φ29

Involvement of φ29 DNA polymerase thumb subdomain in the proper coordination of synthesis and degradation during DNA replication

φ29 DNA polymerase achieves a functional coupling between its 3′–5′ exonuclease and polymerization activities by means of important contacts with the DNA at both active sites. The placement and orientation of residues Lys538, Lys555, Lys557, Gln560, Thr571, Thr573 and Lys575 in a modelled φ29 DNA polymerase–DNA complex suggest a DNA-binding role. In addition, crystal structure of φ29 DNA polymerase–oligo (dT)(5) complex showed Leu567, placed at the tip of the thumb subdomain, lying between the two 3′-terminal bases at the exonuclease site. Single replacement of these φ29 DNA polymerase residues by alanine was made, and mutant derivatives were overproduced and purified to homogeneity. The results obtained in the assay of their synthetic and degradative activities, as well as their coordination, allow us to propose: (1) a primer-terminus stabilization role at the polymerase active site for residues Lys538, Thr573 and Lys575, (2) a primer-terminus stabilization role at the exonuclease active site for residues Leu567 and Lys555 and (3) a primer-terminus binding role in both editing and polymerization modes for residue Gln560. The results presented here lead us to propose φ29 DNA polymerase thumb as the main subdomain responsible for the coordination of polymerization and exonuclease activities

Future teachers' digital competence: what is the perception of current students teachers'?

En el momento actual, el rol de los docentes resulta fundamental para capacitar a los estudiantes utilizando todas las potencialidades que ofrecen las TIC. Los docentes necesitan disponer, no solo de una alfabetización digital básica, sino también ser capaces de integrarlas en sus prácticas didácticas, y para ello, su formación inicial resulta fundamental. El principal objetivo de este estudio es explorar la competencia digital de futuros docentes a partir de su autopercepción, un factor clave para su posterior desempeño. Para ello, una muestra de 149 estudiantes universitarios de educación respondieron a un cuestionario de autopercepción diseñando siguiendo los estándares de ISTE. Según los resultados, la mayoría de los futuros docentes disponen de un nivel alto de competencia digital docente (especialmente en habilidades digitales básicas más que en su aplicación didáctica), asimismo se evidenciaron ciertas diferencias significativas en cuanto a la edad, en el área de las habilidades digitales básicas.Nowadays, the role of teachers is crucial in empowering students with the advantages of ICT. Teachers are required not only to become basically digitally literate, but they should also be able to integrate technology into their teaching, and initial teacher education is one of the most important factors for this purpose. The main aim of this study was to explore the student teachers’ digital competence through their own self-perceptions, a key factor for their future performance. For this purpose, a sample of 149 student teachers’ completed a self-perception questionnaire constructed in accordance with ISTE standards. The results show that most student teachers have a high level of self-perceived digital competence (better basic digital skills that in didactic use of ICT). However, there were significant differences in basic digital skills according to the age of student teachers

Social Learning Analytics en la Educación Superior. Una experiencia en el Grado de Educación Primaria

The concept of Learning Analytics, as we understand it today, is relatively new but the practice of evaluating user behavior is not innovative. For years, technological development, along with other educational aspects, have encouraged, developed and facilitated this practice as a way of providing a personalized quality experience to students. The main goal of this study, carried out in the Primary Education Degree of the University of Murcia, was to research, from the perspective of Social Learning Analytics, how students learn and collaborate in online environments, specifically through their use of social media. With the idea of improving and optimizing future teaching experiences, a pilot study was conducted using weblog, Twitter and Facebook to work with different topics on the subject. The method used in this research was a participant observation and the analysis performed was both quantitative, based mainly on the data gathered from the learning analytics, and qualitative (analyzing students’ content from comments). Results show that there was greater interaction on Facebook than weblogs, where students interacted to deal with aspects related to the learning process and the topic of the subject. This exchange of information grew during the development of the experience. In addition, learning analytics shows that there is a relationship between group members and their interaction and behavior in networks.El concepto de Learning Analytics es relativamente nuevo tal como lo entendemos hoy en día, pero la práctica de evaluar el comportamiento del usuario a través de registros previos de actividad no lo es tanto. Con el tiempo, los avances tecnológicos, junto con otros factores educativos han alentado, desarrollado y facilitado esta práctica para proporcionar una experiencia personalizada de calidad al alumnado. El objetivo general de este estudio, realizado en el Grado de Educación Primaria de la Universidad de Murcia, se centra en conocer desde la perspectiva de Social Learning Analytics, cómo aprende y colabora el alumnado en entornos virtuales, específicamente a través de medios sociales. Con la idea de mejorar y optimizar futuras experiencias docentes, se llevó a cabo un estudio piloto en el que se usó Facebook, Twitter y un blog grupal para el desarrollo de las tareas de la asignatura. El método empleado en esta investigación ha sido el de la observación participante y el tipo de análisis realizado ha sido tanto cuantitativo, basado principalmente en los datos obtenidos de las propias analíticas de aprendizaje, como cualitativo (análisis de contenido de las intervenciones y comentarios del alumnado). Los resultados obtenidos muestran que hubo una mayor interacción en Facebook que en el blog grupal, donde los alumnos interaccionaban para tratar aspectos relacionados con el proceso de aprendizaje y la temática de la asignatura. Este intercambio de información fue creciendo durante el desarrollo de la experiencia. Además, las analíticas de aprendizaje muestran que existe una relación en cuanto a los miembros del grupo y sus interacciones y comportamientos en las redes

Role of the LEXE motif of protein-primed DNA polymerases in the interaction with the incoming nucleotide

The LEXE motif, conserved in eukaryotic type DNA polymerases, is placed close to the polymerization active site. Previous studies suggested that the second Glu was involved in binding a third noncatalytic ion in bacteriophage RB69 DNA polymerase. In the protein-primed DNA polymerase subgroup, the LEXE motif lacks the first Glu in most cases, but it has a conserved Phe/Trp and a Gly preceding that position. To ascertain the role of those residues, we have analyzed the behavior of mutants at the corresponding φ29 DNA polymerase residues Gly-481, Trp-483, Ala-484, and Glu-486. We show that mutations at Gly-481 and Trp-483 hamper insertion of the incoming dNTP in the presence of Mg2+ ions, a reaction highly improved when Mn2+ was used as metal activator. These results, together with previous crystallographic resolution of φ29 DNA polymerase ternary complex, allow us to infer that Gly-481 and Trp-483 could form a pocket that orients Val-250 to interact with the dNTP. Mutants at Glu-486 are also defective in polymerization and, as mutants at Gly-481 and Trp-483, in the pyrophosphorolytic activity with Mg2+. Recovery of both reactions with Mn2+ supports a role for Glu-486 in the interaction with the pyrophosphate moiety of the dNT

Study of additive manufacturing techniques to obtain tactile graphics

Ponència presentada a la 9th Manufacturing Engineering Society International Conference (MESIC 2021) 23rd-25th June 2021, Gijόn, SpainTactile graphics (TG) are intended to facilitate communication for people with total or partial visual impairment. For this purpose, TG include elements in relief that can be perceived through the sense of touch. TG can be fixed or portable. Fixed TG are expensive, as they are typically produced in very short runs, mostly single part production. Portable TG can be made by thermoforming polymer sheets, but a mould is still required, even though production runs are short (some tens). For this reason, the use of Rapid Manufacturing (RM) and Rapid Tooling (RT) strategies to manufacture TG can be of great interest. In this work, a literature review to study the application of Additive Manufacturing (AM) to obtain TG, both as RM and RT, is carried out. The review reveals the suitability of AM techniques to manufacture TG. In addition, some AM techniques are analysed to be used for a new type of TG, which is based on the deposition of glaze on ceramic tiles