Genetic and Molecular Factors in Drug-Induced Liver Injury: A Review

The diagnosis of drug-induced liver injury (DILI) is challenging and based on complex diagnostic criteria. DILI falls into two main categories i) intrinsic 'dose-dependent' Type A reactions ii) 'idiosyncratic' or Type B reactions (which are usually not predictable). Idiosyncratic reactions can be immunoallergic (hypersensitivity), or metabolic, although overlap between categories can occur. The aim of this review is to summarise the general view of underlying mechanisms in DILI and to highlight individual risk factors for developing hepatotoxicity. Polymorphisms of bioactivation/ toxification pathways through CYP450 enzymes (Phase I), detoxification reactions (Phase II) and excretion/transport (Phase III) are explored together with immunological factors that might determine DILI. The importance of establishing a multidisciplinary and multi-centric network to promote the understanding and research in hepatotoxicity is underlined. Challenges such as genetic analyses for association studies and whole genome studies, pharmacogenetic testing and future approaches to study DILI are considered. Knowledge regarding these operational mechanisms could provide further insight for the prospective identification of susceptible patients at risk of developing drug-induced hepatotoxicity.

Can virtual nature improve patient experiences and memories of dental treatment? A study protocol for a randomized controlled trial

Background Dental anxiety and anxiety-related avoidance of dental care create significant problems for patients and the dental profession. Distraction interventions are used in daily medical practice to help patients cope with unpleasant procedures. There is evidence that exposure to natural scenery is beneficial for patients and that the use of virtual reality (VR) distraction is more effective than other distraction interventions, such as watching television. The main aim of this randomized controlled trial is to determine whether the use of VR during dental treatment can improve the overall dental experience and recollections of treatment for patients, breaking the negative cycle of memories of anxiety leading to further anxiety, and avoidance of future dental appointments. Additionally, the aim is to test whether VR benefits dental patients with all levels of dental anxiety or whether it could be especially beneficial for patients suffering from higher levels of dental anxiety. The third aim is to test whether the content of the VR distraction can make a difference for its effectiveness by comparing two types of virtual environments, a natural environment and an urban environment. Methods/design The effectiveness of VR distraction will be examined in patients 18 years or older who are scheduled to undergo dental treatment for fillings and/or extractions, with a maximum length of 30 minutes. Patients will be randomly allocated into one of three groups. The first group will be exposed to a VR of a natural environment. The second group will be exposed to a VR of an urban environment. A third group consists of patients who receive standard care (control group). Primary outcomes relate to patients’ memories of the dental treatment one week after treatment: (a) remembered pain, (b) intrusive thoughts and (c) vividness of memories. Other measures of interest are the dental experience, the treatment experience and the VR experience. Trial registration Current Controlled Trials ISRCTN4144280

Colony size predicts division of labour in Attine ants

Division of labour is central to the ecological success of eusocial insects, yet the evolutionary factors driving increases in complexity in division of labour are little known. The size–complexity hypothesis proposes that, as larger colonies evolve, both non-reproductive and reproductive division of labour become more complex as workers and queens act to maximize inclusive fitness. Using a statistically robust phylogenetic comparative analysis of social and environmental traits of species within the ant tribe Attini, we show that colony size is positively related to both non-reproductive (worker size variation) and reproductive (queen–worker dimorphism) division of labour. The results also suggested that colony size acts on non-reproductive and reproductive division of labour in different ways. Environmental factors, including measures of variation in temperature and precipitation, had no significant effects on any division of labour measure or colony size. Overall, these results support the size–complexity hypothesis for the evolution of social complexity and division of labour in eusocial insects. Determining the evolutionary drivers of colony size may help contribute to our understanding of the evolution of social complexity

Colony size predicts division of labour in Attine ants

Division of labour is central to the ecological success of eusocial insects, yet the evolutionary factors driving increases in complexity in division of labour are little known. The size–complexity hypothesis proposes that, as larger colonies evolve, both non-reproductive and reproductive division of labour become more complex as workers and queens act to maximize inclusive fitness. Using a statistically robust phylogenetic comparative analysis of social and environmental traits of species within the ant tribe Attini, we show that colony size is positively related to both non-reproductive (worker size variation) and reproductive (queen–worker dimorphism) division of labour. The results also suggested that colony size acts on non-reproductive and reproductive division of labour in different ways. Environmental factors, including measures of variation in temperature and precipitation, had no significant effects on any division of labour measure or colony size. Overall, these results support the size–complexity hypothesis for the evolution of social complexity and division of labour in eusocial insects. Determining the evolutionary drivers of colony size may help contribute to our understanding of the evolution of social complexity

Pruning neural network for architecture optimization applied to near-infrared reflectance spectroscopic measurements. Determination of the nitrogen content in wheat leaves

The pruning neural network, based on the algorithm called optimum brain surgeon, was used for network architecture optimization. This network pruning procedure was applied for estimating the nitrogen contents in wheat leaves, using near-infrared diffuse reflectance spectroscopy. The results obtained with pruning were compared with those obtained by using ordinary procedures with neural networks, partial least squares, polynomial partial least squares and neural networks/partial least squares methodologies. Comparison of the results with those obtained by the conventional Kjeldahl method showed that the results with pruning neural networks were as good as those with ordinary neural networks and with PLS/neural networks, but better than those with the other methodologies. Although the comparison was performed for one data set, the pruning procedure has the advantage of introducing an automatic architecture optimization, which is cumbersome when performed by the other neural network procedures used in this work, generating a simplified model with better generalization abilities.124111669167

Assessment of electrophoresis and electroosmosis in construction materials: effect of enhancing electrolytes and heavy metals contamination

Electrokinetic effects are those that take place by application of an electric field to porous materials, with the zeta potential as the key parameter. Specifically, in the case of contaminated construction materials, the generation of an electroosmotic flux, with the corresponding dragging due to water transport, is a crucial mechanism to succeed in the treatment of decontamination. Therefore, it is of great interest trying to optimize the treatment by the addition of specific electrolytes enhancing the electrokinetic phenomena. Most of the data of zeta potential found in literature for construction materials are based in micro-electrophoresis measurements, which are quite far of the real conditions of application of the remediation treatments. In this paper, electrophoretic and electroosmotic experiments, with monolithic and powdered material respectively, have been carried out for mortar, brick and granite clean and contaminated with Cs, Sr, Co, Cd, Cu and Pb. The electrolytes tested have been distilled water (DW), Na2–EDTA, oxalic acid, acetic acid and citric acid. The zeta potential values have been determined through the two different techniques and the results compared and critically analysed

GÊNEROS E SEXUALIDADES NA FORMAÇÃO DE DOCENTE: ANALISANDO SABERES A PARTIR DE OFICINAS PEDAGÓGICAS

O que pensam as estudantes de Pedagogia e Licenciaturas sobre os gêneros e as sexualidades? Quais são suas principais dúvidas sobre esses temas? Quais são as possibilidades de debater a diversidade de gênero e as sexualidades na formação docente? Nesse artigo, analisamos as experiências da aplicação da oficina “Corpo, gênero e sexualidade na escola”, realizada em três turmas, de duas universidades cariocas. Para isso, trazemos reflexões de materiais produzidos pelas alunas. Assim, pretendemos lançar algumas pistas sobre a construção de saberes em gêneros e sexualidades na formação docente.Palavras chave: Gênero. Sexualidade. Formação docente. Oficinas pedagógicas. GENDERS AND SEXUALITIES IN TEACHER TRAINING: ANALYZING KNOWLEDGE FROM PEDAGOGICAL WORKSHOPSWhat do Pedagogy and Undergraduate students think about genders and sexualities? What are your main doubts about these topics? What are the possibilities for discussing gender diversity and sexualities in teacher education? In this article, we analyze the experiences of applying the workshop “Body, gender and sexuality at school”, held in three classes, from two Rio de Janeiro universities. For that, we bring reflections of materials produced by the students. Thus, we intend to launch some clues about the construction of knowledge on gender and sexuality in teacher education.Keywords: Gender. Sexuality. Teacher training. Pedagogical workshops

Application of the PISA design model to monopiles embedded in layered soils

The PISA design model is a procedure for the analysis of monopile foundations for offshore wind turbine applications. This design model has been previously calibrated for homogeneous soils; this paper extends the modelling approach to the analysis of monopiles installed at sites where the soil profile is layered. The paper describes a computational study on monopiles embedded in layered soil configurations comprising selected combinations of soft and stiff clay and sand at a range of relative densities. The study comprises (a) analyses of monopile behaviour using detailed three-dimensional (3D) finite-element analysis, and (b) calculations employing the PISA design model. Results from the 3D analyses are used to explore the various influences that soil layering has on the performance of the monopile. The fidelity of the PISA design model is assessed by comparisons with data obtained from equivalent 3D finite-element analyses, demonstrating a good agreement in most cases. This comparative study demonstrates that the PISA design model can be applied successfully to layered soil configurations, except in certain cases involving combinations of very soft clay and very dense sand. </jats:p

PISA design methods for offshore wind turbine monopiles

Abstract This paper provides an overview of the PISA design model recently developed for laterally loaded offshore wind turbine monopiles through a major European joint-industry academic research project, the PISA Project. The focus was on large diameter, relatively rigid piles, with low length to diameter (L/D) ratios, embedded in clay soils of different strength characteristics, sand soils of different densities and in layered soils combining clays and sands. The resulting design model introduces new procedures for site specific calibration of soil reaction curves that can be applied within a one-dimensional (1D), Winkler-type, computational model. This paper summarises the results and key conclusions from PISA, including design methods for (a) stiff glacial clay till (Cowden till), (b) brittle stiff plastic clay (London clay), (c) soft clay (Bothkennar clay), (d) sand of varying densities (Dunkirk), and, (e) layered profiles (combining soils from (a) to (d)). The results indicate that the homogeneous soil reaction curves applied appropriately for layered profiles in the 1D PISA design model provide a very good fit to the three-dimensional finite element (3D FE) calculations, particularly for profiles relevant to current European offshore wind farm sites. Only a small number of cases, involving soft clay, very dense sand and L/D = 2 monopiles, would appear to require more detailed and bespoke analysis.</jats:p