A pharmacogenetic intervention for the improvement of the safety profile of antipsychotic treatments

Antipsychotic drugs fail to achieve adequate response in 30–50% of treated patients and about 50% of them develop severe and lasting side effects. Treatment failure results in poorer prognosis with devastating repercussions for the patients, carers and broader society. Our study evaluated the clinical benefits of a pharmacogenetic intervention for the personalisation of antipsychotic treatment. Pharmacogenetic information in key CYP polymorphisms was used to adjust clinical doses in a group of patients who started or switched treatment with antipsychotic drugs (PharmG+, N = 123), and their results were compared with those of a group of patients treated following existing clinical guides (PharmG−, N = 167). There was no evidence of significant differences in side effects between the two arms. Although patients who had their antipsychotic dose adjusted according to CYPs polymorphisms (PharmG+) had a bigger reduction in side effects than those treated as usual (PharmG−), the difference was not statistically significant (p > 0.05 for all comparisons). However, PharmG+ patients treated with CYP2D6 substrates that were carriers of CYP2D6 UMs or PMs variants showed a significantly higher improvement in global, psychic and other UKU side effects than PharmG− patients (p = 0.02, p = 0.05 and p = 0.01, respectively). PharmG+ clozapine treated patients with CYP1A2 or CYP2C19 UM and PMs variants also showed higher reductions in UKU scores than PharmG− clozapine patients in general. However, those differences were not statistically significant. Pharmacogenetic interventions may improve the safety of antipsychotic treatments by reducing associated side effects. This intervention may be particularly useful when considering treatment with antipsychotics with one major metabolic pathway, and therefore more susceptible to be affected by functional variants of CYP enzymes.This research was funded by grants from the Institute Carlos III (FIS PI11/02006; FIS PI16/01029). A.G.-R. was partially funded by a private grant from the Jové family. Genotyping was partially conducted by the CEGEN-PRB2-ISCIII node, which is supported by grant PT13/001, ISCIIISGEFI/ FEDER

An Approach for the Customized High-Dimensional Segmentation of Remote Sensing Hyperspectral Images

Abstract: This paper addresses three problems in the field of hyperspectral image segmentation: the fact that the way an image must be segmented is related to what the user requires and the application; the lack and cost of appropriately labeled reference images; and, finally, the information loss problem that arises in many algorithms when high dimensional images are projected onto lower dimensional spaces before starting the segmentation process. To address these issues, the Multi-Gradient based Cellular Automaton (MGCA) structure is proposed to segment multidimensional images without projecting them to lower dimensional spaces. The MGCA structure is coupled with an evolutionary algorithm (ECAS-II) in order to produce the transition rule sets required by MGCA segmenters. These sets are customized to specific segmentation needs as a function of a set of low dimensional training images in which the user expresses his segmentation requirements. Constructing high dimensional image segmenters from low dimensional training sets alleviates the problem of lack of labeled training images. These can be generated online based on a parametrization of the desired segmentation extracted from a set of examples. The strategy has been tested in experiments carried out using synthetic and real hyperspectral images, and it has been compared to state-of-the-art segmentation approaches over benchmark images in the area of remote sensing hyperspectral imaging.Ministerio de Economía y competitividad; TIN2015-63646-C5-1-RMinisterio de Economía y competitividad; RTI2018-101114-B-I00Xunta de Galicia: ED431C 2017/1

Report quality of generalized linear mixed models in psychology: A systematic review

Generalized linear mixed models (GLMMs) estimate fixed and random effects and are especially useful when the dependent variable is binary, ordinal, count or quantitative but not normally distributed. They are also useful when the dependent variable involves repeated measures, since GLMMs can model autocorrelation. This study aimed to determine how and how often GLMMs are used in psychology and to summarize how the information about them is presented in published articles. Our focus in this respect was mainly on frequentist models. In order to review studies applying GLMMs in psychology we searched the Web of Science for articles published over the period 2014-2018. A total of 316 empirical articles were selected for trend study from 2014 to 2018. We then conducted a systematic review of 118 GLMM analyses from 80 empirical articles indexed in Journal Citation Reports during 2018 in order to evaluate report quality. Results showed that the use of GLMMs increased over time and that 86.4% of articles were published in first- or second-quartile journals. Although GLMMs have, in recent years, been increasingly used in psychology, most of the important information about them was not stated in the majority of articles. Report quality needs to be improved in line with current recommendations for the use of GLMMs

Ansiedad Futura en Adultos Jóvenes Españoles : Propiedades Psicométricas de la Dark Future Scale

Background/Objective:The Dark Future Scale (DFS) is a selfreport instrument which assesses the tendency to think about the future with anxiety, fear, and uncertainty. Although it has been applied in different populations, instrumental studies are scarce, and there is no validated Spanish version. The aim was therefore to develop a Spanish version of the scale (DFS-S) and to analyze its psychometric properties in a sample of young adults. Method:Participants were 1,019 individuals aged from 18 to 24 years. They completed the DFS-S and the IPIP-BFM-20. Validity evidence based on the internal structure, including measurement invariance across gender, as well as on relationships with personality traits was obtained. Reliability and gender differences in DFS-S scores were also examined. Results:Results supported a single-factor structure, χ2(5) = 10.79, CFI = .999, RMSEA = .034, SRMR = .016, that was invariant across gender. Reliability of test scores was satisfactory (ω= .92). In the correlation analysis, future anxiety showed a strong positive correlation with neuroticism (.42) and a moderate negative correlation with extraversion (-.25). Females scored higher than males on future anxiety. Conclusions:The DFS-S has sat-isfactory psychometric properties and it is an adequate tool for measuring future anxiety among young adults.Antecedentes/Objetivo: La Dark Future Scale (DFS) evalúa la tendencia a pensar en el futuro con ansiedad, miedo e incertidumbre. Aunque ha sido usada en diferentes poblaciones, los estudios instrumentales son es-casos y no hay una versión adaptada al español. El objetivo del estudio fue adaptarla al español (DFS-S) y analizar sus propiedades psicométricas en una muestra de adultos jóvenes. Método: Participaron 1.019 jóvenes entre 18 y 24 años. Completaron la DFS-S y el IPIP-BFM-20. Se analizan evidencias de validez basadas en la estructura interna, incluyendo la invarianza de medida según el género, y basadas en las relaciones con rasgos de personalidad, así como análisis de la fiabilidad y de las diferencias de género. Resultados: Los resultados apoyaron una estructura de un solo factor, χ2(5) = 10.79, CFI = .999, RMSEA = .034, SRMR = .016, con invarianza respecto al género, y con coeficiente de fiabilidad satisfactorio (ω= .92). Se encontró correlación positiva fuerte entre ansiedad futura y neuroticismo (.42) y una correlación negativa moderada con extraversión (-.25). Las puntuaciones en ansiedad futura fueron mayores en las mujeres. Conclusiones: Los resultados muestran propiedades psicométricas satisfactorias de la DFS-S, siendo un instrumento adecuado para medir la ansiedad futura en adultos jóvenes

Lignin particles for multifunctional membranes, antioxidative microfiltration, patterning and 3D structuring

This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Applied Materials & Interfaces, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acsami.9b16931We introduce a new type of particle-based membrane based on the combination of lignin particles (LPs) and cellulose nanofibrils (CNF), the latter of which are introduced in small volume fractions to act as networking and adhesive agents. The synergies that are inherent to lignin and cellulose in plants are re-engineered to render materials with low surface energy (contact angle measurements) and can be rendered water-resistant with the aid of wet-strength agents (WSAs). Importantly, they are most suitable for antioxidative separation (ABTS•+ radical inhibition): membranes with uniform porous structures (air permeability and capillary flow porosimetry) allow effluent oxidation at 95 mL/cm2, demonstrating, for the first time, the use of unmodified lignin particles in flexible membranes for active microfiltration. Moreover, the membranes are found to be nonfouling (protein adhesion and activity rate). The inherent properties of lignin, including UV radiation blocking capacity (UV transmittance analysis) and reduced surface energy, are further exploited in the development of tailorable and self-standing architectures that are almost entirely comprised of nonbonding LP (solids content as high as 92 w/w%). Despite such composition, the materials develop high toughness (oscillatory dynamic mechanical analysis), owing to the addition of minor amounts of CNF. Multifunctional materials based on thin films (casting), 3D structures (molding), and patterned geometries (extrusion deposition) are developed as a demonstration of the potential use of lignin particles as precursors of new material generation. Remarkably, our observations hold for spherical LPs since a much poorer performance was observed after using amorphous powder, indicating the role of size and shape in related applicationsPostprint (author's final draft

Emotional processing in healthy ageing, mild cognitive impairment, and alzheimer’s disease

Emotional processing, particularly facial expression recognition, is essential for social cognition, and dysfunction may be associated with poor cognitive health. In pathological ageing con-ditions, such as mild cognitive impairment (MCI) and Alzheimer’s disease (AD), in which cognitive impairments are present, disturbed emotional processing and difficulty with social interactions have been documented. However, it is unclear how pathological ageing affects emotional processing and human social behaviour. The aim of this study is to provide insight into how emotional processing is affected in MCI and AD and whether this capacity can constitute a differentiating factor allowing the preclinical diagnosis of both diseases. For this purpose, an ecological emotional battery adapted from five subsets of the Florida Affect Battery was used. Given that emotion may not be separated from cognition, the affect battery was divided into subtests according to cognitive demand, resulting in three blocks. Our results showed that individuals with MCI or AD had poorer performance on the emotional processing tasks, although with different patterns, than that of controls. Cognitive demand may be responsible for the execution patterns of different emotional processing tests. Tasks with moderate cognitive demand are the most sensitive for discriminating between two cognitive impairment entities. In summary, emotional processing tasks may aid in characterising the neurocog-nitive deficits in MCI or AD. Additionally, identifying these deficits may be useful for developing interventions that specifically target these emotional processing problems.This study was supported by FEDER/the Spanish Ministry of Economy and Competitiveness (MINECO, Agencia Estatal de Investigacioón) FEDER, UE/AEI PSI2017-83408-P to C.P. and FEDER, UE/AEI PSI2016-78737-P to M.J.B

Combined flow cytometry and high-throughput image analysis for the study of essential genes in Caenorhabditis elegans

Background: Advances in automated image-based microscopy platforms coupled with high-throughput liquid workflows have facilitated the design of large-scale screens utilising multicellular model organisms such as Caenorhabditis elegans to identify genetic interactions, therapeutic drugs or disease modifiers. However, the analysis of essential genes has lagged behind because lethal or sterile mutations pose a bottleneck for high-throughput approaches, and a systematic way to analyse genetic interactions of essential genes in multicellular organisms has been lacking. Results: In C. elegans, non-conditional lethal mutations can be maintained in heterozygosity using chromosome balancers, commonly expressing green fluorescent protein (GFP) in the pharynx. However, gene expression or function is typically monitored by the use of fluorescent reporters marked with the same fluorophore, presenting a challenge to sort worm populations of interest, particularly at early larval stages. Here, we develop a sorting strategy capable of selecting homozygous mutants carrying a GFP stress reporter from GFP-balanced animals at the second larval stage. Because sorting is not completely error-free, we develop an automated high-throughput image analysis protocol that identifies and discards animals carrying the chromosome balancer. We demonstrate the experimental usefulness of combining sorting of homozygous lethal mutants and automated image analysis in a functional genomic RNA interference (RNAi) screen for genes that genetically interact with mitochondrial prohibitin (PHB). Lack of PHB results in embryonic lethality, while homozygous PHB deletion mutants develop into sterile adults due to maternal contribution and strongly induce the mitochondrial unfolded protein response (UPR mt ). In a chromosome-wide RNAi screen for C. elegans genes having human orthologues, we uncover both known and new PHB genetic interactors affecting the UPR mt and growth. Conclusions: The method presented here allows the study of balanced lethal mutations in a high-throughput manner. It can be easily adapted depending on the user's requirements and should serve as a useful resource for the C. elegans community for probing new biological aspects of essential nematode genes as well as the generation of more comprehensive genetic networks.European Research Council ERC-2011-StG-281691Ministerio de Economía y Competitividad BFU2012–3550

Downy mildew of sweet basil (Ocimum basilicum) caused by Peronospora sp. in Argentina

In the green belt surrounding Buenos Aires and La Plata cities, Argentina, sweet basil (Ocimum basilicum) is grown commercially under greenhouse mainly for fresh consumption. In February 2008, plants showing typical symptoms of downy mildew were found in greenhouses in La Plata. The disease was widespread in the cropped area with 100% prevalence. Infection resulted in chlorotic leaves with a greyish to dark brown fungal-like growth on the lower surfaces. A sample was deposited in the local herbarium (KUS-F23241). Conidiophores were subhyaline, 230­ 460 X 7-11 pm, straight, monopodially branched, in 4-6 orders, and emergent from stomata. Ultimate branchlets were mostly in pairs, slightly curved, 10-25 (-30) pm long and had subtruncate tips. Conidia were broadly ellipsoidal to subglobose, greyish brown, and measured 24*3- 32-5 X 22-5-26-5 pm (length/width ratio = 1-06-1-23). This pathogen is unequivocally in the genus Peronospora, and well concordant with characters ofthe unnamedPeronospora speciesreported in basil (Belbahri et al., 2005).Facultad de Ciencias Agrarias y Forestale

The Phubbing Scale (PS-8) in the Portuguese population: psychometric properties

Phubbing is defined as ignoring other individuals by using a mobile phone during a face-to-face conversation. The Phubbing Scale (PS) was developed to assess this practice. In this study, we analyze the psychometric properties of the 8-item version of the PS (PS-8) in the Portuguese population, providing validity evidence based on internal structure and on relationships with other variables, and examining item properties, reliability, and measurement invariance across gender. Participants were 391 Portuguese adults (132 men, 259 women) who completed a battery of questionnaires. Confirmatory factor analysis yielded satisfactory goodness-of-fit indices for the two-factor structure (communication disturbance and phone obsession), which was invariant across gender. Item homogeneity and reliability of factor scores (McDonald’s omega) were satisfactory. Validity evidence based on relationships with other variables was provided by positive associations with time spent on the Internet on weekdays and at the weekend, time spent on social networking sites, number of social networks used, Internet addiction, problematic mobile phone use, Facebook intrusion, fear of missing out, and depression. These associations show the addictive component of phubbing and its relationship with mental health. The PS-8 is a short and easy-to-administer scale with adequate psychometric properties for measuring phubbing in the Portuguese population.info:eu-repo/semantics/publishedVersio