Multi-center MRI prediction models: Predicting sex and illness course in first episode psychosis patients.

Structural Magnetic Resonance Imaging (MRI) studies have attempted to use brain measures obtained at the first-episode of psychosis to predict subsequent outcome, with inconsistent results. Thus, there is a real need to validate the utility of brain measures in the prediction of outcome using large datasets, from independent samples, obtained with different protocols and from different MRI scanners. This study had three main aims: 1) to investigate whether structural MRI data from multiple centers can be combined to create a machine-learning model able to predict a strong biological variable like sex; 2) to replicate our previous finding that an MRI scan obtained at first episode significantly predicts subsequent illness course in other independent datasets; and finally, 3) to test whether these datasets can be combined to generate multicenter models with better accuracy in the prediction of illness course. The multi-center sample included brain structural MRI scans from 256 males and 133 females patients with first episode psychosis, acquired in five centers: University Medical Center Utrecht (The Netherlands) (n=67); Institute of Psychiatry, Psychology and Neuroscience, London (United Kingdom) (n=97); University of São Paulo (Brazil) (n=64); University of Cantabria, Santander (Spain) (n=107); and University of Melbourne (Australia) (n=54). All images were acquired on 1.5-Tesla scanners and all centers provided information on illness course during a follow-up period ranging 3 to 7years. We only included in the analyses of outcome prediction patients for whom illness course was categorized as either "continuous" (n=94) or "remitting" (n=118). Using structural brain scans from all centers, sex was predicted with significant accuracy (89%; p<0.001). In the single- or multi-center models, illness course could not be predicted with significant accuracy. However, when reducing heterogeneity by restricting the analyses to male patients only, classification accuracy improved in some samples. This study provides proof of concept that combining multi-center MRI data to create a well performing classification model is possible. However, to create complex multi-center models that perform accurately, each center should contribute a sample either large or homogeneous enough to first allow accurate classification within the single-center

CCDC61/VFL3 Is a Paralog of SAS6 and Promotes Ciliary Functions.

Centrioles are cylindrical assemblies whose peripheral microtubule array displays a 9-fold rotational symmetry that is established by the scaffolding protein SAS6. Centriole symmetry can be broken by centriole-associated structures, such as the striated fibers in Chlamydomonas that are important for ciliary function. The conserved protein CCDC61/VFL3 is involved in this process, but its exact role is unclear. Here, we show that CCDC61 is a paralog of SAS6. Crystal structures of CCDC61 demonstrate that it contains two homodimerization interfaces that are similar to those found in SAS6, but result in the formation of linear filaments rather than rings. Furthermore, we show that CCDC61 binds microtubules and that residues involved in CCDC61 microtubule binding are important for ciliary function in Chlamydomonas. Together, our findings suggest that CCDC61 and SAS6 functionally diverged from a common ancestor while retaining the ability to scaffold the assembly of basal body-associated structures or centrioles, respectively

Physical Links: Defining and detecting inter-chain entanglement

Fluctuating filaments, from densely-packed biopolymers to defect lines in structured fluids, are prone to become interlaced and form intricate architectures. Understanding the ensuing mechanical and relaxation properties depends critically on being able to capture such entanglement in quantitative terms. So far, this has been an elusive challenge. Here we introduce the first general characterization of non-ephemeral forms of entanglement in linear curves by introducing novel descriptors that extend topological measures of linking from close to open curves. We thus establish the concept of physical links. This general method is applied to diverse contexts: equilibrated ring polymers, mechanically-stretched links and concentrated solutions of linear chains. The abundance, complexity and space distribution of their physical links gives access to a whole new layer of understanding of such systems and open new perspectives for others, such as reconnection events and topological simplification in dissipative fields and defect lines

Actualitzacions en terapèutica farmacològica: avenços 2015; novetats que canvien la pràctica clínica

Terapèutica farmacològica; Avenços; Pràctica clínicaTerapeutica farmacológica; Avances; Práctica clínicaPharmacological therapy; Advances; Clinical practiceEste informe identifica las cuestiones relacionadas con la terapéutica farmacológica consideradas mas relevantes para la práctica clínica, considerando aspectos muy diversos como son las nuevas estrategias terapéuticas, prácticas relacionadas con la sobreutilización de medicamentos, cuestiones sobre la continuidad, el avance y la suspensión de los tratamientos, los nuevos medicamentos y los pros y contras de alternativas terapéuticas que se han ido planteando específicamente a lo largo del año 2014.Aquest informe identifica les qüestions relacionades amb la terapèutica farmacològica considerades més rellevants per a la pràctica clínica, considerant aspectes ben diversos com ara les noves estratègies terapèutiques, pràctiques relacionades amb la sobreutilització de medicaments, qüestions sobre la continuïtat, l‟avançament i la suspensió dels tractaments, els nous medicaments, i els pros i contres d‟alternatives terapèutiques que s‟han anant plantejat específicament al llarg de l'any 201

Amino Acid Similarity Accounts for T Cell Cross-Reactivity and for “Holes” in the T Cell Repertoire

Background: Cytotoxic T cell (CTL) cross-reactivity is believed to play a pivotal role in generating immune responses but the extent and mechanisms of CTL cross-reactivity remain largely unknown. Several studies suggest that CTL clones can recognize highly diverse peptides, some sharing no obvious sequence identity. The emerging realization in the field is that T cell receptors (TcR) recognize multiple distinct ligands. Principal Findings: First, we analyzed peptide scans of the HIV epitope SLFNTVATL (SFL9) and found that TCR specificity is position dependent and that biochemically similar amino acid substitutions do not drastically affect recognition. Inspired by this, we developed a general model of TCR peptide recognition using amino acid similarity matrices and found that such a model was able to predict the cross-reactivity of a diverse set of CTL epitopes. With this model, we were able to demonstrate that seemingly distinct T cell epitopes, i.e., ones with low sequence identity, are in fact more biochemically similar than expected. Additionally, an analysis of HIV immunogenicity data with our model showed that CTLs have the tendency to respond mostly to peptides that do not resemble self-antigens. Conclusions: T cell cross-reactivity can thus, to an extent greater than earlier appreciated, be explained by amino acid similarity. The results presented in this paper will help resolving some of the long-lasting discussions in the field of T cel

Potential geographic distribution of Hantavirus reservoirs in Brazil

Hantavirus cardiopulmonary syndrome is an emerging zoonosis in Brazil. Human infections occur via inhalation of aerosolized viral particles from excreta of infected wild rodents. Necromys lasiurus and Oligoryzomys nigripes appear to be the main reservoirs of hantavirus in the Atlantic Forest and Cerrado biomes. We estimated and compared ecological niches of the two rodent species, and analyzed environmental factors influencing their occurrence, to understand the geography of hantavirus transmission. N. lasiurus showed a wide potential distribution in Brazil, in the Cerrado, Caatinga, and Atlantic Forest biomes. Highest climate suitability for O. nigripes was observed along the Brazilian Atlantic coast. Maximum temperature in the warmest months and annual precipitation were the variables that most influence the distributions of N. lasiurus and O. nigripes, respectively. Models based on occurrences of infected rodents estimated a broader area of risk for hantavirus transmission in southeastern and southern Brazil, coinciding with the distribution of human cases of hantavirus cardiopulmonary syndrome. We found no demonstrable environmental differences among occurrence sites for the rodents and for human cases of hantavirus. However, areas of northern and northeastern Brazil are also apparently suitable for the two species, without broad coincidence with human cases. Modeling of niches and distributions of rodent reservoirs indicates potential for transmission of hantavirus across virtually all of Brazil outside the Amazon Basin

Push-out bond strength of fiber posts to root dentin using glass ionomer and resin modified glass ionomer cements

OBJECTIVE: The purpose of this study was to assess the push-out bond strength of glass fiber posts to root dentin after cementation with glass ionomer (GICs) and resinmodified glass ionomer cements (RMGICs). MATERIAL AND METHODS: Fifty human maxillary canines were transversally sectioned at 15 mm from the apex. Canals were prepared with a step back technique until the application of a #55 K-file and filled. Post spaces were prepared and specimens were divided into five groups according to the cement used for post cementation: Luting & Lining Cement; Fuji II LC Improved; RelyX Luting; Ketac Cem; and Ionoseal. After cementation of the glass fiber posts, all roots were stored at 100% humidity until testing. For push-out test, 1-mm thick slices were produced. The push-out test was performed in a universal testing machine at a crosshead speed of 0.5 mm/minute and the values (MPa) were analyzed by Kolmogorov-Smirnov and Levene's tests and by two-way ANOVA and Tukey's post hoc test at a significance level of 5%. RESULTS: Fiber posts cemented using Luting & Lining Cement, Fuji II LC Improved, and Ketac Cem presented the highest bond strength to root dentin, followed by RelyX Luting. Ionoseal presented the lowest bond strength values (P>0.05). The post level did not influence the bond strength of fiber posts to root dentin (P=0.148). The major cause of failure was cohesive at the cement for all GICs and RMGICs. CONCLUSIONS: Except for Ionoseal, all cements provided satisfactory bond strength values

Rainwater harvesting systems reduce detergent use

Unidad de excelencia María de Maeztu MdM-2015-0552Purpose: Due to population growth, urban water demand is expected to increase significantly, as well as the environmental and economic costs required to supply it. Rainwater harvesting (RWH) systems can play a key role in helping cities meet part of their water demand as an alternative to conventional water abstraction and treatment. This paper presents an environmental and economic analysis of RWH systems providing households with water for laundry purposes in a life cycle thinking perspective. Conclusions: LCA and LCC present better results for high-density scenarios. Overall, avoided environmental and economic impacts from detergent reduction clearly surpass environmental impacts (in all categories except terrestrial acidification) and economic cost of the RWHsystem in most cases (except two scenarios). Another important finding is that 80%of the savings are achieved by minimizing detergent and fabric softener by using soft rainwater; and the remaining 20% comes from replacing the use of tap water