Selecting the best non-invasive matrix to measure mercury exposure in human biomonitoring surveys.

Exposure to mercury, even at low doses, can affect human health, well-being and life quality at a broad scale. Human biomonitoring is the most straightforward approach to measure and quantify mercury exposure in humans. The objective of the present study is to compare and discuss the relationships between Hg levels in the most used matrices, hair, urine and blood, with the aim to ascertain to what extent mercury exposure and internal mercury levels could be predicted by monitoring non-invasive matrices. The study population (n = 527) is a subsample from Spanish BIOAMBIENT. ES study (18-65 y, both sexes), with data of Hg levels in blood, hair, and urine from the same individuals. We found strong inter-matrix Spearman correlations between blood and hair mercury (r2 = 0.84), while the correlations for urine and blood mercury (r2=0.64) and urine and hair mercury (r2=0.65) were weaker. The geometric mean of the ratios between matrices were (GM, 95%CI): Hair/Blood 280 (271-290), Urine/Blood 0.174 (0.163-0.186) and Hair/Urine 2070 (1953-2194) and Urine/Blood 0.135 (0.128-0.144) for urine corrected by creatinine. High individual variation was observed particularly in those ratios involving urine. Considering the wide range of values observed in the ratios, we do not recommend applying them at individual level. The predictive models indicate that hair Hg was a more accurate predictor than urine. The inclusion of urine values did not increase the predictive accuracy, so, we recommend a cautious interpretation of urine mercury levels. Our study presents clear evidence that in a population highly exposed to food-borne mercury, a large portion of urinary mercury primarily emanates from methylmercury demethylation. We conclude that urine, as a non-invasive matrix, can be used as a reliable qualitative biomarker for Hg exposure when hair measurements not are available. For quantitative individual assessments, still blood measurements are to be preferred.

De novo small deletion affecting transcription start site of short isoform of AUTS2 gene in a patient with syndromic neurodevelopmental defects.

Disruption of the autism susceptibility candidate 2 (AUTS2) gene through genomic rearrangements, copy number variations (CNVs), and intragenic deletions and mutations, has been recurrently involved in syndromic forms of developmental delay and intellectual disability, known as AUTS2 syndrome. The AUTS2 gene plays an important role in regulation of neuronal migration, and when altered, associates with a variable phenotype from severely to mildly affected patients. The more severe phenotypes significantly correlate with the presence of defects affecting the C-terminus part of the gene. This article reports a new patient with a syndromic neurodevelopmental disorder, who presents a deletion of 30 nucleotides in the exon 9 of the AUTS2 gene. Importantly, this deletion includes the transcription start site for the AUTS2 short transcript isoform, which has an important role in brain development. Gene expression analysis of AUTS2 full-length and short isoforms revealed that the deletion found in this patient causes a remarkable reduction in the expression level, not only of the short isoform, but also of the full AUTS2 transcripts. This report adds more evidence for the role of mutated AUTS2 short transcripts in the development of a severe phenotype in the AUTS2 syndrome.

Proficiency Testing of Metagenomics-Based Detection of Food-Borne Pathogens Using a Complex Artificial Sequencing Dataset.

Metagenomics-based high-throughput sequencing (HTS) enables comprehensive detection of all species comprised in a sample with a single assay and is becoming a standard method for outbreak investigation. However, unlike real-time PCR or serological assays, HTS datasets generated for pathogen detection do not easily provide yes/no answers. Rather, results of the taxonomic read assignment need to be assessed by trained personnel to gain information thereof. Proficiency tests are important instruments of validation, harmonization, and standardization. Within the European Union funded project COMPARE [COllaborative Management Platform for detection and Analyses of (Re-) emerging and foodborne outbreaks in Europe], we conducted a proficiency test to scrutinize the ability to assess diagnostic metagenomics data. An artificial dataset resembling shotgun sequencing of RNA from a sample of contaminated trout was provided to 12 participants with the request to provide a table with per-read taxonomic assignments at species level and a report with a summary and assessment of their findings, considering different categories like pathogen, background, or contaminations. Analysis of the read assignment tables showed that the software used reliably classified the reads taxonomically overall. However, usage of incomplete reference databases or inappropriate data pre-processing caused difficulties. From the combination of the participants' reports with their read assignments, we conclude that, although most species were detected, a number of important taxa were not or not correctly categorized. This implies that knowledge of and awareness for potentially dangerous species and contaminations need to be improved, hence, capacity building for the interpretation of diagnostic metagenomics datasets is necessary.

Alarming lack of knowledge about antithrombotic therapy among patients with atrial fibrillation / Terapia antitrombótica: alarmante falta de conhecimento em pacientes com fibrilação atrial

ABSTRACT Large population campaigns have been conducted in Brazil to improve knowledge about the signs and symptoms of stroke and the importance of time to care. Objective: Parallel to these important actions, we aimed to evaluate the lay knowledge of patients with atrial fibrillation, a well-recognized etiology of stroke, adequate treatment and management of which can prevent up to 30% of cerebrovascular events. Methods: We questioned 143 patients with atrial fibrillation about the risks associated with the disease. Results: Ninety-one percent were on anticoagulation treatment. Of the total, 63.6% reported having been informed about the risks and benefits of anticoagulants but only 46.9% were able to correctly mention one of these risks. Ischemic stroke was identified as a risk by only 25.9% and hemorrhagic stroke was not mentioned. A CHADS2 ≥ 2 was scored by 84.0% of the patients. Conclusions: Our study showed an alarming knowledge gap in patients with atrial fibrillation. Difficulty in adherence to treatment resulting from the failure of this communication is possibly one of the factors responsible for the high incidence and recurrence of stroke, and should not go unnoticed.

RESUMO Campanhas populacionais para melhorar o conhecimento sobre os sinais e sintomas do acidente vascular encefálico e a importância do tempo para o tratamento têm sido realizadas no nosso país, visando a melhoria da linha do atendimento. Objetivo: Paralelamente a estas relevantes ações, objetivamos avaliar o conhecimento leigo de pacientes portadores de fibrilação atrial, etiologia determinada e prevalente do acidente vascular encefálico, cujo tratamento e manejo adequado podem prevenir até 30% dos eventos cerebrovasculares. Métodos: Entrevistamos portadores de fibrilação atrial sobre os riscos associados à doença. Resultados: Noventa e um por cento estavam sob uso de anticoagulantes. Do total, 63,6% responderam terem sido informados sobre riscos e benefícios da terapia anticoagulante, mas apenas 46,9% souberam citar corretamente um desses riscos. Acidente vascular encefálico isquêmico foi associado ao risco por apenas 25,9% e acidente vascular encefálico hemorrágico não foi mencionado. CHADS2 ≥ 2 foi pontuado por 84,0% dos pacientes. Conclusões: Nosso estudo demonstra uma alarmante falha no conhecimento do risco de acidente vascular encefálico nos portadores de fibrilação atrial. Dificuldade na aderência ao tratamento resultante da falha dessa comunicação é fator relevante na incidência e recorrência do acidente vascular encefálico e não deve ser negligenciado.

Alarming lack of knowledge about antithrombotic therapy among patients with atrial fibrillation.

OBJECTIVE: Large population campaigns have been conducted in Brazil to improve knowledge about the signs and symptoms of stroke and the importance of time to care. Parallel to these important actions, we aimed to evaluate the lay knowledge of patients with atrial fibrillation, a well-recognized etiology of stroke, adequate treatment and management of which can prevent up to 30% of cerebrovascular events. METHODS: We questioned 143 patients with atrial fibrillation about the risks associated with the disease. RESULTS: Ninety-one percent were on anticoagulation treatment. Of the total, 63.6% reported having been informed about the risks and benefits of anticoagulants but only 46.9% were able to correctly mention one of these risks. Ischemic stroke was identified as a risk by only 25.9% and hemorrhagic stroke was not mentioned. A CHADS2 ≥ 2 was scored by 84.0% of the patients. CONCLUSIONS: Our study showed an alarming knowledge gap in patients with atrial fibrillation. Difficulty in adherence to treatment resulting from the failure of this communication is possibly one of the factors responsible for the high incidence and recurrence of stroke, and should not go unnoticed.

Estimating the position and orientation of a mobile robot with respect to a trajectory using omnidirectional imaging and global appearance.

Along the past years, mobile robots have proliferated both in domestic and in industrial environments to solve some tasks such as cleaning, assistance, or material transportation. One of their advantages is the ability to operate in wide areas without the necessity of introducing changes into the existing infrastructure. Thanks to the sensors they may be equipped with and their processing systems, mobile robots constitute a versatile alternative to solve a wide range of applications. When designing the control system of a mobile robot so that it carries out a task autonomously in an unknown environment, it is expected to take decisions about its localization in the environment and about the trajectory that it has to follow in order to arrive to the target points. More concisely, the robot has to find a relatively good solution to two crucial problems: building a model of the environment, and estimating the position of the robot within this model. In this work, we propose a framework to solve these problems using only visual information. The mobile robot is equipped with a catadioptric vision sensor that provides omnidirectional images from the environment. First, the robot goes along the trajectories to include in the model and uses the visual information captured to build this model. After that, the robot is able to estimate its position and orientation with respect to the trajectory. Among the possible approaches to solve these problems, global appearance techniques are used in this work. They have emerged recently as a robust and efficient alternative compared to landmark extraction techniques. A global description method based on Radon Transform is used to design mapping and localization algorithms and a set of images captured by a mobile robot in a real environment, under realistic operation conditions, is used to test the performance of these algorithms.

Consenso brasileiro multi-institucional de pacientes sobre medicamentos biossimilares / Brazilian patients multi-institutional consensus on biosimilar drugs

Objetivo: O presente trabalho tem como objetivo emitir um consenso de diversas associações de pacientes sobre os produtos biossimilares. Métodos: O consenso foi produzido em reunião presencial com 15 representantes de 11 diferentes associações de pacientes. Previamente ao encontro, realizou- -se exercício Delphi contemplando 12 diferentes tópicos referentes a medicamentos biossimilares, sendo os temas de menor concordância selecionados para aulas informativas. Posteriormente, os participantes reuniram-se para discussão dos temas e elaboração do consenso. Resultados: O consenso concentrou-se em torno de oito temas gerais: nomenclatura, farmacovigilância, mercado nacional, RDC nº 55/2010, extrapolação de indicações, substituição automática, intercambialidade e estudos clínicos. Conclusões: Os medicamentos biossimilares representam avanço referente ao acesso à terapia biológica devido, especialmente, à competitividade econômica. Todavia, sua utilização deve ser respaldada por exercícios clínicos apropriados ­ exercício de biossimilaridade ­, respeitando a autonomia do prescritor e sempre apoiado em metodologias apropriadas de farmacovigilância.

Objective: This paper aims to publish a consensus from diverse patient associations on biossimilar drugs. Methods: The consensus was produced in a live meeting that gathered 15 representatives from 11 different patient associations. Previously to the meeting a Delphi exercise was elaborated contemplating 12 different subjects regarding biosimilar drugs. The subjects with smaller agreement were chosen to be discussed in informative lectures. Posteriorly, the attendants discussed the subjects and elaborated the consensus. Results: The consensus focused on eight different general subjects: nomenclature, pharmacovigilance, national Market, RDC nº 55/2010, extrapolation of controindications, automatic substitution, interchangeability, clinical trials. Conclusions: Biosimilar drugs represent progress regarding the access to biologic treatment, especially due to its economic competitiveness. However, its use must be supported by proper clinical trials ­ biosimilarity exercise ­ respecting the prescritor autonomy and counting on solid pharmacovigilance methods.

Improved Omnidirectional Odometry for a View-Based Mapping Approach.

This work presents an improved visual odometry using omnidirectional images. The main purpose is to generate a reliable prior input which enhances the SLAM (Simultaneous Localization and Mapping) estimation tasks within the framework of navigation in mobile robotics, in detriment of the internal odometry data. Generally, standard SLAM approaches extensively use data such as the main prior input to localize the robot. They also tend to consider sensory data acquired with GPSs, lasers or digital cameras, as the more commonly acknowledged to re-estimate the solution. Nonetheless, the modeling of the main prior is crucial, and sometimes especially challenging when it comes to non-systematic terms, such as those associated with the internal odometer, which ultimately turn to be considerably injurious and compromise the convergence of the system. This omnidirectional odometry relies on an adaptive feature point matching through the propagation of the current uncertainty of the system. Ultimately, it is fused as the main prior input in an EKF (Extended Kalman Filter) view-based SLAM system, together with the adaption of the epipolar constraint to the omnidirectional geometry. Several improvements have been added to the initial visual odometry proposal so as to produce better performance. We present real data experiments to test the validity of the proposal and to demonstrate its benefits, in contrast to the internal odometry. Furthermore, SLAM results are included to assess its robustness and accuracy when using the proposed prior omnidirectional odometry.

Conserved differences in protein sequence determine the human pathogenicity of Ebolaviruses.

Reston viruses are the only Ebolaviruses that are not pathogenic in humans. We analyzed 196 Ebolavirus genomes and identified specificity determining positions (SDPs) in all nine Ebolavirus proteins that distinguish Reston viruses from the four human pathogenic Ebolaviruses. A subset of these SDPs will explain the differences in human pathogenicity between Reston and the other four ebolavirus species. Structural analysis was performed to identify those SDPs that are likely to have a functional effect. This analysis revealed novel functional insights in particular for Ebolavirus proteins VP40 and VP24. The VP40 SDP P85T interferes with VP40 function by altering octamer formation. The VP40 SDP Q245P affects the structure and hydrophobic core of the protein and consequently protein function. Three VP24 SDPs (T131S, M136L, Q139R) are likely to impair VP24 binding to human karyopherin alpha5 (KPNA5) and therefore inhibition of interferon signaling. Since VP24 is critical for Ebolavirus adaptation to novel hosts, and only a few SDPs distinguish Reston virus VP24 from VP24 of other Ebolaviruses, human pathogenic Reston viruses may emerge. This is of concern since Reston viruses circulate in domestic pigs and can infect humans, possibly via airborne transmission.

Sincell: an R/Bioconductor package for statistical assessment of cell-state hierarchies from single-cell RNA-seq.

UNLABELLED: Cell differentiation processes are achieved through a continuum of hierarchical intermediate cell states that might be captured by single-cell RNA seq. Existing computational approaches for the assessment of cell-state hierarchies from single-cell data can be formalized under a general framework composed of (i) a metric to assess cell-to-cell similarities (with or without a dimensionality reduction step) and (ii) a graph-building algorithm (optionally making use of a cell clustering step). The Sincell R package implements a methodological toolbox allowing flexible workflows under such a framework. Furthermore, Sincell contributes new algorithms to provide cell-state hierarchies with statistical support while accounting for stochastic factors in single-cell RNA seq. Graphical representations and functional association tests are provided to interpret hierarchies. The functionalities of Sincell are illustrated in a real case study, which demonstrates its ability to discriminate noisy from stable cell-state hierarchies. AVAILABILITY AND IMPLEMENTATION: Sincell is an open-source R/Bioconductor package available at http://bioconductor.org/packages/sincell. A detailed manual and a vignette are provided with the package. CONTACT: antonio.rausell@isb-sib.ch SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Searching dynamic agents with a team of mobile robots.

This paper presents a new algorithm that allows a team of robots to cooperatively search for a set of moving targets. An estimation of the areas of the environment that are more likely to hold a target agent is obtained using a grid-based Bayesian filter. The robot sensor readings and the maximum speed of the moving targets are used in order to update the grid. This representation is used in a search algorithm that commands the robots to those areas that are more likely to present target agents. This algorithm splits the environment in a tree of connected regions using dynamic programming. This tree is used in order to decide the destination for each robot in a coordinated manner. The algorithm has been successfully tested in known and unknown environments showing the validity of the approach.

Estimation of visual maps with a robot network equipped with vision sensors.

In this paper we present an approach to the Simultaneous Localization and Mapping (SLAM) problem using a team of autonomous vehicles equipped with vision sensors. The SLAM problem considers the case in which a mobile robot is equipped with a particular sensor, moves along the environment, obtains measurements with its sensors and uses them to construct a model of the space where it evolves. In this paper we focus on the case where several robots, each equipped with its own sensor, are distributed in a network and view the space from different vantage points. In particular, each robot is equipped with a stereo camera that allow the robots to extract visual landmarks and obtain relative measurements to them. We propose an algorithm that uses the measurements obtained by the robots to build a single accurate map of the environment. The map is represented by the three-dimensional position of the visual landmarks. In addition, we consider that each landmark is accompanied by a visual descriptor that encodes its visual appearance. The solution is based on a Rao-Blackwellized particle filter that estimates the paths of the robots and the position of the visual landmarks. The validity of our proposal is demonstrated by means of experiments with a team of real robots in a office-like indoor environment.