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In educational environments, technological adoption in the last 10 years has enabled a data-driven and decisionmaking paradigm in organizations. The integration of cloud services in schools and universities is a positive shift in the field of learning, but it also presents threats to all academic roles that need to be discussed in terms of protection, privacy, and confidentiality. Cloud storage brings the ubiquity of data to this technical transition and a delusive opportunity for cost savings. In many cases, this suggests that certain actors, beyond the control of schools and colleges, collect, handle and treat educational data on private servers and data centers. This privatization enables the manipulation of stored records, leaks, and unauthorized access. In this article, we expose the possibilities that open from the viewpoint of local technology adoption. We seek to reduce or even totally solve the detrimental effects of using cloud-based instructional and analytical technology, mixing or only using local technology. Technological methods that conform to this alternate viewpoint and new lines of study are also being suggested and created. The research that has given rise to these results has been carried out through funds from the Secretariat of Universities and Research of the Department of Business and Knowledge of the Generalitat de Catalunya and Ramon Llull University, with the project 2020-URLProj-058. Peer Reviewed Objectius de Desenvolupament Sostenible::16 - Pau, Justícia i Institucions Sòlides::16.6 - Crear unes institucions eficaces, responsables i transparents a tots els nivells Objectius de Desenvolupament Sostenible::16 - Pau, Justícia i Institucions Sòlides::16.b - Promoure i aplicar lleis i polítiques no discriminatòries en favor del desenvolupament sostenible Objectius de Desenvolupament Sostenible::16 - Pau, Justícia i Institucions Sòlides

The endoscopic transorbital approach (eTOA) is a new mini-invasive procedure used to explore different areas of the skull base. Authors propose an extradural anterior clinoidectomy (AC) through this corridor, defining the anatomical landmarks of the anterior clinoid process (ACP) projection onto the posterior orbit wall and the technical feasibility of this approach. We describe the exposure of the opticocarotid region and the surgical freedom and the angles of attack obtained with this novel approach. Five cadaver heads underwent an eTOA at the Laboratory of Surgical Neuroanatomy of the University of Barcelona. A step-by-step description of the extradural endoscopic transorbital clinoidectomy was provided. A volumetric analysis of the morphometrics characteristics of the sphenoid wings was evaluated before and after dissection using CT scans. Pterional approach was performed to ascertain ACP removal. In all the specimens, it was possible to resect the ACP endo-orbitally aiming an optimal optic canal (OC) unroofing. The surface of the triangle corresponding to the ACP projection onto the posterior orbit wall was 0.42 ± 0.20 cm2. The drilled area to perform the extradural clinoidectomy via eTOA was 3.11 ± 2.27 cm2, and the volume of bone removal corresponding to the greater sphenoid wing (GSW) and lesser sphenoid wing (LSW) was 2.55 ± 1.41 and 0.26 ± 0.18 cm3 respectively. The area of surgical freedom provided by the eTOA was (3.11 ± 2.27cm2), and the angles of attack were 21.39 ± 9.13° in the horizontal axel and 30.63 ± 18.51° in the vertical. The described extradural anterior clinoidectomy by eTOA uses specific landmarks to localize the ACP on the posterior orbit wall. Resection of the ACP is a technically feasible approach, achieving the main goals of any clinoidectomy.

Purpose: Immune dysregulation is described in multiple myeloma. While preclinical models suggest a role for altered T-cell immunity in disease progression, the contribution of immune dysfunction to clinical outcomes remains unclear. We aimed to characterize marrow-infiltrating T cells in newly diagnosed patients and explore associations with outcomes of first-line therapy. Experimental Design: We undertook detailed characterization of T cells from bone marrow (BM) samples, focusing on immune checkpoints and features of immune dysfunction, correlating with clinical features and progression-free survival. Results: We found that patients with multiple myeloma had greater abundance of BM regulatory T cells (Tregs) which, in turn, expressed higher levels of the activation marker CD25 compared with healthy donors. Patients with higher frequencies of Tregs had shorter PFS and a distinct Treg immune checkpoint profile (increased PD-1, LAG-3) compared with patients with lower frequencies of Tregs. Analysis of CD4 and CD8 effectors revealed that low CD4effector (CD4eff):Treg ratio and increased frequency of PD-1–expressing CD4eff cells were independent predictors of early relapse over and above conventional risk factors, such as genetic risk and depth of response. Ex vivo functional analysis and RNA sequencing revealed that CD4 and CD8 cells from patients with greater abundance of CD4effPD-1+ cells displayed transcriptional and secretory features of dysfunction. Conclusions: BM-infiltrating T-cell subsets, specifically Tregs and PD-1–expressing CD4 effectors, negatively influence clinical outcomes in newly diagnosed patients. Pending confirmation in larger cohorts and further mechanistic work, these immune parameters may inform new risk models, and present potential targets for immunotherapeutic strategies.

Palm oil has supplied more than 30% of vegetable oil consumption worldwide. Rising demand has pushed oil palm plantations to increase the yield. It is well known that genetic has played a significant role in phenotypic performance. Moreover, in recent years, genomic data has emerged tremendously. Unfortunately on the gene related to oil palm yield. Therefore, a preliminary study to classify and select oil palm candidate genes associated with characteristic by scanning existing genes in oil palm or other in-silico species were conducted. Based on Blast2Go results, 22 genes related to oil biosynthesis, two specifically related to fruit number and fruit weight were analysed. Furthermore, 19 candidate genes were able to amplify.

Integrative analysis of multi-omics data is a powerful approach for gaining functional insights into biological and medical processes. Conducting these multifaceted analyses on human samples is often complicated by the fact that the raw sequencing output is rarely available under open access. The Personal Genome Project UK (PGP-UK) is one of few resources that recruits its participants under open consent and makes the resulting multi-omics data freely and openly available. As part of this resource, we describe the PGP-UK multi-omics reference panel consisting of ten genomic, methylomic and transcriptomic data. Specifically, we outline the data processing, quality control and validation procedures which were implemented to ensure data integrity and exclude sample mix-ups. In addition, we provide a REST API to facilitate the download of the entire PGP-UK dataset. The data are also available from two cloud-based environments, providing platforms for free integrated analysis. In conclusion, the genotype-validated PGP-UK multi-omics human reference panel described here provides a valuable new open access resource for integrated analyses in support of personal and medical genomics., Measurement(s)DNA methylation profiling data • whole genome sequencing assay • bisulfite sequencing assay • transcription profiling assayTechnology Type(s)DNA methylation profiling assay • DNA sequencing • RNA sequencingFactor Type(s)age • sex • smoking statusSample Characteristic - OrganismHomo sapiens Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.9896405

Recent developments in attosecond technology led to tabletop X-ray spectroscopy in the soft X-ray range, thus uniting the element- and state-specificity of core-level x-ray absorption spectroscopy with the time resolution to follow electronic dynamics in real time. We describe recent work in attosecond technology and investigations into materials such as Si, SiO2, GaN, Al2O3, Ti, TiO2, enabled by the convergence of these two capabilities. We showcase the state-of-the-art on isolated attosecond soft x-ray pulses for x-ray absorption near edge spectroscopy (XANES) to observe the 3d-state dynamics of the semi-metal TiS2 with attosecond resolution at the Ti L-edge (460 eV). We describe how the element- and state-specificity at the transition metal L-edge of the quantum material allows to unambiguously identify how and where the optical field influences charge carriers. This precision elucidates that the Ti:3d conduction band states are efficiently photo-doped to a density of 1.9 x 10^21 cm^-3 and that the light-field induces coherent motion of intra-band carriers across 38% of the first Brillouin zone. Lastly, we describe the prospects with such unambiguous real-time observation of carrier dynamics in specific bonding or anti-bonding states and speculate that such capability will bring unprecedented opportunities towards an engineered approach for designer materials with pre-defined properties and efficiency. Examples are composites of semiconductors and insulators like Si, Ge, SiO2, GaN, BN, quantum materials like graphene, TMDCs, or high-Tc superconductors like NbN or LaBaCuO. Exiting are prospects to scrutinize canonical questions in multi-body physics such as whether the electrons or lattice trigger phase transitions., 5 figures

This study analyses the information and tools for citizen participation on the institutional websites of local bodies to improve participation in the management of local resources in a context following the introduction of Spain’s Transparency Law. The method is based on applying 14 indicators to analyse the institutional websites of 605 municipalities that have over 10,000 residents, located in 9 autonomous communities of the Spanish state. The main results show how the institutional information offered on the websites of the councils analysed does not follow journalistic criteria in terms of accountability, meaning that citizens’ decisions regarding their local governments cannot be based on precise, reliable information. In this regard, in this study we have confirmed that council websites publish very little information on the activity of the opposition or on the plenary sessions, debates and agreements, but do publish information on the activity of the government. Furthermore, they do not make use of web resources for citizen participation, which impedes the transparent, collaborative management of political processes between leaders and citizens. Nonetheless, the results show how political and technical managers are not averse to change if they have access to guidance and incentives to improve the management of information and participation on municipal websites.

The New Learning Context (NCA for its initials in Spanish, Nuevo Contexto de Aprendizaje) is the new pedagogical framework that is being designed and implemented at the La Salle Institutions since 2017. The main objective is to deploy the pedagogical design across all educational centers and stages. In the context of NCA, digital technology is another pillar in the educational structure, that is integrated into classrooms as both support and the means to develop learning competences. This integration of digital educational technology in schools and universities transforms learning contexts, but it also creates risks for all educational roles in terms of privacy and data security that must be addressed. In the last 9 years, technology adoption has been accompanied by a data-driven model of analysis and decision-making, as well as a migration to cloud computing. Cloud computing adds to this technological transformation the ubiquity of data, personal data, and metadata. This implies in many cases that third parties collect and process educational data from all the actors involved in the teaching-learning process on remote servers and data centers, outside the control of educational institutions. So this latest technology adoption unfortunately also facilitates leaks, misuse, and improper access to all data collected. In this paper, we propose seven principles as a fundamental framework for NCA, that we have called Local Educational Data Analytics (LEDA). Our aim is to solve or minimize the negative impact of the use of this educational technology, which is based on cloud computing and uses integrated data analysis processes. We also propose both technological solutions that comply with the framework and lines of research that will be incorporated into the NCA pilot tests during the academic year 20-21.

In recent years, there has been a significant increase in whole genome sequencing data of individual genomes produced by research projects as well as direct to consumer service providers. While many of these sources provide their users with an interpretation of the data, there is a lack of free, open tools for generating reports exploring the data in an easy to understand manner.GenomeChronicler was developed as part of the Personal Genome Project UK (PGP-UK) to address this need. PGP-UK provides genomic, transcriptomic, epigenomic and self-reported phenotypic data under an open-access model with full ethical approval. As a result, the reports generated by GenomeChronicler are intended for research purposes only and include information relating to potentially beneficial and potentially harmful variants, but without clinical curation.GenomeChronicler can be used with data from whole genome or whole exome sequencing, producing a genome report containing information on variant statistics, ancestry and known associated phenotypic traits. Example reports are available from the PGP-UK data page (personalgenomes.org.uk/data).The objective of this method is to leverage existing resources to find known phenotypes associated with the genotypes detected in each sample. The provided trait data is based primarily upon information available in SNPedia, but also collates data from ClinVar, GETevidence and gnomAD to provide additional details on potential health implications, presence of genotype in other PGP participants and population frequency of each genotype.The analysis can be run in a self-contained environment without requiring internet access, making it a good choice for cases where privacy is essential or desired: any third party project can embed GenomeChronicler within their off-line safe-haven environments. GenomeChronicler can be run for one sample at a time, or in parallel making use of the Nextflow workflow manager.The source code is available from GitHub (https://github.com/PGP-UK/GenomeChronicler), container recipes are available for Docker and Singularity, as well as a pre-built container from SingularityHub (https://singularity-hub.org/collections/3664) enabling easy deployment in a variety of settings. Users without access to computational resources to run GenomeChronicler can access the software from the Lifebit CloudOS platform (https://lifebit.ai/cloudos) enabling the production of reports and variant calls from raw sequencing data in a scalable fashion.

Percutaneous electrolysis is an emerging intervention proposed for the management of tendinopathies. Tendon pathology is characterized by a significant cell response to injury and gene expression. No study investigating changes in expression of those genes associated with collagen regeneration and remodeling of extracellular matrix has been conducted. The aim of this pilot study was to investigate gene expression changes after the application of percutaneous electrolysis on experimentally induced Achilles tendinopathy with collagenase injection in an animal model. Fifteen Sprague Dawley male rats were randomly divided into three different groups (no treatment vs. percutaneous electrolysis vs. needling). Achilles tendinopathy was experimentally induced with a single bolus of collagenase injection. Interventions consisted of 3 sessions (one per week) of percutaneous electrolysis or just needling. The rats were euthanized, and molecular expression of genes involved in tendon repair and remodeling, e.g., Cox2, Mmp2, Mmp9, Col1a1, Col3a1, Vegf and Scx, was examined at 28 days after injury. Histological tissue changes were determined with hematoxylin&ndash, eosin and safranin O analyses. The images of hematoxylin&ndash, eosin and Safranin O tissue images revealed that collagenase injection induced histological changes compatible with a tendinopathy. No further histological changes were observed after the application of percutaneous electrolysis or needling. A significant increase in molecular expression of Cox2, Mmp9 and Vegf genes was observed in Achilles tendons treated with percutaneous electrolysis to a greater extent than after just needling. The expression of Mmp2, Col1a1, Col3a1, or Scx genes also increased, but did not reach statistical significance. This animal study demonstrated that percutaneous electrolysis applied on an experimentally induced Achilles tendinopathy model could increase the expression of some genes associated with collagen regeneration and remodeling of extracellular matrix. The observed gene overexpression was higher with percutaneous electrolysis than with just needling.

In the version of this article initially published, the list of members and affiliations for The TRACERx Consortium was provided as a Supplementary Note. The list should have been provided in the online version. Also, an incorrect version of Fig. 2b was published. The correct version is provided below. The errors have been corrected in the HTML and PDF versions of the article.

This work seeks to know the narrative, publications, level of participation of users and the type of information generated by the Latin American media on Instagram. Research applies the exploratory method. The observation of the Instagram accounts was carried out and subsequently, social analytics was used, which allowed determining the profile, posts, growth and stories of the accounts, to finally carry out a content analysis. The results indicate that the media use the instalatory to publicize the information and the posts they publish enjoy good acceptance.

Run of river (RoR) hydropower systems, despite being one of the most cost-effective and environmentally benign energy technologies, have the disadvantage that production is not constant because it is subject to a high variability in precipitation and snow cover. In addition, the management of RoR plants has to comply with some particular operating conditions, but also with some environmental flow requirements. This work presents the assessment of the main inputs included in a climate service, historical local data and the seasonal forecast of water inflow to RoR plants, which are used to predict the operability and the expected energy production. The analysis is presented through the application in a pilot RoR system located in the south of Spain, in a semi-arid Mediterranean area impacted by snow, where seasonal forecasting is especially challenging. The results show the high interannual variability of the operation in this kind of facilities. The outcomes indicate that seasonal climate forecast information would improve the prediction of observed river streamflow by 7.4% in reliability and 3.2% in sharpness compared to the current operational forecast based on historical data. The climate forecasts thus provide valuable information for the exploitation of available water resources, which generates a significant value for the operation of the plant and the energy production market.

A few genotype-phenotype correlations have been described in type 1 neurofibromatosis. One deletion, p.Met992del, seems to be responsible for a mild form of the condition, in which there is absence of externally visible neurofibromas. We report a mother and a son with this mutation.

Background: \ud Among patients with non–small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC.\ud \ud Methods: \ud In this prospective cohort study, we performed multiregion whole-exome sequencing on 100 early-stage NSCLC tumors that had been resected before systemic therapy. We sequenced and analyzed 327 tumor regions to define evolutionary histories, obtain a census of clonal and subclonal events, and assess the relationship between intratumor heterogeneity and recurrence-free survival.\ud \ud Results: \ud We observed widespread intratumor heterogeneity for both somatic copy-number alterations and mutations. Driver mutations in EGFR, MET, BRAF, and TP53 were almost always clonal. However, heterogeneous driver alterations that occurred later in evolution were found in more than 75% of the tumors and were common in PIK3CA and NF1 and in genes that are involved in chromatin modification and DNA damage response and repair. Genome doubling and ongoing dynamic chromosomal instability were associated with intratumor heterogeneity and resulted in parallel evolution of driver somatic copy-number alterations, including amplifications in CDK4, FOXA1, and BCL11A. Elevated copy-number heterogeneity was associated with an increased risk of recurrence or death (hazard ratio, 4.9; P=4.4×10−4), which remained significant in multivariate analysis.\ud \ud Conclusions: \ud Intratumor heterogeneity mediated through chromosome instability was associated with an increased risk of recurrence or death, a finding that supports the potential value of chromosome instability as a prognostic predictor. (Funded by Cancer Research UK and others; TRACERx ClinicalTrials.gov number, NCT01888601.)

CVD graphene is a polycrystalline material, with grains typically smaller than a few microns. Although it is known that graphene’s grain size affects its properties, not much attention has been paid to developing methods similar to those existing for metals to perform grain size analysis. Reported strategies thus far are either limited to extremely small areas or incapable of providing real grain size statistics. Here we report a novel, straightforward laboratory-bench method that uses TiO2 suspended in water and UV light to selectively and precisely oxidize copper through graphene defects, resulting in well-contrasted darker copper oxide lines on a light copper background. The graphene grains are then visible via optical microscopy, and the quality is unprecedented. This allows for the statistical measurement of graphene grain size distributions across large areas, in accordance with ASTM standards and automated image analysis. Raman spectroscopy shows further that graphene is only moderately damaged after the photocatalytic process. Measurements of three monolayer CVD graphene samples with grain sizes ranging from 1.4 to 3.9 microns are presented, showing Gaussian distributions. For the first time, an experiment can be used to show how graphene grain size distributions become wider for larger average grain sizes, as it is common for polycrystalline materials.

Frameshift insertion/deletions (fs-indels) are an infrequent but potentially highly immunogenic mutation subtype. Although fs-indel transcripts are susceptible to degradation through the non-sense mediated decay (NMD) pathway, we hypothesise that some fs-indels escape degradation and lead to an increased abundance of tumor specific neoantigens, that are highly distinct from self. We analysed matched DNA and RNA sequencing data from TCGA, and five separate melanoma cohorts treated with immunotherapy. Using allele-specific expression analysis we show that expressed fs-indels were enriched in genomic positions predicted to escape NMD, and associated with higher protein expression, consistent with degradation escape (“NMD-escape”). Across four independent cohorts, fs-indel NMD-escape mutations were found to be significantly associated with clinical benefit to checkpoint inhibitor (CPI) therapy (Pmeta=0.0039), a stronger association than either nsSNV (Pmeta=0.073) or fs-indel (Pmeta=0.064) count. NMD-escape mutations were additionally shown to have independent predictive power in the “low-TMB” setting, and may serve as a biomarker to rescue patients judged ineligible for CPI based on overall TMB, but still with a high chance of response (low-TMB cohort: NMD-escape-positive % clinical benefit=53%, NMD-escape-negative % clinical benefit=16%, P=0.0098). Furthermore, in an adoptive cell therapy (ACT) treated cohort, NMD-escape mutation count was the most significant biomarker associated with clinical benefit (P=0.021). Analysis of functional T-cell reactivity screens from recent personalized vaccine and CPI studies shows direct evidence of fs-indel derived neoantigens eliciting patient anti-tumor immune response (n=15). We additionally observe a subset of fs-indel mutations, with highly elongated neo open reading frames, which are found to be significantly enriched for immunogenic reactivity in these patient studies (P=0.0032). Finally, consistent with the potency of NMD-escape derived neo-antigens and ongoing immune-editing, NMD-escape fs-indels appear to be under negative selective pressure in untreated TCGA cases. Given the strongly immunogenic potential, and relatively rare nature of NMD-escape fs-indels, these alterations may be attractive candidates in immunotherapy biomarker optimisation and neoantigen ACT or vaccine strategies.

Information about the real-time response of carriers to optical fields is paramount to advance information processing or to understand the bottlenecks of light-matter interaction and energy harvesting. Transition-metal dichalcogenide (TMDC) compounds are an emerging class of materials with attractive structural and electronic properties that can be thinned to the 2D limit and TiS 2 is a paradigmatic example for a semi-metallic TMDC, since its electron mobility ranges between that of a metal and a semiconductor.

Integrative analysis of multi-omics data is a powerful approach for gaining functional insights into biological and medical processes. Conducting these multifaceted analyses on human samples is often complicated by the fact that the raw sequencing output is rarely available under open access. The Personal Genome Project UK (PGP-UK) is one of few resources that recruits its participants under open consent and makes the resulting multi-omics data freely and openly available. As part of this resource, we describe the PGP-UK multi-omics reference panel consisting of ten genomic, methylomic and transcriptomic data. Specifically, we outline the data processing, quality control and validation procedures which were implemented to ensure data integrity and exclude sample mix-ups. In addition, we provide a REST API to facilitate the download of the entire PGP-UK dataset. The data are also available from two cloud-based environments, providing platforms for free integrated analysis. In conclusion, the genotype-validated PGP-UK multi-omics human reference panel described here provides a valuable new open access resource for integrated analyses in support of personal and medical genomics.

Background The lack of continuity between health-related quality of life (HRQoL) instruments designed for children and adults hinders change analysis with a life course approach. To resolve this gap, EuroQol (EQ) developed the EQ-5D-Youth (EQ-5D-Y), derived from the EQ-5D for adults. Few studies have assessed the metric properties of EQ-5D-Y in children with specific chronic conditions, and none have done so for children with type I diabetes mellitus (T1DM). Objective This study aimed to evaluate the acceptability, validity, reliability, and responsiveness of the EQ-5D-Y in children and adolescents with T1DM, when administered online. Methods Participants with T1DM were consecutively recruited from July to December 2014, from a list of potential candidates aged 8-19 years, who attended outpatient pediatric endocrinology units. Before every quarterly routine visit, participants received an email/telephone reminder to complete the online version of two generic HRQoL questionnaires: EQ-5D-Y and KIDSCREEN-27. The EQ-5D-Y measures five dimensions, from which an equally weighted summary score was constructed (range: 0-100). Completion rate and distribution statistics were calculated. Construct validity was evaluated through known group comparisons based on general health, acute diabetic decompensations, mental health, family function, and a multitrait, multimethod matrix between EQ-5D-Y and KIDSCREEN by using Spearman correlations. Construct validity hypotheses were stated a priori. Reliability was assessed with the intraclass correlation coefficient and responsiveness by testing changes over time and calculating the effect size. Reliability and responsiveness were tested among the stable and improved subsamples defined by a KIDSCREEN-10 index change of Results Of the 136 participants, 119 (87.5%) responded to the EQ-5D-Y at the last visit. The dimensions that showed higher percentages of participants with problems were “having pain/discomfort” (34.6%) and “worried/sad/unhappy” (28.7%). The mean (SD) of the EQ-5D-Y summary score was 8.5 (10.9), with ceiling and floor effects of 50.7% and 0%, respectively. Statistically significant HRQoL differences between groups defined by their general health (excellent/very good and good/regular/bad) and mental health (Strengths and Difficulties Questionnaire score ≤15 and >16, respectively) were found in three EQ-5D-Y dimensions (“doing usual activities,” “having pain/discomfort,” and “feeling worried/sad/unhappy”), summary score (effect size for general health and mental health groups=0.7 and 1.5, respectively), and KIDSCREEN-10 index (effect size for general health and mental health groups=0.6 and 0.9, respectively). Significant differences in the EQ-5D-Y dimensions were also found according to acute diabetic decompensations in “looking after myself” (P=.005) and according to family function in “having pain/discomfort” (P=.03). Results of the multitrait, multimethod matrix confirmed three of the four relationships hypothesized as substantial (0.21, 0.58, 0.50, and 0.46). The EQ-5D-Y summary score presented an intraclass correlation coefficient of 0.83. Statistically significant change between visits was observed in the improved subsample, with an effect size of 0.7 (P Conclusions These results support the use of the EQ-5D-Y administered online as an acceptable, valid, reliable, and responsive instrument for evaluating HRQoL in children and adolescents with T1DM.

The supply of ecosystem services is largely determined by changes in land use and cover. Here, we analysed how the supply and interactions among four ecosystem services have evolved over five decades in a mountain biosphere reserve largely dominated by human land uses. We modelled pastures for livestock, crop production, aquifer recharge and erosion prevention based on land use maps along five years. Multi-scale analyses were conducted to show the temporal evolution of the spatial patterns and interactions among those ecosystem services at three nested spatial scales (biosphere reserve, watershed and cell level). The overall increase in the supply of pastures and erosion prevention and the decline of crops and aquifer recharge were closely related to the abandonment of traditional land uses, particularly during the first decades. At finer scales, our results revealed that the cell areas with significant interactions among services (i.e. trade-offs and synergies) decreased from 1956 to 2007. Such evolution of trade-offs and synergies seemed to be driven by management decisions on land-use changes. Finally, we discussed the implications of our results in the context of ecosystem services’ optimization through management actions on land uses in mountain areas.

Background: The influence of gonadotropin-releasing hormone analogue (GnRHa) treatment on body mass index (BMI) evolution in girls with idiopathic central precocious puberty (CPP) is unclear. Hence, we aimed to evaluate the effect of GnRHa treatment on BMI-standard deviation score (SDS) from diagnosis of idiopathic CPP until adult height. Methods: An observational study of girls diagnosed with CPP in Spain was carried out between January 2008 and December 2014. A computer program was designed to process clinical and biological data from patients treated in 55 departments of pediatric endocrinology throughout the country. The inclusion criteria were (1) girls diagnosed with CPP before 8 years of age; (2) born after 1992; (3) with a difference between bone and chronological age of at least 1 year, and (4) with a luteinizing hormone peak >7 U/l during luteinizing hormone-releasing hormone testing. The influence of GnRHa treatment on BMI-SDS evolution was analyzed. Results: Data from 333 girls (22.2% adopted) were evaluated. We report follow-up data at 6, 12, 24, 36, 48 and 60 months and adult height from 269, 232, 198, 153, 105, 56 and 49 girls, respectively. During treatment, there was an increase in BMI-SDS of 0.43 ± 1.17 (95% CI: 0.20-0.64). At adult height (n = 49), BMI-SDS was 1.51 ± 1.38, which was 0.60 ± 1.09 higher than at diagnosis (95% CI: 0.43-0.75). Conclusions: During treatment with GnRHa, girls experience a significant increase in BMI-SDS that persists after therapy is stopped and adult height has been reached.

e17500 Background: IT heterogeneity (ITH) is well recognised in prostate cancer (PC), but its role in high-risk disease and patient outcomes are uncertain. Methods: This was a prospective, single-arm, translational study using targeted multi-region prostate biopsies to study genomic and T-cell ITH in clinically high-risk PC aiming to identify drivers and potential therapeutic strategies. A pre-defined exploratory objective was to evaluate the association of ITH, median inflammatory infiltrate (MII), total, clonal and neoantigens, with overall survival (OS) and time-to-next-line of therapy (TTNL). Results: 49 men with elevated prostate-specific antigen (PSA) and multiparametric-magnetic resonance imaging (MRI) detected PC underwent image-guided multiregion transperineal biopsy. 79 tumour regions from 25 patients (pts) with PC underwent sequencing, analysis of mutations, copy number and neoepitopes combined with tumour infiltrating T-cell subset quantification. The median follow-up was 60 months (m) with 10 death events. For %ITH, MII, total, clonal and subclonal neoantigens, patients were split by the median. Conclusions: The PROGENY study provides a diagnostic platform suitable for studying tumour ITH and has the potential to identify poor outcome subgroups in PC. Larger sample numbers in prospective trials are warranted to further investigate this hypothesis. [Table: see text]

Education is regarded as a key area virtually anywhere in the world. Disadvantaged and developing countries are the most committed in this area as they are very aware of the benefits education can bring. Latin America has made progress in this field and to pave the way for a prosperous future it is necessary to document what has been done, what is being done and what is being approached from a scientific point of view. Ultimately, the educational advancement of a country, to a large extent, also depends on the advancement of education as a science. Therefore, this work offers a literature review that aims to identify the aspects that are being addressed in this field, taking education as an object of scientific study within the Latin American community. Based on the analysis of the most-cited research articles, we aim to identify the predominant subjects and geographical locations in research on education in Latin America. The application of a method based on systematic literature review indicates that there is still a low incidence of scientific documents that relate the variables "Education" and "Latin America". Other results speak of an object of study based on geographical totality, not specific countries, and references to generic educational levels. Finally, "social policy" stands as the main sub-theme of study related to education.

Cadena SER and COPE are the two most played full-service radio stations in Spain. They are also the two stations that have bet the most on the production of podcasts, whose consumption is meant for the Internet, not traditional radio. This article discusses the activity generated around these types of programmes in the two social networks in which the aforementioned radio stations have more global presence: Facebook and Twitter. A purely quantitative method is used to analyze the presence of these programmes on the aforementioned social networks and, particularly, number of posts, formats and forms of interaction. The paper concludes that the use of social networks by the radio networks is very heterogeneous and does not reflect patterns of use: while some programmes have many followers, others have very few. In addition, the number of posts they make is also very diverse, and so it is their forms of interaction. As a reflection, it is important to emphasize that not all radio stations take advantage of social networks in the same way and to the same extent.

Improving outcomes in multiple myeloma will involve not only development of new therapies but also better use of existing treatments. We performed RNA sequencing on samples from newly diagnosed patients enrolled in the phase 2 PADIMAC (Bortezomib, Adriamycin, and Dexamethasone Therapy for Previously Untreated Patients with Multiple Myeloma: Impact of Minimal Residual Disease in Patients with Deferred ASCT) study. Using synthetic annealing and the large margin nearest neighbor algorithm, we developed and trained a 7-gene signature to predict treatment outcome. We tested the signature in independent cohorts treated with bortezomib- and lenalidomide-based therapies. The signature was capable of distinguishing which patients would respond better to which regimen. In the CoMMpass data set, patients who were treated correctly according to the signature had a better progression-free survival (median, 20.1 months vs not reached; hazard ratio [HR], 0.40; confidence interval [CI], 0.23-0.72; P = .0012) and overall survival (median, 30.7 months vs not reached; HR, 0.41; CI, 0.21-0.80; P = .0049) than those who were not. Indeed, the outcome for these correctly treated patients was noninferior to that for those treated with combined bortezomib, lenalidomide, and dexamethasone, arguably the standard of care in the United States but not widely available elsewhere. The small size of the signature will facilitate clinical translation, thus enabling more targeted drug regimens to be delivered in myeloma.

Supplemental Digital Content is available in the text., Summary: The authors aimed to present an introduction of patient-specific model in rhinoplasty by introducing a 3D printed surgical guide designed and adapted in an individualized manner for guiding dorsal hump reduction. To introduce the tool, we have designed a six step workflow. First, we obtain a digital 3D model of patient anatomy using computed tomography (CT) images. Second, we conduct a surgical preoperative planning of the rhinoplasty on the mentioned model. Third step consists of designing the guide, while taking into account nasal anthropometries and resection objectives. Fourth step is printing the guide and sterilizing it. Fifth step is performing the surgery. The last step is analyzing the main outcomes of the surgery. Our surgical guide allowed us to perform only 1 step osteotomy instead of the usual multistep osteotomy and remove exactly the amount of dorsum that we decided to remove during the preoperative planning. The duration of intervention was considerably shorter than conventional osteotomy. Using the guide was technically easier than the conventional method and reduced the learning curve from years to minutes (once the guide is printed). Moreover, the patient understanding of the procedure was significantly better after showing the 3D model of the surgery. The surgical guide allows a surgeon to transfer with extreme simplicity the presurgical planning to the surgical field. We have to point out that the design of the study does not allow us to quantify predictability, so future studies are needed to demonstrate an accuracy benefit over the former techniques.

One of the major revolutions of the past century in the field of medical sciences has been the evolution from “disease centred medicine” to “patient centred medicine”. Beyond statistical data and research evidence, there are multiple variables that influence the result and condition the eligibility of a patient for a technique or another: tissue characteristics, comorbidity, expectative, desirables or even the familiarity of the surgeon with the technique. Indeed, well understood EBM reclaims the articulation of the best available evidence with clinical expertise and patient values. The prime objective of this article is to introduce the PSM as an instrument of communication with the patient that allows, thanks to technology to build personalized intraoperative instruments that aids the surgeon to deal with patient variability.

The shell thickness gene Sh is one of the most important genes in oil palm. It controls the fruit type which in turn is associated with palm oil yield. Based on previous information about Sh alleles, we have developed a molecular marker system which is composed of three primer pairs and the application of two restriction enzymes which allows to discriminate between one dura and two pisifera alleles that are currently known. The different components of this marker system have been validated on 207 dura genotypes and 50 pisifera genotypes of different origins, as well as in 242 tenera genotypes derived from crosses of individual dura and pisifera palms. All evaluated genotypes showed the amplification products or restriction fragments, indicating a general applicability of the proposed system. The results of the application of this molecular marker system were compiled for all potentially existing fruit type genotypes, and can be used conveniently for selecting the desired genotypes or for identifying specific genotypes in mixtures. Methodological details were indicated for applying the marker system, as well as limitations with respect to potentially existing genetic variability. Useful applications of the system for breeding and seed certification are discussed.

Calibration and registration are two challenging tasks required by a real-time inspection system for long steel products based on multiple three-dimensional sensors. Spatial calibration is required to transform the information acquired by each sensor into a common reference system. Registration is used to align the calculated shape with the model of the product being inspected, which enables the calculation of quality control parameters. This paper proposes efficient solutions for these two problems. Calibration is performed using a specially designed calibration plate that can be used to detect the position and orientation of each sensor. Registration is applied using an analytic alignment between the data and the model. The proposed methods are specially designed to perform accurately in industrial environments where inspection systems are exposed to adverse conditions, such as dust, oil, or water, which provoke noise in the signals. Moreover, vibrations affect the position of the inspected product randomly, which makes accurate measurements much more difficult to achieve. The proposed procedures are validated with extensive tests using real and simulated data showing excellent performance.

In this paper, a surface inspection system for rails is proposed. There is a lack of commercial systems and publications about surface inspection of rails. Therefore, the quality control developed by rail manufacturers depends on their own developed systems or on the equipment provided by very few sellers. Commercial systems must be configured manually by experts of seller companies. The configuration process requires large sets of all types of manufactured rails along several periods of time and the active participation of the quality engineers of the manufacturer. This is a long, cumbersome, and very expensive process. In this paper, we propose a new system that can be configured using a systematic method that can be performed by the quality engineers of the manufacturer. The proposed inspection system uses differential images of the rail surfaces obtained with a technique called the spectral images differentiation procedure. These images are processed using a computer vision algorithm that looks for variations in the pixel values among the images. In order to offer more information, a neural network approach is used for classifying detected defects into six types. The proposed system is an open solution for the inspection of rail surface, easy to implement at an affordable cost, which can be systematically configured by the quality engineers of the manufacturing company.

This paper studies how several conceptual metaphors (e.g. MORALITY IS LIGHT, MORALITY IS CLEANLINESS, MORAL FREEDOM IS PHYSICAL FREEDOM, DOING IMMORAL DEEDS IS ACCUMULATING DEBT) are able to account for the basic meaning and interpretation of punishments and moral issues in more than twenty popular tales, thus allowing us to explain some of the uncanny elements of tales. The stories, representative of various cultures, have been extracted from the Project Gutenberg online library and belong to the British compiler Andrew Lang (1844-1912). We also suggest that these metaphors, because of their strong experiential grounding, may have contributed to an easier transmission of many fairy tales, and also to make tales alike in different socio-cultural settings.Keywords: Conceptual metaphor, moral and punishment, experiential, uncanny, culture, fairy tales.Resumen:En este artículo tratamos de estudiar cómo varias metáforas conceptuales (p.ej. MORALITY IS LIGHT, MORALITY IS CLEANLINESS, MORAL FREEDOM IS PHYSICAL FREEDOM, DOING IMMORAL DEEDS IS ACCUMULATING DEBT) pueden explicar el significado básico y la interpretación de los castigos y la moralidad en más de veinte cuentos populares, lo que nos permite explicar parte de “lo maravilloso” de los cuentos. Los cuentos, representativos de varias culturas, han sido extraídos de la biblioteca electrónica Project Gutenberg y pertenecen al compilador británico Andrew Lang (1844-1912). También sugerimos que estas metáforas, dado su marcado carácter experiencial, pueden haber contribuido a una transmisión más fácil de muchos cuentos de hadas y a que los cuentos sean similares en diferentes contextos socioculturales.Palabras clave: Metáfora conceptual, moralidad y castigo, experiencial, “lo maravilloso”, cultura, cuentos de hadas.

Background Intratumoural heterogeneity (ITH) is well recognised in prostate cancer (PC), but its role in high-risk disease is uncertain. A prospective, single-arm, translational study using targeted multiregion prostate biopsies was carried out to study genomic and T-cell ITH in clinically high-risk PC aiming to identify drivers and potential therapeutic strategies. Patients and methods Forty-nine men with elevated prostate-specific antigen and multiparametric-magnetic resonance imaging detected PC underwent image-guided multiregion transperineal biopsy. Seventy-nine tumour regions from 25 patients with PC underwent sequencing, analysis of mutations, copy number and neoepitopes combined with tumour infiltrating T-cell subset quantification. Results We demonstrated extensive somatic nucleotide variation and somatic copy number alteration heterogeneity in high-risk PC. Overall, the mutational burden was low (0.93/Megabase), but two patients had hypermutation, with loss of mismatch repair (MMR) proteins, MSH2 and MSH6. Somatic copy number alteration burden was higher in patients with metastatic hormone-naive PC (mHNPC) than in those with high-risk localised PC (hrlPC), independent of Gleason grade. Mutations were rarely ubiquitous and mutational frequencies were similar for mHNPC and hrlPC patients. Enrichment of focal 3q26.2 and 3q21.3, regions containing putative metastasis drivers, was seen in mHNPC patients. We found evidence of parallel evolution with three separate clones containing activating mutations of β-catenin in a single patient. We demonstrated extensive intratumoural and intertumoural T-cell heterogeneity and high inflammatory infiltrate in the MMR-deficient (MMRD) patients and the patient with parallel evolution of β-catenin. Analysis of all patients with activating Wnt/β-catenin mutations demonstrated a low CD8+/FOXP3+ ratio, a potential surrogate marker of immune evasion. Conclusions The PROGENY (PROstate cancer GENomic heterogeneitY) study provides a diagnostic platform suitable for studying tumour ITH. Genetic aberrations in clinically high-risk PC are associated with altered patterns of immune infiltrate in tumours. Activating mutations of Wnt/β-catenin signalling pathway or MMRD could be considered as potential biomarkers for immunomodulation therapies. Clinical Trials.gov Identifier NCT02022371

The present paper elaborates on some of the ideas in Ruiz de Mendoza and Diez (2002), where it is argued that conceptual interaction is fully regulated and constrained by a limited set of interactional patterns. This paper attempts to provide further evidence in support of this thesis through the analysis and exploration of several "eye expressions" (among others to keep an eye on someone, to turn a blind eye to something, to feast one's eyes on something, to be the owner of somebody's eyes, to be the apple of somebody's eyes, etc.), representative of various interactional patterns, and that have been extracted after an exhaustive analysis of more than 500 instances from both the BNC and the Oxford Superlex Dictionary database.On the basis of the analysis of the various patterns, we postulate two possible interaction operations, sequencing and integration, and argue that understanding these two operations sheds light on the definitional relationship between metaphor and metonymy. We also claim that the form sequential arrangement takes in an interactional pattern is related to the ontological status of the result of an integration process.

The optical design of the BOREAS beamline operating at the ALBA synchrotron radiation facility is described. BOREAS is dedicated to resonant X-ray absorption and scattering experiments using soft X-rays, in an unusually extended photon energy range from 80 to above 4000 eV, and with full polarization control. Its optical scheme includes a fixed-included-angle, variable-line-spacing grating monochromator and a pair of refocusing mirrors, equipped with benders, in a Kirkpatrick–Baez arrangement. It is equipped with two end-stations, one for X-ray magnetic circular dichroism and the other for resonant magnetic scattering. The commissioning results show that the expected beamline performance is achieved both in terms of energy resolution and of photon flux at the sample position.

Background Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer associated with HER2 amplification, with high risk of metastasis and an estimated median survival of 2.9 y. We performed an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT01325428) to investigate the efficacy and safety of afatinib, an irreversible ErbB family inhibitor, alone and in combination with vinorelbine in patients with HER2-positive IBC. This trial included prospectively planned exome analysis before and after afatinib monotherapy. Methods and Findings HER2-positive IBC patients received afatinib 40 mg daily until progression, and thereafter afatinib 40 mg daily and intravenous vinorelbine 25 mg/m2 weekly. The primary endpoint was clinical benefit; secondary endpoints were objective response (OR), duration of OR, and progression-free survival (PFS). Of 26 patients treated with afatinib monotherapy, clinical benefit was achieved in 9 patients (35%), 0 of 7 trastuzumab-treated patients and 9 of 19 trastuzumab-naïve patients. Following disease progression, 10 patients received afatinib plus vinorelbine, and clinical benefit was achieved in 2 of 4 trastuzumab-treated and 0 of 6 trastuzumab-naïve patients. All patients had treatment-related adverse events (AEs). Whole-exome sequencing of tumour biopsies taken before treatment and following disease progression on afatinib monotherapy was performed to assess the mutational landscape of IBC and evolutionary trajectories during therapy. Compared to a cohort of The Cancer Genome Atlas (TCGA) patients with HER2-positive non-IBC, HER2-positive IBC patients had significantly higher mutational and neoantigenic burden, more frequent gain-of-function TP53 mutations and a recurrent 11q13.5 amplification overlapping PAK1. Planned exploratory analysis revealed that trastuzumab-naïve patients with tumours harbouring somatic activation of PI3K/Akt signalling had significantly shorter PFS compared to those without (p = 0.03). High genomic concordance between biopsies taken before and following afatinib resistance was observed with stable clonal structures in non-responding tumours, and evidence of branched evolution in 8 of 9 tumours analysed. Recruitment to the trial was terminated early following the LUX-Breast 1 trial, which showed that afatinib combined with vinorelbine had similar PFS and OR rates to trastuzumab plus vinorelbine but shorter overall survival (OS), and was less tolerable. The main limitations of this study are that the results should be interpreted with caution given the relatively small patient cohort and the potential for tumour sampling bias between pre- and post-treatment tumour biopsies. Conclusions Afatinib, with or without vinorelbine, showed activity in trastuzumab-naïve HER2-positive IBC patients in a planned subgroup analysis. HER2-positive IBC is characterized by frequent TP53 gain-of-function mutations and a high mutational burden. The high mutational load associated with HER2-positive IBC suggests a potential role for checkpoint inhibitor therapy in this disease. Trial Registration ClinicalTrials.gov NCT01325428, In a phase 2 clinical trial in which patients received afatinib, plus vinorelbine on disease progression, Charles Swanton and colleagues study the mutational events in HER2-positive inflammatory breast cancers alongside early-stage clinical outcomes., Author Summary Why Was This Study Done? Inflammatory breast cancer (IBC) is a rare and poorly understood form of breast cancer that grows and spreads very quickly. Fifty percent of IBC cases are HER2-positive. Afatinib is an investigational drug that showed promise in early-stage trials in the setting of HER2-positive metastatic breast cancer. Our study was designed to look at how effective and safe afatinib is in treating HER2-positive IBC patients, and to elucidate how afatinib treatment affects the tumours at the genomic level. What Did the Researchers Do and Find? We recruited 26 patients for this study and administered afatinib daily, and 10 patients went on to be treated with daily afatinib and weekly vinorelbine, a chemotherapy drug, upon disease progression. Thirty-five percent (9 of 26) and 20% (2 of 10) of patients had clinical benefit from being treated with afatinib monotherapy and afatinib plus vinorelbine, respectively. We sequenced tumour biopsies before and after afatinib treatment and found that IBC has a higher mutational load and more frequent mutations in the well-known cancer gene TP53, compared to non-IBC. We did not identify any single gene or mutation that led to afatinib resistance, and biopsies before and after treatment were very similar genetically. What Do These Findings Mean? Afatinib appears to be clinically active in HER2-positive IBC, albeit in a relatively small patient cohort. The high mutational load in IBC suggests that checkpoint inhibitors, a type of cancer immunotherapy, might potentially be an effective way of treating patients.

It has been demonstrated that the adi- pose tissue, a highly functional metabolic tissue, is a reservoir of mesenchymal stem cells. The potential use of adipose-derived stem cells (ADSCs) from white adipose tissue (WAT) for organ repair and regenera- tion has been considered because of their obvious benefits in terms of accessibility and quantity of avail- able sample. However, the functional capability of ADSCs from subjects with different adiposity has not been investigated. It has been our hypothesis that ADSCs from adipose tissue of patients with metabolic syndrome and high adiposity may be functionally im- paired. We report that subcutaneous WAT stromal vascular fraction (SVF) from nonobese individuals had a significantly higher number of CD90 cells than SVF from obese patients. The isolated ADSCs from WAT of obese patients had reduced differentiation potential and were less proangiogenic. Therefore, ADSCs in adipose tissue of obese patients have lower capacity for spontaneous or therapeutic repair than ADSCs from nonobese metabolically normal individuals.—Onate, B., Vilahur, G., Ferrer-Lorente, R., Ybarra, J., Diez- Caballero, A., Ballesta-Lopez, C., Moscatiello, F., Her- rero, J., Badimon, L. The subcutaneous adipose tissue reservoir of functionally active stem cells is reduced in obese patients. FASEB J. 26, 000 - 000 (2012). www. fasebj.org

Resumen Introduccion y objetivos El abordaje de la patologia quirurgica de la glandula parotida y los resultados obtenidos son relativamente uniformes. Sin embargo, tanto en la vertiente diagnostica como en la terapeutica, existen algunos aspectos controvertidos cuya discusion planteamos a partir de la experiencia reciente de nuestro servicio. Metodos Se realizo un estudio descriptivo retrospectivo sobre pacientes sometidos a parotidectomia por cualquier indicacion entre julio de 2004 y junio de 2009 (5 anos). Resultados Se realizaron 54 parotidectomias en 52 pacientes. La TC fue el estudio de imagen preoperatorio mas utilizado. La validez de la PAAF fue del 93,3%. El 76% fueron procesos benignos; entre ellos el 7,3% de causa inflamatoria. Todas las intervenciones se realizaron con monitorizacion electrofisiologica del nervio facial a partir de abril de 2005. Se realizo parotidectomia superficial en el 75,6% de los procesos benignos. La incidencia de paresias faciales transitorias en patologia benigna fue del 14,6% (todas grados II y III ). Dos casos (ambos con parotidectomia total) tuvieron secuelas permanentes de movilidad facial. La incision de ritidectomia se utilizo preferentemente en mujeres jovenes. Conclusiones Identificamos como puntos de controversia, bien por discrepancia con la evidencia cientifica o por evidencia insuficiente: el papel diagnostico de la RM, la validez y utilidad de la PAAF, las indicaciones del tratamiento quirurgico, la necesidad de monitorizacion del nervio facial, y la consideracion de los aspectos cosmeticos, en particular las indicaciones de la incision de ritidectomia.

Nature 545, 446–451 (2017); doi:10.1038/nature22364 For 6 of the 96 patients included in this Article (patients CRUK0014, CRUK0030, CRUK0048, CRUK0059, CRUK0096 and CRUK0097) incorrect tumour volumetric data and positron emission tomography (PET) tumour background ratio (TBR) data were analysed. This error occurred because of the incorrect assignment of patient identifiers during the anonymization mandated by the independent review board of pre-operative computed tomography (CT) scans belonging to these patients.

Introduccion y objetivos La relacion coste-efectividad de los programas de cribado universal de la hipoacusia infantil es objeto de una constante revision. En este contexto, el objetivo del presente trabajo es valorar el rendimiento de los potenciales evocados auditivos de tronco cerebral (PEATC) frente a las emisiones otoacusticas (EOA) como prueba de cribado. Metodos Estudio observacional retrospectivo sobre un programa de cribado universal iniciado en 1998. Realizamos un analisis comparativo entre dos grupos de recien nacidos evaluados en periodos consecutivos, separados por una transicion tecnologica. Analizamos los indicadores de resultados del programa como medida de efectividad y los recursos invertidos para valoracion de costes. Resultados Se compara un grupo de 862 neonatos del ano 2003, cribados con EOA transitorias con un equipo clinico, con otro de 2.300 neonatos de 2005 y 2006, cribados con PEATC automatizados. Encontramos una diferencia estadisticamente significativa en el porcentaje de paso en primera fase favorable a los PEATC (el 99,7 frente al 91,8 %; p Conclusiones Hay datos que indican que los PEATC podrian ser mas coste-efectivos como prueba inicial de cribado. Esta ventaja se anadiria a la ya existente de evaluacion mas completa de la via auditiva, y podria llevar a la recomendacion de su uso preferente en los programas de cribado auditivo.

Developments in the ITS area are received with great expectation by both consumers and industry. Despite their huge potential benefits, ITS solutions suffer from the slow pace of adoption by manufacturers. In this paper we propose EYES, an ITS system that aims at helping drivers in overtaking. The system autonomously creates a network of the devices running EYES, and provides drivers with a video feed from the vehicle located just ahead, thus presenting a better view of any vehicles coming from the opposite direction and the road ahead. This is specially useful when the front view of the driver is blocked by large vehicles, and thus the decision whether to overtake can be taken based on the visuals provided by the application. We have validated EYES, the proposed overtaking assistance system, in both indoor and realistic scenarios involving vehicular network, and preliminary results allow being optimistic about its effectiveness and applicability., This work was partially supported by the European Commission under Svagata.eu, the Erasmus Mundus Programme, Action 2 (EMA2) and the Ministerio de Economía y Competitividad, Programa Estatal de Investigación, Desarrollo e Innovación Orientada a los Retos de la Sociedad, Proyectos I+D+I 2014, Spain, under Grant TEC2014-52690-R.

© 2014 Earl et al. Multiple sequence alignments (MSAs) are a prerequisite for a wide variety of evolutionary analyses. Published assessments and benchmark data sets for protein and, to a lesser extent, global nucleotide MSAs are available, but less effort has been made to establish benchmarks in the more general problem of whole-genome alignment (WGA). Using the same model as the successful Assemblathon competitions, we organized a competitive evaluation in which teams submitted their alignments and then assessments were performed collectively after all the submissions were received. Three data sets were used: Two were simulated and based on primate and mammalian phylogenies, and one was comprised of 20 real fly genomes. In total, 35 submissions were assessed, submitted by 10 teams using 12 different alignment pipelines. We found agreement between independent simulation-based and statistical assessments, indicating that there are substantial accuracy differences between contemporary alignment tools. We saw considerable differences in the alignment quality of differently annotated regions and found that few tools aligned the duplications analyzed. We found that many tools worked well at shorter evolutionary distances, but fewer performed competitively at longer distances. We provide all data sets, submissions, and assessment programs for further study and provide, as a resource for future benchmarking, a convenient repository of code and data for reproducing the simulation assessments.

This manuscript describes a combined approach of unsupervised clustering followed by supervised learning that provides an efficient classification of conditions in DNA array gene expression experiments (different cell lines including some cancer types, in the cases shown). Firstly the dimensionality of the dataset of gene expression profiles is reduced to a number of non-redundant clusters of co-expressing genes using an unsupervised clustering algorithm, the Self Organizing Tree Algorithm (SOTA), a hierarchical version of Self Organizing Maps (SOM). Then, the average values of these clusters are used for training a perceptron that produces a very efficient classification of the conditions. This way of reducing the dimensionality of the data set seems to perform better than other ones previously proposed such as principal component analysis (PCA). In addition, the weights that connect the gene clusters to the different experimental conditions can be used to assess the relative importance of the genes in the definition of these classes. Finally, Gene Ontology (GO) terms are used to infer a possible biological role for these groups of genes and to asses the validity of the classification from a biological point of view.

Background Obese children and adolescents have an increased risk for asthma. A few studies have evaluated the association of insulin resistance and asthma in obese pediatric populations. We examined whether there was a relationship between high degrees of insulin resistance and the presence of asthma in obese children and adolescents. Methods A total of 153 patients aged 4–15 years with at or above the 95th percentile BMI for age were prospectively recruited. Assessments included diagnosis of asthma, skin prick test reactivity to common environmental aeroallergens, and HOMA estimated insulin resistance, with the median (2.22) used as a cutoff value to categorize insulin resistance. Results There were 56 (36.6%) asthmatic and 97 (63.4%) non-asthmatic patients. HOMA values were significantly associated with positive skin tests (p = 0.008) and allergic asthma diagnosis (p = 0.016). Baseline insulin value was significantly associated with the risk of presenting asthma with positive skin testing (odds ratio 1.084, p = 0.037). Differences in age, BMI, and waist circumference were found between the groups of HOMA-IR

Endoscopic interventions in the abdominal and thoracic cavity are often hampered by the difficulty to orient in the endoscopic view. This is due to the small field of view and the inhomogeneous illumination, but also because abdominal organs are highly deformable and subject to complex movements. The use of flexible endoscopes further complicates these issues. In the context of a multidisciplinary project involving clinical and technical teams, we report the definition of clinical requirements and surgical workflow of abdominal endoscopic interventions, and present the design and implementation of a planning and navigation system. Some of the implemented features include: segmentation, tracking, landmark-based navigation, and combined surface and volume rendering. Our system is based on open source libraries, and is flexible and applicable to other types of interventions.

Agar plates are widely used in the biomedical field as a medium in which to artificially grow bacteria, algae or fungi. Agar plates (Petri dishes) are used routinely in microbiology laboratories in order to identify the type of micro-organism responsible for infections. Such diagnoses are based on counting the number and type of bacterial colonies growing in the Petri dish. The count of bacterial colonies is a time consuming task prone to human error, so interest in automated counting systems has increased in the recent years. One of the difficulties of automatizing the counting process is the presence of markers and annotations made in the lower part of the agar plate. Efficient removal of such markers can increase the accuracy of the bacterial counting system. This article introduces a fast method for detection, segmentation and removal of annotations in agar plates that improves the results of existing bacterial colony counting algorithms.