A strategy to validate a selection of human effect biomarkers using adverse outcome pathways: Proof of concept for phthalates and reproductive effects

Human biomonitoring measures the concentrations of environmental chemicals or their metabolites in body fluids or tissues. Complementing exposure biomarkers with mechanistically based effect biomarkers may further elucidate causal pathways between chemical exposure and adverse health outcomes. We combined information on effect biomarkers previously implemented in human observational studies with mechanisms of action reported in experimental studies and with information from published Adverse Outcome Pathways (AOPs), focusing on adverse reproductive effects of phthalate exposure. Phthalates constitute a group of chemicals that are ubiquitous in consumer products and have been related to a wide range of adverse health effects. As a result of a comprehensive literature search, we present an overview of effect biomarkers for reproductive toxicity that are substantiated by mechanistic information. The activation of several receptors, such as PPARα, PPARγ, and GR, may initiate events leading to impaired male and female fertility as well as other adverse effects of phthalate exposure. Therefore, these receptors appear as promising targets for the development of novel effect biomarkers. The proposed strategy connects the fields of epidemiology and toxicology and may strengthen the weight of evidence in observational studies that link chemical exposures to health outcomes.This project has received funding from the European Unions' Horizon 2020 research and innovation Programme under grant agreement No 733032 HBM4E

Determination of bisphenol A and related aromatic compounds released from bis-GMA-based composites and sealants by high performance liquid chromatography

'Reproduced with permission from Environmental Health Perspectives'Most of the composites and sealants used in dentistry are based on bisphenol A diglycidylether methacrylate (Bis-GMA). Reports revealed that in situ polymerization is not complete and that free monomers can be detected by different analytic methods. Concerns about the estrogenicity of bisphenol A (BPA) and other aromatic components leached from commercial products have been expressed. We studied biphenolic components eluted from seven composites and one sealant before and after in vitro polymerization using HPLC and gas chromatography/mass spectrometry and we investigated how pH modifications affect the leaching of these components. We found BPA (maximal amount 1.8 microg/mg dental material), its dimethacrylate derivative (Bis-DMA, 1.15 microg/mg), bisphenol A diglycidylether (6. 1 microg/mg), Bis-GMA (2.0 microg/mg), and ethoxylate and propoxylate of bisphenol A in media in which samples of different commercial products were maintained under controlled pH and temperature conditions. Our results confirm the leaching of estrogenic monomers into the environment by Bis-GMA-based composites and sealants in concentrations at which biologic effects have been demonstrated in in vivo experimental models. The main issue with implications for patient care and dentist responsibility is to further determine the clinical relevance of this estrogenic exposure.This research was supported by grants from the Spanish Ministry of Health (FIS, 95/1959) and Education (CICYT, AMB97-1194-CE) and the Andalusian Regional Government, Department of Health (Consejeria de Salud, JA, 231/97)

Produtos químicos como desreguladores endócrinos: substâncias danosas e como devem ser testadas

This paper presents an analysis of the opinions of different groups from: scientists, international regulatory bodies, non-governmental organizations and industry; with an interest in the problem of identifying chemical substances with endocrine disrupting activity. There is also discussion of the consequences that exposure to endocrine disruptors may have for human health, considering concrete issues related to: the estimation of risk; the tests that must be used to detect endocrine disruption; the difficulties to establish an association between dose, time of exposure, individual susceptibility, and effect; and the attempts to create a census of endocrine disruptors. Finally, it is proposed that not all hormonal mimics should be included under the single generic denomination of endocrine disruptors.This work was supported by a 96/99 Research Project from the Health Department of the Andalusian Regional Government

Espacio EpD: una experiencia de desarrollo profesional docente

Describimos una experiencia realizada con un grupo de docentes de diversos niveles educativos: Educación Infantil, Educación Primaria, Educación Secundaria y Universidad, que, a través de un Proyecto de la ONG “Madre Coraje” han desarrollado un proceso de aprendizaje cooperativo en una plataforma digital para compartir experiencias en el diseño y experimentación de propuestas didácticas sobre Educación para el Desarrollo (ED). Entre los resultados destacamos las posibilidades que ofrecen las temáticas relacionadas con la ED para cambiar la concepción de los contenidos curriculares de los docentes, pasando de una visión centrada en el profesor y en su disciplina de referencia a una posición centrada en los alumnos y en sus intereses y necesidades.We describe an experience conducted with a group of teachers of different educational levels: kindergarten, primary school, secondary school and university, which, through a project of the NGO "Mother Courage" have developed a process of cooperative learning in a digital platform to share experiences in the design and testing of didactic proposals on Development Education (ED). The results highlight the potential of topics related to the ED to change the design of the curricula of teachers, moving from a teachercentered vision and discipline reference to a student-centered position and its interests and needs

A K band survey in the Groth Strip Flanking Fields

As a part of our collaboration in the COSMOS Project, devoted to the characterization of galaxies during the ep o c h of maximum star formation in the history of the Universe, we have carried out a deep photometric survey covering about 380 arcmin^(2) in the so-called Groth Strip Flanking Fields. The observations were obtained in the K´ band with the OMEGA-PRIME infrared camera at the 3.5 m telescope at the Hispano–German Calar Alto Observatory . Galaxy counts and photometric redshifts will be computed in order to prepare future observations with EMIR

Service Orchestration and Federation for Verticals

The next generation mobile transport networks shall transform into flexible and agile SDN/NFV-based transport and computing platforms, capable of simultaneously supporting the needs of different vertical industries, e.g., automotive, e-health and media, by meeting a diverse range of networking and computing requirements. Network slicing, has emerged as the most promising approach to address this challenge by enabling per-slice management of virtualized resources and provisioning and managing slices tailored to the needs of different vertical industries. Service orchestration is the key enabler for slicing that allows efficient placement of virtual network functions over the infrastructure as well as optimal allocation of virtual resources among all network slices to deliver guaranteed, reliable and scalable services of different verticals. Besides, due to the limited footprint of infrastructure operators, it is also required to enable the interconnection and federation of multiple administrative domains, to effectively allow services to span across several providers. This paper presents the design of Service Orchestrator (SO) in the 5G- TRANSFORMER system, which deals with service orchestration and federation across multiple domains.This work has been partially funded by the EU H2020 5G-TRANSFORMER Project (grant no. 761536

SIRT7 mediates L1 elements transcriptional repression and their association with the nuclear lamina

Long interspersed elements-1 (LINE-1, L1) are retrotransposons that hold the capacity of self-propagation in the genome with potential mutagenic outcomes. How somatic cells restrict L1 activity and how this process becomes dysfunctional during aging and in cancer cells is poorly understood. L1s are enriched at lamin-associated domains, heterochromatic regions of the nuclear periphery. Whether this association is necessary for their repression has been elusive. Here we show that the sirtuin family member SIRT7 participates in the epigenetic transcriptional repression of L1 genome-wide in both mouse and human cells. SIRT7 depletion leads to increased L1 expression and retrotransposition. Mechanistically, we identify a novel interplay between SIRT7 and Lamin A/C in L1 repression. Our results demonstrate that SIRT7-mediated H3K18 deacetylation regulates L1 expression and promotes L1 association with elements of the nuclear lamina. The failure of such activity might contribute to the observed genome instability and compromised viability in SIRT7 knockout mice. Overall, our results reveal a novel function of SIRT7 on chromatin organization by mediating the anchoring of L1 to the nuclear envelope, and a new functional link of the nuclear lamina with transcriptional repression

Cost-utility and biological underpinnings of Mindfulness-Based Stress Reduction (MBSR) versus a psychoeducational programme (FibroQoL) for fibromyalgia: a 12-month randomised controlled trial (EUDAIMON study)

Background: The EUDAIMON study focuses on fibromyalgia syndrome (FMS), a prevalent chronic condition characterized by pain, fatigue, cognitive problems and distress. According to recent reviews and meta-analyses, Mindfulness-Based Stress Reduction (MBSR) is a promising therapeutic approach for patients with FMS. The measurement of biomarkers as part of the analysis of MBSR effects would help to identify the neurobiological underpinnings of MBSR and increase our knowledge of FMS pathophysiology. The main objectives of this 12-month RCT are: firstly, to examine the effectiveness and cost-utility for FMS patients of MBSR as an add-on to treatment as usual (TAU) versus TAU + the psychoeducational programme FibroQoL, and versus TAU only; secondly, to examine pre-post differences in brain structure and function, as well as levels of specific inflammatory markers in the three study arms and; thirdly, to analyse the role of some psychological variables as mediators of 12-month clinical outcomes. Methods: Effectiveness, cost-utility, and neurobiological analyses performed alongside a 12-month RCT. The participants will be 180 adult patients with FMS recruited at the Sant Joan de Déu hospital (St. Boi de Llobregat, Spain), randomly allocated to one of the three study arms: TAU + MBSR vs. TAU + FibroQol vs. TAU. A comprehensive assessment to collect functional, quality of life, distress, costs, and psychological variables will be conducted pre-, post-intervention, and at 12-month post-intervention. Fifty per cent of study participants will be evaluated at pre- and post-treatment using Voxel-Based Morphometry, Diffusion Tensor Imaging, pseudo-continuous Arterial Spin Labeling, and resting state fMRI. A cytokine multiplex kit of high-sensitivity will be applied (cytokines IL-6, IL-8, IL-10 + high-sensitivity CRP test). Discussion: The findings obtained from this RCT will indicate whether MBSR is potentially cost-effective for FMS and contribute to knowledge of any brain and inflammatory changes associated with MBSR in FMS patients. Specifically, we will determine whether there are morphometric and functional changes associated with participation in MBSR in brain regions related to meta-awareness, body awareness, memory consolidation-reconsolidation, emotion regulation and in networks postulated to underpin the sensory-discriminative, cognitive-evaluative and affective-motivational aspects of the pain experience. Trial registration: NCT02561416. Registered 23 September 201

Cost-utility and biological underpinnings of Mindfulness-Based Stress Reduction (MBSR) versus a psychoeducational programme (FibroQoL) for fibromyalgia: a 12-month randomised controlled trial (EUDAIMON study)

Background: The EUDAIMON study focuses on fibromyalgia syndrome (FMS), a prevalent chronic condition characterized by pain, fatigue, cognitive problems and distress. According to recent reviews and meta-analyses, Mindfulness-Based Stress Reduction (MBSR) is a promising therapeutic approach for patients with FMS. The measurement of biomarkers as part of the analysis of MBSR effects would help to identify the neurobiological underpinnings of MBSR and increase our knowledge of FMS pathophysiology. The main objectives of this 12-month RCT are: firstly, to examine the effectiveness and cost-utility for FMS patients of MBSR as an add-on to treatment as usual (TAU) versus TAU + the psychoeducational programme FibroQoL, and versus TAU only; secondly, to examine pre-post differences in brain structure and function, as well as levels of specific inflammatory markers in the three study arms and; thirdly, to analyse the role of some psychological variables as mediators of 12-month clinical outcomes. Methods: Effectiveness, cost-utility, and neurobiological analyses performed alongside a 12-month RCT. The participants will be 180 adult patients with FMS recruited at the Sant Joan de Deu hospital (St. Boi de Llobregat, Spain), randomly allocated to one of the three study arms: TAU + MBSR vs. TAU + FibroQol vs. TAU. A comprehensive assessment to collect functional, quality of life, distress, costs, and psychological variables will be conducted pre-, post-intervention, and at 12-month post-intervention. Fifty per cent of study participants will be evaluated at pre- and post-treatment using Voxel-Based Morphometry, Diffusion Tensor Imaging, pseudo-continuous Arterial Spin Labeling, and resting state fMRI. A cytokine multiplex kit of high-sensitivity will be applied (cytokines IL-6, IL-8, IL-10 + high-sensitivity CRP test). Discussion: The findings obtained from this RCT will indicate whether MBSR is potentially cost-effective for FMS and contribute to knowledge of any brain and inflammatory changes associated with MBSR in FMS patients. Specifically, we will determine whether there are morphometric and functional changes associated with participation in MBSR in brain regions related to meta-awareness, body awareness, memory consolidation-reconsolidation, emotion regulation and in networks postulated to underpin the sensory-discriminative, cognitive-evaluative and affective-motivational aspects of the pain experience

Interactive handwriting recognition with limited user effort

The final publication is available at Springer via http://dx.doi.org/10.1007/s10032-013-0204-5[EN] Transcription of handwritten text in (old) documents is an important, time-consuming task for digital libraries. Although post-editing automatic recognition of handwritten text is feasible, it is not clearly better than simply ignoring it and transcribing the document from scratch. A more effective approach is to follow an interactive approach in which both the system is guided by the user, and the user is assisted by the system to complete the transcription task as efficiently as possible. Nevertheless, in some applications, the user effort available to transcribe documents is limited and fully supervision of the system output is not realistic. To circumvent these problems, we propose a novel interactive approach which efficiently employs user effort to transcribe a document by improving three different aspects. Firstly, the system employs a limited amount of effort to solely supervise recognised words that are likely to be incorrect. Thus, user effort is efficiently focused on the supervision of words for which the system is not confident enough. Secondly, it refines the initial transcription provided to the user by recomputing it constrained to user supervisions. In this way, incorrect words in unsupervised parts can be automatically amended without user supervision. Finally, it improves the underlying system models by retraining the system from partially supervised transcriptions. In order to prove these statements, empirical results are presented on two real databases showing that the proposed approach can notably reduce user effort in the transcription of handwritten text in (old) documents.The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under Grant Agreement No 287755 (transLectures). Also supported by the Spanish Government (MICINN, MITyC, "Plan E", under Grants MIPRCV "Consolider Ingenio 2010", MITTRAL (TIN2009-14633-C03-01), erudito.com (TSI-020110-2009-439), iTrans2 (TIN2009-14511), and FPU (AP2007-02867), and the Generalitat Valenciana (Grants Prometeo/2009/014 and GV/2010/067).Serrano Martinez Santos, N.; Giménez Pastor, A.; Civera Saiz, J.; Sanchis Navarro, JA.; Juan Císcar, A. (2014). Interactive handwriting recognition with limited user effort. International Journal on Document Analysis and Recognition. 17(1):47-59. https://doi.org/10.1007/s10032-013-0204-5S4759171Agua, M., Serrano, N., Civera, J., Juan, A.: Character-based handwritten text recognition of multilingual documents. In: Proceedings of Advances in Speech and Language Technologies for Iberian Languages (IBERSPEECH 2012), Madrid (Spain), pp. 187–196 (2012)Ahn, L.V., Maurer, B., Mcmillen, C., Abraham, D., Blum, M.: reCAPTCHA: human-based character recognition via web security measures. 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