64 research outputs found

    Creación de un atlas de la sustancia blanca cerebral para la extracción automática de fascículos axonales

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    [EN] Several neurodegenerative diseases are straightly bounded to degeneration of brain white matter. In addition, microstructural and tissue organization changes impair water diffusion in an injured tissue. Therefore, access to nervous connections is crucial to evaluate the stage of the disease or the damages produced by a tumour. Thus, diffusion magnetic resonance imaging methods are powerful techniques for characterizing disease effects at microscopic level. Specifically, using principal directions of the diffusion, brain white matter connectivity patterns estimation may be obtained. This technique, called tractography, allows in vivo noninvasive visualization of the white matter tracts. Thereby, diffusion tensor imaging and tractography provide an excellent opportunity to investigate white matter structures. However, there is non automated methodology that allows regions of interest segmentation, so the white matter tracts extraction depends on the judgement of the health professionals. On the other hand, using diffusion tensor imaging, brain white matter atlas may be created, providing anatomical information equivalent to ancient atlas based on histologic tests and offering a common reference system for different subject evaluation. Thus, with the aim to create a brain white matter atlas and apply automatically regions of interest in new subjects, this final master project was developed, in a collaborative context between Universidad Politecnica de Valencia and Hospital Quiron Valencia. For this purpose, 2 methodologies for the brain white matter atlas creation were established. Subsequently, this atlas was obtained from a sample of 50 healthy subjects. Then, atlas-based segmentation was applied to define 8 of the regions of interest most commonly used in brain pathologies clinical settings. Subsequently, these regiones were automatically applied in a new group of healthy and diseased individuals, getting an optimal implementation of these regions and the consequent automatic extraction of the brain white matter fiber boundles. Thereby, the variability inherently involving manual segmentation was removed. This final master project, was introduced at the International Congress of the European Society for Magnetic Resonance in Medicine and Biology (ESMRMB) 2013, from 3rd to 5th October in Toulouse. Fuerthermore, a scientific paper including an extended validation sample is finalizing to strengthen the results, and progress towards its integration into the clinical setting.[ES] Ciertas patologías neurodegenerativas están estrechamente ligadas a la degeneración de la sustancia blanca cerebral; además, la difusión del agua dentro del tejido afectado se ve alterada por los cambios en la microestructura y organización tisular. Por ello, es crucial poder acceder a las conexiones nerviosas y evaluar el estadio de una enfermedad, la eficacia de un tratamiento o los daños ocasionados por un tumor. Así, los métodos de imagen de resonancia magnética con ponderación en difusión, son potentes técnicas para caracterizar los efectos de la enfermedad a nivel microscópico. En concreto, mediante las direcciones principales de la difusión se puede obtener una estimación de los patrones de conectividad de la sustancia blanca cerebral. Esta técnica, conocida como tractografía, permite visualizar los tractos de sustancia blanca in vivo y de forma no invasiva. Por ello, la imagen de tensor de difusión y la tractografía proporcionan una oportunidad excelente en la investigación de las estructuras de sustancia blanca. No obstante, no existe un procedimiento automatizado que permita segmentar regiones de interés, por lo que la obtención de los tractos de sustancia blanca está sujeta al criterio del profesional sanitario. Por otro lado, utilizando imagen de tensor de difusión se pueden crear atlas de sustancia blanca cerebral, que proporcionan información anatómica equivalente a los antiguos atlas basados en exámenes histológicos y ofrecen un sistema de referencia común para la evaluación de diferentes sujetos. Así, con el fin de crear un atlas de sustancia blanca cerebral y poder aplicar regiones de interés de forma automática a nuevos individuos, se ha desarrollado este trabajo final de máster, fruto del marco colaborativo entre la Universidad Politécnica de Valencia y el Hospital Quirón Valencia. Para ello, se han establecido 2 metodologías de creación de atlas de sustancia blanca cerebral. Posteriormente, se ha obtenido dicho atlas a partir de una muestra de 50 sujetos sanos. En él, se han segmentado 8 de las regiones de interés más utilizadas en el escenario clínico de las patologías cerebrales. Posteriormente, dichas regiones han sido aplicadas de forma automática a un nuevo grupo de individuos sanos y enfermos, obteniendo una aplicación óptima de dichas regiones y la consecuente extracción automática de los fascículos de sustancia blanca cerebral. Con ello, se elimina la variabilidad que inherentemente conlleva la segmentación manual. Este trabajo final de máster, ha sido presentado en el congreso internacional de la European Society for Magnetic Resonance in Medicine and Biology (ESMRMB) 2013, del 3 al 5 de octubre en Toulouse. Además, se está finalizando un artículo científico que incluye una muestra de validación ampliada para afianzar los resultados obtenidos, y progresar hacia su integración en el entorno clínico.Segura Roda, L. (2014). Creación de un atlas de la sustancia blanca cerebral para la extracción automática de fascículos axonales. http://hdl.handle.net/10251/59484Archivo delegad

    Análisis y predicción de la tendencia al rechazo de riñón por perfil genético basado en SNP's

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    El riñón es uno de los órganos encargados de excretar las sustancias tóxicas y seleccionar aquellas útiles, devolviéndolas al organismo. El ser humano dispone de 2 riñones y, a pesar de poder vivir con un único riñón si uno falla, el organismo se resiente. Las sustancias tóxicas son devueltas al organismo y pueden dañarse el resto de órganos. Es por ello que, si se llega a un daño irreversible, es necesario realizar un trasplante. No obstante, el sistema inmunológico del paciente puede reconocer el órgano como un invasor y rechazarlo. Dicho rechazo puede producirse de inmediato, a los 3 meses de la operación o pasado un año. En ese caso tanto el injerto como la salud del paciente sufren un gran deterioro y es necesario reemplazar el órgano trasplantado. Con este trabajo se pretende analizar la relación de los cambios genéticos en el ADN con la presencia del rechazo post-trasplante, así como crear un modelo predictivo que permita predecir si, dado un perfil genético e información clínica del paciente, va a producirse rechazo o no, previniendo dicha problemática y aumentando la calidad de vida de los pacientes que padecen enfermedades renales crónicas con necesidad de trasplante.Segura Roda, L. (2011). Análisis y predicción de la tendencia al rechazo de riñón por perfil genético basado en SNP's. http://hdl.handle.net/10251/11568.Archivo delegad

    Genetic polymorphisms located in genes related to immune and inflammatory processes are associated with end-stage renal disease: a preliminary study

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    Background Chronic kidney disease progression has been linked to pro-inflammatory cytokines and markers of inflammation. These markers are also elevated in end-stage renal disease (ESRD), which constitutes a serious public health problem. Objective To investigate whether single nucleotide polymorphisms (SNPs) located in genes related to immune and inflammatory processes, could be associated with ESRD development. Design and methods A retrospective case-control study was carried out on 276 patients with ESRD and 288 control subjects. Forty-eight SNPs were genotyped via SNPlex platform. Logistic regression was used to assess the relationship between each sigle polymorphism and the development of ESRD. Results Four polymorphisms showed association with ESRD: rs1801275 in the interleukin 4 receptor (IL4R) gene (OR: 0.66 (95%CI=0.46-0.95); p=0.025; overdominant model), rs4586 in chemokine (C-C motif) ligand 2 (CCL2) gene (OR: 0.70 (95%CI=0.54-0.90); p=0.005; additive model), rs301640 located in an intergenic binding site for signal transducer and activator of transcription 4 (STAT4) (OR: 1.82 (95%CI=1.17-2.83); p=0.006; additive model) and rs7830 in the nitric oxide synthase 3 (NOS3) gene (OR: 1.31 (95%CI=1.01-1.71); p=0.043; additive model). After adjusting for multiple testing, results lost significance. Conclusion Our preliminary data suggest that four genetic polymorphisms located in genes related to inflammation and immune processes could help to predict the risk of developing ESRD.This work was supported by grants from Instituto de Salud Carlos III (Ref: PI08/0738 and PI11/00245) to SR and Junta de Castilla y Leon (Ref: GRS 234/A/08) to ET. MAJS is supported by a grant from Instituto de Salud Carlos III (CM10/00105).Jimenez-Sousa, MA.; López, E.; Fernandez-Rodriguez, A.; Tamayo, E.; Fernández-Navarro, P.; Segura Roda, L.; Heredia, M.... (2012). Genetic polymorphisms located in genes related to immune and inflammatory processes are associated with end-stage renal disease: a preliminary study. BMC Medical Genetics. 13(58):1-6. https://doi.org/10.1186/1471-2350-13-58S161358Otero A, de Francisco A, Gayoso P, Garcia F: Prevalence of chronic renal disease in Spain: results of the EPIRCE study. Nefrologia. 2010, 30 (1): 78-86.Kottgen A: Genome-wide association studies in nephrology research. Am J Kidney Dis. 2010, 56 (4): 743-758. 10.1053/j.ajkd.2010.05.018.Gansevoort RT, Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, Jong PE, Coresh J, de Jong PE, El-Nahas M, et al: Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes in both general and high-risk populations. 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Nat Genet. 2010, 42 (5): 376-384. 10.1038/ng.568.Chambers JC, Zhang W, Lord GM, van der Harst P, Lawlor DA, Sehmi JS, Gale DP, Wass MN, Ahmadi KR, Bakker SJ, et al: Genetic loci influencing kidney function and chronic kidney disease. Nat Genet. 2010, 42 (5): 373-375. 10.1038/ng.566.Ribases M, Ramos-Quiroga JA, Sanchez-Mora C, Bosch R, Richarte V, Palomar G, Gastaminza X, Bielsa A, Arcos-Burgos M, Muenke M, et al: Contribution of LPHN3 to the genetic susceptibility to ADHD in adulthood: a replication study. Genes Brain Behav. 2010, 10 (2): 149-157.Sole X, Guino E, Valls J, Iniesta R, Moreno V: SNPStats: a web tool for the analysis of association studies. Bioinformatics. 2006, 22 (15): 1928-1929. 10.1093/bioinformatics/btl268.Fried L, Solomon C, Shlipak M, Seliger S, Stehman-Breen C, Bleyer AJ, Chaves P, Furberg C, Kuller L, Newman A: Inflammatory and prothrombotic markers and the progression of renal disease in elderly individuals. J Am Soc Nephrol. 2004, 15 (12): 3184-3191. 10.1097/01.ASN.0000146422.45434.35.Wolkow PP, Niewczas MA, Perkins B, Ficociello LH, Lipinski B, Warram JH, Krolewski AS: Association of urinary inflammatory markers and renal decline in microalbuminuric type 1 diabetics. J Am Soc Nephrol. 2008, 19 (4): 789-797. 10.1681/ASN.2007050556.Nakamura E, Megumi Y, Kobayashi T, Kamoto T, Ishitoya S, Terachi T, Tachibana M, Matsushiro H, Habuchi T, Kakehi Y, et al: Genetic polymorphisms of the interleukin-4 receptor alpha gene are associated with an increasing risk and a poor prognosis of sporadic renal cell carcinoma in a Japanese population. Clin Cancer Res. 2002, 8 (8): 2620-2625.Burgos PI, Causey ZL, Tamhane A, Kelley JM, Brown EE, Hughes LB, Danila MI, van Everdingen A, Conn DL, Jonas BL, et al: Association of IL4R single-nucleotide polymorphisms with rheumatoid nodules in African Americans with rheumatoid arthritis. Arthritis Res Ther. 2010, 12 (3): R75-10.1186/ar2994.Tachdjian R, Mathias C, Al Khatib S, Bryce PJ, Kim HS, Blaeser F, O'Connor BD, Rzymkiewicz D, Chen A, Holtzman MJ, et al: Pathogenicity of a disease-associated human IL-4 receptor allele in experimental asthma. J Exp Med. 2009, 206 (10): 2191-2204. 10.1084/jem.20091480.Zheng G, Wang Y, Xiang SH, Tay YC, Wu H, Watson D, Coombes J, Rangan GK, Alexander SI, Harris DC: DNA vaccination with CCL2 DNA modified by the addition of an adjuvant epitope protects against "nonimmune" toxic renal injury. J Am Soc Nephrol. 2006, 17 (2): 465-474. 10.1681/ASN.2005020164.Kang YS, Lee MH, Song HK, Ko GJ, Kwon OS, Lim TK, Kim SH, Han SY, Han KH, Lee JE, et al: CCR2 antagonism improves insulin resistance, lipid metabolism, and diabetic nephropathy in type 2 diabetic mice. Kidney Int. 2010, 78 (9): 883-894. 10.1038/ki.2010.263.Dai R, Ahmed SA: MicroRNA, a new paradigm for understanding immunoregulation, inflammation, and autoimmune diseases. Transl Res. 2011, 157 (4): 163-179. 10.1016/j.trsl.2011.01.007.Messeguer X, Escudero R, Farre D, Nunez O, Martinez J, Alba MM: PROMO: detection of known transcription regulatory elements using species-tailored searches. Bioinformatics. 2002, 18 (2): 333-334. 10.1093/bioinformatics/18.2.333.Farre D, Roset R, Huerta M, Adsuara JE, Rosello L, Alba MM, Messeguer X: Identification of patterns in biological sequences at the ALGGEN server: PROMO and MALGEN. Nucleic Acids Res. 2003, 31 (13): 3651-3653. 10.1093/nar/gkg605.Wei L, Vahedi G, Sun HW, Watford WT, Takatori H, Ramos HL, Takahashi H, Liang J, Gutierrez-Cruz G, Zang C, et al: Discrete roles of STAT4 and STAT6 transcription factors in tuning epigenetic modifications and transcription during T helper cell differentiation. 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    Standalone vertex finding in the ATLAS muon spectrometer

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    A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

    Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

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    Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson

    Measurement of the top quark-pair production cross section with ATLAS in pp collisions at \sqrt{s}=7\TeV

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    A measurement of the production cross-section for top quark pairs(\ttbar) in pppp collisions at \sqrt{s}=7 \TeV is presented using data recorded with the ATLAS detector at the Large Hadron Collider. Events are selected in two different topologies: single lepton (electron ee or muon μ\mu) with large missing transverse energy and at least four jets, and dilepton (eeee, μμ\mu\mu or eμe\mu) with large missing transverse energy and at least two jets. In a data sample of 2.9 pb-1, 37 candidate events are observed in the single-lepton topology and 9 events in the dilepton topology. The corresponding expected backgrounds from non-\ttbar Standard Model processes are estimated using data-driven methods and determined to be 12.2±3.912.2 \pm 3.9 events and 2.5±0.62.5 \pm 0.6 events, respectively. The kinematic properties of the selected events are consistent with SM \ttbar production. The inclusive top quark pair production cross-section is measured to be \sigmattbar=145 \pm 31 ^{+42}_{-27} pb where the first uncertainty is statistical and the second systematic. The measurement agrees with perturbative QCD calculations.Comment: 30 pages plus author list (50 pages total), 9 figures, 11 tables, CERN-PH number and final journal adde

    Measurement of the top quark pair cross section with ATLAS in pp collisions at √s=7 TeV using final states with an electron or a muon and a hadronically decaying τ lepton

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    A measurement of the cross section of top quark pair production in proton-proton collisions recorded with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 7 TeV is reported. The data sample used corresponds to an integrated luminosity of 2.05 fb -1. Events with an isolated electron or muon and a τ lepton decaying hadronically are used. In addition, a large missing transverse momentum and two or more energetic jets are required. At least one of the jets must be identified as originating from a b quark. The measured cross section, σtt-=186±13(stat.)±20(syst.)±7(lumi.) pb, is in good agreement with the Standard Model prediction

    Hunt for new phenomena using large jet multiplicities and missing transverse momentum with ATLAS in 4.7 fb−1 of √s=7 TeV proton-proton collisions

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    Results are presented of a search for new particles decaying to large numbers of jets in association with missing transverse momentum, using 4.7 fb−1 of pp collision data at s√=7TeV collected by the ATLAS experiment at the Large Hadron Collider in 2011. The event selection requires missing transverse momentum, no isolated electrons or muons, and from ≥6 to ≥9 jets. No evidence is found for physics beyond the Standard Model. The results are interpreted in the context of a MSUGRA/CMSSM supersymmetric model, where, for large universal scalar mass m 0, gluino masses smaller than 840 GeV are excluded at the 95% confidence level, extending previously published limits. Within a simplified model containing only a gluino octet and a neutralino, gluino masses smaller than 870 GeV are similarly excluded for neutralino masses below 100 GeV

    Search for anomalous production of prompt like-sign muon pairs and constraints on physics beyond the standard model with the ATLAS detector

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    Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMAn inclusive search for anomalous production of two prompt, isolated muons with the same electric charge is presented. The search is performed in a data sample corresponding to 1.6 fb-1 of integrated luminosity collected in 2011 at √s = 7 TeV with the ATLAS detector at the LHC. Muon pairs are selected by requiring two isolated muons of the same electric charge with pT > 20 GeV and |η| < 2.5. Minimal requirements are placed on the rest of the event activity. The distribution of the invariant mass of the muon pair m(μμ) is found to agree well with the background expectation. Upper limits on the cross section for anomalous production of two muons with the same electric charge are placed as a function of m(μμ) within a fiducial region defined by the event selection. The fiducial cross-section limit constrains the like-sign top-quark pair-production cross section to be below 3.7 pb at 95% confidence level. The data are also analyzed to search for a narrow like-sign dimuon resonance as predicted for e.g. doubly charged Higgs bosons (H±±). Assuming pair production of H±± bosons and a branching ratio to muons of 100% (33%), this analysis excludes masses below 355 (244) GeV and 251 (209) GeV for H±± bosons coupling to left-handed and right-handed fermions, respectivelyWe acknowledge the support of ANPCyT, Argentina; YerPhI, Armenia; ARC, Australia; BMWF, Austria; ANAS, Azerbaijan; SSTC, Belarus; CNPq and FAPESP, Brazil; NSERC, NRC and CFI, Canada; CERN; CONICYT, Chile; CAS, MOST and NSFC, China; COLCIENCIAS, Colombia; MSMT CR, MPO CR and VSC CR, Czech Republic; DNRF, DNSRC and Lundbeck Foundation, Denmark; ARTEMIS, European Union; IN2P3-CNRS, CEA-DSM/IRFU, France; GNAS, Georgia; BMBF, DFG, HGF, MPG and AvH Foundation, Germany; GSRT, Greece; ISF, MINERVA, GIF, DIP and Benoziyo Center, Israel; INFN, Italy; MEXT and JSPS, Japan; CNRST, Morocco; FOM and NWO, Netherlands; RCN, Norway; MNiSW, Poland; GRICES and FCT, Portugal; MERYS (MECTS), Romania; MES of Russia and ROSATOM, Russian Federation; JINR; MSTD, Serbia; MSSR, Slovakia; ARRS and MVZT, Slovenia; DST/NRF, South Africa; MICINN, Spain; SRC and Wallenberg Foundation, Sweden; SER, SNSF and Cantons of Bern and Geneva, Switzerland; NSC, Taiwan; TAEK, Turkey; STFC, the Royal Society and Leverhulme Trust, United Kingdom; DOE and NSF, United States of America. The crucial computing support from all WLCG partners is acknowledged gratefully, in particular, from CERN and the ATLAS Tier-1 facilities at TRIUMF (Canada), NDGF (Denmark, Norway, Sweden), CC-IN2P3 (France), KIT/GridKA (Germany), INFNCNAF (Italy), NL-T1 (Netherlands), PIC (Spain), ASGC (Taiwan), RAL (UK) and BNL (USA) and in the Tier-2 facilities worldwid

    Study of jets produced in association with a W boson in pp collisions at s√=7  TeV with the ATLAS detector

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    We report a study of final states containing a W boson and hadronic jets, produced in proton-proton collisions at a center-of-mass energy of 7 TeV. The data were collected with the ATLAS detector at the CERN LHC and comprise the full 2010 data sample of 36 pb(-1). Cross sections are determined using both the electron and muon decay modes of the W boson and are presented as a function of inclusive jet multiplicity, N-jet, for up to five jets. At each multiplicity, cross sections are presented as a function of jet transverse momentum, the scalar sum of the transverse momenta of the charged lepton, missing transverse momentum, and all jets, the invariant mass spectra of jets, and the rapidity distributions of various combinations of leptons and final-state jets. The results, corrected for all detector effects and for all backgrounds such as diboson and top quark pair production, are compared with particle-level predictions from perturbative QCD. Leading-order multiparton event generators, normalized to the next-to-next-to-leading-order total cross section for inclusive W-boson production, describe the data reasonably well for all measured inclusive jet multiplicities. Next-to-leading-order calculations from MCFM, studied here for N-jet <= 2, and BLACKHAT-SHERPA, studied here for N-jet <= 4, are found to be mostly in good agreement with the data
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