992 resultados para Axis 4
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Dissertação de Mestrado, Gestão Empresarial, Faculdade de Economia, Universidade do Algarve, 2015
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BACKGROUND: Left atrial (LA) dilatation is associated with a large variety of cardiac diseases. Current cardiovascular magnetic resonance (CMR) strategies to measure LA volumes are based on multi-breath-hold multi-slice acquisitions, which are time-consuming and susceptible to misregistration. AIM: To develop a time-efficient single breath-hold 3D CMR acquisition and reconstruction method to precisely measure LA volumes and function. METHODS: A highly accelerated compressed-sensing multi-slice cine sequence (CS-cineCMR) was combined with a non-model-based 3D reconstruction method to measure LA volumes with high temporal and spatial resolution during a single breath-hold. This approach was validated in LA phantoms of different shapes and applied in 3 patients. In addition, the influence of slice orientations on accuracy was evaluated in the LA phantoms for the new approach in comparison with a conventional model-based biplane area-length reconstruction. As a reference in patients, a self-navigated high-resolution whole-heart 3D dataset (3D-HR-CMR) was acquired during mid-diastole to yield accurate LA volumes. RESULTS: Phantom studies. LA volumes were accurately measured by CS-cineCMR with a mean difference of -4.73 ± 1.75 ml (-8.67 ± 3.54%, r2 = 0.94). For the new method the calculated volumes were not significantly different when different orientations of the CS-cineCMR slices were applied to cover the LA phantoms. Long-axis "aligned" vs "not aligned" with the phantom long-axis yielded similar differences vs the reference volume (-4.87 ± 1.73 ml vs. -4.45 ± 1.97 ml, p = 0.67) and short-axis "perpendicular" vs. "not-perpendicular" with the LA long-axis (-4.72 ± 1.66 ml vs. -4.75 ± 2.13 ml; p = 0.98). The conventional bi-plane area-length method was susceptible for slice orientations (p = 0.0085 for the interaction of "slice orientation" and "reconstruction technique", 2-way ANOVA for repeated measures). To use the 3D-HR-CMR as the reference for LA volumes in patients, it was validated in the LA phantoms (mean difference: -1.37 ± 1.35 ml, -2.38 ± 2.44%, r2 = 0.97). Patient study: The CS-cineCMR LA volumes of the mid-diastolic frame matched closely with the reference LA volume (measured by 3D-HR-CMR) with a difference of -2.66 ± 6.5 ml (3.0% underestimation; true LA volumes: 63 ml, 62 ml, and 395 ml). Finally, a high intra- and inter-observer agreement for maximal and minimal LA volume measurement is also shown. CONCLUSIONS: The proposed method combines a highly accelerated single-breathhold compressed-sensing multi-slice CMR technique with a non-model-based 3D reconstruction to accurately and reproducibly measure LA volumes and function.
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The Commission on Classification and Terminology and the Commission on Epidemiology of the International League Against Epilepsy (ILAE) have charged a Task Force to revise concepts, definition, and classification of status epilepticus (SE). The proposed new definition of SE is as follows: Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms, which lead to abnormally, prolonged seizures (after time point t1 ). It is a condition, which can have long-term consequences (after time point t2 ), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures. This definition is conceptual, with two operational dimensions: the first is the length of the seizure and the time point (t1 ) beyond which the seizure should be regarded as "continuous seizure activity." The second time point (t2 ) is the time of ongoing seizure activity after which there is a risk of long-term consequences. In the case of convulsive (tonic-clonic) SE, both time points (t1 at 5 min and t2 at 30 min) are based on animal experiments and clinical research. This evidence is incomplete, and there is furthermore considerable variation, so these time points should be considered as the best estimates currently available. Data are not yet available for other forms of SE, but as knowledge and understanding increase, time points can be defined for specific forms of SE based on scientific evidence and incorporated into the definition, without changing the underlying concepts. A new diagnostic classification system of SE is proposed, which will provide a framework for clinical diagnosis, investigation, and therapeutic approaches for each patient. There are four axes: (1) semiology; (2) etiology; (3) electroencephalography (EEG) correlates; and (4) age. Axis 1 (semiology) lists different forms of SE divided into those with prominent motor systems, those without prominent motor systems, and currently indeterminate conditions (such as acute confusional states with epileptiform EEG patterns). Axis 2 (etiology) is divided into subcategories of known and unknown causes. Axis 3 (EEG correlates) adopts the latest recommendations by consensus panels to use the following descriptors for the EEG: name of pattern, morphology, location, time-related features, modulation, and effect of intervention. Finally, axis 4 divides age groups into neonatal, infancy, childhood, adolescent and adulthood, and elderly.
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The early Eocene epoch was characterized by extreme global warmth, which in terrestrial settings was characterized by an expansion of near-tropical vegetation belts into the high latitudes. During the middle to late Eocene, global cooling caused the retreat of tropical vegetation to lower latitudes. In high-latitude settings, near-tropical vegetation was replaced by temperate floras. This floral change has recently been traced as far south as Antarctica, where along the Wilkes Land margin paratropical forests thrived during the early Eocene and temperate Nothofagus forests developed during the middle Eocene. Here we provide both qualitative and quantitative palynological data for this floral turnover based on a sporomorph record recovered at Integrated Ocean Drilling Program (IODP) Site U1356 off the Wilkes Land margin. Following the nearest living relative concept and based on a comparison with modern vegetation types, we examine the structure and diversity patterns of the Eocene vegetation along the Wilkes Land margin. Our results indicate that the early Eocene forests along the Wilkes Land margin were characterized by a diverse canopy composed of plants that today occur in tropical settings; their richness pattern was similar to that of present-day forests from New Caledonia. The middle Eocene forests were characterized by a canopy dominated by Nothofagus and exhibited richness patterns similar to modern Nothofagus forests from New Zealand.
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The chemical composition of shells of the planktonic foraminifer Globigerinoides ruber (white) is frequently used to determine past sea surface conditions. Recently, it has been shown that arbitrarily defined morphotypes within this species exhibit different chemical and isotopic signatures. Here, we investigate the occurrence through time and in space of morphological types of G. ruber (white) in late Quaternary and Holocene sediments of the central and the eastern Mediterranean Sea. In 115 samples representing two distinct time intervals (MIS 1-2 and MIS 9-12) at ODP Site 964 and the piston core GeoTü-SL96, we have defined three morphological types within this species and determined their relative abundances and stable isotopic composition. A quantitative analysis of morphological variation within G. ruber (white) in four samples revealed that the subjectively defined morphotypes occupy separate segments of a continuous and homogenous morphospace. We further show that the abundance of the morphotypes changes significantly between glacials and interglacials and that the three morphotypes of G. ruber show significant offsets in their stable isotopic composition. These offsets are consistent within glacial and interglacial stages but their sign is systematically reversed between the two Sites. Since the isotopic shifts among the three G. ruber morphotypes are systematic and often exceed 1per mil, their understanding is essential for the interpretation of all G. ruber-based proxy records for the paleoceanographic development of the Mediterranean during the late Quaternary.
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Exploration of the Foundation Volcanic Chain (33 degrees S-131 degrees W; 37 degrees S-111 degrees W) revealed the existence of different magmatic provinces with relation to their geological settings. (1) The Pacific-Antarctic Ridge (PAR) is made up of several en echelon segments where both glassy midocean ridge basalts (MORBs) with low incompatible elements (K2O<200 ppm, Zr<120 ppm and Ce <20 ppm) as well as andesites and dacites have erupted, (2) Oblique Ridges located up to 300 lan from the PAR axis are topped with seamounts made up essentially of transitional (T) and enriched (E) MORBs with intermediate incompatible elements (K2O=0.11-0.40 %, Zr=70-140 ppm and Ce=15-30 ppm), (3) the Foundation Seamounts (FS) consisting essentially of isolated volcanoes which have erupted alkalic lavas (alkali basalt, trachybasalt and trachyandesite) with high incompatible elements (K2O (0.50-1.1 %, Zr (>150 ppm) and Ce (>48 ppm)) at about 306-1300 km from the PAR axis, (4) The Old Pacific Seamounts built on a crust older than 23 m. y. located west of longitude 124 degrees W (> 1300 km from the PAR axis) consist of T and EMORB. On the PAR axis, extensive crystal fractionation (>65%) produced the silicic lavas. On the basis of Pacific plate reconstruction using a half spreading rate of about 50 mm/yr and integrating the observed compositional changes with respect to the structural settings, it is inferred that the last volcanic events giving rise to the FS took place at about 110 km from the PAR axis about 5 m. y. ago. The Oblique Ridges built between 5 m. y. and <1 m. y. are believed to represent ancient leaky transforms and/or large discontinuities between accreting ridge segments filled by volcanic cones during the interaction (mixing) of the enriched plume components of the FS with PAR depleted (MORB type) magmatism. The Old Pacific Seamounts built on ancient crust (>23 m. y.) with MORB volcanics comparable to those of the the Oblique Ridge-PAR provinces, could also have been formed by an interaction between the Foundation Seamount (dredge site 28) hotspot magmatism and that of an ancient accreting ridge magmatism precursor of the PAR.
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O Relatório de estágio tem por desígnio, compreender e analisar, o statu quo das dimensões da satisfação (Contemplando o seu bem-estar pessoal e social) dos utentes das valências da Santa Casa da Misericórdia de Évora, por conseguinte, analisando e compreendendo a qualidade de vida desses mesmos utentes, debruçando-se, pois, sobre as potenciais e/ou evidentes necessidades institucionais por suprimir, e problemas sociais por erradicar. O levantamento da actual informação obteve-se através de dois instrumentos metodológicos de recolha de dados: inquérito por questionário de aplicação directa auto-administrada (utentes), e por intermédio de entrevistas semi-estruturadas (diretores técnicos das valências). Relativamente, aos métodos de tratamento de dados, no primeiro instrumento utilizou-se IBM SPSS 22, já no segundo análise de conteúdo. Após a detecção das necessidades existentes, procedeu-se a elaboração de uma proposta de intervenção sócio-organizacional, por forma a solucionar essas mesmas necessidades existentes. O presente documento estrutura-se em 4 eixos: o Eixo 1 – Componente teórica - ; o Eixo 2 – Componente metodológica - ; Eixo 3 – Componente dos resultados - ; Eixo 4 – Componente de intervenção sócio- organizacional; Abstract: Intervention of the Holy House of Mercy of Evora - The quality of the Social Responses and satisfaction perceived Internal SCME of users -. This work is to design, understand and analyze the status quo of the dimensions of satisfaction (Contemplating their personal and social welfare) of users of the valences of the Holy House of Mercy of Evora, therefore, analyzing and understanding the quality life of these same users, addressing therefore, on potential and / or obvious institutional needs to suppress and eradicate social problems. The survey of current information was obtained through two methodological tools for data collection: survey by self-administered direct application questionnaire (users), and through semi-structured interviews (technical directors of valences). With regard to the data processing methods, the first instrument was used SPSS 22, in the second content analysis. After detection of the needs, it proceeded to draw up a proposal for social and organizational intervention in order to solve these same existing needs. This document is divided into four axes: Axis 1 - Theoretical component -; Axis 2 - methodological component -; Axis 3 - Component of results -; Axis 4 - socio-organizational intervention component.
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Background Epidemiological and experimental data suggest that bacteria] lipopolysaccharides (LPS) can either protect from or exacerbate allergic asthma. Lipopolysaccharides trigger immune responses through toll-like receptor 4 (TLR4) that in turn activates two major signalling pathways via either MyD88 or TRIF adaptor proteins. The LPS is a pro-Type 1 T helper cells (Th 1) adjuvant while aluminium hydroxide (alum) is a strong Type 2 T helper cells (Th2) adjuvant, but the effect of the mixing of both adjuvants on the development of lung allergy has not been investigated. Objective We determined whether natural (LPS) or synthetic (ER-803022) TLR4 agonists adsorbed onto alum adjuvant affect allergen sensitization and development of airway allergic disease. To dissect LPS-induced molecular pathways, we used TLR4-, MyD88-, TRIF-, or IL-12/IFN-gamma-deficient mice. Methods Mice were sensitized with subcutaneous injections of ovalbumin (OVA) with or without TLR4 agonists co-adsorbed onto alum and challenged with intranasally with OVA. The development of allergic lung disease was evaluated 24 h after last OVA challenge. Results Sensitization with OVA plus LPS co-adsorbed onto alum impaired in dose-dependent manner OVA-induced Th2-mediated allergic responses such as airway eosinophilia, type-2 cytokines secretion, airway hyper-reactivity, mucus hyper production and serum levels of IgE or IgG1 anaphylactic antibodies. Although the levels of IgG2a, Th1 -affiliated isotype increased, investigation into the lung-specific effects revealed that LPS did not induce a Th1 pattern of inflammation. Lipopolysaccharides impaired the development of Th2 immunity, signaling via TLR4 and MyD88 molecules and via the IL-12/IFN-gamma axis, but not through TRIF pathway. Moreover, the synthetic TLR4 agonists that proved to have a less systemic inflammatory response than LPS also protected against allergic asthma development. Conclusion Toll-like receptor 4 agonists co-adsorbed with allergen onto alum down-modulate allergic lung disease and prevent the development of polarized T cell-mediated airway inflammation.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Pattern recognition receptors for fungi include dectin-1 and mannose receptor, and these mediate phagocytosis, as well as production of cytokines, reactive oxygen species, and the lipid mediator leukotriene B-4 (LTB4). The influence of G protein-coupled receptor ligands such as LTB4 on fungal pattern recognition receptor expression is unknown. In this study, we investigated the role of LTB4 signaling in dectin-1 expression and responsiveness in macrophages. Genetic and pharmacologic approaches showed that LTB4 production and signaling through its high-affinity G protein-coupled receptor leukotriene B4 receptor 1 (BLT1) direct dectin-1-dependent binding, ingestion, and cytokine production both in vitro and in vivo. Impaired responses to fungal glucans correlated with lower dectin-1 expression in macrophages from leukotriene (LT)- and BLT1-deficent mice than their wildtype counterparts. LTB4 increased the expression of the transcription factor responsible for dectin-1 expression, PU.1, and PU.1 small interfering RNA abolished LTB4-enhanced dectin-1 expression. GM-CSF controls PU.1 expression, and this cytokine was decreased in LT-deficient macrophages. Addition of GM-CSF to LT-deficient cells restored expression of dectin-1 and PU.1, as well as dectin-1 responsiveness. In addition, LTB4 effects on dectin-1, PU.1, and cytokine production were blunted in GM-CSF-/- macrophages. Our results identify LTB4-BLT1 signaling as an unrecognized controller of dectin-1 transcription via GM-CSF and PU.1 that is required for fungi-protective host responses. The Journal of Immunology, 2012, 189: 906-915.
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OBJECTIVE: The importance of the costimulatory molecules CD28 and CTLA-4 in the pathologic mechanism of rheumatoid arthritis (RA) has been demonstrated by genetic associations and the successful clinical application of CTLA-4Ig for the treatment of RA. This study was undertaken to investigate the role of the CTLA-4/CD28 axis in the local application of CTLA-4Ig in the synovial fluid (SF) of RA patients. METHODS: Quantitative polymerase chain reaction was used to analyze the expression of proinflammatory and antiinflammatory cytokines in ex vivo fluorescence-activated cell sorted CTLA-4+ and CTLA-4- T helper cells from the peripheral blood and SF of RA patients. T helper cells were also analyzed for cytokine expression in vitro after the blockade of CTLA-4 by anti-CTLA-4 Fab fragments or of B7 (CD80/CD86) molecules by CTLA-4Ig. RESULTS: CTLA-4+ T helper cells were unambiguously present in the SF of all RA patients examined, and they expressed increased amounts of interferon-γ (IFNγ), interleukin-17 (IL-17), and IL-10 as compared to CTLA-4- T helper cells. The selective blockade of CTLA-4 in T helper cells from the SF in vitro led to increased levels of IFNγ, IL-2, and IL-17. The concomitant blockade of CD28 and CTLA-4 in T helper cells from RA SF by CTLA-4Ig in vitro resulted in reduced levels of the proinflammatory cytokines IFNγ and IL-2 and increased levels of the antiinflammatory cytokines IL-10 and transforming growth factor β. CONCLUSION: Our ex vivo and in vitro results demonstrate that the CTLA-4/CD28 axis constitutes a drug target for not only the systemic, but potentially also the local, application of the costimulation blocking agent CTLA-4Ig for the treatment of RA.