208 resultados para endplate irregularity
Resumo:
El desarrollo de nuevas estructuras aeroespaciales optimizadas, utilizan materiales compuestos, para los componentes críticos y subsistemas, principalmente polímeros reforzados con fibra de carbono (CFRP). Un conocimiento profundo del estado de daño por fatiga de estructuras de CFRP avanzado, es esencial para predecir la vida residual y optimizar los intervalos de inspección estructural, reparaciones y/o sustitución de componentes. Las técnicas actuales se basan principalmente en la medición de cargas estructurales a lo largo de la vida útil de la estructura mediante galgas extensométricas eléctricas. Con esos datos, se estima la vida a fatiga utilizando modelos de acumulación de daño. En la presente tesis, se evalúa la metodología convencional para la estimación de la vida a fatiga de un CFRP aeronáutico. Esta metodología está basada en la regla de acumulación de daño lineal de Palmgren-Miner, y es aplicada para determinar la vida a fatiga de estructuras sometidas a cargas de amplitud variable. Se ha realizado una campaña de ensayos con cargas de amplitud constante para caracterizar un CFRP aeronáutico a fatiga, obteniendo las curvas clásicas S-N, en diferentes relaciones de esfuerzo. Se determinaron los diagramas de vida constante, (CLD), también conocidos como diagramas de Goodman, utilizando redes neuronales artificiales debido a la ausencia de modelos coherentes para materiales compuestos. Se ha caracterizado la degradación de la rigidez debido al daño por fatiga. Se ha ensayado un segundo grupo de probetas con secuencias estandarizadas de cargas de amplitud variable, para obtener la vida a fatiga y la degradación de rigidez en condiciones realistas. Las cargas aplicadas son representativas de misiones de aviones de combate (Falstaff), y de aviones de transporte (Twist). La vida a fatiga de las probetas cicladas con cargas de amplitud variable, se comparó con el índice de daño teórico calculado en base a la regla de acumulación de daño lineal convencional. Los resultados obtenidos muestran predicciones no conservativas. Esta tesis también presenta el estudio y desarrollo, de una nueva técnica de no contacto para evaluar el estado de daño por fatiga de estructuras de CFRP por medio de cambios de los parámetros de rugosidad. La rugosidad superficial se puede medir fácilmente en campo con métodos sin contacto, mediante técnicas ópticas tales como speckle y perfilómetros ópticos. En el presente estudio, se han medido parámetros de rugosidad superficial, y el factor de irregularidad de la superficie, a lo largo de la vida de las probetas cicladas con cargas de amplitud constante y variable, Se ha obtenido una buena tendencia de ajuste al correlacionar la magnitud de la rugosidad y el factor de irregularidad de la superficie con la degradación de la rigidez de las probetas fatigadas. Estos resultados sugieren que los cambios en la rugosidad superficial medida en zonas estratégicas de componentes y estructuras hechas de CFRP, podrían ser indicativas del nivel de daño interno debido a cargas de fatiga. Los resultados también sugieren que el método es independiente del tipo de carga de fatiga que ha causado el daño. Esto último hace que esta técnica de medición sea aplicable como inspección para una amplia gama de estructuras de materiales compuestos, desde tanques presurizados con cargas de amplitud constante, estructuras aeronáuticas como alas y colas de aeronaves cicladas con cargas de amplitud variable, hasta aplicaciones industriales como automoción, entre otros. ABSTRACT New optimized aerospace structures use composite materials, mainly carbon fiber reinforced polymer composite (CFRP), for critical components and subsystems. A strong knowledge of the fatigue state of highly advanced (CFRP) structures is essential to predict the residual life and optimize intervals of structural inspection, repairs, and/or replacements. Current techniques are based mostly on measurement of structural loads throughout the service life by electric strain gauge sensors. These sensors are affected by extreme environmental conditions and by fatigue loads in such a way that the sensors and their systems require exhaustive maintenance throughout system life. In the present thesis, the conventional methodology based on linear damage accumulation rules, applied to determine the fatigue life of structures subjected to variable amplitude loads was evaluated for an aeronautical CFRP. A test program with constant amplitude loads has been performed to obtain the classical S-N curves at different stress ratios. Constant life diagrams, CLDs, where determined by means of Artificial Neural Networks due to the absence of consistent models for composites. The stiffness degradation due to fatigue damage has been characterized for coupons under cyclic tensile loads. A second group of coupons have been tested until failure with a standardized sequence of variable amplitude loads, representative of missions for combat aircraft (Falstaff), and representative of commercial flights (Twist), to obtain the fatigue life and the stiffness degradation under realistic conditions. The fatigue life of the coupons cycled with variable amplitude loads were compared to the theoretical damage index calculated based on the conventional linear damage accumulation rule. The obtained results show non-conservative predictions. This thesis also presents the evaluation of a new non-contact technique to evaluate the fatigue damage state of CFRP structures by means of measuring roughness parameters to evaluate changes in the surface topography. Surface roughness can be measured easily on field with non-contact methods by optical techniques such as speckle and optical perfilometers. In the present study, surface roughness parameters, and the surface irregularity factor, have been measured along the life of the coupons cycled with constant and variable amplitude loads of different magnitude. A good agreement has been obtained when correlating the magnitude of the roughness and the surface irregularity factor with the stiffness degradation. These results suggest that the changes on the surface roughness measured in strategic zones of components and structures made of CFRP, could be indicative of the level of internal damage due to fatigue loads. The results also suggest that the method is independent of the type of fatigue load that have caused the damage. It makes this measurement technique applicable for a wide range of inspections of composite materials structures, from pressurized tanks with constant amplitude loads, to variable amplitude loaded aeronautical structures like wings and empennages, up to automotive and other industrial applications.
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El cuerpo, como conjunto organizado de partes que configuran el organismo, es una entidad metamórfica. El ser humano procura dar continuidad a esta condición mutante que le caracteriza, mediante diversas acciones de carácter arquitectónico. A partir de la observación de los procesos naturales, el individuo se autodefine artificialmente, transformando su realidad innata en una versión distorsionada de sí misma. Por adición, sustracción o modificación, la piel como última capa natural, se convierte en lienzo de manipulación plástica primordial para asegurar la existencia y controlar la identidad, individual y colectiva. La evolución experimental de estas intervenciones primarias, permite suplantar la piel natural por una reinterpretación construida; una piel exenta y desmontable con la que proyectar un yo diferente provisionalmente. El uso constante de esta prótesis removible e intercambiable, provoca que el cuerpo desnudo se transforme en un cuerpo vestido, en un entorno social en el que la desnudez deja de ser el estado natural del ser humano. La piel artificial se construye mediante una gran diversidad de procesos proyectuales, siendo la transformación de la superficie bidimensional en envolvente tridimensional el más utilizado a lo largo de la existencia de la vestimenta. El plano, concebido como principal formato de revestimiento humano, se adapta a su irregularidad topográfica por modelado, perforación, fragmentación, trazado, parametrización e interacción, transformándose en una envolvente cada vez más compleja y perfecta. Su diseño implica la consideración de variables como la dimensión y la escala, la función y la forma, la estructura, el material y la construcción, la técnica y los instrumentos. La vestimenta es una arquitectura habitacional individual, un límite corporal que relaciona el espacio entre el exterior e el interior, lo ajeno y lo propio, el tú y el yo; un filtro concreto y abstracto simultáneamente; una interfaz en donde el vestido es el continente y el cuerpo su contenido. ABSTRACT The body as a whole, organized of parts that make up the organism, is a metamorphic entity. The human being seeks to give continuity to this mutant condition which characterizes him through various actions of architectural character. From the observation of the natural processes, the individual defines itself artificially, transforming its innate reality into a distorted version of itself. By addition, subtraction or modification, the skin, as the last natural layer, becomes canvas of primary plastic handling in order to ensure the existence and to control the identity, both individual and collective. The experimental evolution of these primary interventions allows to impersonate the natural skin by a constructed reinterpretation; a free and detachable skin together with which to be able to project, temporarily, a different “I”. The constant use of this removable and interchangeable prosthesis causes the naked body to be transformed into a dressed body, in a social setting in which the nudity is no longer the natural state of the human being. The artificial skin is constructed by a variety of projectual processes; the most used throughout the existence of the outfit is transforming the two-dimensional surface into a three-dimensional covering. The plan, conceived as the main human lining format, adapts to its topographic irregularity by modeling, drilling, fragmentation, outline, parameters and interaction, thus becoming a type of increasingly more complex and perfect covering. Its design implies the consideration of different variables such as the dimension and the scale, the function and the shape, the structure, the material and the construction, the technique and the instruments. The clothing is an individual residential architecture, a body boundary which relates the space between outside and inside, between the external and the self, between “you” and “I”; at the same time a specific and abstract filter; an interface where the dress is the container and the body its content.
Resumo:
A reflexão proposta neste estudo está centrada na possibilidade de o Novo Paradigma Sistêmico , tal qual o concebe o físico norte-americano Fritjof Capra, fundamentar um modelo epistemológico, possível de integrar em seu âmbito os pontos de vista divergentes no debate sobre o tratamento científico do fenômeno religioso. A história das ciências da religião está marcada pelo dilema epistemológico: explicar ou compreender a religião? As ciências da natureza contrapuseram-se às ciências do espírito, que diferiam das primeiras pelo objeto, pelo método e pela relação entre o sujeito e o objeto. O debate que esteve presente no cenário dos séculos XIX e XX mostrou-nos a impossibilidade de se definir um modelo de ciência que incorporasse, em seu seio, uma integração dos pontos de vista divergentes, em razão dos princípios que norteavam o paradigma cientificista. No entanto, a emergência do paradigma dos sistemas vivos ou da complexidade , liderado pela física, veio conceber o caráter sistêmico da realidade; que o concreto material é energia sob o aspecto subatômico; que sob o aspecto subatômico, a matéria não existe em lugares definidos com certeza, mas apenas mostram tendências a existir. Estas e outras descobertas possibilitaram aos cientistas afirmar a existência de um Novo Paradigma , em que as categorias análise, regularidade e objetividade, que caracterizavam o antigo, são substituídas por: síntese, irregularidade e conduta epistêmica. O paradigma emergente possibilitou a construção de um modelo epistemológico do conhecimento científico, que apontamos como legitimador das condutas fenomenológicas, tal qual as concebem G. van der Leeuw e F. Heiler, ao mesmo tempo em que possibilita a integração de pontos de vista divergentes, no debate entre as vertentes, explicação/compreensão.(AU)
Resumo:
A reflexão proposta neste estudo está centrada na possibilidade de o Novo Paradigma Sistêmico , tal qual o concebe o físico norte-americano Fritjof Capra, fundamentar um modelo epistemológico, possível de integrar em seu âmbito os pontos de vista divergentes no debate sobre o tratamento científico do fenômeno religioso. A história das ciências da religião está marcada pelo dilema epistemológico: explicar ou compreender a religião? As ciências da natureza contrapuseram-se às ciências do espírito, que diferiam das primeiras pelo objeto, pelo método e pela relação entre o sujeito e o objeto. O debate que esteve presente no cenário dos séculos XIX e XX mostrou-nos a impossibilidade de se definir um modelo de ciência que incorporasse, em seu seio, uma integração dos pontos de vista divergentes, em razão dos princípios que norteavam o paradigma cientificista. No entanto, a emergência do paradigma dos sistemas vivos ou da complexidade , liderado pela física, veio conceber o caráter sistêmico da realidade; que o concreto material é energia sob o aspecto subatômico; que sob o aspecto subatômico, a matéria não existe em lugares definidos com certeza, mas apenas mostram tendências a existir. Estas e outras descobertas possibilitaram aos cientistas afirmar a existência de um Novo Paradigma , em que as categorias análise, regularidade e objetividade, que caracterizavam o antigo, são substituídas por: síntese, irregularidade e conduta epistêmica. O paradigma emergente possibilitou a construção de um modelo epistemológico do conhecimento científico, que apontamos como legitimador das condutas fenomenológicas, tal qual as concebem G. van der Leeuw e F. Heiler, ao mesmo tempo em que possibilita a integração de pontos de vista divergentes, no debate entre as vertentes, explicação/compreensão.(AU)
Resumo:
O objetivo do presente estudo consistiu em analisar a estabilidade das alterações oclusais em 18 pacientes com má oclusão de Classe II, divisão 1, idade média inicial de 10,77 anos, tratados com o aparelho regulador de função RF-2 durante 18 meses e reavaliados num período de pós-tratamento 7,16 anos, em média. Os 54 modelos de gesso foram avaliados no início do tratamento (T1), no final do tratamento (T2) e decorridos 7,16 anos pós-tratamento (T3). Foram analisadas as alterações transversais e sagitais; o Índice de irregularidade de Little e o Índice de Prioridade de Tratamento (IPT). As alterações ocorridas nos períodos analisados foram verificadas por meio da análise de Variância- ANOVA e, em seguida, pelo teste de comparações múltiplas de Bonferroni, com o valor crítico adotado de 0,05. Os resultados demonstraram que o tratamento com o RF-2 promoveu um aumento transversal estatisticamente significante, tanto no arco dentário superior quanto no inferior, porém, no período pós-tratamento, houve recidiva parcial ou mesmo total deste aumento na maioria das dimensões analisadas. Já o comprimento dos arcos dentários superior e inferior diminuiu durante todo o período avaliado. O Índice de Irregularidade de Little apresentou-se estável durante o tratamento, entretanto aumentou no período pós-tratamento. Além disso, o tratamento com o RF-2 proporcionou uma diminuição estatisticamente significante do IPT, refletindo a eficácia do tratamento realizado uma vez que esta diminuição permaneceu estável no período pós-tratamento. Portanto, o aparelho RF-2 demonstrou ser eficaz na correção dentária da má oclusão de Classe II, divisão 1, com estabilidade dos resultados decorridos 7,16 anos após o tratamento. Porém, em relação ao ganho transversal nos arcos dentários obtido durante o tratamento, houve recidiva parcial ou total de todas as variáveis analisadas.(AU)
Resumo:
O objetivo do presente estudo consistiu em analisar a estabilidade das alterações oclusais em 18 pacientes com má oclusão de Classe II, divisão 1, idade média inicial de 10,77 anos, tratados com o aparelho regulador de função RF-2 durante 18 meses e reavaliados num período de pós-tratamento 7,16 anos, em média. Os 54 modelos de gesso foram avaliados no início do tratamento (T1), no final do tratamento (T2) e decorridos 7,16 anos pós-tratamento (T3). Foram analisadas as alterações transversais e sagitais; o Índice de irregularidade de Little e o Índice de Prioridade de Tratamento (IPT). As alterações ocorridas nos períodos analisados foram verificadas por meio da análise de Variância- ANOVA e, em seguida, pelo teste de comparações múltiplas de Bonferroni, com o valor crítico adotado de 0,05. Os resultados demonstraram que o tratamento com o RF-2 promoveu um aumento transversal estatisticamente significante, tanto no arco dentário superior quanto no inferior, porém, no período pós-tratamento, houve recidiva parcial ou mesmo total deste aumento na maioria das dimensões analisadas. Já o comprimento dos arcos dentários superior e inferior diminuiu durante todo o período avaliado. O Índice de Irregularidade de Little apresentou-se estável durante o tratamento, entretanto aumentou no período pós-tratamento. Além disso, o tratamento com o RF-2 proporcionou uma diminuição estatisticamente significante do IPT, refletindo a eficácia do tratamento realizado uma vez que esta diminuição permaneceu estável no período pós-tratamento. Portanto, o aparelho RF-2 demonstrou ser eficaz na correção dentária da má oclusão de Classe II, divisão 1, com estabilidade dos resultados decorridos 7,16 anos após o tratamento. Porém, em relação ao ganho transversal nos arcos dentários obtido durante o tratamento, houve recidiva parcial ou total de todas as variáveis analisadas.(AU)
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Oligonucleotides that recapitulate the acceptor stems of tRNAs are substrates for aminoacylation by many tRNA synthetases in vitro, even though these substrates are missing the anticodon trinucleotides of the genetic code. In the case of tRNAAla a single acceptor stem G⋅U base pair at position 3·70 is essential, based on experiments where the wobble pair has been replaced by alternatives such as I⋅U, G⋅C, and A⋅U, among others. These experiments led to the conclusion that the minor-groove free 2-amino group (of guanosine) of the G⋅U wobble pair is essential for charging. Moreover, alanine-inserting tRNAs (amber suppressors) that replace G⋅U with mismatches such as G⋅A and C⋅A are partially active in vivo and can support growth of an Escherichia coli tRNAAla knockout strain, leading to the hypothesis that a helix irregularity and nucleotide functionalities are important for recognition. Herein we investigate the charging in vitro of oligonucleotide and full-length tRNA substrates that contain mismatches at the position of the G⋅U pair. Although most of these substrates have undetectable activity, G⋅A and C⋅A variants retain some activity, which is, nevertheless, reduced by at least 100-fold. Thus, the in vivo assays are much less sensitive to large changes in aminoacylation kinetic efficiency of 3·70 variants than is the in vitro assay system. Although these functional data do not clarify all of the details, it is now clear that specific atomic groups are substantially more important in determining kinetic efficiency than is a helical distortion. By implication, the activity of mutant tRNAs measured in the in vivo assays appears to be more dependent on factors other than aminoacylation kinetic efficiency.
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Despite many diverse theories that address closely related themes—e.g., probability theory, algorithmic complexity, cryptoanalysis, and pseudorandom number generation—a near-void remains in constructive methods certified to yield the desired “random” output. Herein, we provide explicit techniques to produce broad sets of both highly irregular finite and normal infinite sequences, based on constructions and properties derived from approximate entropy (ApEn), a computable formulation of sequential irregularity. Furthermore, for infinite sequences, we considerably refine normality, by providing methods for constructing diverse classes of normal numbers, classified by the extent to which initial segments deviate from maximal irregularity.
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Choline acetyltransferase (ChAT; EC 2.3.1.6) catalyzes the reversible synthesis of acetylcholine (ACh) from acetyl CoA and choline at cholinergic synapses. Mutations in genes encoding ChAT affecting motility exist in Caenorhabditis elegans and Drosophila, but no CHAT mutations have been observed in humans to date. Here we report that mutations in CHAT cause a congenital myasthenic syndrome associated with frequently fatal episodes of apnea (CMS-EA). Studies of the neuromuscular junction in this disease show a stimulation-dependent decrease of the amplitude of the miniature endplate potential and no deficiency of the ACh receptor. These findings point to a defect in ACh resynthesis or vesicular filling and to CHAT as one of the candidate genes. Direct sequencing of CHAT reveals 10 recessive mutations in five patients with CMS-EA. One mutation (523insCC) is a frameshifting null mutation. Three mutations (I305T, R420C, and E441K) markedly reduce ChAT expression in COS cells. Kinetic studies of nine bacterially expressed ChAT mutants demonstrate that one mutant (E441K) lacks catalytic activity, and eight mutants (L210P, P211A, I305T, R420C, R482G, S498L, V506L, and R560H) have significantly impaired catalytic efficiencies.
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The human cerebral cortex is notorious for the depth and irregularity of its convolutions and for its variability from one individual to the next. These complexities of cortical geography have been a chronic impediment to studies of functional specialization in the cortex. In this report, we discuss ways to compensate for the convolutions by using a combination of strategies whose common denominator involves explicit reconstructions of the cortical surface. Surface-based visualization involves reconstructing cortical surfaces and displaying them, along with associated experimental data, in various complementary formats (including three-dimensional native configurations, two-dimensional slices, extensively smoothed surfaces, ellipsoidal representations, and cortical flat maps). Generating these representations for the cortex of the Visible Man leads to a surface-based atlas that has important advantages over conventional stereotaxic atlases as a substrate for displaying and analyzing large amounts of experimental data. We illustrate this by showing the relationship between functionally specialized regions and topographically organized areas in human visual cortex. Surface-based warping allows data to be mapped from individual hemispheres to a surface-based atlas while respecting surface topology, improving registration of identifiable landmarks, and minimizing unwanted distortions. Surface-based warping also can aid in comparisons between species, which we illustrate by warping a macaque flat map to match the shape of a human flat map. Collectively, these approaches will allow more refined analyses of commonalities as well as individual differences in the functional organization of primate cerebral cortex.
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El Niño and the related phenomenon Southern Oscillation (ENSO) is the strongest signal in the interannual variation of ocean-atmosphere system. It is mainly a tropical event but its impact is global. ENSO has been drawing great scientific attention in many international research programs. There has been an observational system for the tropical ocean, and scientists have known the climatologies of the upper ocean, developed some theories about the ENSO cycle, and established coupled ocean-atmosphere models to give encouraging predictions of ENSO for a 1-year lead. However, questions remain about the physical mechanisms for the ENSO cycle and its irregularity, ENSO-monsoon interactions, long-term variation of ENSO, and increasing the predictive skill of ENSO and its related climate variations.
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mRNAs for acetylcholine receptor genes are highly concentrated in the endplate region of adult skeletal muscle largely as a result of a transcription restricted to the subneural nuclei. To identify the regulatory elements involved, we employed a DNA injection of a plasmid containing a fragment of the acetylcholine receptor delta-subunit gene promoter (positions -839 to +45) linked to the reporter gene lacZ with a nuclear localization signal. Injection of the wild-type construct into mouse leg muscles yielded preferential expression of the reporter gene in the synaptic region. Analysis of various mutant promoters resulted in the identification of a DNA element (positions -60 to -49), referred to as the N box, that plays a critical role in subneural expression. Disruption of this 12-bp element in the context of a mouse delta-subunit promoter from positions -839 to +45 gives widespread expression of the reporter gene throughout the entire muscle fiber, indicating that this element is a silencer that represses delta-subunit gene transcription in extrajunctional areas. On the other hand, this element inserted upstream of a heterologous basal promoter preferentially enhances expression in the endplate region. This element therefore regulates the restricted expression of the delta-subunit gene both as an enhancer at the endplate level and as a silencer in extrajunctional areas. Furthermore, gel-shift experiments with mouse muscle extracts reveal an activity that specifically binds the 6-bp sequence TTCCGG of this element, suggesting that a transcription factor(s) controls the expression of the delta-subunit gene via this element.
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The main interest of this research project focuses on transit migration, one element of the more general international migration process, where undocumented migrants find themselves in a condition of irregularity and have to face a migratory route under conditions of severe vulnerability. The main question guiding this research is: How to study and define the Transit Migration phenomenon from its specific context, considering its conditions and consequences? This implies also to respond three more questions: How do migrants perceive their irregular transit through Mexico? What are the networks and social links that articulate the trajectories of irregular Transit Migration through Mexico? and what is the meaning of these networks and links from the perspective of those individuals undergoing irregular Transit Migration processes?...
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Purpose. To assess in a sample of normal, keratoconic, and keratoconus (KC) suspect eyes the performance of a set of new topographic indices computed directly from the digitized images of the Placido rings. Methods. This comparative study was composed of a total of 124 eyes of 106 patients from the ophthalmic clinics Vissum Alicante and Vissum Almería (Spain) divided into three groups: control group (50 eyes), KC group (50 eyes), and KC suspect group (24 eyes). In all cases, a comprehensive examination was performed, including the corneal topography with a Placidobased CSO topography system. Clinical outcomes were compared among groups, along with the discriminating performance of the proposed irregularity indices. Results. Significant differences at level 0.05 were found on the values of the indices among groups by means of Mann-Whitney-Wilcoxon nonparametric test and Fisher exact test. Additional statistical methods, such as receiver operating characteristic analysis and K-fold cross validation, confirmed the capability of the indices to discriminate between the three groups. Conclusions. Direct analysis of the digitized images of the Placido mires projected on the cornea is a valid and effective tool for detection of corneal irregularities. Although based only on the data from the anterior surface of the cornea, the new indices performed well even when applied to the KC suspect eyes. They have the advantage of simplicity of calculation combined with high sensitivity in corneal irregularity detection and thus can be used as supplementary criteria for diagnosing and grading KC that can be added to the current keratometric classifications.
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This case report reports the visual rehabilitation obtained with the fitting of a new design of full scleral contact lens (ICD 16.5 contact lens, Paragon Vision Sciences, distributed by Lenticon, Madrid, Spain) in a cornea with advanced keratoconus and previous implantation of intracorneal ring segment with a very limited effect. This eye had a refraction of –3.00 × 55° cylinder, providing a visual acuity of 0.5 LogMAR. The topographic pattern was very irregular with the presence of a significant central protrusion and a significant central corneal thinning. Some previous unsuccessful fittings have been performed with corneal and corneal-scleral lenses. A comfortable wearing was achieved with a fully scleral contact lens of 4600 μm of sagittal height, optical power of –11.25 D, and providing an apical clearance of 196 μm. A visual acuity of 0.0 LogMAR combined with a relevant aberrometric improvement was achieved with this contact lens. The patient was completely satisfied with the fitting. The result was maintained during 1 year after the fitting. Full scleral lenses are then able to provide comfortable wear and a significant increase in visual acuity combined with a significant improvement in the visual quality in eyes with advanced keratoconus.