Computational Tools for Image Processing, Integration, and Visualization of Simultaneous OCT-FLIM Images of Tissue

Multimodal imaging systems have emerged as robust methods for the characterization of atherosclerotic plaques and early diagnosis of oral cancer. Multispectral wide-field Fluorescence Lifetime Imaging Microscopy (FLIM) has been shown to be a capable optical imaging modality for biomedical diagnosis oral cancer. A fiber-based endoscope combined with an intensified charge-coupled device (ICCD) allows to collect and split the fluorescence emission into multiple bands, from which the fluorescence lifetime decay in each spectral channel can be calculated separately. However, for accurate calculations, it is necessary to gather multiple gates increasing the imaging time. Since this time is critical for real-time in vivo applications. This study presents a novel approach to using Rapid Lifetime Determination (RLD) methods to considerably shorten this time period. Moreover, the use of a dual-modality system, incorporating Optical Coherence Tomography (OCT) and FLIM, which simultaneously characterizes 3-D tissue morphology and biochemical composition of tissue, leads to the development of robust computational tools for image processing, integration, and visualization of these imaging techniques. OCTFLIM systems provide 3D structural and 2D biochemical tissue information, which the software tools developed in this work properly integrate to assist the image processing, characterization, and visualization of OCT-FLIM images of atherosclerotic plaques. Additionally, plaque characterization is performed by visual assessment and requires a trained expert for interpretation of the large data sets. Here, we present two novel computational methods for automated intravascular (IV) OCT plaque characterization. The first method is based on the modeling of each A-line of an IV-OCT data set as a linear combination of a number of depth profiles. After estimating these depth profiles by means of an alternating least square optimization strategy, they are automatically classified to predefined tissue types based on their morphological characteristics. The second method is intended to automatically identify macrophage/foam cell clusters in atherosclerotic plaques. Vulnerable plaques are characterized by presenting a necrotic core below a thin fibrous cap, and extensive infiltration of macrophages/foam cells. Thus, the degree of macrophage accumulation is an indicator in determining plaque progression and probability of rupture. In this work, two texture features are introduced, the normalized standard deviation ratio (NSDRatio) and the entropy ratio (ENTRatio), to effectively classify areas in the plaque with macrophage/foam cell infiltration. Since this methodology has low complexity and computational cost, it could be implemented for in vivo real time identification of macrophage/foam cell presence

Computational Tools for Image Processing, Integration, and Visualization of Simultaneous OCT-FLIM Images of Tissue

Multimodal imaging systems have emerged as robust methods for the characterization of atherosclerotic plaques and early diagnosis of oral cancer. Multispectral wide-field Fluorescence Lifetime Imaging Microscopy (FLIM) has been shown to be a capable optical imaging modality for biomedical diagnosis oral cancer. A fiber-based endoscope combined with an intensified charge-coupled device (ICCD) allows to collect and split the fluorescence emission into multiple bands, from which the fluorescence lifetime decay in each spectral channel can be calculated separately. However, for accurate calculations, it is necessary to gather multiple gates increasing the imaging time. Since this time is critical for real-time in vivo applications. This study presents a novel approach to using Rapid Lifetime Determination (RLD) methods to considerably shorten this time period. Moreover, the use of a dual-modality system, incorporating Optical Coherence Tomography (OCT) and FLIM, which simultaneously characterizes 3-D tissue morphology and biochemical composition of tissue, leads to the development of robust computational tools for image processing, integration, and visualization of these imaging techniques. OCTFLIM systems provide 3D structural and 2D biochemical tissue information, which the software tools developed in this work properly integrate to assist the image processing, characterization, and visualization of OCT-FLIM images of atherosclerotic plaques. Additionally, plaque characterization is performed by visual assessment and requires a trained expert for interpretation of the large data sets. Here, we present two novel computational methods for automated intravascular (IV) OCT plaque characterization. The first method is based on the modeling of each A-line of an IV-OCT data set as a linear combination of a number of depth profiles. After estimating these depth profiles by means of an alternating least square optimization strategy, they are automatically classified to predefined tissue types based on their morphological characteristics. The second method is intended to automatically identify macrophage/foam cell clusters in atherosclerotic plaques. Vulnerable plaques are characterized by presenting a necrotic core below a thin fibrous cap, and extensive infiltration of macrophages/foam cells. Thus, the degree of macrophage accumulation is an indicator in determining plaque progression and probability of rupture. In this work, two texture features are introduced, the normalized standard deviation ratio (NSDRatio) and the entropy ratio (ENTRatio), to effectively classify areas in the plaque with macrophage/foam cell infiltration. Since this methodology has low complexity and computational cost, it could be implemented for in vivo real time identification of macrophage/foam cell presence

Development of a computing application for the dimensioning of deployment mechanisms in artificial satellites - Desarrollo de una Aplicación Informática para el Dimensionado de Mecanismos de Despliegue en Satélites Artificiales

Los satélites artificiales a menudo deben desplegar instrumentos una vez puestos en órbita. El diseño de los mecanismos encargados de llevar a cabo este cometido es crítico, ya que un despliegue incorrecto implicaría en muchos casos la pérdida del satélite. En el caso de las antenas, un despliegue incorrecto o descontrolado podría tener como consecuencia impactos excesivamente altos que podrían producir daños estructurales, cambios de actitud del satélite, des alineamiento de las mismas, etc. Los mecanismos encargados de desplegar las antenas usualmente están compuestos por un muelle pretensado que aporta el par necesario para desplegar la misma y un sistema de amortiguación encargado de evitar que desarrolle velocidades excesivamente altas. Basándose en este contexto, se han desarrollado dos aplicaciones informáticas que, partiendo de las características de un despliegue definido por el usuario, son capaces de realizar simulaciones del mismo utilizando distintos mecanismos de despliegue, obtenidos al variar las características del muelle o el sistema de amortiguación, aportando información del comportamiento cinemático y dinámico del elemento a desplegar en cada caso, y clasificando cada uno de los posibles mecanismos de acuerdo con los requisitos de diseño impuestos por las normas ECSS, que son de obligado cumplimiento para la Agencia Espacial Europea

Metodologias Activas en la Asignatura de Mecánica, Resultados de Tres Años de Experiencia.

La asignatura de Mecánica I forma parte de las experiencias piloto de curso completo que la EUIT Aeronáutica viene desarrollando desde 2005 con el fin de adaptar sus enseñanzas al EEES. En todos los casos, la experiencia se ha dirigido a un colectivo de alumnos de nuevo ingreso (Grupo Piloto), pero con tamaños de grupos y notas de corte muy diferentes. La Mecánica I es una asignatura troncal de primer curso que se imparte durante el segundo semestre y, desde 2006, también se ofrece durante el primer semestre con la nueva metodología a un grupo de alumnos repetidores en la modalidad de Docencia complementaria. En este trabajo se presenta, mediante una revisión histórica, la nueva metodología basada en el aprendizaje cooperativo, la evaluación continua y la incorporación de las Tecnologías de la Información y la Comunicación (TIC). Se muestran los resultados académicos obtenidos por los alumnos del Grupo Piloto comparados mediante los indicadores ANECA con los obtenidos por el Grupo de Control constituido por los alumnos de nuevo ingreso de las mismas carreras, y los resultados alcanzados por el grupo de Docencia complementaria. También se expone la valoración cualitativa de los alumnos de disponer de objetos digitales de aprendizaje

MURIN: Multimodal Retinal Imaging and Navigated-laser-delivery for dynamic and longitudinal tracking of photodamage in murine models

IntroductionLaser-induced photodamage is a robust method for investigating retinal pathologies in small animals. However, aiming of the photocoagulation laser is often limited by manual alignment and lacks real-time feedback on lesion location and severity. Here, we demonstrate MURIN: MUltimodal Retinal Imaging and Navigated-laser-delivery, a multimodality OCT and SLO ophthalmic imaging system with an image-guided scanning laser lesioning module optimized for the murine retina. The proposed system enables targeting of focal and extended area lesions under OCT guidance to benefit visualization of photodamage response and the precision and repeatability of laser lesion models of retinal injury.MethodsMURIN optics were optimized for simultaneous near-infrared and visible wavelength imaging/laser lesioning. Custom LabView control software was developed to steer the photocoagulation laser and automatically deliver laser pulses to targets-of-interest. In vivo retinal imaging was performed in transgenic Müller glia-tdTomato reporter mice (Rlbp1:CreER; Rosaai14, 5 animals, 10 eyes) and microglia-GFP/Müller glia-tdTomato reporter mice (Cx3cr1GFP; Rlbp1:CreER; Rosaai14, 9 animals, 15 eyes) to visualize cellular changes in the retina after laser lesion delivery.ResultsReal-time MURIN imaging concurrent with laser lesioning allowed us to visualize lesion formation dynamics and any corresponding changes in retinal morphology. We observe increasing fluorescence photoconversion on SLO and scattering contrast on OCT. Significant morphological changes are visible on MURIN after high-severity photodamage. OCT cross-sections show the spatial extent of the lesions contract over time from diffusion areas of increased scattering to granular scatterers and corresponding SLO images show a radial pattern surrounding severe focal lesions, which may be a result of a change in Müller cell shape or orientation in response to injury. The inner plexiform layer is distorted and increased RPE thickness and scattering are observed, all of which are confirmed on corresponding hematoxylin and eosin (H&E) histology and differential interference contrast (DIC) microscopy.DiscussionMURIN as a unique imaging platform that enables combined SLO and OCT imaging with an integrated image-guided laser lesioning module. This technology has clear benefits over existing multimodal imaging and laser lesioning systems by enabling simultaneous multimodal imaging, independent and precise control of Iridex laser pulse parameters and patterns, and real-time OCT and SLO visualization of lesion formation

How does neighbourhood socio-economic status affect the interrelationships between functioning dimensions in first episode of psychosis? A network analysis approach

The links between psychosis and socio-economic disadvantage have been widely studied. No previous study has analysed the interrelationships and mutual influences between functioning dimensions in first episode of psychosis (FEP) according to their neighbourhood household income, using a multidimensional and transdiagnostic perspective. 170 patients and 129 controls, participants in an observational study (AGES-CM), comprised the study sample. The WHO Disability Assessment Schedule (WHODAS 2.0) was used to assess functioning, whereas participants' postcodes were used to obtain the average household income for each neighbourhood, collected by the Spanish National Statistics Institute (INE). Network analyses were conducted with the aim of defining the interrelationships between the different dimensions of functioning according to the neighbourhood household income. Our results show that lower neighbourhood socioeconomic level is associated with lower functioning in patients with FEP. Moreover, our findings suggest that “household responsibilities” plays a central role in the disability of patients who live in low-income neighbourhoods, whereas “dealing with strangers” is the most important node in the network of patients who live in high-income neighbourhoods. These results could help to personalize treatments, by allowing the identification of potential functioning areas to be prioritized in the treatment of FEP according to the patient's neighbourhood characteristic

The interplay between functioning problems and symptoms in first episode of psychosis: an approach from network analysis

The relationship between psychotic symptoms and global measures of functioning has been widely studied. No previous study has assessed so far the interplay between specific clinical symptoms and particular areas of functioning in first-episode psychosis (FEP) using network analysis methods. A total of 191 patients with FEP (age 24.45 ± 6.28 years, 64.9% male) participating in an observational and longitudinal study (AGES-CM) comprised the study sample. Functioning problems were assessed with the WHO Disability Assessment Schedule (WHODAS), whereas the Positive and Negative Syndrome Scale (PANSS) was used to assess symptom severity. Network analysis were conducted with the aim of analysing the patterns of relationships between the different dimensions of functioning and PANSS symptoms and factors at baseline. According to our results, the most important nodes were “conceptual disorganization”, “emotional withdrawal”, “lack of spontaneity and flow of conversation”, “delusions”, “unusual thought content”, “dealing with strangers” and “poor rapport”. Our findings suggest that these symptoms and functioning dimensions should be prioritized in the clinical assessment and management of patients with FEP. These areas may also become targets of future early intervention strategies, so as to improve quality of life in this populationThis work was supported by the Madrid Regional Government (R&D activities in Biomedicine (grant number S2017/BMD-3740 - AGES-CM 2-CM)) and Structural Funds of the European Union. Ana Izquierdo’s work is supported by the PFIS predoctoral program (FI17/00138) from the Instituto de Salud Carlos III (Spain) and co-funded by the European Union (ERDF/ESF, "A way to make Europe”/ “Investing in your future”) and The Biomedical Research Foundation of La Princesa University Hospital. Angela Ib´a˜nez thanks the support of CIBERSAM and of the Spanish Ministry of Science, Innovation and Universities. Instituto de Salud Carlos III (PI16/00834 and PI19/01295) co-financed by ERDF Funds from the European Commission. Covadonga M. Díaz-Caneja holds a Juan Rod´es Grant from Instituto de Salud Carlos III (JR19/00024). Celso Arango was supported by the Spanish Ministry of Science and Innovation. Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/ 024), co-financed by ERDF Funds from the European Commission, “A way of making Europe”, CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds. European Union Seventh Framework Program under grant agreements FP7-4-HEALTH-2009-2.2.1-2-241909 (Project EU-GEI), FP7- HEALTH- 2013-2.2.1-2-603196 (Project PSYSCAN) and FP7- HEALTH-2013- 2.2.1-2-602478 (Project METSY); and European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115916, Project PRISM, and grant agreement No 777394, Project AIMS-2-TRIALS), Fundaci´on Familia Alonso, Fundaci´on Alicia Koplowitz and Fundaci´on Mutua Madrile˜n

Evaluación frecuente, mentorías y rendimiento académico en el programa mentor de Aeronáuticos

El Programa Mentor de Aeronáuticos se inicia en 2004con una doble vertiente de actuación. Por un lado, Tutores y Mentores facilitan el proceso de integración de los Alumnos de Nuevo Ingreso en la vida universitaria; por otro, el estudio de las dificultades académicas de los Alumnos Tutelados conduce a Cambios Metodológicas en el Aula que ayudan a activar las relaciones profesor-alumno y a mejorar el rendimiento del esfuerzo de todos, profesores y alumnos. Se describen éstas experiencias, así como los resultados obtenidos en los últimos cuatro año

The clinical relevance of oliguria in the critically ill patient : Analysis of a large observational database

Funding Information: Marc Leone reports receiving consulting fees from Amomed and Aguettant; lecture fees from MSD, Pfizer, Octapharma, 3 M, Aspen, Orion; travel support from LFB; and grant support from PHRC IR and his institution. JLV is the Editor-in-Chief of Critical Care. The other authors declare that they have no relevant financial interests. Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Urine output is widely used as one of the criteria for the diagnosis and staging of acute renal failure, but few studies have specifically assessed the role of oliguria as a marker of acute renal failure or outcomes in general intensive care unit (ICU) patients. Using a large multinational database, we therefore evaluated the occurrence of oliguria (defined as a urine output 16 years) patients in the ICON audit who had a urine output measurement on the day of admission were included. To investigate the association between oliguria and mortality, we used a multilevel analysis. Results: Of the 8292 patients included, 2050 (24.7%) were oliguric during the first 24 h of admission. Patients with oliguria on admission who had at least one additional 24-h urine output recorded during their ICU stay (n = 1349) were divided into three groups: transient - oliguria resolved within 48 h after the admission day (n = 390 [28.9%]), prolonged - oliguria resolved > 48 h after the admission day (n = 141 [10.5%]), and permanent - oliguria persisting for the whole ICU stay or again present at the end of the ICU stay (n = 818 [60.6%]). ICU and hospital mortality rates were higher in patients with oliguria than in those without, except for patients with transient oliguria who had significantly lower mortality rates than non-oliguric patients. In multilevel analysis, the need for RRT was associated with a significantly higher risk of death (OR = 1.51 [95% CI 1.19-1.91], p = 0.001), but the presence of oliguria on admission was not (OR = 1.14 [95% CI 0.97-1.34], p = 0.103). Conclusions: Oliguria is common in ICU patients and may have a relatively benign nature if only transient. The duration of oliguria and need for RRT are associated with worse outcome.publishersversionPeer reviewe

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB