Medicina regenerativa del estroma corneal para el tratamiento del queratocono avanzado: resultados clínicos y evolución de la microscopía confocal

Esta investigación tiene como objetivo a largo plazo el poder reemplazar la necesidad de trasplante de córnea clásico en estos pacientes con queratocono terminal. Consideramos que las células madre mesenquimales adultas derivadas del tejido adiposo humano pueden ser una fuente ideal de células madre para la regeneración del estroma corneal. Además de eso, hemos demostrado que las láminas de matriz corneal humana acelular sembradas con estas células madre autólogas mesenquimales derivadas de tejido adiposo humano no causan reacciones de inflamación ni rechazo. Los resultados de esta terapia celular avanzada se estudiarán en esta tesis durante un período de 3 años. CONCLUSIONES. La implantación intraestromal de ADASCs y láminas de estroma corneal humano descelularizado /ADASCs-recelularizado no tuvo complicaciones durante el período de 3 años. La técnica mostró una mejoría moderada en UDVA y CDVA en queratocono avanzado, y una mejoría estadísticamente significativa en todos los casos que recibieron implante intrastromal de una lámina de estroma corneal humano donante descelularizada/recelularizadas con ADASCs. Esta técnica de regeneración del estroma corneal puede proporcionar a los pacientes adecuados una solución alternativa al trasplante de córnea clásico, en una recuperación menos invasiva, más segura y fácil con un período postoperatorio mucho menos prolongado

Calibration of ring oscillator-based integrated temperature sensors for power management systems

ABSTRACT: This paper details the development and validation of a temperature sensing methodology using an un-trimmed oscillator-based integrated sensor implemented in the 0.18-μm SOI XFAB process, with a focus on thermal monitoring in system-on-chip (SoC) based DC-DC converters. Our study identifies a quadratic relationship between the oscillator output frequency and temperature, which forms the basis of our proposed calibration mechanism. This mechanism aims at mitigating process variation effects, enabling accurate temperature-to-frequency mapping. Our research proposes and characterizes several trimming-free calibration techniques, covering a spectrum from zero to thirty-one frequency-temperature measurement points. Notably, the Corrected One-Point calibration method, requiring only a single ambient temperature measurement, emerges as a practical solution that removes the need for a temperature chamber. This method, after adjustment, successfully reduces the maximum error to within ±2.95 °C. Additionally, the Two-Point calibration method demonstrates improved precision with a maximum positive error of +1.56 °C at −15 °C and a maximum negative error of −3.13 °C at +10 °C (R2 value of 0.9958). The Three-Point calibration method performed similarly, yielding an R2 value of 0.9956. The findings of this study indicate that competitive results in temperature sensor calibration can be achieved without circuit trimming, offering a viable alternative or a complementary approach to traditional trimming techniques

Corneal regeneration using adipose-derived mesenchymal stem cells

Producción CientíficaAdipose-derived stem cells are a subtype of mesenchymal stem cell that offers the important advantage of being easily obtained (in an autologous manner) from low invasive procedures, rendering a high number of multipotent stem cells with the potential to differentiate into several cellular lineages, to show immunomodulatory properties, and to promote tissue regeneration by a paracrine action through the secretion of extracellular vesicles containing trophic factors. This secretome is currently being investigated as a potential source for a cell-free based regenerative therapy for human tissues, which would significantly reduce the involved costs, risks and law regulations, allowing for a broader application in real clinical practice. In the current article, we will review the existing preclinical and human clinical evidence regarding the use of such adipose-derived mesenchymal stem cells for the regeneration of the three main layers of the human cornea: the epithelium (derived from the surface ectoderm), the stroma (derived from the neural crest mesenchyme), and the endothelium (derived from the neural crest cells)

Influence of age, gender and delay on overtaking dynamics

"This paper is a preprint of a paper submitted to [journal] and is subject to Institution of Engineering and Technology Copyright. If accepted, the copy of record will be available at IET Digital Library"Overtaking is one of the most dangerous manoeuvres on two-lane rural highways. The most influential factors are related to drivers, so ITS and assistance systems are not yet common. This research is based on experimental data of overtaking manoeuvres collected using an instrumented passenger car, equipped with four cameras, laser rangefinders and a global positioning service (GPS) tracker. This vehicle was driven along four different road segments in the surroundings of Valencia (Spain) at a speed slightly slower than the operating speed of each segment. Overtaking time and speeds were measured. Unlike previous work, the influence of human factor was also considered. Age and gender of overtaking driver, as well as time spent following were used to characterise this influence. More than 200 manoeuvres were recorded and the influence of driver characteristics and delay on gap acceptance, manoeuvre duration and speed differences have been analysed. Results show differences in behaviour between age and gender groups, since young male overtaking drivers have shown a more aggressive behaviour. Overtaking times were around 1 s lower than other drivers, whereas average speed difference was 4 km/h higher. Collected data and their analysis have provided a basis to review design criteria and to develop future assistance systems.Authors would like to thank Spanish Ministry of Economy and Competitiveness that subsidizes the research project with reference code TRA2010-21736. Authors thank also Spanish General Traffic Directorate, Spanish Ministry of Public Works and Valencia Regional Governance for their collaboration during field study.Llorca García, C.; García García, A.; Moreno Chou, AT.; Pérez Zuriaga, AM. (2013). Influence of age, gender and delay on overtaking dynamics. IET Intelligent Transport Systems. 7(2):174-181. https://doi.org/10.1049/iet-its.2012.0147S17418172Farah, H. (2011). Age and Gender Differences in Overtaking Maneuvers on Two-Lane Rural Highways. Transportation Research Record: Journal of the Transportation Research Board, 2248(1), 30-36. doi:10.3141/2248-04Hassan, Y., Easa, S. M., & El Halim, A. O. A. (1996). Passing sight distance on two-lane highways: Review and revision. Transportation Research Part A: Policy and Practice, 30(6), 453-467. doi:10.1016/0965-8564(95)00032-1Wang, Y., & Cartmell, M. P. (1998). New Model for Passing Sight Distance on Two-Lane Highways. Journal of Transportation Engineering, 124(6), 536-545. doi:10.1061/(asce)0733-947x(1998)124:6(536)Polus, A., Livneh, M., & Frischer, B. (2000). Evaluation of the Passing Process on Two-Lane Rural Highways. Transportation Research Record: Journal of the Transportation Research Board, 1701(1), 53-60. doi:10.3141/1701-07Carlson, P., Miles, J., & Johnson, P. (2006). Daytime High-Speed Passing Maneuvers Observed on Rural Two-Lane, Two-Way Highway: Findings and Implications. Transportation Research Record: Journal of the Transportation Research Board, 1961, 9-15. doi:10.3141/1961-02Hegeman, G., Tapani, A., & Hoogendoorn, S. (2009). Overtaking assistant assessment using traffic simulation. Transportation Research Part C: Emerging Technologies, 17(6), 617-630. doi:10.1016/j.trc.2009.04.010El Zarif, J., Hobeika, A., & Rakha, H. (2003). Evaluating a Detection and Warning System to Deter No-Passing Zone Violations. Journal of Transportation Engineering, 129(6), 590-599. doi:10.1061/(asce)0733-947x(2003)129:6(590)Llorca, C., & García, A. (2011). Evaluation of Passing Process on Two-Lane Rural Highways in Spain with New Methodology Based on Video Data. Transportation Research Record: Journal of the Transportation Research Board, 2262(1), 42-51. doi:10.3141/2262-0

Role of non-coding RNA networks in leukemia progression, metastasis and drug resistance.

Early-stage detection of leukemia is a critical determinant for successful treatment of the disease and can increase the survival rate of leukemia patients. The factors limiting the current screening approaches to leukemia include low sensitivity and specificity, high costs, and a low participation rate. An approach based on novel and innovative biomarkers with high accuracy from peripheral blood offers a comfortable and appealing alternative to patients, potentially leading to a higher participation rate.Recently, non-coding RNAs due to their involvement in vital oncogenic processes such as differentiation, proliferation, migration, angiogenesis and apoptosis have attracted much attention as potential diagnostic and prognostic biomarkers in leukemia. Emerging lines of evidence have shown that the mutational spectrum and dysregulated expression of non-coding RNA genes are closely associated with the development and progression of various cancers, including leukemia. In this review, we highlight the expression and functional roles of different types of non-coding RNAs in leukemia and discuss their potential clinical applications as diagnostic or prognostic biomarkers and therapeutic targets

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

A Platform for Enhancing the Vision of Patients Suffering from Age-Related Macular Degeneration Disease

RÉSUMÉ La dégénérescence maculaire liée à l’âge est la principale cause de cécité en Amérique du Nord sans traitement médical fiable. Cette maladie progressive se manifeste par une déficience visuelle sévère de la vision centrale à ses étapes intermédiaires ou par une perte totale de la vision centrale dans ses étapes ultérieures en raison de la dégradation de la couche photoréceptrice de la rétine. Il n’existe actuellement aucun traitement fiable pour ces maladies et très peu de mesures préventives qui ralentissent leur progression. De nombreuses approches ont été proposées pour aider à atténuer ce problème. Une canne et des chiens-guides sont parmi les méthodes les plus fiables au monde pour aider les malvoyants. Les nouvelles approches visent à tirer parti de la puissance de la technologie pour offrir une meilleure expérience au patient grâce à des guides de navigation électroniques ou des aides visuelles. Le travail présenté dans cette thèse est une plate-forme destinée à la stimulation optique pour la dégénérescence maculaire liée à l’âge, ceci en émulant le traitement rétinien se produisant dans la macula en temps réel et en envoyant un signal optogénétique à un dispositif de stimulation photo-électrique à la couche rétinienne souhaitée pour restaurer la vision dans une rétine endommagée. Ceci est réalisé avec un modèle de traitement d’image rapide, simplifié et ajustable de la rétine utilisant un filtrage spatial et temporel. Une capture vidéo en direct et des images à l’échelle sont ensuite utilisées pour adapter la prothèse visuelle à plusieurs résolutions. L’aspect temporel de la macula est émulé à l’aide d’un filtre temporel multi-images personnalisé et d’une intégration décroissante qui correspond à la vitesse de la voie temporelle dans la rétine, tandis que l’aspect spatial est modélisé comme une différence de gaussien. Ensemble, ils se combinent en un modèle simple et puissant qui représente la voie principale de la rétine humaine. Le modèle est mis en œuvre de manière à être extensible et efficace en termes de calcul pour obtenir les meilleurs résultats dans un budget de temps strict. Le modèle implémenté est suffisamment rapide pour fonctionner en temps réel sur les appareils Raspberry Pi 3 et Raspberry Pi 4. La sortie de la plate-forme génère un signal à envoyer à un stimulateur micro-LED conçu par Leila Montazeri et al. Le stimulateur générera un signal lumineux focalisé qui agit sur les cellules ganglionnaires rétiniennes traitées avec des opsines photosensibles, dans le but de restaurer une certaine acuité visuelle dans la vision centrale. En raison des limites de fabrication, seule une matrice micro-LED 8x8 peut être produite. Cela signifie que seule une image 8x8 peut être envoyée au micro-stimulateur, et il est donc important de représenter les images par un très petit nombre de pixels.----------ABSTRACT Age-related macular degeneration is the leading cause of blindness in North America with no reliable medical treatment. This progressive disease manifests itself with severe visual impairment in the central vision in its intermediate stages or with the total loss of central vision in its later stages due to the decay in the photoreceptor layer in the retina. There are currently no reliable treatments for these diseases and very few preventative measures that slow down their progression. There have been many approaches proposed to help mitigate this problem. A walking stick and guide dogs are among the most reliably used around the world to provide aid for the visually impaired. Newer approaches aim to leverage the power of technology to provide a better patient experience through electronic navigation guides or visual aids. The work presented in this thesis is a platform intended for driving age-related macular degeneration optic stimulation by emulating retinal processing occurring in the macula in real-time and sending an optogenetic signal to a photo-electric stimulation device to the desired retinal layer to recreate vision within a damaged retina. This is achieved with a fast, simplified, and tunable image processing model of the retina using spatial and temporal filtering. Live video capture and scaled images are then used to fit the visual prosthesis with multiple resolutions. The temporal aspect of the macula is emulated using a custom-written multi-frame temporal filter and a decaying integration that matches the speed of the temporal pathway in the retina, while the spatial aspect is modeled as a di˙erence of Gaussian. Together they combine into a simple and powerful model that represents the major pathway in the human retina. The model is implemented in a way to be expandable and computationally eÿcient to get the best results under a strict time budget. The implemented model is fast enough to work in real-time on Raspberry Pi 3 and Raspberry Pi 4 devices. The output of the platform generates a signal to be sent to a micro-LED stimulator designed by Leila Montazeri et al. The stimulator will generate a focused light signal that works on retinal ganglion cells treated with light-sensitive opsins, with the aim of restoring some visual acuity in the central vision. Due to manufacturing limitations, only an 8x8 micro-LED matrix can be produced, hence it is important to represent images with a very small number of pixels. We chose to focus on facial expressions since they are crucial for human communication. In addition, facial expression recognition has many uses in several fields, such as entertainment, personalized medicine, and human-machine interaction