Comparación de los modelos de Memoria Episódica en algunas Arquitecturas del mundo con el concepto de Memoria Episódica en Arquitectura Metacognitiva CARINA

Esta investigación presenta una representación formal de un episodio cognitivo en la arquitectura metacognitiva CARINA. Esta investigación es parte del tipo de Metodología llamada Modelado, que pertenece a la categoría de métodos de software que, a su vez, se encuentra entre las metodologías de Investigación + Desarrollo (I + D) utilizadas en informática. Se presenta una representación formal de un episodio en la arquitectura metacognitiva CARINA

In vitro and in vivo development of mice morulae after storage in non-frozen conditions

Background Interchange of genetically modified (GM) mice between laboratories using embryos provides several advantages. Not only is transport stress avoided, but also the health status of the recipient colony is not compromised. Embryos do not need to be shipped in frozen stage, which requires expensive packaging in addition to a certain degree of expertise in order to freeze and thaw them correctly. The aim of this study was to examine different storage conditions and their effect on embryo viability in order to establish the feasibility of practical, non-frozen conditions for embryo shipment. Methods Mouse morulae developed in vivo (collected from donors 2.5d post coitum) or in vitro (zygotes cultured until morulae stage) were stored, combining two different media (KSOMeq or KSOM-H) and temperatures (4 degrees C, 15 degrees C and 37 degrees C) throughout 24 or 48 hours. After storage in vitro viability was assessed determining percentage of development to blastocyst and total cell number. In vivo viability was determined based on the number of implantations and living fetuses after embryo transfer of stored embryos. The storage effect at the molecular level was assessed by studying a gene pool involved in early development by quantitative RT-PCR. Results In vivo-produced morulae stored for 24 hours did not show differences in development up to the blastocyst stage, regardless of the storage type. Even though a decrease in the total cell number in vivo was observed, embryo development after embryo transfer was not affected. All 24 hour storage conditions tested provided a similar number of implantations and fetuses at day 14 of pregnancy. Morulae obtained from in vitro embryo culture collected at the 1-cell stage showed a decreased ability to develop to blastocyst after 24 hours of storage at 15degrees C both in KSOMeq and KSOM-H. Concomitantly, a significant decrease of embryo implantation rates after transfer to recipients was also found. In order to further characterize the effect of non-frozen storage combining a molecular approach with the ordinary in vitro culture evaluation, embryos collected at the morula stage were submitted to the same storage conditions described throughout 48 hours. In vitro culture of those embryos showed a significant decrease in their developmental rate to blastocyst in both KSOMeq and KSOM-H at 15degrees C, which also affected the total number of cells. Gene transcription studies confirmed significant alterations in retrotransposons (Erv4 and Iap) after 48 h of storage at 15degrees C. Conclusions Our results show that both KSOMeq and KSOM-H can be equally used, and that several temperature conditions allow good survival rates in vitro and in vivo. Some of these storage conditions can substitute freezing in order to maintain embryo viability for 24–48 hours, providing a reliable and less demanding technical alternative for embryo interchanges.This work was performed as part of, and financed by, Project AGL2004-00332. JDH received a Ph D. grant from the INIA (Ministry of Science and Innovation). We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its unit of Information Resources for Research (URICI).Peer Reviewe

Guía de recomendaciones para el manejo de brolucizumab

Brolucizumab; Intraocular inflammation; Patient managementBrolucizumab; Inflamación intraocular; Manejo del pacienteBrolucizumab; Inflamació intraocular; Maneig del pacientPurpose: Brolucizumab, a new generation anti-VEGF, has demonstrated efficacy and safety in AMD in the pivotal HAWK and HARRIER trials. Post-marketing, previously undetected adverse events related to intraocular inflammation have been reported. An independent post hoc review of the pivotal trials puts the rate of IOI at 4.6%. The aim of this paper is to propose a set of recommendations for implementing the management of brolucizumab in clinical practice. Methods: The recommendations made by the authors are based on their clinical experience, critical review of (i) the pivotal trials, the post-hoc analysis of the Safety Review Committee, (ii), and (iii) the published literature. Results: In the pivotal trials, brolucizumab showed sustained functional gains, superior anatomical outcomes with potentially longer intervals between injections and a well-tolerated overall safety profile. Adverse events reported post-marketing include retinal vasculitis and retinal vascular occlusion. Based on the available information, experts recommend (i) ruling out non-recommended patient profiles (prior history of ORI), (ii) screening the patient prior to each injection to rule out active ORI, (iii) monitoring the patient for early warning signs, and (iv) treating immediately should any adverse events develop. Conclusions: The adverse events reported are rare, but may be associated with severe and irreversible loss of visual acuity. The recommendations made are intended to facilitate the management of brolucizumab in the routine practice of retinologists, to ensure patient safety and, should any adverse events occur, to minimise their impact on vision.Objetivo Brolucizumab, un anti-VEGF de nueva generación, ha demostrado su eficacia y seguridad en degeneración macular asociada a la edad neovascular exudativa (DMAEn) en los ensayos pivotales HAWK y HARRIER. Tras su comercialización, se han reportado eventos adversos relacionados con la inflamación intraocular no detectados previamente. Una revision post hoc independiente de los ensayos pivotales cifra la tasa de IIO en 4,6%. El objetivo de este trabajo es proponer una serie de recomendaciones para implementar el manejo de brolucizumab en la práctica clínica. Método Las recomendaciones realizadas por los autores se han basado en su experiencia clínica y la revisión crítica de: 1) los ensayos pivotales; 2) el análisis post hoc del Comité de Revisión de Seguridad, y 3) la literatura publicada. Resultados En los ensayos pivotales, brolucizumab mostró ganancias funcionales sostenidas, resultados anatómicos superiores con intervalos entre inyecciones potencialmente más prolongados y un perfil de seguridad global bien tolerado. Los eventos adversos reportados tras la comercialización incluyen vasculitis retiniana y la oclusión vascular retiniana. De acuerdo con la información disponible, los expertos recomiendan 1) descartar los perfiles de pacientes no recomendados (historial previo de IIO), 2) explorar al paciente antes de cada inyección para descartar la presencia de IIO activa, 3) monitorizar al paciente para detectar precozmente los signos de alerta, y 4) tratar de inmediato en el caso de que se desarrolle algún evento adverso. Conclusiones Los eventos adversos reportados son poco frecuentes, pero pueden estar asociados con una pérdida severa e irreversible de agudeza visual. Las recomendaciones realizadas pretenden facilitar el manejo de brolucizumab en la práctica habitual de los retinólogos, garantizar la seguridad del paciente y, en caso de que se produzca alguno de los eventos adversos, minimizar su impacto sobre la visión

GlobalSearchRegression.jl: Building bridges between Machine Learning and Econometrics in Fat-Data scenarios

The aim of this paper is twofold. The first one is to describe a novel research-project designed for building bridges between machine learning and econometric worlds (ModelSelection.jl).The second one is to introduce the main characteristics and comparative performance of the first Julia-native all-subset regression algorithm included in GlobalSearchRegression.jl (v1.0.5). As other available alternatives, this algorithm allows researchers to obtain the best model specification among all possible covariate combinations - in terms of user defined information criteria-, but up to 3165 and 197 times faster than STATA and R alternatives, respectively.Fil: Panigo, Demian Tupac. Universidad Nacional de la Plata. Facultad de Ingenieria. Instituto Malvinas.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Centro de Innovación de los Trabajadores. Universidad Metropolitana para la Educación y el Trabajo. Centro de Innovación de los Trabajadores; ArgentinaFil: Gluzmann, Pablo Alfredo. Universidad Nacional de La Plata. Facultad de Ciencias Económicas. Departamento de Ciencias Económicas. Centro de Estudios Distributivos Laborales y Sociales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Mocskos, Esteban Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; ArgentinaFil: Mauri Ungaro, Adán. Universidad Nacional de La Plata; ArgentinaFil: Mari, Valentin. Universidad Nacional de La Plata; ArgentinaFil: Monzon, Nicolás. Universidad Nacional de La Plata; Argentina. Universidad Nacional de Avellaneda; Argentin

Peripheral blood metabolic and inflammatory factors as biomarkers to ocular findings in diabetic macular edema.

AIMS: To study the association between peripheral blood metabolic and inflammatory factors and presence of diabetic macular edema (DME) and its related anatomic features in type 2 diabetic mellitus (T2DM) patients. MATERIAL AND METHODS: Observational cross-sectional study on a proof of concept basis. Seventy-six T2DM included patients were divided based on the presence (n = 58) or absence of DME (n = 18) according to optical coherence tomography (OCT). Ultra-widefield fluorescein angiography (UWFA) was performed in DME patients. Fasting peripheral blood sample testing included glycemia, glycated hemoglobin, creatinin and lipid levels among others. Serum levels of a broad panel of cytokines and inflammatory mediators were also analysed. OCT findings included central subfoveal thickness, diffuse retinal thickness (DRT), cystoid macular edema (CME), serous retinal detachment and epirretinal membrane. UWFA items included pattern of DME, presence of peripheral retinal ischemia and enlarged foveal avascular zone (FAZ). RESULTS: Metabolic and inflammatory factors did not statistically differ between groups. However, several inflammatory mediators did associate to certain ocular items of DME cases: IL-6 was significantly higher in patients with DRT (p = 0.044), IL-10 was decreased in patients with CME (p = 0.012), and higher IL-8 (p = 0.031) and VEGF levels (p = 0.031) were observed in patients with enlarged FAZ. CONCLUSION: Inflammatory and metabolic peripheral blood factors in T2DM may not be differentially associated to DME when compared to non-DME cases. However, some OCT and UWFA features of DME such as DRT, CME and enlarged FAZ may be associated to certain systemic inflammatory mediators

Complement factor H binding of monomeric C-reactive protein downregulates proinflammatory activity and is impaired with at risk polymorphic CFH variants

Inflammation and immune-mediated processes are pivotal to the pathogenic progression of age-related macular degeneration (AMD). Although plasma levels of C-reactive protein (CRP) have been shown to be associated with an increased risk for AMD, the pathophysiological importance of the prototypical acute-phase reactant in the etiology of the disease is unknown, and data regarding the exact role of CRP in ocular inflammation are limited. In this study, we provide mechanistic insight into how CRP contributes to the development of AMD. In particular, we show that monomeric CRP (mCRP) but not the pentameric form (pCRP) upregulates IL-8 and CCL2 levels in retinal pigment epithelial cells. Further, we show that complement factor H (FH) binds mCRP to dampen its proinflammatory activity. FH from AMD patients carrying the 'risk' His402 polymorphism displays impaired binding to mCRP, and therefore proinflammatory effects of mCRP remain unrestrained

Oxaliplatin-Related Ocular Toxicity

We report the case of a 52-year-old woman with advanced colorectal cancer who was treated with oxaliplatin on a FOLFOX schedule. After 3 cycles of chemotherapy, she started to complain of visual loss, altered color vision and neurological symptoms. Due to the suspicion of ocular and neurological toxicity, antineoplastic treatment was stopped. Her visual field showed a concentric bilateral scotoma and the electrooculogram test revealed severe impairment of the retinal pigment epithelium. Visual acuity, color vision and visual field recovered completely 8 months later, although electrooculogram remained abnormal. Ocular toxicity has been reported as an infrequent adverse event of oxaliplatin. Findings in this case indicate toxicity of this chemotherapeutic agent on the retinal pigment epithelium, which has not been reported before. This damage could be permanent, and it thus differs from previously described oxaliplatin-induced ocular toxicities, which are usually transient and reversible. With increasing use of oxaliplatin as first-line treatment in advanced colorectal cancer, we have to be aware of this possible toxicity

Angiography and En Face Optical Coherence Tomography Findings in Acute Syphilitic Posterior Placoid Chorioretinopathy

Acute syphilitic posterior placoid chorioretinopathy (ASPPC) is one of the rarest ocular manifestations of syphilis. The pathophysiology of this entity is still unknown. We report the outer retinal findings on en face optical coherence tomography (OCT) and the alteration of choriocapillaris flow findings on OCT angiography in a patient with ASPPC at the time of presentation, after penicillin treatment completion and during follow-up

Nitrogen determination on tomato (Lycopersicon esculentum Mill.) seedlings by color image analysis (RGB)

In order to investigate the effectiveness of a new method based on color image analysis and the Minolta SPAD-502 chlorophyll meter for the diagnosis of nitrogen deficiencies of tomato seedlings, a field experiment was conducted. In this study, five levels of nitrogen fertilization were established so as to induce nitrogen deficiencies in tomato seedlings. Thirty-five days after sowing, total nitrogen was evaluated by laboratory analysis. The chlorophyll index was determined using a SPAD-502 chlorophyll meter. Also, color images were taken with a digital camera; the color images were processed in MATLAB in order to determine the averages of the red color, green color and the blue color. The relationships between variables were analyzed by linear regressions and a one way analysis of variance (p < 0.01). Results showed that color image analysis correlated better with the status of plant nitrogen than the SPAD. From the color image analysis, the red and blue colors were more accurate predictors of nitrogen status on plants with R2 above 0.89. Color image analysis provides an accurate and quick way for nitrogen estimation and can contribute for early detection of nitrogen deficiency in tomato seedlings. The SPAD method is not a reliable way to estimate the nitrogen status on tomato seedlings.Keywords: Color image analysis (RGB), chlorophyll meter, nitrogen deficiencyAfrican Journal of Biotechnology Vol. 9(33), pp. 5326-5332, 16 August, 201