455 research outputs found

    Similarity-based Knowledge Transfer for Cross-Domain Reinforcement Learning

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    Transferring knowledge in cross-domain reinforcement learning is a challenging setting in which learning is accelerated by reusing knowledge from a task with different observation and/or action space. However, it is often necessary to carefully select the source of knowledge for the receiving end to benefit from the transfer process. In this article, we study how to measure the similarity between cross-domain reinforcement learning tasks to select a source of knowledge that will improve the performance of the learning agent. We developed a semi-supervised alignment loss to match different spaces with a set of encoder-decoders, and use them to measure similarity and transfer policies across tasks. In comparison to prior works, our method does not require data to be aligned, paired or collected by expert policies. Experimental results, on a set of varied Mujoco control tasks, show the robustness of our method in effectively selecting and transferring knowledge, without the supervision of a tailored set of source tasks.Comment: 30 pages, 7 figure

    New tracheal stainless steel stent pilot study: twelve month follow-up in a rabbit model

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    Background Canine tracheal collapse is a complex airway pathology without promising treatment results. Currently nitinol stents are the best surgical option; however, some professionals are doubting if stent placement is the best option due to the associated complications. Objective Determine the technical feasibility, safety, and long-term follow-up after the implantation of a new tracheal stent designed for canine tracheal collapse. Methods Thirteen healthy, adult female New Zealander rabbits were involved in this pilot study.A new intra-tracheal device (Reference number 902711 patent registered as CasMin-Twine) was implanted in ten animals. Deployment was performed under general anesthesia, making a puncture incision via a 21 Gauge needle in the intra-tracheal space where the stent was introduced with a screwing process. The device was fixed to the tracheal wall with a non-absorbable suture. Computerized Tomography (CT) and an endoscopy to study structural abnormalities were performed after 30, 90 and 365 days after stent placement. Results Technical and clinical success was 100%. There was no significant change in behavior or respiratory disorders. CT studies showed no significant alterations. After the 30 days, 60% of the animals showed partial endothelization in the endoscopy study, and only one animal still presented partial endothelization after 12 months. Mucus accumulation was only present in 40% of cases and classified as low, without respiratory consequences. Only one animal presented a single granuloma at caudal stent tip. Conclusions This new tracheal stent (CasMin-Twine) is an effective and safe procedure with promising results, and also shows the possibility of removing the device after endothelization has been produced. New studies should be carried out to evaluate the effectiveness in patients with tracheomalacia. Clinical Significance/Impact This new product can give veterinarians a new option of treatment for this complicated pathology. Minimizing specific equipment for its deployment, CasMin-Twine will be more accessible for all professionals

    A new airway spiral stent designed to maintain airway architecture with an atraumatic removal after full epithelization - Research of feasibility and viability in canine patients with tracheomalacia

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    Objective: Surgical management of tracheomalacia is a challenge, with current treatments still presenting numerous complications. In the field of veterinary medicine, this same pathology is present in a significant number of dogs. For this reason, we present an experimental clinical trial performed on canines with tracheobronchomalacia, using a new atraumatic removable tracheal spiral stent (SS). Both implantation procedure and clinical improvement have been analyzed in this study.Methods: In this study, four small dogs, a mean weight of 4.89 kg and body condition scores IV‐V, were included. SS was implanted by two different surgical approaches. Image and clinical follow‐up have been performed during 90 days. Symptoms were evaluated from 1 to 10 every week. Results: This study achieved 100% technical and clinical success. Median tracheal diameters were as follows: cervical 10.85 (3.3), inlet 7.75 (2.1), and carina 7.75 (1.9) mm, and length was 77.5 (26) mm. A 12 × 10 × 100‐mm SS was implanted in all cases. Goose honk cough punctuation improved from 8 to 1; also, there were important changes in exercise intolerance, a mean weight loss of 8.76%. The values of modified Karnofsky scale varied from 50 (20) before surgery to 90 (10) after 30 days of surgery. Neither granuloma tissue nor fractures of the prosthesis was observed.Conclusion: The results in dogs are promising, and a new therapeutic alternative seems to be available for veterinarian field. The similarity of this disease between dogs and newborns suggests that this SS design can also be useful for human trials

    Using the FVB strain of mice for the evaluation of clinical and experimental ketamine (IP) associated with phenothiazines, benzodiazepines and α2-agonists

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    El objetivo de este trabajo ha consistido en evaluar el estado fisiológico de los animales mediante el control de las frecuencias respiratoria y cardiaca así como la tasa de saturación de oxígeno durante la anestesia con ketamina asociada a otros fármacos. Para ello hemos utilizado 40 ratones FVB consanguíneos (20 machos y 20 hembras) de 11 semanas de edad, a los que se les administró por vía intraperitoneal ketamina asociada a un depresor del sistema nervioso central: acepromazina, diazepam, medetomidina, midazolam o xilazina. Obtuvimos resultados que difirieron mucho entre sexos, concluyendo que en machos los mejores resultados obtenidos fueron con la asociación a los α2-agonistas, mientras que en las hembras, al menos a las dosis empleadas, no pudimos afirmar que ninguna de las asociaciones fuese óptima.The aim of this work has been to evaluate the physiological status of animals by controlling the respiratory rate and heart rate and oxygen saturation during anesthesia with ketamine in combination with other drugs. We have used 40 consanguine FVB mice (20 males and 20 females) from 11 weeks of age, who were administered intraperitoneally with a ketamine-associated central nervous system depressant:acepromazina, diazepam, medetomidine, midazolam or xylazine. We obtained results that differed greatly between the sexes, in males, concluding that the best results were obtained with the association of α2- agonists, while in females, at least at the doses employed, did not say that none of the associations were optima

    Epigenetic and post-transcriptional regulation of somatostatin receptor subtype 5 (SST5) in pituitary and pancreatic neuroendocrine tumors

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    Somatostatin receptor subtype 5 (SST5) is an emerging biomarker and actionable target in pituitary (PitNETs) and pancreatic (PanNETs) neuroendocrine tumors. Transcriptional and epigenetic regulation of SSTR5 gene expression and mRNA biogenesis is poorly understood. Recently, an overlapping natural antisense transcript, SSTR5-AS1, potentially regulating SSTR5 expression, was identified. We aimed to elucidate whether epigenetic processes contribute to the regulation of SSTR5 expression in PitNETs (somatotropinomas) and PanNETs. We analyzed the SSTR5/SSTR5-AS1 human locus in silico to identify CpG islands. SSTR5 and SSTR5-AS1 expression was assessed by quantitative real-time PCR (qPCR) in 27 somatotropinomas, 11 normal pituitaries (NPs), and 15 PanNETs/paired adjacent (control) samples. We evaluated methylation grade in four CpG islands in the SSTR5/SSTR5-AS1 genes. Results revealed that SSTR5 and SSTR5-AS1 were directly correlated in NP, somatotropinoma, and PanNET samples. Interestingly, selected CpG islands were differentially methylated in somatotropinomas compared with NPs. In PanNETs cell lines, SSTR5-AS1 silencing downregulated SSTR5 expression, altered aggressiveness features, and influenced pasireotide response. These results provide evidence that SSTR5 expression in PitNETs and PanNETs can be epigenetically regulated by the SSTR5-AS1 antisense transcript and, indirectly, by DNA methylation, which may thereby impact tumor behavior and treatment response.Junta de AndalucíaMinisterio de EconomíaMinisterio de Ciencia e Innovació

    Dynamics of excitable cells: spike-adding phenomena in action

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    We study the dynamics of action potentials of some electrically excitable cells: neurons and cardiac muscle cells. Bursting, following a fast–slow dynamics, is the most characteristic behavior of these dynamical systems, and the number of spikes may change due to spike-adding phenomenon. Using analytical and numerical methods we give, by focusing on the paradigmatic 3D Hindmarsh–Rose neuron model, a review of recent results on the global organization of the parameter space of neuron models with bursting regions occurring between saddle-node and homoclinic bifurcations (fold/hom bursting). We provide a generic overview of the different bursting regimes that appear in the parametric phase space of the model and the bifurcations among them. These techniques are applied in two realistic frameworks: insect movement gait changes and the appearance of Early Afterdepolarizations in cardiac dynamics

    Spectral UV measurements within the EUropean BREWer NETwork: COST Action ES1207 (2013-2017)

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    Presentación realizada en: European Conference on Solar UV Monitoring-ECUVM, celebrada en Viena del 12 al 14 de septiembre de 2018

    Understanding Direct Powder Extrusion for Fabrication of 3D Printed Personalised Medicines: A Case Study for Nifedipine Minitablets

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    Fuse deposition modelling (FDM) has emerged as a novel technology for manufacturing 3D printed medicines. However, it is a two-step process requiring the fabrication of filaments using a hot melt extruder with suitable properties prior to printing taking place, which can be a rate-limiting step in its application into clinical practice. Direct powder extrusion can overcome the difficulties encountered with fabrication of pharmaceutical-quality filaments for FDM, allowing the manufacturing, in a single step, of 3D printed solid dosage forms. In this study, we demonstrate the manufacturing of small-weight (<100 mg) solid dosage forms with high drug loading (25%) that can be easily undertaken by healthcare professionals to treat hypertension. 3D printed nifedipine minitablets containing 20 mg were manufactured by direct powder extrusion combining 15% polyethylene glycol 4000 Da, 40% hydroxypropyl cellulose, 19% hydroxy propyl methyl cellulose acetate succinate, and 1% magnesium stearate. The fabricated 3D printed minitablets of small overall weight did not disintegrate during dissolution and allowed for controlled drug release over 24 h, based on erosion. This release profile of the printed minitablets is more suitable for hypertensive patients than immediate-release tablets that can lead to a marked burst effect, triggering hypotension. The small size of the minitablet allows it to fit inside of a 0-size capsule and be combined with other minitablets, of other API, for the treatment of complex diseases requiring polypharmacy within a single dosage form
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