112 research outputs found

    The Cat Is On the Mat. Or Is It a Dog? Dynamic Competition in Perceptual Decision Making

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    Recent neurobiological findings suggest that the brain solves simple perceptual decision-making tasks by means of a dynamic competition in which evidence is accumulated in favor of the alternatives. However, it is unclear if and how the same process applies in more complex, real-world tasks, such as the categorization of ambiguous visual scenes and what elements are considered as evidence in this case. Furthermore, dynamic decision models typically consider evidence accumulation as a passive process disregarding the role of active perception strategies. In this paper, we adopt the principles of dynamic competition and active vision for the realization of a biologically- motivated computational model, which we test in a visual catego- rization task. Moreover, our system uses predictive power of the features as the main dimension for both evidence accumulation and the guidance of active vision. Comparison of human and synthetic data in a common experimental setup suggests that the proposed model captures essential aspects of how the brain solves perceptual ambiguities in time. Our results point to the importance of the proposed principles of dynamic competi- tion, parallel specification, and selection of multiple alternatives through prediction, as well as active guidance of perceptual strategies for perceptual decision-making and the resolution of perceptual ambiguities. These principles could apply to both the simple perceptual decision problems studied in neuroscience and the more complex ones addressed by vision research.Peer reviewe

    Native Cyclodextrins as Complexation Agents for Pterostilbene: Complex Preparation and Characterization in Solution and in the Solid State

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    Pterostilbene (3,5-dimethoxy-4′-hydroxystilbene, PTB) is a natural dietary stilbene, occurring primarily in blueberries and Pterocarpus marsupium heartwood. The interest in this compound is related to its different biological and pharmacological properties, such as its antioxidant, anti-inflammatory, and anticarcinogenic activities and its capacity to reduce and regulate cholesterol and blood sugar levels. Nevertheless, its use in therapy is hindered by its low aqueous solubility; to overcome this limitation we studied the feasibility of the use of cyclodextrins (CDs) as solubility-enhancing agents. CDs are natural macrocyclic oligomers composed of α-d-glucose units linked by α-1,4 glycosidic bonds to form torus-shaped molecules, responsible for inclusion complex formation with organic molecules. In particular, the aim of this study was to evaluate the feasibility of complexation between PTB and native CDs using various preparative methods. The isolated solid products were characterized using differential scanning calorimetry (DSC), simultaneous thermogravimetric/DSC analysis (TGA/DSC), Fourier transform infrared (FT-IR) spectroscopy, and X-ray diffraction (XRD) on powder and single crystals. The results indicated little or no evidence of the affinity of PTB to complex with α-CD using the kneading method. However, with β-CD and γ-CD thermal analysis revealed an interaction which was also corroborated by FT-IR and 1H-NMR spectroscopy. With β-CD, a hydrated complex of PTB was isolated and its characterization by single-crystal XRD revealed, for the first time, the mode of inclusion of the PTB molecule in the cavity of a CD. To complement the solid-state data, liquid-phase studies were carried out to establish the effect of CDs on the aqueous solubility of PTB and to determine the complex stoichiometries and the association constants for complex formation. Phase-solubility studies showed AL-type profiles for α- and β-CD and a BS profile for γ-CD, with K1:1 values of 1144, 4950, and 133 M−1 for α-CD·PTB, β-CD·PTB, and γ-CD·PTB, respectively. The stoichiometry of CD·PTB complexes, determined by Job’s method, revealed for each system a 1:1 molar ratio. The dissolution rate of PTB was approximately doubled just by employing simple physical mixtures, but the best performance was achieved by products obtained via kneading and co-precipitation, which effected the complete dissolution of PTB in 40 and 20 min for β-CD and γ-CD, respectively

    Shape fidelity and sterility assessment of 3D printed polycaprolactone and hydroxyapatite scaffolds

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    AbstractPolycaprolactone (PCL) and hydroxyapatite (HA) composite are widely used in tissue engineering (TE). They are fit to being processed with three-dimensional (3D) printing technique to create scaffolds with verifiable porosity. The current challenge is to guarantee the reliability and reproducibility of 3D printed scaffolds and to create sterile scaffolds which can be used for in vitro cell cultures. In this context it is important for successful cell culture, to have a protocol in order to evaluate the sterility of the printed scaffolds. We proposed a systematic approach to sterilise 90%PCL-10%HA pellets using a 3D bioprinter before starting the printing process. We evaluated the printability of PCL-HA composite and the shape fidelity of scaffolds printed with and without sterilised pellets varying infill pattern, and the sterility of 3D printed scaffolds following the method established by the United States Pharmacopoeia. Finally, the thermal analyses supported by the Fourier Transform Infrared Spectroscopy were useful to verify the stability of the sterilisation process in the PCL solid state with and without HA. The results show that the use of the 3D printer, according to the proposed protocol, allows to obtain sterile 3D PCL-HA scaffolds suitable for TE applications such as bone or cartilage repair

    In Vitro and Ex Vivo Evaluation of Tablets Containing Piroxicam-Cyclodextrin Complexes for Buccal Delivery

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    In the current study, the development of mucoadhesive tablets for buccal delivery of a non-steroidal anti-inflammatory drug was investigated. Binary complexes with piroxicam and cyclodextrins (beta-cyclodextrin (b-CD), methylated-beta-cyclodextrin (Me-b-CD), and hydroxypropyl-beta-cyclodextrin (HP-b-CD)) were prepared by the co-evaporation method. All formulations were characterized by means of diferential scanning calorimetry, infrared spectroscopy and powder X-ray diffractometry. Mucoadhesive tablets of binary systems were formulated by direct compression using chitosan as mucoadhesive polymer. The in vitro release profiles of tablets were conducted in simulated saliva and, the drug permeation studies, across porcine buccal mucosa. The results suggest that the rank order effect of cyclodextrins for the drug release was Me-b-CD >HP-b-CD > b-CD, whereas the ex vivo studies showed that the tablets containing chitosan significantly increased the transport of the drug compared to their free complexes. Finally, histological assessment revealed loss of the superficial cell layers, which might be attributed to the presence of cyclodextrins

    Finding Common Ground When Experts Disagree: Robust Portfolio Decision Analysis

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    Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

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    BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

    Physico-chemical characterisation of Silk-based materials

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    Physico-chemical characterisation is essential to define and to assure quality, safety and efficacy of silk-based materials when intended for pharmaceutical and biomedical use. In fact, the possible interconversion and interactions between the various conformations of the fibroin and sericin, and the transitions from the most stable crystalline forms to the metastable amorphous ones, can modify (i) the release properties of the drugs from the silk-based delivery systems, (ii) the silk-based carrier's superficial properties, determining the targeting mechanisms to the site of action. Thermal analysis and spectrophotometric methods, supported by X-ray diffraction analysis and microscopic techniques, are useful to characterise the main crystal structures and the three conformations, Silk I, Silk II and unstable Silk III, of proteins. This chapter reports some applicative examples of the analyses performed with these techniques concerning the characterisation of silk proteins and silk-based micro/nano-drug delivery systems
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