ABSTRACT
The subject of this paper is the Penrose kite and dart tiling of the plane: an aperiodic tiling where, in his own words, "the tiles may be used to form an instructive game … the virtue of the game lies in the very surprising variety which arises in the fitting together of pieces of only two kinds”. We deal with a teaching experience in collaboration with a lab technician, a high school teacher and a graduating student: how to let high school students project and produce the kite and dart tiles using a Computer Numerical Control (CNC) machine. It is a project of work-related learning with 110 students coming from seven different high schools, in collaboration with the Model and Prototype Laboratory of the Department of Architecture at Roma Tre University. We discuss the effect of this activity on the learning process of the students, the methodology applied, the technical and organizational problems we faced in a Covid related period. Using the software GeoGebra, we will also show the geometric construction of Penrose tiles and how to produce an application to simulate the tessellation making. © Palestine Polytechnic University-PPU 2023.
ABSTRACT
Background: Patients with pre-existing multimorbidity and liver dysfunction (LD) are more likely to develop severe COVID-19 and have a higher risk of mortality. In severe COVID-19 patients who are mechanically ventilated or require supplemental oxygen, the administration of dexamethasone (DEX) may be life-saving, however the impact of LD on the pharmacokinetics (PK) of DEX is unknown. The aim of the study was to apply PBPK modelling to predict the effect of LD on the PK of DEX in the treatment of COVID-19. Methods: A whole-body PBPK model was designed in Simbiology v. 9.6.0 (MATLAB R2019a) and used to simulate 100 adult individuals. First the model was qualified against reported clinical data for oral (PO) and intravenous (IV) DEX in healthy adults. Physiological changes and portal vein shunt were incorporated into the model to provide a mathematical description of LD that was classified by Child-Pugh (CP) scores A, B and C. The LD model was qualified against IV and PO reported clinical data for both propranolol (healthy adults and CP-A,-B and-C patients) and midazolam (healthy adult and cirrhosis patients). The model was assumed to be verified if the simulated values were within 2-fold of the reported clinical values and if the absolute average-fold error (AAFE) was below 2. The qualified model was then used to simulate the administration of DEX 6 mg (COVID-19 protocol) in patients with LD (CP-A,-B and-C) with and without shunting. The mean shunt index (%) considered in the model was 40 ± 18. Results: The PBPK model was successfully qualified across DEX, midazolam and propranolol with an AUC0-24 average fold of 1.1 and 0.95;AAFE value of 1.1 and 1.2 for healthy and LD individuals, respectively. When compared to healthy adults, the simulated systemic clearance of DEX decreased and the plasma concentrations increased in all patients with LD, as shown in Table 1. Moreover, a significant difference was observed between the AUC0-24 of DEX PO when comparing no shunting and shunting in patients with CP-B and-C. Conclusion: The increased exposure of DEX in different stages of LD was predicted through PBPK modelling, providing a rational framework to predict PK in complex clinical scenarios related to COVID-19. Although DEX exposure was predicted to be more than 2 times higher in CP-C individuals, no dose adjustments seem necessary in patients with LD considering DEX's low hepatic extraction, the low dose administered in the COVID-19 protocol and the therapeutic index of DEX.
ABSTRACT
Although the incidence is uncertain, some case reports suggest that COVID 19 infection is associated with an increased risk of venous thromboembolism. We suggest starting prophylactic anticoagulant therapy for all patients hospitalized with a symptomatic infection with COVID-19, unless contraindicated, with enoxaparin 40 mg SC daily if creatinine clearance is greater than 30 ml/min.