3D bioprinting and its applications in vascular surgery: in-vitro and in-vivo tests for future 5D personalised nanomedicine

Three-dimensional printing techniques demonstrated the high potentiality of interactive processes applied to medicine and surgery. The current, wide availability of different materials and bio-inks allows the precise control of chemical and physical properties of the printed objects obtained through additive manufacturing technology. In addition, 3D printing may produce far-reaching changes in surgical pre-operative management, thanks to the potential interactions with medical imaging modalities. We developed a method based on rapid freeze prototyping (RFP) 3D printer, reconstruction cutting, nano-dry-formulation, fast-freeze gelation, disinfection and partial processes for the 3D to 5D digital models functionalization. We processed a computed tomography angiography scan of a human femoral artery bifurcation, and we reconstructed the 3D model of the vessel to obtain and verify the additive manufacturing processes. Afterwards, a biocompatible eluting-freeform coating for a drug-eluting balloon selected on the basis of the 3D-printed vessel was created under a biosafety cabinet. The alginate-printed coating contained 40nm fluorescent nanoparticles (NP), and was reconstructed by means of RFP printer, and gelled with ethanol (EtOH 98%). Feasibility and effectiveness of this 3D-printed scaffold was tested in-vivo and in-vitro. In order to test this method in-vivo, the NP-loaded 5D device was deployed in a rat’s vena cava. The coating dissolved in a few minutes releasing NP, which were rapidly absorbed in the vessel’s wall,specifically interstitial tissue and vascular smooth muscle cells (confirmed with two-photon microscopy). NP internalisation was also confirmed in-vitro, on vascular smooth muscle cells, and on human umbilical vein endothelial cell (HUVEC) line. We developed 5D, high-resolution,self-dissolving devices containing NP, which can be applied to the personalised medicine, specifically vascular and endovascular devices (such as coatings for drug-eluting balloons or stents, or vascular graft substitutes). In fact, NP can potentially be loaded with different drugs or molecules, in order to obtain a biological activity, thus clinical applicability

Design thinking and acceptance requirements for designing gamified software.

Gamification is increasingly applied to engage people in performing tool-supported collaborative tasks. From previous experiences we learned that available gamification guidelines are not sufficient, and more importantly that motivational and acceptance aspects need to be considered when designing gamified software applications. To understand them, stakeholders need to be involved in the design process. This paper aims to (i) identify key requirements for designing gamified solutions, and (ii) understand if existing methods (partially fitting those requirements) can be selected and combined to provide a comprehensive gamification design method. We discuss a set of key requirements for a suitable gamification design method. We illustrate how to select and combine existing methods to define a design approach that fits those requirements using Design Thinking and the Agon framework. Furthermore, we present a first empirical evaluation of the integrated design method, with participants including both requirements analysts and end-users of the gamified software. Our evaluation offers initial ideas towards a more general, systematic approach for gamification design

Hydrologic control on natural land subsidence in the shallow coastal aquifer of the Ravenna coast, Italy

Abstract. Multiple processes contributing to natural land subsidence in a shallow coastal aquifer near Ravenna (Italy) were identified by analysing the relationships among different data set time series (water table level, rainfall, land reclamation drainage, sea level, etc.) and establishing the correlations with vertical ground motion observed at a high-resolution settlement gauge. Our study highlights the presence of three deformation components related to different processes controlling land subsidence: elastic, delayed-elastic, and irreversible (plastic) components. The elastic and delayed-elastic components are closely related to water table fluctuations that change the effective stress in two portions of the coastal aquifer at a daily (in the sandy unconfined portion) and seasonal time scales (in the layered clay-rich semi-confined prodelta portion), respectively. The irreversible component represents the trend in the land subsidence time series and is due to primary consolidation (pore pressure dissipation) of the fine-grained prodelta levels above where the settlement gauge is located. The amplitudes of the elastic component can be up to 0.2–0.3 mm whereas the amplitude of the delayed-elastic component reaches 0.89 mm. The primary consolidation rate of deformation is 0.9 mm yr−1 and constrains the likely age of prodelta sediments deposition to 1300–2800 years before present. The delayed-elastic subsidence rate has similar magnitude to that due to primary consolidation and is connected to poroelastic effects in the prodelta sequence following seasonal variations in water table. Our findings are important for planning land subsidence management and monitoring strategies especially where the surface aquifer structure is heterogeneous due to different depositional settings. The natural land subsidence rate in the Holocene sediments of the shallow coastal aquifer of Ravenna (North eastern Italy) that we measured in this study accounts for 10 %–20 % of the total current land subsidence rate observed in this portion of Ravenna coastal area (10–20 mm yr−1)

Evolutionary testing of autonomous software agents

A system built in terms of autonomous software agents may require even greater correctness assurance than one that is merely reacting to the immediate control of its users. Agents make substantial decisions for themselves, so thorough testing is an important consideration. However, autonomy also makes testing harder; by their nature, autonomous agents may react in different ways to the same inputs over time, because, for instance they have changeable goals and knowledge. For this reason, we argue that testing of autonomous agents requires a procedure that caters for a wide range of test case contexts, and that can search for the most demanding of these test cases, even when they are not apparent to the agents’ developers. In this paper, we address this problem, introducing and evaluating an approach to testing autonomous agents that uses evolutionary optimisation to generate demanding test cases. We propose a methodology to derive objective (fitness) functions that drive evolutionary algorithms, and evaluate the overall approach with two simulated autonomous agents. The obtained results show that our approach is effective in finding good test cases automatically

Critical storm thresholds for significant morphological changes and damage along the Emilia-Romagna coastline, Italy

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Clinical Profiles in Multiple Sclerosis: Cognitive Reserve and Motor Impairment along Disease Duration

(i) Background: Cognitive impairment in people with multiple sclerosis (MS) has been studied in relation to certain clinical variables (e.g., motor disability and disease duration) and lifestyle factors such as cognitive reserve (CR). However, only very few studies have considered the interaction of clinical variables and cognitive reserve in preserving the integrity of the neuropsychological profile. In this paper, we hypothesised that a higher level of CR might predict good cognitive efficiency by modulating the clinical outcome of the disease. (ii) Methods: A sample of 100 participants with MS (age range 30–74), was recruited and assessed remotely with a questionnaire to measure CR and a cognitive screening test. Data were analysed through generalized additive models. (iii) Results: We found that the model analysing the interaction between CR and disease duration, and between CR and motor disability, was able to explain a significant percentage of cognitive performance. In particular, higher levels of CR predicted a better cognitive performance despite a long disease duration, unless the motor disability was severe. (iv) Conclusion: This study highlights the crucial role of CR in modulating cognitive efficiency in people with MS

Trans-synaptic degeneration in the optic pathway. A study in clinically isolated syndrome and early relapsing-remitting multiple sclerosis with or without optic neuritis

Increasing evidence suggest that neuronal damage is an early and diffuse feature of Multiple Sclerosis (MS) pathology. Analysis of the optic pathway may help to clarify the mechanisms involved in grey matter damage in MS. Purpose of our study was to investigate the relationship between inflammation and neurodegeneration and to achieve evidence of trans-synaptic degeneration in the optic pathway in MS at clinical onset