Allergenius, an expert system for the interpretation of allergen microarray results

BACKGROUND: An in vitro procedure based on a microarray containing many different allergen components has recently been introduced for use in allergy diagnosis. Recombinant and highly purified allergens belonging to different allergenic sources (inhalants, food, latex and hymenoptera) are present in the array. These components can either be genuine or cross-reactive, resistant or susceptible to heat and low pH, and innocuous or potentially dangerous. A large number of complex and heterogeneous relationships among these components has emerged, such that sometimes these interactions cannot be effectively managed by the allergist. In the 1960s, specialized languages and environments were developed to support the replacement of human experts with dedicated decision-making information systems. Currently, expert systems (ES) are advanced informatics tools that are widely used in medicine, engineering, finance and trading. METHODS: We developed an ES, named Allergenius ®, to support the interpretation of allergy tests based on microarray technology (ImmunoCAP ISAC ®). The ES was implemented using Flex, a LPA Win-Prolog shell. Rules representing the knowledge base (KB) were derived from the literature and specialized databases. The input data included the patient’s ID and disease(s), the results of either a skin prick test or specific IgE assays and ISAC results. The output was a medical report. RESULTS: The ES was first validated using artificial and real life cases and passed all in silico validations. Then, the opinions of allergists with experience in molecular diagnostics were compared with the ES reports. The Allergenius reports included all of the allergists’ opinions and considerations, as well as any additional information. CONCLUSIONS: Allergenius is a trustable ES dedicated to molecular tests for allergy. In the present version, it provides a powerful method to understand ISAC results and to obtain a comprehensive interpretation of the patient’s IgE profiling

Fragility analysis of prestressed concrete girder bridges affected by corrosion under traffic loads

Italian and European transportation networks include a considerable number of existing bridges, built since the early ‘60s, characterised by simply supported prestressed-concrete (PC) girders with post-tensioned steel tendons. Corrosion of tendons, which may lead to significant loss of structural capacity, cannot be detected by simple visual inspections and requires advanced and expensive testing by bridge owner companies. Therefore, procedures aimed at risk-informed prioritisation for network-scale assessment are needed, to provide fundamental support for drawing up priority lists to be followed for an optimal allocation of resources to be employed for advanced inspections and possible retrofit. The thesis presents a study on the fragility of existing PC girder bridges considering traffic loads, accounting for corrosion-induced effects. An automated framework is proposed, aiming at the efficient probabilistic structural assessment of the investigated bridge class accounting for 1) the influence of knowledge-based uncertainty related to geometric and mechanical properties and 2) different scenarios including diverse critical corrosion levels and code-compliant traffic load models. A simplified analytical method and a refined finite element method are adopted as structure modelling strategies. To simulate corrosion effects, geometric and mechanical characteristics of prestressing steel tendons are modified by reducing the steel area and stiffness, ductility and strength properties. For analytic calculations, such modifications are integrated into a specific algorithm able to estimate variations in flexural and shear bearing capacity of critical cross-sections. In the thesis, the framework is tested with reference to a dataset of case-study superstructures with different span lengths and numbers of beams. The obtained fragility curves are deeply discussed, focusing on the corrosion effect on structural fragility and highlighting the variation of the corrosion-induced increase in fragility among the selected bridge archetypes. Although the proposed methodology presents some simplifications, it could improve the current practices of risk prioritisation, by supporting transportation authorities in ensuring the safety of the existing bridge stock

Analysis and control of three-phase inverters feeding unbalanced loads

LAUREA MAGISTRALEAl giorno d’oggi le microreti stanno trovando sempre più diffusione sul territorio, favorendo la crescita della generazione distribuita e l’integrazione delle FER con la rete di distribuzione esistente, verso un futuro più sostenibile che punti alla riduzione delle emissioni di CO2, a favore delle fonti energetiche rinnovabili e delle cosiddette Smart Grids. Tra le criticità riguardanti la generazione da FER vi è l’impiego di convertitori statici di interfaccia con la microrete, che spesso richiedono lo sviluppo di specifiche tecniche di controllo per garantire la regolazione e la stabilità della rete stessa; in particolare, lo squilibrio dei carichi, che è abbastanza comune nelle microreti, ha un impatto negativo sull’intero sistema. In questo lavoro di tesi viene presentata l’analisi e il controllo di inverter trifase che alimentano carichi squilibrati. Una delle soluzioni pensata per questo tipo di problema prevede l’utilizzo di un particolare inverter trifase di interfaccia, dove vi è un quarto ramo addizionale che garantisce il punto di connessione del centro stella del carico attraverso il conduttore di neutro. Si analizzano due tipi di configurazione: la prima soluzione prevede l’utilizzo di due condensatori in serie sul quarto ramo, garantendo la stabilizzazione della tensione nominale al carico; la seconda è caratterizzata da una quarta gamba identica alle altre tre, che permette il controllo del centro stella del carico, portando il sistema in condizioni bilanciate. L’analisi della prima tipologia di convertitore è focalizzata sulla valutazione del miglioramento dato dall’inserzione di un’induttanza sul conduttore di neutro, dando come risultato un sistema di tensioni al carico simmetrico ed equilibrato. La seconda si concentra sullo schema di controllo e la tecnica di modulazione dell’inverter, analizzando due diversi metodi per il dimensionamento dei regolatori PI. Il primo metodo è basato sulle tradizionali tecniche di dimensionamento per sistemi SISO; la ricerca di una migliore risposta da parte del sistema ha portato a una valutazione differente del sistema stesso, adoperando tecniche di dimensionamento più complesse per sistemi MIMO. Il criterio di analisi non ha portato completamente ai risultati desiderati, ponendo le basi e gli interrogativi per possibili sviluppi futuri.Nowadays microgrids are spreading more and more around territory, promoting the development of the distributed generation and the integration of RES with the existing distribution grid, towards a more sustainable future that aims at the reduction of CO2 emissions, in favour of renewable energy sources and the so-called Smart Grids. Among the critical issues about the generation by RES there is the use of interface static converters for the connection to the microgrid, which often need the implementation of specific control techniques to guarantee the regulation and the stability of the grid itself; in particular, the unbalance of loads, which is quite common in microgrids, has a negative impact on the entire system. In this thesis work the analysis and control of three-phase inverters feeding unbalanced loads is presented. One of the solutions studied for this kind of problem considers the use of a particular interface three-phase inverter, where an additional leg gives the connection point for the load’s neutral point through the neutral conductor. Two kinds of configuration are analysed: the first one considers the use of two series capacitors on the fourth leg, guaranteeing the stabilization of the nominal voltage across the load; the second one is characterized by a fourth leg identical to the others, which gives the controllability of the load’s neutral point, bringing the system to balanced conditions. The analysis about the former converter’s topology is focused on the evaluation of the improvement given by inserting an inductance on the neutral conductor, giving as result a symmetric and balanced load voltage system. The latter one concentrates on the inverter’s control scheme and modulation technique, analysing two different PI regulators design methods. The first modelling method is based on the traditional designing techniques for SISO systems; the search for a better system response has brought to a different view of the system itself, employing more complex design methods for MIMO systems. The analysis criterion has not completely given the desired results, laying foundations and questions for possible future developments

Managing treatment-resistant depression: what do the guidelines say?

Numerous approaches have been used to de ne and stage treatment-resistant depression (TRD) as well as to nd predictors of treatment outcome. Nevertheless, TRD remains a complex disorder, with high morbidity and mortality. This paper brie y reviews current guidelines for managing TRD, summarising the best pharmacological strategies and ‘next steps’ of psychological and physical treatments. When depressed patients fail to remit after two or more conventional antidepressant treatments, combined approaches, targeting multiple molecular, psychological and physical mechanisms, seem to be the most e ective strategy

Effectiveness of the displacement-based seismic performance assessment for continuous RC bridges and proposed extensions

Seismic performance assessment of existing bridges, especially those designed without seismic criteria, is paramount in earthquake-prone countries. To perform this task, the Displacement-Based Assessment (DBA) represents a satisfactory trade-off between simplicity and accuracy. After describing the modal analysis-based DBA procedure, a static-based alternative is proposed in this paper, considering its strengths and limitations. Moreover, an extension of the procedure is proposed to derive the force-displacement curve of the bridge (pseudo-pushover capacity curve). The effectiveness of the DBA methodology, implemented via simplified mechanical models, is discussed through parametric analyses to address its practical applications. The DBA approach, both modal and static, is herein adopted for the transverse analysis of a set of 36 reinforced concrete continuous-deck bridges up to six spans, with pier height in the range 8–20 m and two different values of the deck transverse stiffness. Additional sensitivity analyses (24 case studies) are conducted to investigate the accuracy of the two approaches considering: 1) the length of the bridge, 2) the amount of longitudinal reinforcement in the piers; 3) different pier typologies. The results are compared to numerical pushover and time-history analyses using three suites of 10 scaled, natural ground motions respectively consistent with low-, medium- and high-seismicity sites. For the majority of the case studies, the resulting performance assessments fall within one standard deviation of the results of the time-history analyses. For this reason, the displacement-based modal or static approaches can represent a valid alternative to numerical non-linear static analyses for continuous bridges with six spans or less

RPAS-Based Framework for Simplified Seismic Risk Assessment of Italian RC-Bridges

Existing reinforced concrete (RC) bridges that were designed in the decades between 1950 and 1990 exhibit inadequate structural safety with reference to both traffic loads and hazard conditions. Competent authorities are planning extensive inspections to collect data about these structures and to address retrofit interventions. In this context, Remotely Piloted Aircraft Systems (RPASs) represent a prospect to facilitate in-situ inspections, reducing time, cost and risk for the operators. A practice-oriented methodology to perform RPAS-based surveys is described. After that, a workflow to perform an in-situ RPAS inspection oriented to a photogrammetric data extraction is discussed. With the aim to connect the advantages of the RPAS technologies to the seismic risk assessment of bridges, a simplified mechanic-based procedure is described, oriented to map the structural risk in road networks and support prioritization strategies. A six-span RC bridge of the Basilicata road network, representing a typical Italian bridge typology is selected to practically describe the operating steps of the RPAS inspection and of the simplified seismic risk assessment approach

Nanoparticles decorated with proteolytic enzymes, a promising strategy to overcome the mucus barrier

The intestinal mucus gel layer represents a stumbling block for drug adsorption. This study is aimed to formulate a nanoparticulate system able to overcome this barrier by cleaving locally the glycoprotein substructures of the mucus. Mucolytic enzymes such as papain (PAP) and bromelain (BRO) were covalently conjugated to poly(acrylic acid) (PAA). Nanoparticles (NPs) were then formulated via ionic gelation method and characterized by particle size, zeta potential, enzyme content and enzymatic activity. The NPs permeation quantified by rotating tube studies was correlated with changes in the mucus gel layer structure determined by pulsed-gradient-spin-echo NMR (PGSE-NMR), small-angle neutron scattering (SANS) and spin-echo SANS (SESANS). PAP and BRO functionalized NPs had an average size in the range of 250 and 285 nm and a zeta potential that ranged between -6 and -5 mV. The enzyme content was 242 μg enzyme/mg for PAP modified NPs and 253 μg enzyme/mg for BRO modified NPs. The maintained enzymatic activity was 43% for PAP decorated NPs and 76% for BRO decorated NPs. The rotating tube technique revealed a better performance of BRO decorated NPs compared to PAA decorated NPs, with a 4.8 fold higher concentration of NPs in the inner slice of mucus. Addition of 0.5wt% of enzyme functionalized NPs to 5wt% intestinal mucin led to c.a. 2 fold increase in the mobility of the mucin as measured by PGSE-NMR indicative of a significant break-up of the structure of the mucin. SANS and SESANS measurements further revealed a change in structure of the intestinal mucus induced by the incorporation of the functionalized NPs mostly occurring at a lengthscale longer than 0.5 μm. Accordingly, BRO decorated NPs show higher potential then PAP functionalized NPs as mucus permeating drug delivery systems

Early-Life Adversity, Systemic Inflammation and Comorbid Physical and Psychiatric Illnesses of Adult Life

Recently, the evidence of increased immune activation in patients with schizophrenia has suggested a role for the immune system in the development of psychosis. However, what is causing this increased immune activation and how this leads to the development of psychopathology remain still unclear. In this chapter we discuss the evidence about the role of childhood trauma as possible underlying cause of the increased immune activation in patients with schizophrenia. According to preclinical and clinical models, early adverse events can disrupt the homeostatic control of immune responses and lead to enduring inflammatory dysregulation at a peripheral and central level. In fact, persisting systemic inflammation may facilitate peripheral tissues damage and breach the blood-brain barrier, leading to microglia activation and to neuroinflammation.Such chronic immune dysregulation also appear to partially explain the frequent comorbidity between psychosis and metabolic abnormalities, which have previously mainly considered as side effect of antipsychotic treatment.Overall, this evidence suggests that early stress may contribute to development of schizophrenia spectrum disorders through a modulation of the peripheral and central immune system and support the immune pathways as possible future therapeutic approach for psychosis.</p