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Comprehensive kinematic evaluation, in vivo and under weight-bearing, of a 3-component total ankle replacement.
Get PDFNonostante le importanti ricadute che gli impianti protesici di caviglia hanno nella qualità della vita dei pazienti che si sottopongono ad intervento di sostituzione articolare, le reali proprietà biomeccaniche e cinematiche in-vivo e sotto carico degli impianti protesici sono state scarsamente studiate e descritte in letteratura. Lo scopo di questa trattazione è quella di valutare la cinematica protesica complessiva, in vivo, attraverso l’utilizzo dell’Analisi Radiostereometrica model-based (MB-RSA) e di ulteriori metodiche clinico-strumentali. La valutazione cinematica è stata permessa dall’analisi della posizione degli impianti attraverso la MB-RSA. Tra gli obiettivi secondari, i pazienti sono stati valutati clinicamente mediante AOFAS Ankle-Hindfoot score e SF-36, mediante full-body gait analysis con sensori inerziali e valutazione posturale-stabilometrica mediante Y Balance Test e workstation dedicata Delos DPPS. I pazienti sottoposti ad iter completo con valutazione clinica e strumentale a fine follow-up sono risultati 18 (2 drop-out). Il ROM complessivo a catena cinetica chiusa ha evidenziato una dorsi-plantarflessione complessiva media di 19.84°. Gli score clinici hanno mostrato tutti un netto miglioramento nel post-operatorio. La gait analysis ha evidenziato uno schema del passo composto dai tre principali spike e compatibile con schemi fisiologici. Dal punto di vista cinematico, i risultati angolari MB-RSA ricavati durante questo lavoro di tesi evidenziano tutti e 6 i gradi di libertà, dato coerente con la mobilità di una caviglia nativa. Valori di articolarità differenti sono stati registrati mediante sensori inerziali. Infine, in una valutazione cinematica complessiva, le possibili implicazioni sul bilanciamento posturale e propriocettivo presente nelle caviglie artrosiche e successivamente sottoposte a sostituzione protesica totale sono ampiamente descritte e discusse. I dati raccolti in questo lavoro di tesi rappresentano il risultato di una valutazione cinematica complessiva, e potranno aiutare a definire una tipologia di soggetto artrosico in cui i risultati siano verosimilmente migliori ed eventualmente a migliorare design e strumentari futuri.Despite the important impact that ankle prosthetic implants have on the quality of life of patients undergoing joint replacement surgery, the real biomechanical and kinematic properties in-vivo of prosthetic implants have been poorly studied and described in the literature. The purpose of this project is to evaluate the overall prosthetic kinematics, in vivo, through the use of model-based radiostereometric analysis (MB-RSA) and further clinical-instrumental methods. The kinematic evaluation was enabled by the analysis of the position of the systems through the MB-RSA. Among the secondary objectives, patients were clinically evaluated using AOFAS Ankle-Hindfoot score and SF-36, through full-body gait analysis with inertial sensors and postural-stabilometric evaluation using Y Balance Test and dedicated Delos DPPS workstation. Patients undergone a complete procedure with clinical and instrumental evaluation at the end of the follow-up were 18 (2 drop-outs). The total ROM with closed kinetic chain showed an average overall dorsi-plantarflexion of 19.84°. Clinical scores all showed a marked improvement in post-op. The gait analysis showed a step pattern composed of the three main spikes and compatible with physiological patterns. From the kinematic point of view, the angular MB-RSA results obtained during this thesis work highlight all 6 degrees of freedom, given consistent with the mobility of a native ankle. Different joint values were recorded by inertial sensors. Finally, in an overall kinematic assessment, the possible implications on the postural and proprioceptive balance present in osteoarthritic ankles and subsequently subjected to total prosthetic replacement are widely described and discussed. The data collected are the result of an overall kinematic assessment, and may help to define a type of osteoarthritic subject in which the results are likely to be better and possibly to improve future design and instrumentation
Impacts of trace element pollution on sewage sludge and soil-plant systems: developing remediation techniques and assessing plant uptake prevention measures
Get PDFTrace Elements (TEs) pollution is a significant environmental concern due to its toxic effects on human and ecosystem health and its potential to bioaccumulate in the food chain and to threaten species survival, leading to a decline in biodiversity. Urban areas, industrial and mining activities, agricultural practices, all contribute to the release of TEs into the environment posing a significant risk to human health and ecosystems. Several techniques have been developed to control TEs into the environment. This work presents the findings of three-year PhD program that focused on research on TEs pollution. The study discusses three fundamental aspects related to this topic from the perspective of sustainable development, environmental and human health. (1) High levels of TEs contamination prevent the use of sewage sludge (SS) as a fertilizer in agriculture, despite its potential as a soil amendment. Developing effective techniques to manage TEs contamination in SS is critical to ensure its safe use in agriculture and promote resource efficiency through sludge reuse. Another purpose of the study was to evaluate different strategies to limit the TEs uptake by horticultural crops (specifically, Cucumis Melo L.). This study addressed the effect of seasonality, Trichoderma inoculation and clinoptilolite application on chromium (Cr), copper (Cu) and lead (Pb) content of early- and late-ripening cultivars of Cucumis Melo L.. Finally, the accumulation of copper and the effect of its bioavailable fraction on bacterial and fungal communities in the rhizosphere soil of two vineyards, featuring two different varieties of Vitis vinifera grown for varying lengths of time, were evaluated
Biotechnological approaches to valorize alternative protein source, waste and by-products from food industries
No full textThe PhD research project was a striking example of the enhancement of milling by-product and alternative protein sources from house cricket (Acheta domesticus), conceived as sustainable and renewable sources, to produce innovative food products.
During milling processing of wheat and rye, several by-products with high technological and functional potential, are produced. The use of selected microbial consortia, allowed to obtain a pre-fermented ingredient for use in the bakery. The pre-ferments obtained were characterized by a high technological, functional and nutritional value, also interesting from a nutraceutical point of view. Bakery products obtained by the addition of pre-fermented ingredients were characterized by a greater quantity of aromatic molecules and an increase in SCFA, antioxidant activity, total amino acids and total phenols resulting in positive effect on the functionality. Moreover, the industrial scaling-up of pre-ferment and innovative bakery goods production, developed in this research, underlined the technological applicability of pre-fermented ingredients on a large scale.
Moreover, the identification of innovative protein sources, can address the request of new sustainable ingredients able to less impact on the environment and to satisfy the food global demand. To upscale the insect production and ensure food safety of insect-based products, biotechnological formulations based on Acheta domesticus powder were optimized. The use of Yarrowia lipolytica in the biotechnological transformation of cricket powder led to the achievement of a cricket-based food ingredient characterized by a reduced content of chitin and an increase of antimicrobial and health-promoting molecules. The innovative bakery products containing cricket-based hydrolysates from Y. lipolytica possessed specific sensory, qualitative and functional characteristics to the final product. Moreover, the combination of Y. lipolytica hydrolysis and baking showed promising results regarding a reduced allergenicity in cricket-based baked products. Thus, the hydrolysate of cricket powder may represent a versatile and promising ingredient in the production of innovative foods
Specificity, efficacy, and adaptive responses mediated by TP53 oncosuppressor mutations of Mitochondrial Complex I inhibitors in personalized cancer therapy: from molecular mechanisms to the development of advanced preclinical models
Get PDFL'inibizione del complesso respiratorio I (CI) è una strategia antitumorale emergente, sebbene la specificità e l’efficacia di nuovi farmaci restino poco investigate. La generazione di modelli cellulari tumorali nulli per il CI rivela la specificità di EVP 4593 e BAY 872243 nell’indurre gli effetti antiproliferativi non associati all’apoptosi, selettivamente via CI, riducendo eventuali effetti collaterali. Studi preliminari in vivo evidenziano un rallentamento della crescita tumorale negli animali trattati con EVP 4593, il quale emerge come l’inibitore più potente.
Per il suo ruolo nella riprogrammazione metabolica, e la sua elevata frequenza di mutazioni nelle neoplasie umane, sono stati investigati i potenziali meccanismi di adattamento alla terapia anti-CI sulla base dello stato mutazionale di TP53. L’auxotrofia da aspartato, un hallmark metabolico delle cellule tumorali con un danno al CI, causa un blocco della sintesi proteica mTORC1-dipendente nelle linee cellulari con una p53 mutata o nulla, inducendo un collasso metabolico. Viceversa, l'attivazione del sensore energetico AMPK promuove un recupero parziale della sintesi di aspartato in linee cellulari con la forma wild type di P53, che è in grado di sostenere una migliore anaplerosi attraverso SCO2, fattore di assemblaggio del complesso respiratorio IV.
Al fine di traslare questi risultati in un modello preclinico, si è ottimizzato l’ottenimento di colture di tumori umani espiantati tramite il bioreattore U-CUP. Il modello scelto è stato quello di carcinoma sieroso ad alto grado dell’ovaio (HGSOC), a partire da tessuto congelato, per l’elevata frequenza di mutazioni driver in TP53. I tessuti congelati preservano l'eterogeneità delle componenti cellulari del tessuto di origine e sono caratterizzati da cellule in attiva proliferazione senza attivazione di apoptosi. Dati preliminari mostrano un trend di riduzione dell’area tumorale nei tessuti trattati con EVP 4593 e supportano l’utilizzo del modello preclinico nello studio di nuovi inibitori del CI sfruttando materiale primario di pazienti oncologici.Inhibition of respiratory complex I (CI) is an emerging anticancer strategy, whose specificity and efficacy of numerous inhibitors remain however elusive. Cancer cell models lacking CI reveal the specificity of EVP 4593 and BAY 872243 in inducing antiproliferative effects not associated with apoptosis, selectively via CI, reducing possible side effects. Preliminary in vivo studies show a slowing of tumor growth in animals treated with EVP 4593, which emerges as the most potent inhibitor.
Because of its role in metabolic reprogramming, and its high mutation frequency in human malignancies, potential mechanisms of adaptation to anti-CI therapy based on TP53 mutational status have been investigated. Auxotrophy by aspartate, a metabolic hallmark of tumor cells with CI damage, causes a blockade of mTORC1-dependent protein synthesis in cell lines with mutated or null p53, inducing metabolic collapse. Conversely, activation of the energy sensor AMPK promotes partial recovery of aspartate synthesis in cell lines with the wild-type P53, which is able to sustain enhanced anaplerosis through SCO2, an assembly factor of respiratory complex IV.
In order to translate these results into a preclinical model, cultures of explanted human tumors were optimized using the U-CUP bioreactor. The model chosen was high-grade serous ovarian cancer (HGSOC), from frozen tissue, because of the high frequency of driver mutations in TP53. Frozen tissues preserve the heterogeneity of cellular components of the tissue of origin and they are characterized by actively proliferating cells without activation of apoptosis. Preliminary data show a trend of tumor area reduction in EVP 4593-treated tissues and support the use of the preclinical model in the study of novel CI inhibitors by exploiting primary tissue from cancer patients
The conundrum of human visceral leishmaniasis in Emilia-Romagna, Italy: are wild and peridomestic animals potential reservoirs?
Get PDFLeishmaniasis is a complex parasitic disease caused by intracellular protozoans of the genus Leishmania mainly transmitted by the bite of sand flies. In Italy, leishmaniasis is caused by Leishmania infantum, responsible for the human visceral and canine leishmaniases (HVL and CanL, respectively). Within Emilia-Romagna region, Italy, recent molecular studies indicated that L. infantum strains circulating in dogs and humans are different. This suggests that an animal reservoir other than dog should be evaluated in the epidemiology of HVL in Emilia-Romagna. Therefore, the main aim of this PhD project was to investigate the role of wild and peridomestic mammals as potential animal reservoirs of L. infantum in the regional zones where HVL foci are still active, also evaluating the possible role of arthropod vectors other than phlebotomine sandflies as vectors of Leishmania spp. in the sylvatic cycle of the protozoa.
Overall, 206 specimens of different animal species (roe deer, rats, mice, badgers, hares, polecats, foxes, beech martens, bank voles, hedgehogs, and shrews), collected in Emilia-Romagna were screened for Leishmania with a real-time PCR, revealing a prevalence of 33% for roe deer (first report in this species). Positivity was also found in brown rats (10.6%), black rats (13.1%), mice (10%), badgers (25%), hedgehogs (80%) and bank voles (11%). To distinguish the two strains of L. infantum circulating in Emilia-Romagna, a nested PCR protocol optimized for animal tissues was developed, demonstrating that over 90% of L. infantum infections in roe deer were due to the strain isolated from humans and suggesting their possible role as reservoirs in the study area. Furthermore, the presence of Leishmania kDNA was detected in unfed larvae, nymphs and males of questing Ixodes ricinus ticks collected in regional parks of Emilia-Romagna suggesting their possible role in the transmission of L. infantum in a sylvatic or rural cycle
Neuro-ophthalmological and electrophysiological characterization of mitochondrial diseases.
Get PDFAims and methods: 1) characterization of patients with Dominant Optic Atrophy (DOA) associated with mutations in AFG3L2 and ACO2 genes in comparison with classical OPA1-DOA; 2) characterization of patients with mtDNA mutations causing MELAS and MERRF syndromes and correlation with heteroplasmy; 3) longitudinal evaluation of subacute m.11778G>A/MTND4 Leber’s Hereditary Optic Neuropathy (LHON) patients co-treated with rAAV2/2-ND4 gene therapy and idebenone. We performed a comprehensive neuro-ophthalmological assessment coupled with electrophysiological examination.
Results: 1) We described and compared 23 ACO2 and 13 AFG3L2 patients with 72 OPA1 patients. All patients presented temporally predominant optic atrophy, with ACO2 showing higher RNFL and GCL thicknesses at OCT, while AFG3L2 was virtually-indistinguishable from OPA1. 2) Retinopathy was the most common manifestation in 17/33 MELAS patients, conversely, optic atrophy was the most common finding in 7/8 MERRF patients. Correlation of heteroplasmy with neuro-ophthalmological parameters failed to disclose any significance in MELAS, while it negatively correlated with OCT parameters in MERRF. 3) We compared modifications in visual acuity, OCT and electrophysiological parameters at 3 timepoints in 9 LHON patients. We observed significant decrease of RNFL thickness and reduction of PhNR amplitude. Visual acuity improved of about -0.37 LogMAR, correlating significantly with time from onset and from injection, but not with idebenone therapy duration.
Discussion: 1) ACO2 seems associated to better preservation of retinal ganglion cells, depending on a different pathogenic mechanism involving mtDNA maintenance, as opposed to AFG3L2 which is involved in OPA1 processing. 2) MELAS and MERRF patients presented with a clearly distinct ocular phenotype, possibly reflecting a selective susceptibility of different retinal cell types to global energy defect or oxidative stress. 3) Follow up of LHON patients treated with gene therapy confirmed the deterioration in OCT and electrophysiological parameters, while the amount of visual improvement was similar to the one observed in recent clinical trials
Hacia una regulación de los smart contracts: especial referencia al sector financiero
Get PDFEsta tesis doctoral aborda un tema complejo y de actualidad.
Complejo, porque no es posible estudiarlo desde un punto de vista jurídico, sin un conocimiento previo de la tecnología subyacente - el blockchain. Y de actualidad, porque esta tecnología ya ha tenido un profundo impacto en el sector financiero en general, coincidiendo con una tendencia reguladora en este campo que no tiene precedentes normativos en los que basarse.
El mundo financiero, el derecho bancario, el derecho de valores y los contratos comerciales se enfrentan a retos que no se pueden ignorar. Este trabajo de investigación aborda esta tecnología desde una perspectiva jurídica, valorando en qué medida el ordenamiento jurídico se está adaptando al ritmo exigido; en qué medida el régimen jurídico vigente ofrece soluciones y puede aplicarse, con ligeras adaptaciones, a esta nueva realidad económico-comercial; y, por último, cuáles son los elementos y características diferenciales de las aplicaciones de la tecnología blockchain, que deben tenerse en cuenta para una adecuada regulación de las mismas, que responda a los problemas que plantean. Conocer los beneficios, riesgos y ventajas son elementos esenciales a considerar en el proceso de regulación, ya iniciado y guiado por la UE, en su voluntad de apostar por la innovación digital en la economía de la Eurozona.This doctoral thesis addresses a complex and topical issue.
Complex, because it is not possible to study it from a legal point of view, without prior knowledge of the underlying technology -blockchain. And current, because this technology has already had a profound impact on the financial sector in a broad sense, coinciding with a regulatory trend on the subject that has no regulatory precedent to rely on.
The financial world, banking law, securities law and commercial contracts face challenges that cannot be ignored. In this research work an approach to this technology is made from a legal perspective, assessing to what extent the legal system is adapting to the required pace, to what extent the current legal regime offers solutions and can be applied, with slight adaptations, to this new economic-mercantile reality; and, finally, what are the differential elements and characteristics of the applications of blockchain technology, which must be taken into account for an adequate regulation of the same, which responds to the problems they pose. Knowing the utilities, risks and advantages are essential elements to consider in the regulatory process, which has already been initiated and led by the the EU, in its desire to bet on digital innovation in the economy of the Eurozone.Questa tesi di dottorato affronta un tema complesso e attuale.
Complesso, perché non è possibile studiarlo da un punto di vista giuridico, senza una preventiva conoscenza della tecnologia sottostante - la blockchain. E attuale, perché questa tecnologia ha già avuto un profondo impatto sul settore finanziario in senso lato, coincidendo con una tendenza normativa in materia che non ha precedenti normativi su cui basarsi.
Il mondo finanziario, il diritto bancario, il diritto dei valori mobiliari e i contratti commerciali devono affrontare sfide che non possono essere ignorate. In questo lavoro di ricerca si affronta questa tecnologia da un punto di vista giuridico, valutando in che misura l'ordinamento giuridico si sta adattando al ritmo richiesto, in che misura l'attuale regime giuridico offre soluzioni e può essere applicato, con lievi adattamenti, a questa nuova realtà economico-mercantile; e, infine, quali sono gli elementi e le caratteristiche differenziali delle applicazioni della tecnologia blockchain, che devono essere presi in considerazione per una regolamentazione adeguata delle stesse, che risponda ai problemi che pongono. Conoscere le utilità, i rischi e i vantaggi sono elementi essenziali da considerare nel processo di regolamentazione, che è già stato avviato e guidato dall'UE, nella sua volontà di scommettere sull'innovazione digitale nell'economia dell'Eurozona
Hybrid lead-halide perovskites as novel materials for thin film direct and flexible ionizing radiation detectors
Get PDFIonizing radiations are important tools employed every day in the modern society. For example, in medicine they are routinely used for diagnostic and therapy. The large variety of applications leads to the need of novel, more efficient, low-cost ionizing radiation detectors with new functionalities. Personal dosimetry would benefit from wearable detectors able to conform to the body surfaces. Traditional semiconductors used for ionizing radiation direct detectors offer high performance but they are intrinsically stiff, brittle and require high voltages to operate. Hybrid lead-halide perovskites emerged recently as a novel class of materials for ionizing radiation detection. They combine high absorption coefficient, solution processability and high charge transport capability, enabling efficient and low-cost detection. The deposition from solution allows the fabrication of thin-film flexible devices. In this thesis, I studied the detection properties of different types of hybrid perovskites, deposited from solution in thin-film form, and tested under X-rays, gamma-rays and protons beams. I developed the first ultraflexible X-ray detector with exceptional conformability. The effect of coupling organic layers with perovskites was studied at the nanoscale giving a direct demonstration of trap passivation effect at the grain boundaries. Different perovskite formulations were deposited and tested to improve the film stability. I report about the longest aging studies on perovskite X-ray detectors showing that the addition of starch in the precursors’ solution can improve the stability in time with only a 7% decrease in sensitivity after 630 days of storage in ambient conditions. 2D perovskites were also explored as direct detector for X-rays and gamma-rays. Detection of 511 keV photons by a thin-film device is here demonstrated and was validated for monitoring a radiotracer injection. At last, a new approach has been used: a 2D/3Dmixed perovskite thin-film demonstrated to reliably detect 5 MeV protons, envisioning wearable dose monitoring during proton/hadron therapy treatments
Gwas analysis for the identification of molecular basis responsible for yield related traits and disease resistance in durum wheat
Get PDFThe PhD thesis was developed in the framework of Innovar H2020 project. This project aimed at using genomics, transcriptomics and phenotyping techniques to update varietal registration procedure used in Europe for Value of Cultivation and Use (VCU) and Distinctiness Uniformity and Stability (DUS) protocols. The phenotypic and genotypic diversity of a durum wheat panel were assessed for different agronomic traits, connected with wheat development, disease resistance and spike fertility. A panel of 253 durum wheat varieties was characterized for VCU and DUS traits and genotyped with Illumina 90K SNP Chip array (Wang et al., 2014). GWAS analysis was performed, detecting strong QTLs confirmed also by literature review. Candidate genes were identified for each trait and molecular markers will be developed to be used for marker assisted selection in breeding programs.
As for disease resistance, the panel was evaluated for resistance to Soil-Borne-Cereal-Mosaic-Virus (SBCMV). A major QTL, sbm2, was detected on chromosome 2B responsible for durum wheat resistance (Maccaferri et al., 2011). The sbm2 interval was explored by fine mapping on segregant population using KASP markers and by RNASeq analysis, detecting candidate genes involved in plant-pathogen reaction.
As regards yield related traits, detailed analysis was performed on the GNI-2A QTL (Milner et al., 2016), responsible for increased number spike fertility. Fine mapping analysis was performed on durum panel identifying hox2 a strong candidate gene, codifying for transcription factor protein. The gene is paralogue of GNI-1 (Sakuma et al., 2019), and it has a 4 kbp deletion responsible for increased number of florets per spikelet.
To conclude, the herein reported thesis shows a complete characterization of agronomic and disease resistance traits in modern durum wheat varieties. The results obtained will augment available information for each variety, identifying informative molecular markers for breeding purposes and QTLs/candidate genes responsible for different agronomic traits
Network assimilation methodology and sectorization of water distribution systems by graph mining and optimization algorithm
Get PDFWater Distribution Networks (WDNs) play a vital importance rule in communities, ensuring well-being band supporting economic growth and productivity. The need for greater investment requires design choices will impact on the efficiency of management in the coming decades.
This thesis proposes an algorithmic approach to address two related problems:(i) identify the fundamental asset of large WDNs in terms of main infrastructure;(ii) sectorize large WDNs into isolated sectors in order to respect the minimum service to be guaranteed to users. Two methodologies have been developed to meet these objectives and subsequently they were integrated to guarantee an overall process which allows to optimize the sectorized configuration of WDN taking into account the needs to integrated in a global vision the two problems (i) and (ii). With regards to the problem (i), the methodology developed introduces the concept of primary network to give an answer with a dual approach, of connecting main nodes of WDN in terms of hydraulic infrastructures (reservoirs, tanks, pumps stations) and identifying hypothetical paths with the minimal energy losses.
This primary network thus identified can be used as an initial basis to design the sectors. The sectorization problem (ii) has been faced using optimization techniques by the development of a new dedicated Tabu Search algorithm able to deal with real case studies of WDNs. For this reason, three new large WDNs models have been developed in order to test the capabilities of the algorithm on different and complex real cases. The developed methodology also allows to automatically identify the deficient parts of the primary network and dynamically includes new edges in order to support a sectorized configuration of the WDN. The application of the overall algorithm to the new real case studies and to others from literature has given applicable solutions even in specific complex situations