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Long-term reliability of power GaN HEMTS
Get PDFThe world is quickly changing, and the field of power electronics assumes a pivotal role in addressing the challenges posed by climate change, global warming, and energy management. The introduction of wide-bandgap semiconductors, particularly gallium nitride (GaN), in contrast to the traditional silicon technology, is leading to lightweight, compact and evermore efficient circuitry. However, GaN technology is not mature yet and still presents reliability issues which constrain its widespread adoption. Therefore, GaN reliability is a hotspot for the research community. Extensive efforts have been directed toward understanding the physical mechanisms underlying the performance and reliability of GaN power devices.
The goal of this thesis is to propose a novel in-circuit degradation analysis in order to evaluate the long-term reliability of GaN-based power devices accurately. The in-circuit setup is based on measure-stress-measure methodology where a high-speed synchronous buck converter ensures the stress while the measure is performed by means of full I-V characterizations. The switch from stress mode to characterization mode and vice versa is automatic thanks to electromechanical and solid-state relays controlled by external unit control. Because these relays are located in critical paths of the converter layout, the design has required a comprehensive study of electrical and thermal problems originated by the use of GaN technology. In addition, during the validation phase of the converter, electromagnetic-lumped-element circuit simulations are carried out to monitor the signal integrity and junction temperature of the devices under test. However, the core of this work is the in-circuit reliability analysis conducted with 80 V GaN HEMTs under several operating conditions of the converter in order to figure out the main stressors which contribute to the device's degradation
Prediction of the outcome of external cephalic version for breech presentation using the breech progression angle
Get PDFIntroduzione: La presentazione podalica complica il 3-4% delle gravidanze singole a termine. Sebbene il parto vaginale sia possibile, gli studi in letteratura hanno riportato un aumento del rischio di mortalità e morbilità fetale. Di conseguenza nel mondo il numero di tagli cesarei eseguiti per presentazione podalica è alto. Il rivolgimento per manovre esterne (RME) è una procedura ostetrica sicura che permette il passaggio del feto dalla presentazione podalica a quella cefalica, riducendo il numero dei tagli cesarei. L’angolo di progressione della parte presentata (AoP) è un parametro ecografico descritto in letteratura per la valutazione della progressione della parte presentata attraverso il canale del parto ed è stato recentemente studiato nelle gravidanze con presentazione podalica del feto.
Obiettivi: L’obiettivo primario è valutare la correlazione tra l’AoP e il successo del RME. L’obiettivo secondario è verificare se esiste correlazione tra parametri anamnestici ed ecografici e la riuscita del RME.
Materiali e metodi: È stato condotto uno studio osservazione prospettico monocentrico, sono state reclutate previo consenso informato 54 pazienti afferenti presso l’Ospedale Maggiore di Bologna con gravidanza singola dopo le 36 settimane e feto in presentazione podalica tra gennaio 2020 e giugno 2023.
Risultati: La percentuale di RME riusciti è stata del 48,2%, il 53,7% delle donne ha partorito mediante taglio cesareo. Non abbiamo trovato una correlazione tra AoP e successo del rivolgimento. Tra le altre variabili analizzate l’unica correlata al successo del RME è la quantità di liquido amniotico
Conclusioni: Non abbiamo trovato una correlazione tra AOP e successo del RME. Come descritto in letteratura l’unico parametro ecografico che è risultato associato al successo del RME è la quantità di liquido amniotico. Dato il disegno dello studio e la scarsa numerosità del campione sono necessari ulteriori studi per confermare i risultati.Introduction: Breech presentation complicates 3-4% of single term pregnancies. Although vaginal delivery is possible, some studies reported an increased risk of fetal mortality and morbidity. Consequently, the number of cesarean deliveries for breech presentation is high. External cephalic version (ECV) is a safe obstetric procedure that allows the conversion from breech to cephalic presentation, reducing the number of cesarean sections. The angle of progression (AOP) is an ultrasound parameter for the evaluation of the descent of the fetal head during labor and has recently been investigated in pregnancies with a breech presentation.
Objectives: to evaluate the correlation between the AOP and the success of the ECV. The secondary objective is to verify if there is a correlation between anamnestic and ultrasound parameters and the success of ECV.
Materials and methods: monocentric prospective observational study was performed including 54 patients with single pregnancy and fetal breech presentation at term who underwent to ECV at the Maggiore Hospital of Bologna between January 2020 and June 2023.
Results: No correlation between AOP and success of the ECV was found. The only variable correlated to the success of the ECV was the amount of amniotic fluid.
Conclusions: We have not found a correlation between AOP and success of the ECV. As previously stated in literature, the only ultrasound parameter associated with a successful ECV is the amount of amniotic fluid
Characterization and natural history of different phenotypes in hereditary transthyretin amyloidosis: 40-year experience at a single Italian referral center
Get PDF- Aims: Hereditary Transthyretin Amyloidosis (ATTRv) is one of the leading etiologies of systemic amyloidosis with more than 135 mutations described and a broad spectrum of clinical manifestations. We aimed to provide a systematic description of a population of individuals carrying pathogenic mutations of transthyretin (TTR) gene and to investigate the major clinical events during follow up.
- Methods: Observational, retrospective, cohort study including consecutive patients with mutations of TTR gene, admitted to a tertiary referral center in Bologna, Italy, between 1984 and 2022.
- Results: Three hundred twenty-five patients were included: 106 asymptomatic carriers, 49 cardiac phenotype, 49 neurological phenotype and 121 mixed phenotype. Twenty-three different mutations were found, with Ile68Leu (41.8%), Val30Met (19%), and Glu89Gln (10%) being the most common. After a median follow-up of 51 months data from 290 subjects were analyzed; among them 111 (38.3%) died and 123 (42.4%) had a major clinical event (death or hospitalization for heart failure). Nine (11.5%) of the 78 asymptomatic carriers showed signs and symptoms of the disease. Carriers had a prognosis comparable to healthy population, while no significant differences were seen among the three phenotypes adjusted by age. Age at diagnosis, NYHA functional class, left ventricular ejection fraction, mPND score and disease-modifying therapy were independently associated with survival.
- Conclusions: This study offers a wide and comprehensive overview of ATTRv from the point of view of a tertiary referral center in Italy. Three main phenotypes can be identified (cardiac, neurological and mixed) with specific clinical and instrumental features. Family screening programs are essential to identify paucisymptomatic affected patients or unaffected carriers of the mutation, to be followed through the years. Lastly, disease-modifying therapy represents an evolving cornerstone of the management of ATTRv, with a great impact on mortality
Long-term outcome of anomalous origin of a coronary artery from the pulmonary artery
Get PDFSono stati inclusi nell'analisi ventitrè pazienti (12 femmine, 11 età < 1 anno) con un'età media all'intervento di 12 anni (intervallo di tempo 1998-2023). Il follow-up medio è stato di 8 ± 6 anni. La morte cardiaca improvvisa abortita è stata la presentazione clinica di un singolo paziente adulto in storia naturale. I pazienti < 1 anno di età tendevano ad avere una più severa disfunzione sistolica ventricolare sinistra e richiedevano un decorso post-operatorio più lungo. I risultati chirurgici sono stati eccellenti con un solo decesso post-operatorio e una sola sindrome da bassa portata cardiaca trattata efficacemente con supporto circolatorio meccanico. Durante il follow-up, nella maggior parte dei pazienti si è osservata una completa normalizzazione della funzione ventricolare sinistra e una conseguente riduzione della gravità del rigurgito mitralico. Il burden aritmico era più elevato per i pazienti operati in età adulta. Solo un paziente sottoposto a intervento chirurgico da neonato ha richiesto un'angioplastica percutanea dell'arteria coronaria reimpiantata.Twenty-three patients (12 females, 11 infant-type) with an mean age at surgery of 12 years (time interval 1998-2023) were included in the analysis. The mean follow-up was 8 ± 6 years. Aborted sudden cardiac death was the clinical presentation of a single adult patient in natural history. Patients < 1 year of age tended to have a more severe degree of left ventricular systolic dysfunction and required a longer post-operative course. Surgical results were excellent with only one postoperative death and only one low cardiac output syndrome effectively treated with mechanical circulatory support. During follow-up, in the majority of patients there was a complete normalization of the left ventricular function and a consequent reduction of the severity of mitral regurgitation. The arrhythmic burden was higher for patients operated in adulthood. Only one patient who underwent surgery as an infant required a percutaneous angioplasty of the reimplanted coronary artery
Mediterranean species as main characters in feeding strategy for the development of sustainable systems and resilient farming. Effects evaluation of four experimental diets administered to larvae, juveniles and adults of European Seabass and to Meagre, on growth performance, gut health and animal welfare.
Get PDFAquaculture is a growing wide industry, that until now and in the future represents a sector with enormous potential. Despite that, it is still correlated with environmental issues and ambiental impacts. For several years, both the scientific community and the industry have been working together to make this sector increasingly sustainable and resilient. This doctoral thesis deals with the study and valorisation of alternative ingredients chosen for their nutritional characteristics and potential, with the final aim of giving new inputs to aquaculture to become more sustainable. In particular, this study was focused on:
-Evaluation of green technologies applied to production of microalgae biomass. Renewable energy sources, such as geothermal, can reduce the environmental impact of aquafeed production.
- The use of by-products from fishery and aquaculture in order to replace fish meal fish oil and soybean meal with microalgae.
-Evaluate the effect of experimental diets on different life stages of a commercial species widely distributed in the Mediterranean Sea, European Seabass.
- Among two Mediterranean species considered, Meagre is an emerging species, considered a valid substitute for the most widespread commercial species such as Gilthead Seabream and European Seabass. Emerging species are a very powerful tool to reduce pressure on those species already heavily bred.
- Organic diets were tested on an emerging species, relating both the sustainability of organic diets and the sustainability of emerging species
How to predict treatment response and prognosis in Ewing sarcoma: identification of blood circulating biomarkers.
Get PDFSarcoma di Ewing (SE), il secondo tumore primitivo dell’osso più frequente nella popolazione pediatrica, è un tumore maligno di origine mesenchimale molto aggressivo ed indifferenziato con una elevata tendenza a sviluppare metastasi polmonari e/o ossee. La prognosi dei pazienti con metastasi all’esordio rimane scarsa e sono necessarie nuove strategie per controllare la diffusione nel sangue delle cellule SE. Il sarcoma di Ewing è guidato da alterazioni indotte dal gene chimera EWS-FLI1 che agisce come fattore trascrizionale aberrante che induce la completa riprogrammazione dell'espressione genica. Le cellule dello Ewing sono anche caratterizzate da un'elevata espressione di CD99, una molecola della superficie cellulare che interagisce con EWS-FLI1 per sostenere la malignità del SE. Il sarcoma di Ewing ha un genoma molto stabile con pochissime alterazioni genetiche. A differenza della maggior parte dei tumori, la progressione del SE sembra dipendere da alterazioni epigenetiche. Si ritiene che EWS-FLI1 e CD99 abbiano un impatto considerevole sulla malignità delle cellule di SE, almeno in parte regolandone l'espressione diversi tipi di RNA non codificanti. Lo scopo del presente studio era di indagare il valore di miR-34a-5p (miR34a) come biomarcatore circolante per investigare la progressione della malattia e misurare la risposta terapeutica. Abbiamo valutato l’espressione del miR34a circolante in una coorte di pazienti affetti da EWS con tumore localizzato (PRI, n = 26) o con metastasi rilevabili alla diagnosi (PRI-Met, n = 19). Nel plasma di pazienti con tumori localizzati i livelli di miR34a risultano significativamente più alti rispetto a quelli dei pazienti PRI-Met. Nei pazienti PRI e PRI-Met, l’espressione di miR34a ha mostrato globalmente un aumento alla fine della chemioterapia preoperatoria, tranne che per due pazienti. Questi dati supportano l’idea che la rilevazione di un aumento nei livelli di miR34a possa essere una misura dell’efficacia di terapia.Ewing's arcoma (SE), the second most frequent primary bone tumor in the pediatric population, is a very aggressive and undifferentiated malignant tumor of mesenchymal origin with a high tendency to develop lung and/or bone metastases. The prognosis of patients with metastases at onset remains poor and new strategies are needed to control the spread of SE cells in the blood. Ewing sarcoma is driven by alterations induced by the EWS-FLI1 chimera gene which acts as an aberrant transcriptional factor that induces complete reprogramming of gene expression. Ewing cells are also characterized by high expression of CD99, a cell surface molecule that interacts with EWS-FLI1 to support SE malignancy. Ewing sarcoma has a very stable genome with very few genetic alterations. Unlike most tumors, the progression of SE appears to depend on epigenetic alterations. EWS-FLI1 and CD99 are believed to have a considerable impact on ES cell malignancy, at least in part by regulating the expression of several types of non-coding RNAs. The aim of the present study was to investigate the value of miR-34a-5p (miR34a) as a circulating biomarker to investigate disease progression and measure therapeutic response. We evaluated circulating miR34a expression in a cohort of EWS patients with localized tumor (PRI, n = 26) or with detectable metastases at diagnosis (PRI-Met, n = 19). In the plasma of patients with localized tumors, miR34a levels are significantly higher than those of PRI-Met patients. In PRI and PRI-Met patients, miR34a expression globally showed an increase at the end of preoperative chemotherapy, except for two patients. These data support the idea that the detection of an increase in miR34a levels may be a measure of therapy efficacy
Endothelial damage in pediatric patients diagnosed with Kawasaki Disease, Multisystem Inflammatory Syndrome in children, and acute SARS-CoV-2 infection
Get PDFBackground: La malattia di Kawasaki (KD) e la Sindrome Infiammatoria Multisistemica nei bambini (MIS-C) sono malattie pediatriche caratterizzate da un’intensa infiammazione sistemica e danno vascolare, con potenziale sviluppo di lesioni coronariche (CALs). L'infiammazione multisistemica e la disfunzione endoteliale sono state documentate anche negli adulti con infezione acuta da SARS-CoV-2 (AC19), mentre nei bambini i dati sono ancora scarsi. L’obiettivo primario del presente studio è stato di indagare il danno endoteliale nei pazienti pediatrici con KD, MIS-C e AC19, attraverso la conta delle cellule endoteliali circolanti (CECs).
Metodi: Sono stati arruolati prospettivamente i pazienti con diagnosi di KD e MIS-C tra ottobre 2020 e giugno 2021 in due Unità Operative Pediatriche (IRCCS Azienda Ospedaliera Universitaria di Bologna e Ospedale Ramazzini di Carpi) e i bambini con AC19 ricoverati presso l’IRCCS Azienda Ospedaliera Universitaria di Bologna nello stesso intervallo temporale. Le CECs sono state enumerate mediante la tecnologia CELLSEARCH®, metodica di separazione immunomagnetica di cellule CD146-positive dal sangue intero.
Risultati: Sono stati arruolati 39 pazienti, di cui 9 KD, 20 MIS-C e 10 AC19. Durante la fase acuta, i pazienti con AC19 e KD avevano livelli di CECs più elevati rispetto ai pazienti con MIS-C. Dalla fase acuta a quella subacuta, è stato osservato un aumento significativo delle CECs nei pazienti con KD, e una lieve riduzione nei pazienti con MIS-C. Non è stata trovata alcuna correlazione tra CECs e CALs nei pazienti MIS-C. L'incidenza dei CALs nel gruppo KD è stata troppo bassa per indagare questa correlazione.
Conclusioni: I risultati suggeriscono una profonda differenza nella patogenesi del danno endoteliale tra KD e MIS-C. Inoltre, i livelli di CECs potrebbero rappresentare uno strumento aggiuntivo per differenziare la KD dalla MIS-C all’esordio e per formulare la prognosi cardiovascolare a lungo termine di questi pazienti. Ulteriori studi sono necessari per confermare i risultati ottenuti.Background: Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) are both pediatric diseases characterized by an intense systemic inflammation and vascular damage, with potential development of coronary artery lesions (CALs). Multisystemic inflammation and endothelial dysfunction have also been documented in adults with acute SARS-CoV-2 (AC19) infection, but data on children are still lacking.
The primary aim of this study was to investigate endothelial damage in pediatric patients with KD, MIS-C, and AC19 through the levels of the circulating endothelial cells (CECs).
Methods: A prospective study was conducted, including all patients diagnosed with KD and MIS-C between October 2020 and June 2021 in two Pediatric Units (IRCCS Azienda Ospedaliera Universitaria di Bologna and Ospedale Ramazzini di Carpi) and all children diagnosed with AC19 admitted at the IRCCS Azienda Ospedaliera Universitaria di Bologna in the same time interval. CECs were enumerated using CELLSEARCH® technology, through the immunomagnetic capture of CD146-positive cells from whole blood.
Results: A total of 39 patients were enrolled, including 9 KD, 20 MIS-C and 10 AC19. During the acute phase, patients with AC19 and KD had higher levels of CECs than patients with MIS-C. From the acute to subacute phase, a significant increase in CECs was observed in patients with KD, while a slight decrease was found in patients with MIS-C. No correlation was found between CECs and CALs in MIS-C patients. The incidence of CALs in the KD group was too low to investigate this correlation.
Conclusions: This study suggests a profound difference in the pathogenesis of the endothelial damage between KD and MIS-C. In addition, CECs levels could be an additional tool to differentiate KD from MIS-C at disease onset and to define the long-term cardiovascular prognosis of these patients. Further larger studies are needed to confirm these findings
A reliable and representative simulation study to investigate the risk of impingement in total hip replacement (THR) patients.
Get PDFObjectives
The objective of this doctoral thesis is to construct a reliable and representative, three-dimensional experimental model for the systematic evaluation of the range of motion in Total Hip Replacement (THR), through the integration of specific maneuvers at high-risk of dislocation, and contingent upon variable parameters of pelvic version. A secondary aim is to explicate the underlying mechanisms contributing to impingement phenomena.
Materials and methods
We designed a tridimensional model in a free and open-source simulation environment. Different scenarios were simulated, and the range of motion of the prosthetic hip was assessed. Movements at particular risk of dislocation were assessed, and a study was conducted considering the range of motion of the femur allowed until contact (impingement) between geometries (discriminating bone-to-bone contact, implant-on-implant contact, and implant-on-bone contact). Furthermore, different pelvic version angles were evaluated to assess potential differences.
Results
The anteverted pelvis registered impingement in a greater number of movements (6 out of 9) and presented an overall reduced range of motion until geometries contact, in particular related to posterior dislocation prone movement. Conversely, the pelvic orientation with the average higher range of motion in different simulation scenarios was the neutral pelvis.
The type of impingement that first occurred for most dislocation movements was the implant-on-bone contact. In contrast, the impingement that occurred at higher angles was the implant-on-implant type, which had a relevance only in pure hip extension movements.
Conclusions
The current thesis offers a methodologically rigorous and replicable experimental framework marked by both robustness and high fidelity to average anatomical and biomechanical realities.
The reported findings not only substantiate the importance of pelvic version in THR, defining higher risk for the anteverted pelvis, but also, they highlight the prominent role of implant-on-bone impingement in instability and dislocation
Design for organizational crafting. Design culture and practices for the innovation of contemporary enterprise form
Get PDFI paradigmi organizzativi e di relazione adottati negli ultimi duecento anni dalle imprese- (gerarchia, iperspecializzazione, segregazione di funzioni e competenze) si stanno rivelando poco pronti a gestire progetti caratterizzati da un alto livello di innovazione. Questi progetti richiedono spesso alle imprese, soggetti che operano per definizione nella complessità, capacità di anticipazione, collaborazione ecosistemica e apprendimento nella transizione, attributi propri dell’innovazione trainata dal design. Se da un lato, dunque, tali progetti sono di difficile comprensione per le imprese, dall’altro il problema è specularmente presente anche nella postura del designer verso le imprese in cui si trova ad operare, avendo poca conoscenza del contesto organizzativo. La ricerca analizza il fenomeno da questo duplice punto di vista, laddove considera l’organizzazione come artefatto che il progettista manipola per trasformare l’impresa da struttura a organismo evolutivo. L’organizational crafting è lo schema di progettazione proposto, orientato a lavorare sulla forma dell'organizzazione per adattarla alle sfide di innovazione. Esso può definirsi come un processo collaborativo che coinvolge sia i designer che il management d’azienda ed è orientato alla modellazione di “spazi di attivazione” temporali e decentralizzati, basati su un proposito condiviso, piattaforme e dinamiche collaborative, e creati con l’obiettivo di sbloccare il potenziale dell’intelligenza collettiva dell’organizzazione. La ricerca formalizza, propone e sottopone a critica il framework URSA - Unlocking Spaces for Responsive Activation. A metà strada tra modello e strumento, URSA prova a fungere da diagnostico sia per il designer che per l’impresa e a fornire al contempo una linea-guida per progettare spazi di attivazione che divengono a tutti gli effetti un campo di azione per il progettista. Nella ricerca si fa dunque strada la prospettiva dell’ “Around Design”: il designer lavora nell’organizzazione, sull’organizzazione e per l’organizzazione per dare vita a un nuovo senso, un nuovo contorno, un nuovo “intorno” della “forma-impresa” contemporanea.The enterprise, a multifaceted construct encompassing communal, individual, and semiotic systems, is subject to diverse definitions contingent upon relational structures and procedural interconnections (Bonney, 2010). The starting hypothesis of this research is that the organizational paradigms adopted in the last two hundred years (hierarchy, hyper-specialization, segregation of functions and competences) are proving to be ill-prepared to manage and implement high level innovation projects. Such endeavors necessitate anticipatory capacities, ecosystemic collaboration, and transitional learning inherent in design-driven innovation, challenging enterprises to comprehend their utility, applicability, and feasibility. Furthermore, designers often lack comprehensive insight into organizational dynamics. Consequently, this study scrutinizes this phenomenon, conceiving organizations as malleable artifacts manipulated by designers to metamorphose into adaptive entities capable of contextual assimilation and experiential learning (Stanford, 2018) (Senge, 1990). The inquiry delves into the nexus of design, management, organizational theory and learning, framing designers as transformative agents. The evolving landscape towards decentralized decision-making necessitates the formulation of novel interpretative frameworks for enterprises. Proposed herein is the concept of “organizational crafting”, a collaborative endeavor geared towards sculpting organizational structures to confront emergent innovation challenges. This endeavor entails the delineation of transient, decentralized "spaces of activation," underpinned by shared objectives and collaborative dynamics, aimed at unlocking the organizational collective intelligence. Through empirical exploration within Italian enterprises, with a particular focus on the manufacturing sector, this research introduces and scrutinizes the URSA (Unlocking Spaces Of Responsive Activation) framework. It poised as a diagnostic instrument for designers and enterprises alike, facilitating the design of spaces of activation consonant with organizational needs. Modelling these spaces becomes a designer's endeavor to imbue organizational artifacts with new meanings, shaping the contemporary enterprise environment. Thus, the perspective of "Around Design" emerges, wherein designers work within, on, and for organizations to redefine the contemporary enterprise's essence, form and environment
Informed machine learning for epidemics: from data analysis to time-series forecasting
Get PDFThis research dives deep into the application of Machine Learning (ML) in epidemiology, aiming to craft innovative strategies to address challenges presented by epidemic phenomena.
Recognizing the dual nature of epidemics — as complex physical occurrences and as catalysts of pressure on healthcare systems — we focus on two main areas: data analysis for patient condition assessment and time-series forecasting for epidemiological trend prediction.
In the realm of data analysis, we introduced a tree-based ML pipeline apt at evaluating the severity of infections using patient records. On the forecasting front, we addressed the challenges posed by the scarcity of data and the intricate nature of epidemics, developing methodologies for predicting epidemiological trends.
In this setting, we exploit domain knowledge to guide the learning process, ensuring accurate and reliable predictions even when confronted with incomplete and noisy data