InsubriaSPACE
Not a member yet
702 research outputs found
Sort by
Molecular characterization of nosocomial infections: an Italian (KPC-producing Klebsiella pneumoniae) and a Spanish (Clostridium difficile ribotype 027) experience
No full textDuring the last decade, Clostridium difficile and Klebsiella pneumoniae represented two of the most emblematic cause of nosocomial outbreaks, especially following the spread of epidemic variants, able to produce virulent factors and to present higher resistance against several antimicrobial classes.
The rapid identification of dangerous pathogens circulating in nosocomial environment has been made possible by the contribution of molecular methods in support to the classical diagnostic techniques.
The principal objective of this work is to highlight the effectiveness of different molecular typing techniques in the characterization of nosocomial infections, evidencing the genetic relatedness among isolates and the transmission routes of strains involved in epidemic events.
In the first part of the work (Chapter one), the analysis of the principal molecular and phenotypic features of clinical isolates of KPC-producing K. pneumoniae collected in a 27-months period at Ospedale di Circolo e Fondazione Macchi (Varese, Italy) is reported.
Of the 16 isolates analyzed, 7 were involved in an outbreak occurred the Intensive Care Unit (ICU). We investigated the presence of genes involved in carbapenemases resistance (i.e. blaKPC, blaIMP, blaNDM, blaVIM, and blaOXA), the expression of genes for virulence factors (pili/fimbriae, capsular antigen, hypermucousviscosity protein, and siderophores), and mutations leading to colistin resistance.
We also made a phylogenetic analysis adding all the 16 genomes to 319 genomes that represent the global diversity of K. pneumoniae strains.
We found that all isolates analyzed belong to clonal complex CG258. This finding is not surprising, considering previous reports that showed the worldwide diffusion and high prevalence of this clonal group among carbapenem-resistant K. pneumoniae strains. Interestingly, three of the four previously identified groups of Italian isolates of CG258 were found circulating in the hospital, suggesting that several entrance events of the clones may occur over the study period.
About resistance genes, we showed that all 16 genomes express blaKPC genes and none of them had other known carbapenem-resistance genes. Interestingly, 10 of the sixteen isolates, which were colistin-resistance, presented IS5-like transposons in mgrB gene, conferring resistance to this drug.
The second part of the work (Chapter two) aimed to identify and characterize all the clinical isolates of Clostridium difficile ribotype 027 (here, briefly CD027) collected during a 20-months period in the Hospital General Universitario Gregorio Marañon (Madrid, Spain).
The main objective was to characterize the epidemiological links among the CD027 clinical isolates and to defining their transmission routes. To better understand the epidemiological relationships between the strains, all cases identified since January 2014 were added to the analyses. Besides, presence of genetic markers (i.e. mutation in gyrA gene) characterizing the evolution and spread of specific epidemic lineages of CD027 was investigated.
During a 20-months period (January 2014-August 2015), 132 first episodes of C. difficile ribotype 027 has been detected, distinguishing 9 different subtypes (MLVA-types), organized in 5 different clonal complexes (CC) and 4 unique MLVA-patterns. Specifically, one of the five clonal groups (named MLVA-type 1) was responsible of an outbreak which involved 111 patients, and quickly spread in the hospital from October 2014. MLVA typing analysis showed the close genetic relationship of all the strains, suggesting the evolution from a common ancestor. All CD027 isolates carried a specific mutation in gyrA genes, indicating the presence of high transmissible clones belonging to CD027 lineages, but this do not provide more information on their dissemination course.
Moreover, the clonal complexes showed different capacity of spread, which was evidenced by the dissemination of the only CC of MLVA-type 1 leading to the epidemic event.
For this reason, the second objective of Chapter two aimed to evaluate the possible correlation between the transmissibility of the analyzed CD027 clinical isolates and the ability to sporulate. An in vitro protocol has been performed for the evaluation of sporulation rate of epidemic CD027 strain comparing them with those of the ribotype 001, with the objective of determining whether the increased transmissibility of CD027 is due to the greater ability to release endospores into the environment. Comparison between strains belonging to the same ribotype was performed, to evaluate the possible association between sporulation rate and transmissibility.
We found that CD027 strains possessed higher capacity (p=0.005) to produce spores respect to isolates belonging to CD001 but surprisingly their germination ability was significantly lower (p=0.0008) compared to that of CD001, leading to reflect on the adaptability of this pathogen to the environment and the complexity of the mechanisms regulating pathogenic capacity.
Once characterized the rapid spread of an outbreak due to a particular CD027 clone (MLVA-type 1), a further aim was to highlight the possible differences between the efficiency of sporulation and germination of strains belonging to the same ribotype but with different transmission characteristics, underlying the possible association between the ability of sporulation and the strain transmissibility.
Moreover, analysis showed non-significant strain-to-strain variability between C. difficile isolates belonging to the ribotype 027; in particular, comparison was conducted between highly transmissible MLVA-type 1 isolates and the other MLVA-types, showing that neither in sporulation rate (p value =0.72) nor in germination rate (p value=0.24) significant differences exist.
Our findings suggest that further studies preferably by analysis of the transcriptome must be performed to clarify the features involved in CD027 pathogenicity.
This work shows how is possible, by application of molecular typing, to identify pathogens responsible for epidemic situations and to determine the presence of virulence factors o drug resistance genes associated with pathogenicity of strains. Besides it is possible to obtain useful and additional information as the genetic relationships between analyzed strains and their transmission route.
In conclusion, it is showed that active surveillance and characterization of circulating strains at local and national level is crucial to prevent the spread of more virulent variants, with benefits for the patient and the health system
Valore prognostico delle resistenze microcircolatorie dopo angioplastica coronarica in pazienti con disfunzione ventricolare sinistra post-ischemica.
No full textObiettivo: Valutare se la misurazione delle resistenze microcircolatorie iperemiche dopo angioplastica coronarica (PTCA) abbia un ruolo nel predire il recupero funzionale in pazienti con disfunzione ventricolare sinistra post-ischemica.
Metodi: Quarantotto pazienti con disfunzione ventricolare sinistra post-ischemica distale a una stenosi subocclusiva coronarica sono stati sottoposti a PTCA. Gli indici di severità funzionale (fractional flow reserve [FFR] e coronary flow reserve [CFR]) e gli indici di resistenza della stenosi (hyperemic stenosis resistance [HSR]) e del microcircolo (hyperemic microvascular resistance [HMR]) sono stati misurati prima e dopo PTCA mediante filo guida intracoronarico a doppio sensore di flusso e pressione (ComboWire). La frazione d’eiezione ventricolare sinistra (FEVS) e l’indice di contrazione regionale del territorio miocardico relativo al vaso trattato (Wall Motion Score Index target [WMSI-T]) sono stati valutati mediante ecografia transtoracica prima della PTCA e a 3 mesi dall’intervento. L’indice di perfusione del territorio target (Summed Rest perfusion Score [SRS-T]) è stato valutato mediante tomoscintigrafia miocardica (SPECT) prima della PTCA e a 3 mesi dall’intervento. I pazienti sono stati suddivisi in due gruppi a seconda del valore di HMR post-PTCA utilizzando il cut-off predefinito di normalità di 2.0.
Risultati: I valori di FFR, HSR, CFR e HMR sono migliorati in maniera significativa dopo PTCA. In 17 pazienti (Gruppo I: 35.4%) i valori di HMR sono rimasti elevati (HMR>2.0) e significativamente superiori (3.29±1.77 mmHg/cm/sec vs. 1.35±0.34 mmHg/cm/sec; P<0.001) rispetto ai restanti 31 pazienti (Gruppo II: 64.6%). Non vi erano differenze tra gli indici di severità della stenosi epicardica FFR, CFR e HSR prima e dopo PTCA tra i due gruppi di pazienti. Dopo 3 mesi, nei pazienti del Gruppo I non si sono osservati cambiamenti significativi della FEVS (da 41.2 ± 9.4% a 43.1 ± 9.8%; P=0.28), del WMSI-T (da 2.27 ± 0.57 a 2.24 ± 0.58, P=0.33) e del SRS-T (da 10.6 ± 8.9 a 9.4 ± 9.2; P=0.16). I pazienti del Gruppo II hanno invece mostrato un significativo miglioramento della FEVS (da 34.8 ± 7.9% a 40.5 ± 10.3%; P<0.001), del WMSI-T (da 2.57 ± 0.59 a 2.13 ± 0.76; P<0.001) e del SRS-T (da 13.5 ± 5.7 a 10.0 ± 6.0; P<0.001). L’analisi ROC ha mostrato che l’HMR post-PTCA possiede una capacità predittiva significativa di assenza di recupero funzionale del ventricolo sinistro (ΔFE <5%) con sensibilità del 54%, specificità del 96% e valore predittivo positivo del 96% ad un valore di cut-off 1.95 (area sotto la curva 0.69, IC [0.53-0.86], P=0.038).
Conclusioni: Questo studio dimostra che l’HMR post-PTCA ha un importante valore prognostico in pazienti con disfunzione ventricolare sinistra post-ischemica; il riscontro di HMR post-PTCA ≤2 si associa infatti a un netto miglioramento sia della cinetica regionale che della perfusione miocardica a 3 mesi dalla procedura. Al contrario, il riscontro di HMR post-PTCA >2 è un predittore affidabile di mancato recupero funzionale del ventricolo sinistro a 3 mesi
Tikhonov-type iterative regularization methods for ill-posed inverse problems: theoretical aspects and applications
No full textIll-posed inverse problems arise in many fields of science and engineering. The ill-conditioning and the big dimension make the task of numerically solving this kind of problems very challenging.
In this thesis we construct several algorithms for solving ill-posed inverse problems. Starting from the classical Tikhonov regularization method we develop iterative methods that enhance the performances of the originating method.
In order to ensure the accuracy of the constructed algorithms we insert a priori knowledge on the exact solution and empower the regularization term. By exploiting the structure of the problem we are also able to achieve fast computation even when the size of the problem becomes very big.
We construct algorithms that enforce constraint on the reconstruction, like nonnegativity or flux conservation and exploit enhanced version of the Euclidian norm using a regularization operator and different semi-norms, like the Total Variaton, for the regularization term.
For most of the proposed algorithms we provide efficient strategies for the choice of the regularization parameters, which, most of the times, rely on the knowledge of the norm of the noise that corrupts the data.
For each method we analyze the theoretical properties in the finite dimensional case or in the more general case of Hilbert spaces.
Numerical examples prove the good performances of the algorithms proposed in term of both accuracy and efficiency
Developpement et optimisation de détecteurs de lumière innovants et bolométres scintillants pour une expérience pilote sur la double désintégration bêta sans émission de neutrinos
No full textThe PhD work described in this manuscript was performed in the framework of the LUMINEU project, a pilot search for the neutrinoless double beta decay (0νββ) of the isotope in 100Mo with ZnMoO4 scintillating bolometers. The main PhD activity has consisted the development of a particle detection technology able to fulfill the requirement of a next generation experiment on 0νββ capable of exploring the inverted hierarchy region of the neutrino mass pattern. We report about an experimental physics work involving progress in detector prototype design and tests, and development of tools in view of a large experiment preparation.
The neutrinoless double beta decay is a hypothetical rare nuclear transition with a half life T1/2>1025 years, which is possible for some nuclei with an even number both of protons and neutrons. In the 0νββ transition two neutrons decay simultaneously in two protons with the emission of only two electrons. In a first approximation it can be seen as two simultaneous β-decays where the two neutrinos act as a single virtual particle joining the two decay vertices. It is demonstrated that any process which leads to 0νββ is possible only if ν≡ ν̄ˉ, i.e. the neutrino is a Majorana particle, which is in contrast with the Standard Model assumptions. Therefore, the observation of this phenomenon can determine the Majorana nature of massive neutrinos. This is of fundamental importance to make progress in our understanding of the origin of neutrino masses and mixing and of the symmetries governing the lepton sector of particle interactions. The measurement of the T1/2
of the process would give unvaluable information on the absolute scale of neutrino masses, the type of neutrino mass spectrum and the Majorana phases. The detection approach adopted in this thesis is the homogeneous bolometric technique, which fits well the detector characteristics needed to investigate rare events. The detector provides high efficiency and a very good energy resolution and, thanks to a scintillating absorber, it allows particle discrimination for background suppression. As can be easily understood, the control of the background is crucial to measure such rare decays.
The first part of this thesis focuses on the neutrino physics and on the 0νββ decay; moreover the experimental detection approaches are briey discussed and the sensitivity to the half life of a 0νββ experiment is discussed. To understand the progress achieved in the technology development, the following chapter is dedicated to the detector physics: the components of a bolometer, a simple thermal model, and the detector response are introduced.
The second part of this work is dedicated to the setup. The detectors used work at very low temperatures (~10 mK), thus sophisticated thermal machines are needed; the working principles of these cryogenic systems are presented focusing on the details of the ones used in this work. Since the experimental work discussed in this thesis concerns the detector assembly and measurement, the data acquisition and analysis are discussed in details too.
The final part of the thesis is devoted to the results, starting with the progress made on bolometric light detectors: a description and optimization of the light detector design, the effect of anti-reflective coating and the thermal response enhancement obtained with the Neganov-Luke effect are presented. The results on the development of the LUMINEU prototype detectors and the measurements are summarized, from the working tests to the radioactive contaminant measurements. The growth and purification process of the ZnMoO4 crystals are also presented. Based on these results, a final sensitivity of a future experiment based on this detector is computed.
Finally we present a spin-off of the LUMINEU project consisting in a scintillating bolometer prototype made with an alternative compound absorber, Li2MoO4. We examine the advantages and disadvantages with respect to the ZnMoO4.
This manuscript aims at being a guide to an experimental approach for the search for neutrinoless double beta decay, a manual for scintillating bolometer operations and a report about the successful LUMINEU project. Le travail de doctorat exposé dans ce manuscrit a été développé dans le cadre du projet LUMINEU, une expérience pilote pour la double désintégration bêta sans émission de neutrinos (0νββ) de l'isotope 100Mo avec des bolométres scintillants de ZnMoO4. L'activité principale du doctorat consistait en le développement d'une technologie de détection de particules capable de satisfaire les conditions nécessaire d'une experience de 0νββ de nouvelle génération qui soit capable d'examiner la région de la hiérarchie inversée du modèle de la masse du neutrino. Nous exposons un travail de physique expérimentale qui implique l'avancement du design et des tests des prototypes de détecteurs, et le développement des outils en vue de la préparation d'une expérience importante.
La double désintégration bêta sans émission de neutrinos est une hypothétique transition nucléaire rare avec une demi-vie de T1/2>1025 ans, qui est possible pour certains noyaux avec un nombre pair de protons et de neutrons. Dans la transition 0νββ deux neutrons se désintégrent simultanément en deux protons avec l'émission de deux électrons seulement. Dans une première approximation, ce peut être vu comme deux β désintégrations où les deux neutrinos agissent comme une seule particule virtuelle en joignant les deux sommets de désintégration. Il est prouvé que n'importe quel processus qui conduit au 0νββ est possible seulement si if ν≡ ν̄ˉ, v.g. le neutrino est une particule de Majorana, qui contraste avec les hypothéses du Modèle Standard. Par conséquence, l'observation de ce phénomène peut déterminer la nature Majorana des neutrinos massifs. C'est très important de faire progresser notre compréhension de l'origine de la masse et de la composition des neutrinos et de la symétrie qui régit le secteur des leptons des interactions de particules. La mesure du T1/2 du processus peut fournir des informations inestimables sur l'échelle absolue de la masse des neutrinos, sur le type de spectre de masse des neutrinos et sur les phases de Majorana. La méthode de détection adoptée dans cette thèse est la technique bolométrique, qui s'intègre bien avec les caractéristiques requises des détecteurs pour étudier les événements rares. Le détecteur fournit une grande efficacité et une très bonne résolution en énergie et, grâce à un absorbeur scintillant, il permet la discrimination des particules pour la suppression du fond. Comme on peut bien comprendre, le contrôle du background est crucial pour mesurer ces désintégrations rares. La première partie de cette thèse se concentre sur la physique du neutrino et sur la désintégration 0νββ; en outre, les méthodes de détection expérimentales et la sensibilité de la demi-vie d'une expérience 0νββ sont traitées. Pour comprendre les progrès réalisés dans le développement de la technologie, le chapitre suivant est dédié à la physique des détecteurs: les composants d'un bolomètre, un modèle thermique simple, et la réponse d'un détecteur sont présentés.
La deuxième partie de ce travail est dédiée au setup. Les détecteurs utilisés fonctionnent aux très basses températures (~10 mK), par conséquent, des machines thermique sophistiquées sont nécessaires; les principes de fonctionnement de ces systèmes cryogéniques sont présentés en se concentrant sur les détails de ceux qui ont été utilisés dans ce travail. Puisque l'activité expérimentale présentée dans cette thèse porte sur l'assemblage et sur les mesures du détecteur, aussi l'acquisition et l'analyse des données sont traités en détails.
La dernière partie de la thèse est consacrée aux résultats, à commencer par les progress réalisés dans le détecteurs bolométriques de lumière: une description et optimisation du design des détecteurs de lumiére, l'effet du traitement antireet et l'amélioration de la réponse thermique obtenue avec l'effet Neganov-Luke sont présentés. Les résultats sur le développement des prototypes des détecteurs LUMINEU et les mesures sont résumés. Les processus de croissance et purification des cristaux ZnMoO4 sont aussi présentés. Sur la base de ces résultats nous avons calculé une sensibilité finale sur une expérience à venir basée sur ces détecteurs.
Enfin, nous présentons un spin-off du projet LUMINEU qui consiste dans un prototype d'un bolomètre scintillant réalisé avec un absorbeur composé alternatif, Li2MoO4. Nous examinons les avantages et les désavantages par rapport au ZnMoO4. Ce manuscrit a comme but d'être un guide à une approche expérimentale pour la recherche de la double désintégration bêta sans émission de neutrinos, un manuel pour les opérations de bolomètres scintillants et un rapport sur l'expérience réussie du projet LUMINEU
Interfaces in implant dentistry.
No full textDental implants are a safe and effective solution for the prosthetic rehabilitation of partially and totally edentulous patients, as has been clearly demonstrated by several clinical articles with follow-up up > 20 years. The high percentage of long-term survival (> 95% at 10 years) that characterizes dental implants has made them an essential tool in modern dentistry, and today, implants are commonly used to support various types of prosthetic rehabilitation, such as fixed prostheses (single crowns, fixed partial dentures, fixed full arches) and removable dentures.
If we analyse an implant-fixed prosthetic restoration, it is possible to identify three critical levels or interfaces:
1. Bone/implant interface
2. Implant/abutment interface
3. Restoration/mucosa interface
The strengthening of each of these three interfaces is of fundamental importance in the ability to ensure the survival, biological integration, functional stability and aesthetic success of a prosthetic implant-supported restoration
La fagliazione superficiale all'interno del processo per la localizzazione di un deposito di rifiuti radioattivi
No full textmissin
Optimization and development of new voltammetric methods for the determination of iron in seawater
No full textmissin
Fistole rinoliquorali spontanee: verso un moderno algoritmo diagnostico-terapeutico.
No full textIntroduzione: Le fistole rinoliquorali spontanee sono un eterogeneo gruppo di fistole a cui afferiscono tutti i casi di fistola rinoliquorale per le quali non è stata possibile identificare un meccanismo eziopatogenetico. Permane tuttavia il dubbio da parte di molti autori che in tale gruppo confluiscano fistole rinoliquorali causate da patologie non correttamente diagnosticate. Sebbene siano state effettuate numerose ricerche per meglio identificare l’eziologia e la patogenesi delle fistole rinoliquorali spontanee non si è ancora giunti a formulare un algoritmo diagnostico-terapeutico condiviso. Tale tipologia di fistole, dai dati ricavati dalla analisi della letteratura, è gravata da un maggiore tasso di recidiva rispetto alle fistole a eziologia nota probabilmente proprio poiche' il fattore eziopatogenetico rimane spesso misconosciuto e conseguentemente non trattato.
Materiali e Metodi: Il presente studio, attraverso una valutazione retrospettiva della casistica (2002-2013) delle Cliniche Otorinolaringoiatrica e Neurochirurgica dell’Ospedale del Circolo e Fondazione Macchi-Università degli Studi dell’Insubria di Varese, analizza una popolazione di 103 pazienti sottoposti a intervento chirurgico di riparazione di fistola rinoliquorale spontanea. Scopo di questa tesi è arrivare alla stesura di un algoritmo diagnostico-terapeutico per le fistole rinoliquorali spontanee e in particolare identificare le indagini diagnostiche opportune per una diagnosi precoce delle fistole rinoliquorali spontanee e validare l’approccio endoscopico endonasale come tecnica chirurgica di scelta nel trattamento delle fistole rinoliquorali spontanee.
Discussione: L' algoritmo diagnostico da noi utilizzato ha permesso una rapida diagnosi ed una precisa localizzazione della fistola, e di conseguenza la pianificazione dell’intervento chirurgico più adeguato per il paziente. L’approccio endoscopico endonasale ha inoltre soppiantato nella maggior parte dei casi gli approcci intracranici ed extracranici non endoscopici, relegando quest’ultima tecnica al solo intervento combinato endoscopico-lembo osteoplastico frontale per il trattamento delle fistole rinoliquorali spontanee della parete posteriore del seno frontale. I vantaggi della chirurgia endoscopica consistono soprattutto in una minore invasività, che consente di evitare le principali complicanze dell’approccio intracranico come la lesione del bulbo olfattorio con conseguentemente anosmia, l’edema cerebrale.
Conclusioni: L’utilizzo di un valido algoritmo diagnostico-terapeutico ha infatti permesso una corretta e tempestiva diagnosi, una precisa localizzazione del difetto e un trattamento chirurgico ottimale. La possibilità di scegliere fra le varie tecniche d’approccio e di effettuare il tipo di chiusura ottimale, a seconda delle caratteristiche anatomopatologiche della fistola, risulta determinate per ottenere una bassa percentuale di recidive. Una maggiore comprensione della fisiopatologia delle fistole rinoliquorali spontanee potrebbe portare a un corretto inquadramento e a una adeguata classificazione di tale patologia poiché riconoscerne i meccanismi causali consentirebbe un miglioramento della loro gestione e permetterebbe di intraprendere, quando necessario, il trattamento più adeguato
