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DNA methylation profiling identifies different prognostic clusters of pancreatic neuroendocrine tumors.
No full textThe occurrence and clinical relevance of global DNA hypomethylation and the hypermethylation of gene promoter regions in Pancreatic neuroendocrine tumours (PanNETs) are still largely unknown. The aim of this study was to evaluate the incidence of both epigenetic alterations in PanNETs in order to assess the relation of specific methylation profiles to chromosomal instability and tumour phenotypes.
We analyzed a well-characterized series of 58 PanNETs using DNA from formalin fixed paraffin embedded tissues. Methylation-Sensitive Multiple Ligation-dependent Probe Amplification was performed to assess simultaneously the methylation status of 33 tumour suppressor genes and copy number alterations of 53 chromosomal regions. Global DNA methylation was quantified for Long Interspersed Nucleotide Element-1 using bisulfite pyrosequencing.
Unsupervised hierarchical clustering resulted in three prognostically different hypermethylation groups of PanNETs (p=0.004) with significantly higher methylation levels in cluster 3 that was associated with poor prognosis compared with clusters 1 and 2.
PanNETs were hypomethylated compared to normal pancreas. In average a modest degree of DNA hypomethylation was observed in cluster 1 and 3 tumours, most of which showed low levels of copy number alterations. By contrast, cluster 2 was a group of highly hypomethylated PanNETs showing the highest degree of chromosomal instability. DNA demethylation was strongly correlated with poor prognosis (p<0.0001) and remained the only independent significant predictor of outcome in multivariate analysis that included stage, grading, Ki67 proliferative index and DNA hypermethylation clusters (p=0.006).
The combination of global DNA demethylation and gene hypermethylation analyses allows to define biologically and prognostically distinct subsets of PanNETs. Both alterations can be found in these tumors and each one can promote tumorigenesis by independent processes
Valutazione del funzionamento psicosociale di pazienti in terapia con paliperidone. Confronto con aloperidolo nel "real world".
No full textAims: endpoints of psychotic patients treatments changed a lot in the last years, just as the way of evaluate their efficacy. This happened especially because of the introduction of new psychotropic drugs, able to improve many aspects concerning with psychotic disease. From the ’90s was clear that an improvement only in symptoms could not be identified with a clinical success; actually, interpersonal abilities, quality of life and psychosocial functioning were indicated as the real endpoints of a psychiatric treatment. Paliperidone is an antipsychotic recently introduced in the market. It is a second generation antipsychotic. Many first generation antipsychotics are still widely used in clinical practice, especially haloperidol. A comparison between these two drugs, in terms of social functioning, has been short investigated. First aim of the study is the comparison between patients treated with paliperidone and patients treated with haloperidol, evaluating their social functioning with PSP (Personal and Social Performace Scale). The second aim concerns with symptomatic improvement, evaluated with PANSS (Positive and Negative Syndrome Scale).
Methods: This is a study related to patients from Operative Unity of Psychiatry I and II of Varese. Inclusion methods are a diagnosis of Schizophrenia or other Psychotic Disorders according to DSM IV-TR, and the beginning of a treatment with paliperidone (3-12 mg/day) or haloperidol (2-10 mg/day). Personal data and rating scales scores are marked. Symptomatic recrudescence leading to a new psychiatric hospital admission must not be present in the last three months. Patients are followed up for 6 months.
Risults: 34 patients have been investigated for 6 months (17 treated with paliperidone, 17 treated with haloperidol). The general trend is concerning with a psychosocial and a clinical improvement, both with paliperidone and haloperidol, but no statistically significant difference was found.
Conclusions: Treatment with paliperidone didn’t show a better outcome than haloperidol about psychosocial functioning and symptomatic improvement in psychotic patients
Potenziale angiogenico delle cellule natural killer, isolate da tessuti e da sangue periferico di pazienti affetti da carcinoma del polmone.
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Potestà dei genitori, responsabilità genitoriale e protezione dei minori nel diritto internazionale privato e processuale.
No full textThe purpose of the thesis is to give an overview on the rules of private international law existing at national and at international level and concerning relationships between parents and children, regardless of other conditions. In fact the thesis deals with jurisdiction, applicable law, recognition and enforcement of judgements in the field of parental authority, parental responsibility and child protection.
Whereas the relevant legislation on parents – children relationships does not consider this topic as an unicuum, but takes into account differently the abovementioned categories, the thesis focuses on each of them separately.
As a consequence, the first topic to be addressed is the relationship between the different relevant legislations, with reference to their material scope.
The legislations taken into account are hereafter listed:
- Council Regulation (EC) No 2201/2003 of 27 November 2003 concerning jurisdiction and the recognition and enforcement of judgments in matrimonial matters and the matters of parental responsibility, repealing Regulation (EC) No 1347/2000;
- Hague Convention of 5 October 1961 concerning the powers of authorities and the law applicable in respect of the protection of infants;
- Hague Convention of 19 October 1996 on jurisdiction, applicable law, recognition, enforcement and co-operation in respect of parental responsibility and measures for the protection of the child, that is expected to repeal the 1961 Hague Convention;
- Articles 36, 37 and 42 of Italian Private International Law, n. 218/1995.
After explaining the relationship among the abovementioned legislations, the thesis deals with jurisdiction, focusing on the fundamental principle ruling jurisdiction - the best interest of the child - and on the general criterion for determining jurisdiction: the habitual residence of the child, which is increasingly used in international acts.
On the other hand, nationality is relevant under the 1961 Hague Convention and under Art. 36 of the Italian private international law, as a connecting factor for determining the applicable law. As far as connecting factors in the field of parents - children relationships, the research focuses on several topics, such as the problems arising from the discrimination based on nationality, and on multiple nationalities.
Finally, the research explores the recognition as well as the enforcement of judgments: procedures differ from each other on the basis of where decisions are held, whether in a Member State or not. Also the object of the decision could lead to a different proceeding: for example, a judgment concerning access rights is directly recognized and enforceable in another Member State provided it is accompanied by a certificate, which shall be issued by the judge of origin who stated the judgment. The certificate guarantees that some procedural safeguards have been respected during the procedure in the State where the decision has been adopted. Finally, some recent aspects about public order exception are described.
Parental responsibility is considered by Art. 2 of the Council Regulation (EC) No 2201/2003, and by Art. 1 of the 1996 Hague Convention, which both widely define the concept: in fact “parental responsibility” covers all rights and duties of a parent, guardian or legal representative, relating to the person or the property of the child. This encompasses not only rights of custody and rights of access, but also matters such as the guardianship and the placement of a child in a foster family or in institutional care and child protection.
It is worth underlining that: i) the list of matters qualified as “parental responsibility” pursuant to the Regulation in Art. 2 is not exhaustive, but merely illustrative; ii) it includes also measures for the protection of the child; iii) the concept of parental responsibility pursuant to the 1996 Hague Convention includes parental authority.
As a consequence, parental responsibility may be considered the only relevant category in the field of parents – children relations. This hypothesis may lead to a uniform private international law regulations on family relations
Advanced security aspects on Industrial Control Network.
No full textSecurity threats are one of the main problems of this computer-based era. All systems making use of information and communication technologies (ICT) are prone to failures and vulnerabilities that can be exploited by malicious software and agents. In the latest years, Industrial Critical Installations started to use massively network interconnections as well, and what it is worst they came in contact with the public network, i.e. with Internet.
Industrial networks are responsible for process and manufacturing operations of almost every scale, and as a result the successful penetration of a control system network can be used to directly impact those processes. Consequences could potentially range from relatively benign disruptions, such as the disruption of the operation (taking a facility offline), the alteration of an operational process (changing the formula of a chemical process), all the way to deliberate acts of sabotage that are intended to cause harm.
The interconnectivity of Industrial Control Systems with corporate networks and the Internet has significantly increased the threats to critical infrastructure assets. Meanwhile, traditional IT security solutions such as firewalls, intrusion detection systems and antivirus software are relatively ineffective against attacks that specifically target vulnerabilities in SCADA protocols.
This presents presents an innovative approach to Intrusion Detection in SCADA systems based on the concept of Critical State Analysis and State Proximity. The theoretical framework is supported by tests conducted with an Intrusion Detection System prototype implementing the proposed detection approach
Characterization of the neocortical network excitability with multielectrode arrays: alterations in migraine and epilepsy mouse models.
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Determinants of knowledge flows and their effect on economic growth.
No full textThis thesis consists of three essays that analyse the determinants of the diffusion of knowledge and their impact in terms of economic growth. The first essay analyses the patterns of diffusion of knowledge between European regions during the period 1981-2000. Knowledge flows are measured by two variables: patent citations and collaboration among inventors. A modified gravity model is estimated to show that geographical proximity and territorial borders are important barriers to knowledge flows during the period analysed and that their effects are greater for technological collaboration than for patent citation. We show that inventor propensity to collaborate within the same country decreases and inventor propensity to cite inventors residing in the same country increases. We show also that the geographical distance effect decreases only for inventor collaboration. Finally, we show that the EU enlargement processes during the period analysed have favoured knowledge flows between old and new EU members, although with significant differences for the two measures of knowledge flows. The second essay analyses the impact of knowledge capital on the economic growth of Italian regions for the period 1995-2007. To measure regional knowledge capital we use indicators for the processes of knowledge creation, i.e. R&D and patents, and the processes of diffusion of knowledge, i.e. patent citations and inventor mobility. We use a technology gap model to show that the economic growth of Italian regions can be explained by internal R&D activities and by the interregional mobility of inventors. The third essay analyses the impact of knowledge flows on economic performance at firm level. It distinguishes between various sources of knowledge flows, i.e. suppliers, customers, rivals and research institutions, and between two types of innovative activities, i.e. sales realized by products new to the firm but not to the market (imitation) and sales realized by products new to the firm and to the market (innovation).
We show that knowledge flows from rivals lead to more imitation, while knowledge flows from customers and research institutions enhance original innovation
Integrated experimental and theoretical study of surface properties of TiO2 nanoparticles.
No full textNanostructured titania is rising an increasing interest as one of the key materials for the actual setting of sustainable processes based on the use of sunlight as source of energy. A relevant target is the disclosure of the main structural and surface features that can rule the performances of titania. In this respect, this Ph.D. thesis has been devoted to the study of surface properties of TiO2 nanoparticles with the combined use of IR spectroscopy of adsorbed probe molecules/groups (OH/H2O, CO) and theoretical modeling.
The experimental study of the TiO2 surface sites, with a relevant role for the surface chemistry, allowed to individuate some vibrational bands, due to surface defective sites of TiO2 P25 (Degussa), a kind of benchmark for the photocatalytic applications of titania.
The use of this material represents a source of complexity in this kind of investigations, since the roughness of nanocrystals borders causes the presence of a wide heterogeneity of surface sites with different local structures. Therefore, a TiO2 sample with nanoparticles of regular shape and exposing defined surfaces, has been studied. The a priori knowledge of the surface sites structure has allowed the unambiguous assignment of some of the vibrational bands of the IR spectra of adsorbed probe molecules. These data have been used as reference for the simulation of the IR spectra of adsorbed CO, that allowed the assignment of other signals not attributed on the only basis of experimental data.
The role of the TiO2 surface has also been studied through the TiO2-biomolecules interaction, that provided evidence of the catalytic role of TiO2 surface in promoting the formation of peptidic bond among adsorbed biomolecules
Malattia mentale e imputabilità penale nel dibattito giuridico e medico-scientifico tra Otto e Novecento.
No full textQuesta ricerca si propone di analizzare alcuni aspetti del problema dell'imputabilità penale, con particolare riguardo al vizio di mente giuridicamente rilevante come causa scriminante o scusante, in un periodo di grande fermento, quello dei lavori per il primo codice penale unitario del Regno d'Italia, durante il quale l'intero ambiente giuridico italiano è teso nel massimo sforzo di elaborazione di norme in grado di amalgamare le diverse tradizioni del Paese.
Dopo un breve excursus storico sulle disposizioni preunitarie in materia, si passa ad un esame approfondito della dottrina giuridica e del dibattito interno ad essa, che non solo si concentra sui problemi di formulazione del dettato codicistico, ma indaga sui fondamenti stessi dell'istituto dell'infermità mentale. Il dibattito è influenzato in modo significativo dai numerosi contributi provenienti dall'ambiente medico-scientifico e che per più di venti anni accompagnano il percorso legislativo per supportarlo o, più spesso, per criticarlo e influenzarlo: si è rivelato essenziale, quindi, riportare non solo gli interventi degli esperti del diritto, ma anche le opinioni dei maggiori alienisti italiani della seconda metà dell'Ottocento. Per offrire un'indagine complessiva sulla problematica e sulle principali difficoltà di recepimento della nuova normativa vengono poi illustrate le principali questioni pratiche emerse dopo l’entrata in vigore dell’articolo 46 del Codice Zanardelli, facendo riferimento al corposo materiale giurisprudenziale di fine secolo. Oltre a ciò, data la rilevanza delle problematiche poste al confine tra scienza e diritto, alcune pagine sono dedicate ad un approfondimento della controversa questione della follia morale ed all'influenza sulla responsabilità penale di patologie come la monomania e l'epilessia.
La seconda parte dell'elaborato si concentra, invece, sulla parziale responsabilità di mente, controverso punto di discussione tra Positivisti ed esponenti della Scuola classica, prestando una specifica attenzione alle questioni processuali di compatibilità con alcune cause aggravanti, in particolare la premeditazione.
Infine, il tema del terzo capitolo è il tentativo di Zanardelli, rivelatosi poi fallimentare, di introdurre il manicomio criminale (pensato come un istituto di reclusione per gli imputati assolti per vizio di mente) all'interno del codice in via di promulgazione, e sul dibattito suscitato da una simile proposta nell'ambiente medico e giuridico, con l'insanabile contrasto tra le due grandi Scuole del diritto penale italiano che emerge con prepotenza dalle pagine dei resoconti parlamentari e dai numerosi contributi dottrinali
