International cooperation in endourology: percutaneous and flexible ureteroscopic treatment of lower pole kidney stones

Introduction Lower pole kidney stones represent at time a challenge for the urologist. The gold standard treatment for intrarenal stones <2 cm is Extracorporeal Shock Wave Lithotripsy (ESWL) while for those >2 cm is Percutaneous Nephrolithotomy (PCNL). The success rate of ESWL, however, decreases when it is employed for lower pole stones, and this is particularly true in the presence of narrow calices or acute infundibular angles. Studies have proved that ureteroscopy (URS) is an efficacious alternative to ESWL for lower pole stones <2 cm, but this is not reflected by either the European or the American guidelines. The aim of this study is to present the results of a large series of flexible ureteroscopies and PCNLs for lower pole kidney stones from high-volume centers, in order to provide more evidences on the potential indications of the flexible ureteroscopy for the treatment of kidney stones. Materials and Methods A database was created and the participating centres retrospectively entered their data relating to the percutaneous and flexible ureteroscopic management of lower pole kidney stones. Patients included were treated between January 2005 and January 2010. Variables analyzed included case load number, preoperative and postoperative imaging, stone burden, anaesthesia (general vs. spinal), type of lithotripter, access location and size, access dilation type, ureteral access sheath use, visual clarity, operative time, stone-free rate, complication rate, hospital stay, analgesic requirement and follow-up time. Stone-free rate was defined as absence of residual fragments or presence of a single fragment <2 mm in size at follow-up imaging. Primary end-point was to test the efficacy and safety of flexible URS for the treatment of lower pole stones; the same descriptive analysis was conducted for the PCNL approach, as considered the gold standard for the treatment of lower pole kidney stones. In this setting, no statistical analysis was conducted owing to the different selection criteria of the patients. Secondary end-point consisted in matching the results of stone-free rates, operative time and complications rate of flexible URS and PCNL in the subgroup of patients harbouring lower pole kidney stones between 1 and 2 cm in the higher diameter. Results A total 246 patients met the criteria for inclusion. There were 117 PCNLs (group 1) and 129 flexible URS (group 2). Ninety-six percent of cases were diagnosed by CT KUB scan. Mean stone burden was 175±160 and 50±62 mm2 for groups 1 and 2, respectively. General anaesthesia was induced in 100 % and 80% of groups 1 and 2, respectively. Pneumo-ultrasonic energy was used in 84% of cases in the PCNL group, and holmium laser in 95% of the cases in the flexible URS group. The mean operative time was 76.9±44 and 63±37 minutes for groups 1 and 2 respectively. There were 12 major complications (11%) in group 1 (mainly Grade II complications according to Clavidien classification) and no major complications in group 2. Mean hospital stay was 5.7 and 2.6 days for groups 1 and 2, respectively. Ninety-five percent of group 1 and 52% of group 2 required analgesia for a period longer than 24 hours. Intraoperative stone-free rate after a single treatment was 88.9% for group 1 and 79.1% for group 2. Overall, 6% of group 1 and 14.7% of group 2 required a second look procedure. At 3 months, stone-free rates were 90.6% and 92.2% for groups 1 and 2, respectively, as documented by follow-up CT KUB (22%) or combination of intra-venous pyelogram, regular KUB and/or kidney ultrasound (78%). In the subanalysis conducted comparing 82 vs 65 patients who underwent PCNL and flexible URS for lower pole stones between 1 and 2 cm, intreoperative stone-free rates were 88% vs 68% (p= 0.03), respectively; anyway, after an auxiliary procedure which was necessary in 6% of the cases in group 1 and 23% in group 2 (p=0.03), stone-free rates at 3 months were not statistically significant (91.5% vs 89.2%; p=0.6). Conversely, the patients undergoing PCNL maintained a higher risk of complications during the procedure, with 9 cases observed in this group versus 0 in the group of patients treated with URS (p=0.01) Conclusions These data highlight the value of flexible URS as a very effective and safe option for the treatment of kidney stones; thanks to the latest generation of flexible devices, this new technical approach seems to be a valid alternative in particular for the treatment of lower pole kidney stones less than 2 cm. In high-volume centres and in the hands of skilled surgeons, this technique can approach the stone-free rates achievable through PCNL in lower pole stones between 1 and 2 cm, with a very low risk of complications. Furthermore, the results confirm the high success rate and relatively low morbidity of modern PCNL for lower pole stones, with no difference detectable between the prone and supine position.

Role of nitric oxide and endocannabinoids in synaptic plasticity in the perirhinal cortex and in visual recognition memory

Introduction and aims of the research Nitric oxide (NO) and endocannabinoids (eCBs) are major retrograde messengers, involved in synaptic plasticity (long-term potentiation, LTP, and long-term depression, LTD) in many brain areas (including hippocampus and neocortex), as well as in learning and memory processes. NO is synthesized by NO synthase (NOS) in response to increased cytosolic Ca2+ and mainly exerts its functions through soluble guanylate cyclase (sGC) and cGMP production. The main target of cGMP is the cGMP-dependent protein kinase (PKG). Activity-dependent release of eCBs in the CNS leads to the activation of the Gαi/o-coupled cannabinoid receptor 1 (CB1) at both glutamatergic and inhibitory synapses. The perirhinal cortex (Prh) is a multimodal associative cortex of the temporal lobe, critically involved in visual recognition memory. LTD is proposed to be the cellular correlate underlying this form of memory. Cholinergic neurotransmission has been shown to play a critical role in both visual recognition memory and LTD in Prh. Moreover, visual recognition memory is one of the main cognitive functions impaired in the early stages of Alzheimer’s disease. The main aim of my research was to investigate the role of NO and ECBs in synaptic plasticity in rat Prh and in visual recognition memory. Part of this research was dedicated to the study of synaptic transmission and plasticity in a murine model (Tg2576) of Alzheimer’s disease. Methods Field potential recordings. Extracellular field potential recordings were carried out in horizontal Prh slices from Sprague-Dawley or Dark Agouti juvenile (p21-35) rats. LTD was induced with a single train of 3000 pulses delivered at 5 Hz (10 min), or via bath application of carbachol (Cch; 50 μM) for 10 min. LTP was induced by theta-burst stimulation (TBS). In addition, input/output curves and 5Hz-LTD were carried out in Prh slices from 3 month-old Tg2576 mice and littermate controls. Behavioural experiments. The spontaneous novel object exploration task was performed in intra-Prh bilaterally cannulated adult Dark Agouti rats. Drugs or vehicle (saline) were directly infused into the Prh 15 min before training to verify the role of nNOS and CB1 in visual recognition memory acquisition. Object recognition memory was tested at 20 min and 24h after the end of the training phase. Results Electrophysiological experiments in Prh slices from juvenile rats showed that 5Hz-LTD is due to the activation of the NOS/sGC/PKG pathway, whereas Cch-LTD relies on NOS/sGC but not PKG activation. By contrast, NO does not appear to be involved in LTP in this preparation. Furthermore, I found that eCBs are involved in LTP induction, but not in basal synaptic transmission, 5Hz-LTD and Cch-LTD. Behavioural experiments demonstrated that the blockade of nNOS impairs rat visual recognition memory tested at 24 hours, but not at 20 min; however, the blockade of CB1 did not affect visual recognition memory acquisition tested at both time points specified. In three month-old Tg2576 mice, deficits in basal synaptic transmission and 5Hz-LTD were observed compared to littermate controls. Conclusions The results obtained in Prh slices from juvenile rats indicate that NO and CB1 play a role in the induction of LTD and LTP, respectively. These results are confirmed by the observation that nNOS, but not CB1, is involved in visual recognition memory acquisition. The preliminary results obtained in the murine model of Alzheimer’s disease indicate that deficits in synaptic transmission and plasticity occur very early in Prh; further investigations are required to characterize the molecular mechanisms underlying these deficits.

Il Libro del naufragio. Edizione e commento

Edizione e commento della raccolta di miracoli mariani denominata "Libro del Naufragio" secondo la lezione del ms Firenez, Laurenziana, Ashburham 546

Social aspects of organic agriculture and other multifunctional benefits - Successful EU models compared with possibilities for organic developments in Croatia

Main objective of the dissertation is to illustrate how social and educational aspects (in close interaction with other multifunctional aspects in organic agriculture) which are developed on different multifunctional organic farms in Italy and Netherlands, as well as established agricultural policy frameworks in these countries, can be compared with the situation in Croatian organics and can contribute to further developent of organic issues in the Repubic of Croatia. So, through different chapters, the dissertation describes the performance of organic agriculture sectors in Italy, Netherlands and Croatia within the national agricultural policy frameworks, it analyzes the role of national institutions and policy in Croatia in connection with Croatia's status of candidate country for enterance into EU and harmonization of legislation with the CAP, as well as analyzes what is the role of national authorities, universities, research centres, but also of private initiatives, NGOs and cooperatives in organic agriculture in Netherlands, Italy and Croatia. Its main part describes how social and educational aspects are interacting with other multifunctional aspects in organic agriculture and analyzes the benefits and contribution of multifunctional activites performed on organic farms to education, healthy nourishment, environment protection and health care. It also assess the strengths and weaknesses of organic agriculture in all researched countries. The dissertation concludes with development opportunities for multifunctional organic agriculture in Croatia, as well as giving perspectives and recommendations for different approaches on the basis of experiences learned from successful EU models accompanied with some personal ideas and proposals.

Il corretto finanziamento dell'impresa societaria

Nel corso del lavoro sono state affrontare le tematiche relative al finanziamento dell’impresa organizzata in forma societaria, in particolare, approfondendo i profili inerenti al ruolo del socio nelle dinamiche relative all’afflusso di risorse finanziarie alla società partecipata e al rimborso o, a seconda dei casi, alla distribuzione dei corrispondenti valori. È stato analizzato il fenomeno della sottocapitalizzazione, sottolineando l’importanza, nella prospettiva della tutela dell’integrità del patrimonio sociale e delle pretese dei creditori, della complessiva consistenza del patrimonio netto. Si è cercato di ricostruire la disciplina applicabile alla riserva costituita mediante imputazione dei versamenti in conto capitale. Ampia parte della trattazione è stata, poi, dedicata al tema dei finanziamenti dei soci con diritto al rimborso. Più in particolare sono stati affrontati il problema dell’individuazione della fattispecie di finanziamento dei soci di s.r.l. di cui all’art. 2467 c.c. e quello della ricostruzione della disciplina applicabile alla suddetta fattispecie. Particolare attenzione è stata dedicata I) all’argomento dell’applicabilità della postergazione legale anche al di fuori di una procedura di liquidazione volontaria o concorsuale II) alla questione delle disciplina applicabile ai finanziamenti postergati nella liquidazione volontaria III) alla disciplina dei crediti postergati nel fallimento. Un certo spazio è stato poi riservato al tema dell’applicabilità dell’art. 2467, comma,1 ai finanziamenti concessi nell’ambito dell’esercizio di attività di direzione e coordinamento; per poi concludere con un’analisi critica della questione dell’applicabilità analogica dell’art. 2467 c.c. alle società per azioni con compagine sociale coesa e ristretta

Ingegneria di Manutenzione

Lo scopo di questa tesi di dottorato di ricerca consiste nel fornire la giusta collocazione della manutenzione fra le discipline dell'ingegneria, raccogliendo e formalizzando le metodologie di analisi di affidabilità e di pianificazione degli interventi all'interno di un unico processo di progettazione e di controllo. In linea di principio, un processo di analisi dei guasti e di programmazione della manutenzione deve essere in grado di fornire chiare e sicure risposte ai seguenti interrogativi: Quali sono le funzioni richieste e con quali criteri di prestazioni il sistema è chiamato ad assolverle? Qual'è l'andamento della disponibilità del sistema in funzione del tempo? Quanti guasti e di quale tipo si possono verificare durante la vita del sistema? Quali possono essere le conseguenze che ledono la sicurezza e la protezione ambientale? Quanti pezzi di ricambio sono necessari? Che tipo di interventi di manutenzione preventiva risultano tecnicamente fattibili? A quali scadenze devono essere programmati? A quanto ammonta la previsione del costo di esercizio del sistema? Quante squadre di manutenzione devono essere assegnate al sistema? Come deve essere organizzata la logistica di manutenzione? Con quali tecniche si prevede di riconoscere i guasti e quali procedure devono essere attivate per farvi fronte? E' possibile implementare tecniche di `condition monitoring' delle macchine? Su quali tempi di preavviso sui guasti si può contare? In tal senso, la manutenzione necessita delle tecniche e degli opportuni strumenti che siano in grado di misurarne l'efficacia e l'efficienza. L'efficacia in primo luogo, in quanto l'obiettivo principe consiste nel garantire che il sistema oggetto di studio continui a svolgere le proprie funzioni nei limiti di prestazioni accettabili, secondo le specifiche richieste degli utilizzatori. L'efficienza in secondo luogo, ma non per questo di minore importanza, in quanto perseguendo l'obiettivo di cui sopra, occorre impegnare il minimo di risorse possibili, organizzando con razionalità il supporto logistico del sistema al fine di raggiungere i massimi livelli di rendimento di gestione. La migliore strategia di manutenzione può essere pianificata, a priori, solo se si è in grado di prevedere con la necessaria precisione l'evoluzione del sistema nel suo contesto operativo futuro. E' allora possibile formulare un modello matematico del sistema, studiarne la dinamica ed osservare le reazioni alla simulazione di eventuali stimoli esterni. I metodi ed i modelli noti dell'ingegneria dei sistemi possono essere molto utili per la risoluzione di casi semplici, ma sovente richiedono la formulazione di ipotesi troppo restrittive che aumentano in modo inaccettabile la distanza del modello dalla realtà. Una strada alternativa ed affascinante, che ho percorso con entusiasmo durante questi tre anni di studi e ricerca, consiste nella simulazione numerica della vita del sistema, utilizzando il metodo Monte Carlo per la gestione dei processi stocastici di guasto e per l'esecuzione degli interventi di manutenzione. Ho quindi messo a punto il codice di simulazione RAMSES, perseguendo l'idea di costruire uno strumento di misura dell'efficacia e dell'efficienza di una politica di manutenzione simulata al calcolatore. Nella tesi si presentano i concetti di base dell'ingegneria dei sistemi applicata al caso della manutenzione e si introduce il formalismo della Reliability Centred Maintenance come miglior guida nella pianificazione delle schede di manutenzione. Si introducono le nozioni di base per fornire una struttura solida e corretta alla simulazione numerica dei sistemi riparabili e si presenta il codice RAMSES corredando le informazioni tecniche con i dovuti esempi ed applicazioni pratiche. Si conclude il lavoro, infine, con la presentazione di un modello di massima verosimiglianza particolarmente utile per le analisi dei dati sperimentali di guasto dei componenti.

Reexamining the Role of Incarceration and Stigma in Criminal Law

One of the ways by which the legal system has responded to different sets of problems is the blurring of the traditional boundaries of criminal law, both procedural and substantive. This study aims to explore under what conditions does this trend lead to the improvement of society's welfare by focusing on two distinguishing sanctions in criminal law, incarceration and social stigma. In analyzing how incarceration affects the incentive to an individual to violate a legal standard, we considered the crucial role of the time constraint. This aspect has not been fully explored in the literature on law and economics, especially with respect to the analysis of the beneficiality of imposing either a fine or a prison term. We observed that that when individuals are heterogeneous with respect to wealth and wage income, and when the level of activity can be considered a normal good, only the middle wage and middle income groups can be adequately deterred by a fixed fines alone regime. The existing literature only considers the case of the very poor, deemed as judgment proof. However, since imprisonment is a socially costly way to deprive individuals of their time, other alternatives may be sought such as the imposition of discriminatory monetary fine, partial incapacitation and other alternative sanctions. According to traditional legal theory, the reason why criminal law is obeyed is not mainly due to the monetary sanctions but to the stigma arising from the community’s moral condemnation that accompanies conviction or merely suspicion. However, it is not sufficiently clear whether social stigma always accompanies a criminal conviction. We addressed this issue by identifying the circumstances wherein a criminal conviction carries an additional social stigma. Our results show that social stigma is seen to accompany a conviction under the following conditions: first, when the law coincides with the society's social norms; and second, when the prohibited act provides information on an unobservable attribute or trait of an individual -- crucial in establishing or maintaining social relationships beyond mere economic relationships. Thus, even if the social planner does not impose the social sanction directly, the impact of social stigma can still be influenced by the probability of conviction and the level of the monetary fine imposed as well as the varying degree of correlation between the legal standard violated and the social traits or attributes of the individual. In this respect, criminal law serves as an institution that facilitates cognitive efficiency in the process of imposing the social sanction to the extent that the rest of society is boundedly rational and use judgment heuristics. Paradoxically, using criminal law in order to invoke stigma for the violation of a legal standard may also serve to undermine its strength. To sum, the results of our analysis reveal that the scope of criminal law is narrow both for the purposes of deterrence and cognitive efficiency. While there are certain conditions where the enforcement of criminal law may lead to an increase in social welfare, particularly with respect to incarceration and stigma, we have also identified the channels through which they could affect behavior. Since such mechanisms can be replicated in less costly ways, society should first try or seek to employ these legal institutions before turning to criminal law as a last resort.

"Tracciature Digitali": la conoscenza nell'era informazionale

La specificità dell'acquisizione di contenuti attraverso le interfacce digitali condanna l'agente epistemico a un'interazione frammentata, insufficiente da un punto di vista computazionale, mnemonico e temporale, rispetto alla mole informazionale oggi accessibile attraverso una qualunque implementazione della relazione uomo-computer, e invalida l'applicabilità del modello standard di conoscenza, come credenza vera e giustificata, sconfessando il concetto di credenza razionalmente fondata, per formare la quale, sarebbe invece richiesto all'agente di poter disporre appunto di risorse concettuali, computazionali e temporali inaccessibili. La conseguenza è che l'agente, vincolato dalle limitazioni ontologiche tipiche dell'interazione con le interfacce culturali, si vede costretto a ripiegare su processi ambigui, arbitrari e spesso più casuali di quanto creda, di selezione e gestione delle informazioni che danno origine a veri e propri ibridi (alla Latour) epistemologici, fatti di sensazioni e output di programmi, credenze non fondate e bit di testimonianze indirette e di tutta una serie di relazioni umano-digitali che danno adito a rifuggire in una dimensione trascendente che trova nel sacro il suo più immediato ambito di attuazione. Tutto ciò premesso, il presente lavoro si occupa di costruire un nuovo paradigma epistemologico di conoscenza proposizionale ottenibile attraverso un'interfaccia digitale di acquisizione di contenuti, fondato sul nuovo concetto di Tracciatura Digitale, definito come un un processo di acquisizione digitale di un insieme di tracce, ossia meta-informazioni di natura testimoniale. Tale dispositivo, una volta riconosciuto come un processo di comunicazione di contenuti, si baserà sulla ricerca e selezione di meta-informazioni, cioè tracce, che consentiranno l'implementazione di approcci derivati dall'analisi decisionale in condizioni di razionalità limitata, approcci che, oltre ad essere quasi mai utilizzati in tale ambito, sono ontologicamente predisposti per una gestione dell'incertezza quale quella riscontrabile nell'istanziazione dell'ibrido informazionale e che, in determinate condizioni, potranno garantire l'agente sulla bontà epistemica del contenuto acquisito.

Fingerprint Recognition: Enhancement, Feature Extraction and Automatic Evaluation of Algorithms

The identification of people by measuring some traits of individual anatomy or physiology has led to a specific research area called biometric recognition. This thesis is focused on improving fingerprint recognition systems considering three important problems: fingerprint enhancement, fingerprint orientation extraction and automatic evaluation of fingerprint algorithms. An effective extraction of salient fingerprint features depends on the quality of the input fingerprint. If the fingerprint is very noisy, we are not able to detect a reliable set of features. A new fingerprint enhancement method, which is both iterative and contextual, is proposed. This approach detects high-quality regions in fingerprints, selectively applies contextual filtering and iteratively expands like wildfire toward low-quality ones. A precise estimation of the orientation field would greatly simplify the estimation of other fingerprint features (singular points, minutiae) and improve the performance of a fingerprint recognition system. The fingerprint orientation extraction is improved following two directions. First, after the introduction of a new taxonomy of fingerprint orientation extraction methods, several variants of baseline methods are implemented and, pointing out the role of pre- and post- processing, we show how to improve the extraction. Second, the introduction of a new hybrid orientation extraction method, which follows an adaptive scheme, allows to improve significantly the orientation extraction in noisy fingerprints. Scientific papers typically propose recognition systems that integrate many modules and therefore an automatic evaluation of fingerprint algorithms is needed to isolate the contributions that determine an actual progress in the state-of-the-art. The lack of a publicly available framework to compare fingerprint orientation extraction algorithms, motivates the introduction of a new benchmark area called FOE (including fingerprints and manually-marked orientation ground-truth) along with fingerprint matching benchmarks in the FVC-onGoing framework. The success of such framework is discussed by providing relevant statistics: more than 1450 algorithms submitted and two international competitions.