Path-dependent SDEs with jumps and irregular drift: well-posedness and Dirichlet properties

We discuss a concept of path-dependent SDE with distributional drift with possible jumps. We interpret it via a suitable martingale problem, for which we provide existence and uniqueness. The corresponding solutions are expected to be Dirichlet processes, nevertheless we give examples of solutions which do not fulfill this property. In the second part of the paper we indeed state and prove significant new results on the class of Dirichlet processes

An approach based on Support Vector Machines and a K-D Tree search algorithm for identification of the failure domain and safest operating conditions in nuclear systems

The safety of a Nuclear Power Plant (NPP) is verified by analyzing the system responses under normal and accidental conditions. This is done by resorting to a Best-Estimate (BE) Thermal-Hydraulic (TH) code, whose outcomes are compared to given safety thresholds enforced by regulation. This allows identifying the limit-state function that separates the failure domain from the safe domain. In practice, the TH model response is affected by uncertainties (both epistemic and aleatory), which make the limit-state function and the failure domain probabilistic. The present paper sets forth an innovative approach to identify the failure domain together with the safest plant operating conditions. The approach relies on the use of Reduced Order Models (ROMs) and K-D Tree. The model failure boundary is approximated by Support Vector Machines (SVMs) and, then, projected onto the space of the controllable variables (i.e., the model inputs that can be manipulated by the plant operator, such as reactor control-rods position, feed-water flow-rate through the plant primary loops, accumulator water temperature and pressure, repair times, etc.). The farthest point from the failure boundary is, then, computed by means of a K-D Tree-based nearest neighbor algorithm; this point represents the combination of input values corresponding to the safest operating conditions. The approach is shown to give satisfactory results with reference to one analytical example and one real case study regarding the Peak Cladding Temperature (PCT) reached in a Boiling Water Reactor (BWR) during a Station-Black-Out (SBO), simulated using RELAP5-3D

Follia e reato nella storia della Psichiatria. Osservazioni storiche sul rapporto tra assistenza psichiatrica e carcere

The paper examines the relations between psychiatry and prison between the beginning of the Nineteenth century and the first years of the Twentieth century to gather affinity and differences with the themes of today's debate. The Reunions of the Italian Scientists had the worth to represent an important moment of national scientific debate before the political realization of the unity of Italy. At the beginning of the forties of the Nineteenth century they studied, among many other themes, the effects of the different formes of detention (particularly the systems of Philadelphia and Auburn) on the health, and particularly on the mental health, of the prisoner. These matters were also debated passionately in that years in other European countries, with the intervention of some intellectuals as Alexis de Tocqueville, Gustave de Beaumont, Charles Lucas and Charles Dickens. During this debate it emerged with clarity the risk, for the physicians, to unconsciously involve themselves in  a punitive mission or in necessities of public order; but the prevailing orientation in the Reunions, nevertheless, was that to reject this tendency, and to ask to the physicians to assume as their principal task that to pronounce themselves on the salubriousness or unhealthiness of the prison systems. Subsequently, the psychiatrist Serafino Biffi studied with competence and passion to the issue of the psychological effects of the the juvenile incarceration, leaving us some suggestive texts in which he shows to prefere a management of the juvenile deviance based on small educational facilities, with a familial atmosphere, rather than on the concentration of the boys in greater institutions. The main attention of the Italian psychiatrists moved then, however, in greater measure from the reflexes of the incarceration on the mental health to the psychiatric examination during the judgement and to the search of the physical and psychological stigmates of the criminal. The attention for the consequences of the incarceration on the mental health appears testified by the Italian reflexes of the debate, that  involved in Italy a limited number of experts and was late in comparison to other European countries, as Germany, where the main psychiatrists as Ganser and Kraepelin were authoritatively dealt with the matter on the nosographic autonomy of the psychotic conditions beginning during the incarceration. During this debate, discussing on the nosographic autonomy of the psychoses beginning in the jail, they take in consideration four different possibilities:that the detention represents a possible risk factor for the mental illnesses; that it represents an environmental factor favouring the onset and making worse the course of the illness in subjects already predisposed, or sicks in a subclinical way; that it represents a morphological factor able, only, to give a particular coloring to some clinical pictures developing in prison in the same way in which they would develope elsewhere; or that it represents an irrelevant element so in determining, that in the offer of some environment favouring conditions, that in the morphology of the mental illnesses. The authors believe that the relation between psychiatry and jail among the Nineteenth and the Twentieth century doesn't have now only an interest on an historical ground, but that it is particularly actual today, when some new legislative orientations and an exigence of equity in the access to the health care determine a greater involvement of the Departments of Mental Health in the problemof the health care of the prisoners. L’articolo esamina il rapporto tra la psichiatria e l’istituzione carceraria tra l’inizio dell’Ottocento e i primi anni del Novecento, per cogliere affinità e differenze con i temi all’ordine del giorno del dibattito odierno. Le Riunioni degli Scienziati Italiani ebbero il merito di rappresentare un importante momento di confronto scientifico nazionale prima della realizzazione politica dell’unità d’Italia. All’inizio degli anni quaranta dell’Ottocento esse studiarono, tra molti altri temi, gli effetti delle diverse modalità di detenzione (in particolare i sistemi di Filadelfia e di Auburn) sulla salute, e in particolare sulla salute mentale, del detenuto. Questi argomenti erano appassionatamente dibattuti in quegli anni anche in altri paesi europei, e al dibattito presero parte intellettuali come Alexis de Tocqueville, Gustave de Beaumont, Charles Lucas e Charles Dickens. Durante questo dibattito emerse con chiarezza il rischio, per i medici, di farsi inconsapevolmente carico di istanze punitive di necessità di ordine pubblico; l’orientamento prevalente nelle Riunioni, tuttavia, fu alla fine quello di respingere questa tendenza, e chiedere ai medici di assumere come proprio mandato principale quello di pronunciarsi sulla salubrità o insalubrità dei sistemi carcerari studiati. Successivamente, lo psichiatra lombardo Serafino Biffi si dedicò con competenza e passione al tema degli effetti psicologici della carcerazione minorile, lasciandoci scritti suggestivi nei quali mostra di prediligere una gestione della devianza minorile basata su piccole realtà custodialistico-educative a dimensione familiare, anziché sulla concentrazione dei ragazzi in istituzioni di grandi dimensioni. L’attenzione prioritaria degli psichiatri italiani si sposta, però, in misura sempre maggiore dai riflessi della carcerazione sulla salute mentale alla perizia psichiatrica e alla ricerca intorno alle stigmate fisiche e psicologiche del criminale, mentre l’attenzione  per le conseguenze della carcerazione sulla salute mentale appare testimoniata dai riflessi italiani del dibattito, che coinvolse in Italia un limitato numero di specialisti e fu tardivo rispetto ad altri paesi europei, come la Germania, dove si erano autorevolmente occupati dell’argomento psichiatri come Ganser e Kraepelin, sull’autonomia nosografica delle condizioni psicotiche insorte nel corso della carcerazione. Durante questo dibattito, discutendo dell’autonomia nosografica o meno delle psicosi insorte in carcere, furono prese in considerazione quattro diverse possibilità: che la detenzione rappresenti un fattore eziologico possibile per le malattie mentali; un fattore ambientale favorente l’insorgenza e peggiorante il decorso in soggetti già predisposti o malati in forma subclinica; un fattore morfologico in grado, soltanto, di dare una particolare coloritura a quadri insorti e sviluppandosi con le stesse modalità con cui sarebbero insorti altrove; un elemento pressoché irrilevante tanto nell’eziologia, che nell’offerta di condizioni ambientali favorenti, che nella morfologia delle malattie mentali. Gli autori ritengono che il rapporto tra psichiatria e carcere tra Ottocento e Novecento non rivesta soltanto un interesse di carattere storico, ma sia particolarmente attuale oggi, che nuovi orientamenti legislativi oltre che esigenze di equità nell’accesso alle cure stanno determinando un maggiore coinvolgimento dei Dipartimenti di Salute Mentale nel problema dell’assistenza sanitaria alle persone detenute

Growth Inhibition of Retinoblastoma Cell Line by Exosome-Mediated Transfer of miR-142-3p

Retinoblastoma (Rb) is the most common ocular paediatric malignancy and is caused by a mutation of the two alleles of the tumor suppressor gene, RB1. The tumor microenvironment (TME) represents a complex system whose function is not yet well defined and where microvesicles, such as exosomes, play a key role in intercellular communication. Micro-RNAs (mRNAs) have emerged as important modifiers of biological mechanisms involved in cancer and been able to regulate tumor progression. Methods: Co-culture of monocytes with retinoblastoma cell lines, showed a significant growth decrease. Given the interaction between Rb cells and monocytes, we investigated the role of the supernatant in the cross-talk between cell lines, by taking the product of the co-culture and then using it as a culture medium for Rb cells. Results: miR-142-3p showed to be particularly over-expressed both in the Rb cell line and in the medium used for their culture, comparing to control cell line and the normal supernatant, respectively. Therefore, we provided evidence that miR-142-3p is released by monocytes in the co-culture medium's exosomes and that it is subsequently up-taken by Rb cells, causing the inhibition of proliferation of Rb cell line by affecting cell cycle progression. Conclusion: This study highlights the role of exosomic miR-142-3p in the TME of Rb and identifies new molecular targets, which are able to control tumor growth aiming the development of a forward-looking miR-based strategy

Graphene-Oxide Mediated Chemodivergent Ring-Opening of Cyclobutanols

The chemodivergent ring-opening of cyclobutanols is described under the carbocatalytic assistance of graphene oxide (GO). The protocol enables the synthesis of diversely functionalized dienes or indenes (26 examples) based on the amount of GO employed. Spectroscopic (XPS and ssNMR) as well as experimental investigations revealed a direct involvement of the π-domains of GO in tuning the stability of carbocationic intermediates during the reaction

Single-Cell NGS-Based Analysis of Copy Number Alterations Reveals New Insights in Circulating Tumor Cells Persistence in Early-Stage Breast Cancer

Simple Summary Circulating tumor cells (CTCs) are crucial for the identification of patients with a higher risk of relapse, including those diagnosed with breast cancer (BC). The aim of this study was to explore their molecular aspects in 11 early-stage BC patients during patient management, focusing on copy number alterations (CNAs) and exploiting a single-CTC next-generation sequencing approach. CTCs showed different degrees of aberration based on access time. Moreover, CTCs, in particular those persisting even months after tumor resection, shared CNAs with matched tumor tissue. Enrichment analyses of CNAs on CTCs highlighted peculiar aberrations, especially associated with interferon (IFN)-associated terms. The study of CTCs CNAs can provide information about the molecular mechanisms involving CTC-related processes and their survival ability in occult niches, supporting the goal of exploiting their application in patients' surveillance and follow-up. Circulating tumor cells (CTCs) are a rare population of cells representing a key player in the metastatic cascade. They are recognized as a validated tool for the identification of patients with a higher risk of relapse, including those diagnosed with breast cancer (BC). However, CTCs are characterized by high levels of heterogeneity that also involve copy number alterations (CNAs), structural variations associated with gene dosage changes. In this study, single CTCs were isolated from the peripheral blood of 11 early-stage BC patients at different time points. A label-free enrichment of CTCs was performed using OncoQuick, and single CTCs were isolated using DEPArray. Libraries were prepared from single CTCs and DNA extracted from matched tumor tissues for a whole-genome low-coverage next-generation sequencing (NGS) analysis using the Ion Torrent S5 System. The analysis of the CNA burden highlighted that CTCs had different degrees of aberration based on the time point and subtype. CTCs were found even six months after surgery and shared CNAs with matched tumor tissue. Tumor-associated CNAs that were recurrent in CTCs were patient-specific, and some alterations involved regions associated with BC and survival (i.e., gains at 1q21-23 and 5p15.33). The enrichment analysis emphasized the involvement of aberrations of terms, associated in particular with interferon (IFN) signaling. Collectively, our findings reveal that these aberrations may contribute to understanding the molecular mechanisms involving CTC-related processes and their survival ability in occult niches, supporting the goal of exploiting their application in patients' surveillance and follow-up

Detection and Investigation of Extracellular Vesicles in Serum and Urine Supernatant of Prostate Cancer Patients

none13no: Prostate Cancer (PCa) is one of the most frequently identified urological cancers. PCa patients are often over-diagnosed due to still not highly specific diagnostic methods. The need for more accurate diagnostic tools to prevent overestimated diagnosis and unnecessary treatment of patients with non-malignant conditions is clear, and new markers and methods are strongly desirable. Extracellular vesicles (EVs) hold great promises as liquid biopsy-based markers. Despite the biological and technical issues present in their detection and study, these particles can be found highly abundantly in the biofluid and encompass a wealth of macromolecules that have been reported to be related to many physiological and pathological processes, including cancer onset, metastasis spreading, and treatment resistance. The present study aims to perform a technical feasibility study to develop a new workflow for investigating EVs from several biological sources. Serum and urinary supernatant EVs of PCa, benign prostatic hyperplasia (BPH) patients, and healthy donors were isolated and investigated by a fast, easily performable, and cost-effective cytofluorimetric approach for a multiplex detection of 37 EV-antigens. We also observed significant alterations in serum and urinary supernatant EVs potentially related to BPH and PCa, suggesting a potential clinical application of this workflow.openSalvi, Samanta; Bandini, Erika; Carloni, Silvia; Casadio, Valentina; Battistelli, Michela; Salucci, Sara; Erani, Ilaria; Scarpi, Emanuela; Gunelli, Roberta; Cicchetti, Giacomo; Guescini, Michele; Bonafè, Massimiliano; Fabbri, FrancescoSalvi, Samanta; Bandini, Erika; Carloni, Silvia; Casadio, Valentina; Battistelli, Michela; Salucci, Sara; Erani, Ilaria; Scarpi, Emanuela; Gunelli, Roberta; Cicchetti, Giacomo; Guescini, Michele; Bonafè, Massimiliano; Fabbri, Francesc