A Penalty Method for the Numerical Solution of Hamilton-Jacobi-Bellman (HJB) Equations in Finance

We present a simple and easy to implement method for the numerical solution of a rather general class of Hamilton-Jacobi-Bellman (HJB) equations. In many cases, the considered problems have only a viscosity solution, to which, fortunately, many intuitive (e.g. finite difference based) discretisations can be shown to converge. However, especially when using fully implicit time stepping schemes with their desirable stability properties, one is still faced with the considerable task of solving the resulting nonlinear discrete system. In this paper, we introduce a penalty method which approximates the nonlinear discrete system to first order in the penalty parameter, and we show that an iterative scheme can be used to solve the penalised discrete problem in finitely many steps. We include a number of examples from mathematical finance for which the described approach yields a rigorous numerical scheme and present numerical results.Comment: 18 Pages, 4 Figures. This updated version has a slightly more detailed introduction. In the current form, the paper will appear in SIAM Journal on Numerical Analysi

An Integro-Differential Conservation Law arising in a Model of Granular Flow

We study a scalar integro-differential conservation law. The equation was first derived in [2] as the slow erosion limit of granular flow. Considering a set of more general erosion functions, we study the initial boundary value problem for which one can not adapt the standard theory of conservation laws. We construct approximate solutions with a fractional step method, by recomputing the integral term at each time step. A-priori L^\infty bounds and BV estimates yield convergence and global existence of BV solutions. Furthermore, we present a well-posedness analysis, showing that the solutions are stable in L^1 with respect to the initial data

Technical peculiarities in Giovanni Santi’s paintings on canvas

Giovanni Santi (Colbordolo ca. 1439–Urbino 1494) was one of the most important painters active in Urbino (Marche region, Italy) during the last decades of the fifteenth century, where he was employed at the court of the celebrated Federico da Montefeltro. He is known mainly as the father of Raphael, but he had a remarkable production of paintings, especially on wood but also on canvas and on wall. This paper focuses on technical peculiarities related to Santi’s paintings on canvas, including some practices that have not yet been noted in relation to his panel paintings. In particular, two works painted on herringbone-weave linen canvases were investigated: Tobias and the Archangel Raphael and Saint Roch (both dated ca. 1490–94), in the collection of the Galleria Nazionale delle Marche. The results presented are a part of a large research project based on noninvasive and micro-invasive investigations carried out on twenty-eight works attributed to Giovanni Santi, only partially published in a recent exhibition catalog dedicated to the artist (Palazzo Ducale, Urbino, 2018). Black underdrawing, characterized by a thinly applied network of close hatching for some of the shadows, was observed and, regarding the different hues, a complex use of pigments. The binder detected is siccative oil, with the addition of a large amount of transparent glass particles, which would have been added both to give body to the pigment without using white fillers and to improve drying, a technique that Santi presumably learned from the Flemish painter Justus van Ghent (act. Urbino ca. 1473–1475) and something that he possibly transmitted to his son Raphael as a workshop practice. In fact, Giovanni Santi’s workshop survived his death

IDENTIFICATION OF MOLECULAR MECHANISMS RESPONSIBLE FOR DEGRADATION OF THE TUMOR SUPPRESSOR PROTEIN NUMB IN CANCER.

ABSTRACT NUMB was initially described as a cell fate determinant involved in neurogenesis. More recently, NUMB has been implicated in different types of human cancers, in which it has a tumor suppressor role. In particular, data from our laboratory revealed that loss of NUMB protein occurred in approximately 50% of breast cancers and 30% of non-small cell lung cancers, and leads to increased oncogenic NOTCH activity and decreased p53 tumor suppressor function. Mechanistically, loss of NUMB in human breast cancers is due to its deregulated ubiquitination and ensuing proteasomal degradation, as witnessed by the restoration of physiological NUMB levels in NUMB-deficient primary breast tumor cells upon proteasome inhibition with MG-132. Therefore, the molecular mechanism underlying NUMB degradation in cancer most likely involves deregulation of components of the cellular machinery normally regulating the ubiquitination/phosphorylation status of the NUMB protein, such as E3-ubiquitin ligases/kinases. In this thesis, we devised a high-throughput phenotypic screening to identify the molecular determinants responsible for NUMB loss among E3 ligase family. The screening assay measures restoration of NUMB expression upon siRNA-mediated silencing of candidate enzymes, in a NUMB-deficient model-system. We identified the breast cancer epithelial cell line MDA-MB-361, as a suitable cell model system for the screening assay as it recapitulates the phenotype of NUMB-deficient primary tumor cells. Indeed, NUMB protein levels in these cells are restored to physiological levels by MG-132 treatment. For the high-throughput phenotypic assay, we developed and optimized for a miniaturized format, a NUMB capture ELISA assay. Using the high-throughput screening platform, we assessed the involvement of over 600 E3 ligases in NUMB downregulation, and identified 21 candidate E3 ligases. We then went through the validation of these 21 candidate hits, which is the topic of this thesis. Upon validation of the top six candidates of E3 ligases list, we confirmed that the E3 ligase, RBX1 (RING-Box 1), mediates the downregulation of NUMB in both MDA-MB-361 cells and human primary NUMB-deficient breast and lung tumor cells. Indeed, we demonstrated that silencing RBX1 in these cells restores NUMB protein levels, while no effect was observed in NUMB-proficient cell lines or primary tumor cells. Moreover, we also established a physical interaction between NUMB and RBX1 in MDA-MB-361 cells indicating that RBX1 directly mediates NUMB degradation. RBX1 belongs to the tetrameric E3 ligase complex, Skp1/Cullin1/F-box (SCF), in which the specificity for substrates is mediated by the F-box protein. Intriguingly, among the 21 candidates from the high-throughput screening, we identified the F-box protein, FBXW8 (F-box and WD repeat domain containing 8), which has been described to form a complex with RBX1. We, therefore, assessed the role of FBXW8 in NUMB donwregulation in high-resolution studies in MDA-MB-361 cells and confirmed its involvement. We are currently validating FBXW8 also in primary tumors cells from human breast and lung cancers. In conclusion, our data indicate that an SCF E3 ligase complex involving RBX1 and FBXW8, likely mediates NUMB hyperdegradation in human cancers. This result has potential translational ramifications as RBX1 and FBXW8 could represent novel molecular targets for therapeutic intervention in NUMB-deficient cancers

Increase of reports of suspected adverse drug reactions in oncology

Methods: An observational study was conducted in 7 cancer centersin the Emilia Romagna region over a period of 2 years, from January 2012 to January 2014. This study was based on an analysis of ADRs reported. Several parameters were utilised in the data evaluation, including drug and reaction characteristics.Results: From January 2012 to January 2014 No. 884 ADRs were included in National Network of pharmacovigilance. The highest ADR rate (57.4%) was found in the adult femaleswith a mean age of 62. The oncology drug most frequently reported were taxanes and platinum derivates.Conclusion: The results obtained will contribute to the development of strategies for the pharmacovigilance service in 7 cancer centers, which will improve the quality of ADR reporting and ensure safer oncology drug use.Objective: The information of safety of antineoplastic agents derives solely from clinical studies that have a number of limitations, such as the number of patients enrolled, selected case studies, follow-up of short duration; therefore, it is not possible to identify the complete profile of safety and possible side effects of the drugs under study. ADRs monitoring and reporting programmes aim to identifying and quantifying the risks associated with the use of drugs provided in a hospital setting. The main objectives of this study were to evaluate the ADRs that occurred during hospitalization for chemotherapy in 7 cancer centers, and to facilitate the development of a monitoring system of pharmacovigilance

Is there any correlation between otitis media and dental malocclusion in children? A systematic review

PurposeThis study aims to evaluate whether there is a correlation between otitis and dental malocclusions.MethodsElectronic databases were searched for observational studies published until July 2021 without language or time restrictions. PROSPERO: CRD42021270760. Observational studies on children with and without OM and/or malocclusion were included. After removing duplicates and excluding not-eligible articles, two reviewers screened relevant articles independently. Two reviewers independently extracted data and assessed data quality and validity through the Newcastle-Ottawa Scale (NOS) quality assessment tool for non-randomized studies.ResultsFive studies met the selection inclusion criteria and were included in the studies for a total of 499 patients. Three studies investigated the relationship between malocclusion and otitis media, while the remaining two studies analyzed the inverse relationship and one of them considered eustachian tube dysfunction as a proxy of OM. An association between malocclusion and otitis media and vice versa emerged, although with relevant limitations.ConclusionThere is some evidence that there is an association between otitis and malocclusion; however, it is not yet possible to establish a definitive correlation

INCREASE OF REPORTS OF SUSPECTED ADVERSE DRUG REACTIONS IN ONCOLOGY

Objective: The information of safety of antineoplastic agents derives solely from clinical studies that have a number of limitations, such as the number of patients enrolled, selected case studies, follow-up of short duration; therefore, it is not possible to identify the complete profile of safety and possible side effects of the drugs under study. ADRs monitoring and reporting programmes aim to identifying and quantifying the risks associated with the use of drugs provided in a hospital setting. The main objectives of this study were to evaluate the ADRs that occurred during hospitalization for chemotherapy in 7 cancer centers, and to facilitate the development of a monitoring system of pharmacovigilance. Methods: An observational study was conducted in 7 cancer centers in the Emilia Romagna region over a period of 2 years, from January 2012 to January 2014. This study was based on an analysis of ADRs reported. Several parameters were utilised in the data evaluation, including drug and reaction characteristics. Results: From January 2012 to January 2014 No. 884 ADRs were included in National Network of pharmacovigilance. The highest ADR rate (57.4%) was found in the adult females with a mean age of 62. The oncology drug most frequently reported were taxanes and platinum derivates. Conclusion: The results obtained will contribute to the development of strategies for the pharmacovigilance service in 7 cancer centers, which will improve the quality of ADR reporting and ensure safer oncology drug use

Healthcare workers training courses on vaccinations: A flexible format easily adaptable to different healthcare settings.

Since 2017, Italy has expanded the compulsory vaccination from 4 to 10 for those aged 0 to 16 years. Because of the great organizational effort required for the immunization services, minor attention was given to the vaccinations not included among the mandatory ones. This situation led to a real difficulty in harmonizing the vaccination procedures even inside a single region. In the Lazio region, the Laboratory of Vaccinology of the University of Rome Tor Vergata established a working group to create a new training model for healthcare professionals. The course program proposed an update of three vaccinations which are not mandatory but actively offered. It included the same part of scientific updating and a variable part based on local experiences. A specific anonymous questionnaire on knowledge and attitude was administered. The study aimed to propose a general format of training courses for vaccination centers adaptable to the individual local health units (ASLs) and to evaluate through questionnaires. The results show differences in knowledge and attitudes toward non‐mandatory vaccinations among the ASLs of Lazio, confirming the usefulness of a support to make knowledge and procedures homogeneous. This model could be adapted to any healthcare setting and exported to other services

New Insight on Medieval Painting in Sicily: The Virgin Hodegetria Panel in Monreale Cathedral (Palermo, Italy)

: The Virgin Hodegetria, located in the Cathedral of Santa Maria Nuova in Monreale, near Palermo (Italy), probably dating the first half of the 13th century, is one of the earliest examples of medieval panel painting in Sicily. A diagnostic campaign was carried out on the panel aiming to identify the constituting materials and the executive technique, as well as to assess the state of conservation for supporting the methodological choice of the restoration intervention. Both non invasive (X-ray radiography, digital microscope, multispectral imaging, ED-X-ray fluorescence) and micro-invasive (polarised light microscopy, ESEM-EDX, ATR-FTIR spectroscopy and micro-Raman spectroscopy) analyses were performed. According to the results, the executive technique followed the 13th–14th-century Italian painting tradition. A complex structure was applied on the wooden support, consisting of a double layer of canvas and several ground layers of gypsum and glue based binder. The underdrawing was made by a brush using carbonaceous black pigment. The original palette includes red ochre, red lead, azurite, carbon black and bone black. During the several restorations, mercury-based red, indigo, smalt blue, orpiment and synthetic mars were used. The original silver leaf of the frame was covered with red tin-based lake and subsequently regilded with gold leaf. Proteinaceous and oil binders were also detecte