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

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

vandetanib improves anti tumor effects of l19mtnfα in xenograft models of esophageal cancer

Purpose: Targeting the tumor vasculature by vascular disrupting agents (VDAs) has shown therapeutic activity in mouse models. In most cases, however, VDA efficacy is substantially compromised by the inability of these drugs to completely kill tumor cells located at the periphery of the tumor mass. In this study, we investigated anti-tumor effects of L19mTNFα, a fusion protein composed of L19 (scFv), specific for the angiogenesis-associated ED-B containing fibronectin isoform, and murine TNFα, in xenograft models of esophageal cancer. Experimental design: We evaluated ED-B expression in esophageal cancer samples. Subsequently, we generated subcutaneous xenografts from primary tumors, treated them with the L19mTNFα scFv, and determined effects on tumor vasculature, viability and proliferation, and VEGF expression and infiltration by hematopoietic cells. To overcome tumor resistance, L19mTNFα scFv was combined with vandetanib, a tyrosine kinase inhibitor of VEGF receptor, epidermal growth factor receptor, and RET signaling. Results: ED-B was broadly expressed by esophageal cancer cell lines, as well as xenografts and primary surgical samples of esophageal cancer. Administration of L19mTNFα acutely damaged tumor vasculature and increased necrosis, indicating a VDA-like activity of this immunoconjugate. This event was followed, however, by rapid tumor growth recovery associated with increased expression of VEGF and recruitment of CD11b+Gr1+ myeloid cells into tumors. Combination of L19mTNFα with vandetanib severely impaired vascular functions in tumors, leading to a reduction of cell proliferation and increased necrosis, without apparent signs of toxicity. Conclusion: These findings indicate that a combination of vascular damaging agents with anti-angiogenic drugs could represent a promising therapeutic strategy for esophageal cancer. Clin Cancer Res; 17(3); 447–58. ©2010 AACR

Response to oxidative stress as a welfare parameter in swine

In pigs, the genetic selection for lean, large muscle blocks and fast growth has been linked to an increased prevalence of metabolic diseases such as porcine stress syndrome and mulberry heart disease. These diseases are associated with cardiovascular inadequacy, which may lead to oxidative stress. In the present study, reactive oxygen metabolites (ROMs) and the anti-oxidant power (OXY) in sera of different swine groups were investigated. The following groups were selected (each around 80 kg body weight): wild boars (WB), Cinta Senese (CS), and Landrace x Large White (LxLW), the latter as both specific pathogen-free (SPF) and intensively farmed animals. In addition, a group of LxLW agonic sows (AS) was also investigated; this group is known to be under oxidative stress. Two colorimetric micro-methods were used to measure ROMs and OXY; ROMs were expressed as mM H(2)O(2) and OXY as microM HOCl neutralised. Between groups, average ROM and OXY values were found to be significantly different by one-way ANOVA (P0.001). ROM levels were lower in WB (13.41 +/- 1.85) and CS (19.27 +/- 1.68), and highest in LxLW (42.00 +/- 1.36). OXY values ranged from 260.10 +/- 22.13 (WB) to 396.90 +/- 9.83 (LxLW). Only one swine group (the CS group) showed a significant, positive correlation between ROM and OXY values. The AS group even showed a negative correlation between ROM and OXY values. These results imply satisfactory environmental coping occurred only within the CS group. Results are discussed in the light of animal welfare legislation, food safety and consumers' protection

Holomorphic transforms with application to affine processes

In a rather general setting of It\^o-L\'evy processes we study a class of transforms (Fourier for example) of the state variable of a process which are holomorphic in some disc around time zero in the complex plane. We show that such transforms are related to a system of analytic vectors for the generator of the process, and we state conditions which allow for holomorphic extension of these transforms into a strip which contains the positive real axis. Based on these extensions we develop a functional series expansion of these transforms in terms of the constituents of the generator. As application, we show that for multidimensional affine It\^o-L\'evy processes with state dependent jump part the Fourier transform is holomorphic in a time strip under some stationarity conditions, and give log-affine series representations for the transform.Comment: 30 page

Metformin plus chemotherapy versus chemotherapy alone in the first-line treatment of HER2-negative metastatic breast cancer. The MYME randomized, phase 2 clinical trial

Purpose: To investigate the efficacy of metformin (M) plus chemotherapy versus chemotherapy alone in metastatic breast cancer (MBC). Methods: Non-diabetic women with HER2-negative MBC were randomized to receive non-pegylated liposomal doxorubicin (NPLD) 60 mg/m2 + cyclophosphamide (C) 600 mg/m2 × 8 cycles Q21 days plus M 2000 mg/day (arm A) versus NPLD/C (arm B). The primary endpoint was progression-free survival (PFS). Results: One-hundred-twenty-two patients were evaluable for PFS. At a median follow-up of 39.6 months (interquartile range [IQR] 24.6-50.7 months), 112 PFS events and 71 deaths have been registered. Median PFS was 9.4 months (95% CI 7.8-10.4) in arm A and 9.9 (95% CI 7.4-11.5) in arm B (P = 0.651). In patients with HOMA index < 2.5, median PFS was 10.4 months (95% CI 9.6-11.7) versus 8.5 (95% CI 5.8-9.7) in those with HOMA index ≥ 2.5 (P = 0.034). Grade 3/4 neutropenia was the most common toxicity, occurring in 54.4% of arm A patients and 72.3% of the arm B group (P = 0.019). M induced diarrhea (G2) was observed in 8.8% of patients in Arm A. The effect of M was similar in patients with HOMA index < 2.5 and ≥ 2.5, for PFS and OS. Conclusions: The MYME trial failed to provide evidence in support of an anticancer activity of M in combination with first line CT in MBC. A significantly shorter PFS was observed in insulin-resistant patients (HOMA ≥ 2.5). Noteworthy, M had a significant effect on CT induced severe neutropenia. Further development of M in combination with CT in the setting of MBC is not warranted

Use of Diltiazem in Chronic Rate Control for Atrial Fibrillation: A Prospective Case-Control Study

Atrial fibrillation (AF) is a multifaceted disease requiring personalised treatment. The aim of our study was to explore the prognostic impact of a patient-specific therapy (PT) for rate control, including the use of non-dihydropyridine calcium channel blockers (NDDC) in patients with heart failure (HF) or in combination with beta-blockers (BB), compared to standard rate control therapy (ST), as defined by previous ESC guidelines. This is a single-centre prospective observational registry on AF patients who were followed by our University Hospital. We included 1112 patients on an exclusive rate control treatment. The PT group consisted of 125 (11.2%) patients, 93/125 (74.4%) of whom were prescribed BB + NDCC (±digoxin), while 85/125 (68.0%) were HF patients who were prescribed NDCC, which was diltiazem in all cases. The patients treated with a PT showed no difference in one-year overall survival compared to those with an ST. Notably, the patients with HF in ST had a worse prognosis (p &lt; 0.001). To better define this finding, we performed three sensitivity analyses by matching each patient in the PT subgroups with three subjects from the ST cohort, showing an improved one-year survival of the HF patients treated with PT (p = 0.039). Our results suggest a potential outcome benefit of NDCC for rate control in AF patients, either alone or in combination with BB and in selected patients with HF