Robust estimation of multivariate location and scatter with application to financial portfolio selection.

The thesis studies robust methods for estimating location and scatter of multivariate distributions and contributes to the development of some aspects regarding the detection of multiple outliers. A variety of methods have been designed for detecting single point outliers which, when applied to groups of contaminated data, lead to problems of "masking", that is when an outlier appears as a "good" data. Robust high-breakdown estimators overcome the masking effect, also allowing for a high tolerance of "bad" data. The Minimum Volume Ellipsoid (MVE) and the Minimum Covariance Determinant estimator (MCD) are the most widely used high-breakdown estimators. The central problem when identifying an anomaly is setting a decision rule. The exact distribution of the MCD and MVE is not known, implying that the diagnostics constructed as a function of these robust estimates have also an unknown distribution. Single point oultiers can be recognized using Mahalanobis distances; multivariate outliers are detected by robust (via MCD and MVE) distances of Mahalanobis type. The thesis obtains the small sample distribution of the first ones in an alternative simpler way than the proof existing in the literature. Furthermore, some empirical evidences show the need of a correction factor to improve the approximation to the expected distribution. Some graphical devices are suggested to enhance the results. One of the limiting aspects of the literature on robustness is the lack of real data applications beside the literature examples. The personal interest in financial subjects has driven the thesis to consider applications in this area. Particular attention is paid to methods for optimal selection of financial portfolios. Mean-Variance portfolio theory selects the assets which maximize the return and minimize the risk of the investment using Maximum Likelihood Estimates (MLE). However, MLE are known to be sensitive to relatively small fractions of outliers. Furthermore, a wide financial literature provides evidence of the non-gaussian distribution of the stock returns. All these reasons motivate the construction of a robust portfolio selection model proposed in the thesis

The Forms and Structure of International Voluntary Service

International voluntary service (IVS) has a significant and growing presence worldwide. IVS is a policy and program tool used for international development aid, humanitarian relief, and promotion of international understanding. In the last century, forms of IVS have proliferated, while research on scope, effectiveness, and impacts has lagged behind. We propose a typology that addresses duration, nature of service, and degree of “internationality.” Further, we identify IVS networks and support organizations that bolster the capacity of IVS sending and hosting organizations, and in this process create large and little recognized international institutions of cooperation. Building on the typology, we suggest program, policy, and research implications to advance knowledge of the role of IVS, its role in global civil society, and impacts it may have on human conditions and cross-cultural understanding

The Forms and Structure of International Voluntary Service

International voluntary service (IVS) has a significant and growing presence worldwide. IVS is a policy and program tool used for international development aid, humanitarian relief, and promotion of international understanding. In the last century, forms of IVS have proliferated, while research on scope, effectiveness, and impacts has lagged behind. We propose a typology that addresses duration, nature of service, and degree of “internationality.” Further, we identify IVS networks and support organizations that bolster the capacity of IVS sending and hosting organizations, and in this process create large and little recognized international institutions of cooperation. Building on the typology, we suggest program, policy, and research implications to advance knowledge of the role of IVS, its role in global civil society, and impacts it may have on human conditions and cross-cultural understanding

A Water Soluble 2-Phenyl-5-(pyridin-3-yl)-1,3,4-oxadiazole Based Probe: Antimicrobial Activity and Colorimetric/Fluorescence pH Response

The growing demand of responsive tools for biological and biomedical applications pushestowards new low-cost probes easy to synthesize and versatile. Current optical probes are theranostictools simultaneously responsive to biological parameters/analyte and therapeutically operating.Among the optical methods for pH monitoring, simple small organic molecules including multifunc-tional probes for simultaneous biological activity being highly desired by scientists and technicians.Here, we present a novel pH-responsive probe with a three-ring heteroaromatic pattern and a flexiblecationic chain. The novel molecule shows real-time naked-eye colorimetric and fluorescence responsein the slightly acidic pH range besides its excellent solubility both in the organic phase and in water.In addition, the small probe shows significant antibacterial activity, particularly againstEscherichia coli.Single-crystal X-ray study and density functional theory (DFT) calculations rationalize the moleculespectroscopic response. Finally, molecular dynamics (MD) elucidate the interactions between theprobe and a model cell membrane

Three-Dimensional Cell Cultures: The Bridge between In Vitro and In Vivo Models

Although historically, the traditional bidimensional in vitro cell system has been widely used in research, providing much fundamental information regarding cellular functions and signaling pathways as well as nuclear activities, the simplicity of this system does not fully reflect the heterogeneity and complexity of the in vivo systems. From this arises the need to use animals for experimental research and in vivo testing. Nevertheless, animal use in experimentation presents various aspects of complexity, such as ethical issues, which led Russell and Burch in 1959 to formulate the 3R (Replacement, Reduction, and Refinement) principle, underlying the urgent need to introduce non-animal-based methods in research. Considering this, three-dimensional (3D) models emerged in the scientific community as a bridge between in vitro and in vivo models, allowing for the achievement of cell differentiation and complexity while avoiding the use of animals in experimental research. The purpose of this review is to provide a general overview of the most common methods to establish 3D cell culture and to discuss their promising applications. Three-dimensional cell cultures have been employed as models to study both organ physiology and diseases; moreover, they represent a valuable tool for studying many aspects of cancer. Finally, the possibility of using 3D models for drug screening and regenerative medicine paves the way for the development of new therapeutic opportunities for many diseases

Assessment of seasonal influenza vaccine effectiveness in patients from a central Italy reference hospital: pitfalls and intricacies from a pilot case-control study

Objectives: Influenza vaccination protects high-risk populations from severe outcomes. We assessed the feasibility of testing influenza vaccine effectiveness against hospitalization with laboratory-confirmed influenza. Methods: All hospitalized patients with influenza-like illness within 14 days, were swabbed. Cases were positive at RT-PCR for influenza A/B. Results: AtRome “GemelliHospital” (Season 2011-2012) 104 patients were contacted and 62 recruited. Considering total sample and target group (n= 47, 76%), only 29% and 38% had been vaccinated. Eighteen patients were laboratory-confirmed for influenza. Conclusions: RecruitedILI patients and prevalence of vaccinated subjects were less than expected. Larger numbers are warranted to study vaccine effectiveness against severe influenza outcomes. &nbsp

Synthesis of novel cognition enhancer with pyrazolo[5,1-c][1,2,4]benzotriazine core acting at gamma-aminobutyric acid type A (GABAA) receptor.

Memory dysfunction associated with aging, neurodegenerative and psychiatric disorders represents an increasing medical need. Advances in research exploring the biological mechanisms underlying learning and memory have opened new potential approaches for development of memory-enhancing therapies addressed to selective neuronal targets. In this work, we synthesized some derivatives with a pyrazolo[5,1-c][1,2,4]benzotriazine core to identify ligands on GABA A receptors subtype (benzodiazepine site on GABAA- receptor) endowed with the potential of enhancing cognition activity without the side effects usually associated with non-selective GABAA modulators. In fact, there is much evidence that GABAA-R (γ-aminobutyric acid, type A receptor) subtype ligands have relevance in learning and memory. In vitro and in vivo tests have been performed. Pharmacological data indicate that compounds 7, 13, 14 and 22 act as dual functional modulators of GABA A-Rs (promnemonic and anxiolytic agents) while only compounds 3 and 10 stand out as selectively displaying good antiamnesic and procognitive activity (1 and 3 mg/kg, respectively). © 2013 Elsevier Ltd. All rights reserved

Prevention of postoperative atrial fibrillation in open heart surgery patients by preoperative supplementation of n-3 polyunsaturated fatty acids: An updated meta-analysis

BackgroundSeveral randomized clinical trials evaluated whether preoperative supplementation of omega-3 (n-3) polyunsaturated fatty acids protects against postoperative atrial fibrillation after cardiac surgery, a condition associated with increased cardiac and cerebral mortality. However, their efficacy remains still controversial. An updated meta-analysis was performed to clarify if preoperative n-3 polyunsaturated fatty acid supplementation prevents postoperative atrial fibrillation in patients undergoing cardiac surgery.MethodsArticles were retrieved until November 2012 by screening electronic databases (PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials) and cross references. Two of us independently reviewed articles and agreed to select 8 randomized clinical trials. For each study, the incidence of atrial fibrillation in both the intervention and placebo groups was extracted to calculate odd ratio and 95% confidence intervals (CIs). Weighted study-specific estimates were combined using fixed (Mantel-Haenszel method) and random-effects (DerSimonian-Laird method) models.ResultsThis meta-analysis includes 2687 patients (1337 in the intervention group) who underwent cardiac surgery. Pooled analysis using fixed-effects models showed a significant reduction (average, 16%; 95% CI, 1%-29%) in postoperative atrial fibrillation by preoperative n-3 polyunsaturated fatty acids. There was a low heterogeneity among studies (P = .07 and I2 = 46%). By using a random-effects model, the reduction averaged 25% (odds ratio, 0.75; 95% CI, 0.57-1.00; P = .05). When isolated coronary artery bypass graft surgery was only considered (7 studies), a significant protection averaging 34% was observed in a fixed model (odds ratio, 0.66; 95% CI, 0.50-0.87; P = .003; I2 = 26%, P = .23).ConclusionsA preoperative supplementation of n-3 polyunsaturated fatty acids significantly prevents the occurrence of postoperative atrial fibrillation in patients undergoing cardiac surgery, in particular coronary artery bypass surgery

Citral-Enriched Fraction of Lemon Essential Oil Mitigates LPS-Induced Hepatocyte Injuries

Simple Summary To date, essential oil fractions are emerging as functional compounds of interest for the food and perfume industries. The aim of this study is to evaluate the ability of citral-enriched fractions obtained from lemon essential oil (Cfr-LEO) to counteract, in healthy human hepatocytes, the activity of lipopolysaccharide (LPS), a trigger of inflammation, oxidative stress, and epithelial-mesenchymal transition. In our paper, we report that the pretreatment of hepatocytes with Cfr-LEO counteracts the effects induced by LPS. The data obtained lay the basis for the development of commercial products such as food and drink aimed at preventing or alleviating chronic conditions associated with liver dysfunction.Abstract Lemon essential oil (LEO) is known for its aromatic and healthy properties; however, less consideration is given to the biological properties of the fractions obtained from LEO. This study aims to evaluate the ability of a citral-enriched fraction obtained from LEO (Cfr-LEO) to counteract lipopolysaccharide (LPS)-mediated inflammation, oxidative stress, and epithelial-mesenchymal transition (EMT) in healthy human hepatocytes. Human immortalized hepatocytes (THLE-2 cell line) were pretreated with Cfr-LEO and subsequently exposed to LPS at various time points. We report that the pretreatment with Cfr-LEO counteracts LPS-mediated effects by inhibiting inflammation, oxidative stress, and epithelial-mesenchymal transition in THLE-2. In particular, we found that pretreatment with Cfr-LEO reduced NF-kappa B activation and the subsequent proinflammatory cytokines release, ROS production, and NRF2 and p53 expression. Furthermore, the pretreatment with Cfr-LEO showed its beneficial effect in counteracting LPS-induced EMT. Taken together, these results support Cfr-LEO application in the nutraceutical research field not only for its organoleptic properties, conferred by citral enrichment, but also for its biological activity. Our study could lay the basis for the development of foods/drinks enriched with Cfr-LEO, aimed at preventing or alleviating chronic conditions associated with liver dysfunction