Planning Agreements in the Mezzogiorno: a Principal-Agent Analysis

In this paper we analyse the so-called "planning contracts" which are adopted for the Italian Mezzogiorno from the point of view of the theory of incentives. The Italian Government is the principal who wants to promote economic development in Southern regions of the country. Large firms, both Italian or foreign, are the agents who are keen on locating new plants or restructuring existing ones, provided that expected profits are sufficiently high. Incentives are necessary in order to smooth out any extra-costs encountered when investing and operating in a less favourable environment. We suggest that planning contracts can be interpreted as a case of procurement where Government is the sole buyer of a public good. We refer to a model by Laffont and Tirole (1993) in order to show that under conditions which may be relevant for the Italian experience, firms will enjoy rents that imply allocative inefficiency because of an excess of investment

First body of evidence suggesting a role of a tankyrase-binding motif (TBM) of vinculin (VCL) in epithelial cells

Background: Adherens junctions (AJ) are involved in cancer, infections and neurodegeneration. Still, their composition has not been completely disclosed. Poly(ADP-ribose) polymerases (PARPs) catalyze the synthesis of poly(ADP-ribose) (PAR) as a posttranslational modification. Four PARPs synthesize PAR, namely PARP-1/2 and Tankyrase-1/2 (TNKS). In the epithelial belt, AJ are accompanied by a PAR belt and a subcortical F-actin ring. F-actin depolymerization alters the AJ and PAR belts while PARP inhibitors prevent the assembly of the AJ belt and cortical actin. We wondered which PARP synthesizes the belt and which is the PARylation target protein. Vinculin (VCL) participates in the anchorage of F-actin to the AJ, regulating its functions, and colocalized with the PAR belt. TNKS has been formerly involved in the assembly of epithelial cell junctions. Hypothesis: TNKS poly(ADP-ribosylates) (PARylates) epithelial belt VCL, affecting its functions in AJ, including cell shape maintenance. Materials and Methods: Tankyrase-binding motif (TBM) sequences in hVCL gene were identified and VCL sequences from various vertebrates, Drosophila melanogaster and Caenorhabditis elegans were aligned and compared. Plasma membrane-associated PAR was tested by immunocytofluorescence (ICF) and subcellular fractionation in Vero cells while TNKS role in this structure and cell junction assembly was evaluated using specific inhibitors. The identity of the PARylated proteins was tested by affinity precipitation with PAR-binding reagent followed by western blots. Finally, MCF-7 human breast cancer epithelial cells were subjected to transfection with Tol2-plasmids, carrying a dicistronic expression sequence including Gallus gallus wt VCL (Tol-2-GgVCL), or the same VCL gene with a point mutation in TBM-II (Tol2-GgVCL/*TBM) under the control of a β-actin promoter, plus green fluorescent protein following an internal ribosome entry site (IRES-GFP) to allow the identification of transfected cells without modifying the transfected protein of interest. Results and discussion: In this work, some of the hypothesis predictions have been tested. We have demonstrated that: (1) VCL TBMs were conserved in vertebrate evolution while absent in C. elegans; (2) TNKS inhibitors disrupted the PAR belt synthesis, while PAR and an endogenous TNKS pool were associated to the plasma membrane; (3) a VCL pool was covalently PARylated; (4) transfection of MCF-7 cells leading to overexpression of Gg-VCL/*TBM induced mesenchymal-like cell shape changes. This last point deserves further investigation, bypassing the limits of our transient transfection and overexpression system. In fact, a 5th testable prediction would be that a single point mutation in VCL TBM-II under endogenous expression control would induce an epithelial to mesenchymal transition (EMT). To check this, a CRISPR/Cas9 substitution approach followed by migration, invasion, gene expression and chemo-resistance assays should be performed.Fil: Vilchez Larrea, Salomé Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Valsecchi, Wanda Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Fernandez Villamil, Silvia Hebe. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Lafon Hughes, Laura I.. Universidad de la Republica. Centro Universitario del Litoral Norte.; Urugua

Migration of Jupiter-family comets and resonant asteroids to near-Earth space

We estimated the rate of comet and asteroid collisions with the terrestrial planets by calculating the orbits of 13000 Jupiter-crossing objects (JCOs) and 1300 resonant asteroids and computing the probabilities of collisions based on random-phase approximations and the orbital elements sampled with a 500 yr step. The Bulirsh-Stoer and a symplectic orbit integrator gave similar results for orbital evolution, but sometimes give different collision probabilities with the Sun. A small fraction of former JCOs reached orbits with aphelia inside Jupiter's orbit, and some reached Apollo orbits with semi-major axes less than 2 AU, Aten orbits, and inner-Earth orbits (with aphelia less than 0.983 AU) and remained there for millions of years. Though less than 0.1% of the total, these objects were responsible for most of the collision probability of former JCOs with Earth and Venus. Some Jupiter-family comets can reach inclinations i>90 deg. We conclude that a significant fraction of near-Earth objects could be extinct comets that came from the trans-Neptunian region.Comment: Proc. of the international conference "New trends in astrodynamics and applications" (20-22 January 2003, University of Maryland, College Park

Active TB screening among homeless people attending soup kitchens in Verona (Italy)

BACKGROUND: The hard-to-reach populations, including the homeless, are particularly vulnerable to the development of active tuberculosis. According to the World Health Organization, tuberculosis rates among the homeless in industrialized Countries are up to 20 times higher if compared with the general population, representing a relevant public health problem. The aim of our study was to describe the results of an active tuberculosis screening applied in order to find out suspected active TB cases among the homeless in Verona.METHODS: As part of a partnership between the non-profit association Medici per la Pace and one of the Local Health Units of Veneto Region (ULSS 9 Scaligera) in 2018, a tuberculosis screening, based on thoracic radiographs, was offered to the homeless guests of two Verona's soup kitchens.RESULT: The studied population included 139 people, and three cases of suspected active tuberculosis, all in males, were observed. Among these, two received a diagnostic confirmation of active tuberculosis (a prevalence of 1.44% - CI: 0,17 - 5,1). Moreover, radiographic patterns of tuberculosis aftermaths were found in six additional subjects.CONCLUSION: Interventions specifically dedicated to hard-to-reach populations, can be useful in identifying tuberculosis active cases and controlling the disease in low tuberculosis burden countries. In particular, the active research of subjects, the screening carried out with mobile X-ray, and also the constant caring of the patients with active disease, could be the right method to keep under control this relevant public health problem

The evolution of the orbit distance in the double averaged restricted 3-body problem with crossing singularities

We study the long term evolution of the distance between two Keplerian confocal trajectories in the framework of the averaged restricted 3-body problem. The bodies may represent the Sun, a solar system planet and an asteroid. The secular evolution of the orbital elements of the asteroid is computed by averaging the equations of motion over the mean anomalies of the asteroid and the planet. When an orbit crossing with the planet occurs the averaged equations become singular. However, it is possible to define piecewise differentiable solutions by extending the averaged vector field beyond the singularity from both sides of the orbit crossing set. In this paper we improve the previous results, concerning in particular the singularity extraction technique, and show that the extended vector fields are Lipschitz-continuous. Moreover, we consider the distance between the Keplerian trajectories of the small body and of the planet. Apart from exceptional cases, we can select a sign for this distance so that it becomes an analytic map of the orbital elements near to crossing configurations. We prove that the evolution of the 'signed' distance along the averaged vector field is more regular than that of the elements in a neighborhood of crossing times. A comparison between averaged and non-averaged evolutions and an application of these results are shown using orbits of near-Earth asteroids.Comment: 29 pages, 8 figure

Acute kidney injury and acute kidney disease in high-dose cisplatin-treated head and neck cancer

Background: In locally advanced head and neck squamous cell carcinoma (LA-SCCHN) at least 200mg/m2 (standard dose 300 mg/m2) of cisplatin concomitant with radiotherapy represents the standard of care, both in postoperative and conservative settings. Nevertheless, high dose administration every 3 weeks is often replaced with low dose weekly cisplatin to avoid toxicities like kidney injury, though often failing to reach the therapeutic dose. Our aim was to investigate the incidence of renal impairment in the real-life setting, integrating high dose cisplatin with adequate supportive therapy, and to explore both Acute Kidney Injury (AKI) and Acute Kidney Disease (AKD), a recently described clinical renal syndrome that encompasses functional alterations of the kidney lasting fewer than 3 months. Methods: One hundred and nine consecutive patients affected by LA-SCCHN and treated with at least a cumulative dosage of 200 mg/m2 of cisplatin concomitant with radiotherapy were enrolled in this prospective observational study. Results: AKI was reported in 12.8% of patients, 50% of whom were stage 1 (KDIGO criteria), while 25.7% of the cohort developed AKD. Patients with baseline estimated Glomerular Filtration Rate (eGFR) < 90 ml/min showed a higher incidence of AKD (36.2% vs 17.7%). Hypertension, baseline eGFR, and therapy with Renin-angiotensin-aldosterone system inhibitors proved to be significant factors associated with both AKI and AKD. Conclusion: AKI and AKD are not rare complications of high-dose cisplatin, but an appropriate prevention strategy and accurate monitoring of patients during treatment could lead to a reduction of the burden of these conditions

In-stent restenosis in the drug eluting stent assayed by optical coherence tomography

Hospital of Holy Pope Giovanni XXIII, Bergamo, Italy, Department of Interventional Cardiology, Institute of Cardiology, Chisinau, the Republic of MoldovaBackground: In order to study the mechanisms and morphological aspects of the in-stent restenosis (ISR) have been evaluated restenosis lesions referred to drug eluting stent (DES) of the first generation using optical coherence tomography technique (OCT). Material and methods: The study underwent 39 patients with ISR induced recurrent angina or acute coronary syndrome including 66 stents from which were: 44 stents (28 patients) of the first generation of DES (19 – Cypher TM and 23 – Taxus®), and 22 stents (11 patients) of the second DES generation (9 Xience TM 2 Promus TM), 10 ZES (Resolute TM), and one stent Nobori TM. Has been made quantitative and morphological analysis of tissue pattern of ISR using the following OCT criteria: 1) morphologically homogenous neointima; 2)morphologically heterogeneous neointima; and 3) neoatherosclerosis. Results: It has been established that in the first generation of DES morphological homogenous pattern was present in both ISR developed after 1 year and later. However, the optical aspect with heterogeneous presentation had a prevalence decline in dynamics. The heterogeneous model had a higher prevalence in actual generation of DES in both incipient (< 1 year) and late presentation. Conclusions: The phenomenon of neoatherosclerosis has presented a significantly less frequency in the late restenosis of actual generation of DES. Our results suggest that restenosis phenomenon in actual generation of DES has a different morphological and evolution pattern in time in comparison with ISR of the first generation of DES

Intracoronary optical coherence tomography

The cardiovascular departments of the hospital of Holy Pope Giovanni XXIII in Bergamo, Italy and of the Institute of Cardiology in Chisinau, the Republic of Moldova have a fruitful history of collaboration in the field of interventional cardiology and intracoronary imaging in particular. We have recently expanded our collaboration by adding the method of Optical Coherence Tomography (OCT) into the armamentarium of imaging in the catheterization laboratory. OCT is an innovative, real time, tomographic imaging modality able to visualize tissues at microstructure level. It delivers the rays of near-infrared light through the wall of the coronary artery using small diameter optical fibres. The light that illuminates the vessel is absorbed and backscattered or reflected by the structures of the tissues with different degrees of density, thus creating an image with an axial resolution of 10-20 µm. This technology allows acquiring high definition images of long segments of coronaries for a few seconds. For the time being, OCT is mainly used in the researches, providing insights into the pathophysiology of the atherosclerotic plaque and the vascular response to stenting. It also has a potential for clinical application, such as pre-interventional evaluation of coronary arteries, procedures guidance and follow-up assessment of vascular healing after the stent implantation. A joined database has been created by the two institutions in an effort to study in vivo the morphology of the coronary arteries in different pathologies. This review is focused on the potential fields of application of OCT in different clinical and scientific institutions

Evaluation of a New, Rapid, Fully Automated Assay for the Measurement of ADAMTS13 Activity

Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy (TMA) characterized by the severe deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity (&lt; 10%). Rapid ADAMTS13 testing is crucial for an early diagnosis and optimal management of acute TTP. We evaluated the performance of the HemosIL AcuStar ADAMTS13 activity assay (Instrumentation Laboratory, Bedford, Massachusetts, United States), a fully automated chemiluminescent immunoassay with an analytical time of 33 minutes. A method comparison study was performed on 176 samples from 49 healthy donors and 127 TMA patients (109 TTP, 7 atypical hemolytic uremic syndrome, 11 other TMAs), comparing this new assay with an in-house FRETS-VWF73 assay and a commercial enzyme-linked immunosorbent assay (ELISA) (TECHNOZYM ADAMTS-13 Activity, Technoclone GmbH, Vienna, Austria). Agreement between methods was assessed with focus on ADAMTS13 activity less than 10%, the medical decision level relevant for TTP diagnosis. The HemosIL AcuStar ADAMTS13 Activity showed good correlation with both the FRETS-VWF73 (r = 0.96) and ELISA (r = 0.96) methods. Slope of the Passing-Bablok regression was 1.05 for FRETS-VWF73 and 1.02 for ELISA, and absolute bias at the medical decision level was +0.1 and +0.3%, respectively. The study also revealed high agreement with FRETS-VWF73 (kappa 0.97) and ELISA (kappa 0.98) methods in classifying TTP patients with a severe deficiency of ADAMTS13 activity. Because of its short turnaround time and full automation, the HemosIL AcuStar ADAMTS13 activity assay might become the assay of choice to rapidly test ADAMTS13 activity in plasma and thus establish the diagnosis of acute TTP in emergency settings