Commissioning and Field Tests of a Van-Mounted System for the Detection of Radioactive Sources and Special Nuclear Material

MODES-SNM project aimed at developing a mobile/portable modular detection system for radioactive sources and Special Nuclear Material (SNM). Its main goal was to deliver a tested prototype capable of passively detecting weak or shielded radioactive sources with accuracy higher than that of currently available systems. By the end of the project all the objectives have been successfully achieved. Results from the laboratory commissioning and the field tests are presented in this publication

Computational studies of the interaction between the HIV-1 integrase tetramer and the cofactor LEDGF/p75: Insights from molecular dynamics simulations and the informational spectrum method

A crystal structure of the integrase binding domain (IBD) of the lens epithelium-derived growth factor (LEDGF/p75) in complex with the dimer of the HIV-1 integrase (IN) catalytic core domain (CCD) provides useful information that might help in the understanding of essential protein-protein contacts in HIV-1. However, mutagenic studies indicated that interactions between the full-length proteins were more extensive than the contacts observed in the co-crystal structure of the isolated domains. On the other hand, the biochemical characterization of the interaction between full-length IN and LEDGF/p75 has recently proved that LEDGF/p75 promotes IN tetramerization with two LEDGF/p75 IBD molecules bound to the IN tetramer. This experimental evidence suggests that to obtain a complete structural description of the interactions between the two proteins, the full-length tetrameric structure of IN should be considered. Our aim was to obtain a detailed picture of HIV-1 IN interactions with cellular co-factors that was of general interest, particularly for the development of small molecule IN inhibitors, which mimic the IBD of LEDGF/p75. To this end, we performed bioinformatics analyses to identify protein sequence domains involved in long-range recognition. Subsequently, we applied molecular dynamics techniques to investigate the detailed interactions between the complete tetrameric form of IN and two molecules of the IBD of LEDGF/p75. Our dynamic picture is in agreement with experimental data and, thereby, provides new details of the IN-LEDGF/p75 interaction

Percutaneous Application of High Power Microwave Ablation With 150 W for the Treatment of Tumors in Lung, Liver, and Kidney: A Preliminary Experience

Objective: The aim of this study is to evaluate the feasibility, safety, and short-term effectiveness of a high-power (150 W) microwave ablation (MWA) device for tumor ablation in the lung, liver, and kidney. Methods: Between December 2021 and June 2022, patients underwent high-power MWA for liver, lung, and kidney tumors. A retrospective observational study was conducted in accordance with the Declaration of Helsinki. The MWA system utilized a 150-W, 2.45-GHz microwave generator (Emprint™ HP Ablation System, Medtronic). The study assessed technical success, safety, and effectiveness, considering pre- and post-treatment diameter and volume, lesion location, biopsy and/or cone beam computed tomography (CBCT) usage, MWA ablation time, MWA power, and dose-area product (DAP). Results: From December 2021 to June 2022, 16 patients were enrolled for high-power MWA. Treated lesions included hepatocellular carcinoma (10), liver metastasis from colon cancer (1), liver metastasis from pancreatic cancer (1), squamous cell lung carcinoma (2), renal cell carcinoma (1), and renal oncocytoma (1). Technical success rate was 100%. One grade 1 complication (6.25%) was reported according to CIRSE classification. Overall effectiveness was 92.8%. Pre- and post-treatment mean diameters for liver lesions were 19.9 mm and 37.5 mm, respectively; for kidney lesions, 34 mm and 35 mm; for lung lesions, 29.5 mm and 31.5 mm. Pre- and post-treatment mean volumes for liver lesions were 3.4 ml and 24 ml, respectively; for kidney lesions, 8.2 ml and 20.5 ml; for lung lesions, 10.2 ml and 32.7 ml. The mean ablation time was 48 minutes for liver, 42.5 minutes for lung, and 42.5 minutes for renal ablation. The mean DAP for all procedures was 40.83 Gcm2. Conclusion: This preliminary study demonstrates the feasibility, safety, and effectiveness of the new 150 W MWA device. Additionally, it shows reduced ablation times for large lesions

The Challenges of the External Vote

UID/CPO/04627/2019Over the last few decades, emigrants all over the world have gained expanded voting rights. Despite the normative debates about this issue, there are few empirical studies on why states decide to implement external voting and how electoral systems perform. This chapter seeks to fill this gap by looking at the Portuguese case. Our study suggests that a combination of political and socio-economic factors explains the implementa tion of external voting. On the other hand, the interests of political parties and the low level of civil society engagement are key factors in the failure of both electoral reforms and attempts to overcome the shortcomings of external voting.publishersversionpublishe

Effectiveness of cardiac resynchronization therapy in heart failure patients with valvular heart disease: comparison with patients affected by ischaemic heart disease or dilated cardiomyopathy. The InSync/InSync ICD Italian Registry

AimsTo analyse the effectiveness of cardiac resynchronization therapy (CRT) in patients with valvular heart disease (a subset not specifically investigated in randomized controlled trials) in comparison with ischaemic heart disease or dilated cardiomyopathy patients.Methods and resultsPatients enrolled in a national registry were evaluated during a median follow-up of 16 months after CRT implant. Patients with valvular heart disease treated with CRT (n = 108) in comparison with ischaemic heart disease (n = 737) and dilated cardiomyopathy (n = 635) patients presented: (i) a higher prevalence of chronic atrial fibrillation, with atrioventricular node ablation performed in around half of the cases; (ii) a similar clinical and echocardiographic profile at baseline; (iii) a similar improvement of LVEF and a similar reduction in ventricular volumes at 6-12 months; (iv) a favourable clinical response at 12 months with an improvement of the clinical composite score similar to that occurring in patients with dilated cardiomyopathy and more pronounced than that observed in patients with ischaemic heart disease; (v) a long-term outcome, in term of freedom from death or heart transplantation, similar to patients affected by ischaemic heart disease and basically more severe than that of patients affected by dilated cardiomyopathy.ConclusionIn 'real world' clinical practice, CRT appears to be effective also in patients with valvular heart disease. However, in this group of patients the outcome after CRT does not precisely overlap any of the two other groups of patients, for which much more data are currently available

Targets Looking for Drugs: A Multistep Computational Protocol for the Development of Structure-Based Pharmacophores and Their Applications for Hit Discovery.

Pharmacophoresthree-dimensional (3D) arrangements of essential features enabling a molecule to exert a particular biological effectconstitute a very useful tool in drug design both in hit discovery and hit-to-lead optimization process. Two basic approaches for pharmacophoric model generation can be used by chemists, depending on the availability or not of the target 3D structure. In view of the rapidly growing number of protein structures that are now available, receptor-based pharmacophore generation methods are becoming more and more used. Since most of them require the knowledge of the 3D structure of the ligand-target complex, they cannot be applied when no compounds targeting the binding site of interest are known. Here, a GRID-based procedure for the generation of receptor-based pharmacophores starting from the knowledge of the sole protein structure is described and successfully applied to address three different tasks in the field of medicinal chemistry