Il confronto della tutela della persona disabile e a mobilità ridotta nel trasporto aereo, marittimo e terrestre

COMPARISON OF THE PROTECTION PROVIDED FOR THE DISABLED AND PERSONS WITH REDUCED MOBILITY IN AIR, MARITIME AND LAND TRANSPORT The research on real means of protection for the disabled in order to guarantee their right to mobility and access to means of transport has received growing attention of the international and national regulations in the last 20 years. The measures that have derived, both in the EU legal system and in the national legislation, aim at guaranteeing not only to the disabled but also to the "persons with reduced mobility" (p.r.m.) a full exercise of their right to mobility and free movement on conditions comparable to those granted to the other users. The object of the present dissertation is, therefore, the comparison of the different sector-specific regulations that regulate the transport of all the persons that can be counted within the vast "p.r.m." category. Upon careful evaluation of the points of contact as well as of the ongoing differences among the applicable regulations, we shall try to identify proposals, modifications and solutions (also of a practical nature) that are appropriate, at least, to foster (if not to attain yet) the level of uniformity desired by the EU institutions with the aim of achieving greater protection for the p.r.m

pH dependence of bovine mast cell tryptase catalytic activity and of its inhibition by 4′,6-diamidino-2-phenylindole

AbstractTryptases are oligomeric enzymes localized in the secretory granules of mast cells. Their role(s) in vivo has yet to be clarified and the lack of powerful and specific inhibitors has hampered the comprehension of the biological functions of these enzymes. In this paper, we identify 4′,6-diamidino-2-phenylindole as a potent inhibitor for bovine tryptase. This inhibitory effect and the enzyme catalyzed hydrolysis of the synthetic substrate Boc-Phe-Ser-Arg-methyl-coumarin were investigated in the pH range of 6.0–9.0. On the basis of the pK shifts occurring upon formation of the inhibitor(substrate)/enzyme complexes, some aminoacidic groups are proposed to play a role in such interactions

Management of potential drug interactions in community pharmacies: a questionnaire-based survey in Switzerland

Objective: To analyze the current drug-interaction management in Swiss community pharmacies, with a particular focus on electronic systems, and to compare the results with those expressed by German general practitioners in a recent survey. Methods: Data were collected with a postal questionnaire which was randomly sent to 500 out of 833 community pharmacies in the German part of Switzerland. Results: The response rate was 57.4%, and only 24.7% pharmacists reported that they were confronted less than daily with potential drug interactions. Use of computer software to identify potential drug interactions was widespread in community pharmacies (90.2%), and the software was the primary source of information (81.2 ± 29.6%). The quality of the interaction software was judged sensitive (identifying all dangerous interactions) by 80.5 ± 21.5%, but specific (identifying only relevant interactions) by only 38.3 ± 32%. Pharmacists declared a low override rate (14%) of drug interaction alerts, although unjustified alerts were reported by 60.6 ± 33.1%. In contrast to general practitioners, pharmacists opted less often for information on the mechanism of the interaction, and more frequently for details for dose adjustment. Both groups complained about deficient information on non-interacting alternatives. Conclusion: The information needs of community pharmacists differed considerably from general practitioners, and pharmacists were overwhelmed by inappropriate alerts because of a lack of specificity of their drug-interaction systems. Substantial improvement of drug-interaction software systems is thus required at least in two important aspects, the suppression of inappropriate alerts and the tailoring to the needs of the use

Proposal for a New Diagnostic Histopathological Approach in the Evaluation of Ki-67 in GEP-NETs

Abstract Introduction: Studies have shown that the Ki-67 index is a valuable biomarker for the diagnosis, and classification of gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). We re-evaluated the expression of Ki-67 based on the intensity of the stain, basing our hypothesis on the fact that the Ki-67 protein is continuously degraded. Background: The aim was to evaluate whether a new scoring method would be more effective in classifying NETs by reducing staining heterogeneity. Methods: Patients with GEP-NET (n = 87) were analyzed. The classification difference between the two methods was determined. Results: The classification changed significantly when the Ki-67 semiquantal index was used. The percentage of G1 patients increased from 18.4% to 60.9%, while the G2 patients decreased from 66.7% to 29.9% and the G3 patients also decreased from 14.9% to 9.2%. Moreover, it was found that the traditional Ki-67 was not significantly related to the overall survival (OS), whereas the semiquantal Ki-67 was significantly related to the OS. Conclusions: The new quantification was a better predictor of OS and of tumor classification. Therefore, it could be used both as a marker of proliferation and as a tool to map tumor dynamics that can influence the diagnosis and guide the choice of therapy

From preclinical development to clinical application : kit formulation for radiolabelling the minigastrin analogue CP04 with In-111 for a first-in-human clinical trial

Introduction A variety of radiolabelled minigastrin analogues targeting the cholecystokinin 2 (CCK2) receptor were developed and compared in a concerted preclinical testing to select the most promising radiotracer for diagnosis and treatment of medullary thyroid carcinoma (MTC). DOTA-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 (CP04) after labelling with 111In displayed excellent characteristics, such as high stability, receptor affinity, specific and persistent tumour uptake and low kidney retention in animal models. Therefore, it was selected for further clinical evaluation within the ERA-NET project GRAN-T-MTC. Here we report on the development of a pharmaceutical freeze-dried formulation of the precursor CP04 for a first multi-centre clinical trial with 111In-CP04 in MTC patients. Materials and methods The kit formulation was optimised by adjustment of buffer, additives and radiolabelling conditions. Three clinical grade batches of a final kit formulation with two different amounts of peptide (10 or 50 μg) were prepared and radiolabelled with 111In. Quality control and stability assays of both the kits and the resulting radiolabelled compound were performed by HPLC analysis. Results Use of ascorbic acid buffer (pH 4.5) allowed freeze-drying of the kit formulation with satisfactory pellet-formation. Addition of methionine and gentisic acid as well as careful selection of radiolabelling temperature was required to avoid extensive oxidation of the Met11-residue. Trace metal contamination, in particular Zn, was found to be a major challenge during the pharmaceutical filling process in particular for the 10 μg formulation. The final formulations contained 10 or 50 μg CP04, 25 mg ascorbic acid, 0.5 mg gentisic acid and 5 mg l-methionine. The radiolabelling performed by incubation of 200-250 MBq 111InCl3 at 90°C for 15 min resulted in reproducible radiochemical purity (RCP) > 94%. Kit-stability was proven for > 6 months at + 5°C and at + 25°C. The radiolabelled product was stable for > 4 h at + 25°C. Conclusion A kit formulation to prepare 111In-CP04 for clinical application was developed, showing high stability of the kit as well as high RCP of the final product

State of the art of 18F-FDG PET/CT application in inflammation and infection: a guide for image acquisition and interpretation

Aim The diagnosis, severity and extent of a sterile inflammation or a septic infection could be challenging since there is not one single test able to achieve an accurate diagnosis. The clinical use of 18F-fluorodeoxyglucose ([F-18]FDG) positron emission tomography/computed tomography (PET/CT) imaging in the assessment of inflammation and infection is increasing worldwide. The purpose of this paper is to achieve an Italian consensus document on [F-18]FDG PET/CT or PET/MRI in inflammatory and infectious diseases, such as osteomyelitis (OM), prosthetic joint infections (PJI), infective endocarditis (IE), prosthetic valve endocarditis (PVE), cardiac implantable electronic device infections (CIEDI), systemic and cardiac sarcoidosis (SS/CS), diabetic foot (DF), fungal infections (FI), tuberculosis (TBC), fever and inflammation of unknown origin (FUO/IUO), pediatric infections (PI), inflammatory bowel diseases (IBD), spine infections (SI), vascular graft infections (VGI), large vessel vasculitis (LVV), retroperitoneal fibrosis (RF) and COVID-19 infections. Methods In September 2020, the inflammatory and infectious diseases focus group (IIFG) of the Italian Association of Nuclear Medicine (AIMN) proposed to realize a procedural paper about the clinical applications of [F-18]FDG PET/CT or PET/MRI in inflammatory and infectious diseases. The project was carried out thanks to the collaboration of 13 Italian nuclear medicine centers, with a consolidate experience in this field. With the endorsement of AIMN, IIFG contacted each center, and the pediatric diseases focus group (PDFC). IIFG provided for each team involved, a draft with essential information regarding the execution of [F-18]FDG PET/CT or PET/MRI scan (i.e., indications, patient preparation, standard or specific acquisition modalities, interpretation criteria, reporting methods, pitfalls and artifacts), by limiting the literature research to the last 20 years. Moreover, some clinical cases were required from each center, to underline the teaching points. Time for the collection of each report was from October to December 2020. Results Overall, we summarized 291 scientific papers and guidelines published between 1998 and 2021. Papers were divided in several sub-topics and summarized in the following paragraphs: clinical indications, image interpretation criteria, future perspectivess and new trends (for each single disease), while patient preparation, image acquisition, possible pitfalls and reporting modalities were described afterwards. Moreover, a specific section was dedicated to pediatric and PET/MRI indications. A collection of images was described for each indication. Conclusions Currently, [F-18]FDG PET/CT in oncology is globally accepted and standardized in main diagnostic algorithms for neoplasms. In recent years, the ever-closer collaboration among different European associations has tried to overcome the absence of a standardization also in the field of inflammation and infections. The collaboration of several nuclear medicine centers with a long experience in this field, as well as among different AIMN focus groups represents a further attempt in this direction. We hope that this document will be the basis for a "common nuclear physicians' language" throughout all the country

Life history, seasonal variation and production of Andesiops torrens (Lugo-Ortiz and McCafferty) and Andesiops peruvianus (Ulmer) (Ephemeroptera: Baetidae) in a headwater Patagonian stream

Life history descriptors of mayfly species are increasingly used in ecological assessment studies as indicator of environmental stress and also to evaluate the potential effects of climate change. We investigated the life history, annual production and competition of two congeneric mayflies: Andesiops torrens and Andesiops peruvianus in a Patagonian mountain headwater stream (La Hoya). From July 2004 to June 2005 a monthly sampling was conducted at riffle areas using a Surber net. Mean density of A. torrens ranged from 26 to 1080indm-2 whereas that of A. peruvianus ranged from 7 to 629indm-2. The annual production and P/B ratios of A. torrens (0.18gm-2, 3.90) and A. peruvianus (0.11gm-2, 3.35) at La Hoya stream were low, but within the expected values for cold water environments at high elevations. The two species had a similar larval life history with small larvae predominating in late summer and early autumn, middle size larvae being represented throughout winter, and mature larvae and emergence occurring in summer. As a result A. torrens and A. peruvianus showed moderately synchronized univoltine life cycles. The temporal interspecific overlap on both density and biomass was very low. This suggests that these two species of grazers reduce the competition for resources by having a marked temporal segregation.Fil: Epele, Luis Beltran. Universidad Nacional de la Patagonia "San Juan Bosco"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Miserendino, Maria Laura. Universidad Nacional de la Patagonia "San Juan Bosco"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pessacq, Pablo. Universidad Nacional de la Patagonia "San Juan Bosco"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

A Global Building Occupant Behavior Database

This paper introduces a database of 34 field-measured building occupant behavior datasets collected from 15 countries and 39 institutions across 10 climatic zones covering various building types in both commercial and residential sectors. This is a comprehensive global database about building occupant behavior. The database includes occupancy patterns (i.e., presence and people count) and occupant behaviors (i.e., interactions with devices, equipment, and technical systems in buildings). Brick schema models were developed to represent sensor and room metadata information. The database is publicly available, and a website was created for the public to access, query, and download specific datasets or the whole database interactively. The database can help to advance the knowledge and understanding of realistic occupancy patterns and human-building interactions with building systems (e.g., light switching, set-point changes on thermostats, fans on/off, etc.) and envelopes (e.g., window opening/closing). With these more realistic inputs of occupants’ schedules and their interactions with buildings and systems, building designers, energy modelers, and consultants can improve the accuracy of building energy simulation and building load forecasting

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come