GPR and IRT Tests in two Historical Buildings in Gravina in Puglia

This paper describes a noninvasive investigation conducted in two important churches, namely the Cathedral of Santa Maria Assunta and the church Santa Croce, both placed in Gravina in Puglia (close to Bari, southern Italy). The church of Santa Croce, now deconsecrated, lies below the Cathedral. Therefore, indeed the two churches constitute a unique building body. Moreover, below the church of Santa Croce there are several crypts, only partially known. The prospecting was performed both with a pulsed commercial GPR system and with a prototypal reconfigurable stepped frequency system. The aim was twofold, namely to achieve some information about the monument and to test the prototypal system. The GPR measurements have been also integrated with an IRT investigation performed on part of the vaulted ceiling of the church of Santa Croce, in order to confirm or deny a possible interpretation of some GPR results

GPR activities in Italy: a review

Ground-penetrating radar has been increasingly played an important role over the last 15 years in Italy due to its high reliability in assisting the assessment of the built environment for civil engineering purposes, and in being used for geophysical investigations within many other fields of application. In line with this, original works involving fundamental aspects of this technique and implementing its use more practically in a number of interesting projects have been developed over years, both under a research and an enterprise point of view. This paper will endeavour to review the current status of ground-penetrating radar activities in Italy. Efforts have been devoted to single out the most interesting national research projects, both recent and ongoing, involving ground-penetrating radar in Italy, such as the ARCHEO project in the 90s, funded by the Italian Ministry for Universities, wherein a stepped frequency ultra-wide band radar suited for archaeological surveys was manufactured. In this framework, it is worth citing another important and more recent project, European Community funded, namely, ORFEUS, which started in the late 2006 with the overall aim of providing the capability to locate buried infrastructure accurately and reliably by means of a bore-head ground-penetrating radar for horizontal directional drilling. A review on the main use of this non-destructive technique in management activities of national resources and infrastructures has been also performed, ranging from the applications made by Anas S.p.A., i.e. the main management authority for the Italian road and motorway network, up to private enterprises specialized in both services providing and ground-penetrating radar manufacturing such as, to cite a few, Sineco S.p.A. and IDS Ingegneria dei Sistemi S.p.A., respectively. Current national guidelines, rules or protocols to be followed during radar surveys have been also reviewed. Unlike well-established international standards such as the ASTM D 4748-98 and the ASTM D 6432-99 dealing with, respectively, thicknesses evaluation of bound layers in road pavements, and equipment, field procedures and data-interpretation for the electromagnetic evaluation of subsurface materials, it has to be noted that the Italian body of laws and rules tackles the ground-penetrating radar applications under an indirect and partial approach. Despite of such situation, national guidelines concerning utilities-detection activities as well as other theoretical and practical guidelines established by the major Italian private enterprises on this field can be also considered highly relevant. Moreover, a further focus on the activities and main devices of the major Italian ground-penetrating radar manufacturers have been thoroughly described. Under a research and innovation perspective, the most important test sites, such as the site of the University of Salento to reconstruct archaeological and urban subsurface scenarios have been listed along with the main advances reached in integrating ground-penetrating radar with other non-destructive techniques, to inform and potentially improve the possibility of new developments and collaborations

Neural stem cell transplantation in patients with progressive multiple sclerosis: an open-label, phase 1 study

Innovative pro-regenerative treatment strategies for progressive multiple sclerosis (PMS), combining neuroprotection and immunomodulation, represent an unmet need. Neural precursor cells (NPCs) transplanted in animal models of multiple sclerosis have shown preclinical efficacy by promoting neuroprotection and remyelination by releasing molecules sustaining trophic support and neural plasticity. Here we present the results of STEMS, a prospective, therapeutic exploratory, non-randomized, open-label, single-dose-finding phase 1 clinical trial (NCT03269071, EudraCT 2016-002020-86), performed at San Raffaele Hospital in Milan, Italy, evaluating the feasibility, safety and tolerability of intrathecally transplanted human fetal NPCs (hfNPCs) in 12 patients with PMS (with evidence of disease progression, Expanded Disability Status Scale >= 6.5, age 18-55 years, disease duration 2-20 years, without any alternative approved therapy). The safety primary outcome was reached, with no severe adverse reactions related to hfNPCs at 2-year follow-up, clearly demonstrating that hfNPC therapy in PMS is feasible, safe and tolerable. Exploratory secondary analyses showed a lower rate of brain atrophy in patients receiving the highest dosage of hfNPCs and increased cerebrospinal fluid levels of anti-inflammatory and neuroprotective molecules. Although preliminary, these results support the rationale and value of future clinical studies with the highest dose of hfNPCs in a larger cohort of patients

Growth arrest-specific transcript 5 associated snoRNA levels are related to p53 expression and DNA damage in colorectal cancer

BACKGROUND The growth arrest-specific transcript 5 gene (GAS5) encodes a long noncoding RNA (lncRNA) and hosts a number of small nucleolar RNAs (snoRNAs) that have recently been implicated in multiple cellular processes and cancer. Here, we investigate the relationship between DNA damage, p53, and the GAS5 snoRNAs to gain further insight into the potential role of this locus in cell survival and oncogenesis both in vivo and in vitro. METHODS We used quantitative techniques to analyse the effect of DNA damage on GAS5 snoRNA expression and to assess the relationship between p53 and the GAS5 snoRNAs in cancer cell lines and in normal, pre-malignant, and malignant human colorectal tissue and used biological techniques to suggest potential roles for these snoRNAs in the DNA damage response. RESULTS GAS5-derived snoRNA expression was induced by DNA damage in a p53-dependent manner in colorectal cancer cell lines and their levels were not affected by DICER. Furthermore, p53 levels strongly correlated with GAS5-derived snoRNA expression in colorectal tissue. CONCLUSIONS In aggregate, these data suggest that the GAS5-derived snoRNAs are under control of p53 and that they have an important role in mediating the p53 response to DNA damage, which may not relate to their function in the ribosome. We suggest that these snoRNAs are not processed by DICER to form smaller snoRNA-derived RNAs with microRNA (miRNA)-like functions, but their precise role requires further evaluation. Furthermore, since GAS5 host snoRNAs are often used as endogenous controls in qPCR quantifications we show that their use as housekeeping genes in DNA damage experiments can lead to inaccurate results

Improved clinical investigation and evaluation of high-risk medical devices: the rationale and objectives of CORE-MD (Coordinating Research and Evidence for Medical Devices)

: In the European Union (EU) the delivery of health services is a national responsibility but there are concerted actions between member states to protect public health. Approval of pharmaceutical products is the responsibility of the European Medicines Agency, whereas authorizing the placing on the market of medical devices is decentralized to independent 'conformity assessment' organizations called notified bodies. The first legal basis for an EU system of evaluating medical devices and approving their market access was the medical device directives, from the 1990s. Uncertainties about clinical evidence requirements, among other reasons, led to the EU Medical Device Regulation (2017/745) that has applied since May 2021. It provides general principles for clinical investigations but few methodological details-which challenges responsible authorities to set appropriate balances between regulation and innovation, pre- and post-market studies, and clinical trials and real-world evidence. Scientific experts should advise on methods and standards for assessing and approving new high-risk devices, and safety, efficacy, and transparency of evidence should be paramount. The European Commission recently awarded a Horizon 2020 grant to a consortium led by the European Society of Cardiology and the European Federation of National Associations of Orthopaedics and Traumatology, that will review methodologies of clinical investigations, advise on study designs, and develop recommendations for aggregating clinical data from registries and other real-world sources. The CORE-MD project (Coordinating Research and Evidence for Medical Devices) will run until March 2024; here we describe how it may contribute to the development of regulatory science in Europe

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Automated Detection of Reflection Hyperbolas in Complex GPR Images With No <italic>A Priori</italic> Knowledge on the Medium

In this paper, we propose an automated detection algorithm for well- and ill-shaped ground-penetrating radar reflection hyperbolas for complex media, calibrated with human recognition principles. The algorithm detects the apex of the hyperbolas by fitting an analytical function of a hyperbola to the profile edge dots detected with a Canny filter. The existence of a hyperbola is determined using a set of carefully chosen criteria calibrated in order to fit the ambiguity zone for the human brain. The inherent misshapedness of field hyperbolas is further considered by defining a buffer zone around the theoretical hyperbola. First, the method was tested in the laboratory over tree roots and PVC pipes and on field images over tree root systems. Both timeand frequency-domain radars were used on-ground. After around 1–3 min of computation time for 10 000 edge dots in a MATLAB environment (single 1.96-GHz processor), the results showed rates of false alarm and nondetection of maximum 20% and 28%, respectively. In comparison with the semiautomated hyperbola detection provided by a commercial software, these rates were lower. Second, we conducted a sensitivity analysis to estimate the validity of the fitting of a hyperbola equation neglecting the object radius. The fitting was close, but the derivation of the relative permittivity from the analytical equation neglecting the radius led to high errors. In conclusion, owing to the low computational time and its good performances, the proposed algorithm is suitable for complex environments

Use of GPR and standard geophysical methods to explore the subsurface : example from the Maltese Archipelago

The aim of this work is to illustrate the results of Ground Penetrating Radar (GPR) and passive seismic measurements in selected sites in Malta. The data were gathered during a Short-Term Scientific Mission (STSM) performed under the COST Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar." The purpose of the measures has been twofold, namely to test the performances of an innovative GPR system [1], recently upgraded, and to perform GPR and passive seismic analyses in several sites of interest in Malta, in order to get an insight about their geological conditions as well as about the internal status of some historical monuments. The exploited GPR system was a prototypal stepped-frequency reconfigurable GPR, implemented by IBAM-CNR together with the University of Florence and the IDS Corporation within the research project AITECH (www.aitechnet.com/ibam.html). This system contains three equivalent couples of antennas with the same gap, achieved from two series of switches along the arms. The on and off state of the switches make equivalently longer or shorter the antennas, so to achieve efficient transmission on three bands that cover the comprehensive frequency range from 50 MHz to 1 GHz. Passive seismic techniques where used in order to gather useful data to be compared and integrated with those obtained with the GPR. Ambient noise was recorded using a three-component seismometer. Data were gathered at the following sites a) on a cliff area close to the Golden Bay tower; b) Madliena tower; c) Laferla Cross; d) santa Maria Church. We were able to locate and determine fractures on the cliff area as well as to locate graves and buried structures at the investigated sites.peer-reviewe