Landslide susceptibility in the Belt and Road Initiative

The Belt and Road Initiative (BRI) is a project launched by the Chinese Government whose main goal is to connect more than 65 countries in Asia, Europe, Africa and Oceania developing infrastructures and facilities. To support the prevention or mitigation of landslide hazards, which may affect the mainland infrastructures of BRI, a landslide susceptibility analysis in the countries involved has been carried out. Due to the large study area, the analysis has been carried out using a multi-scale approach which consists of mapping susceptibility firstly at continental scale, and then at national scale. The study area selected for the continental assessment is the south-Asia, where a pixel-based landslide susceptibility map has been carried out using the Weight of Evidence method and validated by Receiving Operating Characteristic (ROC) curves. Then, we selected the regions of west Tajikistan and north-east India to be investigated at national scale. Data scarcity is a common condition for many countries involved into the Initiative. Therefore in addition to the landslide susceptibility assessment of west Tajikistan, which has been conducted using a Generalized Additive Model and validated by ROC curves, we have examined, in the same study area, the effect of incomplete landslide dataset on the prediction capacity of statistical models. The entire PhD research activity has been conducted using only open data and open-source software. In this context, to support the analysis of the last years an open-source plugin for QGIS has been implemented. The SZ-tool allows the user to make susceptibility assessments from the data preprocessing, susceptibility mapping, to the final classification. All the output data of the analysis conducted are freely available and downloadable. This text describes the research activity of the last three years. Each chapter reports the text of the articles published in international scientific journal during the PhD.

Cellular Proliferation in the Prognosis of Intermediate Grade Mast Cell Tumour in Dogs

This was a retrospective study including ninety samples of dogs with a histological diagnosis of intermediate grade cutaneous mast cell tumour (MCT). The objectives of the study were to validate Minichromosome Maintenance Protein 7 (MCM7) as a prognostic marker in MCTs and to compare the ability of mitotic index (MI), Ki67 and MCM7 to predict outcome. The median survival for the entire population was not reached at 2099 days. The mean survival time was 1708 days. Seventy-two cases were censored after a median follow up of 1136 days and eighteen dogs died for causes related to the MCT after a median of 116 days. For each sample MI, Ki67 and MCM7 were determined. The Receiver Operating Characteristic (ROC) curve was obtained for each prognostic marker to evaluate the performance of the test, expressed as area under the curve, and whether the published threshold value was adequate. Kaplan-Meier and corresponding logrank test for MI, Ki67 and MCM7 as binary variables was highly significant (P<0.0001). Multivariable regression analysis of MI, Ki67 and MCM7 corrected for age and surgical margins indicated that the higher risk of dying of MCT was associated with MCM7 > 0.18 (Hazard Ration [HR] 14.7; P<0.001) followed by MI > 5 (HR 13.9; P<0.001) and Ki67 > 0.018 (HR 8.9; P<0.001). Concluding, the present study confirmed that MCM7 is an excellent prognostic marker in cutaneous MCTs being able to divide Patnaik intermediate grade tumours in two categories with different prognosis. Ki67 was equally good confirming its value as a prognostic marker in intermediate grade MCTs. The mitotic index was extremely specific, but lacked of sensitivity. Interestingly, mitotic index, Ki67 and MCM7 were independent from each other suggesting that their combination would improve their individual prognostic value.

Prediction Nomogram for 68Ga-PSMA-11 PET/CT in different clinical settings of PSA failure after radical treatment for Prostate Cancer

Objective The objective of this study was to develop a clinical nomogram to predict gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA-11-PET/CT) positivity in different clinical settings of PSA failure. Materials and methods Seven hundred three (n = 703) prostate cancer (PCa) patients with confirmed PSA failure after radical therapy were enrolled. Patients were stratified according to different clinical settings (first-time biochemical recurrence [BCR]: group 1; BCR after salvage therapy: group 2; biochemical persistence after radical prostatectomy [BCP]: group 3; advanced stage PCa before second-line systemic therapies: group 4). First, we assessed 68Ga-PSMA-11-PET/CT positivity rate. Second, multivariable logistic regression analyses were used to determine predictors of positive scan. Third, regression-based coefficients were used to develop a nomogram predicting positive 68Ga-PSMA-11-PET/CT result and 200 bootstrap resamples were used for internal validation. Fourth, receiver operating characteristic (ROC) analysis was used to identify the most informative nomogram’s derived cut-off. Decision curve analysis (DCA) was implemented to quantify nomogram’s clinical benefit. Results 68Ga-PSMA-11-PET/CT overall positivity rate was 51.2%, while it was 40.3% in group 1, 54% in group 2, 60.5% in group 3, and 86.9% in group 4 (p < 0.001). At multivariable analyses, ISUP grade, PSA, PSA doubling time, and clinical setting were independent predictors of a positive scan (all p ≤ 0.04). A nomogram based on covariates included in the multivariate model demonstrated a bootstrap-corrected accuracy of 82%. The nomogram-derived best cut-off value was 40%. In DCA, the nomogram revealed clinical net benefit of > 10%. Conclusions This novel nomogram proved its good accuracy in predicting a positive scan, with values ≥ 40% providing the most informative cut-off in counselling patients to 68Ga-PSMA-11-PET/CT. This tool might be important as a guide to clinicians in the best use of PSMA-based PET imaging.

Identification of a molecular signature as potential biomarker in blood of symptomatic and asymptomatic patients with carotid atherosclerosis

Background and Objectives: Carotid revascularization to prevent future vascular events is reasonable in patients with high-grade carotid stenosis. Currently, several biomarkers to predict carotid plaque development and progression have been investigated, among which microRNAs (miRs) are promising tools for the diagnosis of atherosclerosis. Methods and Results: A total of 49 participants were included in the study, divided into two main populations: Population 1 comprising symptomatic and asymptomatic inpatients, and Population 2 comprising asymptomatic outpatients. The study consisted of two main phases: a preliminary discovery phase and a validation phase, applying different techniques. MiR-profiles were performed on plasma and plaque tissue samples obtained from 4 symptomatic and 4 asymptomatic inpatients. MiRs emerging from profiling comparisons, i.e. miR-126-5p, miR-134-5p, miR-145-5p, miR-151a-5p, miR-34b, miR-451a, miR-720 and miR-1271-5p, were subjected to validation through RT-qPCR analysis in the total cohort of donors. Comparing asymptomatic and symptomatic inpatients, significant differences were reported in the expression levels of c-miRs for miR-126-5p and miR-1271-5p in blood, being more expressed in symptomatic subjects. In contrast, simultaneous evaluation of the selected miRs in plaque tissue samples did not confirm data obtained by the miR profiling, and no significant differences were observed. Using Receiver-Operating Characteristic (ROC) analysis, a circulating molecular signature (mir-126-5p, miR-1271-5p, albumin, C-reactive protein, and monocytes) was identified, allowing the distinction of the two groups in Population 1 (AUC = 0.795). Conclusions: Data emerging from this thesis suggest that c-miRs (i.e. miR-126-5p, miR-1271-5p) combined with selected haemato-biochemical parameters (albumin, C-reactive protein, and monocytes) produced a good molecular 'signature' to distinguish asymptomatic and symptomatic inpatients. C-miRs in blood do not necessarily reflect the expression levels of the same miRs in carotid plaque tissues since different mechanism can influence their expression.

The Hitchin map for one-nodal base curves of compact type

Studying moduli spaces of semistable Higgs bundles (E, \phi) of rank n on a smooth curve C, a key role is played by the spectral curve X (Hitchin), because an important result by Beauville-Narasimhan-Ramanan allows us to study isomorphism classes of such Higgs bundles in terms of isomorphism classes of rank-1 torsion-free sheaves on X. This way, the generic fibre of the Hitchin map, which associates to any semistable Higgs bundle the coefficients of the characteristic polynomial of \phi, is isomorphic to the Jacobian of X. Focusing on rank-2 Higgs data, this construction was extended by Barik to the case in which the curve C is reducible, one-nodal, having two smooth components. Such curve is called of compact type because its Picard group is compact. In this work, we describe and clarify the main points of the construction by Barik and we give examples, especially concerning generic fibres of the Hitchin map. Referring to Hausel-Pauly, we consider the case of SL(2,C)-Higgs bundles on a smooth base curve, which are such that the generic fibre of the Hitchin map is a subvariety of the Jacobian of X, the Prym variety. We recall the description of special loci, called endoscopic loci, such that the associated Prym variety is not connected. Then, letting G be an affine reductive group having underlying Lie algebra so(4,C), we consider G-Higgs bundles on a smooth base curve. Starting from the construction by Bradlow-Schaposnik, we discuss the associated endoscopic loci. By adapting these studies to a one-nodal base curve of compact type, we describe the fibre of the SL(2,C)-Hitchin map and of the G-Hitchin map, together with endoscopic loci. In the Appendix, we give an interpretation of generic spectral curves in terms of families of double covers.