Large-scale risk analysis in the Arno river basin (Italy)

We present the methodologies adopted and the outcomes obtained in the analysis of landslide risk in the basin of the Arno River (Central Italy) in the framework of a project sponsored by the Basin Authority of the Arno River, started in the year 2002 and completed at the beginning of 2005. A new landslide inventory of the whole area was realized, using conventional (aerialphoto interpretation and field surveys) and non-conventional methods (e.g. remote sensing techniques such as DInSAR and PS-InSAR). The great majority of the mapped mass movements are rotational slides (75%), solifluctions and other shallow slow movements (17%) and flows (5%), while soil slips, and other rapid landslides, seem less frequent everywhere within the basin. The assessment of landslide hazard in terms of probability of occurrence in a given time, based for mapped landslides on direct and indirect observations of the state of activity and recurrence time, has been extended to landslide-free areas through the application of statistical methods implemented in an artificial neural network (ANN). Unique conditions units (UCU) were defined by the map overlay of landslide preparatory factors (lithology, land cover, slope gradient, slope curvature and upslope contributing area) and afterwards used to construct a series of model vectors for the training and test of the ANN. Model validation confirms that prediction results are very good, with an average percentage of correctly recognized mass movements of about 85%. The analysis also revealed the existence of a large number of unmapped mass movements, thus contributing to the completeness of the final inventory. Temporal hazard was estimated via the translation of state of activity in recurrence time and hence probability of occurrence. The definition of position, typology and characteristics of the elements at risk has been carried out with two different methodologies, partially derived from the “Plans d’Exposition au Risque” proposed in France: i) buildings and infrastructures were directly extracted from digital terrain cartography at the 1:10,000 scale, whilst ii) nonurban land use was identified and mapped based on an updated and improved CORINE land cover map at the 1:50,000 scale. The definition of the exposure of the elements at risk relies upon contingent valuation methods and form-based interviews. Landslide intensity, usually defined as proportional to kinetic energy, was obtained considering landslide typology as a proxy for expected velocity. In the case of the Arno River Basin the definition of intensity is influenced by the fact that the large majority of mass movements are deep-seated reactivated slides evolving into flows. Two main cases were so considered: deep-seated rotational slides and shallow flows or planar slides with virtually constant depth. In the latter case, intensity as a function of volume was set proportional to the area of the mapped phenomenon. In the former case, a simple geometric model was used to compute the volume. Intersection of hazard values with vulnerability and exposure figures, obtained by reclassification of digital vector mapping at 1:10,000 scale, lead to the definition of risk values for each terrain unit for different periods of time into the future. Numerical results indicate that in absence of mitigation measures, large economic losses must be expected due to landslide activity in the few next years. The final results of the research are now undergoing a process of integration and implementation within land planning and risk prevention policies and practices at local and national level

18F-FDG PET-Derived Volume-Based Parameters to Predict Disease-Free Survival in Patients with Grade III Breast Cancer of Different Molecular Subtypes Candidates to Neoadjuvant Chemotherapy

We investigated whether baseline [F-18] Fluorodeoxyglucose (F-18-FDG) positron emission tomography (PET)-derived semiquantitative parameters could predict disease-free survival (DFS) in patients with grade III breast cancer (BC) of different molecular subtypes candidate to neoadjuvant chemotherapy (NAC). For each F-18-FDG-PET/CT scan, the following parameters were calculated in the primary tumor (SUVmax, SUVmean, MTV, TLG) and whole-body (WB_SUVmax, WB_MTV, and WB_TLG). Receiver operating characteristic (ROC) analysis was used to determine the capability to predict DFS and find the optimal threshold for each parameter. Ninety-five grade III breast cancer patients with different molecular types were retrieved from the databases of the University Hospital of Padua and the University Hospital of Ferrara (luminal A: 5; luminal B: 34; luminal B-HER2: 22; HER2-enriched: 7; triple-negative: 27). In luminal B patients, WB_MTV (AUC: 0.75; best cut-off: WB_MTV > 195.33; SS: 55.56%, SP: 100%; p = 0.002) and WB_TLG (AUC: 0.73; best cut-off: WB_TLG > 1066.21; SS: 55.56%, SP: 100%; p = 0.05) were the best predictors of DFS. In luminal B-HER2 patients, WB_SUVmax was the only predictor of DFS (AUC: 0.857; best cut-off: WB_SUVmax > 13.12; SS: 100%; SP: 71.43%; p < 0.001). No parameter significantly affected the prediction of DFS in patients with grade III triple-negative BC. Volume-based parameters, extracted from baseline F-18-FDG PET, seem promising in predicting recurrence in patients with grade III luminal B and luminal B- HER2 breast cancer undergoing NAC

CTCF binding site classes exhibit distinct evolutionary, genomic, epigenomic and transcriptomic features

CTCF DNA binding sites are classified into distinct functional classes, with distinct biological properties, shedding light on the differing functional roles of CTCF binding

Analisi della suscettibilità da frana a scala di bacino (Bacino del Fiume Arno, Toscana-Umbria, Italia)

In questa nota vengono presentati i metodi applicati e i risultati ottenuti in una recente analisi della pericolosità da frana, condotta sul territorio del Bacino del Fiume Arno nell’ambito di una convenzione tra l’Autorità di Bacino e il Dipartimento di Scienze della Terra dell’Università di Firenze (2002-2005). Tutti i dati acquisiti, confluiti in una banca dati GIS, sono stati sintetizzati in carte tematiche e in una carta inventario delle frane. La sovrapposizione dei fattori predisponenti selezionati (pendenza, litologia, uso del suolo, curvatura di profilo e area drenata) ha permesso di definire le unità elementari per il trattamento statistico (Unità Territoriali Omogenee: UTO). La valutazione della pericolosità è stata estesa alle aree prive di movimenti franosi utilizzando metodi statistici multivariati implementati in Reti Neurali Artificiali. L’area di studio è stata suddivisa in cinque Macroaree morfologicamente e geologicamente omogenee: per ogni Macroarea, i predittori neurali sono stati addestrati su un opportuno sottoinsieme di dati, applicando poi i migliori all’intero data-set al fine di generare valori previsti dell’indice di suscettibilità per ogni UTO. Infine, i valori di uscita sono stati riclassificati in differenti livelli di pericolosità in base a criteri di soglia e validati per confronto con l’inventario. Una percentuale di area in frana compresa tra l’81 e il 96% risulta correttamente classificata dalla previsione nelle varie Macroare

Clinical Management of Neuroendocrine Neoplasms in Clinical Practice: A Formal Consensus Exercise

Many treatment approaches are now available for neuroendocrine neoplasms (NENs). While several societies have issued guidelines for diagnosis and treatment of NENs, there are still areas of controversy for which there is limited guidance. Expert opinion can thus be of support where firm recommendations are lacking. A group of experts met to formulate 14 statements relative to diagnosis and treatment of NENs and presented herein. The nominal group and estimate-talk-estimate techniques were used. The statements covered a broad range of topics from tools for diagnosis to follow-up, evaluation of response, treatment efficacy, therapeutic sequence, and watchful waiting. Initial prognostic characterization should be based on clinical information as well as histopathological analysis and morphological and functional imaging. It is also crucial to optimize RLT for patients with a NEN starting from accurate characterization of the patient and disease. Follow-up should be patient/tumor tailored with a shared plan about timing and type of imaging procedures to use to avoid safety issues. It is also stressed that patient-reported outcomes should receive greater attention, and that a multidisciplinary approach should be mandatory. Due to the clinical heterogeneity and relative lack of definitive evidence for NENs, personalization of diagnostic–therapeutic work-up is crucial

Phenolic extracts from extra virgin olive oils inhibit dipeptidyl peptidase iv activity: In vitro, cellular, and in silico molecular modeling investigations

Two extra virgin olive oil (EVOO) phenolic extracts (BUO and OMN) modulate DPP-IV activity. The in vitro DPP-IV activity assay was performed at the concentrations of 1, 10, 100, 500, and 1000 μg/mL, showing a dose-dependent inhibition by 6.8 ± 1.9, 17.4 ± 6.1, 37.9 ± 2.4, 57.8 ± 2.9, and 81 ± 1.4% for BUO and by 5.4 ± 1.7, 8.9 ± 0.4, 28.4 ± 7.2, 52 ± 1.3, and 77.5 ± 3.5% for OMN. Moreover, both BUO and OMN reduced the DPP-IV activity expressed by Caco-2 cells by 2.9 ± 0.7, 44.4 ± 0.7, 61.2 ± 1.8, and 85 ± 4.2% and by 3 ± 1.9, 35 ± 9.4, 60 ± 7.2, and 82 ± 2.8%, respectively, at the same doses. The concentration of the most abundant and representative secoiridoids within both extracts was analyzed by nuclear magnetic resonance ((1)H-NMR). Oleuropein, oleacein, oleocanthal, hydroxytyrosol, and tyrosol, tested alone, reduced the DPP-IV activity, with IC(50) of 472.3 ± 21.7, 187 ± 11.4, 354.5 ± 12.7, 741.6 ± 35.7, and 1112 ± 55.6 µM, respectively. Finally, in silico molecular docking simulations permitted the study of the binding mode of these compounds

Three-dimensional conformation at the H19/Igf2 locus supports a model of enhancer tracking

Insight into how the mammalian genome is structured in vivo is key to understanding transcriptional regulation. This is especially true in complex domains in which genes are coordinately regulated by long-range interactions between cis-regulatory elements. The regulation of the H19/Igf2 imprinted region depends on the presence of several cis-acting sequences, including a methylation-sensitive insulator between Igf2 and H19 and shared enhancers downstream of H19. Each parental allele has a distinct expression pattern. We used chromosome conformation capture to assay the native three-dimensional organization of the H19/Igf2 locus on each parental copy. Furthermore, we compared wild-type chromosomes to several mutations that affect the insulator. Our results show that promoters and enhancers reproducibly co-localize at transcriptionally active genes, i.e. the endodermal enhancers contact the maternal H19 and the paternal Igf2 genes. The active insulator blocks traffic of the enhancers along the chromosome, restricting them to the H19 promoter. Conversely, the methylated inactive insulator allows the enhancers to contact the upstream regions, including Igf2. Mutations that either remove or inhibit insulator activity allow unrestricted access of the enhancers to the whole region. A mutation that allows establishment of an enhancer-blocker on the normally inactive paternal copy diminishes the contact of the enhancer with the Igf2 gene. Based on our results, we propose that physical proximity of cis-acting DNA elements is vital for their activity in vivo. We suggest that enhancers track along the chromosome until they find a suitable promoter sequence to interact with and that insulator elements block further tracking of enhancers

Extra virgin olive oil phenol extracts exert hypocholesterolemic effects through the modulation of the LDLR pathway: In vitro and cellular mechanism of action elucidation

This study was aimed at investigating the hypocholesterolemic effects of extra virgin olive oil (EVOO) phenols and the mechanisms behind the effect. Two phenolic extracts were prepared from EVOO of different cultivars and analyzed using the International Olive Council (IOC) official method for total phenols, a recently validated hydrolytic procedure for total hydroxytyrosol and tyrosol, and 1H-NMR analysis in order to assess their secoiridoid profiles. Both of the extracts inhibited in vitro the 3-hydroxy-3-methylglutaryl co-enzyme A reductase (HMGCoAR) activity in a dose-dependent manner. After the treatment of human hepatic HepG2 cells (25 µg/mL), they increased the low-density lipoprotein (LDL) receptor protein levels through the activation of the sterol regulatory element binding proteins (SREBP)-2 transcription factor, leading to a better ability of HepG2 cells to uptake extracellular LDL molecules with a final hypocholesterolemic effect. Moreover, both of the extracts regulated the intracellular HMGCoAR activity through the increase of its phosphorylation by the activation of AMP-activated protein kinase (AMPK)-pathways. Unlike pravastatin, they did not produce any unfavorable effect on proprotein convertase subtilisin/kexin 9 (PCSK9) protein level. Finally, the fact that extracts with different secoiridoid profiles induce practically the same biological effects suggests that the hydroxytyrosol and tyrosol derivatives may have similar roles in hypocholesterolemic activity

Extra virgin olive oil phenol extracts exert hypocholesterolemic effects through the modulation of the LDLR pathway: In vitro and cellular mechanism of action elucidation

This study was aimed at investigating the hypocholesterolemic effects of extra virgin olive oil (EVOO) phenols and the mechanisms behind the effect. Two phenolic extracts were prepared from EVOO of different cultivars and analyzed using the International Olive Council (IOC) official method for total phenols, a recently validated hydrolytic procedure for total hydroxytyrosol and tyrosol, and1 H-NMR analysis in order to assess their secoiridoid profiles. Both of the extracts inhibited in vitro the 3-hydroxy-3-methylglutaryl co-enzyme A reductase (HMGCoAR) activity in a dose-dependent manner. After the treatment of human hepatic HepG2 cells (25 µg/mL), they increased the low-density lipoprotein (LDL) receptor protein levels through the activation of the sterol regulatory element binding proteins (SREBP)-2 transcription factor, leading to a better ability of HepG2 cells to uptake extracellular LDL molecules with a final hypocholesterolemic effect. Moreover, both of the extracts regulated the intracellular HMGCoAR activity through the increase of its phosphorylation by the activation of AMP-activated protein kinase (AMPK)-pathways. Unlike pravastatin, they did not produce any unfavorable effect on proprotein convertase subtilisin/kexin 9 (PCSK9) protein level. Finally, the fact that extracts with different secoiridoid profiles induce practically the same biological effects suggests that the hydroxytyrosol and tyrosol derivatives may have similar roles in hypocholesterolemic activity