Development and validation of an algorithm to predict the success of the ablation of macroreentrant atrial tachycardia.

Ablation of macroreentrant atrial tachycardia (MRAT) is challenging because of complex anatomy and multiple reentrant loops. In order to define an effective ablation strategy, 3-dimensional electroanatomic mapping proved very useful. To identify predictors of ablation procedure failure may be helpful for patients treatment. In the first part of our study we analyzed into details the electroanatomical features of the reentry circuit in MRAT and we compared the characteristics of successfully versus unsuccessfully consecutive treated patients undegoing electroanatomic mapping and ablation of MRAT in order to identify variables predicting the ablation outcome. Ablation was linearly placed at the mid-diastolic isthmus (MDI) to achieve arrhythmia interruption and conduction block. Variables were analyzed for predictors of both procedural failure and cumulative failure. We demonstrated a significant difference as to the electroanatomic mapping characteristics: successfully treated cases showed a narrower target isthmus with a slower conduction velocity across the isthmus itself. In the second part of our research, we analyzed the relation between the strongest predictors of procedure outcome identified in part I (MDI width and conduction velocity across the MDI) and the chance of success of the ablation procedure. In order to analyze this relation and to predict the difficulty of the ablation procedure, we developed an algorithm and we validated prospectively the accuracy of the developed model in a second patient series

Development and validation of an algorithm to predict the success of the ablation of macroreentrant atrial tachycardia.

Ablation of macroreentrant atrial tachycardia (MRAT) is challenging because of complex anatomy and multiple reentrant loops. In order to define an effective ablation strategy, 3-dimensional electroanatomic mapping proved very useful. To identify predictors of ablation procedure failure may be helpful for patients treatment. In the first part of our study we analyzed into details the electroanatomical features of the reentry circuit in MRAT and we compared the characteristics of successfully versus unsuccessfully consecutive treated patients undegoing electroanatomic mapping and ablation of MRAT in order to identify variables predicting the ablation outcome. Ablation was linearly placed at the mid-diastolic isthmus (MDI) to achieve arrhythmia interruption and conduction block. Variables were analyzed for predictors of both procedural failure and cumulative failure. We demonstrated a significant difference as to the electroanatomic mapping characteristics: successfully treated cases showed a narrower target isthmus with a slower conduction velocity across the isthmus itself. In the second part of our research, we analyzed the relation between the strongest predictors of procedure outcome identified in part I (MDI width and conduction velocity across the MDI) and the chance of success of the ablation procedure. In order to analyze this relation and to predict the difficulty of the ablation procedure, we developed an algorithm and we validated prospectively the accuracy of the developed model in a second patient series

Synthesis and characterization of group IV and V metal diboride nanocrystals via borothermal reduction of metal oxide with NaBH4

Group IV and V metal diborides (MB2) have a unique combination of properties such as a very high melting point (\u3e3000°C), high hardness, good solid-state phase stability, high thermal and electrical conductivity. Metal diboride-based ceramics are expected to be potential candidate materials for ultra-high-temperature applications in the aerospace industry [1]. Due to the poor sinterability of commercial powders, the availability of nanometric boride particles has indeed the potential to improve several stages of ceramic processing [2], or for instance to facilitate the sintering of bulk ceramics due to enhanced particle reactivity [3]. Several synthesis have been developed to achieve nanoborides: chemical route from inorganic precursors, mechanical alloying and self-propagating high-temperature synthesis [4–6]. In this work we proposed the synthesis of group IV and V metal diboride (MB2, M= Ti, Zr, Hf, Nb, Ta) nanocrystals by a thermal treatment of the metal oxide and sodium borohydride (NaBH4) at 700°C under atmospheric pressure [7]. The reaction occurs first via decomposition of NaBH4, followed by the formation of amorphous boron and crystalline ternary species with general formula NaxMyOz and NaxByOz. Finally all of the intermediary species yield metal diboride (MB2) and sodium meta-borate (NaBO2). Synthesized TiB2 nanocrystals have an average size of 11 nm and the powder has a specific surface area (s.s.a) of 33.45 m2/g. ZrB2 grains have a platelet morphology with an aspect ratio of 10, average size of 22.5 nm and s.s.a of 24.97 m2/g; HfB2 has a similar morphology with a crystals size of 28 nm, while the s.s.a is even higher, 36.36 m2/g. As far as we know, the latter is the finest powder obtained via borothermal reduction of metal oxides ever reported. Synthesized NbB2 powder consists of crystallites around 12 nm and has a s.s.a of 21.09 m2/g. TaB2 powder has a s.s.a of 11.38 m2/g and consists of 200 nm agglomerates of spherical and needle-shaped nanocrystals with average size of 11 nm

Introduction to H2020 project C3HARME: Next generation ceramic composites for combustion harsh environments and space

Materials for aeronautical and space applications largely involve ceramic matrix composites, CMCs, made of carbon or silicon carbide. However, C/C composites suffer from poor erosion resistance while silicon-based ceramics, SiC/SiC or C/SiC composites, may undergo strong ablation due to the formation and volatilization of silica. In recent years, Ultra-High Temperature Ceramics, UHTCs, have shown outstanding erosion resistance at temperatures up to 2000°C or even higher but they still cannot resist to thermal shocks and damage. Therefore, there is an increasing demand for advanced materials with temperature capability in highly corrosive environments to enable space vehicles to resist several launches and re-entries. The EU-funded project C3HARME aims at combining the best features of CMCs and UHTCs to design, develop, manufacture and test a new class of Ultra-High Temperature Ceramic Matrix Composite (UHTCMCs) with self-healing capabilities. Applications selected to implement the new materials are near-zero erosion nozzles and near- zero ablation TPS tiles. This talk aims at giving an introduction to a dedicated session that illustrates the most important challenges addressed by C3HARME project; including the integration between well-established and novel techniques for CMCs and UHTCs production, the need for very high temperature characterization, the meaning of self-healing capability for UHTCMCs, the contribution of modeling to materials development and to investigation of the relationships between microstructure and thermo-mechanical properties. Acknowledgements: This work has received funding from the European Union’s Horizon 2020 “Research and innovation programme” under grant agreement N°685594 (C3HARME

Introduction to H2020 project C3HARME – next generation ceramic composites for combustion harsh environment and space

There is an increasing demand for advanced materials with enhanced temperature capability in highly corrosive environments, for instance enable space vehicles to resist several launches and re-entries. The EU-funded project C3HARME aims at combining the best features of CMCs and UHTCs to design, develop, manufacture and qualify a new class of Ultra-High Temperature Ceramic Matrix Composite (UHTCMCs) with self-healing capabilities. Applications selected to implement the new materials are near-zero erosion nozzles and near-zero ablation thermal protection systems. This paper aims at giving an introduction to the challenges addressed by C3HARME project including (i) the integration between well-established and novel techniques for CMCs and UHTCs production, (ii) the need for very high temperature characterisation, (iii) the meaning of self-healing capability for UHTCMCs, (iv) the contribution of modelling to materials development and (V) the investigation of the microstructure/ thermo-mechanical property correlations

Processing and characterization of layered UHTCMCs reinforced with continuous or discontinuous carbon fibers

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3D Virtual Modeling for Morphological Characterization of Pituitary Tumors: Preliminary Results on Its Predictive Role in Tumor Resection Rate

Among potential factors affecting the surgical resection in pituitary tumors, the role of tumor three-dimensional (3D) features is still unexplored. The aim of this study is to introduce the use of 3D virtual modeling for geometrical and morphological characterization of pituitary tumors and to evaluate its role as a predictor of total tumor removal. A total of 75 patients operated for a pituitary tumor have been retrospectively reviewed. Starting from patient imaging, a 3D tumor model was reconstructed, and 3D characterization based on tumor volume (Vol), area, sphericity (Spher), and convexity (Conv) was provided. The extent of tumor removal was then evaluated at post-operative imaging. Mean values were obtained for Vol (9117 +/- 8423 mm(3)), area (2352 +/- 1571 mm(2)), Spher (0.86 +/- 0.08), and Conv (0.88 +/- 0.08). Total tumor removal was achieved in 57 (75%) cases. The standard prognostic Knosp grade, Vol, and Conv were found to be independent factors, significantly predicting the extent of tumor removal. Total tumor resection correlated with lower Knosp grades (p = 0.032) and smaller Vol (p = 0.015). Conversely, tumors with a more irregular shape (low Conv) have an increased chance of incomplete tumor removal (p = 0.022). 3D geometrical and morphological features represent significant independent prognostic factors for pituitary tumor resection, and they should be considered in pre-operative planning to allow a more accurate decision-making process

Study of molecular mechanisms of pro-apoptotic activity of NCX 4040, a novel nitric oxide-releasing aspirin, in colon cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Despite numerous studies aimed at verifying the antitumor activity of nitric oxide-releasing nonsteroidal antiflammatory drugs (NO-NSAIDs), little is known about the molecular targets responsible for their antineoplastic properties. In the present study, we investigated the mechanisms underlying the cytotoxicity of NCX 4040, a novel NO-aspirin with promising antineoplastic action, in <it>in vitro </it>human colon cancer models.</p> <p>Methods</p> <p>The effect on tumor growth was evaluated in four human colon cancer cell lines (LoVo, LRWZ, WiDr and LoVo Dx) by sulforhodamine B assay, oxidative stress by immunohistochemistry, apoptosis by laddering assay, mitochondrial membrane potential (ΔΨ_m) by flow cytometry, and apoptosis- and chemoresistance-related markers by western-blot and real-time method, respectively. Prostaglandin E₂levels were determined by ELISA.</p> <p>Results</p> <p>NCX 4040 produced a higher cytotoxic effect in all the cell lines than that produced by other NO donors tested. In particular, in LoVo and LRWZ cells, NCX 4040 induced a cytocidal effect and apoptosis through p53 and NAG-1 expression, an early ΔΨ_mcollapse, and a sequential release of cytoplasmatic cytochrome c and caspase -9 and -3 active forms. 8-hydroxyguanine lesions, indicative of oxidative stress, were also observed. Conversely, in WiDr line, the drug caused a cytocidal effect, albeit not through apoptosis, and a concomitant increase in COX-2 activity. In LoVo Dx line, characterized by high levels drug resistance and DNA repair-related markers, only a cytostatic effect was observed, again in concomitance with the increase in COX-2 enzyme activity.</p> <p>Conclusion</p> <p>This study highlights the multiplicity of mechanisms involved in sensitivity or resistance to NCX 4040 and could provide useful indications for tailored therapy by identifying potentially drug-responsive tumors.</p

KRAS, BRAF and PIK3CA status in squamous cell anal carcinoma (SCAC)

Anti-EGFR therapy appears to be a potential treatment option for squamous cell anal carcinoma (SCAC). KRAS mutation is a rare event in SCAC, indicating the absence of the principal mechanism of resistance to this type of therapy. However, no information is available from the literature regarding the status of BRAF or PIK3CA in this cancer type. We analysed KRAS, BRAF and PIK3CA status in SCAC patients in relation to the clinical-pathological characteristics of patients and to the presence of the human papilloma virus (HPV). One hundred and three patients were treated with the Nigro scheme for anal cancer from March 2001 to August 2012. Fifty patients were considered for the study as there was insufficient paraffinembedded tumour tissue to perform molecular analysis the remaining 53. DNA was extracted from paraffin-embedded sections. KRAS, BRAF and PIK3CA gene status and HPV genotype were evaluated by pyrosequencing. KRAS and BRAF genes were wild-type in all cases. Conversely, PIK3CA gene was found to be mutated in 11 (22%) cases. In particular, 8 mutations occurred in exon 9 and 3 in exon 20 of the PIK3CA gene. These findings suggest that SCAC could potentially respond to an anti-EGFR drug. PIK3CA mutation may be involved in the process of carcinogenesis in some cases of SCAC. \ua9 2014 Casadei Gardini et al