Hindcast high-resolution simulation of the most catastrophic rainfall event in Genoa City (7-8 October 1970): hydro-meteorological and geomorphological analysis

Liguria region is historically affected by severe hydro-meteorological events often resulting in dramatic death tolls and large socio-economic impacts. On 7-8 October 1970, Genoa, region capital city, was struck by the most catastrophic flood event of its history. On the evening of 7 October pre-frontal storms affected the western side of the city (Voltri, Prà and Pegli municipalities), while on 8 October 1970 an anticyclone block generated recurring convective systems that hit Genoa city and above all the Bisagno Valley. The heavy rainfall continued more than 24 h with highs at Bolzaneto rain gauge (Polcevera Valley, northwest of Genoa city center) where over 950 mm of rainfall in 24 hours was measured. Over the city center and the Bisagno Valley, 400 mm in 24 h was recorded. The Bisagno stream channels overflowed, submerging the city center. The 1970 event in Genoa City was also the most dramatic in terms of damage: 44 fatalities occurred and over 2000 individuals were evacuated. This study hindcasts the meteorological evolution of this event at high spatial resolution (1.5 km) and temporal one (1 hour) using the Weather and Research Forecasting (WRF) model by downscaling the ERA5 climatology developed by European Center for Medium-Range Weather Forecast (ECMWF). The weather hindcast scenario is compared with available meteorological observations as well as with recorded geomorphological impacts on Genoa city center and municipalities

Takotsubo is not a cardiomyopathy

Unraveling the mechanisms underlying Takotsubo (TTS) leads to question the current inclusion of the condition within the spectrum of cardiomyopathies. Indeed, the clinical presentation and pathophysiology of TTS clearly differ from cardiomyopathies, i.e. diseases of heart muscle unexplained by abnormal loading conditions or coronary artery disease, which cannot recover spontaneously and may cause sudden death often in minimally symptomatic individuals or result in a gradual deterioration in ventricular function and end-stage heart failure. Furthermore, the term 'cardiomyopathy' can no longer be applied when functional or morphologic abnormalities of the coronary arteries leading to acute myocardial ischemia are deemed responsible for left ventricular (LV) systolic dysfunction. After 27years of investigation, time has come to recognize that patients with TTS do suffer from severe myocardial ischemia and fulfill all criteria of acute coronary syndromes, i.e. acute chest pain, typical electrocardiographic changes, cardiac troponin rise, as well as LV wall motion abnormalities. Accordingly, we propose that TTS should be labeled as an acute 'syndrome' to be included more appropriately within the spectrum of ischemic heart disease. With regard to the term 'stress', it may imply that the catecholamine surge is essential to produce the typical transient myocardial injury. Thus, the terminology 'Takotsubo (stress) syndrome' would more accurately reflect recent advances in the pathophysiology

The Impact of Right Coronary Artery Chronic Total Occlusion on Clinical Outcome of Patients Undergoing Percutaneous Coronary Intervention for Unprotected Left Main Disease

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Inflammatory and antioxidant pattern unbalance in "clopidogrel-resistant" patients during acute coronary syndrome.

Background. In acute coronary syndrome (ACS), inflammation and redox response are associated with increased residual platelet reactivity (RPR) on clopidogrel therapy. We investigated whether clopidogrel interaction affects platelet function and modulates factors related to inflammation and oxidation in ACS patients differently responding to clopidogrel. Material andMethods. Platelet aggregation was measured in 29 ACS patients on dual (aspirin/clopidogrel) antiplatelet therapy. Nonresponders (NR) were defined as RPR ≥70% by ADP. Several inflammatory and redox parameters were assayed and platelet proteome was determined. Results. Eight (28%) out of 29 ACS patients resulted NR to clopidogrel. At 24 hours, the levels of Th2-type cytokines IL-4, IFN, andMCP-1 were higher in NR, while blood GSH (r-GSHbl) levels were lower in NR than responders (R). Proteomic analysis evidenced an upregulated level of platelet adhesion molecule, CD226, and a downregulation of the antioxidant peroxiredoxin-4. In R patients the proinflammatory cytokine IL-6 decreased, while the anti-inflammatory cytokine IL-1Ra increased. Conclusions. In patients with high RPR on clopidogrel therapy, an unbalance of inflammatory factors, platelet adhesion molecules, and circulatory and platelet antioxidantmolecules was observed during the acute phase. Proinflammatory milieu persists in nonresponders for a long time after the acute event while antioxidant blood factors tend to conform to normal responsiveness

Integration of Spatial Distortion Effects in a 4D Computational Phantom for Simulation Studies in Extra-Cranial MRI-guided Radiation Therapy: Initial Results.

PurposeSpatial distortions in magnetic resonance imaging (MRI) are mainly caused by inhomogeneities of the static magnetic field, nonlinearities in the applied gradients, and tissue‐specific magnetic susceptibility variations. These factors may significantly alter the geometrical accuracy of the reconstructed MR image, thus questioning the reliability of MRI for guidance in image‐guided radiation therapy. In this work, we quantified MRI spatial distortions and created a quantitative model where different sources of distortions can be separated. The generated model was then integrated into a four‐dimensional (4D) computational phantom for simulation studies in MRI‐guided radiation therapy at extra‐cranial sites.MethodsA geometrical spatial distortion phantom was designed in four modules embedding laser‐cut PMMA grids, providing 3520 landmarks in a field of view of (345 × 260 × 480) mm3. The construction accuracy of the phantom was verified experimentally. Two fast MRI sequences for extra‐cranial imaging at 1.5 T were investigated, considering axial slices acquired with online distortion correction, in order to mimic practical use in MRI‐guided radiotherapy. Distortions were separated into their sources by acquisition of images with gradient polarity reversal and dedicated susceptibility calculations. Such a separation yielded a quantitative spatial distortion model to be used for MR imaging simulations. Finally, the obtained spatial distortion model was embedded into an anthropomorphic 4D computational phantom, providing registered virtual CT/MR images where spatial distortions in MRI acquisition can be simulated.ResultsThe manufacturing accuracy of the geometrical distortion phantom was quantified to be within 0.2 mm in the grid planes and 0.5 mm in depth, including thickness variations and bending effects of individual grids. Residual spatial distortions after MRI distortion correction were strongly influenced by the applied correction mode, with larger effects in the trans‐axial direction. In the axial plane, gradient nonlinearities caused the main distortions, with values up to 3 mm in a 1.5 T magnet, whereas static field and susceptibility effects were below 1 mm. The integration in the 4D anthropomorphic computational phantom highlighted that deformations can be severe in the region of the thoracic diaphragm, especially when using axial imaging with 2D distortion correction. Adaptation of the phantom based on patient‐specific measurements was also verified, aiming at increased realism in the simulation.ConclusionsThe implemented framework provides an integrated approach for MRI spatial distortion modeling, where different sources of distortion can be quantified in time‐dependent geometries. The computational phantom represents a valuable platform to study motion management strategies in extra‐cranial MRI‐guided radiotherapy, where the effects of spatial distortions can be modeled on synthetic images in a virtual environment

Bleeding events and maintenance dose of prasugrel: BLESS pilot study

OBJECTIVE: To evaluate changes in residual platelet reactivity (RPR) over time, and bleeding and ischaemic events rate using 5 vs 10 mg maintenance dose (MD) regimens of prasugrel 1 month after acute coronary syndrome (ACS). BACKGROUND: The optimal level of RPR with prasugrel may change over time after an ACS. METHODS: After 60 mg loading dose of prasugrel (T0) followed by 10 mg/day for 1 month, patients were randomised to receive prasugrel 10 mg/day (n=95, group A) or 5 mg/day MD (n=98, group B) up to 1 year. RPR was assessed at T0, 37 (T1) and 180 days (T2). The primary end point was Bleeding Academic Research Consortium (BARC) bleeding events ≥2 between 1 and 12 months, and the secondary composite end point was cardiac death, myocardial infarction, stroke and definite/probable stent thrombosis. RESULTS: From T0 to T1, RPR significantly increased in both groups A and B and the increase was higher for group B (δ ADP 10 µmol: 13.8%±14.7% vs 23.5%±19.2%, p=0.001). At T2 a lower rate of high RPR patients were found in group A (2.6% vs13.3%; p=0.014). The BARC type ≥2 bleeding occurred in 12.6% of group A versus 4.1% of group B (OR 0.29, 95% CI 0.09 to 0.94) and secondary end point in 2.1% vs 1.0% (p=0.542), respectively, without stent thrombosis. CONCLUSIONS: RPR increases shifting from 60 mg loading dose to 10 mg/day prasugrel MD with a further increase of RPR reducing prasugrel MD to 5 mg 1 month after ACS. Clinical value of these pharmacodynamic findings should be proved in larger clinical trials. TRIAL REGISTRATION NUMBER: NCT01790854