Seismic Assessment and Strengthening Interventions of Atop Single-Block Rocking Elements in Monumental Buildings: the Case Study of the San Felice sul Panaro Fortress

The paper describes the seismic assessment of the San Felice sul Panaro Fortress (Italy), focusing the attention on the activation of the out-of-plane response of the North walkway, characterized by the presence of an apparatus of merlons which highlighted a significant damage after the Emilia earthquake (2012). Nonlinear kinematic analyses have been performed, referring to a macro-block model and considering both the original configuration and two different possible strengthened strategies. For the definition of the seismic input in terms of floor spectra, the analyses also benefitted from the results obtained for the global response through a detailed 3D model of the whole fortress. The results were coherent with the observed damage after the seismic event, highlighting in this way the reliability of the adopted modelling strategies and analysis method, and allowed to outline possible strengthening solutions targeted to minimize the impact on the monument and guarantee its preservation

Spin dynamics in molecular ring nanomagnets: Significant effect of acoustic phonons and magnetic anisotropies

The nuclear spin-lattice relaxation rate 1/T_1_ is calculated for magnetic ring clusters by fully diagonalizing their microscopic spin Hamiltonians. Whether the nearest-neighbor exchange interaction J is ferromagnetic or antiferromagnetic, 1/T_1_ versus temperature T in ring nanomagnets may be peaked at around k_B_T=|J| provided the lifetime broadening of discrete energy levels is in proportion to T^3^. Experimental findings for ferromagnetic and antiferromagnetic Cu^II^ rings are reproduced with crucial contributions of magnetic anisotropies as well as acoustic phonons.Comment: 5 pages with 5 figures embedded, to be published in J. Phys. Soc. Jpn. 75, No. 10 (2006

The Geometric Phase and Ray Space Isometries

We study the behaviour of the geometric phase under isometries of the ray space. This leads to a better understanding of a theorem first proved by Wigner: isometries of the ray space can always be realised as projections of unitary or anti-unitary transformations on the Hilbert space. We suggest that the construction involved in Wigner's proof is best viewed as an use of the Pancharatnam connection to ``lift'' a ray space isometry to the Hilbert space.Comment: 17 pages, Latex file, no figures, To appear in Pramana J. Phy

Thermal Transient Measurements of an Ultra-Low-Power MOX Sensor

This paper describes a system for the simultaneous dynamic control and thermal characterization of the heating of an Ultra Low Power (ULP) micromachined sensor. A Pulse Width Modulated (PWM) powering system has been realized using a microcontroller to characterize the thermal behavior of a device. Objectives of the research were to analyze the relation between the time period and duty cycle of the PWM signal and the operating temperature of such ULP micromachined systems, to observe the thermal time constants of the device during the heating phase and to measure the total thermal conductance. Constant target heater resistance experiments highlighted that an approximately constant heater temperature at regime can only be obtained if the time period of the heating signal is smaller than 50 s. Constant power experiments show quantitatively a thermal time constant that decreases during heating in a range from 2.3 ms to 2 ms as a function of an increasing temperature rise between the ambient and the operating temperature. Moreover, we calculated the total thermal conductance. Finally, repeatability of experimental results was assessed by guaranteeing the standard deviation of the controlled temperature which was within C in worst case conditions

CEA and CYFRA 21-1 as prognostic biomarker and as a tool for treatment monitoring in advanced NSCLC treated with immune checkpoint inhibitors

Aims: To assess prognostic value of pre-therapy carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1) blood levels in non-small cell lung cancer (NSCLC) patients treated with immune-checkpoint inhibitors (ICIs) and their early change as predictor of benefit. Materials and methods: This is a retrospective cohort study including patients with stage IIIB–IV NSCLC who received anti PD-1/PD-L1 in first or advanced lines of therapy in two institutions. A control cohort of patients treated only with chemotherapy has been enrolled as well. Results: A total of 133 patients treated with nivolumab or atezolizumab were included in the test set, 74 treated with pembrolizumab first line in the validation set and 89 in the chemotherapy only cohort. CYFRA 21-1 >8 ng/mL was correlated with overall survival (OS) in the test set, validation set and in univariate and multivariate analysis (pooled cohort hazard ratio (HR) 1.90, 95% confidence interval (CI) 1.24–2.93, p 0.003). Early 20% reduction after the third cycle was correlated with OS for CEA (HR 0.12; 95% CI 0.04–0.33; p < 0.001), and for CYFRA 21-1 (HR 0.19; 95% CI 0.07–0.55; p 0.002) Conclusions: CYFRA 21-1 pre-therapy assessment provides clinicians with relevant prognostic information about patients treated with ICI. CEA and CYFRA 21-1 repeated measures could be useful as an early marker of benefit

INTRAHEPATIC CHOLANGIOCARCINOMA DEVELOPMENT IN A PATIENT WITH A NOVEL BAP1 GERMLINE MUTATION AND LOW EXPOSURE TO ASBESTOS

BRCA1 associated protein-1 (BAP1) germline mutations define a novel hereditary cancer syndrome, namely BAP1 tumor predisposition syndrome (BAP1-TPDS), characterized by an increased susceptibility to develop different cancer types, including mesothelioma, uveal and cutaneous melanoma, renal cell carcinoma, and basal cell and squamous cell carcinoma. Currently, the role of BAP1 germline mutations in intrahepatic cholangiocarcinoma (iCCA) pathogenesis is less known. Here we report the first clinical case of a female patient who developed an iCCA when she was 47-years-old and was found to carry a novel germline mutation at a splicing site of exon 4 in BAP1 gene (NM_004656.4: c.255_255+6del). An accurate anamnesis revealed the absence of risk factors linked to iCCA development, except for a low occupational exposure to asbestos. In tumor tissue, BAP1 sequencing, multiplex ligation-dependent probe amplification and immunoistochemistry showed the loss of heterozygosity and lack of nuclear expression, suggesting that BAP1 wild-type allele and functional protein were lost in cancer cells, in line with the classical two-hit model of tumor suppressor genes. Further studies are needed to confirm whether iCCA may be included into BAP1-TPDS cancer phenotypes and whether minimal asbestos exposure may facilitate the development of this malignancy in individuals carrying BAP1 germline mutations

Percutaneous radiofrequency ablation in intrahepatic cholangiocarcinoma: a retrospective single-center experience

Background & aims: Very few data are available in literature about the role of radiofrequency ablation (RFA) in intrahepatic cholangiocarcinoma (ICC) and previous studies are mainly case reports and case series on a very small number of patients and nodules. In this study, we aimed to evaluate effectiveness and safety of RFA for the treatment of unresectable ICC. Methods: This is a retrospective observational cohort study comprising all consecutive patients treated with RFA for unresectable ICC at Policlinico Sant’Orsola Malpighi Hospital, Bologna, Italy. Primary endpoint was Local Tumor Progression-Free Survival (LTPFS) while Overall Survival (OS) was also assessed as secondary endpoint. Results: From January 2014 to June 2019, 29 patients with 117 nodules underwent RFA. Technique effectiveness 1 month after RFA was 92.3%; median LTPFS was 9.27 months. Univariate analysis and multivariate analysis showed that LTPFS was significantly related to tumor size ≥20 mm. At a median follow up of 39.9 months, median OS from the date of RFA was 27.5 months, with an OS of 89%, 45% and 11% at 1, 2 and 4 years, respectively. Number of overall lesions and the sum of their diameter at the moment of the first RFA significantly affected OS in multivariate analysis. Minor and major complication rates were 14% and 7%, respectively. Conclusion: Tumor size ≥20 mm was associated with lower LTPFS, representing a potential useful threshold value. A careful evaluation of tumor burden appears as a crucial element in choosing the best therapeutic strategy in unresectable ICC

Model Exact Low-Lying States and Spin Dynamics in Ferric Wheels; Fe6_6 to Fe12_{12}

Using an efficient numerical scheme that exploits spatial symmetries and spin-parity, we have obtained the exact low-lying eigenstates of exchange Hamiltonians for ferric wheels up to Fe$_{12}$. The largest calculation involves the Fe$_{12}$ ring which spans a Hilbert space dimension of about 145 million for M$_s$=0 subspace. Our calculated gaps from the singlet ground state to the excited triplet state agrees well with the experimentally measured values. Study of the static structure factor shows that the ground state is spontaneously dimerized for ferric wheels. Spin states of ferric wheels can be viewed as quantized states of a rigid rotor with the gap between the ground and the first excited state defining the inverse of moment of inertia. We have studied the quantum dynamics of Fe$_{10}$ as a representative of ferric wheels. We use the low-lying states of Fe$_{10}$ to solve exactly the time-dependent Schr\"odinger equation and find the magnetization of the molecule in the presence of an alternating magnetic field at zero temperature. We observe a nontrivial oscillation of magnetization which is dependent on the amplitude of the {\it ac} field. We have also studied the torque response of Fe$_{12}$ as a function of magnetic field, which clearly shows spin-state crossover.Comment: Revtex, 24 pages, 8 eps figure

Subclinical liver fibrosis in patients with idiopathic 1 pulmonary fibrosis.

Background - Data on the presence of subclinical fibrosis across multiple organs in patients with idiopathic lung fibrosis (IPF) are lacking. Our study aimed at investigating through hepatic transient elastography (HTE) the prevalence and clinical impact of subclinical liver fibrosis in a cohort of patients with IPF. Methods - Patients referred to the Centre for Rare Lung Disease of the University Hospital of Modena (Italy) from March 2012 to February 2013with established diagnosis of IPF and without a documented history of liver diseases were consecutively enrolled and underwent HTE. Based on hepatic stiffness status as assessed through METAVIR score patients were categorized as \u201c with liver fibrosis \u201d (corresponding to a METAVIR score of F1-F4) and \u201c without liver fibrosis\u201d (METAVIR F0). Potential predictors of liver fibrosis were investigated through logistic regression model among clinical and serological variables. The overall survival (OS) was assessed according to liver fibrosis and multivariate Cox regression analysis was used to identify independent predictors. Results - In 13 out of 37 patients (35%) with IPF a certain degree of liver fibrosis was documented.No correlation was found between liver stiffness and clinical-functional parameters. OS was lower in patients \u2018 with liver fibrosis\u2019 than in patients \u2018 without liver fibrosis\u2019 (median months 33[23-55] vs. 63[26-94], p=0.038). Patients \u2018 with liver fibrosis\u2019 presented a higher risk of death at seven years as compared to patients \u2018without liver fibrosis\u2019 (HR=2.6, 95%CI[1.003\u20136.7],p= 0.049). Higher level of AST to platelet ratio Index (APRI)was an independent predictor of survival (HR=4.52 95%CI[1.3\u201315.6], p=0.02). Conclusions - In our cohort, more than one third of IPF patients had concomitant subclinical liver fibrosis that negatively affected OS. These preliminary claims further investigation aimed at clarifying the mechanisms beyond multiorgan fibrosis and its clinical implication in patients with IPF