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Purpose:Metastasis requires malignant cell circulation from the primary to a distant tissue. Elevated levels of circulating tumor cells (CTC) portend a poor prognosis in breast and other cancers. Recent studies have suggested that CTC clusters may be a factor in the metastatic process. We conducted a prospective retrospective study of the SWOG0500 clinical trial to test whether CTC clusters are associated with poorer prognosis.Experimental Design:CTC CellSearch galleries from SWOG0500 trial were reread using prespecified criteria for CTC clusters, doublets, and enumeration. Survival analysis methods include Kaplan–Meier plots and log-rank tests.Results:Patients were classified into three prognostic subgroups based on baseline CTC/7.5 mL whole blood (WB): Arm A: P < 0.0001). Furthermore, doublets or clusters were significantly more common in patients who were ultimately assigned to Arm C versus B (54% vs. 25%; P < 0.0001). In Arm C, doublets and clusters were associated with worse overall survival than only doublets, clusters, or no doublets nor clusters at baseline (P = 0.008) and first follow-up (P = 0.010). When compared with enumeration alone, doublets, clusters, or both were not prognostic in patients who had 5–19 or ≥20 CTC/7.5 mL WB.Conclusions:In patients with metastatic breast cancer starting first-line chemotherapy, mortality is independent of the presence of CTC clusters, but rather depends on the number of CTC/7.5 mL WB.

Supplementary Figures: Supplementary Figure 1. Summary of duration on AZD9496 therapy, previous therapies, and circulating biomarkers status at baseline for each patient ranked by ascending dose; Supplementary Figure 2. Tumor pharmacodynamics. Supplementary Tables: Supplementary Table 1. Study Plan showing time-points of collection of biosamples for exploratory research; Supplementary Table 2. ddPCR primers and probes;Supplementary Table 3. Antibodies and conditions for IHC analysis Antibodies for IHC analysis; Supplementary Table 4. Patients with {greater than or equal to}1 CTC/7.5 mL WB within 120 days of fulvestrant wash-out period prior C1D1.

Purpose:Common resistance mechanisms to endocrine therapy (ET) in estrogen receptor (ER)–positive metastatic breast cancers include, among others, ER loss and acquired activating mutations in the ligand-binding domain of the ER gene (ESR1LBDm). ESR1 mutational mediated resistance may be overcome by selective ER degraders (SERD). During the first-in-human study of oral SERD AZD9496, early changes in circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) were explored as potential noninvasive tools, alongside paired tumor biopsies, to assess pharmacodynamics and early efficacy.Experimental Design:CTC were enumerated/phenotyped for ER and Ki67 using CellSearch in serial blood draws. ctDNA was assessed for the most common ESR1LBDm by droplet digital PCR (BioRad).Results:Before starting AZD9496, 11 of 43 (25%) patients had ≥5 CTC/7.5 mL whole blood (WB), none of whom underwent reduction to +, two of whom had CTC-ER+ reduction. CTC-Ki67 status did not change appreciably. Patients with ≥5 CTC/7.5 mL WB before treatment had worse progression-free survival (PFS) than patients with P = 0.0003). Fourteen of 45 (31%) patients had ESR1LBDm+ ctDNA at baseline, five of whom had ≥2 unique mutations. Baseline ESR1LBDm status was not prognostic. Patients with persistently elevated CTC and/or ESR1LBDm+ ctDNA at C1D15 had worse PFS than patients who did not (P = 0.0007).Conclusions:Elevated CTC at baseline was a strong prognostic factor in this cohort. Early on-treatment changes were observed in CTC-ER+ and ESR1LBDm+ ctDNA, but not in overall CTC number. Integrating multiple biomarkers in prospective trials may improve outcome prediction and ET resistance mechanisms' identification over a single biomarker.

PURPOSE Circulating tumor cells (CTCs) are strongly prognostic for overall survival (OS) in metastatic breast cancer although additional prognostic biomarkers are needed. We evaluated the complementary prognostic value of tumor‐derived extracellular vesicles (tdEVs) next to CTCs. METHODS We applied the open-source ACCEPT software to archived CellSearch images from the prospective clinical trial SWOG0500 to enumerate CTCs and tumor-derived extracellular vesicles (tdEVs) before and after one cycle of chemotherapy. RESULTS CTCs enumerated by ACCEPT were strongly correlated with classical ocular enumeration (correlation r = 0.98). OS was worse with elevated tdEVs (median OS for high/medium/low groups: 17.1 v 29.0 v 43.3 months; P < .0001). In patients with longer OS by CTC counts (< 5 CTC/7.5 mL blood), elevated tdEV levels were independently associated with poorer OS (multivariable analysis P < .001). OS was also longer for patients with low tdEVs after one cycle of chemotherapy (median OS for high/medium/low group: 10.8 v 17.8 v 26.7; P < .0001). CONCLUSION This study highlights the complementary prognostic significance of tdEVs in metastatic breast cancer before and after one cycle of chemotherapy.

We report the rate of cosmic ray air showers with multiplicities exceeding 15 muon tracks recorded in the NOvA Far Detector between May 2016 and May 2018. The detector is located on the surface under an overburden of 3.6 meters water equivalent. We observe a seasonal dependence in the rate of multiple-muon showers, which varies in magnitude with multiplicity and zenith angle. During this period, the effective atmospheric temperature and surface pressure ranged between 210 K and 230 K and 940 mbar and 990 mbar, respectively; the shower rates are anticorrelated with the variation in the effective temperature. The variations are about 30% larger for the highest multiplicities than the lowest multiplicities and 20% larger for showers near the horizon than vertical showers.

Circulating tumor cells (CTC) are prognostic in metastatic breast cancer (MBC). The CTC-endocrine therapy index (CTC-ETI), consisting of CTC-ER (estrogen receptor), BCL2, human epidermal growth factor receptor (HER2), and Ki67 expression, might predict resistance to endocrine therapy (ET) in patients with ER-positive MBC. One hundred twenty-one patients with ER-positive/HER2-negative MBC initiating a new ET after ≥1 lines of ET were enrolled in a prospective, multi-institutional clinical trial. CTC-ETI and clinical/imaging follow-up were performed at baseline and serial time points. Progression-free survival (PFS) and rapid progression (RP; determined at the 3-month time point) were primary endpoints. Associations with clinical outcomes used logrank and Fisher’s exact tests. At baseline, 36% (38/107) of patients had ≥5 CTC/7.5 ml whole blood (WB). Patients with ≥5 vs. P = 0.03). Elevated CTC at 1 month was associated with even worse PFS (1.9 vs. 5.0 months from the 1-month sample, P P = 0.008). Patients with high vs. low CTC and CTC-ETI more frequently experienced RP (CTC: 66% vs. 41%; P = 0.03; CTC-ETI: 79% vs. 40%; P = 0.002). In conclusion, CTC enumeration and the CTC-ETI assay are prognostic at baseline and follow-up in patients with ER-positive/HER2-negative MBC starting new ET. CTC at first follow-up might identify a group of patients with ER-positive MBC that could forego ET, but CTC-ETI did not contribute further.

This Letter reports results from the first long-baseline search for sterile antineutrinos mixing in an accelerator-based antineutrino-dominated beam. The rate of neutral-current interactions in the two NOvA detectors, at distances of 1 km and 810 km from the beam source, is analyzed using an exposure of $12.51\times10^{20}$ protons-on-target from the NuMI beam at Fermilab running in antineutrino mode. A total of $121$ of neutral-current candidates are observed at the Far Detector, compared to a prediction of $122\pm11$(stat.)$\pm15$(syst.) assuming mixing between three active flavors. No evidence for $\bar{\nu}_{\mu}\rightarrow\bar{\nu}_{s}$ oscillation is observed. Interpreting this result within a 3+1 model, constraints are placed on the mixing angles ${\theta}_{24} < 25^{\circ}$ and ${\theta}_{34} < 32^{\circ}$ at the 90% C.L. for $0.05$eV$^{2} \leq \Delta m^{2}_{41} \leq 0.5$eV$^{2}$, the range of mass splittings that produces no significant oscillations at the Near Detector. These are the first 3+1 confidence limits set using long-baseline accelerator antineutrinos., Comment: 8 pages, 4 figures

Clinical decisions for precision and immuno-oncology therapies are based on predictive biomarkers commonly obtained from a single metastatic biopsy, or from archived primary tumor material. Circulating genomic biomarkers present a minimally invasive way to monitor the intra-patient tumor heterogeneity and its fluctuations in order to provide a real-time evaluation of the changing clonal architecture with potential therapeutic implications. Single-cell DNA next generation sequencing (scNGS) of circulating tumor cells (CTC) is a particularly well-suited method of unraveling and monitoring that heterogeneity to complement biomarker information obtained from tissue and cell-free circulating tumor DNA (ctDNA). In this proof-of-concept study we analyzed 123 CTC, 15 white blood cells (WBC), and ctDNA from 15 CTC-positive lobular breast cancer patients, five of whom had CTC available at both metastatic baseline and after progression on a variety of therapies chosen at their physician’s discretion. CTC were enriched with the CellSearch® system and isolated as single cells with the DEPArray™ system. Whole genome amplified CTC DNA underwent scNGS with the Oncomine Comprehensive Assay covering ~500 genes and 1.1Mb of genomic space to detect mutations, copy number alterations, tumor mutation burden (TMB) and microsatellite instability (MSI). 99.1% of cells were informative, with a mean sequencing depth of 664x. Using our previously developed, CTC-based precision medicine reporting platform, MI-CTCSeq, multiple CTC in seven of 15 patients (47%) had mutations that were actionable by FDA-approved targeted therapies including in the oncogenes PIK3CA (alpelisib) and FGFR2 (erdafitinib). 13 patients (87%) displayed intra-patient, inter-CTC genomic heterogeneity of putative driver mutations. Two of five (40%) patients with CTC at both baseline and progression displayed fluctuations in their CTC subclonal makeup between timepoints. One of the two harbored a baseline ESR1 (estrogen receptor α) p.D538G activating mutation that largely disappeared at progression and was replaced by a CTC subclone with a different ESR1 activating mutation, p.Y537S. Intriguingly, this patient’s CTC also harbored an FGFR2 p.K659M mutation in an actionable “hotspot” at progression, which was absent at baseline, suggesting potential utility of serial monitoring by CTC scNGS. TMB scores and MSI status in CTC were highly concordant with those measured in clinical tissue biopsies. Taken together, these data suggest the non-invasive interrogation of the CTC genomic landscape and its serial monitoring to inform precision and immuno-oncology treatments in real time. Citation Format: Andi K. Cani, Emily M. Dolce, Elizabeth P. Darga, Kevin Hu, Chia-Jen Liu, James M. Rae, Daffyd G. Thomas, Scott A. Tomlins, Arul M. Chinnaiyan, Aaron M. Udager, Costanza Paoletti, Erin F. Cobain, Daniel F. Hayes. Serial monitoring of single-cell circulating tumor cell genomics in metastatic lobular breast cancer to identify precision and immuno-oncology biomarkers with therapeutic implications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1700.

The success of immune checkpoint inhibitors rests on biomarkers such as tumor mutation burden (TMB) and microsatellite instability (MSI), both FDA-approved predictors of anti PD-1/L1 therapy benefit. Tissue biopsies often collected once in the metastatic setting through an invasive procedure, or archived primary tumor tissue often collected much prior to treatment consideration, are the specimen types of choice for biomarker identification. The tissue sample originates from a limited region of one disease site, which may limit its usefulness given intra-patient tumor heterogeneity. TMB and MSI measurement by liquid biopsy, including proteins, circulating tumor cells (CTC), and cell-free circulating tumor DNA (ctDNA), is an attractive, minimally-invasive way to obtain a real-time picture of the entire disease. While TMB and MSI assessment from ctDNA have been reported, their measurement can be limited by low ctDNA tumor fraction. Single-cell next generation sequencing of CTC, on the other hand, is a particularly well-suited, but largely unexplored method of measuring TMB and MSI to complement tissue and ctDNA for better overall specificity of detection. In this proof-of-concept study, we show the ability to detect single-cell TMB and MSI. We analyzed 14 CTC and 4 ctDNA samples from 6 metastatic breast cancer patients, as well as 3 single cells and 1 cell pellet sample each from HCT-116 (MSI-High) and WiDr (MSI-Low) cell lines. CTC and cell line cells were enriched with the CellSearch® system and/or isolated with the DEPArray™ system. Whole genome amplified single-cell DNA was sequenced with the Oncomine Comprehensive Assay covering ~500 genes and 1.1Mb of genomic space. TMB and MSI scores obtained in CTC and ctDNA were compared to those measured in matched clinical tissue biopsies. Single-cell TMB scores and MSI status were assessable in all CTC tested. CTC TMB scores were highly concordant with the matched tissue samples (r=1.00), as were ctDNA TMB scores (r=0.98) in patients with assessable TMB scores in both biospecimen types compared. Importantly, TMB was detectable in CTC from one patient whose tissue sample was inadequate for clinical sequencing, and from another patient with inadequate, low tumor fraction ctDNA. Intriguingly, one patient harbored 3 TMB-high and 2 TMB-low CTC, potentially indicating intra-patient TMB heterogeneity. The known MSI-low status from clinical tumor tissue sequencing was correctly detected in CTC and ctDNA from all patients. MSI status and scores from single cells of HCT-116 and WiDr cell lines purified with the DEPArray™ system (mimicking CTC isolation), perfectly matched that of the corresponding cell pellet samples (r=1.00). Taken together, these data suggest the potential validity and continued interrogation of potential utility of CTC TMB and MSI detection to complement tissue and ctDNA in guiding checkpoint inhibitor immunotherapy. Citation Format: Andi K. Cani, Emily M. Dolce, Chia-Jen Liu, Brittany Rupp, Elizabeth P. Darga, Costanza Paoletti, Dafydd G. Thomas, Yi-Mi Wu, Dan R. Robinson, Sunitha Nagrath, Arul M. Chinnaiyan, Scott A. Tomlins, Aaron M. Udager, John M. Carethers, Erin F. Cobain, Daniel F. Hayes. Assessment of tumor mutation burden and microsatellite instability by single-cell circulating tumor cell genomic profiling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 611.

Aims: Outdoor play, physical activity, and social cohesion are crucial indicators of community health. PlayStreets, a street play initiative to engage local children and families in outdoor play, physical activity, and social interactions, were implemented in a low-income neighborhood in Columbus, Ohio throughout the summer of 2019. This article aims to describe the implementation of a hospital-sponsored PlayStreets model executed through support from a community health initiative and to assess neighborhood impact through parent and child surveys. Methods: Approximately 350 children attended the events and 69 surveys were collected. Descriptive statistics were used to analyze survey data. Results: The mean age of children was 7 years, and the majority of children who attended were male. If not for PlayStreets, 55% of caregivers reported that their children would be inside. Event satisfaction levels were high, and 54% of caregivers said that they had more contact with their neighbors because of the events. Conclusions: Hospital buy-in and community support were crucial to the success of the event. We found that this model can successfully engage the local community while increasing opportunity for childhood outdoor play, physical activity, and neighborhood social interaction.

Background Immune checkpoint inhibition is effective in several cancers. Expression of programmed death-ligand 1 (PD-L1) on circulating tumor or immune effector cells could provide insights into selection of patients for immune checkpoint inhibition. Methods Whole blood was collected at serial timepoints from metastatic breast cancer patients and healthy donors for circulating tumor cell (CTC) and platelet PD-L1 analysis with a phycoerythrin-labeled anti-human PD-L1 monoclonal antibody (Biolegend clone 29E.2A3) using the CellSearch® assay. CTC PD-L1 was considered positive if detected on at least 1% of the cells; platelet PD-L1 was considered positive if ≥100 platelets per CellSearch frame expressed PD-L1. Results A total of 207 specimens from 124 metastatic breast cancer patients were collected. 52/124 (42%) samples at timepoint-1 (at or close to time of progressive disease) had ≥5 CTC/7.5ml whole blood. Of those, 21 (40%) had positive CTC PD-L1. In addition, platelet PD-L1 expression was observed in 35/124 (28%) at timepoint-1. Platelet PD-L1 was not detected in more than 70 specimens from 12 healthy donors. Platelet PD-L1 was associated with ≥5 CTC/7.5ml whole blood (p = 0.0002), less likely in patients with higher red blood cell counts (OR = 0.72, p Conclusion PD-L1 expression was found in metastatic breast cancer patients on both CTC and platelets in an independent fashion. Inter-patient platelet PD-L1 expression was highly heterogeneous suggesting that it is a biological event associated with cancer in some but not all patients. Taken together, our data suggest that CTC and platelet PD-L1 expression could play a role in predicting which patients should receive immune checkpoint inhibition and as a pharmacodynamics biomarker during treatment.

The reconstruction process of residential buildings of historical centers damaged by L'Aquila 2009 earthquake started from August 2012 with the emanation of Law n.134/2012. With this law, the Special Offices for the Reconstruction of the city of L'Aquila (USRA) and the Municipalities of the Crater (USRC) were established. Each office developed a parametric model to manage the reconstruction and to define the maximum public grant to repair and strengthen the damaged buildings. The public grant was released according to funding requests made by practitioners. The parametric models were necessary to take into account the peculiarities of the buildings of the historical centres, which are grouped in such a way as to form complex agglomerates of buildings, called building aggregates (namely AE) made by Aggregate Minimum Unit (namely UMI) in turn made by several buildings (ED). The paper deals with the reconstruction models adopted by the two offices, the analysis of building characteristics and repair/strengthening intervention as well as data actual costs data obtained by funding requests. Furthermore, a comparison between the main statistics related to the damage, reconstruction procedures and peculiarities of residential buildings outside historical centers and inside historical centers is herein presented

Purpose: Metastasis requires malignant cell circulation from the primary to a distant tissue. Elevated levels of circulating tumor cells (CTC) portend a poor prognosis in breast and other cancers. Recent studies have suggested that CTC clusters may be a factor in the metastatic process. We conducted a prospective retrospective study of the SWOG0500 clinical trial to test whether CTC clusters are associated with poorer prognosis. Experimental Design: CTC CellSearch galleries from SWOG0500 trial were reread using prespecified criteria for CTC clusters, doublets, and enumeration. Survival analysis methods include Kaplan–Meier plots and log-rank tests. Results: Patients were classified into three prognostic subgroups based on baseline CTC/7.5 mL whole blood (WB): Arm A: Conclusions: In patients with metastatic breast cancer starting first-line chemotherapy, mortality is independent of the presence of CTC clusters, but rather depends on the number of CTC/7.5 mL WB.

Purpose:Common resistance mechanisms to endocrine therapy (ET) in estrogen receptor (ER)–positive metastatic breast cancers include, among others, ER loss and acquired activating mutations in the ligand-binding domain of the ER gene (ESR1LBDm). ESR1 mutational mediated resistance may be overcome by selective ER degraders (SERD). During the first-in-human study of oral SERD AZD9496, early changes in circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) were explored as potential noninvasive tools, alongside paired tumor biopsies, to assess pharmacodynamics and early efficacy.Experimental Design:CTC were enumerated/phenotyped for ER and Ki67 using CellSearch in serial blood draws. ctDNA was assessed for the most common ESR1LBDm by droplet digital PCR (BioRad).Results:Before starting AZD9496, 11 of 43 (25%) patients had ≥5 CTC/7.5 mL whole blood (WB), none of whom underwent reduction to Conclusions:Elevated CTC at baseline was a strong prognostic factor in this cohort. Early on-treatment changes were observed in CTC-ER+ and ESR1LBDm+ ctDNA, but not in overall CTC number. Integrating multiple biomarkers in prospective trials may improve outcome prediction and ET resistance mechanisms' identification over a single biomarker.

The single-phase liquid argon time projection chamber (LArTPC) provides a large amount of detailed information in the form of fine-grained drifted ionization charge from particle traces. To fully utilize this information, the deposited charge must be accurately extracted from the raw digitized waveforms via a robust signal processing chain. Enabled by the ultra-low noise levels associated with cryogenic electronics in the MicroBooNE detector, the precise extraction of ionization charge from the induction wire planes in a single-phase LArTPC is qualitatively demonstrated on MicroBooNE data with event display images, and quantitatively demonstrated via waveform-level and track-level metrics. Improved performance of induction plane calorimetry is demonstrated through the agreement of extracted ionization charge measurements across different wire planes for various event topologies. In addition to the comprehensive waveform-level comparison of data and simulation, a calibration of the cryogenic electronics response is presented and solutions to various MicroBooNE-specific TPC issues are discussed. This work presents an important improvement in LArTPC signal processing, the foundation of reconstruction and therefore physics analyses in MicroBooNE., Comment: 54 pages, 36 figures; the first part of this work can be found at arXiv:1802.08709

Ischia Island is a densely populated volcanic area located in the North-Western sector of the Gulf of Napoli (South Italy), whose activity is characterized by eruptions (the last one occurred in 1302 A.D.), earthquakes (the most disastrous ones occurred in 1881 and in 1883), fumarolic-hydrothermal manifestations and ground deformation. In this work we carry out the surface deformation time-series analysis occurring at the Island by jointly exploiting data collected via two different monitoring systems. In particular, we take advantage from the large amount of periodic and continuous geodetic measurements collected by the GPS (campaign and permanent) stations deployed on the Island and belonging to the INGV-OV monitoring network. Moreover, we benefit from the large, free and open archive of C-band SAR data acquired over the Island by the Sentinel-1 constellation of the Copernicus Program, and processed via the advanced Differential SAR Interferometry (DInSAR) technique referred to as Small BAseline Subset (SBAS) algorithm [Berardino et al., 2002]. We focus on the 2014-2017 time period to analyze the recent surface deformation phenomena occurring on the Island, thus extending a previous study aimed at investigating the temporal evolution of the ground displacements affecting the Island and limited to the 1992-2003 time interval [Manzo et al., 2006]. The performed integrated analysis provides relevant spatial and temporal information on the Island surface deformation pattern. In particular, it reveals a rather complex deformative scenario, where localized phenomena overlap/interact with a spatially extended deformation pattern that involves many Island sectors, with no evidence of significant uplift phenomena. Moreover, it shows a good agreement and consistency between the different kinds of data, thus providing a clear picture of the recent dynamics at Ischia Island that can be profitably exploited to deeply investigate the physical processes behind the observed deformation phenomena.

There are experimental data which suggest that the primary immune effector cell responsible for maintaining immune surveillance against the outgrowth of EBV-transformed B cells in humans is the CTL, but in vivo proof of this is lacking. In this study we perform a series of cellular and molecular assays to characterize an autologous, endogenous immune response against a transplantation-associated, monoclonal, EBV+ posttransplant lymphoproliferative disorder (PTLD). Following allogeneic bone marrow transplantation, a patient developed a monoclonal PTLD of donor B cell origin. With a decrease in immune suppression, we document the emergence of endogenous, donor-derived CD3+CD8+ CTLs, followed by regression of the PTLD. The TCR Vβ repertoire went from a polyclonal pattern prior to the development of PTLD to a restricted TCR Vβ pattern during the outgrowth and regression of PTLD. Donor-derived CD3+CD8+ T lymphocytes displayed MHC class I-restricted cytolytic activity against the autologous EBV+ B cells ex vivo without additional in vitro sensitization. The striking temporal relationship between the endogenous expansion of a TCR Vβ-restricted, CD3+CD8+ population of MHC class I-restricted CTL, and the regression of an autologous monoclonal PTLD, provides direct evidence in humans that endogenous CD3+CD8+ CTLs can be responsible for effective immune surveillance against malignant transformation of EBV+ B cells.

The growing need for alternative sources of transportation fuels encourages the development of new hydrotreatment catalysts. These catalysts must be active and more hydrogen efficient than the current commercial hydrotreatment catalysts. Molybdenum nitrides and carbides are attractive candidate materials possessing properties that are comparable or superior to those of commercial sulfide catalysts. This research investigated the catalytic properties of γ-Al2O3-supported molybdenum nitrides and carbides. These catalysts were synthesized via temperature-programmed reaction of supported molybdenum oxides with ammonia or methane/hydrogen mixtures. Phase constituents and compositions were determined by X-ray diffraction, elemental analysis, and neutron activation analysis. Oxygen chemisorption was used to probe the surface properties of the catalysts. Specific activities of the molybdenum nitrides and carbides were competitive with those of a commercial sulfide catalyst for hydrodenitrogenation (HDN), hydrodes...

Seismic vulnerability assessment of existing constructions is a key issue for seismic engineering, in particular for existing buildings with public functions. An accurate evaluation of seismic vulnerability for a certain construction can be achieved by numerical simulations. However, reliability of analyses is influenced by the level of knowledge in the case of existing buildings. If the level of knowledge is not accurate, results are affected by uncertainties at a higher degree. Knowledge about the dynamic behaviour of existing constructions can be improved by means of dynamic tests in operational conditions. They allow identification of fundamental dynamic properties of structures to be used, for instance, for calibration of numerical models. Development of output-only modal analysis techniques has made possible testing of large civil structures and infrastructures measuring the response to ambient vibration, thus overcoming the problem of input application and control on large civil structures and infrastructures. In the present paper, the main aspects related to the dynamic identification through Operational Modal Analysis (OMA) of a large steel building are reviewed. It belongs to a block of buildings identified as “D” in the area of the Guardia di Finanza Non-Commissioned Officers’ School “V. Giudice” in Coppito, L’Aquila, Italy. Tests were carried during the seismic crisis in Abruzzo, April 2009. The work herein described is a part of an extended experimental campaign carried out under the coordination of the Italian Civil Protection In particular, an extensive dynamic characterization of the constructions has been carried out to support inspections and provide information to the Civil Protection during post-mainshock emergency management of buildings and implementation of permanent monitoring systems. The description of such a complex activity is not however reported. Availability of experimental results represents a fundamental aid for accurate implementation and refinement of numerical models. In the present paper, after a short description of the tested building, details about test execution are given and the main identification results are illustrated. Furthermore, some results of the numerical modelling of the structure are reported and compared with experimental outcomes. 4 International Conference on Steel & Composite Structures Wednesday 21 – Friday 23 July 2010 Sydney, Australia

A seguito del terremoto che ha colpito il Molise nel 2002 la Regione ha avviato una campagna di indagini per la verifica delle condizioni di sicurezza sismico-statica degli edifici pubblici, con priorità per quelli scolastici, ai sensi della legge regionale n. 38/2002. L'intervento, nel marzo 2003, della OPCM 3274 è stata l'occasione che ha indotto la Regione Molise a coordinare ed indirizzare il lavoro di verifica avviato con apposite "Linee guida per la valutazione della vulnerabilità sismica degli edifici scolastici". L'obiettivo fissato per le indagini ha riguardato il controllo delle condizioni statiche e conservative degli edifici e la determinazione della vulnerabilità sismica degli stessi. Con tale finalità è stato stabilito lo svolgimento di una serie di attività, tra cui la ricerca dei documenti progettuali esecutivi e di collaudo e l'esecuzione di rilievi e prove per poter definire le caratteristiche della struttura e delle parti non strutturali che forniscono un contributo alla resistenza sismica. Nel presente lavoro è sintetizzata l'attività svolta e gli aspetti più significativi dell'intera esperienza di indagine, vengono presentati alcuni risultati parziali relativi alle scuole indagate per l'intera regione e i criteri assunti per la formazione di graduatorie di intervento e la determinazione dei relativi costi. Viene infine illustrata l'applicazione delle linee guida ad un edificio scolastico in muratura ubicato nel Comune di Morrone del Sannio (CB), danneggiato dal sisma del 2002, per il quale è stata scelta la soluzione della demolizione e della ricostruzione adottando una struttura in cemento armato su isolatori sismici.

A seguito del terremoto del 2002, la Regione Molise ha promosso un'indagine sulle condizioni di sicurezza sismico-statica degli edifici scolastici. L'operazione ha previsto l'espletamento di incarichi professionali per l'esecuzione di indagini ed analisi strutturali per consentire alla Regione di acquisire una conoscenza organica delle condizioni di rischio delle strutture scolastiche, indispensabile per formulare programmi di prevenzione articolati su scelte di adeguamento, dismissione, utilizzo alternativo o sostituzione. Nonostante la complessità ed i limiti imposti dalle risorse utilizzate, l'esteso programma di verifica delle scuole del Molise è in corso di completamento. La memoria intende illustrare alcune osservazioni e valutazioni su questa esperienza ed alcune risultanze parziali di uno studio, in corso di svolgimento in ambito CNR-ITC-L'Aquila, che è finalizzato a fornire alla Regione l'attesa base conoscitiva delle condizioni di rischio sismico delle scuole e gli strumenti per un suo proficuo utilizzo ai fini delle sopraccitate esigenze di prevenzione. Attraverso la raccolta e l'analisi degli elaborati prodotti con le indagini e le verifiche, il lavoro realizza un archivio complessivo georeferenziato del patrimonio scolastico esaminato, nella cui base dati sono raccolte ed organizzate tutte le informazioni dei progetti di indagine che riguardano le caratteristiche tipologico - costruttive, i materiali, i tipi di indagini e le prove sperimentali effettuate ed i relativi risultati, dati e risultati delle valutazioni di vulnerabilità sismica semplificate e le condizioni di rischio conseguenti. In particolare, si sintetizza lo stato di avanzamento dello studio e si illustrano i dati disponibili sulle caratteristiche tipologiche, di vulnerabilità e rischio degli edifici scolastici della Regione.

Early transition metal carbides and nitrides have been shown to be active for the hydrotreatment of model compounds and petroleum crudes. In this paper we describe our investigations of the structural and compositional properties of γ-Al2O3-supported molybdenum carbides and efforts to correlate these properties with their pyridine and quinoline hydrodenitrogenation (HDN) activities. The HDN activities of the materials scaled linearly with the loading and oxygen chemisorptive uptake. Oxygen chemisorption results also suggested that the molybdenum carbide particles were highly dispersed and perhaps raft-like. Using temperature programmed desorption and infrared spectroscopy of carbon monoxide, we were able to identify two types of sites on the carbides; sites “on top” of the particle and sites at the perimeter. We have tentatively concluded that the most active sites for HDN were “on top” of the supported carbide particles.

Molybdenum nitrides have been shown to be active hydrotreating catalysts. We explored the hydrotreating activities of supported Mo nitrides. It was observed that the hydrodenitrogenation and hydrodesulfurization activities were inverse functions of the molybdenum loading. By using oxygen chemisorption and carbon monoxide temperature programmed desorption, we were able to characterize the particle morphology of the nitrides.

The intraosseous (IO) route provides a rapid and effective alternative venous access in the pediatric population when the conventional intravenous (IV) route cannot be easily obtained. DL-propranolol, a beta-adrenoceptor antagonist, exhibits antiepileptic activity in various animal seizure models. This study assessed the efficacy of IO propranolol in suppressing pentylenetetrazol (PTZ)-induced seizure activity in pigs. Domestic swine (13-20 kg) were prepared for recordings of arterial blood pressure, ECG and electrocortical activity. Seizure activity was induced by pentylenetetrazol (PTZ; 100 mg/kg; IV). Sixty seconds after the onset of seizure activity, the animals either received no drug (control) or propranolol (IV or IO via an 18-gauge spinal needle placed in the right proximal tibia). A transient increase (16.3-50.0%) in the mean arterial blood pressure (MAP) was observed following PTZ administration. Both IO and IV propranolol significantly suppressed the seizure duration (SD) (sec/min interval) at 1 min following drug administration; SD control, 36.3 +/- 4.8; IV propranolol, 12.3 +/- 5.1; IO propranolol, 18.3 +/- 6.0. In addition, both IV and IO propranolol produced a maximal decrease of 32-38% in the basal heart rate; and reduced the transient increase in MAP elicited by PTZ, with no significant effect on the basal MAP. The data demonstrate that 1) propranolol possesses anticonvulsant activity against PTZ-induced seizure in the pig, and 2) the intraosseous route is a rapid and effective alternative venous access for propranolol administration in swine.

The AA. have evaluated the effects of anaesthesia and surgical trauma on the ability of lymphocytes from 10 patients to release Leukocyte Inhibiting Factor (LIF) after stimulation with phytohaemoagglutinin (PHA). In addition, they have studied the electrophoretic mobility of Polymorphonuclear-cells (PMN) and lymphocytes of 8 patients after incubation in autologus plasma. The experimental results show decrease of LIF production after operation in 6 individuals and reduction of eletrophoretic mobility of PMN and lymphocytes. The last finding is not significant on statistical point of view.

Glass facades are widely used in building structures, due to a series of aesthetic, thermal, lightening aspects. Wide transparent surfaces are realized in commercial, residential but also strategic buildings (airports, museums, offices, etc.). From a structural point of view, however, these envelopes represent a critical component for buildings, due to the brittle behaviour and limited tensile resistance of glass, as well as to possible criticalities deriving from connections, detailing, etc., hence requiring specific fail-safe design concepts (Haldimann et al., 2008; Feldmann et al., 2014). The estimation of the vulnerability and actual dynamic behaviour of glazing systems under exceptional loads (seismic events, explosions, fire, natural hazards, see Figs.1a to 1c - including their interaction with the building they belong - is currently an open topic, attracting the attention of several studies (Behr et al., 1995; Zhang et al., 2013; Mackalicka et al., 2016; Behr, 2009; Masters et al., 2010; Bedon and Amadio, 2017a; Larcher et al., 2016). However, further efforts are still required. In this paper, the seismic performance of glass curtain walls is investigated. The feasibility and potential of special mechanical connectors interposed at the interface between a given multi-storey building and the enclosing curtain are numerically investigated in ABAQUS (2017). The final result, as shown, consists in a full 3D assembly in which the facade works as a passive control system for the building, in the form of a distributed Tuned-Mass Damper (TMD), with enhanced global and local structural benefits (Bedon and Amadio, 2017).

Le opere di ingegneria civile, durante il loro periodo di esercizio, sono soggette ad azioni dinamiche la cui entità viene stimata - in fase di progetto - sulla base di valutazioni probabilistiche. Solo per opere di una certa rilevanza è previsto un collaudo atto a valutarne con accuratezza il comportamento strutturale, e solo un numero limitato di queste potrà disporre in esercizio di un sistema di monitoraggio continuo. Le informazioni raccolte dai sistemi di monitoraggio strutturale, in tal senso, hanno fondamentale importanza per l’intervento tempestivo atto a salvaguardare le vite umane. Inoltre, le stesse misure sono di notevole supporto nei processi decisionali legati alla pianificazione degli interventi di restauro o ripristino, i quali necessitano di precise valutazioni dello stato di danno. La ricerca applicativa, in tale ottica, si sta sempre più concentrando verso la concezione di sistemi affidabili ma economici e versatili, dotati di sensori basati su tecnologia MEMS (Micro Electro-Mechanical Systems), (Cochran et al., 2009). Tali sistemi possono assolvere sia le funzioni di acquisitori per eventi di tipo ‘strong motion’ (anche in strutture molto rigide, (Beskhyroun and Ma, 2012), che quelle di sensori di monitoraggio continuo per strutture flessibili (ponti, passerelle pedonali, ecc. (Haritos, 2009). Il continuo miglioramento dei processi produttivi di tale tipologia di sensori sta inoltre rendendo disponibili - a costi sempre più contenuti - elementi sensore sempre più performanti, rendendo il monitoraggio strutturale una possibilità più accessibile di quanto non fosse in passato. In tale contesto, la presente ricerca ha come obiettivo la valutazione sperimentale della performance ed affidabilità di sistemi MEMS per il monitoraggio strutturale. Lo studio prevede, in particolare, una prima fase di prototipazione hardware di schede elettroniche, nonché una serie di validazioni sperimentali (sia in laboratorio che in situ) atte a testare l’accuratezza dei sensori accelerometrici così assemblati.