HER2 Copy Number and Resistance Mechanisms in Patients with HER2-positive Advanced Gastric Cancer Receiving Initial Trastuzumab-based Therapy in JACOB Trial

Resistance mechanisms; Advanced gastric cancer; TrastuzumabMecanismos de resistencia; Cáncer gástrico avanzado; TrastuzumabMecanismes de resistència; Càncer gàstric avançat; TrastuzumabPurpose: In JACOB trial, pertuzumab added to trastuzumab-chemotherapy did not significantly improve survival of patients with HER2-positive metastatic gastric cancer, despite 3.3 months increase versus placebo. HER2 copy-number variation (CNV) and AMNESIA panel encompassing primary resistance alterations (KRAS/PIK3CA/MET mutations, KRAS/EGFR/MET amplifications) may improve patients’ selection for HER2 inhibition. Experimental Design: In a post hoc analysis of JACOB on 327 samples successfully sequenced by next-generation sequencing (NGS; Oncomine Focus DNA), HER2 CNV, HER2 expression by IHC, and AMNESIA were correlated with overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) by univariable/multivariable models. Results: Median HER2 CNV was 4.7 (interquartile range, 2.2–16.9). HER2 CNV-high versus low using the median as cutoff was associated with longer median PFS (10.5 vs. 6.4 months; HR = 0.48; 95% confidence interval: 0.38–0.62; P < 0.001) and OS (20.3 vs. 13.0 months; HR = 0.54; 0.42–0.72; P < 0.001). Combining HER2 CNV and IHC improved discriminative ability, with better outcomes restricted to HER2-high/HER2 3+ subgroup. AMNESIA positivity was found in 51 (16%), with unadjusted HR = 1.35 (0.98–1.86) for PFS; 1.43 (1.00–2.03) for OS. In multivariable models, only HER2 CNV status remained significant for PFS (P < 0.001) and OS (P = 0.004). Higher ORR was significantly associated with IHC 3+ [61% vs. 34% in 2+; OR = 3.11 (1.89–5.17)] and HER2-high [59% vs. 43% in HER2-low; OR = 1.84 (1.16–2.94)], with highest OR in the top CNV quartile. These biomarkers were not associated with treatment effect of pertuzumab. Conclusions: HER2 CNV-high assessed by NGS may be associated with better ORR, PFS, and OS in a JACOB subgroup, especially if combined with HER2 3+. The negative prognostic role of AMNESIA requires further clinical validation

Identifying Strategies for Energy Consumption Reduction and Energy Efficiency Improvement in Fruit and Vegetable Producing Cooperatives: A Case Study in the Frame of TESLA Project☆

Abstract TESLA (Transfering Energy Save Laid on Agroindustry) is a EU project pointing to the reduction of energy consumption and the improvement of energy efficiency in key agro-food sectors' cooperatives, as those processing fruit and vegetables. After a general analysis of energy consumptions during the first phase of the project, the processes responsible for the higher energy consumptions in these fruit and vegetable industries, as cold storage, have been identified. In the second phase of the project, a few case studies aimed at proposing customized solutions for reducing energy wastage and for improving energy efficiency in specific selected cooperatives have been performed. In this manuscript we report preliminary results of a case study carried out in an Italian horticulture cooperative having several production lines for fresh (1 st range) and minimally processed (4 th range) fruit and vegetable products. In this cooperative, an in-depth energy audit has been performed, and additionally a process simulation software has been applied to model, evaluate and improve the operations in this processing centre and in the supply chain from the primary production sites. Such case study may be used as an example for similar cooperatives of the fruit and vegetables sector, thus contributing in making this sector more economically and energetically sustainable

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P &lt; .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

PIO MANZU'. Quando il mondo era moderno.

"PIO MANZU'. Quando il mondo era moderno". Mostra a cura di Giacinto Di Pietrantonio, Enrico Leonardo Fagone, Beppe Finessi. GAMeC - Galleria d'Arte Moderna e Contemporanea, Bergamo. 1 ottobre 2008 - 8 febbraio 200

Guided lamb wave electroacoustic devices on micromachined AlN/Al plates

An electroacoustic micro-device based on the propagation of guided acoustic Lamb waves in AlN/Al plate is described. The AlN thin film is deposited by sputtering technique, optimized to achieve a high degree of orientation(rocking curve full-width at half-maximum ≈ 3.5°) of the c-axis perpendicular to the plate surface. The AlN plate is micromachined using anisotropic reactive ion etching (RIE), followed by isotropic RIE to remove the silicon underlayer. Simulation results for the dispersion phase velocity curves and the electromechanical coupling coefficient (K2) are obtained by the matrix method and by the finite element method and compared with experimental data. A delay line is implemented on the structure and tested for the propagation of the first symmetrical Lamb mode (s0) at the frequency of 1.22 GHz. Measurements have shown that the structure is suitable for implementation of arrays of electroacoustic devices on a single chip for application to both sensing devices and signal processing systems

75 kN LOX/PARAFFIN FLIGHT-WEIGHT HYBRID MOTOR DEVELOPMENT

HyImpulse is developing a 75 kN hybrid rocket motor based on a LOx (liquid oxygen)/paraffin propellants combination that will equip SR75 (sounding rocket) and SL1 (3 stages small launcher) rockets in the coming years. The development of such thrust level hybrid motor is challenging and has been supported by a 10 kN small-scale motor to investigate and optimize different components of the large motor, such as paraffin mixture, nozzle erosion, oxidizer injection etc. More than hundred firing tests have been performed with this motor which provided highly valuable data and knowledge. The paper will provide an overview of the hybrid motors production and testing capabilities of HyImpulse. It will also present some results obtained from combustion tests to highlight the progress that was achieved so far

The interseismic velocity field of the central Apennines from a dense GPS network

Since 1999, we have repeatedly surveyed the central Apennines through a dense survey-style geodetic network, the Central Apennines Geodetic Network (CAGeoNet). CAGeoNet consists of 123 benchmarks distributed over an area of ca. 180 km × 130 km, from the Tyrrhenian coast to the Adriatic coast, with an average inter-site distance of 3 km to 5 km. The network is positioned across the main seismogenic structures of the region that are capable of generating destructive earthquakes. Here, we show the horizontal GPS velocity field of both CAGeoNet and continuous GPS stations in this region, as estimated from the position–time series in the time span from 1999 to 2007. We analyzed the data using both the Bernese and GAMIT software, rigorously combining the two solutions to obtain a validated result. Then, we analyzed the strain-rate field, which shows a region of extension along the axis of the Apennine chain, with values from 2 × 10–9 yr–1 to 66·× 10–9 yr–1, and a relative minimum of ca. 20 × 10–9 yr–1 located in the L'Aquila basin area. Our velocity field represents an improved estimation of the ongoing elastic interseismic deformation of the central Apennines, and in particular relating to the area of the L'Aquila earthquake of April 6, 2009

Eighteen years of GPS surveys in the Aeolian Islands (southern Italy): open data archive and velocity field

Since the early 1970s, geodetic networks became a most important tool to monitor the present day deformations of the volcanic arc of the Aeolian Islands. The first benchmarks were installed in this region at Lipari and Vulcano Islands and the number of GPS benchmarks increased in time since the early ’90s. These networks were periodically surveyed in the frame of national and international geodynamic projects and for Civil Protection programs devoted to the mitigation of the volcanic hazard. The Istituto Nazionale di Geofisica e Vulcanologia (INGV) played a fundamental role in the realization and periodical reoccupation of these networks, with the goal to investigate the tectonic and volcanic processes, still active in this crucial area of the central Mediterranean. An updated GPS velocity map for this region, both for the horizontal and vertical component of land motion, with details for Lipari, Vulcano and Panarea Islands, is provided in this paper. The presented GPS velocity field also includes a set of additional discrete stations located in northern Sicily and Calabria together with data from the available CGPS networks active in southern Italy. Here we show the results from eighteen years of repeated GPS surveys performed in this region in the time span 1995-2013 and the open access AINET-GPS data archive, now freely available for the scientific community. Data will support scientific research and hopefully improve the assessment of volcanic and seismic hazard in this region