Historical comparison of the damage caused by the propagation of a dam break wave in a pre-alpine valley

Study region: Valle Camonica basin and Lake Iseo in the Italian pre-alpine and alpine region. Study focus: This paper provides the first hydraulic reconstruction of the terminal part of the Gleno dam break with the propagation of the flood wave along a wide pre-alpine valley. The reconstruction of this part of the event, accomplished with a new 2D Shallow Water Equations solver, provides the occasion to tackle some important issues related to the computation of flood damage, a topic of paramount practical importance for which there is no widely accepted procedure in the literature. New hydrological insights for the region: The hydraulic reconstruction provides insights into the propagation of the flood through the floodplain as far as the inlet of Lake Iseo. A methodology for damage computation is presented that considers a physically based criterion for the vulnerability of human life, with significant implications with respect to the use of simpler approaches based only on the density of the population. The economic evaluation of the damage to the built environment and to agricultural activities is included through a comprehensive recent approach. We discuss the variations of the expected damage due to the hydraulic works accomplished over the last 100 years to decrease the flood hazard, showing that its reduction has been followed by an increase in the expected damage in the surrounding areas

Identification and characterization of Neofusicoccum stellenboschiana in branch and twig dieback-affected olive trees in Italy and comparative pathogenicity with N. mediterraneum

For about a decade, olive groves in Apulia (Southern Italy) have been progressively destroyed by Olive Quick Decline Syndrome (OQDS), a disease caused by the bacterium Xylella fastidiosa subsp. pauca (Xfp). Recently, we described an additional wilting syndrome affecting olive trees in that area. The botryosphaeriaceous fungus Neofusicoccum mediterraneum was found associated with the diseased trees, and its high virulence toward olive trees was demonstrated. Given the common features with Branch and Twig Dieback (BTD) of olive tree, occurring in Spain and California, we suggested that the observed syndrome was BTD. During our first survey, we also found a botryosphaeriaceous species other than N. mediterraneum. In the present article, we report the morphological and molecular characterization of this fungal species which we identified as Neofusicoccum stellenboschiana. In the study, we also included for comparison additional N. stellenboschiana isolates obtained from olive trees in Latium and Tuscany region (Central Italy). The occurrence of N. stellenboschiana in olive trees is reported here for the first time in the northern hemisphere. The pathogenicity and virulence were tested in nine inoculation trials, where the Apulian N. stellenboschiana isolate was compared with the isolate from Latium and with the Apulian isolate of N. mediterraneum. Both isolates of N. stellenboschiana proved pathogenic to olive trees. They caused evident bark canker and wood discolouration when inoculated at the base of the stem of two/three-year-old trees and on one-year-old twigs. However, virulence of N. stellenboschiana was significantly lower, though still remarkable, compared with N. mediterraneum in term of necrosis rogression in the bark and the wood and capacity of wilting the twigs. Virulence of N. stellenboschiana and N. mediterraneum did not substantially change when noculations were performed in spring/summer and in autumn, suggesting that these fungal species have the potential to infect and damage olive trees in all seasons. The high thermotolerance of N. stellenboschiana was also revealed with in vitro growth and survival tests. The high virulence of these otryosphaeriaceae species highlights their contribution in BTD aetiology and the necessity to investigate right away their diffusion and, possibly, the role of additional factors other than Xfp in the general decline of olive groves in Apulia. Hence the importance of assessing the degree of overlap of BTD/Botryosphariaceae with OQDS/Xfp is discussed

A Technological Platform and a Process to Implement the Informative Marketing Strategy

The context There is large evidence in the literature that digitalisation improves the market performance of enterprises and, as a consequence, it helps the growth of their businesses. Through digital platforms companies connect with people, improve awareness of their brands, influence consumer's attitudes, collect feedback from them, improve products and services on sale and, at last, increase their incomes. Clark et al. [2] conclude that providing basic information should be the dominant role of advertising. This typology of advertising is called Informational in [3]. The informational message strategy presents factual product/services information in clear and concrete terms. In order for an informational advertisement to become informative the message must be perceived as such by the consumers. Materials & Methods In this paper we adopt the IT-platform conceptual model given by Sun et al. (2015) [6] and the linked definition they propose. Results We instantiate the platform conceptual model proposed by by Sun et al.[6]. The website technology is the "heart" of our digital platform. There is large evidence in the literature that websites are largely used across companies all over the world [12, 13]. The cost necessary for setting up the platform is low, therefore such a technological solution is within the reach of most enterprises. Moreover, the paper describes the steps of the Informative Marketing process based on the adoption of the proposed Technological Platform. We use the adjective informative instead of informational because the advertisings about the product/service are sent to a community of ad hoc recruited stakeholders, therefore we can assume as relevant the information they receive. Conclusion The emphasis of the paper is oriented towards companies whose primary goal is selling, but it is worth notice that the proposed technological platform can be very useful, for example, to national institutes of health to promote campaigns on healthy (and sustainable) food consumption [17]. References Yogesh K. Dwivedi et al.: Setting the future of digital and social media marketing research: Perspectives and research propositions International Journal of Information Management 2020 (in press) Clark, C.K., Doraszelski, U., and Draganska, M.: The effect of advertising on brand awareness and perceived quality: An empirical investigation using panel data. Quantitative Marketing and Economics 2009 7, 207–236 DOI 10.1007/s11129-009-9066-z Puto, C.P. and Wells, W.D.: "Informational and Transformational Advertising: the Differential Effects of Time", in Advances in Consumer Research Volume 11, eds. Thomas C. Kinnear, Provo, UT, 1984 638–643. Tafesse,W. andWien, A.: Using message strategy to drive consumer behavioral engagement on social media. The Journal of Consumer Marketing 2018, 35(3), 241–253. Tiwana, A.: Platform ecosystems: Aligning architecture, governance, and strategy. Burlington, Morgan Kaufmann, 2014. Sun, R., Gregor, S., and Keating, B.: Information Technology Platforms: Conceptualisation and a Review of Emerging Research in IS Research, Australasian Conference on Information Systems, Dec. 2015, Adelaide, Australia. Parker, G.G., Van Alstyne, M.W., and Choudary, S.P. Platform revolution. W.W. Norton& company 2016. de Reuver,M., Sorensen, C.,& Basole, R. The digital platform: A research agenda. Journal of Information Technology, 2017 33(2), 124–135. Asadullah, A., Faik, I., and Kankanhalli, A. Digital Platforms: A Review and Future Directions. Twenty-Second Pacific Asia Conference on Information Systems, Japan, Sept. 2018. Hein, A., Schreieck, M., Wiesche, M., Bohm,M., and Krcmar, H. The Emergence of Native Multi-Sided Platforms and Their Influence on Incumbents. Electronic Markets 2019. https://doi.org/10.1007/s12525-019-00350-1 Hein, A., Schreieck, M., and Riasanow, T. David Soto Setzke, ManuelWiesche, Markus Bohm, and Helmut Krcmar: Digital platform ecosystems. Electronic Markets 2020 30:87–98 https://doi.org/10.1007/s12525-019-00377-4 Sharma, A., Sharma, S., and Chaudhary, M.: Are small travel agencies ready for digital marketing? Views of travel agency managers Tourism Management 79 2020 104078 Said, Y.B., Bragazzi, N.L. and Pyatigorskaya, N.V.: Prevalence and Perceived Effectiveness of Pharmaceutical Digital Marketing among Community Pharmacies in Saudi Arabia: A Cross-Sectional Questionnaire-Based Survey Pharmacy 2020, 8, 9; doi:10.3390/pharmacy8010009 Egria, G. and Bayrakb, C.: The Role of Search Engine Optimization on Keeping the User on the Site. Procedia Computer Science 36 2014 335 – 342 doi: 10.1016/j.procs.2014.09.102 Brogia, S.: Online brand communities: a literature review. 2nd World Conference on Business, Economics and Management 2003 Procedia - Social and Behavioral Sciences 109 2014 385–389. Mudambi, S.M., Oliva, T.A., and Thomas, E.F.: Industrial marketing firms and knowledge transfer: Toward a basic typology of community structures. Industrial Marketing Management 38 2009 181–190 doi:10.1016/j.indmarman.2008.12.006 Formoso, G. et al.: An Italian Innovative Small-Scale Approach to Promote the Conscious Consumption of Healthy Food. Applied Sciences 2020, 10, 5678; doi:10.3390/app1016567

Interlaboratory performance of a Real-Time PCR method for detection of Ceratocystis platani, the agent of canker stain of Platanus spp

Ceratocystis platani (CP), an ascomycetous fungus, is the agent of canker stain, a lethal vascular disease of Platanus species. Ceratocystis platani has been listed as a quarantine pest (EPPO A2 list) due to extensive damage caused in Southern Europe and the Mediterranean region. As traditional diagnostic assays are ineffective, a Real-Time PCR detection method based on EvaGreen, SYBR Green, and Taqman assays was previously developed, validated in-house, and included in the official EPPO standard PM7/14 (2). Here, we describe the results of a test performance study performed by nine European laboratories for the purpose of an interlaboratory validation. Verification of the DNA extracted from biological samples guaranteed the high quality of preparations, and the stability and the homogeneity of the aliquots intended for the laboratories. All of the laboratories reproduced nearly identical standard curves with efficiencies close to 100%. Testing of blind-coded DNA extracted from wood samples revealed that all performance parameters-diagnostic sensitivity, diagnostic specificity, accuracy and reproducibility-were best fit in most cases both at the laboratory and at the assay level. The previously established limit of detection, 3 fg per PCR reaction, was also validated with similar excellent results. The high interlaboratory performance of this Real-Time PCR method confirms its value as a primary tool to safeguard C. platani-free countries by way of an accurate monitoring, and to investigate the resistance level of potentially canker stain-resistant Platanus genotypes

Gene expression profiling of advanced ovarian cancer: characterization of a molecular signature involving fibroblast growth factor 2

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Characterization of a debris flow event using an affordable monitoring system

This study presents monitoring data of a debris flow event in the Central Italian Alps. The debris flow occurred on August 16, 2021 in the Blè basin (Val Camonica valley, Lombardia Region) and was recorded by a monitoring station installed just few weeks before. The monitoring system was deployed to document the hydrologic response of the catchment to rainfall, and was designed to be lightweight, relatively cheap, and easy to deploy in the field. To this purpose, we combined video cameras with geophysical sensors (geophones and infrasound) and optimized the power supply system. The data recorded during the event allowed to identify the triggering rainfall, document the flow behaviour, and estimate surface flow velocity and flow rate using Particle Image Velocimetry algorithms. Moreover, the seismic signal generated by the debris flow revealed a peculiar frequency spectrum compared to regular streamflow. These results show that even a relatively simple monitoring system may provide valuable data on real debris flow events

The evolution of lung cancer and impact of subclonal selection in TRACERx

Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource

The evolution of non-small cell lung cancer metastases in TRACERx

Metastatic disease is responsible for the majority of cancer-related deaths. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse

Genomic–transcriptomic evolution in lung cancer and metastasis

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response