Effect of retrofit interventions on seismic fragility of Italian residential masonry buildings

In this paper, the vulnerability of ordinary unreinforced masonry (URM) buildings is analyzed, and the literature related to possible seismic retrofit interventions is reviewed in order to investigate their feasibility and effectiveness. These interventions are then simulated on a data-base of 445 buildings through Vulnus_4.0 software, that performs simplified mechanical analyses accounting for both global and local behavior of masonry buildings. The fragility of each building is assessed both in its as-built state and after the simulation of retrofit interventions. Fragility curves are then processed, and a fragility model for four building typologies is obtained for the as -built and the seismic retrofitted configurations. Lastly, mean damage maps are elaborated, and the performance of the proposed retrofit interventions is analyzed. The results of this work allow evaluating and comparing the improvement of seismic behavior brought by various retrofit in-terventions and could serve as a basis for further theoretical studies and for practical design in real cases

Mechanics-based fragility curves for Italian residential URM buildings

Seismic risk assessment at the territorial level is now widely recognised as essential for countries with intense seismic activity, such as Italy. Academia is called to give its contribution in order to synergically deepen the knowledge about the various components of this risk, starting from the complex evaluation of vulnerability of the built heritage. In line with this, a mechanics-based seismic fragility model for Italian residential masonry buildings was developed and presented in this paper. This model is based on the classification of the building stock in macro-typologies, defined by age of construction and number of storeys, which being information available at national level, allow simulating damage scenarios and carrying out risk analyses on a territorial scale. The model is developed on the fragility of over 500 buildings, sampled according to national representativeness criteria and analysed through the Vulnus_4.0 software. The calculated fragility functions were extended on the basis of a reference model available in the literature, which provides generic fragilities for the EMS98 vulnerability classes, thus obtaining a fragility model defined on the five EMS98 damage states. Lastly, to assess the reliability of the proposed model, this was used to simulate damage scenarios due to the 2009 L’Aquila earthquake. Overall, the comparison between model results and observed damage showed a good fit, proving the model effectiveness

Damage assessment in single-nave churches and analysis of the most recurring mechanisms after the 2016–2017 central Italy earthquakes

Assessment of churches based on empirical data at a territorial scale is a suitable tool to have an overview of the seismic behaviour of this peculiar structural typology and to evaluate their current state of vulnerability. Fragility and vulnerability curves are also aimed to perform the analysis of different seismic scenarios. The paper presents a detailed typological analysis of 633 single-nave churches, as a selected subset of the database previously examined by the authors, with the aim of evaluating more in detail the influence of some parameters, such as masonry typology, church dimensions and presence of the bell tower, on the vulnerability of the overall church. Then, specific analyses are carried out to assess the influence played by single mechanisms on the definition of the overall damage index, with the focus of providing qualitative evaluations and explicit vulnerability and fragility curves related to the most recurring and significant collapse mechanisms. This is an original contribution of the paper in the field of the vulnerability assessment of churches, since nowadays little information is available in the literature about the damage levels related to specific mechanisms, while most attention is still focused on global damage

A multi-center, real-life experience on liquid biopsy practice for EGFR testing in non-small cell lung cancer (NSCLC) patients

Background: circulating tumor DNA (ctDNA) is a source of tumor genetic material for EGFR testing in NSCLC. Real-word data about liquid biopsy (LB) clinical practice are lacking. The aim of the study was to describe the LB practice for EGFR detection in North Eastern Italy. Methods: we conducted a multi-regional survey on ctDNA testing practices in lung cancer patients. Results: Median time from blood collection to plasma separation was 50 min (20\u2013120 min), median time from plasma extraction to ctDNA analysis was 24 h (30 min\u20135 days) and median turnaround time was 24 h (6 h\u20135 days). Four hundred and seventy five patients and 654 samples were tested. One hundred and ninety-two patients were tested at diagnosis, with 16% EGFR mutation rate. Among the 283 patients tested at disease progression, 35% were T790M+. Main differences in LB results between 2017 and 2018 were the number of LBs performed for each patient at disease progression (2.88 vs. 1.2, respectively) and the percentage of T790M+ patients (61% vs. 26%)

Real-world data on treatment outcomes in EGFR-mutant non-small-cell lung cancer patients receiving osimertinib in second or further lines

Aims: This study describes real-world outcomes of pretreated EGFR T790M-positive (T790M+) advanced non-small-cell lung cancer patients progressing after first- or second-generation tyrosine kinase inhibitors and receiving osimertinib, compared with T790M-negative (T790M-) patients. We have also described progression patterns and treatment sequences. Patients & methods: This is a retrospective multicenter Italian observational study including consecutive Caucasian patients referred between 2014 and 2018. Results: 167 patients were included. Median progression-free survival was 9.8 months (95% CI: 8.3-13.3) for T790M+ and 6.0 months (95% CI: 4.9-7.2) for T790M- patients, respectively. Median overall survival was 20.7 months (95% CI: 18.9-28.4) for T790M+ and 10.6 months (95% CI: 8.6-23.6) for T790M- patients, respectively. The T790M mutation correlated with absence of new sites of disease. After progression, most T790M+ patients continued osimertinib, whereas most T790M- patients received a different treatment line. Conclusion: Better outcomes were shown in patients receiving osimertinib. A more limited progression pattern for T790M+ was suggested

Using Recombinant Proteins from Lutzomyia longipalpis Saliva to Estimate Human Vector Exposure in Visceral Leishmaniasis Endemic Areas

During the blood meal, female sand flies (insects that transmit the parasite Leishmania) inject saliva containing a large variety of molecules with different pharmacological activities that facilitate the acquisition of blood. These molecules can induce the production of anti-saliva antibodies, which can then be used as markers for insect (vector) biting or exposure. Epidemiological studies using sand fly salivary gland sonicate as antigens are hampered by the difficulty of obtaining large amounts of salivary glands. In the present study, we have investigated the use of two salivary recombinant proteins from the sand fly Lutzomyia longipalpis, considered the main vector of visceral leishmaniasis, as an alternative method for screening of exposure to the sand fly. We primarily tested the suitability of using the recombinant proteins to estimate positive anti-saliva ELISA test in small sets of serum samples. Further, we validated the assay in a large sample of 1,077 individuals from an epidemiological survey in a second area endemic for visceral leishmaniasis. Our findings indicate that these proteins represent a promising epidemiological tool that can aid in implementing control measures against leishmaniasis

Vaccines for the Leishmaniases: Proposals for a Research Agenda

The International Symposium on Leishmaniasis Vaccines, held in Olinda, Brazil, on March 9–11, 2009, congregated international experts who conduct research on vaccines against the leishmaniases. The questions that were raised during that meeting and the ensuing discussions are compiled in this report and may assist in guiding a research agenda. A group to further discussion on issues raised in this policy platform has been set up at http://groups.google.com/group/leishvaccines-l

Discovery of Markers of Exposure Specific to Bites of Lutzomyia longipalpis, the Vector of Leishmania infantum chagasi in Latin America

Leishmania parasites are transmitted by the bite of an infected vector sand fly that injects salivary molecules into the host skin during feeding. Certain salivary molecules can produce antibodies and can be used as an indicator of exposure to a vector sand fly and potentially the disease it transmits. Here we identified potential markers of specific exposure to the sand fly Lutzomyia longipalpis, the vector of visceral leishmaniasis in Latin America. Initially, we determined which of the salivary proteins produce antibodies in humans, dogs, and foxes from areas endemic for the disease. To identify potential specific markers of vector exposure, we produced nine different recombinant salivary proteins from Lu. longipalpis and tested for their recognition by individuals exposed to another human-biting sand fly, Lu. intermedia, that transmits cutaneous leishmaniasis and commonly occurs in the same endemic areas as Lu. longipalpis. Two of the nine salivary proteins were recognized only by humans exposed to Lu. longipalpis, suggesting they are immunogenic proteins and may be useful in epidemiological studies. The identification of specific salivary proteins as potential markers of exposure to vector sand flies will increase our understanding of vector–human interaction, bring new insights to vector control, and in some instances act as an indicator for risk of acquiring disease

BALB/c Mice Infected with Antimony Treatment Refractory Isolate of Leishmania braziliensis Present Severe Lesions due to IL-4 Production

Leishmaniasis is a neglected disease that affects more than 12 million people worldwide. In Brazil, the cutaneous disease is more prevalent with about 28,000 new cases reported each year, and L. braziliensis is the main causative agent. The interesting data about the infection with this parasite is the wide variety of clinical manifestations that ranges from single ulcerated lesions to mucocutaneous and disseminated disease. However, experimental models to study the infection with this parasite are difficult to develop due to high resistance of most mouse strains to the infection, and the mechanisms underlying the distinct manifestations remain poorly understood. Here, the authors use a mouse experimental model of infection with different L. braziliensis isolates, known to induce diseases with distinct severity in the human hosts, to elucidate immune mechanisms that may be involved in the different manifestations. They showed that distinct parasite isolates may modulate host response, and increased IL-4 production and Arg I expression was related to more severe disease, resulting in longer length of disease with larger lesions and reduced parasite clearance. These findings may be useful in the identification of immunological targets to control L. braziliensis infection and potential clinical markers of disease progression