Discussion on Possible Approaches for the Management of Pollutants in Tunneling in Rock Formations Containing Asbestos Minerals

Workers’ exposure to asbestos minerals is a major factor in the Occupational Safety and Health risks typical of tunneling. For, as well as being a carcinogen, the distribution of asbestos minerals in rock formations is highly irregular since their possible formation during the metamorphic process depends on various parameters. This makes a special risk assessment and management necessary. Many case studies of specific risk assessment and management of pollutants applied in tunneling are available in literature, so the aim of this research study is to define which can be implemented in case of formations containing asbestos minerals, in combination also with other solutions, and organize them in hierarchical order. Initially, to achieve this goal, a literature review was carried out in accordance with the PRISMA statement, to select the current solutions used to manage possible workers’ exposure to asbestos minerals. Subsequently, the various solutions selected (e.g., specific excavation techniques, catcher systems near the source, ventilation systems etc.) were given a hierarchy by order of priority and compared to each other. The selection of solutions and the priority order were achieved by taking into account the safety requirements for the construction of the base tunnel of the Turin-Lyon railway line. The study highlighted the fact that despite technological progress there are still some critical aspects in the management of pollutants and in particular of asbestos mineral

Forensic investigation techniques contribution in the occupational safety & health risk assessment and management

Occupational Safety and Health –OS&H- Risks Assessment and Management is a particularly demanding task: the European Directives - and the derived Italian laws and regulations - stress the importance of a pro-active approach, the one able to reach effective results. To simply focus on localized situations, and carry out a bird’s-eye survey cannot ensure a systematic evaluation of the operating contexts in complex settlements such as the Large Public Facilities, where the most serious criticalities are not of direct identification. The paper –developed within The General Safety Issues and Goals in Turin Universities research program, funded by Politecnico di Torino, discusses a special sub-part of the well-tested Guideline set up, for Large Public Facilities, in cooperation between Politecnico di Torino and Università degli Studi di Torino, aimed to grant a sufficient detail in the aforesaid situations. The approach is based on an original development for OS&H Risk Assessment and Management of some Forensic Investigations techniques for a thorough Hazard Identification on shell, services and interior spaces of settlements containing workplaces, and on their not-operative content. The analysis of some case histories confirms the effectiveness of the approach in terms of completeness and repeatability, and makes possible to draw suggestions on the selection of the better investigation technique in different scenarios

Tumor Resistance against ALK Targeted Therapy-Where It Comes From and Where It Goes

Anaplastic lymphoma kinase (ALK) is a validated molecular target in several ALK-rearranged malignancies, particularly in non-small-cell lung cancer (NSCLC), which has generated considerable interest and effort in developing ALK tyrosine kinase inhibitors (TKI). Crizotinib was the first ALK inhibitor to receive FDA approval for ALK-positive NSCLC patients treatment. However, the clinical benefit observed in targeting ALK in NSCLC is almost universally limited by the emergence of drug resistance with a median of occurrence of approximately 10 months after the initiation of therapy. Thus, to overcome crizotinib resistance, second/third-generation ALK inhibitors have been developed and received, or are close to receiving, FDA approval. However, even when treated with these new inhibitors tumors became resistant, both in vitro and in clinical settings. The elucidation of the diverse mechanisms through which resistance to ALK TKI emerges, has informed the design of novel therapeutic strategies to improve patients disease outcome. This review summarizes the currently available knowledge regarding ALK physiologic function/structure and neoplastic transforming role, as well as an update on ALK inhibitors and resistance mechanisms along with possible therapeutic strategies that may overcome the development of resistance

Protection from angiotensin II–mediated vasculotoxic and hypertensive response in mice lacking PI3Kγ

Hypertension affects nearly 20% of the population in Western countries and strongly increases the risk for cardiovascular diseases. In the pathogenesis of hypertension, the vasoactive peptide of the renin-angiotensin system, angiotensin II and its G protein–coupled receptors (GPCRs), play a crucial role by eliciting reactive oxygen species (ROS) and mediating vessel contractility. Here we show that mice lacking the GPCR-activated phosphoinositide 3-kinase (PI3K)γ are protected from hypertension that is induced by administration of angiotensin II in vivo. PI3Kγ was found to play a role in angiotensin II–evoked smooth muscle contraction in two crucial, distinct signaling pathways. In response to angiotensin II, PI3Kγ was required for the activation of Rac and the subsequent triggering of ROS production. Conversely, PI3Kγ was necessary to activate protein kinase B/Akt, which, in turn, enhanced L-type Ca2+ channel–mediated extracellular Ca2+ entry. These data indicate that PI3Kγ is a key transducer of the intracellular signals that are evoked by angiotensin II and suggest that blocking PI3Kγ function might be exploited to improve therapeutic intervention on hypertension