A Systematic Review and International Web-Based Survey of Randomized Controlled Trials in the Perioperative and Critical Care Setting: Interventions Reducing Mortality

The authors aimed to identify interventions documented by randomized controlled trials (RCTs) that reduce mortality in adult critically ill and perioperative patients, followed by a survey of clinicians’ opinions and routine practices to understand the clinicians’ response to such evidence. The authors performed a comprehensive literature review to identify all topics reported to reduce mortality in perioperative and critical care settings according to at least 2 RCTs or to a multicenter RCT or to a single-center RCT plus guidelines. The authors generated position statements that were voted on online by physicians worldwide for agreement, use, and willingness to include in international guidelines. From 262 RCT manuscripts reporting mortality differences in the perioperative and critically ill settings, the authors selected 27 drugs, techniques, and strategies (66 RCTs, most frequently published by the New England Journal of Medicine [13 papers], Lancet [7], and Journal of the American Medical Association [5]) with an agreement ≥67% from over 250 physicians (46 countries). Noninvasive ventilation was the intervention supported by the largest number of RCTs (n = 13). The concordance between agreement and use (a positive answer both to “do you agree” and “do you use”) showed differences between Western and other countries and between anesthesiologists and intensive care unit physicians. The authors identified 27 clinical interventions with randomized evidence of survival benefit and strong clinician support in support of their potential life-saving properties in perioperative and critically ill patients with noninvasive ventilation having the highest level of support. However, clinician views appear affected by specialty and geographical location

Arvedi ESP Technology -The Hot Rolling of HS and AHS Thin Gauge Steel Strips

Abstract. After 5 years from start-up, Arvedi ESP Technology has achieved outstanding performances in terms of production, products and quality. The technology has proved particularly suitable for the production of thin gauge strips (< 2 mm). This paper presents the experiences in the production of high strength and advanced high strength steels, such as micro-alloyed S550MC, dual phase DP600 and ferritic bainitic HR60 in thin gauge strips on the ESP line of Acciaieria Arvedi S.p.A. in Cremona. Some aspects of the industrial production process for these steel grades are highlighted on the basis of casting and rolling parameters and microstructural and mechanical investigation

Arvedi ESP Technology -The Hot Rolling of HS and AHS Thin Gauge Steel Strips

Abstract. After 5 years from start-up, Arvedi ESP Technology has achieved outstanding performances in terms of production, products and quality. The technology has proved particularly suitable for the production of thin gauge strips (< 2 mm). This paper presents the experiences in the production of high strength and advanced high strength steels, such as micro-alloyed S550MC, dual phase DP600 and ferritic bainitic HR60 in thin gauge strips on the ESP line of Acciaieria Arvedi S.p.A. in Cremona. Some aspects of the industrial production process for these steel grades are highlighted on the basis of casting and rolling parameters and microstructural and mechanical investigation

MutAIT: an online genetic toxicology data portal and analysis tools

Assessment of genetic toxicity and/or carcinogenic activity is an essential element of chemical screening programs employed to protect human health. Dose–response and gene mutation data are frequently analysed by industry, academia and governmental agencies for regulatory evaluations and decision making. Over the years, a number of efforts at different institutions have led to the creation and curation of databases to house genetic toxicology data, largely, with the aim of providing public access to facilitate research and regulatory assessments. This article provides a brief introduction to a new genetic toxicology portal called Mutation Analysis Informatics Tools (MutAIT) (www.mutait.org) that provides easy access to two of the largest genetic toxicology databases, the Mammalian Gene Mutation Database (MGMD) and TransgenicDB. TransgenicDB is a comprehensive collection of transgenic rodent mutation data initially compiled and collated by Health Canada. The updated MGMD contains approximately 50 000 individual mutation spectral records from the published literature. The portal not only gives access to an enormous quantity of genetic toxicology data, but also provides statistical tools for dose–response analysis and calculation of benchmark dose. Two important R packages for dose–response analysis are provided as web-distributed applications with user-friendly graphical interfaces. The ‘drsmooth’ package performs dose–response shape analysis and determines various points of departure (PoD) metrics and the ‘PROAST’ package provides algorithms for dose–response modelling. The MutAIT statistical tools, which are currently being enhanced, provide users with an efficient and comprehensive platform to conduct quantitative dose–response analyses and determine PoD values that can then be used to calculate human exposure limits or margins of exposure

Pheophorbide A and Paclitaxel Bioresponsive Nanoparticles as Double-Punch Platform for Cancer Therapy

Cancer therapy is still a challenging issue. To address this, the combination of anticancer drugs with other therapeutic modalities, such as light-triggered therapies, has emerged as a promising approach, primarily when both active ingredients are provided within a single nanosystem. Herein, we describe the unprecedented preparation of tumor microenvironment (TME) responsive nanoparticles exclusively composed of a paclitaxel (PTX) prodrug and the photosensitizer pheophorbide A (PheoA), e.g., PheoA≅PTX2S. This system aimed to achieve both the TME-triggered and controlled release of PTX and the synergistic/additive effect by PheoA-mediated photodynamic therapy. PheoA≅PTX2S were produced in a simple one-pot process, exhibiting excellent reproducibility, stability, and the ability to load up to 100% PTX and 40% of PheoA. Exposure of PheoA≅PTX2S nanoparticles to TME-mimicked environment provided fast disassembly compared to normal conditions, leading to PTX and PheoA release and consequently elevated cytotoxicity. Our data indicate that PheoA incorporation into nanoparticles prevents its aggregation, thus providing a greater extent of ROS and singlet oxygen production. Importantly, in SK-OV-3 cells, PheoA≅PTX2S allowed a 30-fold PTX dose reduction and a 3-fold dose reduction of PheoA. Our data confirm that prodrug-based nanocarriers represent valuable and sustainable drug delivery systems, possibly reducing toxicity and expediting preclinical and clinical translation

A Systematic Review and International Web-Based Survey of Randomized Controlled Trials in the Perioperative and Critical Care Setting: Interventions Increasing Mortality

Reducing mortality is a key target in critical care and perioperative medicine. The authors aimed to identify all nonsurgical interventions (drugs, techniques, strategies) shown by randomized trials to increase mortality in these clinical settings