Advantages of the recursive operability analysis in updating the risk assessment

With the introduction of new regulations and sustainable technologies, revamping and upgrading already existing chemical plants is nowadays an important element in the framework of process engineering. Such important modifications must come along in parallel improvement of process safety. In this sense, risk assessment is a tool that should be versatile and easy to update by definition. However, even the most common methods currently used for accidental scenarios identification and risk assessment estimation (such as HazOp) may prove to be very time-consuming when discussing about safety from process modifications. The availability of a reliable and easy-to-update tool for safety engineering is crucial for process industries. In this work, we compare a risk analysis on a chemical plant subject of modifications performed with two different tools: HazOp and FTA vs Recursive Operability Analysis (ROA) and FTA. Both techniques have been applied to a tank dedicated to dust mixing that was subject of process modifications. Both methods come to the same conclusions, highlighting new failures and process criticalities, associated with the introduction of flow alarms and interlocks in case of excessive depressurizing. It is shown that the Recursive Operability Analysis, with its cause-consequence structure tied with process variable interactions, is much more effective in a risk assessment update

Non-Newtonian and flow pulsatility effects in simulation models of a stented intracranial aneurysm

Permission to redistribute provided by publishers.Three models of different stent designs implanted in a cerebral aneurysm, originating from the Virtual Intracranial Stenting Challenge'07, are meshed and the flow characteristics simulated using commercial computational fluid dynamics (CFD) software in order to investigate the effects of non-Newtonian viscosity and pulsatile flow. Conventional mass inflow and wall shear stress (WSS) output are used as a means of comparing the cfd simulations. In addition, a WSS distribution is presented, which clearly discriminates in favour of the stent design identified by other groups. It is concluded that non-Newtonian and pulsatile effects are important to include in order to avoid underestimating wss, to understand dynamic flow effects, and to discriminate more effectively between stent designs. © Authors 2011

An integrated approach for the analysis and modeling of road tunnel ventilation. Part I: Continuous measurement of the longitudinal airflow profile

The knowledge of the flow field inside road tunnels under normal operation, let alone fire conditions, is only approximate and partial. The reason is that while the full three-dimensional, unsteady problem is out of reach of numerical methods, on the other hand accurate measurement of the airflow in road and railway tunnels constitutes an extremely demanding task. The present work, structured as a twofold study, takes up the challenge and proposes an original integrated experimental and numerical approach for the analysis and modeling of flow inside a road tunnel and its ventilation systems, aiming at defining a methodology for the creation of “digital twins” of the system itself, on which advanced ventilation and smoke control strategies can be tested and fine-tuned. In this first part, an innovative experimental facility for the continuous acquisition of the longitudinal velocity profile along the whole length of a road tunnel has been designed and built. The facility consists of a survey rake with five bidirectional vane anemometers, which is mounted on a small electric vehicle that can travel through the tunnel at constant speed. This paper reports the design procedure of the measurement facility, with particular focus on the conception and realization of the vehicle carrying the survey rake. Results of the first experimental campaign carried out under the 11611 meters long Mont Blanc road tunnel are presented to corroborate the validity of the approach adopted and the accuracy of the measurement chain

Specific modulation of airway epithelial tight junctions by apical application of an occludin peptide

Tight junctions are directly involved in regulating the passage of ions and macromolecules (gate functions) in epithelial and endothelial cells. The modulation of these gate functions to transiently regulate the paracellular permeability of large solutes and ions could increase the delivery of pharmacological agents or gene transfer vectors. To reduce the inflammatory responses caused by tight junction-regulating agents, alternative strategies directly targeting specific tight junction proteins could prove to be less toxic to airway epithelia. The apical delivery of peptides corresponding to the first extracellular loop of occludin to transiently modulate apical paracellular flux has been demonstrated in intestinal epithelia. We hypothesized that apical application of these occludin peptides could similarly modulate tight junction permeability in airway epithelia. Thus, we investigated the effects of apically applied occludin peptide on the paracellular permeability of molecular tracers and viral vectors in well differentiated human airway epithelial cells. The effects of occludin peptide on cellular toxicity, tight junction protein expression and localization, and membrane integrity were also assessed. Our data showed that apically applied occludin peptide significantly reduced transepithelial resistance in airway epithelia and altered tight junction permeability in a concentration-dependent manner. These alterations enhanced the paracellular flux of dextrans as well as gene transfer vectors. The occludin peptide redistributed occludin but did not alter the expression or distribution of ZO-1, claudin-1, or claudin-4. These data suggest that specific targeting of occludin could be a better-suited alternative strategy for tight junction modulation in airway epithelial cells compared with current agents that modulate tight junctions

Study of the Interaction Between a High-Pressure Jet and Horizontal Tanks using CFD

Accidental high-pressure flammable gas releases are among the most relevant hazards in the process safety, and consequences could be severe. In the recent decades, there have been numerous efforts to study high-pressure jets in open field (i.e., free jets). Easy-to-use mathematical models have been developed, to rapidly assess the main physical variables involved in safety evaluations. However, in a realistic scenario, the accidental leak may involve either the ground or a piece of equipment. As demonstrated by recent works, when a jet interacts with an obstacle, its behavior can significantly change. Therefore, the mathematical models extrapolated for the free jet scenario could be a source of incorrect predictions. Focusing on the scenario of an accidental high-pressure unignited flammable jet, this work shows how the presence of one or two obstacles, placed at a different distance from the source of the leak, can influence the lower flammability limit cloud extent of methane. Varying the height of the source term, the effect of the interaction among the jet, both the obstacles, and the ground was systematically studied through a Computational Fluid Dynamics analysis

A Revised Approach for One-Dimensional Time-Dependent Heat Conduction in a Slab

Classical Green's and Duhamel's integral formulas are enforced for the solution of one dimensional heat conduction in a slab, under general boundary conditions of the first kind. Two alternative numerical approximations are proposed, both characterized by fast convergent behavior. We first consider caloric functions with arbitrary piecewise continuous boundary conditions, and show that standard solutions based on Fourier series do not converge uniformly on the domain. Here, uniform convergence is achieved by integrations by parts. An alternative approach based on the Laplace transform is also presented, and this is shown to have an excellent convergence rate also when discontinuities are present at the boundaries. In both cases, numerical experiments illustrate the improvement of the convergence rate with respect to standard methods

Fatal herpesvirus-6 encephalitis in a recipient of a T-cell-depleted peripheral blood stem cell transplant from a 3-loci mismatched related donor

Human herpesvirus-6 (HHV-6), like all the other herpes viruses, remains latent in host cells after primary infection but can be reactivated In immuno-compromised patients causing fever, skin rash, bone marrow (BM) suppression, pneumonitis, Sinusitis and meningoencephalitis. We describe the case of a man with chronic myelogenous leukemia who developed encephalitis associated with acute graft-versus-host disease two months after a T-cell-depleted mismatched peripheral blood stem cell transplant. Magnetic resonance images of the brain revealed multiple bilateral foci of signal abnormality. HHV-6 was the only pathogen detected in cerebrospinal fluid by PCR. treatment with both ganciclovir and foscarnet was unsuccessful and the patient gradually deteriorated and died. Other cases of HHV-6 encephalitis after bone marrow transplantation are reviewed

MR Imaging in Menière Disease: Is the Contact between the Vestibular Endolymphatic Space and the Oval Window a Reliable Biomarker?

BACKGROUND AND PURPOSE: No reliable MR imaging marker for the diagnosis of Meniere disease has been reported. Our aim was to investigate whether the obliteration of the inferior portion of the vestibule and the contact with the stapes footplate by the vestibular endolymphatic space are reliable MR imaging markers in the diagnosis of Meniere disease. MATERIALS AND METHODS: We retrospectively enrolled 49 patients, 24 affected by unilateral sudden hearing loss and 25 affected by definite Meniere disease, who had undergone a 4-hour delayed 3D-FLAIR sequence. Two readers analyzed the MR images investigating whether the vestibular endolymphatic space bulged in the third inferior portion of the vestibule contacting the stapes footplate. This sign was defined as the vestibular endolymphatic space contacting the oval window. RESULTS: We analyzed 98 ears: 27 affected by Meniere disease, 24 affected by sudden sensorineural hearing loss, and 47 that were healthy. The vestibular endolymphatic space contacting the oval window showed an almost perfect interobserver agreement (Cohen κ = 0.87; 95% CI, 0.69–1). The vestibular endolymphatic space contacting oval window showed the following: sensitivity = 81%, specificity = 96%, positive predictive value = 88%, and negative predictive value = 93% in differentiating Meniere disease ears from other ears. The vestibular endolymphatic space contacting the oval window showed the following: sensitivity = 81%, specificity = 96%, positive predictive value = 96%, negative predictive value = 82% in differentiating Meniere disease ears from sudden sensorineural hearing loss ears. CONCLUSIONS: The vestibular endolymphatic space contacting the oval window has high specificity and positive predictive value in differentiating Meniere disease ears from other ears, thus resulting in a valid tool for ruling in Meniere disease in patients with mimicking symptoms

Multiparametric flow cytometry for MRD monitoring in hematologic malignancies: Clinical applications and new challenges

In hematologic cancers, Minimal Residual Disease (MRD) monitoring, using either molecular (PCR) or immunophenotypic (MFC) diagnostics, allows the identification of rare cancer cells, readily detectable either in the bone marrow or in the peripheral blood at very low levels, far below the limit of classic microscopy. In this paper, we outlined the state-of-the-art of MFC-based MRD detection in different hematologic settings, highlighting main recommendations and new challenges for using such a method in patients with acute leukemias or chronic hematologic neoplasms. The combination of new molecular technologies with advanced flow cytometry is progressively allowing clinicians to design a personalized therapeutic path, proportionate to the biological aggressiveness of the disease, in particular by using novel immunotherapies, in view of a modern decision-making process, based on precision medicine. Along with the evolution of immunophenotypic and molecular diagnostics, the assessment of Minimal Residual Disease (MRD) has progressively become a keystone in the clinical management of hematologic malignancies, enabling valuable post-therapy risk stratifications and guiding risk-adapted therapeutic approaches. However, specific prognostic values of MRD in different hematological settings, as well as its appropriate clinical uses (basically, when to measure it and how to deal with different MRD levels), still need further investigations, aiming to improve standardization and harmonization of MRD monitoring protocols and MRD-driven therapeutic strategies. Currently, MRD measurement in hematological neoplasms with bone marrow involvement is based on advanced highly sensitive methods, able to detect either specific genetic abnormalities (by PCRbased techniques and next-generation sequencing) or tumor-associated immunophenotypic profiles (by multiparametric flow cytometry, MFC). In this review, we focus on the growing clinical role for MFC-MRD diagnostics in hematological malignancies-from acute myeloid and lymphoblastic leukemias (AML, B-ALL and T-ALL), to chronic lymphocytic leukemia (CLL) and multiple myeloma (MM)-providing a comparative overview on technical aspects, clinical implications, advantages and pitfalls of MFC-MRD monitoring in different clinical settings