Transcriptional profiling of the acute pulmonary inflammatory response induced by LPS: role of neutrophils

<p>Abstract</p> <p>Background</p> <p>Lung cancer often develops in association with chronic pulmonary inflammatory diseases with an influx of neutrophils. More detailed information on inflammatory pathways and the role of neutrophils herein is a prerequisite for understanding the mechanism of inflammation associated cancer.</p> <p>Methods</p> <p>In the present study, we used microarrays in order to obtain a global view of the transcriptional responses of the lung to LPS in mice, which mimics an acute lung inflammation. To investigate the influence of neutrophils in this process, we depleted mice from circulating neutrophils by treatment with anti-PMN antibodies prior to LPS exposure.</p> <p>Results</p> <p>A total of 514 genes was greater than 1.5-fold differentially expressed in the LPS induced lung inflammation model. 394 of the 514 were up regulated genes mostly involved in cell cycle and immune/inflammation related processes, such as cytokine/chemokine activity and signalling. Down regulated genes represented nonimmune processes, such as development, metabolism and transport. Notably, the number of genes and pathways that were differentially expressed, was reduced when animals were depleted from circulating neutrophils, confirming the central role of neutrophils in the inflammatory response. Furthermore, there was a significant correlation between the differentially expressed gene list and the promutagenic DNA lesion M₁dG, suggesting that it is the extent of the immune response which drives genetic instability in the inflamed lung. Several genes that were specifically regulated by the presence of activated neutrophils could be identified and these were mostly involved in interferon signalling, oxidative stress response and cell cycle progression. The latter possibly refers to a higher rate of cell turnover in the inflamed lung with neutrophils, suggesting that the neutrophil influx is associated with a higher risk for the accumulation and fixation of mutations.</p> <p>Conclusion</p> <p>Gene expression profiling identified specific genes and pathways that are related to neutrophilic inflammation and could be associated to cancer development and indicate an active role of neutrophils in mediating the LPS induced inflammatory response in the mouse lung.</p

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

complex AND/OR precedence relationships

We present a Petri net (PN)-based approach to automatically generate disassembly process plans (DPPs) for product recycling or remanufacturing. We define an algorithm to generate a geometrically-based disassembly precedence matrix (DPM) from a CAD drawing of the product. We then define an algorithm to automatically generate a disassembly Petri net (DPN) from the DPM; the DPN is live, bounded, and reversible. The resulting DPN can be analyzed using the reachability tree method to generate feasible DPPs, and cost functions can be used to determine the optimal DPP, Since reachability tree generation is NP-complete, we develop a heuristic to dynamically explore the v likeliest lowest cost branches of the tree, to identify optimal or near-optimal DPPs. The cost function incorporates tool changes, changes in direction of movement, and individual part characteristics (e.g., hazardous). An example is used to illustrate the procedure. This approach can be used for products containing AND, OR, and complex AND/OR disassembly precedence relationships. (C) 2001 Elsevier Science B.V. All rights reserved

Constraint-based simulated annealing (CBSA) approach to solve the disassembly scheduling problem

Globalization, coupled with environmental requirements, has spearheaded new levels of requirements for product end-of-life, the last phase of product lifecycle management especially for product remanufacturing and recycling which involves product disassembly to retrieve the desired parts and subassemblies. Selection of optimal disassembly schedule is a major challenge for remanufacturing and recycling industries as it directly affects the inventory of the manufacturing unit and influences the final product cost. This paper proposes a constraint-based simulated annealing (CBSA) algorithm methodology to determine the ordering and disassembly schedule to minimize inventory level for products with general assembly product structure, i.e., taking into consideration part commonalities. The proposed CBSA algorithm uses the constraint-based genetic operators integrated with the simulated annealing (SA) approach that makes the algorithm more search exploratory (guarantee the optimal or near-optimal solution) and converge efficiently to the optimal solutions (less time-consuming). The proposed algorithm has higher likelihood of avoiding local optima as compared with standard SA and genetic algorithms. This is achieved by exploring a population of points, rather than a single point in the solution space. The proposed methodology is validated using a numerical case study for disassembly scheduling problem with part commonality