Medication non-adherence remains a substantial obstacle in asthma care, prompting the exploration of novel therapeutic modalities that prioritize rapid symptom relief, anti-inflammatory activity and facilitate patients’ compliance. This task is well served by a new form of therapy - inhaled triple-combination medications ICS/LABA/LAMA (inhaled glucocorticosteroid/long-acting beta2-agonist/long-acting muscarinic antagonist). The integration of three medications within a singular inhalation device culminates in the reduction of the effective dose of the principal therapeutic agent for asthma management, namely, ICS. This consolidation yields a dual benefit of minimizing the likelihood of adverse effects typically linked with ICS while concurrently optimizing bronchodilator efficacy. The accumulated evidence suggests that adding LAMA to a medium- or high-dose ICS/LABA results in a decrease of asthma exacerbations compared to medium- or high-dose ICS/LABA alone, accompanied by sustained enhancements in lung function parameters. We propose in adult patients experiencing suboptimal asthma control despite medium/high-dose ICS/LABA treatment - regardless of adherence to GINA-recommended strategies, such as MART therapy as a first-line approach or alternative second-line strategies - the preferred course for intensifying asthma therapy involves the addition of a LAMA, ideally in the form of SITT.

Asthma is a chronic inflammatory airway disease induced by many environmental factors. The inhalation of allergens and pollutants promote the reactive oxygen species (ROS) production leading to airway inflammation, hyper-responsiveness and remodeling in allergic asthma. The effects of asthma medications on ROS production are unclear. The present study investigated the anti-ROS effects of current asthma medications including inhaled corticosteroid (ICS; budesonide and fluticasone), leukotriene receptor antagonist (LTRA; montelukast), long acting β2 agonists (LABAs; salmeterol and formoterol) and a new extra-LABA (indacaterol). The human monocyte cell line THP-1 cells were pre-treated with different concentrations of the asthma medications at different time-points after hydrogen peroxide (H₂O₂) stimulation. H₂O₂ production was measured with DCFH-DA by flow cytometry. Montelukast, fluticasone and salmeterol suppressed H₂O₂-induced ROS production. Indacaterol enhanced H₂O₂-induced ROS production. Budesonide and formoterol alone had no anti-ROS effects, but the combination of these two drugs significantly suppressed H₂O₂-induced ROS production. Different asthma medications have different anti-ROS effects on monocytes. The combination therapy with LABA and ICS seemed not be the only choice for asthma control. Montelukast may be also a good supplemental treatment for the poorly-controlled asthma because of its powerful anti-ROS effects. Our findings provide a novel therapeutic view in asthma.

Industrial Control Systems (ICS) are integral to managing and optimizing processes in various industries, including manufacturing, power generation, and more. However, the scarcity of widely adopted ICS datasets hampers research efforts in areas like optimization and security. This scarcity arises due to the substantial cost and technical expertise required to create physical ICS environments. In response to these challenges, this paper presents a groundbreaking approach to generating synthetic ICS data through a data-driven ICS network simulation. We circumvent the need for expensive hardware by recreating the entire ICS environment in software. Moreover, rather than manually replicating the control logic of ICS components, we leverage existing data to autonomously generate control logic. The core of our method involves the stochastic setting of setpoints, which introduces randomness into the generated data. Setpoints serve as target values for controlling the operation of the ICS process. This approach enables us to augment existing ICS datasets and cater to the data requirements of machine learning-based ICS intrusion detection systems and other data-driven applications. Our simulated ICS environment employs virtualized containers to mimic the behavior of real-world PLCs and SCADA systems, while control logic is deduced from publicly available ICS datasets. Setpoints are generated probabilistically to ensure data diversity. Experimental results validate the fidelity of our synthetic data, emphasizing its ability to closely replicate temporal and statistical characteristics of real-world ICS networks. In conclusion, this innovative data-driven ICS network simulation offers a cost-effective and scalable solution for generating synthetic ICS data. It empowers researchers in the field of ICS optimization and security with diverse, realistic datasets, furthering advancements in this critical domain. Future work may involve refining the simulation model and exploring additional applications for synthetic ICS data.

Clock Network Design (CDN) is a critical step while designing any Integrated-Circuits (ICs). It holds vital importance in the performance of entire circuit. Due to continuous scaling, 3D ICs stacked with TSV are gaining importance, with an objective to continue with the Moore's law. Through-Silicon-Via (TSV) provides the vertical interconnection between two die, which allows the electrical signal to flow through it. 3D ICs has many advantages over conventional 2D planar ICs like reduced power, area, cost, wire-length etc. The proposed work is mainly focused on power reduction and obstacle avoidance for 3D ICs. Various techniques have already been introduced for minimizing clock power within specified clock constraints of the 3D CND network. Proposed 3D Clock Tree Synthesis (CTS) is a combination of various algorithms with an objective to meet reduction in power as well as avoidance of obstacle or blockages while routing the clock signal from one sink to other sink. These blockages like RAM, ROM, PLL etc. are fixed during the placement process. The work is carried out mainly in three steps- first is Generation of 3D Clock tree avoiding the blockages, then Buffering and Embedding and finally validating the results by SPICE simulation. The experimental result shows that our CTS approach results in significant 9% reduction in power as compare to the existing work.

The performance of a small reconfigurable unmanned aerial vehicle (UAV) is evaluated, 1 combining a multidisciplinary approach in computational analysis of additive manufactured struc- 2 tures, fluid dynamics, and experiments. Reconfigurable UAVs promise cost savings and efficiency 3 without sacrificing performance, while demonstrating versatility to fulfill different military mission 4 profiles. The use of computational fluid dynamics (CFD) in UAV design produces higher accuracy 5 aerodynamic data, which is particularly important for complex aircraft concepts such as blended 6 wing bodies. To address challenges relating to anisotropic materials, the Tsai-Wu failure criterion is 7 applied to structural analysis, using CFD solutions as load inputs. Aerodynamic performance results 8 show the low-speed variant attains an endurance of 1 hour, 48 minutes, whereas for its high-speed 9 counterpart, it is 29 minutes at 66.7% higher cruise speed. Each variant serves different aspects of 10 small UAS deployment in combat, with low-speed envisioned for close surveillance, and high-speed 11 for incursions. Experimental and simulation results suggest room for design iteration, in wing area 12 and geometry adjustments. Structural simulations demonstrated the need for airframe improvements 13 in the low-speed configuration. This paper highlights the potential of reconfigurable UAVs to disrupt 14 the industry, advocating for further research and design improvements.