Search Results (12)

Background: Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype of B-cell ALL characterized by a gene expression profile similar to BCR::ABL1-positive leukemia, but lacking the BCR::ABL1 fusion gene. It is frequently associated with kinase-activating alterations, such as CRLF2 rearrangements, JAK-STAT pathway mutations, and ABL-class fusions. Patients with Ph-like ALL typically experience poor outcomes with conventional chemotherapy, underscoring the need for intensified and targeted therapeutic approaches. Methods: This review summarizes current evidence regarding the role of hematopoietic stem cell transplantation (HSCT) in patients with Ph-like ALL. We analyzed retrospective cohort studies, registry data, and ongoing clinical trials, focusing on transplant indications, molecular risk stratification, measurable residual disease (MRD) status, timing of transplant, and post-transplant strategies. Results: Retrospective data suggest that HSCT in first complete remission (CR1) may improve survival in patients with high-risk molecular lesions or MRD positivity at the end of induction. However, the lack of prospective data specific to Ph-like ALL limits definitive conclusions. Post-transplant relapse remains a challenge, and novel strategies, including the use of tyrosine kinase inhibitors or JAK inhibitors as post-HSCT maintenance therapy, are being explored. Emerging immunotherapies, such as chimeric antigen receptor (CAR) T cells, may reshape the therapeutic landscape and potentially alter the indications for transplantation. Conclusions: HSCT remains a crucial therapeutic option for selected patients with Ph-like ALL, particularly those with poor molecular risk features or persistent MRD. However, further prospective studies are needed to evaluate the indication for HSCT in CR1 and the potential integration of transplantation with targeted and immunotherapeutic strategies. Personalized treatment approaches based on genomic profiling and MRD assessment are essential to improve outcomes in this high-risk subset. Full article

Background: Nucleophosmin-1 (NPM1) mutation accounts for 30% of acute myeloid leukemia (AML) cases and defines either low- or intermediate-risk AML, depending on FLT3-ITD mutation. New combination regimens (NCRs), adding midostaurin and gemtuzumab ozogamicin (GO) to the 3 + 7 scheme, are commonly used, though there are no data that compare NCRs with intensive induction chemotherapy. Methods: To evaluate the efficacy and safety of NCRs and FLAI in NPM1+ AML, we retrospectively analyzed 125 patients treated with FLAI (n = 53) or NCRs (n = 72) at seven Italian Centers. Results: The median age was 61 years and 51/125 (41%) were FLT3-ITD+. The complete remission (CR) rate was 77%, slightly better with NCRs (83% vs. 68%; p = 0.054). NCRs yielded a superior median overall survival (OS) (not reached (NR) vs. 27.3 months; p = 0.002), though the median event-free survival (EFS) was similar (NR vs. 20.5 months; p = 0.07). In low-risk AML, CR was higher in NCRs (94% vs. 72%, p = 0.02), as were median OS (NR vs. 41.6 months; p = 0.0002) and EFS (NR vs. 17.8 months; p = 0.0085). In intermediate-risk AML (FLT3-ITD+), there were no differences in CR (60% vs. 71%; p = 0.5), OS (p = 0.27), or EFS (p = 0.86); only allogeneic transplantation improved OS (NR vs. 13.4 months; p = 0.005), regardless of induction regimen. The safety profile was similar, except for delayed platelet recovery with FLAI (22 vs. 18 days; p = 0.0024) and higher-grade II–IV gastrointestinal toxicity with NCRs (43% vs. 18.8%; p = 0.0066). Conclusions: Our data suggest the superiority of NCRs over FLAI in low-risk patients, while all outcomes were comparable in intermediate-risk patients, a setting in which only transplants positively impacted on survival. Full article

Shipping is a highly energy-intensive sector, and fleet decarbonization initiatives can significantly reduce greenhouse gas emissions. In the short-to-medium term, internal combustion engines will continue to be used for propulsion or as electricity generators onboard ships. Natural gas is an effective solution which can be used to mitigate greenhouse gas emissions from the marine sector. Considered to be a transitional fuel, it can provide a potential reduction in CO₂ emissions of around 20–30%, compared with conventional marine fuels. This work investigated the influence of diesel-injection strategies on the performance and emissions of a single-cylinder prototype compression-ignition engine for marine applications, retrofitted to run as a Low-Pressure Dual-Fuel Engine using natural gas. Two different injection systems were used: a mass flow controller enabling continuous-mode gas feeding, and a Solenoid-Operated Gas Admission Valve for marine applications, the latter allowing phased natural-gas injection. Experimental tests were focused on partial-load conditions, which are critical for dual-fuel engines, with a natural gas/diesel mass ratio of 4:1. Phased injection resulted in reductions in fuel consumption, compared to continuous mode, of up to 11%. Further experiments demonstrated reductions in fuel consumption of up to 20.7% (in equivalent diesel); on the other hand, the unburned hydrocarbon emissions which resulted were an order of magnitude larger than the reference values for full diesel, reducing the benefits in terms of greenhouse gas emissions, with a reduction in Global Warming Potential of only 3% compared to full diesel. Full article

Phased injection of natural gas into internal combustion marine engines is a promising solution for optimizing performance and reducing harmful emissions, particularly unburned methane, a potent greenhouse gas. This innovative practice distinguishes itself from continuous injection because it allows for more precise control of the combustion process with only a slight increase in system complexity. By synchronizing the injection of natural gas with the intake and exhaust valve opening and closing times while also considering the gas path in the manifolds, methane release into the atmosphere is significantly reduced, making a substantial contribution to efforts to address climate change. Moreover, phased injection improves the efficiency of marine engines, resulting in reduced overall fuel consumption, lower fuel costs, and increased ship autonomy. This technology was tested on a single-cylinder, large-bore, four-stroke research engine designed for marine applications, operating in dual-fuel mode with diesel and natural gas. Performance was compared with that of the conventional continuous feeding method. Evaluation of the effect on equivalent CO₂ emissions indicates a potential reduction of up to approximately 20%. This reduction effectively brings greenhouse gas emissions below those of the diesel baseline case, especially when injection control is combined with supercharging control to optimize the air–fuel ratio. In this context, the boost pressure in DF was reduced from 3 to 1.5 bar compared with the FD case. Full article

This article delves into sensitivity analysis within simulation models of real systems, focusing on the impact of variability in independent input factors (x) on dependent system outputs (y). It discusses linear and nonlinear regression to analyse and represent relationships between input factors and system responses. This study encompasses three sensitivity analysis areas: factor screening, local sensitivity analysis, and global sensitivity analysis, highlighting their roles in understanding the significance of factors in simulation models. The practical application of sensitivity analysis becomes clear through a case study in a manufacturing system. The case study utilises the Simio simulation system to investigate the impact of input factors on production lead time and work in process (WIP). The analysis uses regression to quantify the impact of seven factors, showcasing the most significant ones with tornado charts and emphasising the application of sensitivity analysis to optimise system responses. Full article

The need for certification standards for new convergence products, such as a smart LED streetlight system, has been identified as a critical issue. This study proposes simulation modeling for smart LED streetlight systems and suggests three certification standards: the minimum time to initiate dimming-up, the duration of the dimming-up period, and the number of concurrently controlled streetlights. We utilized Relux to model streetlights and roads in terms of luminance levels, and used analytical formulas to compute the braking distances of oncoming vehicles. The two models were integrated into a smart LED streetlight system model using Simio. Simulation experiments were conducted with two objectives: to provide certification standards, and to apply and verify them in real-world cases. We experimented with 630 scenarios, modeling various dynamic situations involving roads and vehicles, and applied the model to two actual roads in the Republic of Korea to test its validity. The model was subsequently applied to roads for which traffic-volume data were available, to determine potential energy savings. The proposed simulation method can be applied to a smart LED streetlight system and to new products that lack certification standards. Furthermore, the proposed certification standards offer alternative approaches to operating streetlight systems more efficiently. Full article

The simple assembly line balancing (SALB) problem is a significant challenge faced by industries across various sectors aiming to optimise production line efficiency and resource allocation. One important issue when the decision-maker balances a line is how to keep the cycle time under a given time across all cells, even though there is variability in some parameters. When there are stochastic elements, some approaches use constraint relaxation, intervals for the stochastic parameters, and fuzzy numbers. In this paper, a three-part algorithm is proposed that first solves the balancing problem without considering stochastic parameters; then, using simulation, it measures the effect of some parameters (in this case, the inter-arrival time, processing times, speed of the material handling system which is manually performed by the workers in the cell, and the number of workers who perform the tasks on the machines); finally, the add-on OptQuest in SIMIO solves an optimisation problem to constrain the cycle time using the stochastic parameters as decision variables. A Gearbox instance from literature is solved with 15 tasks and 14 precedence rules to test the proposed approach. The deterministic balancing problem is solved optimally using the open solver GLPK and the Pyomo programming language, and, with simulation, the proposed algorithm keeps the cycle time less than or equal to 70 s in the presence of variability and deterministic inter-arrival time. Meanwhile, with stochastic inter-arrival time, the maximum cell cycle is 72.04 s. The reader can download the source code and the simulation models from the GitHub page of the authors. Full article

This study presents an approach to solving the assembly line balancing problem (ALBP) using the Methods-Time Measurement (MTM) time standard and simulation software. ALBP is a common problem in manufacturing where a set of tasks with fixed times must be assigned to a series of sequential workstations in order to minimize the total idle time and reduce the assembly cost per product. This study uses MTM, a widely used production process scheduling method, to create a new time analysis of an assembly process that was previously balanced using the Work-Factor method and time study. This literature review shows that there are a lack of combinations of updated time analyses with newer simulation approaches in the current literature, and this was the motivation for the present work. An assembly line simulation was performed using Simio software to evaluate different design options and operating scenarios. The results show that the use of MTM and simulation can help minimize idle time and improve assembly line performance, thereby reducing costs and increasing efficiency. This study shows that the approach of using MTM and simulation is effective in solving ALBP and is a useful tool for manufacturing companies to improve the performance of their assembly lines and reduce costs. Full article

The mathematical study known as queueing theory has recently become a major point of interest for many government agencies and private companies for increasing efficiency. One such application is vehicle queueing at an international port-of-entry (POE). When queueing, fumes from idling vehicles negatively affect the overall health and well-being of the community, especially the U.S. Customs and Border Protection (CBP) agents that work at the POEs. As such, there is a need to analyze and optimize the border crossing queuing operations to minimize wait times and number of vehicles in the queue and, thus, reduce the vehicle emissions. For this research, the U.S.–Mexico POE located at The Gateway International Bridge in Brownsville, Texas, is used as a case study. Due to data privacy concerns, the hourly wait times for vehicles arriving at the border had to be extracted manually each day using a live wait time tracker online. The data extraction was performed for the month of March 2022. Using these wait times, a queueing simulation software, SIMIO, was used to develop an interactive simulation model and calibrate the service rates. The output from the SIMIO model was then used to develop an artificial neural network (ANN) to predict hourly particulate matter content with an R² of 0.402. From the ANN, a predictive equation has been developed, which may be used by CBP to make operational decisions and improve the overall efficiency of this POE. Thus, lowering the average wait times and the emissions from idling vehicles in the queue. Full article

LNG technologies have long been used but only recently found widespread employment on medium and small scales compared to the traditional cycle of liquefaction, transport by ship, regasification and injection into the gas network. This has increased the direct use of LNG with the problem of limiting greenhouse gas emissions, linked to gas released principally in the event of prolonged absence of fuel drawing from the cryogenic tank. This study analyzes the energetic exploitation of BOG in small internal combustion engines. The effect on CO₂ equivalent emissions was evaluated, making a comparison with the BOG emission into the atmosphere directly or after burning. A 1 kW gasoline engine was selected for a 500-litre LNG tank and converted to gas fueling. The measured consumption and emissions resulted in compliance with a lower environmental impact compared to direct BOG release into the atmosphere despite simplified technical solutions, such a cheap and light 2-stroke engine. In contrast, only a 4-stroke engine has performance such as achieving a reduction in GHG emissions, up to zero, even compared to the case of BOG combustion before releasing it into the atmosphere. Full article

The paper deals with the experimental study of a medium-load spark ignition engine under operation with different fuel mixtures among those deemed as promising for the transition towards carbon-free energy systems. In particular, the performance of a non-conventional ignition system, which permits the variation of the ignition energy, the spark intensity and duration, was studied fuelling the engine with 60–40% hydrogen–methane blends, three real syngas mixtures and one biogas. The paper is aimed to find the optimal ignition timing for minimum specific fuel consumption and the best setup of the ignition system for each of the fuel mixtures considered. To this end, a series of steady-state tests were performed at the dynamometer by varying the parameters of the ignition system and running the engine with surrogate hydrogen–methane–nitrogen mixtures that permit the simulation of hydrogen–methane blends, real syngas, and biogas. The results quantify the increase of spark advance associated with the decrease of the fuel quality and discuss the risk of knock onset during methane–hydrogen operation. It was demonstrated that the change of the ignition system parameters does not affect the value of optimum spark advance and, except for the ignition duration, all the parameters’ values are generally not very relevant at full load operation. In contrast, at partial load operation with low-quality syngas or high exhaust gas recirculation rate, it was found that an increase of the maximum ignition energy (to 300 mJ) allows for operation down to approximately 66% of the maximum load before combustion becomes incomplete. Further reductions, down to 25% of the maximum load, can be achieved by increasing the gap between the spark plug electrodes (from 0.25 to 0.5 mm). Full article

As a well-known NP-hard problem, the dynamic job shop scheduling problem has significant practical value, so this paper proposes an Improved Heuristic Kalman Algorithm to solve this problem. In Improved Heuristic Kalman Algorithm, the cellular neighbor network is introduced, together with the boundary handling function, and the best position of each individual is recorded for constructing the cellular neighbor network. The encoding method is introduced based on the relative position index so that the Improved Heuristic Kalman Algorithm can be applied to solve the dynamic job shop scheduling problem. Solving the benchmark example of dynamic job shop scheduling problem and comparing it with the original Heuristic Kalman Algorithm and Genetic Algorithm-Mixed, the results show that Improved Heuristic Kalman Algorithm is effective for solving the dynamic job shop scheduling problem. The convergence rate of the Improved Heuristic Kalman Algorithm is reduced significantly, which is beneficial to avoid the algorithm from falling into the local optimum. For all 15 benchmark instances, Improved Heuristic Kalman Algorithm and Heuristic Kalman Algorithm have obtained the best solution obtained by Genetic Algorithm-Mixed. Moreover, for 9 out of 15 benchmark instances, they achieved significantly better solutions than Genetic Algorithm-Mixed. They have better robustness and reasonable running time (less than 30 s even for large size problems), which means that they are very suitable for solving the dynamic job shop scheduling problem. According to the dynamic job shop scheduling problem applicability, the integration-communication protocol was presented, which enables the transfer and use of the Improved Heuristic Kalman Algorithm optimization results in the conventional Simio simulation environment. The results of the integration-communication protocol proved the numerical and graphical matching of the optimization results and, thus, the correctness of the data transfer, ensuring high-level usability of the decision-making method in a real-world environment. Full article