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Outcomes for children with relapsed or refractory acute myeloid leukaemia remain poor. The BCL-2 inhibitor, venetoclax, has shown promising activity in combination with hypomethylating agents and low-dose cytarabine in older adults for whom chemotherapy is not suitable with newly diagnosed acute myeloid leukaemia. We aimed to determine the safety and explore the activity of venetoclax in combination with standard and high-dose chemotherapy in paediatric patients with relapsed or refractory acute myeloid leukaemia. We did a phase 1, dose-escalation study at three research hospitals in the USA. Eligible patients were aged 2–22 years with relapsed or refractory acute myeloid leukaemia or acute leukaemia of ambiguous lineage with adequate organ function and performance status. During dose escalation, participants received venetoclax orally once per day in continuous 28-day cycles at either 240 mg/m2 or 360 mg/m2, in combination with cytarabine received intravenously every 12 h at either 100 mg/m2 for 20 doses or 1000 mg/m2 for eight doses, with or without intravenous idarubicin (12 mg/m2) as a single dose, using a rolling-6 accrual strategy. The primary endpoint was the recommended phase 2 dose of venetoclax plus chemotherapy and the secondary endpoint was the proportion of patients treated at the recommended phase 2 dose who achieved complete remission or complete remission with incomplete haematological recovery. Analyses were done on patients who received combination therapy. The study is registered with ClinicalTrials.gov (NCT03194932) and is now enrolling to address secondary and exploratory objectives. Between July 1, 2017, and July 2, 2019, 38 patients were enrolled (aged 3–22 years; median 10 [IQR 7–13]), 36 of whom received combination therapy with dose escalation, with a median follow-up of 7·1 months (IQR 5·1–11·2). The recommended phase 2 dose of venetoclax was found to be 360 mg/m2 (maximum 600 mg) combined with cytarabine (1000 mg/m2 per dose for eight doses), with or without idarubicin (12 mg/m2 as a single dose). Overall responses were observed in 24 (69%) of the 35 patients who were evaluable after cycle 1. Among the 20 patients treated at the recommended phase 2 dose, 14 (70%, 95% CI 46–88) showed complete response with or without complete haematological recovery, and two (10%) showed partial response. The most common grade 3–4 adverse events were febrile neutropenia (22 [66%]), bloodstream infections (six [16%]), and invasive fungal infections (six [16%]). Treatment-related death occurred in one patient due to colitis and sepsis. The safety and activity of venetoclax plus chemotherapy in paediatric patients with heavily relapsed and refractory acute myeloid leukaemia suggests that this combination should be tested in newly diagnosed paediatric patients with high-risk acute myeloid leukaemia. US National Institutes of Health, American Lebanese Syrian Associated Charities, AbbVie, and Gateway for Cancer Research.

In light of the blood cells motion inside the vein or artery, there is no knowledge available about the importance of the flow of a non-deformable micropolar drop inside a circular cylindrical pipe filled with a micropolar fluid. This paper provides a two-fluid phase motion problem of an axially symmetrical quasisteady movement of a micro-structure fluid drop embedded in another micro-structure fluid of micropolar kind on the axis of an impermeable cylindrical pipe that is discussed under the low Reynolds number conditions. The interfacial tension between the immiscible fluid phases at the drop’s interface is assumed to be very large to ensure that the droplet remains spherical in shape. Also, the microrotation and couple stress relations at the droplet’s interface are used. The general solutions for the differential equations are fulfilled by the stream functions of the micropolar fluids, which are constructed by combining fundamental solutions in cylindrical and spherical coordinates, and then the conditions on the boundaries are fulfilled at the inner surface of the pipe by the Fourier-transform and also at the interface of the drop using collocation methods. The paper’s significance is to discuss and see the effectiveness of the pipe’s inner surface on the hydrodynamic normalised force influencing the drop sphere because of its filling with and existence in a micropolar fluid. Findings indicate that the hydrodynamic normalised force is increasing monotonically with the increase of the droplet-to-pipe radius ratio, and tends to infinity when the droplet’s interface touches the pipe’s inner surface. Additionally, the findings show that when the micropolarity parameters increase, so does the normalised drag force. Our findings for the normalised force agree well with the solutions that are provided in publications. The current study is also significant in the domains of industrial and biomedical operations like coagulation, sedimentation, and rheology of suspension, to name a few.

The performance of single slope solar still with an enhanced condenser at different saline water mediums in the basin is studied and assessed based on productivity, energy, exergy, economic, and enviroeconomic methodologies. Six solar still configurations are considered: conventional solar still (CSS); modified solar still (MSS) which is a still with heat sink condenser; MSS having an umbrella (MSS + U); MSS with forced-air cooling (MSS + FA); MSS with forced-water cooling (MSS + FW); and finally, MSS with forced-water cooling and contains sand in the basin (MSS + FW + SD). Experiments are conducted under hot and cold climate conditions of Sohag city, Egypt. The results indicate that the MSS + FW + SD has a maximum daily yield of 5.37 kg/m 2 in summer and 2.74 kg/m 2 in winter with an increase of 36% in summer and 26% in winter compared with CSS. It was found that the maximum increase of the energy and exergy efficiency compared with CSS is achieved in the case of MSS + FW + SD of 39% and 33%, respectively. Furthermore, the maximum and minimum cost of freshwater is achieved in cases of MSS + U and MSS + FW + SD, respectively. Finally, among all studied systems, MSS + FW + SD achieves the best performance based on the exergoeconomic approach.

Smart Technology is a quickly and constantly evolving concept; it has different applications that cover a wide range of areas, such as healthcare, education, business, agriculture, and manufacturing. An effective application of these technologies increases productivity and performance within complex systems. On one side, trends show a lack of appeal for rural environments as people prefer to move to cities, looking for better opportunities and lifestyles. On the other side, recent studies and reports show that the attractiveness of rural areas as places with opportunities is increasing. Sustainable solutions are needed to enhance development in the rural context, and technological innovation is expected to lead and support the stability for people and organizations in rural regions. While Smart City is progressively becoming a reality and a successful model for integrating Smart Technology into different aspects of everyday life, its effective application in a rural context according to a Sustainable Development approach is not yet completely defined. This study adopts comparative and categorial content analysis to address the different applications and the specific characteristics of rural regions, which often present significant peculiarities depending on the country and the context. The main goal is to investigate and discuss how the Smart City model may be adopted and effectively applied within rural contexts, looking at major gaps and challenges. Additionally, because of the complexity of the topic, we provide an overview of the current adoption of Smart Technology in the different applications in rural areas, including farming, education, business, healthcare, and governance. The study highlights the huge difficulties in rural life and the potentiality of Smart Technology to enhance their Sustainable Development, which is still challenging. While the holistic analysis clearly points out a gap, there is no specific strategic roadmap to re-use or adapt existing models, such as Smart City. The study does not address fine-grained indicators.

Therapy targeting Bruton's tyrosine kinase (BTK) with ibrutinib has transformed the treatment of chronic lymphocytic leukaemia. However, patients who are refractory to or relapse after ibrutinib therapy have poor outcomes. Venetoclax is a selective, orally bioavailable inhibitor of BCL-2 active in previously treated patients with relapsed or refractory chronic lymphocytic leukaemia. In this study, we assessed the activity and safety of venetoclax in patients with chronic lymphocytic leukaemia who are refractory to or relapse during or after ibrutinib therapy. In this interim analysis of a multicentre, open-label, non-randomised, phase 2 trial, we enrolled patients aged 18 years or older with a documented diagnosis of chronic lymphocytic leukaemia according to the 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria and an Eastern Cooperative Oncology Group performance score of 2 or lower. All patients had relapsed or refractory disease after previous treatment with a BCR signalling pathway inhibitor. All patients were screened for Richter's transformation and cases confirmed by biopsy were excluded. Eligible patients received oral venetoclax, starting at 20 mg per day with stepwise dose ramp-up over 5 weeks to 400 mg per day. Patients with rapidly progressing disease received an accelerated dosing schedule (to 400 mg per day by week 3). The primary endpoint was overall response, defined as the proportion of patients with an overall response per investigator's assessment according to IWCLL criteria. All patients who received at least one dose of venetoclax were included in the activity and safety analyses. This study is ongoing; data for this interim analysis were collected per regulatory agencies' request as of June 30, 2017. This trial is registered with ClinicalTrials.gov, number NCT02141282. Between September, 2014, and November, 2016, 127 previously treated patients with relapsed or refractory chronic lymphocytic leukaemia were enrolled from 15 sites across the USA. 91 patients had received ibrutinib as the last BCR inhibitor therapy before enrolment, 43 of whom were enrolled in the main cohort and 48 in the expansion cohort recruited later after a protocol amendment. At the time of analysis, the median follow-up was 14 months (IQR 8–18) for all 91 patients, 19 months (9–27) for the main cohort, and 12 months (8–15) for the expansion cohort. 59 (65%, 95% CI 53–74) of 91 patients had an overall response, including 30 (70%, 54–83) of 43 patients in the main cohort and 29 (60%, 43–72) of 48 patients in the expansion cohort. The most common treatment-emergent grade 3 or 4 adverse events were neutropenia (46 [51%] of 91 patients), thrombocytopenia (26 [29%]), anaemia (26 [29%]), decreased white blood cell count (17 [19%]), and decreased lymphocyte count (14 [15%]). 17 (19%) of 91 patients died, including seven because of disease progression. No treatment-related deaths occurred. The results of this interim analysis show that venetoclax has durable clinical activity and favourable tolerability in patients with relapsed or refractory chronic lymphocytic leukaemia whose disease progressed during or after discontinutation of ibrutinib therapy. The durability of response to venetoclax will be assessed in the final analysis in 2019. AbbVie, Genentech.

This research validates An Adaptive Fuzzy Logic Controller (AFLC) has been developed for grid-connected photovoltaic (PV) systems. The primary objective of this implementation is to enhance the PV system’s power generation efficiency. For achieving this, techniques of Maximum Power Point Tracking (MPPT) are utilized, which are essential to extract the highest possible power outing from PV panels. Recent developments in MPPT methods focus on improving control strategies to ensure efficient operation and smooth integration with the grid. The performance of the AFLC is extensively evaluated and compared with other controllers, like fuzzy-logic controller (FLC) and Proportional Integral (PI). The proposed AFLC controller’s performance is evaluated with other methods to verify its effectiveness. To validate this method, the system is tested using MATLAB/Simulink simulations, along with experimental evaluations conducted on the control strategies are executed in real-time utilizing the DSpace DS1104 control. Experimental results show that the AFLC outperforms both the FLC and PI controllers in several key performance areas. Specifically, the AFLC demonstrates faster response times, higher convergence rates, decreased peak overshoot, minimal undershoot, and lower the error of the mean square. Additionally, the Compared to conventional Fuzzy Logic Control (FLC) and PI controllers, the AFLC delivers superior efficiency and transient response, and oscillation reduction. Compared to the FLC, the AFLC enhances tracking of power by 68.26%, and it achieves 86.25% improvement over the PI controller. These findings highlight the AFLC’s potential as a highly effective and reliable optimization tool for maximizing the output power of the systems of PV. Furthermore, integral absolute error (IAE) is used as a performance metric for the PV system connected to grid to assess the efficiency of the AFLC. The AFLC demonstrated superior performance over other methods, achieving a 20% increase in PV output power compared to traditional FLC and a 30% improvement over PI controllers. The errors of the PI, FLC and AFLC approaches, each utilizing five controllers, are estimated. The error of mean square is reduced by 79.67% in comparison to PI and by 66.5% in comparison to FLC.

In today’s data-driven digital culture, there is a critical demand for optimized solutions that essentially reduce operating expenses while attempting to increase productivity. The amount of memory and processing time that can be used to process enormous volumes of data are subject to a number of limitations. This would undoubtedly be more of a problem if a dataset contained redundant and uninteresting information. For instance, many datasets contain a number of non-informative features that primarily deceive a given classification algorithm. In order to tackle this, researchers have been developing a variety of feature selection (FS) techniques that aim to eliminate unnecessary information from the raw datasets before putting them in front of a machine learning (ML) algorithm. Meta-heuristic optimization algorithms are often a solid choice to solve NP-hard problems like FS. In this study, we present a wrapper FS technique based on the sparrow search algorithm (SSA), a type of meta-heuristic. SSA is a swarm intelligence (SI) method that stands out because of its quick convergence and improved stability. SSA does have some drawbacks, like lower swarm diversity and weak exploration ability in late iterations, like the majority of SI algorithms. So, using ten chaotic maps, we try to ameliorate SSA in three ways: (i) the initial swarm generation; (ii) the substitution of two random variables in SSA; and (iii) clamping the sparrows crossing the search range. As a result, we get CSSA, a chaotic form of SSA. Extensive comparisons show CSSA to be superior in terms of swarm diversity and convergence speed in solving various representative functions from the Institute of Electrical and Electronics Engineers (IEEE) Congress on Evolutionary Computation (CEC) benchmark set. Furthermore, experimental analysis of CSSA on eighteen interdisciplinary, multi-scale ML datasets from the University of California Irvine (UCI) data repository, as well as three high-dimensional microarray datasets, demonstrates that CSSA outperforms twelve state-of-the-art algorithms in a classification task based on FS discipline. Finally, a 5%-significance-level statistical post-hoc analysis based on Wilcoxon’s signed-rank test, Friedman’s rank test, and Nemenyi’s test confirms CSSA’s significance in terms of overall fitness, classification accuracy, selected feature size, computational time, convergence trace, and stability.

This article outlines the synthesis of two derivatives of 4-amino-5-hydrazineyl-4 H -1,2,4-triazole-3-thiol for the prevention of carbon steel corrosion in 1M HCl solution. These derivatives are ( Z )-3-(1-(2-(4-amino-5-mercapto-4 H -1,2,4-triazol-3-yl)hydrazono)ethyl)-2 H -chromen-2-one ( TZ1 ) and 5-(2-(9 H -fluoren-9-ylidene)hydrazineyl)-4-amino-4 H -1,2,4-triazole-3-thiol ( TZ2 ). Weight loss, electrochemical experiments, surface examinations, and theoretical computation are used to evaluate the effectiveness of the two compounds to be used as corrosion inhibitors. Weight loss and electrochemical studies demonstrate that these derivatives reduce the corrosion rate of carbon steel. To examine the morphology and constitution of the carbon steel surface submerged in HCl solution as well as after adding inhibitors, surface examination tests are performed. Analysis of the test solution via UV–visible spectroscopy is employed to check the possibility of complex formation between inhibitor molecules and Fe 2+ ions released during the corrosion process. In order to explore their biological activity, the antibacterial activity was investigated against ( E. coli and Bacillus subtilis ). Finally, theoretical confirmation of the experimental findings is provided by quantum chemical (DFT) and Monte Carlo (MC) simulation studies. More adsorption sites are present in the derivatives of 4-amino-5-hydrazineyl-4 H -1,2,4-triazole-3-thiol, which offer a novel perspective for developing new classes of corrosion inhibitors with substantial protective efficacy, especially at high temperatures.

The latest research in computer vision highlighted the effectiveness of the vision transformers (ViT) in performing several computer vision tasks; they can efficiently understand and process the image globally unlike the convolution which processes the image locally. ViTs outperform the convolutional neural networks in terms of accuracy in many computer vision tasks but the speed of ViTs is still an issue, due to the excessive use of the transformer layers that include many fully connected layers. Therefore, we propose a real-time ViT-based monocular depth estimation (depth estimation from single RGB image) method with encoder-decoder architectures for indoor and outdoor scenes. This main architecture of the proposed method consists of a vision transformer encoder and a convolutional neural network decoder. We started by training the base vision transformer (ViT-b16) with 12 transformer layers then we reduced the transformer layers to six layers, namely ViT-s16 (the Small ViT) and four layers, namely ViT-t16 (the Tiny ViT) to obtain real-time processing. We also try four different configurations of the CNN decoder network. The proposed architectures can learn the task of depth estimation efficiently and can produce more accurate depth predictions than the fully convolutional-based methods taking advantage of the multi-head self-attention module. We train the proposed encoder-decoder architecture end-to-end on the challenging NYU-depthV2 and CITYSCAPES benchmarks then we evaluate the trained models on the validation and test sets of the same benchmarks showing that it outperforms many state-of-the-art methods on depth estimation while performing the task in real-time (∼20 fps). We also present a fast 3D reconstruction (∼17 fps) experiment based on the depth estimated from our method which is considered a real-world application of our method.

The effect of posaconazole, a strong cytochrome P450 3A (CYP3A) inhibitor and commonly used antifungal agent, on the pharmacokinetic properties of venetoclax, a CYP3A substrate, was evaluated in patients with acute myeloid leukemia to determine the dose adjustments needed to manage this potential interaction. Twelve patients received 20- to 200-mg ramp-up treatment with oral venetoclax and 20 mg/m2 of intravenous decitabine on days 1 through 5, followed by 400 mg of venetoclax alone on days 6 through 20. On days 21 through 28, patients received 300 mg of posaconazole plus reduced doses of venetoclax (50 or 100 mg) to account for expected increases in venetoclax plasma concentrations. Blood samples were collected before dosing and up to 24 hours after the venetoclax dose on days 20 and 28. Compared with a venetoclax dose of 400 mg when administered alone (day 20), coadministration of venetoclax at a 50-mg dose with multiple doses of posaconazole increased mean venetoclax Cmax and AUC0–24 by 53% and 76%, respectively, whereas coadministration of venetoclax at a 100-mg dose with posaconazole increased mean venetoclax Cmax and AUC0–24 by 93% and 155%, respectively. When adjusted for different doses and nonlinearity, posaconazole was estimated to increase venetoclax Cmax and AUC0–24 by 7.1- and 8.8-fold, respectively. Both the 50- and 100-mg venetoclax doses administered with posaconazole were well tolerated. The results are consistent with inhibition of CYP3A-mediated metabolism of venetoclax. Posaconazole can be used for antifungal prophylaxis in patients with acute myeloid leukemia receiving venetoclax after reducing the venetoclax dose by at least 75%. ClinicalTrials.gov identifier: NCT02203773.