Crossover Rate Research Articles

Water and heat management of vapor-fed direct methanol fuel cells with a non-isothermal triple-phase mass transfer model

Direct methanol fuel cells (DMFCs) operating with methanol vapor tends to operate under higher temperature, which contributes to improve cell performance and specific energy. However, the design of vapor-fed DMFCs with high performance and adaptability are still hindered by the complex water and heat management. To provide a comprehensive understanding of the critical multiphase heat and mass transfer, we develop a two-dimensional non-isothermal triple-phase mass transfer model for a passive vapor-fed DMFC. Effects of the electrochemical reactions and related thermal effect are fully investigated. Increasing the current density raises the operating temperature, thus enhancing the generation rate of methanol vapor and reducing concentration polarization under high current densities. With the enlargement of the open area ratio (from 0.1 to 0.3), an excessive methanol supply rate may cause deteriorated methanol crossover rates and excessively high temperatures, resulting in severe dehydration of polymer electrolytes and a degraded cathode overpotential (from −0.48V to −0.54V). For the DMFC with Nafion 112 membrane, the maximum current density and peak power density are 33.3% and 36.0% greater than that of Nafion 117 membrane. The simulation work will provide an exhaustive theoretical guidance for the efficient management of water and heat in DMFCs fed with neat methanol.

High-resolution mapping reveals hotspots and sex-biased recombination in Populus trichocarpa.

Fine-scale meiotic recombination is fundamental to the outcome of natural and artificial selection. Here, dense genetic mapping and haplotype reconstruction were used to estimate recombination for a full factorial Populus trichocarpa cross of 7 males and 7 females. Genomes of the resulting 49 full-sib families (N = 829 offspring) were resequenced, and high-fidelity biallelic SNP/INDELs and pedigree information were used to ascertain allelic phase and impute progeny genotypes to recover gametic haplotypes. The 14 parental genetic maps contained 1,820 SNP/INDELs on average that covered 376.7 Mb of physical length across 19 chromosomes. Comparison of parental and progeny haplotypes allowed fine-scale demarcation of cross-over regions, where 38,846 cross-over events in 1,658 gametes were observed. Cross-over events were positively associated with gene density and negatively associated with GC content and long-terminal repeats. One of the most striking findings was higher rates of cross-overs in males in 8 out of 19 chromosomes. Regions with elevated male cross-over rates had lower gene density and GC content than windows showing no sex bias. High-resolution analysis identified 67 candidate cross-over hotspots spread throughout the genome. DNA sequence motifs enriched in these regions showed striking similarity to those of maize, Arabidopsis, and wheat. These findings, and recombination estimates, will be useful for ongoing efforts to accelerate domestication of this and other biomass feedstocks, as well as future studies investigating broader questions related to evolutionary history, perennial development, phenology, wood formation, vegetative propagation, and dioecy that cannot be studied using annual plant model systems.

An Analysis of the Operation Factors of Three PSO-GA-ED Meta-Heuristic Search Methods for Solving a Single-Objective Optimization Problem.

In this study, we evaluate several nongradient (evolutionary) search strategies for minimizing mathematical function expressions. We developed and tested the genetic algorithms, particle swarm optimization, and differential evolution in order to assess their general efficacy in optimization of mathematical equations. A comparison is then made between the results and the efficiency, which is determined by the number of iterations, the observed accuracy, and the overall run time. Additionally, the optimization employs 12 functions from Easom, Holder table, Michalewicz, Ackley, Rastrigin, Rosen, Rosen Brock, Shubert, Sphere, Schaffer, Himmelblau's, and Spring Force Vanderplaats. Furthermore, the crossover rate, mutation rate, and scaling factor are evaluated to determine the effectiveness of the following algorithms. According to the results of the comparison of optimization algorithms, the DE algorithm has the lowest time complexity of the others. Furthermore, GA demonstrated the greatest degree of temporal complexity. As a result, using the PSO method produces different results when repeating the same algorithm with low reliability in terms of locating the optimal location.

Visualization of Combustion in Polymer-Electrolyte-Membrane Fuel Cell - Mechanism on Abrupt Change from Moderate to Accidental Scale-

This study is focused on elucidating the catalytic combustion phenomenon in proton-exchange membrane fuel cells. A visualization cell and an infrared (IR) camera are used to capture the thermal behavior under combined chemical and mechanical accelerated stress conditions in situ. A 3.4 cm2 catalyst coated membrane (CCM) embedded in the cell is subjected to a relative humidity (RH) cycling test at atmospheric pressure and a cell temperature of 80 °C under open-circuit voltage (OCV) conditions. The temperature distribution on the gas diffusion layer surface at the cathode is captured using a high-transmittance glass window (ZnS window). Continuous IR imaging revealed a hot spot at ca. 500 RH cycles, suggesting the existence of a pinhole in the degraded CCM and the occurrence of catalytic combustion there. The occurrence of the hot spot coincides with the time at which the electrochemical indicators detect membrane failure, i.e., hydrogen crossover rate, OCV. Furthermore, the post mortem analysis revealed a 105-micrometer diameter pinhole, the position of which matched that of the hotspot. An accidental combustion during the durability test could cause the formation of a pinhole. This pinhole is responsible for the rapid increase in the hydrogen crossover rate as well as the significant decrease in the OCV at 500 RH cycles until the end of the durability test. Figure 1

Operando Measurement of Hydrogen Crossover in Proton Exchange Membrane Electrolysis Cells at Differential Pressures

Low temperature water electrolysis (LTE) using proton exchange membrane electrolysis cells (PEMECs) is a promising approach for producing green H2 that can use electricity from renewable sources. In practice, H2 is stored and dispensed at high pressures. To alleviate efficiency losses associated with pressurizing the product hydrogen, PEMECs can be operated at high differential pressures, e.g., >30bar on the cathode side. However, high differential pressure operation can result in undesirable H2 crossover to the anode (O2) side. This not only reduces the Faradaic efficiency of the cell, but also can result in flammability hazards. H2 crossover in PEMECs is a function of both materials properties such as membrane thickness, water uptake, and permeability, and operating conditions such as temperature, differential pressure, and current density. Example data are shown in Figure 1. While thinner membranes are susceptible to higher H2 crossover rates, they are a desirable material to use because they can result in significantly improved cell performance and lower material and production costs. To mitigate safety concerns related to H2 crossover, gas recombination catalyst (GRC) layers can be introduced into the membrane electrode assembly. The GRCs will react the crossover H2 with O2 to produce water, thereby minimizing the amount of H2 entering the O2 stream. In this talk we will present data from operando crossover measurements of PEMECs employing a variety of membrane materials, both with and without GRCs. The experiments are complimented by modeling results that allow further insights into the processes at hand. Multiple temperatures, differential pressures, and current densities are studied. The results will investigate the tradeoff between performance and capturable H2 production that occurs when thinner membranes are used, and how this effect responds to differential pressure operation. Figure 1

The Impacts of Membrane Pinholes on Performance and Hydrogen Crossover in PEM Water Electrolysis

Polymer electrolyte membrane (PEM) water electrolysis is a promising energy storage technology to produce highly pure hydrogen with high efficiency 1. However, to implement it on a larger scale, it is essential to understand the effects of defects and the required tolerances and quality controls during manufacturing or subsequent handling. Inhomogeneities in membrane electrode assembly (MEA) component materials caused by the manufacturing process or subsequent handling can lead to performance loss and failure 2. Defects such as membrane pinholes, cuts, tears, abrasions, or perforations can all potentially impact MEA performance. In terms of impact, a loss of integrity of the membrane can allow bulk gas transport (crossover) and/or electrical shorting 3.In particular, hydrogen crossover is a crucial issue for PEM water electrolysis in terms of safe operation and efficiency losses, especially at increased hydrogen pressures. Crossover reduces the overall efficiency of the system and poses flammability hazards under certain conditions 4. Pinholes that form during the manufacturing process or during operation through degradation of the membrane lead to dramatically increased hydrogen crossover.In this study, the impacts of membrane pinholes on the performance and hydrogen crossover of PEM water electrolyzer cells are studied. Pinholes with different sizes are artificially introduced to the MEA to investigate the effects on the initial cell performance and hydrogen crossover rate under various backpressure and current density conditions. Reference Liu, C.; Shviro, M.; Gago, A. S.; Zaccarine, S. F.; Bender, G.; Gazdzicki, P.; Morawietz, T.; Biswas, I.; Rasinski, M.; Everwand, A., Exploring the Interface of Skin‐Layered Titanium Fibers for Electrochemical Water Splitting. Adv Energy Mater 2021, 11 (8), 2002926.Ulsh, M.; DeBari, A.; Berliner, J. M.; Zenyuk, I. V.; Rupnowski, P.; Matvichuk, L.; Weber, A. Z.; Bender, G., The development of a through-plane reactive excitation technique for detection of pinholes in membrane-containing MEA sub-assemblies. Int J Hydrogen Energ 2019, 44 (16), 8533-8547.Phillips, A.; Ulsh, M.; Mackay, J.; Harris, T.; Shrivastava, N.; Chatterjee, A.; Porter, J.; Bender, G. J. F. C., The effect of membrane casting irregularities on initial fuel cell performance. 2020, 20 (1), 60-69.Martin, A.; Trinke, P.; Stähler, M.; Stähler, A.; Scheepers, F.; Bensmann, B.; Carmo, M.; Lehnert, W.; Hanke-Rauschenbach, R. J. J. o. T. E. S., The Effect of Cell Compression and Cathode Pressure on Hydrogen Crossover in PEM Water Electrolysis. 2022, 169 (1), 014502.

PFSA Membrane Thickness Impact on Chemical Degradation Rates

As the large-scale commercialization of proton exchange membrane fuel cells (PEMFC) for numerous applications, including heavy-duty trucks draws nearer, there is increasing interest in optimizing fuel cell membranes for both improved efficiency and durability. One of the major membrane attributes being considered for optimization is thickness. The current range of (perfluorosulfonic acid) PFSA membrane thicknesses employed for commercial applications range from 8 -25 µm. As with most adjustable materials parameters, there are a host of properties (cost, gas permeability, proton conductivity, etc.) that require co-optimization to provide the overall preferred position. For example, thin membranes will minimize proton resistance, facilitating high power densities, but will simultaneously allow increased gas crossover fluxes that can contribute to both reduced fuel efficiency and increased oxidative stress. On the other end of the spectrum, thick membranes will decrease gas crossover fluxes, offering improved fuel efficiency while simultaneously decreasing power density. A major question surrounding the tradeoffs of membrane thickness involves the chemical durability impact. Here, we report our investigations of PFSA membrane chemical durability as a function of thickness. For the studies reported here, a thickness series (8, 12 and 20 µm) of ePTFE reinforced Nafion®-like PFSA standalone membranes (SAMs) were prepared.A two-pronged approach was taken for this study. The first involves investigation of intrinsic chemical stability of the ionomer as a function of membrane thickness using an ex-situ H2O2 vapor test. The second investigative mode, which targets the oxidative stress generated by crossover gas flux, employs OCV durability tests of full MEAs. In addition to membrane thickness, gas crossover rates are known to be functions of membrane hydration and gas pressures.1,2 Accordingly, a 3(4-1) fractional factorial experimental design was executed to probe the role of membrane thickness as well as the other factors known to affect gas crossover. The fractional factorial design allows all main effects to be determined and further allows estimation of two factor interactions, if present.References T. Sakai, H. Tanenaka, E, Torikai, “Gas Diffusion in Dried and Hydrated Nations” J. Electrochem. Soc., 1986, 133, 88-92R. Jiang, T. Fuller, S. Brawn, C. Gittleman, “Perfluorocyclobutane and poly(vinylidene fluoride) blend membranes for fuel cells” Electrochimica, Acta, 2013, 110, 306-315

A NSGA-II variant for the dynamic economic emission dispatch considering plug-in electric vehicles

The dynamic economic emission dispatch considering plug-in electric vehicles (DEED-PEV) belongs to a nonlinear constrained optimization problem and has the multimodal and discontinuity characteristics. The first characteristic mainly comes from the cost function with valve-point effects, and the second one is associated with the constraints of prohibited operating zones. In this paper, a novel NSGA-II (NNSGA-II) is proposed to deal with DEED-PEV. NNSGA-II replaces the simulated binary crossover operator by the one based on Gaussian distribution, and adaptively adjusts the crossover rate of each individual according to its rank in population. Also, it incorporates a rewarding coefficient into the crowding distance in density estimation, which gives considerations to both density and evenness of solutions. Accordingly, NNSGA-II is able to perform extensive searches in solution space and achieve a series of individuals with high diversity and good evenness. Experimental results suggest that NNSGA-II outperforms the other seven MOEAs for nine DEED-PEV problems with different charging and discharging scenarios of plug-in electric vehicles, and its obtained solutions are superior to those of the other seven MOEAs according to the hypervolume and coverage indicators. In short, NNSGA-II is a potential alternative for minimizing the generation cost and pollutant emission of DEED-PEV.

Radial crossover and unsuccessful radial access during coronary angiography or percutaneous coronary intervention: insights from the FORCE-ACS registry

Abstract Background Radial crossover and unsuccessful radial access during coronary angiography or percutaneous coronary intervention (PCI) are associated with worse outcomes compared to successful radial access. The MATRIX score estimates the risk of radial crossover, but the predictive value of this novel risk score has not been evaluated in real-world acute coronary syndrome (ACS) patients. Purpose To evaluate (i) the temporal trends in the incidence for radial crossover and unsuccessful radial access, (ii) the reasons for unsuccessful radial access and (iii) the odds ratio for radial crossover and unsuccessful radial access in patients with a high MATRIX score. Methods Data from 4,514 ACS patients managed invasively and enrolled in the FORCE-ACS registry between January 2015 and December 2019 were used. Radial crossover was defined as a failure to either start or complete coronary angiography or PCI via radial access and subsequent crossover to femoral or brachial access. Unsuccessful radial access was defined as failure to complete the procedure via radial access and crossover to the femoral or brachial access. Reasons for unsuccessful radial access were: (i) issues during puncture or sheath insertion, (ii) failure to complete angiography and (iii) failure to complete PCI. The odds ratio for radial crossover and unsuccessful radial access of patients with a high MATRIX score (≥41) compared to patients with a low score (<41) was calculated using logistic regression. Results The observed rate of radial crossover was 20.7%. The radial crossover rate decreased throughout the years from 38.8% to 14.8% as shown in Figure 1A. The most common reasons for radial crossover was that the operator did not choose radial access as the initial access site and proceed directly to a femoral or brachial approach (18.3% of all procedures). If radial access was attempted but ultimately unsuccessful (2.9% of all radial access attempts), the most common reasons were failure to start or complete coronary angiography and issues with atrial puncture or sheath insertion (Figure 1B). Failure to complete PCI after successfully coronary angiography was rare. The rate of unsuccessful radial access relative to all radial access attempts was consistent over time between 1.8% and 4.2%. Patients with a high MATRIX score had a fourfold higher risk of radial crossover as compared to patients with a low score (odds ratio 4.07, 95%-CI: 3.47–4.78) and an almost twofold risk of unsuccessful radial access (odds ratio 1.87, 95%-CI: 1.19–2.93) (Figure 2). Conclusion The incidence of radial crossover declined throughout the years, while the rate of unsuccessful radial access was consistent over time. The MATRIX score is able to identify patients at higher risk of radial crossover and unsuccessful radial access. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The FORCE-ACS registry is supported by grants from ZonMw, the St. Antonius Research Fund and AstraZeneca.

Post-protocol therapies in first-line immunotherapy trials in non–small cell lung cancer (NSCLC).

125 Background: The advent of immunotherapy (IO) has led to significant improvement in outcomes for patients (pts) with advanced non-small cell lung cancer (adv NSCLC). The rate of crossovers and receipt of post-protocol IO in pivotal trials leading to FDA approvals of IO in NSCLC has not been systematically evaluated. Here, we evaluate crossover rates and post protocol therapies for pts with adv NSCLC across multiple first-line (1L) IO monotherapy and chemotherapy/IO (chemo/IO) combination trials. Methods: We utilized the publicly available data from pivotal clinical trials leading to approvals of IO or chemo/IO regimens in 1L treatment of adv NSCLC. We extracted data on outcomes, rate of crossover from control arm to IO, proportion of pts in control arm receiving IO and the start dates of these clinical trials. The primary outcomes were the rates of crossover and the proportion of patients in control arms who received post-control IO. Results: The study included 4 trials with IO monotherapy and 12 trials with chemo/IO combinations in 1L adv NSCLC. The primary endpoints for these trials were PFS (25%), OS (19%), and both PFS and OS (56%). The crossover rate from control arm to experimental arm (with IO) ranged from 0-74% in IO monotherapy trials and 0-49% in chemo/IO trials. Two IO monotherapy trials and five chemo/IO trials did not allow crossover; among them, 3 trials had a PFS/OS co-primary endpoint, while others had OS as primary endpoint. Ten of 16 trials provided explicit information on use of subsequent post-protocol therapies in their publications. Among the two IO monotherapy trials which did not allow crossover, post-protocol IO was administered in only 20-30% of patients. Among the six chemo/IO trials with information on post-protocol therapies, 30%-59% patients on the control arm subsequently received some form of IO on progression. Nine of 12 trials started accrual after 10/2015, when nivolumab was approved in the United States as second-line (2L) therapy for adv NSCLC regardless of tumor PD-L1 expression. Conclusions: Despite the highly significant OS benefit from 2L IO, which was the standard of care (SOC) in the United States, the rates of crossover and post-protocol IO administration was distressingly low in 1L IO monotherapy and chemo/IO trials for 1L adv NSCLC. This low rate of 2L treatment with IO may have been due to limited global availability prior to widespread regulatory approval during the conduct of these trials. There is an increased need for consistency in reporting of crossover treatment and post-protocol treatments to allow adequate assessment of the true 1L benefit with IO. Control arms in pivotal trials require scrutiny to ensure confirmation with SOC to provide access to optimal treatments for patients and prevent magnification of observed benefits in experimental arms. The difficulty lies in the global conduct of large randomized clinical trials with differing regulatory approvals.

K-Means-Based Multigroup Differential Evolution Optimization Framework for Design of MIMO Antenna With Decoupling Elements

A novel differential evolution optimization method named <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">K</i> -means-based multigroup differential evolution (KMGDE) framework is proposed for multiple-input–multiple-output (MIMO) antenna design. The KMGDE algorithm divides the population into three groups using the <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">K</i> -means clustering method in each iteration. Different mutation strategies are assigned for each group according to its average fitness value. The groups are then combined for crossover operation with an adaptive crossover rate value to balance local search and global search. The fitness function considering the characteristics of the MIMO antenna is proposed to speed up optimization. The performance of the proposed method is evaluated and compared with six state-of-the-art optimization algorithms using an MIMO antenna example. The optimization results and the experimental results show that the proposed KMGDE algorithm has a faster convergence than state-of-the-art optimization algorithms, which significantly improves the efficiency of MIMO antenna design.

Effect of Genetic Algorithm on Prediction of Heart Disease Stadium using Fuzzy Hierarchical Model

The Fuzzy Hierarchical Model method can be used to predict the stage of heart disease. The use of the Fuzzy Hierarchical Model on complex problems is still not optimal because it is difficult to find a fuzzy set that provides a more optimal solution. This method can be improved by changing the membership function constraints using Genetic Algorithm to get better predictions. Tests carried out using 282 heart disease patient data resulted in a Root Mean Squared Error (RMSE) value of 0.55 using the best Genetic Algorithm parameters, including population size of 140, number of generations of 125, and a combination of cross-over rate and mutation rate of 0.4 and 0.6 whereas the RMSE value generated by the Fuzzy Hierarchical Model before being optimized by the Genetic Algorithm was 0.89. These results indicate an increase in the predictive value of the Fuzzy Hierarchical Model after being optimized using the Genetic Algorithm.

A galvanostatic charging method for quantitative measurements of hydrogen crossover in fuel cell stack

Hydrogen crossover rate has emerged as a key indicator for characterizing the aging process of proton exchange membrane fuel cell. Electrochemical techniques are the most common for quantifying hydrogen crossover. However, for the present, most existing methods are only applicable to the scenario of single fuel cell. There is still a lack of efficient methods for the quantification of hydrogen crossover in stack configuration. In this paper, we establish a galvanostatic charging method with high accuracy and strong operability to measure hydrogen crossover in fuel cell stack for the first time. The fundamentals of this presented method are expounded through comprehensively analyzing the electrochemical processes occurring on fuel cell electrode under galvanostatic conditions. The effectiveness of the galvanostatic charging method is fully validated on a single cell and a multi-cell stack. Furthermore, necessary details for practical implementation of our method are discussed, and a data processing procedure allowing automatic and quick data extraction is correspondingly developed. This new characterization methodology for stack-level fuel cells offers significant advantages of being accurate, high-efficiency and non-invasive, and it will provide a powerful tool for lifespan evaluation, inconsistency analysis and failure diagnosis of fuel cell stacks.

Best Fit DNA-Based Cryptographic Keys: The Genetic Algorithm Approach.

DNA (Deoxyribonucleic Acid) Cryptography has revolutionized information security by combining rigorous biological and mathematical concepts to encode original information in terms of a DNA sequence. Such schemes are crucially dependent on corresponding DNA-based cryptographic keys. However, owing to the redundancy or observable patterns, some of the keys are rendered weak as they are prone to intrusions. This paper proposes a Genetic Algorithm inspired method to strengthen weak keys obtained from Random DNA-based Key Generators instead of completely discarding them. Fitness functions and the application of genetic operators have been chosen and modified to suit DNA cryptography fundamentals in contrast to fitness functions for traditional cryptographic schemes. The crossover and mutation rates are reducing with each new population as more keys are passing fitness tests and need not be strengthened. Moreover, with the increasing size of the initial key population, the key space is getting highly exhaustive and less prone to Brute Force attacks. The paper demonstrates that out of an initial 25 × 25 population of DNA Keys, 14 keys are rendered weak. Complete results and calculations of how each weak key can be strengthened by generating 4 new populations are illustrated. The analysis of the proposed scheme for different initial populations shows that a maximum of 8 new populations has to be generated to strengthen all 500 weak keys of a 500 × 500 initial population.

Crossover in Adjuvant Trastuzumab Trials: Sparing Toxicity in Patient Care.

Design and reporting of randomized control trials for drug therapies in the adjuvant setting require a nuanced consideration of patient crossover. Adjuvant trials can be susceptible to the misuse of crossover and may distort the interpretation of findings. We sought to investigate and describe crossover and/or postprogression access to trastuzumab within adjuvant trastuzumab randomized control trials for human epidermal growth factor receptor 2-positive breast cancer patients. Seven clinical trials for adjuvant trastuzumab in human epidermal growth factor receptor 2-positive breast cancer were identified through a meta-analysis published in the Lancet . Primary study publications were located through MEDLINE, Google Scholar, and trials were identified, when possible, using Clincialtrials.gov. Sixteen publications, describing 7 studies, were reviewed. Four (57%) trials reported offering patients within the control arm the opportunity to crossover and receive trastuzumab in the adjuvant setting. Two (29%) trials did not report nor discuss crossover within the publication. Five (71%) trials reported the total number of patients who crossed over among the control arms. No trials specified the proportion of control patients who received trastuzumab at recurrence. Trials for adjuvant trastuzumab did not disambiguate between crossover (1) in the adjuvant setting or (2) at recurrence. Due to the low reported rate of crossover, it is questionable if participants received the standard of care.

LBA54 Three years survival outcome and continued cemiplimab (CEMI) beyond progression with the addition of chemotherapy (chemo) for patients (pts) with advanced non-small cell lung cancer (NSCLC): The EMPOWER-Lung 1 trial

In the EMPOWER-Lung 1 trial, CEMI monotherapy provided a significantly improved overall survival (OS) and an acceptable safety profile vs chemo in pts with newly diagnosed advanced NSCLC. We are reporting the 3-year survival data of the trial. Also, we are presenting the first efficacy data of pts who continued CEMI at progression (PD) with addition of histology-specific chemo. Pts were randomized 1:1 to CEMI 350 mg IV every 3 weeks for 2 years or investigator’s choice of chemo. Pts randomized to CEMI with PD, confirmed by a blinded independent review committee (BIRC), were allowed to continue CEMI with the addition of up to 4 cycles of chemo. To be included in the post PD analysis, pts had to receive at least one dose of chemo and have at least one scan following PD on CEMI. Response to continued CEMI + chemo was assessed by BIRC against a new baseline, defined as the last scan prior to the initial dose of chemo. At median follow-up of 37.1 months (m; range: 24.0 : 56.5), median OS (mOS) was 23.4 m (19.4, 27.4) for CEMI pts (N=357) vs 13.7 m (11.2, 16.2) for chemo pts (N=355), with hazard ratio (HR) of 0.634 (0.524, 0.768); median progression free survival (mPFS) was 6.3 m (4.6, 8.3) vs 5.3 m (4.3, 6.0), HR 0.560 (0.470, 0.666). 64 pts continued CEMI + chemo as 2L therapy. Continued CEMI + chemo as 2L therapy resulted in a 31.3% objective response rate and a mOS of 15.1 m (11.3, 18.7), and was generally tolerated, with 19 pts (29.7%) experiencing serious treatment-emergent adverse event (TEAE), and 3 pts each with TEAE resulting in discontinuation of study treatment or death. At 3 year follow-up, HRs of CEMI vs. chemo improved (vs at 13 m follow-up) for both PFS and OS despite 76% crossover rate, an exceptional finding in the NSCLC field. Continued CEMI + chemo as 2L therapy provided meaningful and durable ORR and OS benefits and these results compare favorably to historical data of pts receiving chemo alone as 2L therapy (after immune-checkpoint inhibitor monotherapy). This data is the first report from a Phase 3 study providing therapeutic advantage to pts who progress after 1L PD1 monotherapy.

974MO 5-year update from KEYNOTE-407: Pembrolizumab plus chemotherapy in squamous non-small cell lung cancer (NSCLC)

Pembrolizumab (pembro) + platinum-based chemotherapy (chemo) significantly prolonged OS and PFS compared with placebo + chemo in patients (pts) with previously untreated, metastatic squamous NSCLC in the phase III KEYNOTE-407 study (NCT02775435). We report the 5-y outcomes in the ITT population and in pts who completed 35 cycles of pembro (∼2 y). Eligible pts were randomized 1:1 to receive pembro 200 mg or placebo + carboplatin and paclitaxel/nab-paclitaxel Q3W for 4 cycles, followed by pembro or placebo up to 35 cycles. Eligible pts in the placebo + chemo group were allowed to crossover on-study to up to 35 cycles of open-label pembro monotherapy upon unblinding after verification of PD by BICR. Primary endpoints were OS and PFS per RECIST v1.1 by BICR. Pts were randomized to pembro + chemo (n = 278) or placebo + chemo (n = 281). As of Feb 23, 2022, median time from randomization to data cutoff was 56.9 (range, 49.9–66.2) mo; 117 pts crossed over from the placebo + chemo group to receive pembro monotherapy, and an additional 26 pts received subsequent anti–PD-(L)1 therapy; the effective crossover rate was 51.1%. Median OS in the ITT population was 17.2 mo for the pembro + chemo group and 11.6 mo for the placebo + chemo group; HR, 0.71 (95% CI, 0.59–0.85). Respective 5-y OS rates were 18.4% and 9.7%. Additional efficacy outcomes are described in the table. Grade 3‒5 AEs occurred in 74.8% and 70.0% of pts in the pembro + chemo and placebo + chemo groups, respectively. Among 55 pts who completed 35 cycles of pembro, ORR was 90.9%, and 3-y OS rate after completion of 35 cycles (⁓5 y after randomization) was 69.5%.Table: 974MOITT populationPembrolizumab + chemotherapy n = 278Placebo + chemotherapy n = 281Median OS (95% CI), mo17.2 (14.4‒19.7)11.6 (10.1‒13.7)OS HR (95% CI)0.71 (0.59‒0.85)5-year OS rate, %18.49.7Median PFS (95% CI), mo8.0 (6.3‒8.5)5.1 (4.3‒6.0)PFS HR (95% CI)0.62 (0.52‒0.74)5-year PFS rate, %10.83.5ORR (95% CI), %62.2 (56.2‒68.0)38.8 (33.1‒44.8)Median DOR (range), mo9.0 (1.3+ to 61.5+)4.9 (1.3+ to 58.6+)–DOR ≥4 y; %21.616.0+ indicates no PD by time of last assessment. Open table in a new tab + indicates no PD by time of last assessment. After 5 y of follow-up, pembro + chemo continued to demonstrate prolonged OS and PFS vs chemo alone without increased toxicity. Most pts who completed 35 cycles had objective responses and were alive at data cutoff. These long-term data support use of pembro + chemo as a standard first-line treatment option for metastatic squamous NSCLC.

Diversity and determinants of recombination landscapes in flowering plants.

During meiosis, crossover rates are not randomly distributed along the chromosome and their location may have a strong impact on the functioning and evolution of the genome. To date, the broad diversity of recombination landscapes among plants has rarely been investigated and a formal comparative genomic approach is still needed to characterize and assess the determinants of recombination landscapes among species and chromosomes. We gathered genetic maps and genomes for 57 flowering plant species, corresponding to 665 chromosomes, for which we estimated large-scale recombination landscapes. We found that the number of crossover per chromosome spans a limited range (between one to five/six) whatever the genome size, and that there is no single relationship across species between genetic map length and chromosome size. Instead, we found a general relationship between the relative size of chromosomes and recombination rate, while the absolute length constrains the basal recombination rate for each species. At the chromosome level, we identified two main patterns (with a few exceptions) and we proposed a conceptual model explaining the broad-scale distribution of crossovers where both telomeres and centromeres play a role. These patterns correspond globally to the underlying gene distribution, which affects how efficiently genes are shuffled at meiosis. These results raised new questions not only on the evolution of recombination rates but also on their distribution along chromosomes.

An improved imperialist competition algorithm with adaptive differential mutation assimilation strategy for function optimization

In imperialist competition algorithm (ICA), the assimilation is an important step, which is responsible for exploring potential better position or solution for an optimization problem. In this paper, an improved ICA equipped with an adaptive differential mutation (ADM) assimilation strategy was proposed inspired by differential evolution (DE). The proposed algorithm is called ICA-ADM. The ADM assimilation strategy generates new positions for colonies in an empire using the “DE/best/1” mutation operator and crossover operator with adaptively varied mutation and crossover rate. Since the “DE/best/1” mutation and crossover can produce high quality solutions, ICA-ADM possesses good exploration capability. Meanwhile, since the mutation and crossover rates are adaptively varied, ICA-ADM also preserves a good population diversity. Thus, the performance of ICA-ADM is greatly increased. Optimization results on 16 well-known benchmark functions and comparisons verify that the proposed ICA-ADM exceeds the initial ICA and its several variants.

Transradial versus transfemoral access without closure device for transarterial chemoembolization in patients with hepatocellular carcinoma: a randomized trial.

To compare patient satisfaction, procedural variables, and safety with transradial access (TRA) and transfemoral access (TFA) in patients undergoing transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). From February 2019 to August 2021, 130 patients undergoing TACE for HCC were randomly allocated to the TRA (n = 65) or TFA (n = 65) group. Vascular closure devices were not used after TFA-TACE. All patients completed the post-catheterization questionnaire and 8-item Short-Form Health Survey 1 day after TACE. Technical success rate, crossover rate, contrast agent dose, fluoroscopy time, procedure time, air kerma, dose-area product, length of hospital stay, and total cost were similar between the two groups (all p > 0.05). The incidence and severity of adverse events were also similar between the two groups (all p > 0.05). However, overall discomfort, difficulty going to the bathroom, difficulty feeding or self-caring, difficulty walking, general health, physical function, role physical function, social function, mental health, and role emotional function were better in the TRA group than in the TFA group (all p < 0.001). Consequently, more patients preferred the current access for their next procedure in the TRA group than in the TFA group (90.8% vs. 24.6%; p < 0.001). In patients undergoing TACE for HCC, using TRA instead of TFA can improve patient satisfaction without compromising procedural variables and safety. • Transradial access (TRA) enabled early ambulation after transarterial chemoembolization (TACE), resulting in significant increase in activities of daily living and health-related quality of life (HRQoL) compared to transfemoral access (TFA) when vascular closure devices were not used. • Procedural variables (contrast agent dose, fluoroscopy time, procedure time, air kerma, dose-area product, length of hospital stay, and total cost) were not significantly different between patients who received TRA-TACE and TFA-TACE. • The incidence and severity of adverse events were similar between patients who received TRA-TACE and TFA-TACE.