Additional Points Research Articles

Sjögren's Versus Non-Sjögren's Ocular Features: Similar Symptoms, But Significantly Worse Signs.

To examine the ocular signs and symptoms in participants of the Sjögren's International Collaborative Clinical Alliance cohort, and to compare them across Sjögren's disease (SjD) status. Our study population comprised 3380 Sjögren's International Collaborative Clinical Alliance participants who had no missing data relevant to this study. Participants' SjD status was assessed using the updated 2016 American College of Rheumatism/European League Against Rheumatism SjD classification criteria. Participants completed baseline questionnaires of ocular symptoms and underwent ocular examinations. Differences in the ocular signs and symptoms between SjD and non-SjD groups were assessed. We used multivariable linear and linear mixed-effects models to investigate the impact of SjD on Ocular Surface Disease Index-6 and OSS. Among 1532 participants classified as SjD, their Ocular Surface Disease Index-6 did not clinically differ from those classified as non-SjD (adjusted difference, -0.97; 95% confidence interval, -1.52 to -0.41). However, SjD participants exhibited an elevated ocular staining score (adjusted difference, 3.47; 95% confidence interval, 3.36-3.57; P<0.001) compared with non-SjD participants. In addition, SjD was associated with increased odds of ocular signs, such as reduced tear break-up time, abnormal Schirmer I test, and corneal abnormalities, and was strongly related to more intense corneal and conjunctival staining, as well as additional corneal staining points. SjD is associated with a higher risk of ocular signs and pathology compared with non-SjD, whereas ocular symptoms remain similar. In addition, corneal abnormalities and corneal staining patterns could serve as a potential biomarker in identifying SjD-related dry eye.

Assessment of the effectiveness of the reconstraction of social-everyday skills on the hardware-training complex of audio-visual reconstruction of the environment of patients after acute cerebrovascular accident

BACKGROUND: Motor disorders as a result of аcute cerebrovascular accident are the most common cause of disability and not only significantly reduce the quality of life of patients, but also cause restriction of social and household independence of patients in a familiar environment.&#x0D; AIM: the evaluation of the effectiveness for restoring the social and domestic activity skill ― shopping in the supermarket in patients undergoing stroke in the right middle cerebral artery after course of the special apparat trainings with audio-visual reconstruction of the environment.&#x0D; MATERIALS AND METHODS: The study included 65 participants, they were divided into 3 groups, the first and the second group ― the patients who undergoing the stroke (main and control groups): the main group of patients received a base standard rehabilitation program (kinesiotherapy, mechanotherapy on cyclic apparatгs, massage) and additional the social and domestic trainings with audio-visual reconstruction of the environment. The control group ― a base standard rehabilitation program. The duration of the rehabilitation course was 21 days. The third comparison group are the healthy participants, who were necessary for defining "etalon" options for training of socially important skill.&#x0D; RESULTS: As a result of the study in both groups (main and control) as compared with the initial findings the lowering of the heaviness ischemic stroke outcome (NIHSS): 6.2±0.4 in the first group and 6.8±0.7 in the second group vs. 4.2±0.2 and 5.9±0.8 (р ≤0.05). By comparison the first and the second groups with the health participants were defined the statistically significant changes of the studing time options in the main group during making these skills: take the bag and sling it through the shoulder, open the pockets of the bag (2 pockets), take the jacket from the clothes hanger and put on. Although in patients of the first group after restoring threatment course with using method of functional spatially-oriented rehabilitation it was authentic lesser disturbance of everyday life activity: in estimating Bartel Index 61.3±4.9 vs. 43.75±5.1 (initial) (р ≤0.05), what was signuficantly higher be comparison with control group results. In estimating functional independence by Modified Scale FIM: 71.4±4.9 in the main group vs. 53.7±3.1 (initial) (р ≥0.05), what was although significantly higher in comparison with the second group. By HADS it was lowering of the anxiety symptoms in the first group from 13.02±1.9 till 10.12±1.2 (р ≤0.05) as compared with the control group where the level of anxiety was staying quietly high and was 12.6±0.6 by comparison the initial findings 13.14±1.5 (р ≥0.05).&#x0D; CONCLUSION: The obtained resalts point at the effectiveness of using functional spatially-oriented rehabilitation in restoring threatment programs for patient undergoing stroke for elevation of the independence level in real life terms. An additional point is that this kind training promote significantly positive influence on the patient’s motivation for actualization of active movement to improvement of the social and domestic adaptation.

Teaching respect for body donors: A US medical student perspective.

Recent controversies over the mismanagement of body donors in US medical schools have raised public concerns over the ethical treatment of bodies in "anatomical gift" programs. Despite widespread moral outrage at such cases, medical students may still make seemingly inconsequential mistakes or jokes that in fact constitute acts of disrespect. This may partially be attributed to the process of desensitization in working with human remains, and indicates a further need to inculcate into medical students the ethical responsibilities of working with body donors. Donation agreement statements that lack specific information about the respectful treatment of bodies in the anatomy laboratory may serve as an additional point of concern for potential donors seeking reassurance about the future treatment of their bodies. This viewpoint draws from the anecdotal experiences of medical students to portray two scenarios of medical students' disrespectful conduct toward body donors, and constructs an account of moral respect for human remains based on respect for posthumous autonomy and respect in attitude. It then provides suggestions for US medical schools to incorporate this ethical framework into their anatomy curricula to instill respectful dispositions in its students and facilitate a more robust informed consent process for potential donors who entrust their bodies to medical students.

Conspiracy Mentality Versus Belief in Conspiracy Theories

Abstract: In this research spotlight, we respond to Nera’s (2024 , this issue) critique of the conspiracy mentality. We agree that the concept of the conspiracy mentality – and its relation to belief in conspiracy theories – requires further clarification. We also agree that the causal relationship between conspiracy mentality and belief in conspiracy theories may be bidirectional. We elaborate on these arguments by adding additional critical points and providing recommendations for researchers. We see the chief value of the construct as making it possible to tease apart (e.g., in covariance analyses) belief in conspiracy theories from the political attitudes that underlie them.

Genetic susceptibility to low-level lead exposure in men: Insights from ALAD polymorphisms

The genetic susceptibility to low-level lead (Pb) exposure in general populations has been poorly investigated and is limited to the single nucleotide polymorphism (SNP) rs1800435 in the delta-aminolevulinic acid dehydratase gene (ALAD). This study explored associations between ten selected ALAD SNPs with Pb concentrations in blood (BPb) and urine (UPb) among 281 men aged 18–49 years from Slovenia, including 20 individuals residing in a Pb-contaminated area. The geometric mean (range) of BPb and UPb were 19.6 (3.86–84.7) μg/L and 0.69 (0.09–3.82) μg/L SG, respectively. The possible genetic influence was assessed by examining SNP haplotypes, individual SNPs, and the combination of two SNPs using multiple linear regression analyses. While no significant associations were found for haplotypes, the presence of variant alleles of rs1800435 and rs1805312 resulted in an 11% and 13% decrease in BPb, respectively, while the presence of variant allele of rs1139488 (homozygous only) exhibited significant 20% increase in BPb, respectively. Additionally, variant allele of rs1800435 resulted in lower UPb. Individual SNPs in the model explained only around 1 additional percentage point of BPb variability. In contrast, combination analyses identified six combinations of two SNPs, which significantly explained 3–22 additional percentage points of BPb variability, with the highest explanatory power observed for the rs1800435-rs1139488 and rs1139488-rs1805313 combinations. Moreover, excluding participants from the Pb-contaminated area indicated that exposure level influenced SNPs-Pb associations.Our results confirm the importance of the ALAD gene in Pb kinetics even at low exposure levels. Additionally, we demonstrated that identifying individuals with specific combinations of ALAD SNPs explained a larger part of Pb variability, suggesting that these combinations, pending confirmation in other populations and further evaluation through mechanistic studies, may serve as superior susceptibility biomarker in Pb exposure compared to individual SNPs.

A Pharmacodynamic Study of Aminoglycosides against Pathogenic E. coli through Monte Carlo Simulation.

This research focuses on combating the increasing problem of antimicrobial resistance, especially in Escherichia coli (E. coli), by assessing the efficacy of aminoglycosides. The study specifically addresses the challenge of developing new therapeutic approaches by integrating experimental data with mathematical modeling to better understand the action of aminoglycosides. It involves testing various antibiotics like streptomycin (SMN), kanamycin (KMN), gentamicin (GMN), tobramycin (TMN), and amikacin (AKN) against the O157:H7 strain of E. coli. The study employs a pharmacodynamics (PD) model to analyze how different antibiotic concentrations affect bacterial growth, utilizing minimum inhibitory concentration (MIC) to gauge the effective bactericidal levels of the antibiotics. The study's approach involved transforming bacterial growth rates, as obtained from time-kill curve data, into logarithmic values. A model was then developed to correlate these log-transformed values with their respective responses. To generate additional data points, each value was systematically increased by an increment of 0.1. To simulate real-world variability and randomness in the data, a Gaussian scatter model, characterized by parameters like κ and EC50, was employed. The mathematical modeling was pivotal in uncovering the bactericidal properties of these antibiotics, indicating different PD MIC (zMIC) values for each (SMN: 1.22; KMN: 0.89; GMN: 0.21; TMN: 0.32; AKN: 0.13), which aligned with MIC values obtained through microdilution methods. This innovative blend of experimental and mathematical approaches in the study marks a significant advancement in formulating strategies to combat the growing threat of antimicrobial-resistant E. coli, offering a novel pathway to understand and tackle antimicrobial resistance more effectively.

Determination of Membrane Degradation in Polymer Electrolyte Fuel Cells with in-Situ and Ex-Situ Measurements

Fuel cells convert chemical energy directly into electrical energy with high efficiency and without pollutants. The decomposition products in the clean exhaust gas caused by the chemical degradation of the membrane of polymer electrolyte fuel cells (PEFCs) can be used to monitor the service life of the cell. For perfluorinated sulfonic acid (PFSA)-based membranes, chemical degradation is investigated via ex situ monitoring of the effluent water. The decomposition of the PFSA backbone, which is part of the polymer electrolyte membrane (PEM), can be detected by the degradation products such as fluoride or fluorinated compounds [1]. There are multiple methods for measuring fluoride in water. We have developed a new method for the simple and precise measurement of fluoride based on the optical change caused by the quenching of a zirconium complex. This method requires only 900 µL of the sample and 100 µL of the complex [2].We have extended the two fluoride measurement methods, namely fluoride sensitive electrode (FSE) and photometry (PM), to include ion chromatography (IC). This serves as an additional point of comparison with high accuracy and expands the measuring scope to include other ions like sulfate and their potential influence on photometric measurements.The electrochemical characterization of the materials has been improved by adapted electrochemical impedance spectroscopy (EIS) equivalent circuits, which include a more detailed analysis of the contribution of degradation processes. Linear sweep voltammetry (LSV) was used to measure the gas crossover through the membrane. Cyclic voltammetry provides information about the change in electrochemical surface area. Electrochemical characterizations and fluoride measurements are supplemented by ex situ imaging methods to determine membrane thinning.[1] M. A. Yandrasits, A. Komlev, K. Kalstabakken, M. J. Kurkowski, and M. J. Lindell, “Liquid Chromatography/Mass Spectrometry Analysis of Effluent Water from PFSA Membrane Fuel Cells Operated at OCV,” J. Electrochem. Soc., vol. 168, no. 2, p. 024517, Feb. 2021, doi: 10.1149/1945-7111/abe56a.[2] M. Heidinger, E. Kuhnert, K. Mayer, D. Sandu, V. Hacker, and M. Bodner, “Photometric Method to Determine Membrane Degradation in Polymer Electrolyte Fuel Cells,” Energies 2023, Vol. 16, Page 1957, vol. 16, no. 4, p. 1957, Feb. 2023, doi: 10.3390/EN16041957.

Chronic kidney disease and cardiovascular disease reduce survival rates after burn injury: A retrospective study over 20 years

BackgroundThe Abbreviated Burn Severity Index and comparable scores are used to assess the probability of survival in burned patients. These scores may be useful during the initial management of the patient and in addition to the clinical evaluation. As current models do not include the influence of chronic diseases, we evaluated the impact of comorbidities on survival probability, aiming to improve the existing scoring systems and survival probability accuracy further. MethodsIn this retrospective single-center study, patient data from a center for Severe Burn Injury were collected. Over a period of 20 years (2000–2019), a total of 1,193 patients were recorded. The influence of comorbidities (chronic kidney disease, diabetes mellitus type II, and cardiovascular diseases) on the survival probability was analyzed using regression models. These analyses were stratified for sex and period. ResultsPre-existing chronic kidney disease, as well as pre-existing cardiovascular disease, had a significant influence on the survival of patients. For chronic kidney disease, the influence was stronger in men than in women. Women were more likely to survive a burn injury with a history of chronic renal insufficiency. An improved Abbreviated Burn Severity Index model, which assigns an additional point for chronic kidney disease, best-described survival probability in our patient cohort. ConclusionCardiovascular disease and chronic kidney disease both have an impact on the survival probability of severely burned patients, but this impact is more severe for chronic kidney disease. An additional Abbreviated Burn Severity Index point for chronic kidney disease would be a proposed adaptation to predict the outcome of burn patients better.

A new active learning method for reliability analysis based on local optimization and adaptive parallelization strategy

In recent years, an active learning method combining Kriging and Monte Carlo Simulation (AK-MCS), has been developed for calculating the failure probability. However, the original AK-MCS only uses serial computing, which limits its ability to take advantage of distributed computing. Thus, this work introduces a novel adaptive learning approach for reliability analysis by combining local optimization and a parallelization strategy. The new approach identifies the points of greatest uncertainty through local optimization and adds them into the design of experiments. An inner learning loop is implemented, searching for additional best points with a pseudo Kriging model so that the performance function can be evaluated in parallel. Furthermore, an adaptive strategy is proposed to determine the amount of additional points during iteration based on the minimum value of the learning function. We conducted a comparison between the proposed method and the original AK-MCS as well as a few additional methods in order to assess its efficacy and precision. Five examples were considered to assess performance.

Tailoring allocation policies and improving access to paediatric liver transplantation over a 16-year period

Mortality on the paediatric liver transplantation (pLT) waiting list (WL) is still an issue. We analysed the Italian pLT WL to evaluate the intention-to-treat (ITT) success rate and to identify factors influencing success. All children (<18 years) listed for pLT in Italy between 2002-2018 were included (Era 1 [2002-2007]: centre-based allocation; Era 2 [2008-2014]: national allocation; Era 3 [2015-2018]: national allocation+mandatory-split policy). A total of 1,424 patients (median age: 2.0 [IQR 1.0-9.0] years; median weight: 12.0kg [IQR 7-27]) were listed for pLT. Median WL time was 2 days (IQR 1-5) for Status 1 and 44 days (IQR 15-120) for non-Status 1 patients; 1,302 children (91.4%) were transplanted (67.3% with split grafts), while 50 children (3.5%) dropped off the WL (2.5% death, 1.0% clinical deterioration). Predictive factors for receiving LT included Status 1 (hazard ratio [HR] 1.66, p= 0.001), Status 1B (HR 1.96, p= 0.016), Status 2A (HR 2.15, p= 0.024) and each 1-point increase in PELD/MELD score. Children with recipient's weight >25kg, blood group O or awaiting pLT combined with other organs had less chance of being transplanted. ITT patient survival rates were 90.5% at 1 year and 87.5% at 5 years, remaining stable across eras. Risk factors for ITT survival were re-transplantation (HR 5.83, p <0.001), Status 1 (HR 2.28, p= 0.006), Status 1B (HR 2.90, p= 0.014), Status 2A (HR 9.12, p <0.001), recipient weight <6kg (HR 4.53, p <0.001) and low-volume activity (HR 4.38, p= 0.001). In Italy, continuous adaption of paediatric organ allocation policies via the introduction of national allocation, paediatric prioritisation rules and a mandatory-split policy have helped maximise the use of donors for paediatric candidates and to minimise WL mortality without compromising outcomes. Globally, paediatric liver transplant candidates still suffer from high mortality. Over recent decades, the continuous adaption of organ allocation policies in Italy has led to excellent outcomes for children awaiting liver transplantation. The mortality rate of paediatric liver transplant candidates has been minimised to almost zero, mainly using grafts from deceased donors. Paediatric prioritisation rules, national organ exchange organisation and a mandatory-split liver policy have resulted in a unique allocation model for paediatric liver transplant candidates and represent a landmark for the paediatric transplant community.

Outcomes following intensive day rehabilitation for young people in Western Australia.

Intensive rehabilitation aims to improve and maintain functioning in young people who experience disability due to illness or injury. Day rehabilitation may have advantages for families and healthcare systems over inpatient models of rehabilitation. This study evaluated the goals and outcomes of a cohort of young people in Western Australia who attended a specialist intensive day rehabilitation programme ("iRehab") at Perth Children's Hospital. Analysis of the iRehab service database was performed. Rehabilitation goals and outcomes were recorded as per the Canadian Occupational Performance Measure (COPM), Children's Functional Independence Measure (WeeFIM), and Goal Attainment Scale (GAS). There were 586 iRehab admissions between August 11, 2011, and December 31, 2018. Admissions were divided by diagnosis: Cerebral Palsy (228, 38.5%), Acquired Brain Injury (125, 21.3%), Spinal Cord Disorders (91, 15.5%), and Other (141, 24.2%). Mean COPM Performance increased by 2.78 points from admission to discharge (95% CI 2.58 to 2.98, p < 0.001). Mean COPM Satisfaction was 3.29 points higher at discharge than admission (95% CI 3.07 to 3.51, p < 0.001). Mean total WeeFIM score improved by 6.51 points between admission and discharge (95% CI 5.56 to 7.45, p < 0.001), and by 3.33 additional points by six months post discharge (95% CI 2.14 to 4.53, p < 0.001). Mean GAS T-scores increased by 27.85 (95% CI 26.73 to 28.97, p < 0.001) from admission to discharge, and by 29.64 (95% CI 28.26 to 31.02, p < 0.001) from admission to six months post discharge, representing improvement consistent with team expectations. This study describes a model by which intensive rehabilitation can be delivered in a day rehabilitation setting. A diverse population of young people who experienced disability achieved significant improvements in occupational performance, independence, and goal attainment after accessing intensive day rehabilitation. Improvements were measured in all diagnostic subgroups and were maintained six months after discharge.

Women's Satisfaction with Breastfeeding and Risk of Exclusive Breastfeeding Interruption.

This prospective cohort study was conducted to evaluate the association between women's satisfaction with breastfeeding at 1 month post-partum and the risk of exclusive breastfeeding (EBF) interruption before 6 months. 287 mother-infant dyads randomly selected from two maternity hospitals were followed from birth to 24 months of infant's age. Women's satisfaction with breastfeeding was assessed using the Maternal Breastfeeding Evaluation Scale (MBFES) at 1 month. The association between women's satisfaction with breastfeeding and risk of EBF interruption before 6 months was estimated using Cox proportional hazards model. Kaplan-Meier survival curves for EBF were compared between women with lower satisfaction with breastfeeding (MBFES score < median 124) and those with higher satisfaction (MBFES score ≥ 124). Median EBF duration in women with higher satisfaction was 120 days (95%CI 109-131), vs. 26 days (95%CI 19-33) in less satisfied women. Each additional point on MBFES promoted a reduction of 2.0% in the risk of EBF interruption. Among women with satisfaction scores < 124, the risk of EBF interruption was 86% higher when compared with those ≥ 124 (adjusted hazard ratio 1.86; 95%CI 1.41-2.46). Lower maternal satisfaction with breastfeeding in the first month post-partum is associated with a higher risk of EBF interruption before 6 months.

The current status and implications of the medical insurance fee schedule in Japan

Background: Korea has the most rapidly aging population in the world. Medical costs for the elderly are quickly increasing, which raises concerns about the sustainability of health insurance finances. Accordingly, the need to allocate limited medical resources efficiently has increased, with improving the fee schedule seen as an effective way to achieve this. Japan has experienced a super-aging society for at least 20 years prior to Korea and has been successful in improving its fee schedule. Korea’s fee schedule, however, needs to overcome the challenge of being relatively limited in type and simplicity.Current Concepts: The new patient consultation fee in Japan is the same regardless of the type of medical institution and is approximately 40% higher than found in Korea. In the case of established patient consultations, the fee for medical institutions with fewer than 200 beds are substantially higher than for large medical institutions, thereby suppressing re-examination at large hospitals. Japan’s additional points consist of 71 types of items, which is more diverse than Korea’s 28 types, and the additional points for children under six years of age, holidays, and late nights are set significantly higher than that found in Korea.Discussion and Conclusion: Japan designed its fee schedule to structurally reduce the consumption of medical resources and to effectively compensate for the behavior of medical providers. This policy is a standard which Korea’s fee schedule should aim for. In the future, it will be necessary to prepare measures to respond to the super-aging environment through detailed research concerning Japan’s fee schedule.

Energy-conserving hyper-reduction and temporal localization for reduced order models of the incompressible Navier-Stokes equations

A novel hyper-reduction method is proposed that conserves kinetic energy and momentum for reduced order models of the incompressible Navier-Stokes equations. The main advantage of conservation of kinetic energy is that it endows the hyper-reduced order model (hROM) with a nonlinear stability property. The new method poses the discrete empirical interpolation method (DEIM) as a minimization problem and subsequently imposes constraints to conserve kinetic energy. Two methods are proposed to improve the robustness of the new method against error accumulation: oversampling and Mahalanobis regularization. Mahalanobis regularization has the benefit of not requiring additional measurement points. Furthermore, a novel method is proposed to perform energy- and momentum-conserving temporal localization with the principle interval decomposition: new interface conditions are derived such that energy and momentum are conserved for a full time-integration instead of only during separate intervals. The performance of the new energy- and momentum-conserving hyper-reduction methods and the energy- and momentum-conserving temporal localization method is analysed using three convection-dominated test cases; a shear-layer roll-up, two-dimensional homogeneous isotropic turbulence and a time-periodic inviscid flow consisting of a vortex in a uniform background flow. Our main finding is that energy conservation in combination with oversampling or regularization leads to a robust method with excellent long time stability properties. When any of these two ingredients is missing, accuracy and/or stability is significantly impaired.

Influence of gas density on void fraction and pressure drop in upward vapor–liquid flow

The influence of gas density on the void fraction, flow map, and pressure drop was examined for an upward vapor–liquid flow. The knowledge of the flow map is necessary to ensure a safe operational condition in a nuclear zone at high pressure. Moreover, the pressure gradient and its volumetric flow rate are related to the profitability of petroleum wells. Considering these scenarios, a modified cascade refrigeration cycle was constructed to generate and measure single-phase streams with different liquid and vapor density ratios. These single-phase liquid and vapor streams were mixed and injected into an upward vertical test section with an inner diameter of 26.64 mm and length of 5.8 m. The pressure ranged from 1.7 to 2.3 MPa, liquid–vapor density ratio ranged from 10.2 to 15.2, and total mass flux ranged from 733.1 to 882.9 kg.s−1.m−2. The void fraction, pressure gradient, and frictional pressure component were measured using quick-closing valves, temperature probes, and absolute and differential pressure sensors. The experimental data and transition line behavior of the flow map at high pressures in an upward two-phase flow as well as the proposed correction factors for the pressure gradient and its frictional component reflect the novelty of this study. Most existing studies have focused only on the influence of the gas density on the horizontal flow. A key observation of our study is that the liquid–vapor density ratio significantly changes the churn and annular transition lines. According to a vertical flow map found in the literature, the disappearance of the churn region can be foreseen and an annular transition occurs at lower gas velocities. The liquid–vapor density ratio does not influence the void fraction or slip velocity ratio; both increase with the superficial vapor velocity. Correction factors for the pressure gradient and its frictional component were proposed. The mean deviation for the pressure gradient was reduced from 27 % to 16 % after application of the correction factor. Half of the experimental points presented absolute relative errors lower than 30 % for the frictional pressure gradient. A cross-validation between the experimental data reported by other authors and the proposed correction factors was conducted to assess their response. In this cross-validation, 126 additional experimental points were used for the pressure gradient whereas 1270 points were used for its frictional component. Overall, the mean deviation of the pressure gradient was reduced from 92.7 % to 31.9 % after the application of the correction factor. Similarly, the mean deviation of the frictional gradient was reduced from 70.7 % to 31.3 % after the application of the correction factor. There was no evident influence of the liquid–vapor density ratio on the total pressure gradient and drift relationships for Froude numbers spanning from 2.6 to 7.4.

Design Optimization of Alloy Wheels Based on a Dynamic Cornering Fatigue Test Using Finite Element Analysis and Multi-Additional Sampling of Efficient Global Optimization

An alloy wheel is generally a symmetrically shaped part integral to a vehicle because its weight and strength can improve driving performance. Therefore, alloy wheel design is essential, and a novel design method should be considered. Currently, the Multi-Additional Sampling Efficient Global Optimization (MAs-EGO) has been proposed and widely implemented in various fields of engineering design. This study employed a surrogate model to maximize Expected Hypervolume Improvement (EHVI) for multi-objectives by increasing multi-sampling per iteration to update a surrogate model and evaluate an optimal point for alloy wheel design. Latin Hypercube Sampling (LHS) was used to generate an initial design of an alloy wheel, including the thickness and width of the spoke wheel. The maximum principal stress according to the dynamic cornering fatigue simulation was then evaluated for risk of failure using Finite Element (FE) analysis. The objectives were to minimize both the principal stress and weight of the symmetric alloy wheel. The Kriging method was used to construct a surrogate model, including a Genetic Algorithm (GA), which was performed to maximize hypervolume improvement to explore the next additional sampling point, and that point was also an optimal point for the process when computation had converged. Finally, FE results were validated through a designed apparatus to confirm the numerical solution. The results exhibit thatMulti-Additional Sampling Efficient Global Optimization can achieve an optimal alloy shape. The maximum principal stress distribution occurs in the spoke area and exhibits a symmetrical pattern around the axis following the cyclic bending load. The optimal design point of the alloy wheel can reduce 20.181% and 3.176% of principal stress and weight, respectively, compared to the initial design. The experimental results are consistent trend in the same direction as FEA results.

Calorific Value Prediction Model Using Structure Composition of Heat-Treated Lignocellulosic Biomass

This study aims to identify an equation for predicting the calorific value for heat-treated biomass using structural analysis. Different models were constructed using 129 samples of cellulose, hemicellulose, and lignin, and calorific values obtained from previous studies. These models were validated using 41 additional datasets, and an optimal model was identified using its results and following performance metrics: the coefficient of determination (R2), mean absolute error (MAE), root-mean-squared error (RMSE), average absolute error (AAE), and average bias error (ABE). Finally, the model was verified using 25 additional data points. For the overall dataset, R2 was ~0.52, and the RMSE range was 1.46–1.77. For woody biomass, the R2 range was 0.78–0.83, and the RMSE range was 0.9626–1.2810. For herbaceous biomass, the R2 range was 0.5251–0.6001, and the RMSE range was 1.1822–1.3957. The validation results showed similar or slightly poorer performances. The optimal model was then tested using the test data. For overall biomass and woody biomass, the performance metrics of the obtained model were superior to those in previous studies, whereas for herbaceous biomass, lower performance metrics were observed. The identified model demonstrated equal or superior performance compared to linear models. Further improvements are required based on a wider range of structural biomass data.

High-quality 3D Object Detection Based on Instance-aware Sampling

Most existing 3D object detection that is researched on point clouds uses random down-sampling algorithms, which preserve the primary shape and feature information of the point clouds and extract robust features of sampling point clouds to decrease the consumption of computing resources and improve processing inference efficiency. On the other hand, this method of sampling may disregard significant areas within the point clouds, thereby diminishing the precision of detecting comparatively minute entities such as pedestrians and cyclists. In this research, an instance perception-based object detection method is presented that adaptively chooses additional foreground points in response to the properties of smaller objects in the initial point clouds. In addition, it offers end-to-end training and addresses the issue that the typical hand-designed multi-scale grouping receptive fields do not accurately reflect the size of the item. To effectively enhance the recall rate of foreground points, we present an instance-aware algorithm, which relies on farthest point sampling. Specifically, we employ dynamic gating networks to attain instance perception. This approach enables sample candidates to encompass a larger number of foreground objects. Then we use an aggregation layer to efficiently capture robust contextual features with rich spatial information. Through experiments performed on the KITTI dataset, we substantiate the effectiveness of our IAS when compared with current advanced 3D object detection methods. We have achieved a notable enhancement, especially in identifying diminutive objects.

Long-Term Follow up for SWOG 1318: Combination of Dasatinib, Prednisone, and Blinatumomab for Older Patients with Philadelphia-Chromosome (Ph) Positive Acute Lymphoblastic Leukemia (ALL)

Tyrosine kinase inhibitors (TKIs) have improved the outcomes of patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). Many older patients (pts) are not good candidates for intensive chemotherapy and are treated with TKIs plus corticosteroids or low-intensity chemotherapy. Although the remission rates with this approach have been high, the median disease-free survival (DFS) has been short. Therefore, novel treatment strategies are needed. This trial evaluated the feasibility of combining the TKI dasatinib with prednisone and blinatumomab in older pts with Ph+ ALL. Here we present updated results (median follow-up, 4.3 years). Methods: This trial was activated through the NCTN in January 2015 and closed to accrual in April 2021. Pt eligibility included: age ≥ 65 years; Ph+ or Ph-like ALL (with dasatinib-sensitive fusions or mutations); newly diagnosed or relapsed/ refractory; no evidence of central nervous system (CNS) disease; and adequate organ function. Treatment: For induction, pts received dasatinib 140 mg/d orally (PO) Days 1-56 along with prednisone 60 mg/m 2/d PO Days 1-24. Pts achieving complete remission (CR) or CR with incomplete count recovery (CRi) (Day 28 or Day 56) continued dasatinib until Day 84, followed by 3 cycles of post-remission therapy (PRT) with blinatumomab/ dasatinib. Pts not achieving CR or CRi by Day 56 received re-induction with blinatumomab. The response rate was assessed on Day 35 of blinatumomab. Pts not achieving CR/ CRi could receive a second cycle of blinatumomab. This was followed by 3 cycles of PRT with blinatumomab/ dasatinib. Maintenance therapy consisted of prednisone 60 mg/m 2/d x 5 days every 28 days for a total of 18 cycles, along with dasatinib 140 mg po qd indefinitely. CNS prophylaxis included intrathecal (IT) methotrexate every 4-6 weeks x 8 doses. IT methotrexate was given at least 2 days apart from blinatumomab. Response was assessed at Days 28, 56, and 84, and additional time points were dependent on response. Minimal residual disease (MRD) was assessed centrally by multi-color flow cytometry on Day 28. Statistics: A total of 24 eligible patients were accrued. The primary objective was the feasibility of the combination therapy. The combination was to be deemed feasible if the dose-limiting toxicity (DLT) was &amp;lt; 33%. DLT included: &amp;gt; Grade 3 non-hematologic toxicities (excluding nausea, vomiting, diarrhea) and Grade 4 neutropenia lasting &amp;gt; 42 days. The primary results were reported in 2022 with a median of 2.7 years of follow-up. Herein, we report long-term outcomes for these patients. Results: The median age was 73 years (range 65-87). All pts had newly diagnosed Ph+ ALL; 79% of Ph+ pts had additional cytogenetic abnormalities. During induction, 2 pts experienced treatment-related non-hematologic Grade 4 toxicities. No Grade 4 or higher treatment-related non-hematologic toxicities occurred during post-remission therapy or maintenance. The toxicity of the combination was deemed acceptable. Twenty-two of 24 pts (92%) achieved a CR during dasatinib and prednisone induction therapy. Four did not receive PRT (2 due to adverse events, 1 to receive a transplant, and 1 because of insurance issues). Sixteen pts who achieved CR had MRD data. Six of 16 pts (38%) were MRD undetectable by multi-color flow cytometry on Day 28. Most sites also monitored patients' blood or bone marrow with real-time quantitative PCR to quantify the BCR-ABL1 transcript for molecular response. Of 19 patients analyzed, 17 (89%) were in a major or complete molecular remission at some time point after treatment, with at least 12 of these patients achieving complete molecular remission. Four patients remain on maintenance. The median follow- up for pts who are alive is 4.3 years (range 2.6-6.5 years). The median overall survival (OS) is 6.5 years (95% CI 3-NA) and the median DFS has not been reached as of June 29, 2023. Kaplan-Meier 3-year estimates of OS and DFS are 75% (95% CI 52%-88%) and 72% (95% CI 49%-87%), respectively (Figure). Of the 8 relapses, 4 patients were CD19+ and 3 had T315I mutations. Conclusions: Median DFS and OS with dasatinib and blinatumomab in this older group of Ph+ ALL patients remain excellent despite only 1 patient proceeding to an allogeneic transplant. Further correlative studies (single cell transcriptomics and DNA methylation sequencing) are being planned to evaluate predictors of relapse and will be presented at the meeting.

CD16, CD57 and DNAM-1 Positive NK Cells Predict MRD Negativity in Newly Diagnosed Multiple Myeloma Patients Treated with Daratumumab, Bortezomib, Thalidomide and Dexamethasone

Introduction: Daratumumab-based quadruplets are the current standard of care for newly diagnosed transplant-eligible multiple myeloma (MM) patients, because of improved depth of response and survival, compared with triplet regimens without daratumumab. Since one of the primary mechanisms of action of daratumumab is the induction of antibody-dependent cellular cytotoxicity (ADCC) via the Fc-gamma receptor CD16 on natural killer (NK) cells, it is crucial to understand the role of NK cells in combination therapy. We therefore set out to comprehensively profile NK cells by flow cytometry in newly diagnosed MM (NDMM) patients treated with either daratumumab, bortezomib, thalidomide, and dexamethasone (D-VTD) or VTD. Methods: A subset of NDMM patients (n = 152) who were treated in the Cassiopeia trial (EudraCT: 2014-004781-15) was included in this immunomonitoring analysis. In this trial, patients were first randomized to receive either four induction cycles and two consolidation cycles of D-VTD or VTD in conjunction with autologous stem cell transplantation (ASCT). In the second part of this trial, patients who achieved partial response or better at day 100 post-ASCT were randomized to either receive daratumumab maintenance or observation for the duration of two years. Bone marrow (BM) and peripheral blood (PB) samples were collected at study entry (baseline), and for PB at additional time points: cycle 1 day 28, cycle 4 day 28, day 100 (post-ASCT) and week 52 (maintenance). All baseline BM and PB samples and a selection of longitudinal PB samples were profiled by flow cytometry, with a focus on NK cell phenotype (CD56, CD16, CD57, DNAM-1, TIGIT, KLRG1, PD1, TIM3, NKG2A, NKG2C, NKG2D). To identify NK cell profiles associated with minimal residual disease (MRD) negativity, baseline PB and BM data were compared between MM patients based on MRD status after consolidation. Additionally, longitudinal data of PB samples collected during treatment were assessed to understand the impact of D-VTD and VTD on NK cell profiles. Results: In this cohort, 49 patients out of 77 (64%) randomized to the D-VTD arm achieved MRD negativity post-consolidation, while this was the case in 28 out of 75 patients (37%) in the VTD arm (fisher exact-test, p = 0.008). Patients with a higher proportion of BM-residing NK cells expressing the ADCC receptor CD16 (median 86 vs 72%, p = 0.007), the activating receptor DNAM-1 (median 94 vs 89%, p = 0.029), or the maturation marker CD57 (median 58 vs 48 %, p = 0.049) at baseline were more likely to achieve MRD-negativity post-consolidation in the D-VTD arm (Figure 1). Notably, this association was not present in the VTD arm. Although not significant, we found a similar trend for CD16 in PB in the D-VTD arm. During D-VTD treatment, we observed an increase in the proportion of CD56 bright and NKG2A + in PB NK-cells, and a corresponding decline in cells expressing CD16, CD57 and DNAM-1 (linear mixed effect model (LME) p &amp;lt;0.001). During VTD treatment we also observed a decrease in CD16 + NK-cells and an increase in CD56 bright and NKG2A + NK-cells (LME p &amp;lt;0.05), although these changes were more pronounced in the D-VTD arm. In patients who were assigned D-VTD at the first randomization and were subsequently randomized to the observation arm, we observed a restoration of the proportion of CD16 +, CD57 +, and CD56 bright NK cells to baseline values at week 52 after ASCT (Figure 2). As expected, the daratumumab associated NK cell changes persisted in the group that was randomized to the daratumumab maintenance arm. Conclusion: This study highlights the importance of NK cell immunophenotypic profiles in bone marrow as predictive markers for MRD negativity in NDMM patients treated with D-VTD in in conjunction with ASCT. Additionally, our findings illustrate that NK cell changes associated with daratumumab return to baseline levels after treatment cessation, indicating the potential for sequential NK cell-based therapies. In conclusion, this study not only provides valuable insights into the role of NK cells in the treatment of NDMM patients with D-VTD and ASCT, but also indicates that further research to optimize NK cell function in the context of combination therapies is warranted.