Relational Grade Research Articles

State of Health Estimation for Lithium-Ion Batteries Using IAO–SVR

The state of health (SOH) of lithium-ion batteries (LIBs) needs to be accurately estimated to ensure the safety and stability of electric vehicles (EVs) while in operation. In this paper, we proposed a SOH estimation method based on Improved Aquila Optimizer (IAO) and Support Vector Regression (SVR) to achieve an accurate estimation of SOH. During the charging and discharging phases of the battery, we analyzed the trends in current, voltage, and energy, then extracted four features. We used the Kendall coefficient and gray relational grade to prove that features and SOH were highly correlated. On the other hand, IAO was used to optimize the penalty factor and kernel function parameters of the SVR to further improve the generalization and mapping ability. The proposed method was verified under different operating conditions using the CACLE battery data set; the results show that high accuracy can be achieved in SOH estimation via IAO–SVR, and the estimation error of mean MAE is remaining within 2%.

Optimization of process parameters in ECDM machining using Taguchi based grey relation analysis

Electrochemical discharge machining (ECDM) is a hybrid machining process capable of micromachining conductive and nonconductive materials. The recent development and application of nonconductive materials, such as glass, composites, and ceramics in MEMS and microfluidic devices, have emphasized studying the ECDM process for micro holes and channel formation. The current study uses Taguchi's L27 orthogonal array to design the experiments, evaluate responses by the signal-to-noise ratio, analyze the variance of process parameters (ANOVA), and predict optimal settings for a multi-objective response using grey relation analysis (GRA). The experiments were conducted using two tools, a bare copper tool and Nickel coated copper tool, over a glass substrate. The machining process's output characteristics (radial overcut, heat-affected zone, and hole circularity) were studied by varying input parameters such as applied voltage, tool feed rate, and machining time. The experimental results revealed that Nickel coated Cu tool reduces the average hole overcut and heat-affected zone width and increases the overall circularity of the hole as compared to the bare Cu tool. Based on grey relational grade analysis, the optimal parameters were identified: the applied voltage of 36 V, tool feed rate of 110 µm/min, and one-minute machining time with Nickel coated copper tool. In contrast, a bare copper tool electrode provides optimal process parameters as an applied voltage of 36 V, 110 µm/min tool feed, and a machining time of two minutes for drilling holes in borosilicate glass.

An Inclusive Approach Toward Success in Undergraduate Anatomy and Physiology

With a diverse group of students taking undergraduate Anatomy and Physiology (A&P), it is imperative to find methods that enable every student to be more successful. At National University, we have been applying a new approach in our online and onsite classes that includes more learners: offering multiple attempt homework assessments. The A&P homework is scaffolded to be done with either unlimited attempts or limited to 10 attempts, depending on the specific section. The homework is given online, while subsequent assessments are either given onsite or online. The homework assignments precede more traditional, single-attempt quizzes and/or exams. Some students only complete a homework assessment once, while other students complete the homework assessment multiple times (occasionally over 50 times) in order to achieve their desired grade. The number of attempts per student is specific to each student and not to the specific topic of the homework; some students routinely carry out multiple attempts while others do not. Although making multiple attempts available may seem to allow for grade inflation, our results show that is not the case. Analysis of the number of homework attempts in relation to homework assessment grade had no correlation. Further, the number of homework attempts has no correlation with the grade students earned on quizzes or the entire course. However, a positive correlation has been established between the achieved homework grade in relation to quizzes, exams, and course grade. This positive correlation exists in both online and onsite classes. Our results indicate that enabling students to work through homework assignments according to their needs until they master each topic increases their opportunities for success in the A&P course. Our approach of offering multiple homework attempts is inclusive because it provides any learner with an opportunity to succeed. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Optimisation of extrusion process parameters to make ABS-PC filament for 3D printing using Taguchi-GRA technique

ABSTRACT This paper attempts to optimise the single screw extrusion (SSE) process parameters for extruding Acrylonitrile-butadiene-styrene (ABS) and Polycarbonate (PC) blend filament, having improved tensile strength and melt flow rate. The melt flow and mechanical properties of ABS-PC blend filament are highly reliant on the SSE process parameters. Thus, optimising the process parameters to fabricate the blend filaments with high performance has become essential. Grey relational analysis has been integrated with the Taguchi method to optimise the SSE process parameters by evaluating the grey relational grades in terms of the performance index. Experimentation has been carried out according to Taguchi’s L9 orthogonal array (OA), which has been designed considering three SSE process parameters, i.e. screw rotation, blend composition and chamber temperature. The co-continuous structure and compatibility between the phases of the blend obtained at ABS:PC 50:50 by wt%. Micrographs and thermographs support the results. The tensile strength of the 3D printed ABS:PC 50:50 by wt.% composite specimen has improved by 38.02% as compared to virgin ABS.

OPTIMIZATION OF MACHINING CHARACTERISTICS OF TITANIUM-BASED BIOMATERIALS: APPROACH TO OPTIMIZE SURFACE INTEGRITY FOR IMPLANTS APPLICATIONS

Nowadays, there has been continuous development of metallic biomaterials to meet special needs in the manufacturing of biomedical implants, units and systems so as to function well in the required environment. Developed biomaterials which possess exceptional properties in terms of biocompatibility and biomechanical compatibility require precision processing and machining to obtain the desired dimensional tolerances. Electrical discharge machining (EDM) is the noncontact or nontraditional process of machining that suits the precision machining of biomaterials. In this work, an effort was made to optimize the EDM parameters during machining of titanium-based biomaterials Ti-6AL-4V, so that the multi-objective responses could be obtained. The response surface method was used in designing the experiment, while the grey relational method was used to analyze the effect of multiple objectives into a single unit. The electrical parameters that were considered in this study include peak current, gap voltage, pulse turn-on and duty cycle. These parameters were set within the acceptable limits of the equipment. Three responses were studied, which are tool wear rates (TWRs), material removal rate (MRR) and surface roughness (SR). Using the signal-to-noise ratio and ANOVA optimum tool/electrode wear rate (TWR) is obtained at [Formula: see text][Formula: see text]g/min with process parameters [Formula: see text] A, [Formula: see text][Formula: see text]V, [Formula: see text][Formula: see text][Formula: see text]s, [Formula: see text]%. Optimum values of material removal rate (MRR) are obtained as 0.01035[Formula: see text]g/min with process parameters [Formula: see text] A, [Formula: see text][Formula: see text]V, [Formula: see text][Formula: see text][Formula: see text]s, [Formula: see text]%. Optimum SR is observed as 2.258[Formula: see text][Formula: see text]m with EDM process parameters [Formula: see text] A, [Formula: see text][Formula: see text]V, [Formula: see text][Formula: see text][Formula: see text]s, [Formula: see text]%. Surface characteristics are verified with SEM micrographs. Whereas, grey relation analysis predicted the multi-objective optimum response characteristics. Based on the grey relation grade, experiment number 7 ([Formula: see text][Formula: see text]A, [Formula: see text][Formula: see text]V, [Formula: see text][Formula: see text][Formula: see text]s, [Formula: see text]%) secured the first rank among the experiments/trails.

Application of grey relational analysis and Taguchi method in cutter working parameters for tea-leaf mechanical harvester

The tea tree is a type of horticultural crop and agricultural crop, its leaves are used to be an important ingredient in many beverages. However, the tea-leaf harvest is mainly accomplished by hands, which has an enormous impact on the yield of tea leaves. The wide application of tea-leaf mechanical harvester could improve the harvest efficiency of the tea-leaf, and then increase the harvest yield of the tea-leaf. To improve the harvest yield of the tea-leaf, the working parameters (structural and kinematic parameter) of the cutter on tea-leaf mechanical harvester need to be considered. And the cutting diagram of the cutter was used to optimize the working parameters. In this paper, the tooth top width, tooth root width, tooth depth, teeth space and cutting speed ratio were selected as working parameters of cutter that were considered to enhance the harvest efficiency. Taguchi method coupled with grey relational analysis (GRA) was used to determine the optimal combination of working parameters. Besides, the variance analysis method was performed to statistical analyse the influence of multiple parameters. The results showed that the key parameters of the variation of cutting, re-cutting and blank ratio was the teeth space. The optimal parameter combination was 4.5 mm tooth top width, 12.5 mm tooth root width, 26.0 mm tooth depth, 45.0 mm teeth space and 0.8 cutting speed ratio. Grey relational grade of the optimal parameter combination increased 0.367 compared to the grade with initial parameter combination. Based on the optimal parameter combination, the tea-leaf harvest flatness, efficiency and quality were completely in conformity with the requirements of the tea-leaf mechanical harvester. So that, the Taguchi method coupled with GRA is a practical one to optimize the working parameters of the cutter on the tea-leaf mechanical harvester.

Heat-reflux processing of black peppercorn into bioactive antioxidant oleoresins: a three-functioned Taguchi-based grey relational grading

Heat-reflux processing of black peppercorn into bioactive antioxidant oleoresins: a three-functioned Taguchi-based grey relational grading

Evolution of grades and social comparison concern within an introductory physics course

This study investigates the evolution and associations between exam grades and social comparison concern (SCC) among students in an introductory calculus-based physics course. We begin with a descriptive characterization of midterm and final exam scores as well as pre-post SCC scores, including the concurrent evolution of these scores during the course. We hypothesize a feedback loop in which changes in SCC scores are mediated by exam grades, and changes in exam scores are mediated by SCC scores. We employ a structural equation model to determine whether the data are consistent with these hypotheses. Results indicate that there were significant within-student changes in the relative grade standing from exam to exam and that changes in SCC scores depended on both the pre-SCC scores and scores on the first midterm exam. Further, we find evidence that exam scores partially mediate the association between pre- and post-SCC scores, and in turn, post-SCC scores partially mediate associations between midterm and final exam scores, though the mediation effects are somewhat small, comprising 5%–10% of the total effects between exam scores and SCC. We also find that while SCC scores are somewhat correlated with exam scores, they are only very weakly correlated with nonexam grade components, consistent with the idea that exam scores (rather than nonexam scores) are driving changes in SCC and vice versa. Overall, the results provide empirical, correlational evidence to motivate further experimental investigation into a hypothesized dynamic and iterative feedback loop in which student concern about ability or performance compared to others (SCC) can either negatively or positively interfere with student performance on exams.1 MoreReceived 5 January 2023Accepted 28 March 2023DOI:https://doi.org/10.1103/PhysRevPhysEducRes.19.010129Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.Published by the American Physical SocietyPhysics Subject Headings (PhySH)Research AreasDiversity & inclusionLearning environmentPhysics Education Research

Optimization and Characterization of Centrifugal-Cast Functionally Graded Al-SiC Composite Using Response Surface Methodology and Grey Relational Analysis

In this study, an optimization approach was employed to determine the optimal main parameters that improve the performance of functionally graded composites manufactured using a combination of stirring and horizontal centrifugal casting. Pure aluminum reinforced with silicon carbide particles was used as the material for the composites. The effects of key input parameters such as mold speed, pouring temperature, stirring speed, and radial distance were optimized using a combination of grey relational analysis and response surface methodology. The statistical significance of the predicted grey relational grade model was assessed through an analysis of variance to identify the appropriate main parameters. The results showed that radial distance had the greatest impact on the performance of the composites, followed by pouring temperature. The optimal combination of main parameters was determined to be a mold speed of 1000 rpm, a pouring temperature of 750 °C, a stirring speed of 150 rpm, and a radial distance of 1 mm. Confirmation tests using these optimal values resulted in a 54.69% improvement in the grey relational grade.

Pre-transfusion Testing Using Crossmatching Agglutination Reaction Grades Combined With Rh Subgroup Phenotyping in Patients With Autoantibodies: A Three-year Experience at a Tertiary Hospital.

The currently recommended pre-transfusion testing techniques for patients with autoantibodies are complex, time-consuming, and labor-intensive. Therefore, although the red blood cell (RBC) selection method using crossmatched RBC agglutination reaction grades (i.e., the "least incompatible" transfusion) is discouraged, many institutions still use it. We aimed to evaluate the effectiveness of this method combined with Rh subgroup phenotyping. We retrospectively investigated RBC transfusions from January 2019 to December 2021 in patients presenting as auto-control-positive via antibody identification (auto-control (+) group), where Rh subgroup phenotype-matched RBCs were selected based on the agglutination reaction grades of crossmatched units. For each study patient, an auto-control-negative patient was matched based on age, sex, department, and pre-transfusion Hb levels (auto-control (-) group). The mean Hb change per unit, transfusion-associated symptom/sign reports, and agglutination reaction grades upon crossmatching were analyzed. In the auto-control (+) group, the Hb change per unit among different agglutination reaction grades of transfused RBCs and among different relative grades of transfused RBCs and crossmatching auto-controls was not significantly different (P=0.392 and P= 0.132, respectively). No significant difference was observed in Hb changes and transfusion-associated symptom/sign occurrence between the auto-control (+) and auto-control (-) groups (P=0.121 and P=0.822, respectively). In addition, no definite evidence of hemolysis in the auto-control (+) group was observed in the medical record review. Together with Rh subgroup phenotyping, selecting the RBC unit with the lowest agglutination reaction grade upon crossmatching does not adversely affect transfusion efficiency.

Multi-Objective Optimization of Epoxy Resin Adhesive for Pavement Toughened by Self-Made Toughening Agent.

Epoxy resin adhesive for pavement is often insufficient in flexibility and toughness. Therefore, a new type of toughening agent was prepared to overcome this shortcoming. To achieve the best toughening effect of a self-made toughening agent on an epoxy resin adhesive, its ratio to the epoxy resin needs to be optimally selected. A curing agent, a toughening agent, and an accelerator dosage were chosen as independent variables. The epoxy resin's adhesive tensile strength, elongation at break, flexural strength, and flexural deflection were used as response values to establish a single-objective prediction model of epoxy resin mechanical property indexes. Response surface methodology (RSM) was used to determine the single-objective optimal ratio and analyze the effect of factor interaction on epoxy resin adhesive's performance indexes. Based on principal component analysis (PCA), multi-objective optimization was performed using gray relational analysis (GRA) to construct a second-order regression prediction model between the ratio and gray relational grade (GRG) to determine the optimal ratio and to validate it. The results showed that the multi-objective optimization using response surface methodology and gray relational analysis (RSM-GRA) was more effective than the single-objective optimization model. The optimal ratio of epoxy resin adhesive was 100 parts of epoxy resin, 160.7 parts curing agent, 16.1 parts toughening agent, and 3.0 parts accelerator. The measured tensile strength was 10.75 MPa, elongation at break was 23.54%, the bending strength was 6.16 MPa, and the bending deflection was 7.15 mm. RSM-GRA has excellent accuracy for epoxy resin adhesive ratio optimization and can provide a reference for the epoxy resin system ratio optimization design of complex components.

Abstract LB205: Feasibility and immunogenicity of adjuvant TG4050, a patient tailored cancer vaccine in head and neck and ovarian cancer

Abstract Background: Head and Neck (HNSCC) and Ovarian cancer (OC) are two indications for which immunotherapy had limited impact so far. Current treatments achieve high rates of initial success through surgery and adjuvant chemo/radiotherapy, but patients (pts) remain at high risk of relapse in both indications. Immune stimulation using a vaccine is a promising strategy to a clinically meaningful improvement. Herein we report phase I data of TG4050, a vaccine engineered to carry a pt tailored antigen payload, in pts with HNSCC (NCT04183166) or OC (NCT03839524). Methods: Tumor specific variants are identified using next generation sequencing of tumor and normal samples whereby immune relevant mutations are predicted using a machine learning algorithm factoring in parameters known to affect immunogenicity including MHC binding, level of expression, prevalence across clones, and antigen processing. DNA sequences of the mutations of interest, typically 30 per pt, are cloned in a viral vector (Modified Vaccinia Virus Ankara). Following curative intent treatment, HNSCC pts in complete remission were randomized to an immediate vaccination arm to receive weekly doses of TG4050 for 6 weeks followed by a maintenance period of one dose every 3 weeks for up to 20 doses or to a delayed vaccination arm where the same vaccination regimen is initiated at relapse. OC pts received the vaccine upon onset of signs of relapse. PBMC were collected at Baseline and after 6 doses of vaccine. Primary endpoint was vaccine safety and secondary endpoints included feasibility, immunogenicity. Results: 18 pts received TG4050 (5 OC and 13 HNSCC) treatment with no related grade ≥ 3 adverse events. Tumor mutational burden (TMB) was on average 3.00±0.98 and 2.43±0.69 mutations per megabase for HNSCC and OC respectively. Despite this low TMB, all pts had sufficient cancer specific neoantigens to design a vaccine. Ex-vivo ELISPOT was completed for 7 pts at the time of submission. A mean of 44% of selected mutations were associated with a reactive T cell responses either spontaneously or after TG4050 stimulation ranging from 6 to 22 mutations per pt. Vaccination induced a stimulation of T cell response in all tested pts on an average of 10 targeted mutations, induction of de novo responses was seen in all 7 tested pts and amplification of pre-existing response in 6/7 pts. None of the evaluable HNSCC pts receiving TG4050 immediately after first line treatment had relapse after a median follow-up of 7 months while 2 pts had relapse in the delayed vaccination arm. Furthermore, in OC pts treated at early relapse, TG4050 has normalized disease markers (ctDNA and/or CA-125) for 2/4 pts with stable disease for 9 and 11 months. Conclusion: TG4050 treatment is feasible and immunogenic in pts with low to moderate TMB. It is effective in inducing T cell responses and first signs of antitumor activity are encouraging for the continuation of development. Citation Format: Ana Lalanne, Camille Jamet, Christian H. Ottensmeier, Jean-Pierre Delord, Christophe Le Tourneau, Matthew S. Block, Gerardo Colon-Otero, Keith L. Knutson, Annette Tavernaro, Gisele Lacoste, Benoit Grellier, Xavier Noiriel, Thierry Huss, Bernard Burtin, Yoshiko Yamashita, Kousuke Onoue, Kazuhide Onoguchi, Brandon Malone, Olivier Lantz, Oliver Baker, Naoko Yamagata, Yuki Tanaka, Eric Quemeneur, Maud Brandely, Kaidre Bendjama. Feasibility and immunogenicity of adjuvant TG4050, a patient tailored cancer vaccine in head and neck and ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB205.

Transarterial Chemoembolization With Drug-Eluting Beads Versus Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Outcomes From a Multicenter, Randomized, Phase 2 Trial (the TRENDY Trial)

To compare transarterial chemoembolization delivered with drug eluting beads (TACE-DEB) with stereotactioc body radiation therapy (SBRT) in patients with hepatocellular carcinoma (HCC) in a multicenter randomized trial. Patients were included if they were eligible for TACE. They could also be recruited if they required treatment prior to liver transplantation. A maximum of four TACE-DEB procedures and ablation after incomplete TACE-DEB were both allowed. SBRT was delivered in six fractions of 8-9Gy. Primary end point was time to progression (TTP). Secondary endpoints were local control (LC), overall survival (OS), response rate (RR), toxicity, and quality of life (QoL). The calculated sample size was 100 patients. Between May 2015 and April 2020, 30 patients were randomized to the study. Due to slow accrual the trial was closed prematurely. Two patients in the SBRT arm were considered ineligible leaving 16 patients in the TACE-DEB arm and 12 in the SBRT arm. Median follow-up was 28.1 months. Median TTP was 12 months for TACE-DEB and 19 months for SBRT (p=0.15). Median LC was 12 months for TACE-DEB and >40 months (not reached) for SBRT (p=0.075). Median OS was 36.8 months for TACE-DEB and 44.1 months for SBRT (p=0.36). A post-hoc analysis showed 100% for SBRT 1- and 2-year LC, and 54.4% and 43.6% for TACE-DEB (p=0.019). Both treatments resulted in RR>80%. Three episodes of possibly related toxicity grade ≥3 were observed after TACE-DEB. No episodes were observed after SBRT. QoL remained stable after both treatment arms. In this trial, TTP after TACE-DEB was not significantly improved by SBRT, while SBRT showed higher local antitumoral activity than TACE-DEB, without detrimental effects on OS, toxicity and QoL. To overcome poor accrual in randomized trials that include SBRT, and to generate evidence for including SBRT in treatment guidelines, international cooperation is needed.

Experimental Investigation On Machining Performance of Ti6Al4V On Electro Discharge Machining Using Stationary and Rotary Electrode

Titanium alloys are commonly used in different industries due to its high strength and less in weight. Even though the machinability of titanium alloys is very less, due to its high strength, it becomes more useful in aerospace and medical industries. In this paper, the performance of stationary and rotary copper electrodes on machining of Titanium alloy Ti-6Al-4V with Electro Discharge Machining (EDM) have been studied. Material removal rate (MRR), tool ware rate (TWR) and surface roughness (SR) were analyzed with three controllable input parameters such as pulse on time (Ton), Peak Current (Ip) and Gap Voltage (V). The design of experiment is chosen for the experimentation as the Box-Behnken response surface design method. The results are analyzed using grey relational analysis (GRA) coupled with firefly algorithm. In both the case of stationary and rotary electrode, it was revealed that gap voltage is significant for overall grey relational grade. The machining performance of Titanium alloy Ti-6Al-4V in the case of rotary mode of electrode is quite better as compared to the stationary mode of operation.

Multi-response optimization for a low-cost multi-dimpling process

PurposeThis study aims to identify the significant factors of the multi-dimpling process, determine the most influential parameters of multi-dimpling to increase the dimple sheet strength and make a low-cost model of the multi-dimpling for sheet metal industries. To create an empirical expression linking process performance to different input factors, the percentage contribution of these elements is also calculated.Design/methodology/approachTaguchi grey relational analysis is used to apply a new effective strategy to experimental data in order to optimize the dimpling process parameters while taking into account several performance factors and low-cost model. In addition, a statistical method called ANOVA is used to ensure that the results are adequate. The optimal process parameters that generate improved mechanical properties are determined via grey relational analysis (GRA). Every level of the process variables, a response table and a grey relational grade (GRG) has been established.FindingsThe factors created for experiment number 2 with 0.5 mm as the sheet thickness, 2 mm dimple diameter, 0.5 mm dimple depth, 8 mm dimples spacing and the material of SS 304 were allotted rank one, which belonged to the optimal parameter values giving the greatest value of GRG.Practical implicationsThe study demonstrates that the process parameters of any dimple sheet manufacturing industry can be optimized, and the effect of process parameters can be identified.Originality/valueThe proposed low-cost model is relatively economical and readily implementable to small- and large-scale industries using newly developed multi-dimpling multi-punch and die.

MP13-06 AQUABLATION FOR BENIGN PROSTATIC HYPERPLASIA IN LARGE PROSTATES (80-150 ML): FINAL 5-YEAR RESULTS

You have accessJournal of UrologyCME1 Apr 2023MP13-06 AQUABLATION FOR BENIGN PROSTATIC HYPERPLASIA IN LARGE PROSTATES (80-150 ML): FINAL 5-YEAR RESULTS Naeem Bhojani and Mitchell R. Humphreys Naeem BhojaniNaeem Bhojani More articles by this author and Mitchell R. HumphreysMitchell R. Humphreys More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003233.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To report 5-year safety and efficacy outcomes of the Aquablation procedure for the treatment of men with symptomatic benign prostatic hyperplasia (BPH) and large-volume prostate glands. METHODS: 101 men with moderate-to-severe BPH symptoms and prostate volumes between 80-150 mL underwent a robotic-assisted Aquablation procedure in a prospective multicenter international trial. Herein we report the final 5-year results. RESULTS: The study successfully met its safety and efficacy performance goal, which was based upon TURP outcomes typically done in smaller prostates, at three months. Mean prostate volume was 107 mL (range 80-150 mL). Mean operative time (TRUS in to catheter in), was 55 minutes (range 24-111 minutes) and mean Aquablation resection time was 8 minutes (range 2.5-17 minutes). Most (89%) adverse events were low grade defined as either non-procedure related or Clavien-Dindo grade 2 or less. There was no reported de novo erectile dysfunction and 15% of patients developed ejaculatory dysfunction. The TRUS results showed a 42% reduction in prostate volume at 3 months, which aligned to the 44% reduction in serum PSA at 6 months. At 5-years, IPSS scores improved from 23.2 at baseline to 6.9 and Qmax improved from 8.7 cc/sec at baseline to 18.6 cc/sec. Improvements in both IPSS, IPSS Quality of Life, Qmax, and PVR were immediate (p<.0001) and sustained (p<.0001) throughout the follow-up period, Figure 1. The annualized retreatment rate was less than 1% per year. CONCLUSIONS: At 5-year of prospective follow-up, the Aquablation procedure was shown to be safe and effective in men with large prostates (80-150 mL). ClinicalTrials.gov number, NCT03123250. Source of Funding: Procept BioRobotics © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e175 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Naeem Bhojani More articles by this author Mitchell R. Humphreys More articles by this author Expand All Advertisement PDF downloadLoading ...

5589320 FOLLOW-UP RESULTS OF A PHASE 2 STUDY ASSESSING THE SAFETY AND EFFICACY OF MITAPIVAT TREATMENT, AN ORAL PYRUVATE KINASE ACTIVATOR, FOR UP TO 60 WEEKS IN SUBJECTS WITH SICKLE CELL DISEASE

Background: Sickle cell disease (SCD) is a devastating red blood cell (RBC) disorder. The root cause of SCD is polymerization of sickle hemoglobin (HbS) upon deoxygenation, resulting in poorly deformable sickled RBCs with shortened lifespan. 2,3-diphosphyglycerate (2,3-DPG), a glycolytic intermediate in RBCs, promotes deoxygenation by lowering hemoglobin (Hb)-oxygen affinity. Mitapivat (AG-348) is an oral allosteric activator of pyruvate kinase (PK), a key enzyme in RBC glycolysis generating adenosine triphosphate (ATP) and reducing 2,3-DPG levels. Aims: To report follow-up data of the safety and efficacy of mitapivat treatment in subjects with SCD (ESTIMATE study; www.trialregister.nl NL8517; EudraCT 2019-003438-18). Methods: The ESTIMATE study is a phase 2, investigator initiated, open-label study. Subjects ≥16 years with SCD (HbSS, HbS/β0 or HbS/β+), 1-10 vaso-occlusive crises (VOCs) in the prior year and/or prior SCD-related complications, a Hb level >6.1 g/dL and ≤11.1 g/dL, and no chronic transfusions are eligible and treated with mitapivat after obtaining informed content. In the 8-week dose finding period, initial dosing is 20 mg twice daily, escalated to max. 100 mg twice daily, and followed by an up to 52-week fixed dose extension period (FDEP). Primary endpoints are safety, based on adverse events (AEs), and efficacy of mitapivat treatment on RBC sickling (Point of Sickling (PoS), oxygen gradient ektacytometry). Key secondary endpoints are changes in Hb level, markers of hemolysis, ATP/2,3-DPG levels, and Hb-oxygen affinity (p50, Hemox Analyzer). Results: Until Jan. 2022, 9 subjects were treated with mitapivat. Baseline characteristics were: median age 22 years (range 16-59 years), 6/9 (67%) female, and 6/9 (67%) used hydroxyurea. 7/9 (78%) had HbSS, 1/9 (11%) had HbS/β0, and 1/9 (11%) had HbS/β+. One subject with a non-treatment related serious AE (SAE) of a urinary tract infection (grade 4), was lost to follow-up shortly after first dosing. No other SAEs or treatment-emergent AEs (TEAEs) grade ≥3 occurred. The remaining 8 subjects had a median treatment duration of 38 weeks (range 11-60 weeks). 6/8 (75%) took 100 mg mitapivat twice daily in the FDEP, and 2/8 (25%) took 50 mg mitapivat twice daily after a single dose reduction because of progressive transaminase increase. The most common TEAEs were (n>2 subjects): ALT or AST increase (both 5/9, 56%; all grade 1), and headache (4/9, 44%; grade 1-2). Three VOCs occurred: one related to excessive alcohol consumption with no need for hospitalization, and two in subjects with documented noncompliance the week before hospitalization. Mean annual VOC rate and SCD-related hospital admission days were, respectively, 1.5±1.3 and 5.9±7.1 days at baseline, and reduced to 0.5±0.7 and 1.6±3.1 days when weighting cases by follow-up duration (p=0.021 and p=0.134, respectively). Table 1 summarizes mean changes in parameters of primary and key secondary endpoints of scheduled visits in the FDEP compared to baseline. Hb level significantly increased, accompanied by a decrease in markers of hemolysis (absolute reticulocyte count, total bilirubin, lactate dehydrogenase). Mean PoS decreased, and p50, 2,3-DPG level and ATP/2,3-DPG ratio significantly improved. Conclusion: Treatment with mitapivat for up to 60 weeks in subjects with SCD showed no treatment related TEAEs grade ≥3. Improvements in anemia, markers of hemolysis, oxygen affinity, 2,3-DPG level and ATP/2,3-DPG ratio were seen.

MP63-13 TRIALS IN PROGRESS: A PHASE I/II TRIAL OF INTRAVESICAL CHEMOIMMUNOTHERAPY WITH GEMCITABINE AND BACILLUS CALMETTE-GUÉRIN (BCG) FOR PATIENTS WITH BCG-EXPOSED HIGH-GRADE NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC)

You have accessJournal of UrologyCME1 Apr 2023MP63-13 TRIALS IN PROGRESS: A PHASE I/II TRIAL OF INTRAVESICAL CHEMOIMMUNOTHERAPY WITH GEMCITABINE AND BACILLUS CALMETTE-GUÉRIN (BCG) FOR PATIENTS WITH BCG-EXPOSED HIGH-GRADE NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) Christopher Gaffney, NEETA D'Souza, Christian Hernandez, Melissa McCarter, Patricia Moran, Kristen Staci, Kara Worth, Guido Dalbagni, Timothy Donahue, Sherri Donat, Bernard Bochner, Judy Sarungbam, Dean Bajorin, Hikmat AL-Ahmadie, Daniel Sjoberg, Alvin Goh, and Eugene Pietzak Christopher GaffneyChristopher Gaffney More articles by this author , NEETA D'SouzaNEETA D'Souza More articles by this author , Christian HernandezChristian Hernandez More articles by this author , Melissa McCarterMelissa McCarter More articles by this author , Patricia MoranPatricia Moran More articles by this author , Kristen StaciKristen Staci More articles by this author , Kara WorthKara Worth More articles by this author , Guido DalbagniGuido Dalbagni More articles by this author , Timothy DonahueTimothy Donahue More articles by this author , Sherri DonatSherri Donat More articles by this author , Bernard BochnerBernard Bochner More articles by this author , Judy SarungbamJudy Sarungbam More articles by this author , Dean BajorinDean Bajorin More articles by this author , Hikmat AL-AhmadieHikmat AL-Ahmadie More articles by this author , Daniel SjobergDaniel Sjoberg More articles by this author , Alvin GohAlvin Goh More articles by this author , and Eugene PietzakEugene Pietzak More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003321.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The standard of care for high-risk NMIBC after exposure to induction only BCG or relapse >12 months after “adequate” BCG is retreatment with BCG. However, ∼50% will relapse within 6 months. Intravesical Gemcitabine (GEM) is a well-tolerated, common treatment for NMIBC with better efficacy after BCG than mitomycin C which may synergistically enhance the efficacy of BCG by augmenting the immune tumor microenvironment. We are evaluating gemcitabine and BCG (GemBCG) intravesical chemoimmunotherapy to address the need for more effective and less toxic bladder preserving treatments by enhancing BCG efficacy. METHODS: This is an investigator-initiated Phase I/II trial of GemBCG for BCG-exposed NMIBC enrolling patients with BCG-exposed carcinoma in-situ (CIS±Ta/T1) that recurred within 24 months of last BCG (BCG-exposed/BCG-relapsing NMIBC, Figure 1). Patients with BCG-unresponsive disease, contraindication to BCG, or prostatic/ureteral urothelial disease are excluded. The primary endpoint for Phase I was safety and dose tolerability. The primary endpoint for Phase II is clinical complete response (CR) at 6 months (absence of high-grade disease on cystoscopy/TURBT and negative cytology). Using a Simon’s optimal 2-stage design testing the null hypothesis of a true CR of 55% at 6 months (based on historical outcomes of BCG alone) we plan to enroll 19 and 24 patients in the first and second stage, respectively. Phase I patients treated at the maximum tolerated dose (MTD) are included in phase II. Secondary outcomes include recurrence progression, and cystectomy-free survival. Correlative studies explore immune and molecular predictors of response and resistance to chemoimmunotherapy in tumor tissue, urine, and blood. RESULTS: Of the 25 patients who completed Phase I, 14/25 were treated at the MTD and processed to Phase II. Treatment was well-tolerated (no treatment related grade ≥3 adverse events) and demonstrated promising early efficacy (95% [19/20] CR at 6-months). CONCLUSIONS: A combination of intravesical GEM and BCG appears safe and well tolerated in patients with BCG-relapsed/BCG-exposed NMIBC. Promising early efficacy data requires completion of Phase II for confirmation (NCT04179162). Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e876 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christopher Gaffney More articles by this author NEETA D'Souza More articles by this author Christian Hernandez More articles by this author Melissa McCarter More articles by this author Patricia Moran More articles by this author Kristen Staci More articles by this author Kara Worth More articles by this author Guido Dalbagni More articles by this author Timothy Donahue More articles by this author Sherri Donat More articles by this author Bernard Bochner More articles by this author Judy Sarungbam More articles by this author Dean Bajorin More articles by this author Hikmat AL-Ahmadie More articles by this author Daniel Sjoberg More articles by this author Alvin Goh More articles by this author Eugene Pietzak More articles by this author Expand All Advertisement PDF downloadLoading ...

ISSLS PRIZE in Clinical Science 2023: comparison of degenerative MRI features of the intervertebral disc between those with and without chronic low back pain. An exploratory study of two large female populations using automated annotation

ObjectivesThe relationship of degeneration to symptoms has been questioned. MRI detects apparently similar disc degeneration and degenerative changes in subjects both with and without back pain. We aimed to overcome these problems by re-annotating MRIs from asymptomatic and symptomatics groups onto the same grading system.MethodsWe analysed disc degeneration in pre-existing large MRI datasets. Their MRIs were all originally annotated on different scales. We re-annotated all MRIs independent of their initial grading system, using a verified, rapid automated MRI annotation system (SpineNet) which reported degeneration on the Pfirrmann (1–5) scale, and other degenerative features (herniation, endplate defects, marrow signs, spinal stenosis) as binary present/absent. We compared prevalence of degenerative features between symptomatics and asymptomatics.ResultsPfirrmann degeneration grades in relation to age and spinal level were very similar for the two independent groups of symptomatics over all ages and spinal levels. Severe degenerative changes were significantly more prevalent in discs of symptomatics than asymptomatics in the caudal but not the rostral lumbar discs in subjects < 60 years. We found high co-existence of degenerative features in both populations. Degeneration was minimal in around 30% of symptomatics < 50 years.ConclusionsWe confirmed age and disc level are significant in determining imaging differences between asymptomatic and symptomatic populations and should not be ignored. Automated analysis, by rapidly combining and comparing data from existing groups with MRIs and information on LBP, provides a way in which epidemiological and ‘big data’ analysis could be advanced without the expense of collecting new groups.Level of evidence IDiagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Development of a New Micro Drilling Tool with H-Shaped Chisel Edge

In order to improve the tool life and micro-hole machining quality, the H-shaped chisel edge micro-drill (HCE-MD) was developed in this paper. The HCE-MD was characterized by the inner edge formed through the chisel edge thinning. In the micro-drilling process, the inner edge can perform positive rake cutting, so the machining area of the workpiece extruded by cutting edge with a negative rake angle is reduced. Based on this, the distribution of rake angle near the chisel edge corner is improved. Then, the HCE-MD was fabricated on the six-axis CNC grinding machine. The grinding process parameters of the micro-drill were optimized based on the orthogonal grinding test and grey relational grade theory. The size and shape accuracy of the micro-drill were controlled by the multi-axis linkage grinding method and the movement-axis micro compensation method. Finally, the 0.25 mm HCE-MD was fabricated with the cutting edge radius of 1.94 μm and the flank surface roughness of 0.25 μm. The drilling performance of HCE-MD was evaluated through comparative drilling experiments. The experimental results show that, compared with common micro drill, the HCE-MD produced lower thrust force and better micro-hole roundness accuracy, and reduced the micro-drill wear on the chisel edge and the flank.