A Review On Investigation Of Process Parameters Of Mig Welding Machine

This paper discusses about the investigation of process parameters of MIG welding of various parts of a material. The main purpose of the experiment is; to study the role of Voltage, Welding Current & Shielding Gas Flow Rate on the various responses like Welding Penetration, Surface Roughness, Hardness & Ultimate Tensile Strength of the finalized material. The responses are calculated using the variety of orthogonal array design, followed by the priority of response table prepared by the Taguchi approach. The various responses are analyzed by the Response Table, as handled using ANOVA. The regression model is well executed. Hence, the optimization of the process parameters was executed. With optimization, the effect of various process parameters on the responses can be easily studied and a well satisfied relationship is maintained between them.

Measurable residual disease response in acute myeloid leukemia treated with venetoclax and azacitidine.

7018 Background: In the phase 3 VIALE-A trial, rates of composite complete remission (CRc; complete remission [CR] + CR with incomplete hematologic recovery [CRi]) and measurable residual disease response (MRD<10-3) were higher in patients (pts) treated with venetoclax (Ven) + azacitidine (Aza) compared to Aza alone (23.4%/7.6%, p<0.001). There is limited evidence of the clinical significance of MRD monitoring in pts receiving low-intensity chemotherapy. Herein, we explored the outcomes of pts treated with Ven+Aza who achieved both CRc and MRD<10-3 in the VIALE-A trial (NCT02993523). Methods: Enrolled pts were ≥18 years and unfit for intensive chemotherapy. Pts received Ven 400 mg orally; days 1–28 and Aza 75 mg/m2; days 1-7/28-day cycle. Bone marrow aspirate samples for multiparametric flow cytometry assessments by integrated leukemia-associated immunophenotypes and different than normal procedures were collected for central analysis (Covance Central Laboratory Services) at baseline, end of cycle 1, and every 3 cycles thereafter. Assessments were performed independent of disease responses. MRD response was defined as <1 residual blast /1000 leukocytes (<10-3). CRc, DoR, OS, and EFS were assessed. Disease assessments were per modified International Working Group response criteria for AML. Results: 211/286 (74%) pts treated with Ven+Aza with at least one valid post-baseline MRD assessment were considered MRD evaluable; 78/211 (37%) achieved MRD<10-3 and 133/211 (63%) had MRD≥10-3. Median age (MRD<10-3/ MRD≥10-3) was 76 (range: 49-89)/77 (58-91) yrs. Pts (MRD<10-3/ MRD≥10-3) received median of 14.5 (range: 1-28) /7.0 (1-30) cycles of Ven+Aza. At median follow-up of 22.0 (range: 20.1-23.0)/20.8 (19.8-22.3) months (mos), CRc + MRD<10-3/ MRD≥10-3 was achieved by 67 (86%)/ 97 (73%); 20/67 (30%) achieved CRc + MRD<10-3 by end of cycle 1. Median DoR, OS, and EFS were not reached in pts with CRc + MRD<10-3 response (Table). The 12-mo estimates for DoR, OS, and EFS for pts with CRc + MRD<10-3response were 81.2%, 94.0%, and 83.2%, respectively. Adverse events ≥grade 3 (MRD<10-3/ MRD≥10-3) were febrile neutropenia (50%/43%), neutropenia (50%/35%), and thrombocytopenia (44%/44%), similar to the overall population. Conclusions: Pts with best response of CRc who achieved MRD<10-3 response with Ven+Aza treatment had longer DoR, OS, and EFS than pts who were CRc and MRD positive. Clinical trial information: NCT02993523. [Table: see text]

Changes in ctDNA levels after MIBG therapy in patients with relapsed or refractory neuroblastoma.

10012 Background: Circulating tumor DNA (ctDNA) is detectable in children with neuroblastoma. Less is known about how levels change during treatment and the implications of these changes. We evaluated ctDNA pre- and post- 131I-metaiodobenzylguanidine (MIBG) therapy. Methods: We utilized plasma samples from NANT11-01 (NCT02035137), a multi-center, open label, randomized phase II clinical trial evaluating MIBG with or without radiation sensitizers for patients with relapsed or refractory neuroblastoma. Plasma was collected at Baseline prior to MIBG, 72 hours (Hr72), 96 hours (Hr96), 15 days after MIBG (D15), and prior to a second course among patients without progression who received a second course (C2). Samples were analyzed for percent ctDNA levels using ultra-low passage whole genome sequencing. We evaluated associations between ctDNA findings with baseline disease measures of percent involvement in bone marrow, Curie score, and RECIST disease sum of diameters as well as overall response by NANT Response Criteria v1.2 (complete response or partial response coded as responders). Results: Eighty-four patients had a baseline sample and were included in this analysis. Of the 37 patients (44%) with detectable ctDNA at baseline, the median ctDNA level was 32% (range 3.9-91%). Baseline ctDNA levels showed a significant positive correlation with percent involvement in bone marrow (r=0.37; p=0.0004) and Curie score (r=0.26; p = 0.018), but not RECIST sum of diameters for soft tissue sites (r=0.065; p=0.56). Following therapy, the proportions of patients with detectable ctDNA were: Hr72 47% (34/73; median level 28%); Hr96 50% (26/52; median 28%); D15 33% (7/21; median 4%); and C2 14% (3/21; median 50%). Rate of ctDNA detection was similar between responders and non-responders at baseline, Hr72, and Hr96, but lower among responders at D15 and C2 (Table). Among the 21 patients with C2 data, ctDNA levels were either undetectable (n=18) or lower than Cycle 1 Baseline (n=3). Among patients with detectable baseline ctDNA, the median relative ctDNA level at Hr72 (Hr72 ctDNA/baseline ctDNA) for non-responders was 0.87 (n=24) vs. 1.16 for responders (n=7). In contrast, the median relative ctDNA level at C2 for non-responders was 0.56 (n=4) vs. 0 for responders (n=4). Conclusions: ctDNA is detectable in a substantial proportion of patients with relapsed / refractory neuroblastoma, with levels correlated with conventional measures of disease burden. Following MIBG therapy, early timepoints (Hr72 and Hr96) are less informative, whereas ctDNA becomes undetectable at D15 and C2 more commonly in patients with clinical response.[Table: see text]

Association between prior radical surgery (RS) and outcomes with immune checkpoint inhibitor (ICI) therapy for advanced urothelial carcinoma (aUC).

444 Background: It is unclear whether prior RS of primary tumor is associated with response and outcomes with ICI in aUC. We hypothesized that such response and outcomes would not differ based on prior RS. Methods: We performed a retrospective cohort study including patients (pts) with aUC who received ICI. We compared overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) between pts with vs without RS [cystectomy or (nephro)-ureterectomy]. Analysis was stratified based on ICI therapy line (first-line vs salvage). A separate comparison between pts with prior RS or radiation (RT) only or none was also pursued. ORR was compared between groups using logistic regression, as well OS and PFS using cox regression analysis; a multivariable model was built adjusting for calculated Bellmunt score. P<0.05 was significant. Results: We identified 984 pts from 24 institutions; 682, 704 and 673 were included in OS, PFS and ORR analyses, respectively; 54% of pts had prior RS with median age 68 at ICI initiation with RS vs 71 without RS with similar proportion of men (73-74%) and ever smokers (70-71%). The RS group had higher proportion (%) of white pts (77% vs 71%), lower % of pts with Hb<10g/dL at ICI initiation (23% vs 32%) but not significantly higher % of liver metastasis at ICI initiation (23% vs 17%). Bellmunt score with vs without RS was 16% vs 11%, 50% vs 48%, 27% vs 37%, 7% vs 4% for 0, 1, 2, and 3, respectively. ORR and PFS were not significantly different between groups, while prior RS was associated with longer OS (unadjusted HR 0.8, p=0.03). However, after adjustment for Bellmunt score, this association was not significant (table). Upon stratification based on treatment line, OS was longer with prior RS (0.7, p=0.03) for those treated with salvage ICI but this was not significant after adjusting for Bellmunt score. ORR, PFS and OS were not significantly different between pts receiving prior RT only vs RS vs none. Conclusions: Prior RS was not significantly associated with longer OS in pts with aUC receiving ICI after adjusting for Bellmunt score. Further work is needed to interrogate tumor-host immune interactions and identify biomarkers that can be prognostic and/or predictive of ICI response. [Table: see text]

Analysis of Surface Roughness and Burr Height in Drilling of Aluminium Matrix Composites using Taguchi Technique

The present research involves the opportunity of utilising the signal to noise (S/N) ratio analysis to set machining factors in the drilling of aluminium alloy LM6-Fly ash composites (AMCs). The purpose of this research is to understand, during drilling of AMCs, the consequences of variables, feed rate, spindle speed, drill material and amount of reinforcing material on surface roughness and burr height. AMCs are formed with LM6 (Al alloy) as continuous component via the stir casting process and fly ash as reinforced content. The Taguchi design strategy is a widely accepted method which is used to produce quality products that require minimum commitment. Likewise, the L27 orthogonal array is used for conducting experiments. The response table, response graphs and analysis of variance (ANOVA) illustrate the prospective atmosphere and the impacts of input process variables. Taguchi technique considerably enhances the drilling operation.

Circulating tumor cells (CTCs) with small-cell like pathology are prevalent in metastatic castration-resistant prostate cancer (mCRPC) and show selective pharmacodynamic reductions in patients treated with platinum but not ARSI or taxane.

5572 Background: The increasing availability and earlier use of life prolonging drugs targeting the androgen receptor signaling axis (ARSI) has resulted in an increase in the frequency of late state tumors with “small cell/neuroendocrine (NESC) phenotypes” similar to small-cell lung cancer (SCLC). Definitive pathologic criteria to diagnose the “entity” are lacking, and the eligibility criteria across trials are inconsistent, limiting the ability to relate outcomes between studies. We hypothesized that an analytically valid assay for a rigorously defined “small-cell CTC” phenotype might serve as a unifying biomarker for the presence of NESC-like tumors in an individual for use in clinical trials. Methods: Using the WHO guidelines for small-cell diagnosis in tissue as reference, we defined an equivalent set of single-cell CTC criteria for defining a CTC with small-cell histology: a small and circular CD45-, CK+ cell with high N/C ratio lacking detectable nucleoli. Small-cell subtype pharmacodynamic changes were studied in 233 patients with progressing mCRPC about to start an AR signaling inhibitor ARSi (N=111), taxane (N=89), or platinum (N=33). Results: CTCs with small-cell morphology had lower AR protein expression compared with non-small-cell CTCs (P<0.0001) and increased with therapy line. The small-cell CTC subtype decreased in number from baseline to on-therapy in patients treated with platinum but not in those treated with ARSi or taxane (Table). Conclusions: Digital pathology analysis of CTCs defined a CTC subtype consistent with that of small-cell carcinoma that were only reduced in number with platinum-based therapy. The tracking of CTC subtypes after treatment with different drug classes may help assess drug activity in heavily treated patients that often have heterogeneous disease that of which may not be captured using standard measures of response. [Table: see text]

Abstract P260: Determinants of Statin Response: A Secondary Analysis of the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER)

Introduction: Wide variability in LDLC change is observed with statins, yet determinants of statin response are uncertain. Hypotheses: Some markers of inflammation are associated with decreased statin response. Components of metabolic syndrome and older age are associated with better response. Methods: JUPITER (NCT00239681) randomized participants with LDLC<130 mg/dL and hs-CRP≥2 mg/L to rosuvastatin 20 mg/d or placebo. Baseline and 1-year levels of LDLC and a panel of 20 other biomarkers were measured. We defined optimal statin response as ≥50% LDLC reduction; suboptimal response as <50% reduction; and non-response as no change or increase in LDLC. χ 2 , t-tests and ANOVA were used to compare variables across optimal (N=3,801), suboptimal (N=3,235) and non-responders (N=868). Multinomial regression models evaluated associations of determinants of statin response after adjusting for risk factors including compliance. Backward selection identified variables that associated with response. t-distributed Stochastic Neighbor Embedding (t-SNE) suggested predictor clusters for statin response. Results: Compliance was the strongest determinant of statin response (Table). On multivariable analyses, blacks and Hispanics were at higher risk for suboptimal/non-response compared with whites as were greater alcohol use and HbA1c. Higher baseline levels of lipids [lipoprotein(a), apolipoprotein (apo) AI and B], inflammatory biomarkers, and lower branched-chain amino acids associated with decreased statin response (Table). By contrast, determinants of better response included older age, female sex, and higher waist circumference and baseline levels of LDLC, triglycerides, and blood pressure. We observed systematic patterns in t-SNE clustering for statin response by LDLC, LDL particle number, and apo B. Conclusions: This study identified determinants for high-intensity statin response and suggests other pathways of CVD risk beyond those addressed by statin treatment that require further investigation.

An Improved Taguchi Algorithm Based on Fitting and Prediction for Linear Antenna Array Synthesis

In this paper, a Taguchi method based on fitting and prediction is proposed to accelerate the optimization process in antenna array synthesis. The implementation procedure combines the normal Taguchi method and the curve fitting technique. A possible solution is determined by prediction based on fitting curves. Specifically, the fitting curves are obtained by using the dynamic points calculated and updated as the Taguchi method progress and recorded in the response table necessarily produced in the procedure. Test functions are used for conducting some confirmation experiments, and the results verify the validity of the proposed method. In order to illustrate its good practicability, two linear antenna arrays with a null controlled pattern and a flat top pattern, respectively, are successfully optimized by using both of the normal Taguchi method and the proposed one. Some comparisons and discussions of their results are given in the paper, which proves that the proposed method has a better practicability, not only because it inherits the global optimization characteristics of the normal Taguchi method but also because it accelerates the convergence process.

Association of polybromo-associated BAF (PBAF) complex mutations with overall survival (OS) in cancer patients (pts) treated with checkpoint inhibitors (ICIs).

103 Background: ICIs have shown benefit across several metastatic carcinomas, yet predictive biomarkers are still lacking. 20% of malignancies harbor alterations in ≥1gene that is part of PBAF complex. With recent data suggesting an association between PBRM1 mutations (mts) and outcomes in renal cell carcinoma (RCC) pts treated with ICIs (Miao, Science, 2018), we examined the association between PBAF mts and OS in ICI-treated patients across several solid cancer (ca) types. Methods: Of 6007 pts with different ca histologies and targeted exome sequencing (Oncopanel) at Dana Farber Cancer institute (DFCI), 138 pts had truncating mts in any PBAF gene (SMARCA4, PBRM1, and ARID2) or oncogenic missense mts in SMARCA4 and were treated with ICIs. 138 histology-matched DFCI pts had none. A publicly-available cohort (2:1 histology matched) from Memorial Sloan Kettering (MSKCC) (Samstein et al., Nature Genetics, 2019) of 621 ca pts (PBAF mutant [MT] = 207, PBAF wild type [WT] = 414) treated with ICIs was analyzed for association between PBAF mts and OS. OS was defined from time from ICI initiation. OS was compared by Cox regression between PBAF MT and PBAF WT. Hazard ratio (HR) was derived using univariable and multivariable analysis (MVA) adjusted for ICI regimen (single vs combination) and age. Results: Median (Md) follow-up for the combined cohort (n = 897) was 27 months (m). Major histologies were non-small cell lung ca (268; 29.9%), melanoma (220; 24.5%), RCC (181; 20.2%), and bladder ca (65; 7.2%). Results on univariable and MVA analyses from individual and combined cohorts are presented below. Conclusions: PBAF mts are associated with survival in ICI-treated ca pts. Work in progress with non-ICI treated pts will determine if this is prognostic or predictive of response. [Table: see text]