Examination of Dust in AVR Pipe Components

2008 ◽  
Author(s):  
Johannes Fachinger ◽  
Heiko Barnert ◽  
Alexander P. Kummer ◽  
Guido Caspary ◽  
Manuel Seubert ◽  
...  
Keyword(s):  
Particle Size ◽  
Optical Microscopy ◽  
Phase 1 ◽  
Median Number ◽  
Primary Circuit ◽  
Pipe Surface ◽  
Dose Rates ◽  
The Core ◽  
Chemical Decontamination ◽  
Dust Surface

Pebble Bed HTGR’s like the AVR in Ju¨lich have the advantage of continuous fuelling. However the multiple passes of the fuel pebbles through the core have the disadvantage that the pebble’s movement through the fuelling system and the core produces graphite dust. This dust is transported from the core to other parts of the primary circuit and deposits on components. Although previous experiments performed during AVR operation have given some insight into the dust particle size and activity, there is little information on the behaviour of the dust that was deposited in the system. The decommissioning of the AVR has provided the opportunity to sample and characterise such dust from a number of components and gauge the adhesion strength. From the side of PBMR Pty Ltd this opportunity is considered important to enhance the knowledge about dust characteristics before the PBMR Demonstration Power Plant (DPP) is operational and able to produce specific plant information through sampling and analysis. AVR GmbH has provided a number of pipes and joints for investigation of loose and bound dust. Phase 1 of the analysis was used to determine the best techniques to be used on larger items. No measurable loose dust could be collected. Thereupon rings were cut from a T-section and subdivided into eight segments. The surface of the untreated segments were photographed and documented by optical microscopy, the dose rates were measured and gamma-spectrometry performed. Following this a mechanical or chemical decontamination was carried out to remove and isolate the bound dust. The average isolated dust amount was about 2 mg/cm2. Both decontamination processes indicates a strong bonding of the dust surface layer. In the case of mechanical decontamination about 60% and by chemical decontamination about 95% of the radionuclide inventory could be removed. The contribution of removed metal needs to be investigated in more detail. The median number related particle size measured by optical microscopy was found to be in the range of 0.2 to 0.7 μm whereas the median weight related size is in the range of 0.8 to 1.5 μm. The initial results indicate that this dust sticks very strongly to the pipe surface. Phase 2 will concentrate on longer pieces of piping where hopefully more loose dust can be obtained and analysed. If the same strong bonding is observed the reason for this phenomenon needs to be explained and perhaps tested with non-active dust.

scholarly journals Influence of size polydispersity on magnetic field tunable structures in magnetic nanofluids containing superparamagnetic nanoparticles.

2021 ◽  
Author(s):  
Dillip Kumar Mohapatra ◽  
Philip James Camp ◽  
John Philip
Keyword(s):  
Magnetic Field ◽  
Particle Size ◽  
Light Scattering ◽  
Optical Microscopy ◽  
Brownian Dynamics ◽  
Phase Contrast ◽  
Superparamagnetic Nanoparticles ◽  
Magnetic Nanofluids ◽  
Dynamics Simulations ◽  
Brownian Dynamics Simulations

We probe the influence of particle size polydispersity on field-induced structures and structural transitions in magnetic fluids (ferrofluids) using phase contrast optical microscopy, light scattering and Brownian dynamics simulations. Three...

scholarly journals CTNI-18. FINAL RESULTS OF A PHASE 2 STUDY OF EFFICACY, SAFETY AND INTRATUMORAL PHARMACOKINETICS (PK) OF SELINEXOR MONOTHERAPY IN RECURRENT GLIOBLASTOMA (rGBM)

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii46-ii46
Author(s):  
Andrew Lassman ◽  
Patrick Wen ◽  
Martin van den Bent ◽  
Scott Plotkin ◽  
Annemiek Walenkamp ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Median Number ◽  
Recurrent Glioblastoma ◽  
Phase 2 ◽  
Nuclear Retention ◽  
Phase 2 Trial ◽  
Human Gbm

Abstract BACKGROUND Selinexor is an FDA-approved first-in-class, oral selective nuclear export inhibitor which forces nuclear retention of many tumor suppressor proteins. METHODS We conducted a phase 2 trial of selinexor monotherapy for adults with recurrent GBM including a surgical arm to explore intratumoral PK and 3 medical arms to optimize dosing. Prior treatment with radiotherapy and temozolomide was required; prior bevacizumab was exclusionary. The primary endpoint was 6-month progression-free survival (6mPFS) rate. RESULTS Selinexor administered ~2 hours pre-operatively yieleded average intratumoral concentration (136 nM, n=6) comparable to the in vitro IC50 (130 nM) from 7 primary human GBM cell lines. Among all 68 patients accrued to 3 medical arms (~85 mg BIW, n=24; 60 mg BIW, n=14; 80 mg QW, n=30), median age was 56 years (21–78). Median number of prior lines of therapies was 2 (1–7). At 80 mg QW, 28% patients were progression-free at the end of cycle 6; the 6mPFS was 17%; disese control rate by RANO was 37% (1 CR, 2 PRs, 7 SD) among 27 evaluable patients; responses were durable (median 11.1 months), and treatment lasted for 442, 547 and 1282 days in 3 responders, as of data lock, with one responder remaining on treatment off study; median overall survival was 10.2 months with 95% CI (7.0, 15.4). The ~85 mg BIW-schedule was abandoned due to poor tolerability. The related adverse events (all grades) in patients on ~85 mg BIW/60 mg BIW/80 mg QW were nausea (41.7%/64.3%/66.7%), fatigue (70.8%/71.4%/50.0%), neutropenia (29.2%/14.3%/33.3%), decreased appetite (45.8%/71.4%/26.7%), thrombocytopenia (66.7%/28.6%/23.3%) and weight loss (16.7%,/42.9%/6.7%). CONCLUSION Selinexor monotherapy demonstrated encouraging intratumoral penetration and efficacy, with durable disease control in rGBM. Monotherapy dose at 80 mg QW is recommended for further development in rGBM. A phase 1/2 study of combination therapy for newly diagnosed or rGBM has been initiated (NCT04421378).

Anakinra (AKR) prophylaxis (ppx) in patients (pts) with relapsed/refractory multiple myeloma (RRMM) receiving orvacabtagene autoleucel (orva-cel).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2537-2537
Author(s):  
Luciano J. Costa ◽  
Sham Mailankody ◽  
Paul Shaughnessy ◽  
Parameswaran Hari ◽  
Jonathan L. Kaufman ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Phase 1 ◽  
Median Number ◽  
Control Group ◽  
T Cell Therapy ◽  
Disease Response ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

2537 Background: Orva-cel is a B-cell maturation antigen–targeted chimeric antigen receptor (CAR) T cell therapy being evaluated in the phase 1/2 EVOLVE study (NCT03430011) in pts with RRMM who had at least 3 prior lines of therapy (Tx). We previously reported safety and efficacy in the phase 1 study and established the recommended dose (RD) of orva-cel as 600 × 106 CAR+ T cells (Mailankody et al, ASCO 2020). Cytokine release syndrome (CRS), a dominant toxicity of CAR T cell therapy, is mediated in part by IL-1. We explore the role of ppx with AKR, an IL-1 signaling inhibitor, on reducing the incidence of grade (G) ≥2 CRS after orva-cel treatment at the RD. Methods: Fourteen pts were enrolled sequentially for AKR ppx and treated with orva-cel at the RD. The non-AKR ppx control group comprised the remainder of the phase 1 pts receiving orva-cel at the RD (n = 19). The median follow-up (range) was 3.0 mo (1.8–6.2) for the AKR ppx group and 8.8 mo (5.3–12.2) for the non-AKR ppx group. AKR was administered as 100 mg SC the night before orva-cel infusion, 3 h before the infusion (Day 1), and q24 h on Days 2–5. Dosing was increased to q12 h if CRS developed. CRS was graded by Lee (2014) criteria. Tocilizumab (T) and steroids (S) were used per protocol-specified treatment management guidelines. Results: Disease characteristics and outcomes are shown in the table. In AKR ppx and non-AKR ppx groups, median number of prior regimens was 6 and 5, and bridging Tx was used in 57% and 68% of pts, respectively. The total frequency of CRS was similar in the 2 groups, but with less G 2 in the AKR ppx pts; relative risk (95% CI) = 0.54 (0.21, 1.38). No G ≥3 CRS was seen in either group. The incidence of neurological events (NE), G ≥3 infection, and macrophage activation syndrome/hemophagocytic lymphohistiocytosis (MAS/HLH) was similar. T and S use was numerically lower with AKR ppx. Orva-cel expansion kinetics were similar in the 2 groups. All pts had a 2-month efficacy assessment, with ORR in 100% of AKR ppx and 95% of non–AKR ppx pts. Conclusions: In this nonrandomized evaluation of AKR ppx with orva-cel treatment, the incidence of G ≥2 CRS was lower in pts receiving AKR ppx. The use of AKR ppx produced no adverse effect on the incidence of NE, infection, or MAS/HLH, nor on orva-cel expansion or disease response. These results warrant further study of AKR ppx in CAR T cell therapy. Clinical trial information: NCT03430011. [Table: see text]

Phase 1/2 study of cirmtuzumab and ibrutinib in mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7556-7556
Author(s):  
Hun Ju Lee ◽  
Michael Y. Choi ◽  
Tanya Siddiqi ◽  
Jacqueline Claudia Barrientos ◽  
William G. Wierda ◽  
...  
Keyword(s):  
Phase 1 ◽  
Single Agent ◽  
Objective Response ◽  
Median Number ◽  
Lymphocytic Leukemia ◽  
Synergistic Activity ◽  
Best Response ◽  
Car T ◽  
Treatment Naïve

7556 Background: Cirmtuzumab (Cirm) is a humanized monoclonal antibody that inhibits the tumor promoting activity of ROR1 and had demonstrated additive/synergistic activity with many anti-cancer agents including ibrutinib (Ibr). Methods: Patients (Pts) with relapsed or refractory (RR) MCL or treatment naïve (TN) or RR CLL were enrolled. In Part 1 (Dose Escalation), doses of Cirm IV q2wks x5 then q4wks of 2-16 mg/kg and 300 or 600 mg were examined. Safety of Cirm alone was assessed during the first 28 days, then Ibr was started at approved doses for each indication. Cirm 600 mg IV q2wks x3 then q4wks in combination with Ibr starting day 0 was chosen as the recommended dosing regimen for use in Part 2 (Expansion) and Part 3 (CLL only, Cirm/Ibr vs. Ibr alone). Results: Twelve evaluable MCL pts were enrolled into Part 1, and 5 into Part 2. Median number of prior regimens was 2 (1-5), including pts relapsing after Ibr (4), auto-SCT (3), auto-SCT/ allo-SCT (1), auto-SCT/CAR-T (1). In CLL, 34 evaluable pts (12 TN and 22 RR) enrolled into Part 1 (18) or Part 2 (16). At least 74% of CLL pts in Parts 1 and 2 were high risk as determined by unmutated IGHV, del17p, and/or del11q. In Part 3, 22 evaluable pts received Cirm/Ibr (15) or Ibr (7). As of the 30OCT2020 safety cut-off for MCL and CLL, common TEAEs (all grades) included diarrhea (41%), contusion (39%), fatigue (39%), URI (31%), hypertension (25%) arthralgia (23%). Grade ≥3 neutropenia was 13% and thrombocytopenia 1%. There were no Cirm dose reductions or discontinuations for toxicity. Overall, Cirm did not appear to negatively impact the safety of Ibr. Efficacy (MCL): As of the 02FEB2021 efficacy cutoff, the best response of 17 evaluable pts in Parts 1 and 2 included an objective response rate (ORR) of 82%, 41% CR/CMR, 41% PR, 12% SD, and 6% PD. CR/CMR remain durable from 8-28+ mos. Most responses occurred rapidly after ̃3 mos of Cirm/Ibr. Notably, responses were achieved in all pts who received prior SCT+/- CAR-T (4CR, 1PR) or prior Ibr (2CR, 2PR). At a median follow-up of 14.6 mos, the median PFS (mPFS) had not been reached (NR) (95% CI: 17.5, NA). Efficacy (CLL): The best response of 34 evaluable pts in Parts 1 and 2 included 91% ORR, 3% CR, 88% PR/PR-L, 9% SD, 0% PD. In Part 3, both arms achieved 100% ORR (all PRs). At a median follow-up of 20.2 mos, the mPFS was NR (95% CI: NA, NA), and the PFS estimate at 24 months was 95% for R/R, and 87% for TN, respectively, for evaluable CLL pts receiving Cirm/Ibr. Conclusions: Cirm/Ibr is a well-tolerated, active regimen in both MCL and CLL. For MCL, the mPFS of NR (95% CI: 17.5, NA) and CRR (41%), with all CRs remaining without PD, compare favorably to mPFS of 12.8 mos (95% CI 8.5-16.6) and CRR (20%) reported for single agent Ibr (Rule 2017). For CLL, the high ORR and PFS are encouraging, particularly for RR CLL. The study is ongoing, with MCL enrollment expanded to study Cirm + Ibr in pts who have had a suboptimal response to an Ibr regimen, or who have failed other approved BTKi agents. Clinical trial information: NCT03088878.

Calculation studies of coated particles performance in sodium-cooled fast reactor

Kerntechnik ◽  
2021 ◽  
Vol 86 (1) ◽  
pp. 45-49
Author(s):  
N. V. Maslov ◽  
E. I. Grishanin ◽  
P. N. Alekseev
Keyword(s):  
Fast Reactor ◽  
Reactor Core ◽  
Heat Removal ◽  
Design Solution ◽  
Fast Neutrons ◽  
Steel Shell ◽  
Primary Circuit ◽  
Coated Particles ◽  
The Core ◽  
Fuel Assemblies

Abstract This paper presents results of calculation studies of the viability of coated particles in the conditions of the reactor core on fast neutrons with sodium cooling, justifying the development of the concept of the reactor BN with microspherical fuel. Traditional rod fuel assemblies with pellet MOX fuel in the core of a fast sodium reactor are directly replaced by fuel assemblies with micro-spherical mixed (U,Pu)C-fuel. Due to the fact that the micro-spherical (U, Pu)C fuel has a developed heat removal surface and that the design solution for the fuel assembly with coated particles is horizontal cooling of the microspherical fuel, the core has additional possibilities of increasing inherent (passive) safety and improve the competitiveness of BN type of reactors. It is obvious from obtained results that the microspherical (U, Pu)C fuel is limited with the maximal burn-up depth of ∼11% of heavy atoms in conditions of the sodium-cooled fast reactor core at the conservative approach; it gives the possibility of reaching stated thermal-hydraulic and neutron-physical characteristics. Such a tolerant fuel makes it less likely that fission products will enter the primary circuit in case of accidents with loss of coolant and the introduction of positive reactivity, since the coating of microspherical fuel withstands higher temperatures than the steel shell of traditional rod-type fuel elements.

PF-06939999, a potent and selective PRMT5 inhibitor, in patients with advanced or metastatic solid tumors: A phase 1 dose escalation study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3019-3019
Author(s):  
Jordi Rodon Ahnert ◽  
Cesar Augusto Perez ◽  
Kit Man Wong ◽  
Michael L. Maitland ◽  
Frank Tsai ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Dose Escalation ◽  
Urothelial Cancer ◽  
Phase 1 ◽  
Dose Range ◽  
Median Number ◽  
Splicing Factor ◽  
Dose Escalation Study ◽  
Study Objective ◽  
Dose Dependent

3019 Background: Protein arginine methyltransferase 5 (PRMT5) methylates multiple substrates known to be dysregulated in cancer, including components of the spliceosome machinery. PF-06939999 is a selective small-molecule inhibitor of PRMT5. Here we report the safety, PK, PD, and preliminary activity of PF-06939999 in patients (pts) with selected advanced/metastatic solid tumors. Methods: This phase 1 dose escalation trial (NCT03854227) enrolled pts with solid tumor types marked by potential frequent splicing factor mutations, including advanced/metastatic endometrial cancer, head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), urothelial cancer, cervical cancer, or esophageal cancer. PF-06939999 monotherapy was continuously administered orally QD or BID in 28-day cycles. A Bayesian Logistic Regression Model was used to inform dose level decisions. Primary objectives were to assess dose limiting toxicities (DLTs), AEs and laboratory abnormalities. Tumor response was assessed using RECIST v1.1. PK and PD were assessed by determining PF-06939999 plasma concentration after dosing and changes in plasma levels of symmetric di-methyl arginine (SDMA), the product of PRMT5 enzymatic activity. Results: 28 pts received PF-06939999 at doses from 0.5-12 mg daily (QD or BID) during dose escalation. Median number of cycles was 2 (range, 1-13). Most were female (54%) with a median age of 61.5 (range, 32-84) y. Median number of prior therapies was 4. Overall, 4/24 (17%) pts reported DLTs: thrombocytopenia (n=2, 6 mg BID); anemia (n=1, 8 mg QD); and neutropenia (n=1, 6 mg QD). Treatment-related AEs occurred in 24 (86%) pts. Most common (≥20%) treatment-related AEs across all cycles were anemia (43%), thrombocytopenia (32%), dysgeusia, fatigue and nausea (29% each). Grade ≥3 treatment-related AEs included anemia (25%), thrombocytopenia (21%), fatigue, neutropenia and lymphocyte count decreased (4% each). One pt (6mg BID) had Grade 4 treatment-related thrombocytopenia. All cytopenias were dose-dependent and reversible with dose modification. No pts discontinued treatment for treatment-related toxicity. There were no treatment-related deaths. Exposure to PF-06939999 increased with doses in the dose range tested. Plasma SDMA was reduced at steady state (58.4-87.5%), indicating robust PD target inhibition. Two pts had confirmed partial response (HNSCC and NSCLC). 6 mg QD was identified as the recommended monotherapy dose for expansion. Conclusions: PF-06939999 showed dose-dependent and manageable toxicities in this phase 1 dose escalation study. Objective tumor responses were observed in pts with HNSCC and NSCLC. Analysis of archival tissue for the presence of splicing factor mutations and other potential predictive biomarkers is ongoing. Enrollment to part 2 dose expansion is ongoing in pts with NSCLC, HNSCC and urothelial cancer. Clinical trial information: NCT03854227.

scholarly journals Simulation of Volcanic Ash Ingestion Into a Large Aero Engine: Particle–Fan Interactions

2018 ◽  
Vol 141 (1) ◽  
Author(s):  
Andreas Vogel ◽  
Adam J. Durant ◽  
Massimo Cassiani ◽  
Rory J. Clarkson ◽  
Michal Slaby ◽  
...  
Keyword(s):  
Particle Size ◽  
Stream Flow ◽  
Mass Concentration ◽  
Volcanic Ash ◽  
Particle Mass ◽  
Core Flow ◽  
Turbine Engine ◽  
The Core ◽  
Core Section ◽  
Particle Mass Concentration

Volcanic ash (VA) clouds in flight corridors present a significant threat to aircraft operations as VA particles can cause damage to gas turbine engine components that lead to a reduction of engine performance and compromise flight safety. In the last decade, research has mainly focused on processes such as erosion of compressor blades and static components caused by impinging ash particles as well as clogging and/or corrosion effects of soft or molten ash particles on hot section turbine airfoils and components. However, there is a lack of information on how the fan separates ingested VA particles from the core stream flow into the bypass flow and therefore influences the mass concentration inside the engine core section, which is most vulnerable and critical for safety. In this numerical simulation study, we investigated the VA particle–fan interactions and resulting reductions in particle mass concentrations entering the engine core section as a function of particle size, fan rotation rate, and for two different flight altitudes. For this, we used a high-bypass gas-turbine engine design, with representative intake, fan, spinner, and splitter geometries for numerical computational fluid dynamics (CFD) simulations including a Lagrangian particle-tracking algorithm. Our results reveal that particle–fan interactions redirect particles from the core stream flow into the bypass stream tube, which leads to a significant particle mass concentration reduction inside the engine core section. The results also show that the particle–fan interactions increase with increasing fan rotation rates and VA particle size. Depending on ingested VA size distributions, the particle mass inside the engine core flow can be up to 30% reduced compared to the incoming particle mass flow. The presented results enable future calculations of effective core flow exposure or dosages based on simulated or observed atmospheric VA particle size distribution, which is required to quantify engine failure mechanisms after exposure to VA. As an example, we applied our methodology to a recent aircraft encounter during the Mt. Kelud 2014 eruption. Based on ambient VA concentrations simulated with an atmospheric particle dispersion model (FLEXPART), we calculated the effective particle mass concentration inside the core stream flow along the actual flight track and compared it with the whole engine exposure.

Solution-Responsive Particle Size Adaptivity in Lagrangian Vortex Particle Methods

2021 ◽  
Author(s):  
Mark J. Stock ◽  
Adrin Gharakhani
Keyword(s):  
Particle Size ◽  
Particle Method ◽  
Adaptive Method ◽  
Particle Methods ◽  
Core Size ◽  
Large Particle Size ◽  
The Core ◽  
Vortex Particle Method ◽  
Computational Resources ◽  
Vortex Particle

Abstract In order to minimize the computational resources necessary for a given level of accuracy in a Lagrangian Vortex Particle Method, a novel particle core size adaptivity scheme has been created. The method adapts locally to the solution while preventing large particle size gradients, and optionally adapts globally to focus effort on important regions. It is implemented in the diffusion solver, which uses the Vorticity Redistribution Method, by allowing and accounting for variations in the core radius of participating particles. We demonstrate the effectiveness of this new method on the diffusion of a δ-function and impulsively started flow over a circular cylinder at Re = 9,500. In each case, the adaptive method provides solutions with marginal loss of accuracy but with substantially fewer computational elements.

Effect of olutasidenib (FT-2102) on complete remissions in patients with relapsed/refractory (R/R) mIDH1 acute myeloid leukemia (AML): Results from a planned interim analysis of a phase 2 clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7006-7006
Author(s):  
Stéphane De Botton ◽  
Karen W. L. Yee ◽  
Christian Recher ◽  
Andrew Wei ◽  
Pau Montesinos ◽  
...  
Keyword(s):  
Clinical Trial ◽  
High Risk ◽  
Median Duration ◽  
Interim Analysis ◽  
Phase 1 ◽  
Median Number ◽  
Clinical Activity ◽  
Phase 2 ◽  
Duration Of Treatment ◽  
Transfusion Independence

7006 Background: Olutasidenib, a potent, selective, oral, small molecule inhibitor of mutant IDH1 (m IDH1), has exhibited favorable tolerability and clinical activity in high-risk AML patients (pts) in a phase 1 trial (Watts, Blood 2019). Here, we present interim analysis results of a phase 2 trial (NCT02719574) in R/R m IDH1 AML pts receiving olutasidenib monotherapy 150 mg twice daily. Methods: The efficacy evaluable (EE) set comprised m IDH1R132X pts whose first dose was ≥180 days before the data cut-off (18-JUN-20). The primary endpoint was CR+CRh (complete remission [CR] or CR with partial hematologic recovery [CRh] according to modified IWG 2003 criteria) rate. CRh was defined as bone marrow blasts <5%, absolute neutrophil count >0.5×109/L, and platelet count >50×109/L. Overall response rate (ORR) comprised CR+CRh+CR with incomplete recovery (CRi) + morphologic leukemia-free state (MLFS) + partial response (PR). Duration of treatment (DOT), duration of response (DOR), and overall survival (OS) were estimated using Kaplan-Meier methodology. Results: This clinical trial met its pre-specified early enrollment-stopping criteria for efficacy. A total of 153 pts with R/R AML received olutasidenib; median DOT, 5.5 mo (95% CI: 4.4, 8.7). 43 pts (28%) remain on treatment and 110 (72%) discontinued, most commonly due to: disease progression, 31%; AEs, 14%; death, 10%; and transplant, 8%. For the EE set (123 pts), the median age was 71 y (range: 32‒87) with a median number of prior therapies of 2 (1‒7). The CR+CRh rate was 33% including 30% of pts in CR (Table). Median duration of CR+CRh was not reached (NR) and 13.8 mo in a sensitivity analysis when HSCT or relapse was deemed end of response. ORR was 46% and median duration of ORR was 11.7 mo. Of responders who were transfusion-dependent at baseline, 56-day platelet transfusion independence (TI) and RBC TI were gained by 100% and 83%, respectively, of pts who achieved CR+CRh, and by 56% and 50% who did not. Median OS was 10.5 mo (EE set). In CR+CRh responders, median OS was NR and the estimated 18-mo OS was 87%. TEAEs in ≥25% of pts were nausea, 38%; constipation, 25%; leukocytosis, 25%. Grade 3/4 all-causality TEAEs in >10% of pts were febrile neutropenia, 20%; anemia, 19%; thrombocytopenia, 16%; neutropenia, 13%. Investigator-assessed IDH1 differentiation syndrome (any grade) was observed in 21 pts (14%); most cases resolved with treatment management; one case was fatal; 19 pts had concomitant leukocytosis. Conclusions: Olutasidenib was well tolerated and induced durable CR in a subset of high-risk R/R m IDH1 AML pts. TI was achieved in all response groups. Clinical benefit, per DOR and OS, extended beyond CR+CRh responders. Clinical trial information: NCT02719574. [Table: see text]

Ice Crystal Icing Investigation on a Honeywell Uncertified Research Engine in an Altitude Simulation Icing Facility

2020 ◽  
Author(s):  
Ashlie B. Flegel
Keyword(s):  
Particle Size ◽  
Guide Vane ◽  
Leading Edge ◽  
Inlet Guide Vane ◽  
Inlet Temperature ◽  
Ice Crystal ◽  
Guide Vanes ◽  
Inlet Guide Vanes ◽  
The Core ◽  
Break Up

Abstract A Honeywell Uncertified Research Engine was exposed to various ice crystal conditions in the NASA Glenn Propulsion Systems Laboratory. Simulations using NASA’s 1D Icing Risk Analysis tool were used to determine potential inlet conditions that could lead to ice crystal accretion along the inlet of the core flowpath and into the high pressure compressor. These conditions were simulated in the facility to develop baseline conditions. Parameters were then varied to move or change accretion characteristics. Data were acquired at altitudes varying from 5 kft to 45 kft, at nominal ice particle Median Volumetric Diameters from 20 μm to 100 μm, and total water contents of 1 g/m3 to 12 g/m3. Engine and flight parameters such as fan speed, Mach number, and inlet temperature were also varied. The engine was instrumented with total temperature and pressure probes. Static pressure taps were installed at the leading edge of the fan stator, front frame hub, the shroud of the inlet guide vane, and first two rotors. Metal temperatures were acquired for the inlet guide vane and vane stators 1–2. In-situ measurements of the particle size distribution were acquired three meters upstream of the engine forward fan flange and one meter downstream of the fan in the bypass in order to study particle break-up behavior. Cameras were installed in the engine to capture ice accretions at the leading edge of the fan stator, splitter lip, and inlet guide vane. Additional measurements acquired but not discussed in this paper include: high speed pressure transducers installed at the trailing edge of the first stage rotor and light extinction probes used to acquire particle concentrations at the fan exit stator plane and at the inlet to the core and bypass. The goal of this study was to understand the key parameters of accretion, acquire particle break-up data aft of the fan, and generate a unique icing dataset for model and tool development. The work described in this paper focuses on the effect of particle break-up. It was found that there was significant particle break-up downstream of the fan in the bypass, especially with larger initial particle sizes. The metal temperatures on the inlet guide vanes and stators show a temperature increase with increasing particle size. Accretion behavior observed was very similar at the fan stator and splitter lip across all test cases. However at the inlet guide vanes, the accretion decreased with increasing particle size.

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