ALBERT

Description: Biomass is gaining increased attention as a sustainable and low-cost hard carbon (HC) precursor. However, biomass properties are often unexplored and unrelated to HC performance. Herein, we used pine, beechwood, miscanthus, and wheat straw precursors to synthesize HCs at 1000 °C, 1200 °C and 1400 °C by a two-steps pyrolysis treatment. The final physicochemical and electrochemical properties of the HC evidenced dissimilar trends, mainly influenced by the precursor’s inorganic content, and less by the thermal treatment. Pine and beechwood HCs delivered the highest reversible capacity and coulombic efficiency (CE) at 1400 °C of about 300 mAh·g−1 and 80%, respectively. This performance can be attributed to the structure derived from the high carbon purity precursors. Miscanthus and wheat straw HC performance was strongly affected by the silicon, potassium, and calcium content in the biomasses, which promoted simultaneous detrimental phenomena of intrinsic activation, formation of a silicon carbide phase, and growth of graphitic domains with temperature. The latter HCs delivered 240–200 mAh·g−1 of reversible capacity and 70–60% of CE, respectively, at 1400 °C. The biomass precursor composition, especially its inorganic fraction, seems to be a key parameter to control, for obtaining high performance hard carbon electrodes by direct pyrolysis process.

Description: The interaction of a turbulent flow with the leading edge of a blade is a main noise source mechanism for fans and wind turbines. Motivated by the silent flight of owls, the present paper describes an experimental study performed to explore the noise-reducing effect of comb-like extensions, which are fixed to the leading edge of a low-speed airfoil. The measurements took place in an aeroacoustic wind tunnel using the microphone array technique, while the aerodynamic performance of the modified airfoils was captured simultaneously. It was found that the comb structures lead to a noise reduction at low frequencies, while the noise at high frequencies slightly increases. The most likely reasons for this frequency shift are that the teeth of the combs break up large incoming turbulent eddies into smaller ones or that they shift turbulent eddies away from the airfoil surface, thereby reducing pressure fluctuations acting on the airfoil. The aerodynamic performance does not change significantly.

Description: In situ, continuous and real-time monitoring of respiration (R) and respiratory quotient (RQ) are crucial for identifying the optimal conditions for the long-term storage of fresh produce. This study reports the application of a gas sensor (RMS88) and a modular respirometer for in situ real-time monitoring of gas concentrations and respiration rates of strawberries during storage in a lab-scale controlled atmosphere chamber (190 L) and of Pinova apples in a commercial storage facility (170 t). The RMS88 consisted of wireless O2 (0% to 25%) and CO2 sensors (0% to 0.5% and 0% to 5%). The modular respirometer (3.3 L for strawberries and 7.4 L for apples) consisted of a leak-proof arrangement with a water-containing base plate and a glass jar on top. Gas concentrations were continuously recorded by the RMS88 at regular intervals of 1 min for strawberries and 5 min for apples and, in real-time, transferred to a terminal program to calculate respiration rates ( R O 2 and R CO 2 ) and RQ. Respiration measurement was done in cycles of flushing and measurement period. A respiration measurement cycle with a measurement period of 2 h up to 3 h was shown to be useful for strawberries under air at 10 °C. The start of anaerobic respiration of strawberries due to low O2 concentration (1%) could be recorded in real-time. R O 2 and R CO 2 of Pinova apples were recorded every 5 min during storage and mean values of 1.6 and 2.7 mL kg−1 h−1, respectively, were obtained when controlled atmosphere (CA) conditions (2% O2, 1.3% CO2 and 2 °C) were established. The modular respirometer was found to be useful for in situ real-time monitoring of respiration rate during storage of fresh produce and offers great potential to be incorporated into RQ-based dynamic CA storage system.

Description: The simple sugars glucose and fructose share a common “sweet” taste quality mediated by the T1R2+T1R3 taste receptor. However, when given the opportunity to consume each sugar, rats learn to affectively discriminate between glucose and fructose on the basis of cephalic chemosensory cues. It has been proposed that glucose has a unique sensory property that becomes more hedonically positive through learning about the relatively more rewarding post-ingestive effects that are associated with glucose as compared to fructose. We tested this theory using intragastric (IG) infusions to manipulate the post-ingestive consequences of glucose and fructose consumption. Food-deprived rats with IG catheters repeatedly consumed multiple concentrations of glucose and fructose in separate sessions. For rats in the “Matched” group, each sugar was accompanied by IG infusion of the same sugar. For the “Mismatched” group, glucose consumption was accompanied by IG fructose, and vice versa. This condition gave rats orosensory experience with each sugar but precluded the differential post-ingestive consequences. Following training, avidity for each sugar was assessed in brief access and licking microstructure tests. The Matched group displayed more positive evaluation of glucose relative to fructose than the Mismatched group. A second experiment used a different concentration range and compared responses of the Matched and Mismatched groups to a control group kept naïve to the orosensory properties of sugar. Consistent with results from the first experiment, the Matched group, but not the Mismatched or Control group, displayed elevated licking responses to glucose. These experiments yield additional evidence that glucose and fructose have discriminable sensory properties and directly demonstrate that their different post-ingestive effects are responsible for the experience-dependent changes in the motivation for glucose versus fructose.

Description: A series of 2-methoxypyridine-3-carbonitrile (5a–i)-bearing aryl substituents were successfully synthesized in good yields by the condensation of chalcones (4a–i) with malononitrile in basic medium. The condensation process, in most cases, offers a route to a variety of methoxypyridine derivatives (6a–g) as side products in poor yields. All new compounds were fully characterized using different spectroscopic methods. Mass ESI-HMRS measurements were also performed. Furthermore, these compounds were screened for their in vitro cytotoxicity activities against three cancer cell lines; namely, those of the liver (line HepG2), prostate (line DU145) and breast (line MBA-MB-231). The cytotoxicity assessment revealed that compounds 5d, 5g, 5h and 5i exhibit promising antiproliferative effects (IC50 1–5 µM) against those three cancer cell lines.

Description: BACKGROUND: Symptom burden in essential thrombocythemia (ET) and polycythemia vera (PV) is severe even among individuals with low risk disease (Blood 2012. 12;123(24):3803-10). New therapies exist which alleviate the severe symptom burden and reduce splenomegaly in ET and PV patients (N Engl J Med 2015; 372:426-435). This analysis is the first to date to evaluate thresholds at which symptom-based treatment can be considered for ET and PV patients who are intolerant or resistant to hydroxyurea (HU). METHODS: Patient demographics, symptom burden, and disease traits were collected from ET and PV patients at a single time point during therapy. The MPN-10 total symptom score (TSS, JCO 2012;30(33)4098-103) was utilized to assess symptom burden. Symptom criteria models were determined as previously described among a population of MF patients (Scherber et. al. EHA 2016: a2250). Cutoffs were then evaluated in a cohort of ET and PV patients to assess for utility as a symptom model among this population. RESULTS: Demographics and symptom burden: 838 PV and 867 ET patients with previous hydroxyurea therapy were included in this analysis. Patients were of mean age (54.9 years ET, 64.0 years PV) and gender (69.2% female ET, 55.7% female). Mean disease duration was 6.0 years for ET and 7.3 years for PV.Among ET and PV patients, 15.0% and 24.2% had prior thrombosis respectively. In evaluating prognostic risk, ET patients tended to be low (45.5%) or intermediate risk (42.9%) with only a minority of patient meeting criteria forhigh risk disease (11.6%). Laboratory findings: ET patients had a mean platelet value of 598.7x 109/L(SD=283.4). Among PV patients, mean hematocrit was 45.8% (SD=8.1) and 42.6% of patients had a hematocrit of greater than 45%. White blood cell count was normal between the two groups (ET mean 8.3 x 109/L, PV mean 9.0 x 109/L). Symptoms: Mean worst symptom severity was 6.4 out of 10 (SD=2.7). Among ET patients, worst symptom was most frequently fatigue (32.7%, mean 5.0/10, SD=3.1, overall prevalence 88%) followed by night sweats (13.6%, mean 2.0/10, SD=3.0, overall prevalence 53%) and concentration difficulties (8.6%, mean 3.1/10, SD=3.0, overall prevalence 68%). For PV, worst individual symptom items were most frequently fatigue (29.2%, mean 5.2/10, SD=3.0, overall prevalence 91%), pruritus (14.1%, mean 3.2/10, SD=3.2, overall prevalence 69%), and night sweats (12.8%, mean 2.5/10, SD=3.0, overall prevalence 57%). Cutoff Scoring: 47.0% of ET patients fit criteria for TSSgreater than to equal to 20; 59.0%% had a single itemgreater than 5; and 45.7% had both a TSS greater than or equal to 20 and a single item greater than 5. Among PV participants, 54.5% had aTSS greater than to equal to 20; 66.1% had a single itemgreater than 5; and 51.5% had both a TSS greater than or equal to 20 and a single item greater than 5. Each scoring method was significantly associated with individual item scores (Table 1). Prognostic scoring was not significantly associated with any of the symptom cutoffs evaluated. Correlations: Among ET patients, a prior history of thrombosis was significantly associated with having a worst symptom item greater than 5 (p=0.043). ET patients with lower hemoglobin were significantly more likely to meet criteria for a MPN-10 score greater than or equal to 20 or to meet combined criteria for a MPN-10 greater than or equal to 20 and single worst item greater than 5 (for both p=0.01 or less). For PV, lower hematocrit levels were significantly associated with having an individual worst symptom score of greater than 5 (44.9% versus 46.7%, p=0.0376). CONCLUSION: Assessment of ET and PV symptoms, now measurable through standardized and practical instruments such as the MPN-10, is an integral part of determining therapeutic impact of newer therapies in both clinical practice and trial settings. In our modeling, patients with severe symptom burden profiles are well represented by utilizing cutoff criteria including aworst individual symptom item of greater than 5 out of 10, an MPN-10 score of greater than or equal to 20, or combined criteria of both cutoffs. These cutoffs can be considered when determiningwhich HU intolerant or resistant patients would most benefit fromsymptom orientedtreatment. Disclosures Kiladjian: AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Research Funding. Schouten:Novartis: Consultancy; Sanofi: Consultancy. Etienne:BMS: Speakers Bureau; ARIAD: Speakers Bureau; Pfizer: Speakers Bureau; novartis: Consultancy, Speakers Bureau. Harrison:Incyte Corporation: Honoraria, Speakers Bureau; Shire: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Baxaltra: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: travel, accommodations, expenses, Research Funding, Speakers Bureau. Radia:Pfizer: Honoraria; Novartis: Honoraria. Cervantes:AOP Orphan: Membership on an entity's Board of Directors or advisory committees; Baxalta: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Mesa:Promedior: Research Funding; Celgene: Research Funding; CTI: Research Funding; Gilead: Research Funding; Incyte: Research Funding; Galena: Consultancy; Ariad: Consultancy; Novartis: Consultancy.

Description: Abstract 44 CALGB (now part of the Alliance for Clinical Trials in Oncology) performed a non-randomized phase II study testing one year (yr) of investigational maintenance therapy with decitabine for newly diagnosed adult AML patients (pts) 1 × 109/L, platelets 〉75 × 109/L, and be within 90 days after day 1 of the final consolidation. Decitabine 20mg/m2 was given IV over 1 hour for 4–5 days, every 6 weeks, for 8 cycles. 546 pts enrolled with a median age of 48 yrs (range, 17–60) and median presenting white blood count (WBC) of 12.6 × 109/L (range, 0.3–380 × 109/L). 75% achieved CR (412/546). Reasons for CR pts not receiving maintenance were mainly early relapse, alloHCT in 1st CR, inadequate count recovery, and patient refusal (Blum et al. ASH 2011). 33% of CR pts (134/412) received investigational maintenance. Of these, 46 (34%) were favorable risk; among the remaining 88 pts, 73 were consolidated with autoHCT, and 15 received HiDAC-based consolidation. The median time from initial study registration to initiation of maintenance therapy was 6.3 months. Pts receiving decitabine had a median age of 45 yrs (range, 18–60) and presenting WBC of 13.5 × 109/L (range, 0.4–221 × 109/L). Treatment with decitabine maintenance was feasible and reasonably well tolerated; the primary toxicity was myelosuppression. Preplanned dose reduction criteria for neutropenia were met after the first 20 pts had been treated. After this early timepoint, all subsequent pts who had been consolidated with autoHCT received only 4 days of decitabine per cycle (HiDAC consolidated pts continued to receive 5 days per cycle). The median number of cycles of decitabine received was 7 (range, 1–8); 46% of pts (62/134) received all 8 cycles, and 75% completed at least 4 cycles. Reasons for discontinuation of decitabine before completing 8 cycles included relapse (28%, 38/134), pt refusal (13%), adverse events (4%), and others. In this selected cohort of pts who received post-CR maintenance with decitabine, 1-yr and 3-yr overall survival (OS) were 96% and 66%; 1-yr and 3-yr disease-free survival (DFS) were 80% and 53%. 1-yr “failure-free survival” calculated from the time of registration to decitabine was 68% (70% for favorable risk, 68% for others). These results are similar to the outcomes for comparable pts enrolled on our prior CALGB study 19808 who received identical chemotherapy for induction and consolidation and then were randomized to observation or maintenance with interleukin-2 (3-yr OS 61% and 68%, 3-yr DFS 45% and 56%, for observation and IL-2 respectively). Post-consolidation maintenance with decitabine appears to provide only modest, if any, benefit overall. Correlative studies for CALGB 10503 are ongoing, including investigations into the impact of decitabine in unique molecular and cytogenetic subsets of disease, the prognostic/predictive value of aberrant methylation and other molecular markers, and assessment of minimal residual disease. Supported by CA33601 and CA128377. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction: Blinatumomab is a bispecific, CD19-directed CD3 T-cell engager (BiTE®) that activates endogenous cytotoxic T cells to kill target B cells and is FDA-approved for the treatment of relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukemia (B-ALL). Subgroup analyses of pivotal trials revealed lower response rates and higher risk of cytokine release syndrome (CRS) in blinatumomab recipients with high pre-treatment tumor (B-ALL) burden. It has therefore been hypothesized that cytoreduction prior to blinatumomab initiation may improve response and reduce risk of severe CRS in patients (pts) with high baseline B-ALL burden. We therefore sought to describe pt and disease characteristics at diagnosis, patterns of pre-blinatumomab cytoreduction, and treatment outcomes in pts with high burden of R/R B-ALL treated with blinatumomab at our institution. Methods: We retrospectively reviewed medical records of adult (≥ 18 years-old) pts with morphologic R/R B-cell ALL (i.e. ≥5% BM blasts and/or radiographically evident EM disease) treated with blinatumomab at Memorial Sloan Kettering Cancer Center (MSKCC) between January 2011 and March 2019 and characterized pts with ≥ 50% bone marrow (BM) blasts by morphology or ≥ 15,000 peripheral blood blasts/µL as having "high-burden" B-ALL. CRS and neurologic toxicity (NTX) were graded per Common Terminology Criteria for Adverse Events v5.0. Objectives included describing cytoreductive therapy given pre-blinatumomab and determining rates of NTX and CRS (any grade and grade ≥3) and morphologic complete response (CR) following 1-2 cycles of blinatumomab. Results: We identified 14 pts with high-burden R/R B-ALL prior to blinatumomab. These pts had a median age of 52 years (range, 23 - 69 years) and median BM blasts of 73% (range, 52 - 〉95%, n=12 pts with evaluable BM). Of these 14 pts, 8 received cytoreductive therapy prior to blinatumomab initiation. Cytoreductive regimens included dexamethasone alone (n=4), cyclophosphamide + dexamethasone (n=2), dexamethasone and vincristine (n=1), or cyclophosphamide + vincristine + dexamethasone (n=1). One pt transitioned to hospice care prior to completing cycle 1 (C1) of blinatumomab and was considered non-evaluable for response. CR was achieved in 6 of the 13 evaluable pts, including 4 of 7 evaluable pts who received cytoreductive therapy and 2 of 6 pts who did not receive cytoreductive therapy. One pt achieved CR in BM but exhibited refractory extramedullary disease. CRS was observed during C1 of blinatumomab in 11/14 pts (grade 1, n=7; grade 2, n=3; grade 3, n=1). The pt with grade 3 CRS had received blinatumomab without cytoreductive therapy. In 4 pts, blinatumomab was temporarily discontinued for management of CRS. NTX of any grade occurred in 4/13 pts during C1, including 1 pt w/grade 3 NTX (depressed level of consciousness), and was reversible in all cases; the pt with grade 3 NTX had full resolution of symptoms following brief interruption of blinatumomab and administration of dexamethasone. Conclusions: Real-world clinical experience with blinatumomab in pts with high-burden B-ALL at a single institution suggested an efficacy and safety profile comparable to what has been reported in the overall population in clinical trials. Compared to published clinical trial experience, rates and severity of CRS following blinatumomab were similar and rates of NTX appeared slightly higher in this small series. Administration of cytoreductive therapy prior to blinatumomab for pts with high-burden B-ALL appears safe, with no additional toxicities. Larger studies will be required to assess whether pts with high-burden B-ALL treated (vs not treated) with cytoreductive therapy prior to blinatumomab exhibit significantly higher rates of CR. Disclosures King: Incyte: Other: Advisory Board; Genentech: Other: Advisory Board ; Astrazeneca: Other: Advisory board. Bolanos:Amgen Inc.: Employment. Velasco:Amgen Inc.: Employment. Tu:Amgen Inc.: Employment. Zaman:Amgen Inc.: Employment. Geyer:Dava Oncology: Honoraria; Amgen: Research Funding. Park:Allogene: Consultancy; Amgen: Consultancy; AstraZeneca: Consultancy; Autolus: Consultancy; GSK: Consultancy; Incyte: Consultancy; Kite Pharma: Consultancy; Novartis: Consultancy; Takeda: Consultancy.