ALBERT

Description: Volcanic gas emissions are intimately linked to the dynamics of magma ascent and outgassing and, on geological time scales, constitute an important source of volatiles to the Earth's atmosphere. Measurements of gas composition and flux are therefore critical to both volcano monitoring and to determining the contribution of volcanoes to global geochemical cycles. However, significant gaps remain in our global inventories of volcanic emissions, (particularly for CO2, which requires proximal sampling of a concentrated plume) for those volcanoes where the near‐vent region is hazardous or inaccessible. Unmanned Aerial Systems (UAS) provide a robust and effective solution to proximal sampling of dense volcanic plumes in extreme volcanic environments. Here we present gas compositional data acquired using a gas sensor payload aboard a UAS flown at Volcán Villarrica, Chile. We compare UAS‐derived gas time series to simultaneous crater rim multi‐GAS data and UV camera imagery to investigate early plume evolution. SO2 concentrations measured in the young proximal plume exhibit periodic variations that are well correlated with the concentrations of other species. By combining molar gas ratios (CO2/SO2 = 1.48–1.68, H2O/SO2 = 67–75, and H2O/CO2 = 45–51) with the SO2 flux (142 ± 17 t/day) from UV camera images, we derive CO2 and H2O fluxes of ~150 t/day and ~2,850 t/day, respectively. We observe good agreement between time‐averaged molar gas ratios obtained from simultaneous UAS‐ and ground‐based multi‐GAS acquisitions. However, the UAS measurements made in the young, less diluted plume reveal additional short‐term periodic structure that reflects active degassing through discrete, audible gas exhalations.

Description: Published

Description: 730-750

Description: 6V. Pericolosità vulcanica e contributi alla stima del rischio

Description: JCR Journal

Description: Volcanic emissions are a critical pathway in Earth's carbon cycle. Here, we show that aerial measurements of volcanic gases using unoccupied aerial systems (UAS) transform our ability to measure and monitor plumes remotely and to constrain global volatile fluxes from volcanoes. Combining multi-scale measurements from ground-based remote sensing, long-range aerial sampling, and satellites, we present comprehensive gas fluxes-3760 ± [600, 310] tons day-1 CO2 and 5150 ± [730, 340] tons day-1 SO2-for a strong yet previously uncharacterized volcanic emitter: Manam, Papua New Guinea. The CO2/ST ratio of 1.07 ± 0.06 suggests a modest slab sediment contribution to the sub-arc mantle. We find that aerial strategies reduce uncertainties associated with ground-based remote sensing of SO2 flux and enable near-real-time measurements of plume chemistry and carbon isotope composition. Our data emphasize the need to account for time averaging of temporal variability in volcanic gas emissions in global flux estimates.

Description: This research was enabled through the Alfred P. Sloan Foundation's support of the Deep Carbon Observatory Deep Earth Carbon Degassing program (DECADE). Part funding also came from the EPSRC CASCADE programme grant (EP/R009953/1). EJL was supported by a Leverhulme Trust Early Career Fellowship. KW was supported by the National Center for Nuclear Robotics (NCNR) EPSRC grant (EP/R02572X/1).

Description: Published

Description: eabb9103

Description: 7TM.Sviluppo e Trasferimento Tecnologico

Description: JCR Journal

Description: Glabrous canaryseeds were recently approved for human consumption as a novel cereal grain in Canada and the United States. Previously, canaryseeds were exclusively used as birdseed due to the presence of carcinogenic silica fibers; therefore the nutritional value of the seeds has been seriously overlooked. Two cultivars of glabrous canaryseeds (yellow and brown) were created from the hairy varieties. They are high in protein compared to other cereal grains, and contain high amounts of tryptophan, an amino acid normally lacking in cereals, and are gluten-free. Bioactive peptides of canaryseeds produced by in vitro gastrointestinal digestion have shown antioxidant, antidiabetic, and antihypertensive activity. The seeds contain other constituents with health promoting effects, including unsaturated fatty acids, minerals, and phytochemicals. Anti-nutritional components in the seeds are comparable to other cereal grains. Because of their beneficial health effects, canaryseeds should be regarded as a healthy food and have immense potential as a functional food and ingredient. Further research is required to determine additional bioactive peptide activity and capacity, as well as differences between the yellow and brown cultivars.

Description: Background: Ten to 15% of diffuse large B cell lymphoma (DLBCL) patients exhibit primary refractory disease (nonresponse or relapse within 3 months of therapy) and an additional 20-25% relapse following initial response. There is an unmet need for effective therapeutic regimens in relapsed/refractory (R/R) DLBCL. Lenalidomide is an immune modulator that reverses T cell dysfunction and also inhibits the NFκB pathway, which is constitutively active in non-germinal center (non-GCB) DLBCL. Lenalidomide and nivolumab, an anti-PD-1 antibody, each have single agent activity in R/R DLBCL. Here, we report the results of the dose-escalation cohort of this investigator-initiated, single-arm open-label study of the combination of nivolumab, lenalidomide and rituximab (NiLeRi) in R/R non-GCB DLBCL. Methods: Adult patients with R/R non-GCB DLBCL, as determined by the Hans algorithm, with adequate organ function and an ECOG performance status of ≤2 were eligible for the study. The primary objective was to evaluate the safety of NiLeRi, and determine the maximum tolerated dose (MTD) of lenalidomide in combination with fixed doses of rituximab and nivolumab, using a 3+3 dose escalation design. The secondary objectives were to determine efficacy in terms of overall response rate (ORR), progression free survival (PFS), and overall survival (OS) of patients treated with NiLeRi. All patients received nivolumab IV 3 mg/kg on days 1 and 15 and rituximab IV 375mg/m2 on day 1 of each 28-day cycle. Lenalidomide was initiated at 5 mg po once daily on days 1-21. Additional planned dose levels were 10 mg, 15 mg and 20 mg. Patients were evaluable for toxicity if they received all doses of nivolumab and rituximab and at least 16 doses of lenalidomide during cycle 1 or if they experienced a dose limiting toxicity (DLT), regardless of the number of doses. NiLeRi was given for 8 cycles and patients with partial response could receive lenalidomide and nivolumab for an additional 4 cycles. Response was assessed by PET-CT after 2, 5 and 8 cycles and defined by Lugano criteria. Results: Six patients with non-GCB subtype of DLBCL were enrolled in this study. The median age was 60.5 years (range 28-79), and 5 patients were male. The median number of prior lines of therapy was 4 (range 2-5), and the median IPI score was 3. None of the patients had bone marrow involvement. One patient each had been treated with autologous stem cell transplant (Auto-SCT) and CAR-T cell therapy. One patient withdrew consent before completing cycle 1 and was not evaluable for safety or efficacy. Safety: Five out of the six enrolled patients were evaluable for safety. All patients received lenalidomide 5 mg dose. Two patients experienced DLTs (grade 3 rash) resulting in lenalidomide discontinuation during cycle 2. The most common grade 3/4 toxicities were fatigue (20%), neutropenia (60%), thrombocytopenia (40%), and rash (40%). A total of 3 patients experienced grade 1/2 diarrhea and elevated liver enzymes. One patient experienced a grade 1 infusion reaction with rituximab. Efficacy: Patients who completed at least 1 cycle of therapy were evaluable for response, and this included 5 out of the 6 enrolled patients. The ORR and complete response (CR) rate were both 40%. Patients who responded did so early, with one patient achieving CR after 2 cycles and another patient achieving CR after 5 cycles. The best response seen in patients with primary refractory disease was PR. At a median follow up of 9.5 months, median PFS was 8.4 months (95% CI; 4.3 to not reached), and median OS was not reached. Discussion: This is the first study reporting the safety results of the combination of lenalidomide, nivolumab and rituximab in non-Hodgkin lymphoma. Rash was the most common DLT, limiting dose escalation of lenalidomide above 5mg in this cohort of patients. Two patients experienced durable CR early in the study after 2 and 5 cycles, respectively. This ORR and CR rate of 40% each in this small cohort of patients who had relapsed after multiple prior lines of therapy is encouraging. Correlative studies, including whole exome sequencing of patient samples, are underway, in an attempt to explore predictive markers for response and toxicity. Figure. Disclosures Mason: Sysmex: Honoraria. Oluwole:Pfizer: Consultancy; Spectrum: Consultancy; Gilead Sciences: Consultancy; Bayer: Consultancy. Morgan:Biogen: Equity Ownership; Eli Lilly: Equity Ownership; Vertex: Equity Ownership; Zoetis: Equity Ownership; Pfizer: Equity Ownership; Novo Nordisk: Equity Ownership; Gilead: Equity Ownership; Johnson and Johnson: Equity Ownership; Merck: Equity Ownership. Reddy:Abbvie: Consultancy; Genentech: Research Funding; Celgene: Consultancy; BMS: Consultancy, Research Funding; KITE Pharma: Consultancy. OffLabel Disclosure: Nivolumab and lenalidomide are not FDA approved for use in diffuse large B cell lymphoma

Description: Introduction: Previously, we reported that CD30 expression was not acquired at time of relapse in patients with diffuse large B-cell lymphoma (DLBCL) utilizing conventional immunohistochemistry (IHC; Calzada et al., ASH 2016). However, novel approaches to detection of CD30 expression may improve the detection of low levels of expression and thus may have implications regarding the use of CD30-directed therapies in DLBCL and other lymphomas. We utilized a computational tissue analysis mechanism to evaluate CD30 expression using patient samples that had previously been considered CD30 negative by IHC. Methods: We included patients with relapsed DLBCL with available archived tissue samples from the time of relapse (and when feasible, from the time of diagnosis) that was sufficient to prepare a slide for staining. CD30 IHC staining was completed for all involved tissue at Emory using our standard antibody (Ber-H2). Samples were manually annotated to indicate regions for inclusion and exclusion in image analysis. CD30 status was assessed by Flagship Biosciences using their proprietary CD30/DLBCL computational tissue analysis (cTA) algorithm. The primary endpoint for this analysis was the number and percentage of CD30+ cells in each tissue sample. Clinical, demographic and laboratory variables were also collected for each case, and overall survival (OS) was estimated using the Kaplan-Meier method. We divided the cohort into CD30 high vs. low expression using the median percentage of CD30+ cells and also performed a cut point analysis to identify a clinically significant cut-off for high vs. low using an outcome-oriented approach (Contal 1999). Results: We included 25 patients with relapsed/refractory DLBCL (including 9 with available paired tissue from the time of initial diagnosis). Among all patients, the median age at diagnosis was 58 years (range 34-76), 72% presented with elevated LDH, 56% were Stage III/IV, 62% had B-symptoms, and 83% had extranodal disease (not including bone marrow). The median time from diagnosis to relapse was 9.4 months. Eighty-eight percent of patients received R-CHOP as frontline therapy. Cell of origin by the Hans algorithm was germinal center B-cell-like (GCB) for 9 patients, non-GCB for 5 patients, and unknown for 11 patients. Utilizing conventional IHC, none of the diagnostic or relapsed samples had detectable CD30 expression. Upon image analysis, 11/19 available samples were CD30-positive at relapse using ≥0.1% as a cutoff. Range of percentage of CD30 positive cells was 0.1 to 23.6%, and the median percentage of CD30 positive cells was 0.25%. Among the 9 patients with paired samples, 5 were positive at diagnosis and 5 were positive at relapse. One patient went from negative to positive and 1 patient transitioned from positive to negative. Most patients who were positive at baseline were still positive at relapse, and the median change in percentage of CD30+ cells between diagnosis and relapse was 0.35%. There were no statistical differences between the CD30 high vs low patients with regards to baseline patient- or disease-related characteristics or time to relapse using the median value of 0.25 as the cut point. In addition, CD30 expression was not associated with OS from the date of relapse or from diagnosis (p=0.406 & p=0.316, respectively). None of the included patients were treated with brentuximab vedotin or any other CD30-directed therapy. Conclusions: This analysis identifies a novel way to detect CD30 expression in patients with DLBCL and suggests that more patients may be CD30+ than previously thought. Prior studies in T-cell lymphoma suggest that even patients with a very low percentage of CD30+ cells may respond to CD30-directed treatment (Kim 2017), although expression using this novel method was not part of those studies. Assaying the CD30 status of relapsed/refractory DLBCL using this novel platform in a larger cohort is warranted as patients with such low level CD30 expression may benefit from future evaluation of CD30-directed treatments. Figure. Figure. Disclosures Calzada: Seattle Genetics: Research Funding. Flowers:Genentech/Roche: Research Funding; Janssen Pharmaceutical: Research Funding; Acerta: Research Funding; BeiGene: Research Funding; Gilead: Consultancy; Pharmacyclics: Research Funding; OptumRx: Consultancy; Karyopharm: Consultancy; V Foundation: Research Funding; Abbvie: Research Funding; Eastern Cooperative Oncology Group: Research Funding; Gilead: Research Funding; Millennium/Takeda: Research Funding; Pharmacyclics/ Janssen: Consultancy; National Cancer Institute: Research Funding; Burroughs Wellcome Fund: Research Funding; TG Therapeutics: Research Funding; Genentech/Roche: Consultancy; Celgene: Research Funding; Spectrum: Consultancy; Abbvie: Consultancy, Research Funding; Bayer: Consultancy; Denovo Biopharma: Consultancy. Cohen:Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; BioInvent: Consultancy; BioInvent: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding.

Description: Many epilepsy patients are refractory to conventional antiepileptic drugs. Resurgent and persistent currents can be enhanced by epilepsy mutations in the Nav1.2 channel, but conventional antiepileptic drugs inhibit normal transient currents through these channels, along with aberrant resurgent and persistent currents that are enhanced by Nav1.2 epilepsy mutations. Pharmacotherapies that specifically target aberrant resurgent and/or persistent currents would likely have fewer unwanted side effects and be effective in many patients with refractory epilepsy. This study investigated the effects of cannbidiol (CBD) and GS967 (each at 1 μM) on transient, resurgent, and persistent currents in human embryonic kidney (HEK) cells stably expressing wild-type hNav1.2 channels. We found that CBD preferentially inhibits resurgent currents over transient currents in this paradigm; and that GS967 preferentially inhibits persistent currents over transient currents. Therefore, CBD and GS967 may represent a new class of more targeted and effective antiepileptic drugs.

Description: The bioactive properties and health-promoting effects of two novel yellow (C09052, C05041) and two brown (Calvi, Bastia) hairless canary seed (Phalaris canariensis L.) cultivars were investigated in comparison to two common cereal grains (wheat and oat). The cereal flours were digested using the standardized INFOGEST in vitro human gastrointestinal digestion model. The three-kilo dalton molecular weight cutoff (3 kDa MWCO) permeate of the generated digestates was assessed in vitro for their antioxidant, chelating, antihypertensive and antidiabetic activities. The results showed no significant differences in studied bioactivities between yellow and brown canary seed cultivars, except for antioxidant activity by the DPPH and chelating Fe2+ assays, where brown cultivars had higher activities. Canary seeds had superior or equivalent antioxidant activity than those from oat and wheat. The anti-hypertensive activity (Angiotensin-converting enzyme (ACE) inhibition) in yellow canary seed cultivars was significantly higher than that of oat and wheat, particularly for C09052 and Calvi varieties. Peptides exhibiting the highest antihypertensive activity from the permeate of the C09052 canary seed variety were further fractionated and identified by mass spectrometry. Forty-six peptides were identified belonging to 18 proteins from the Pooideae subfamily. Fourteen of the parent proteins were homologous to barley proteins. Peptides were analyzed in silico to determine potential bioactivity based on their amino acid composition. All 46 peptides had potential anti-hypertensive and anti-diabetic activities and 20 had potential antioxidant activity, thereby validating the in vitro assay data. Canary seed peptides also exhibited potential antiamnestic, antithrombotic, immunostimulating, opioid and neuro-activity, demonstrating important potential for health promoting effects, particularly against cardiovascular disease.

Description: Follicular Lymphoma (FL) is the most common indolent lymphoma derived from light zone germinal center B cells and characterized by a t(14;18) translocation resulting in upregulation of BCL2 in over 80% of cases. This translocation alone is not sufficient for tumorogenesis, and must be combined with additional genetic mutations to transform B cells. FL is incurable and the disease course can be highly varied, with survival ranging from a few months to decades following diagnosis and treatment with standard chemoimmunotherapy. The heterogeneity of FL poses major challenges to identifying the association of genetic alterations and clinical outcome. Current WHO guidelines recommend establishing grade for each FL case with grade 3 thought to be more aggressive than 1 and 2. The genetic basis and clinical implications of grade in FL are unclear. Recent sequencing studies have identified many genes found to be recurrently mutated in FL including KMT2D and CREBBP. However, the degree to which genetic alterations cooperate with each other or contribute to clinical outcome is unclear. Based on the observed mutational rates in follicular lymphoma, we estimated 900 cases were needed to comprehensively delineate the genetic alterations that underlie histologic grade and clinical outcome. Accordingly, we enrolled a cohort of 1042 patients with newly diagnosed FL. All treated patients received rituximab-containing standard regimens. To go beyond the identification of gene-coding events, we developed a very large panel of 110 Mbp covering exonic (~40Mbp) and non-exonic regions (~70Mbp) of interest to enable a wide range of genomic analysis including mutation calling in both coding and non-coding regions, rearrangement detection, viral identification, and copy number analysis. In addition to the whole exome, we extended coverage to include introns, promoters, and untranslated regions of all known driver genes in cancer. We included the entirety of the immunoglobulin loci, T-cell receptor loci and CD3 loci to detect clonotypes and rearrangements. We also included lymphoma-relevant long non-coding RNAs, microRNAs, enhancers, and breakpoint-prone regions. For viral detection, we targeted the genomes of eight cancer-related viruses: Epstein-Barr virus, human papillomavirus, human immunodeficiency virus, hepatitis B, hepatitis C, Kaposi's sarcoma-associated herpesvirus, human T-lymphotropic virus, and Merkel cell polyomavirus. In addition, to enable high resolution identification of copy number variation (CNV) calls, the entire genome was tiled with probes spaced 10kb apart. DNA and RNA were extracted from all tumors and their paired normal samples, prepared into DNA and RNA sequencing libraries and subjected to sequencing on the Illumina platform to a targeted coverage of 150X. Somatic events were identified and further filtered to identify driver events in both coding and non-coding regions. FLs demonstrated a significant degree of genetic heterogeneity with over 100 genes mutated with a frequency of at least 2%. Nearly 100% of FL cases had a mutation in at least one chromatin-modifying gene. The most frequently mutated genes in follicular lymphoma were KMT2D, BCL2, IGLL5 and CREBBP. In addition, we identified frequent mutations in SPEN, BIRC6 and SETD2. To our knowledge, this is the first description of alterations in these genes in FL. Transcriptome analysis indicated a strong correlation between BIRC6 mutations and the previously described immune response 2 signature that is associated with a poor prognosis. We further performed unbiased clustering of genetic alterations in these FL cases. We identified a cluster that was specifically enriched in BCL6 and TP53 alterations and was strongly associated with grade 3 FLs which are predicted to have poorer outcomes with low intensity therapies. We further examined the genetic profiles of 1001 DLBCLs in comparison to this cohort of FLs. Our data indicate a continuum of highly overlapping genetic alterations with DLBCL displaying more complex patterns that included alterations in MYC, TP53 and CDKN2A (mainly copy number losses), indicating shared pathogenetic mechanisms underlying FL and DLBCL, particularly those germinal center B cell origin. Disclosures Koff: Burroughs Wellcome Fund: Research Funding; V Foundation: Research Funding; Lymphoma Research Foundation: Research Funding; American Association for Cancer Research: Research Funding. Leppä:Roche: Honoraria, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees. Gang:ROCHE: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Hsi:Abbvie: Research Funding; Eli Lilly: Research Funding; Cleveland Clinic&Abbvie Biotherapeutics Inc: Patents & Royalties: US8,603,477 B2; Jazz: Consultancy. Flowers:AbbVie: Consultancy, Research Funding; Denovo Biopharma: Consultancy; BeiGene: Consultancy, Research Funding; Burroughs Wellcome Fund: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; V Foundation: Research Funding; Optimum Rx: Consultancy; Millenium/Takeda: Research Funding; TG Therapeutics: Research Funding; Gilead: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Karyopharm: Consultancy; AstraZeneca: Consultancy; Pharmacyclics/Janssen: Consultancy, Research Funding; Spectrum: Consultancy; Bayer: Consultancy; Acerta: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding. Neff:Enzyvant: Consultancy; EUSA Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees. Fedoriw:Alexion Pharmaceuticals: Other: Consultant and Speaker. Reddy:Genentech: Research Funding; BMS: Consultancy, Research Funding; Celgene: Consultancy; KITE Pharma: Consultancy; Abbvie: Consultancy. Mason:Sysmex: Honoraria. Behdad:Loxo-Bayer: Membership on an entity's Board of Directors or advisory committees; Thermo Fisher: Membership on an entity's Board of Directors or advisory committees; Pfizer: Other: Speaker. Burton:Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dave:Data Driven Bioscience: Equity Ownership.

Description: Background: Ivosidenib (Ivo) and enasidenib (Ena) are potent, mutant-specific oral inhibitors of the IDH1 and IDH2 proteins, respectively, and are approved as single agents for the treatment of newly diagnosed (Ivo) and/or relapsed/refractory (Ivo and Ena) AML. When used as single agents, these inhibitors induce differentiation of leukemic blasts, often without a period of bone marrow (BM) aplasia (PMID 28588020, 29860938). A phase 1 study (NCT02632708) examining the safety and efficacy of Ivo or Ena in combination with intensive induction chemotherapy (IDHi/7+3) in newly diagnosed AML with mutant IDH1 or IDH2 (mIDH) has yielded encouraging response rates in preliminary reports (Stein et al. ASH 2018; Abstract 560). The effect of IDHi/7+3 on BM morphology and whether features of differentiation are seen in this context is unknown. Here, we report the clinicopathologic findings in a cohort of patients treated with IDHi/7+3 and describe a distinct pattern of BM response with implications for post-therapy disease monitoring. Methods: Investigators from participating sites for NCT02632708 were invited to contribute cases. 36 patients from 4 sites were included with IRB approval at all sites. For each patient, the diagnostic BM biopsy and aspirate smear (BMBx) and all subsequent BMBx performed until end of induction (EOI) or removal from study were reviewed at individual sites based on consensus criteria. A subset of cases was re-reviewed by all pathologists via photomicrographs and digital whole slide images. Patients were categorized into 3 groups based on their Day 14 (D14) BMBx: 1) Aplasia (D14A = 5% blasts at D14; with morphologic or flow cytometric evidence of blast differentiation at D14 or D21); or 3) Persistent AML (D14P = 〉10% cellular; and 〉5% blasts; and no differentiation or clearance of blasts at D14 or later time points). Clinicopathologic data was collected from the electronic medical record and from the study database. IDH mutation clearance (MC) was defined as a reduction in the mIDH variant allele frequency in BM mononuclear cells to a level below the limit of detection of the assay (0.02-0.04%) for ≥1 on-treatment time point on or after D28 of induction. Results: The cohort included 17 mIDH1 patients who received Ivo and 19 mIDH2 patients who received Ena (Table 1, Fig 1); 1 patient in each treatment group had mIDH1 and mIDH2. In the 31 patients evaluable for response at EOI, 27 achieved CR or CRi/p; 2 MLFS; and 2 SD. Of 29 patients with a morphologic response (CR, CRi/p, MLFS), 19 (66%) were classified as D14A (median 5% cellularity; median

Description: Volcanic gas emissions are intimately linked to the dynamics of magma ascent and outgassing and, on geological time scales, constitute an important source of volatiles to the Earth's atmosphere. Measurements of gas composition and flux are therefore critical to both volcano monitoring and to determining the contribution of volcanoes to global geochemical cycles. However, significant gaps remain in our global inventories of volcanic emissions, (particularly for CO 2 , which requires proximal sampling of a concentrated plume) for those volcanoes where the near-vent region is hazardous or inaccessible. Unmanned Aerial Systems (UAS) provide a robust and effective solution to proximal sampling of dense volcanic plumes in extreme volcanic environments. Here we present gas compositional data acquired using a gas sensor payload aboard a UAS flown at Volcán Villarrica, Chile. We compare UAS-derived gas time series to simultaneous crater rim multi-GAS data and UV camera imagery to investigate early plume evolution. SO 2 concentrations measured in the young proximal plume exhibit periodic variations that are well correlated with the concentrations of other species. By combining molar gas ratios (CO 2 /SO 2  = 1.48–1.68, H 2 O/SO 2  = 67–75, and H 2 O/CO 2  = 45–51) with the SO 2 flux (142 ± 17 t/day) from UV camera images, we derive CO 2 and H 2 O fluxes of ~150 t/day and ~2,850 t/day, respectively. We observe good agreement between time-averaged molar gas ratios obtained from simultaneous UAS- and ground-based multi-GAS acquisitions. However, the UAS measurements made in the young, less diluted plume reveal additional short-term periodic structure that reflects active degassing through discrete, audible gas exhalations. ©2018. American Geophysical Union. All Rights Reserved.