Trajectory sensitivity to rawinsonde data resolution

Meteorological measurements collected during the Cross Appalachian Tracer Experiment (CAPTEX) were used to evaluate the sensitivity of trajectory calculations to variations in the spatial and temporal density of rawinsonde data. Data resolution was systematically adjusted in order to separately evaluate the effects of enhanced spatial and temporal resolution. Variable mixed layer, constant layer, and constant level trajectories were more sensitive to increases in spatial resolution than to increases in temporal resolution. For mixed layer, 0-400-m layer and 400-m level trajectories, sensitivity to combined increases in both spatial and temporal rawinsonde data resolution was dominated by the effects of spatial resolution alone. This dominance was not observed for trajectories calculated at higher levels and layers.Trajectory case studies corresponding to two CAPTEX tracer releases were presented. These examples illustrate the potential effects of a single additional measurement at an existing National Weather Service rawinsonde station, and the importance of specifying the initial transport wind accurately.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27606/1/0000650.pd

Relationships between synoptic-scale transport and interannual variability of inorganic cations in surface snow at Summit, Greenland: 1992-1996

Version of RecordTo fully utilize the long-term chemical records retrieved from central Greenland ice cores, specific relationships between atmospheric circulation and the variability of chemical species in the records need to be better understood. This research examines associations between the variability of surface snow inorganic cation chemistry at Summit, Greenland (collected during 1992-1996 summer field seasons) and changes in air mass transport pathways and source regions, as well as variations in aerosol source strength. Transport patterns and source regions are determined through 10-day isentropic backward air mass trajectories during a 1 month (late May to late June) common season over the 5 years. Changes in the extent of exposed continental surfaces in source regions are evaluated to estimate aerosol-associated calcium and magnesium ion source strength, while forest fire activity in the circumpolar north is investigated to estimate aerosol ammonium ion source strength. During the 1995 common season, 3 times more calcium and magnesium accumulated in the snowpack than the other study years. Also, an increasing trend of ammonium concentration was noted throughout the 5 years. Anomalous transport pathways and velocities were observed during 1995, which likely contributed to the high levels of calcium and magnesium. Increased forest fire activity in North America was concurrent with increased levels of ammonium and potassium, except for 1996, when ion levels were above average and forest fire activity was below average. Because of the ubiquitous nature of soluble ions, we conclude that it is very difficult to establish a quantitative link between the ion content of snow and firn at Summit and changes in aerosol source regions and source strength.Slater, J. F., Dibb, J. E., Keim, B. D., & Kahl, J. D. w. (2001). Relationships between synoptic-scale transport and interannual variability of inorganic cations in surface snow at Summit, Greenland: 1992-1996. Journal of Geophysical Research 106(D18), 20,897-20,91

Diel variations of H2O2 in Greenland: A discussion of the cause and effect relationship

Atmospheric hydrogen peroxide (H2O2) measurements at Summit, Greenland, in May–June, 1993 exhibited a diel variation, with afternoon highs typically 1–2 parts per billion by volume (ppbv) and nighttime lows about 0.5 ppbv lower. This variation closely followed that for temperature; specific humidity exhibited the same general trend. During a 17-day snowfall-free period, surface snow was accumulating H2O2, apparently from nighttime cocondensation of H2O and H2O2. Previous photochemical modeling (Neftel et al., 1995) suggests that daytime H2O2 should be about 1 ppbv, significantly lower than our measured values. Previous equilibrium partitioning measurements between ice and gas phase (Conklin et al., 1993) suggest that air in equilibrium with H2O2 concentrations measured in surface snow (15–18 μM) should have an H2O2 concentration 2–3 times what we measured 0.2–3.5 m above the snow surface. A simple eddy diffusion model, with vertical eddy diffusion coefficients calculated from balloon soundings, suggested that atmospheric H2O2 concentrations should be affected by any H2O2 degassed from surface snow. However, field measurements showed the absence of either high concentrations of H2O2 or a measurable concentration gradient between inlets 0.2 and 3 m above the snow. A surface resistance to degassing, that is, slow release of H2O2 from the ice matrix, is a plausible explanation for the differences between observations and modeled atmospheric profiles. Degassing of H2O2 at a rate below our detection limit would still influence measured atmospheric concentrations and help explain the difference between measurements and photochemical modeling. The cumulative evidence suggests that surface snow adjusts slowly to drops in atmospheric H2O2 concentration, over timescales of at least weeks. The H2O2 losses previously observed in pits sampled over more than 1 year are thought to have occurred later in the summer or fall, after the May–July field season

On the potential of regional-scale emissions zoning as an air quality management tool for the grand canyon

Air arriving at the Grand Canyon of the Colorado River during 1988-1989 is attributed to one of four geographic quadrants--NE, SE, SW, NW--on the basis of routinely calculated back-trajectories. Most of the haze observed at the Canyon is attributed to the SW quadrant, which contains the populous and industrialized areas of southern California. Air from either northern quadrant tends to be significantly clearer than air from either southern quadrant. Clear northern air is most common during the winter, and is rarely observed during the summer tourist season, when steady flow from the southwest is the norm. Various possible interpretations of these empirical results are discussed, with varying implications for emissions management policy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31947/1/0000900.pd

A phase II study of dacetuzumab (SGN-40) in patients with relapsed diffuse large B-cell lymphoma (DLBCL) and correlative analyses of patient-specific factors

BACKGROUND: Patients with DLBCL who are ineligible for or have relapsed after aggressive salvage chemotherapy have a poor prognosis. CD40 is expressed on multiple B-cell neoplasms including DLBCL and is a potential target for immunotherapy. Dacetuzumab (SGN-40), a non-blocking, partial agonist, humanized IgG1, anti-CD40 monoclonal antibody, has previously demonstrated anti-lymphoma activity in a phase I study. METHODS: A phase II study was undertaken to evaluate the rate and duration of objective responses and safety of single-agent dacetuzumab in relapsed DLBCL. Forty-six adult patients with relapsed/refractory DLBCL received up to 12 cycles of intravenous dacetuzumab using intrapatient dose-escalation to a target dose of 8 mg/kg/week in an initial 5-week cycle, followed by 4-week cycles of 8 mg/kg/week. Study endpoints included rate and duration of objective responses, safety, survival, pharmacokinetics, immunogenicity, and exploratory correlative studies. RESULTS: Overall response rate was 9% and disease control rate (complete remission + partial remission + stable disease) was 37%. Common non-hematologic adverse events (AEs) included fatigue, headache, chills, fever, and nausea. The most frequent Grade 3–4 non-hematologic AE was deep venous thrombosis (3 patients). Grade 3–4 lymphopenia (41%), neutropenia (13%), or thrombocytopenia (19%) occurred without associated infection or bleeding. Reversible ocular events, including conjunctivitis and ocular hyperemia, occurred in 8 patients (17%). Patient-specific factors, including Fc-gamma-RIIIa polymorphism, did not appear to correlate with antitumor activity. CONCLUSIONS: Single-agent dacetuzumab has modest activity and manageable toxicity in unselected patients with relapsed DLBCL. Combination regimens and robust methods of patient selection may be necessary for further development. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00435916

Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: subset analysis of randomized trial intergroup SWOG S9704

Double hit lymphoma (DHL) and double protein-expressing (MYC and BCL2) lymphomas (DPL) fare poorly with R-CHOP; consolidative autologous stem cell transplant (ASCT) may improve outcomes. S9704, a phase III randomized study of CHOP +/−R with or without ASCT allows evaluation of intensive consolidation. Immunohistochemical analysis identified 27 of 198 patients (13.6%) with MYC IHC overexpression and 20 (74%) harboring concurrent BCL2 overexpression. Four had DHL and 16 had DPL only. With median follow-up 127 months, there is a trend favoring outcomes after consolidative ASCT in DPL and MYC protein overexpressing patients, whereas all DHL patients have died irrespective of ASCT

Is local review of positron emission tomography scans sufficient in diffuse large B-cell lymphoma clinical trials? A CALGB 50303 analysis

BACKGROUND: Quantitative methods of Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) interpretation, including the percent change in FDG uptake from baseline (ΔSUV), are under investigation in lymphoma to overcome challenges associated with visual scoring systems (VSS) such as the Deauville 5-point scale (5-PS). METHODS: In CALGB 50303, patients with DLBCL received frontline R-CHOP or DA-EPOCH-R, and although there were no significant associations between interim PET responses assessed centrally after cycle 2 (iPET) using 5-PS with progression-free survival (PFS) or overall survival (OS), there were significant associations between central determinations of iPET ∆SUV with PFS/OS. In this patient cohort, we retrospectively compared local vs central iPET readings and evaluated associations between local imaging data and survival outcomes. RESULTS: Agreement between local and central review was moderate (kappa = 0.53) for VSS and high (kappa = 0.81) for ∆SUV categories (\u3c66% vs. ≥66%). ∆SUV ≥66% at iPET was significantly associated with PFS (p = 0.03) and OS (p = 0.002), but VSS was not. Associations with PFS/OS when applying local review vs central review were comparable. CONCLUSIONS: These data suggest that local PET interpretation for response determination may be acceptable in clinical trials. Our findings also highlight limitations of VSS and call for incorporation of more objective measures of response assessment in clinical trials

RB but not R-HCVAD is a feasible induction regimen prior to auto-HCT in frontline MCL: results of SWOG Study S1106

Aggressive induction chemotherapy followed by autologous haematopoietic stem cell transplant (auto-HCT) is effective for younger patients with mantle cell lymphoma (MCL). However, the optimal induction regimen is widely debated. The Southwesterm Oncology Group S1106 trial was designed to assess rituximab plushyperCVAD/MTX/ARAC (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone, alternating with high dose cytarabine and methotrexate) (RH) versus rituximab plus bendamustine (RB) in a randomized phase II trial to select a pre-transplant induction regimen for future development. Patients had previously untreated stage III, IV, or bulky stage II MCL and received either 4 cycles of RH or 6 cycles of RB, followed by auto-HCT. Fifty-three of a planned 160 patients were accrued; an unacceptably high mobilization failure rate (29%) on the RH arm prompted premature study closure. The estimated 2-year progression-free survival (PFS) was 81% vs. 82% and overall survival (OS) was 87% vs. 88% for RB and RH, respectively. RH is not an ideal platform for future multi-centre transplant trials in MCL. RB achieved a 2-year PFS of 81% and a 78% MRD negative rate. Premature closure of the study limited the sample size and the precision of PFS estimates and MRD rates. However, RB can achieve a deep remission and could be a platform for future trials in MCL

RB but not R‐HCVAD is a feasible induction regimen prior to auto‐HCT in frontline MCL: results of SWOG Study S1106

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136294/1/bjh14480_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136294/2/bjh14480.pd

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of hematologic malignancies: multiple myeloma, lymphoma, and acute leukemia

Increasing knowledge concerning the biology of hematologic malignancies as well as the role of the immune system in the control of these diseases has led to the development and approval of immunotherapies that are resulting in impressive clinical responses. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a hematologic malignancy Cancer Immunotherapy Guidelines panel consisting of physicians, nurses, patient advocates, and patients to develop consensus recommendations for the clinical application of immunotherapy for patients with multiple myeloma, lymphoma, and acute leukemia. These recommendations were developed following the previously established process based on the Institute of Medicine’s clinical practice guidelines. In doing so, a systematic literature search was performed for high-impact studies from 2004 to 2014 and was supplemented with further literature as identified by the panel. The consensus panel met in December of 2014 with the goal to generate consensus recommendations for the clinical use of immunotherapy in patients with hematologic malignancies. During this meeting, consensus panel voting along with discussion were used to rate and review the strength of the supporting evidence from the literature search. These consensus recommendations focus on issues related to patient selection, toxicity management, clinical endpoints, and the sequencing or combination of therapies. Overall, immunotherapy is rapidly emerging as an effective therapeutic strategy for the management of hematologic malignances. Evidence-based consensus recommendations for its clinical application are provided and will be updated as the field evolves