Several concepts for platinum-based catalysts for the oxygen reduction reaction (ORR) are presented that exceed the US Department of Energy targets for Pt-related ORR mass activity. Most concepts ...achieve their high ORR activity by increasing the Pt specific activity at the expense of a lower electrochemically active surface area (ECSA). In the potential region controlled by kinetics, such a lower ECSA is counterbalanced by the high specific activity. At higher overpotentials, however, which are often applied in real systems, a low ECSA leads to limitations in the reaction rate not by kinetics, but by mass transport. Here we report on self-supported platinum-cobalt oxide networks that combine a high specific activity with a high ECSA. The high ECSA is achieved by a platinum-cobalt oxide bone nanostructure that exhibits unprecedentedly high mass activity for self-supported ORR catalysts. This concept promises a stable fuel-cell operation at high temperature, high current density and low humidification.
Improving outcomes in older adults with acute myeloid leukemia remains a formidable challenge. Lintuzumab (SGN-33; HuM195) is a humanized monoclonal antibody directed against CD33, which is expressed ...on the majority of myeloblasts in acute myeloid leukemia. The primary objective of this randomized, double-blinded, placebo-controlled trial was to determine whether addition of lintuzumab to low-dose cytarabine would increase overall survival in adults aged 60 years and over with untreated acute myeloid leukemia. Randomization was stratified by age, previous hematologic disorder, and performance status. All patients received cytarabine (20 mg subcutaneously twice daily) on Days 1-10 of each 28-day cycle. Patients received lintuzumab (600 mg) or placebo intravenously once weekly in Cycle 1 and once every other week in Cycles 2-12. A total of 211 patients (107 lintuzumab, 104 placebo) were randomized. Median age was 70 years (range 60-90). Survival was not significantly prolonged with lintuzumab treatment (hazard ratio 0.96; 95% confidence interval (CI) 0.72-1.28; P=0.7585). Median survival was similar between treatment arms (4.7 months lintuzumab vs. 5.1 months placebo) and in the subgroup of patients with high-risk cytogenetics (4.5 months). Infusion-related reactions, predominantly Grades 1-2, occurred more commonly in the lintuzumab arm (51% vs. 7% placebo); no other clinically significant difference in safety was noted. These results confirm that lintuzumab in combination with low-dose cytarabine did not prolong survival and that low-dose cytarabine remains a valid comparator for trials of non-intensive therapies in older patients with acute myeloid leukemia, regardless of cytogenetic profile.
To determine the safety and efficacy of arsenic trioxide (ATO) in patients with relapsed acute promyelocytic leukemia (APL).
Forty patients experiencing first (n = 21) or > or = second (n = 19) ...relapse were treated with daily infusions of ATO to a maximum of 60 doses or until all leukemic cells in bone marrow were eliminated. Patients who achieved a complete remission (CR) were offered one consolidation course of ATO that began 3 to 4 weeks later. Patients who remained in CR were eligible to receive further cycles of ATO therapy on a maintenance study.
Thirty-four patients (85%) achieved a CR. Thirty-one patients (91%) with CRs had posttreatment cytogenetic tests negative for t(15;17). Eighty-six percent of the patients who were assessable by reverse transcriptase polymerase chain reaction converted from positive to negative for the promyelocytic leukemia/retinoic acid receptor-alpha transcript by the completion of their consolidation therapy. Thirty-two patients received consolidation therapy, and 18 received additional ATO as maintenance. Eleven patients underwent allogeneic (n = 8) or autologous (n = 3) transplant after ATO treatment. The 18-month overall and relapse-free survival (RFS) estimates were 66% and 56%, respectively. Twenty patients (50%) had leukocytosis (> 10,000 WBC/microL) during induction therapy. Ten patients developed signs or symptoms suggestive of the APL syndrome and were effectively treated with dexamethasone. Electrocardiographic QT prolongation was common (63%). One patient had an absolute QT interval of > 500 msec and had an asymptomatic 7-beat run of torsades de pointe. Two patients died during induction, neither from drug-related causes.
This study establishes ATO as a highly effective therapy for patients with relapsed APL.
We report a B-mode power spectrum measurement from the cosmic microwave background (CMB) polarization anisotropy observations made using the SPTpol instrument on the South Pole Telescope. This work ...uses 500 deg2 of SPTpol data, a five-fold increase over the last SPTpol B-mode release. As a result, the bandpower uncertainties have been reduced by more than a factor of two, and the measurement extends to lower multipoles: 52 < ℓ < 2301 . Data from both 95 and 150 GHz are used, allowing for three cross-spectra: 95 GHz × 95 GHz , 95 GHz × 150 GHz , and 150 GHz × 150 GHz . B -mode power is detected at very high significance; we find P ( B B < 0 ) = 5.8 × 10−71, corresponding to a 18.1σ detection of power. With a prior on the galactic dust from Planck, WMAP and BICEP2/Keck observations, the SPTpol B-mode data can be used to set an upper limit on the tensor-to-scalar ratio, r < 0.44 at 95% confidence (the expected 1σ constraint on r given the measurement uncertainties is 0.22). We find the measured B-mode power is consistent with the Planck best-fit Λ CDM model predictions. Scaling the predicted lensing B-mode power in this model by a factor Alens, the data prefer Alens = 1.17 ± 0.13 . These data are currently the most precise measurements of B-mode power at ℓ > 320.
Three open-label, multicenter trials were conducted to evaluate the efficacy and safety of single-agent Mylotarg (gemtuzumab ozogamicin; CMA-676; Wyeth Laboratories, Philadelphia, PA), an ...antibody-targeted chemotherapy agent, in patients with CD33-positive acute myeloid leukemia (AML) in untreated first relapse.
The study population comprised 142 patients with AML in first relapse with no history of an antecedent hematologic disorder and a median age of 61 years. All patients received Mylotarg as a 2-hour intravenous infusion, at a dose of 9 mg/m(2), at 2-week intervals for two doses. Patients were evaluated for remission, survival, and treatment-emergent adverse events.
Thirty percent of patients treated with Mylotarg obtained remission as characterized by 5% or less blasts in the marrow, recovery of neutrophils to at least 1,500/microL, and RBC and platelet transfusion independence. Although patients treated with Mylotarg had relatively high incidences of myelosuppression, grade 3 or 4 hyperbilirubinemia (23%), and elevated hepatic transaminase levels (17%), the incidences of grade 3 or 4 mucositis (4%) and infections (28%) were relatively low. There was a low incidence of severe nausea and vomiting (11%) and no treatment-related cardiotoxicity, cerebellar toxicity, or alopecia. Many patients received Mylotarg on an outpatient basis (38% and 41% of patients for the first and second doses, respectively). Among the 142 patients, the median total duration of hospitalization was 24 days; 16% of patients required 7 days of hospitalization or less.
Administration of the antibody-targeted chemotherapy agent Mylotarg to patients with CD33-positive AML in first relapse induces complete remissions with what appears to be a favorable safety profile.
We present a search for anisotropic cosmic birefringence in 500 deg2 of southern sky observed at 150 GHz with the SPTpol camera on the South Pole Telescope. We reconstruct a map of cosmic ...polarization rotation anisotropies using higher-order correlations between the observed cosmic microwave background (CMB) E and B fields. We then measure the angular power spectrum of this map, which is found to be consistent with zero. The nondetection is translated into an upper limit on the amplitude of the scale-invariant cosmic rotation power spectrum, L(L + 1) CααL/2π < 0.10 × 10−4 rad2 (0.033 deg2, 95% C.L.). This upper limit can be used to place constraints on the strength of primordial magnetic fields, B1 Mpc < 17 nG (95% C.L.), and on the coupling constant of the Chern-Simons electromagnetic term gaγ < 4.0 × 10−2/HI (95% C.L.), where HI is the inflationary Hubble scale. For the first time, we also cross-correlate the CMB temperature fluctuations with the reconstructed rotation angle map, a signal expected to be nonvanishing in certain theoretical scenarios, and find no detectable signal. We perform a suite of systematics and consistency checks and find no evidence for contamination.
We present measurements of the E-mode polarization angular auto-power spectrum (EE) and temperature-E-mode cross-power spectrum (TE) of the cosmic microwave background (CMB) using 150 GHz data from ...three seasons of SPTpol observations. We report the power spectra over the spherical harmonic multipole range and detect nine acoustic peaks in the EE spectrum with high signal-to-noise ratio. These measurements are the most sensitive to date of the EE and TE power spectra at and , respectively. The observations cover 500 , a fivefold increase in area compared to previous SPTpol analyses, which increases our sensitivity to the photon diffusion damping tail of the CMB power spectra enabling tighter constraints on ΛCDM model extensions. After masking all sources with unpolarized flux mJy, we place a 95% confidence upper limit on residual polarized point-source power of at , suggesting that the EE damping tail dominates foregrounds to at least with modest source masking. We find that the SPTpol data set is in mild tension with the ΛCDM model ( ), and different data splits prefer parameter values that differ at the level. When fitting SPTpol data at , we find cosmological parameter constraints consistent with those for Planck temperature. Including SPTpol data at results in a preference for a higher value of the expansion rate ( ) and a lower value for present-day density fluctuations ( ).
Abstract
We report new measurements of millimeter-wave power spectra in the angular multipole range 2000 ≤
ℓ
≤ 11,000 (angular scales
). By adding 95 and 150 GHz data from the low-noise 500 deg
2
...SPTpol survey to the SPT-SZ three-frequency 2540 deg
2
survey, we substantially reduce the uncertainties in these bands. These power spectra include contributions from the primary cosmic microwave background, cosmic infrared background, radio galaxies, and thermal and kinematic Sunyaev–Zel’dovich (SZ) effects. The data favor a thermal SZ (tSZ) power at 143 GHz of
and a kinematic SZ (kSZ) power of
. This is the first measurement of kSZ power at ≥3
σ
. However, different assumptions about the CIB or SZ models can reduce the significance down to 2.4
σ
in the worst case. We study the implications of the measured kSZ power for the epoch of reionization under the Calabrese et al. model for the kSZ power spectrum and find the duration of reionization to be
(
at 95% confidence), when combined with our previously published tSZ bispectrum measurement. The upper limit tightens to
if the assumed homogeneous kSZ power is increased by 25% (∼0.5
μ
K
2
) and relaxes to
if the homogeneous kSZ power is decreased by the same amount.
In order to compare the outcomes of unrelated umbilical cord blood transplants (UCBTs) or bone marrow transplants, 541 children with acute leukemia (AL) transplanted with umbilical cord blood (n = ...99), T-cell–depleted unrelated bone marrow transplants (T-UBMT) (n = 180), or nonmanipulated (UBMT) (n = 262), were analyzed in a retrospective multicenter study. Comparisons were performed after adjustment for patient, disease, and transplant variables. The major difference between the 3 groups was the higher number in the UCBT group of HLA mismatches (defined by serology for class I and molecular typing for DRB1). The donor was HLA mismatched in 92% of UCBTs, in 18% of UBMTs, and in 43% of T-UBMTs (P < .001). Other significant differences were observed in pretransplant disease characteristics, preparative regimens, graft-versus-host disease (GVHD) prophylaxis, and number of cells infused. Nonadjusted estimates of 2-year survival and event-free survival rates were 49% and 43%, respectively, in the UBMT group, 41% and 37% in the T-UBMT group, and 35% and 31% in the UCBT group. After adjustment, differences in outcomes appeared in the first 100 days after the transplantation. Compared with UBMT recipients, UCBT recipients had delayed hematopoietic recovery (Hazard ratio HR = 0.37; 95% confidence interval 95CI: 0.27-0.52; P < .001), increased 100 day transplant-related mortality (HR = 2.13; 95CI: 1.20-3.76;P < .01) and decreased acute graft-versus-host disease (aGVHD) (HR = 0.50; 95CI: 0.34-0.73; P < .001). T-UBMT recipients had decreased aGVHD (HR = 0.25; 95CI: 0.17-0.36;P < .0001) and increased risk of relapse (HR = 1.96; 95CI: 1.11-3.45; P = .02). After day 100 posttransplant, the 3 groups achieved similar results in terms of relapse. Chronic GVHD was decreased after T-UBMT (HR = 0.21; 95CI: 0.11-0.37;P < .0001) and UCBT (HR = 0.24; 95CI: 0.01-0.66;P = .002), and overall mortality was higher in T-UBMT recipients (HR = 1.39; 95CI: 0.97-1.99; P < .07). In conclusion, the use of UCBT, as a source of hematopoietic stem cells, is a reasonable option for children with AL lacking an acceptably matched unrelated marrow donor.
Approximately 40% of children with acute myeloid leukemia (AML) who respond to initial therapy subsequently relapse. Multidimensional flow cytometry employing a standardized panel of monoclonal ...antibodies enables the detection of small numbers of occult leukemic cells that persist during therapy using technology adaptable by most clinical laboratories. We performed a prospective, blinded evaluation of bone marrow specimens obtained from 252 pediatric patients with de novo AML to determine whether detection of occult leukemia defined as more than or equal to 0.5% blasts with aberrant surface antigen expression as determined by flow cytometry was predictive of subsequent relapse. Occult leukemia was detected in 41 (16%) of the 252 patients who responded to initial induction therapy. In time-dependent multivariate analyses that controlled for allogeneic marrow transplantation, variable intervals between sample submission, age, sex, white blood cell count at diagnosis, presence of splenomegaly or hepatomegaly, and presence of more than 15% blasts in the marrow after the first course of induction, patients harboring occult leukemia were 4.8 times more likely to relapse (95% confidence interval CI = 2.8 to 8.4,P < .0001) and 3.1 times more likely to die (95% CI; 1.9 to 5.1, P < .0001) than those lacking leukemia detectable by flow cytometry. In this analysis, flow cytometric evidence of leukemia after the initiation of therapy emerged as the most powerful independent prognostic factor associated with poor outcome. Among patients in whom a marrow sample was available for analysis at the end of consolidation therapy, overall survival at 3 years was 41% versus 69% for patients with and without occult leukemia, respectively (P = .0058).
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