Daratumumab showed promising efficacy alone and with lenalidomide and dexamethasone in a phase 1-2 study involving patients with relapsed or refractory multiple myeloma.
In this phase 3 trial, we ...randomly assigned 569 patients with multiple myeloma who had received one or more previous lines of therapy to receive lenalidomide and dexamethasone either alone (control group) or in combination with daratumumab (daratumumab group). The primary end point was progression-free survival.
At a median follow-up of 13.5 months in a protocol-specified interim analysis, 169 events of disease progression or death were observed (in 53 of 286 patients 18.5% in the daratumumab group vs. 116 of 283 41.0% in the control group; hazard ratio, 0.37; 95% confidence interval CI, 0.27 to 0.52; P<0.001 by stratified log-rank test). The Kaplan-Meier rate of progression-free survival at 12 months was 83.2% (95% CI, 78.3 to 87.2) in the daratumumab group, as compared with 60.1% (95% CI, 54.0 to 65.7) in the control group. A significantly higher rate of overall response was observed in the daratumumab group than in the control group (92.9% vs. 76.4%, P<0.001), as was a higher rate of complete response or better (43.1% vs. 19.2%, P<0.001). In the daratumumab group, 22.4% of the patients had results below the threshold for minimal residual disease (1 tumor cell per 10
white cells), as compared with 4.6% of those in the control group (P<0.001); results below the threshold for minimal residual disease were associated with improved outcomes. The most common adverse events of grade 3 or 4 during treatment were neutropenia (in 51.9% of the patients in the daratumumab group vs. 37.0% of those in the control group), thrombocytopenia (in 12.7% vs. 13.5%), and anemia (in 12.4% vs. 19.6%). Daratumumab-associated infusion-related reactions occurred in 47.7% of the patients and were mostly of grade 1 or 2.
The addition of daratumumab to lenalidomide and dexamethasone significantly lengthened progression-free survival among patients with relapsed or refractory multiple myeloma. Daratumumab was associated with infusion-related reactions and a higher rate of neutropenia than the control therapy. (Funded by Janssen Research and Development; POLLUX ClinicalTrials.gov number, NCT02076009 .).
Most massive stars, the progenitors of core-collapse supernovae, are in close binary systems and may interact with their companion through mass transfer or merging. We undertake a population ...synthesis study to compute the delay-time distribution of core-collapse supernovae, that is, the supernova rate versus time following a starburst, taking into account binary interactions. We test the systematic robustness of our results by running various simulations to account for the uncertainties in our standard assumptions. We find that a significant fraction, 15+9-8%, of core-collapse supernovae are “late”, that is, they occur 50–200 Myr after birth, when all massive single stars have already exploded. These late events originate predominantly from binary systems with at least one, or, in most cases, with both stars initially being of intermediate mass (4–8 M⊙). The main evolutionary channels that contribute often involve either the merging of the initially more massive primary star with its companion or the engulfment of the remaining core of the primary by the expanding secondary that has accreted mass at an earlier evolutionary stage. Also, the total number of core-collapse supernovae increases by 14+15-14% because of binarity for the same initial stellar mass. The high rate implies that we should have already observed such late core-collapse supernovae, but have not recognized them as such. We argue that φ Persei is a likely progenitor and that eccentric neutron star – white dwarf systems are likely descendants. Late events can help explain the discrepancy in the delay-time distributions derived from supernova remnants in the Magellanic Clouds and extragalactic type Ia events, lowering the contribution of prompt Ia events. We discuss ways to test these predictions and speculate on the implications for supernova feedback in simulations of galaxy evolution.
The Atmospheric Chemistry and Climate Model Intercomparison Project (ACCMIP) examined the short-lived drivers of climate change in current climate models. Here we evaluate the 10 ACCMIP models that ...included aerosols, 8 of which also participated in the Coupled Model Intercomparison Project phase 5 (CMIP5). The models reproduce present-day total aerosol optical depth (AOD) relatively well, though many are biased low. Contributions from individual aerosol components are quite different, however, and most models underestimate east Asian AOD. The models capture most 1980–2000 AOD trends well, but underpredict increases over the Yellow/Eastern Sea. They strongly underestimate absorbing AOD in many regions. We examine both the direct radiative forcing (RF) and the forcing including rapid adjustments (effective radiative forcing; ERF, including direct and indirect effects). The models' all-sky 1850 to 2000 global mean annual average total aerosol RF is (mean; range) −0.26 W m−2; −0.06 to −0.49 W m−2. Screening based on model skill in capturing observed AOD yields a best estimate of −0.42 W m−2; −0.33 to −0.50 W m−2, including adjustment for missing aerosol components in some models. Many ACCMIP and CMIP5 models appear to produce substantially smaller aerosol RF than this best estimate. Climate feedbacks contribute substantially (35 to −58%) to modeled historical aerosol RF. The 1850 to 2000 aerosol ERF is −1.17 W m−2; −0.71 to −1.44 W m−2. Thus adjustments, including clouds, typically cause greater forcing than direct RF. Despite this, the multi-model spread relative to the mean is typically the same for ERF as it is for RF, or even smaller, over areas with substantial forcing. The largest 1850 to 2000 negative aerosol RF and ERF values are over and near Europe, south and east Asia and North America. ERF, however, is positive over the Sahara, the Karakoram, high Southern latitudes and especially the Arctic. Global aerosol RF peaks in most models around 1980, declining thereafter with only weak sensitivity to the Representative Concentration Pathway (RCP). One model, however, projects approximately stable RF levels, while two show increasingly negative RF due to nitrate (not included in most models). Aerosol ERF, in contrast, becomes more negative during 1980 to 2000. During this period, increased Asian emissions appear to have a larger impact on aerosol ERF than European and North American decreases due to their being upwind of the large, relatively pristine Pacific Ocean. There is no clear relationship between historical aerosol ERF and climate sensitivity in the CMIP5 subset of ACCMIP models. In the ACCMIP/CMIP5 models, historical aerosol ERF of about −0.8 to −1.5 W m−2 is most consistent with observed historical warming. Aerosol ERF masks a large portion of greenhouse forcing during the late 20th and early 21st century at the global scale. Regionally, aerosol ERF is so large that net forcing is negative over most industrialized and biomass burning regions through 1980, but remains strongly negative only over east and southeast Asia by 2000. Net forcing is strongly positive by 1980 over most deserts, the Arctic, Australia, and most tropical oceans. Both the magnitude of and area covered by positive forcing expand steadily thereafter.
We prepared a simple, low-cost membrane suitable for gravity-driven oil–water separation and water purification. Composite membranes with selective wettability were fabricated from a mixture of ...aqueous poly(diallyldimethylammonium chloride) solution, sodium perfluorooctanoate, and silica nanoparticles. Simply dip-coating a stainless steel mesh using this mixture produced the oil–water separator. The contact angles (CAs) of hexadecane and water on the prepared composite membranes were 95 ± 2° and 0°, respectively, showing the oleophobicity and superhydrophilicity of the membrane. In addition, a graphene plug was stacked below the membrane to remove water-soluble organics by adsorption. As a result, this multifunctional device not only separates hexadecane from water, but also purifies water by the permeation of the separated water through the graphene plug. Here, methylene blue (MB) was removed as a demonstration. Membranes were characterized by high-resolution scanning electron microscopy (HRSEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FT-IR) spectroscopy to elucidate the origin of their selective wettability.
Abstract
We present the analysis of ∼100 pc scale compact radio continuum sources detected in 63 local (ultra)luminous infrared galaxies (U/LIRGs;
L
IR
≥ 10
11
L
⊙
), using FWHM ≲ 0.″1–0.″2 ...resolution 15 and 33 GHz observations with the Karl G. Jansky Very Large Array. We identify a total of 133 compact radio sources with effective radii of 8–170 pc, which are classified into four main categories—“AGN” (active galactic nuclei), “AGN/SBnuc” (AGN-starburst composite nucleus), “SBnuc” (starburst nucleus), and “SF” (star-forming clumps)—based on ancillary data sets and the literature. We find that “AGN” and “AGN/SBnuc” more frequently occur in late-stage mergers and have up to 3 dex higher 33 GHz luminosities and surface densities compared with “SBnuc” and “SF,” which may be attributed to extreme nuclear starburst and/or AGN activity in the former. Star formation rates (SFRs) and surface densities (Σ
SFR
) are measured for “SF” and “SBnuc” using both the total 33 GHz continuum emission (SFR ∼ 0.14–13
M
⊙
yr
−1
, Σ
SFR
∼ 13–1600
M
⊙
yr
−1
kpc
−2
) and the thermal free–free emission from H
ii
regions (median SFR
th
∼ 0.4
M
⊙
yr
−1
,
Σ
SFR
th
∼
44
M
⊙
yr
−1
kpc
−2
). These values are 1–2 dex higher than those measured for similar-sized clumps in nearby normal (non-U/LIRGs). The latter also have a much flatter median 15–33 GHz spectral index (∼−0.08) compared with “SBnuc” and “SF” (∼−0.46), which may reflect higher nonthermal contribution from supernovae and/or interstellar medium densities in local U/LIRGs that directly result from and/or lead to their extreme star-forming activities on 100 pc scales.
As part of the Atmospheric Chemistry and Climate Model Intercomparison Project (ACCMIP), we evaluate the historical black carbon (BC) aerosols simulated by 8 ACCMIP models against observations ...including 12 ice core records, long-term surface mass concentrations, and recent Arctic BC snowpack measurements. We also estimate BC albedo forcing by performing additional simulations using offline models with prescribed meteorology from 1996-2000. We evaluate the vertical profile of BC snow concentrations from these offline simulations using the recent BC snowpack measurements. Despite using the same BC emissions, the global BC burden differs by approximately a factor of 3 among models due to differences in aerosol removal parameterizations and simulated meteorology: 34 Gg to 103 Gg in 1850 and 82 Gg to 315 Gg in 2000. However, the global BC burden from preindustrial to present-day increases by 2.5-3 times with little variation among models, roughly matching the 2.5-fold increase in total BC emissions during the same period.We find a large divergence among models at both Northern Hemisphere (NH) and Southern Hemisphere (SH) high latitude regions for BC burden and at SH high latitude regions for deposition fluxes. The ACCMIP simulations match the observed BC surface mass concentrations well in Europe and North America except at Ispra. However, the models fail to predict the Arctic BC seasonality due to severe underestimations during winter and spring. The simulated vertically resolved BC snow concentrations are, on average, within a factor of 2-3 of the BC snowpack measurements except for Greenland and the Arctic Ocean. For the ice core evaluation, models tend to adequately capture both the observed temporal trends and the magnitudes at Greenland sites. However, models fail to predict the decreasing trend of BC depositions/ice core concentrations from the 1950s to the 1970s in most Tibetan Plateau ice cores. The distinct temporal trend at the Tibetan Plateau ice cores indicates a strong influence from Western Europe, but the modeled BC increases in that period are consistent with the emission changes in Eastern Europe, the Middle East, South and East Asia. At the Alps site, the simulated BC suggests a strong influence from Europe, which agrees with the Alps ice core observations. At Zuoqiupu on the Tibetan Plateau, models successfully simulate the higher BC concentrations observed during the non-monsoon season compared to the monsoon season but overpredict BC in both seasons. Despite a large divergence in BC deposition at two Antarctic ice core sites, some models with a BC lifetime of less than 7 days are able to capture the observed concentrations. In 2000 relative to 1850, globally and annually averaged BC surface albedo forcing from the offline simulations ranges from 0.014 to 0.019Wm−2 among the ACCMIP models. Comparing offline and online BC albedo forcings computed by some of the same models, we find that the global annual mean can vary by up to a factor of two because of different aerosol models or different BC-snow parameterizations and snow cover. The spatial distributions of the offline BC albedo forcing in 2000 show especially high BC forcing (i.e., over 0.1W/sq. m) over Manchuria, Karakoram, and most of the Former USSR. Models predict the highest global annual mean BC forcing in 1980 rather than 2000, mostly driven by the high fossil fuel and biofuel emissions in the Former USSR in 1980.
Capecitabine plus oxaliplatin (XELOX) has shown modest activity and tolerable toxicity in a phase II trial for biliary tract cancers (BTCs). Meanwhile, gemcitabine plus oxaliplatin (GEMOX) has been ...the reference arm in recent phase II and III trials for BTCs. We aimed to investigate the efficacy of XELOX versus GEMOX as first-line therapy for advanced BCTs.
In this open-label, randomized, phase III, noninferiority trial, we randomly selected patients with metastatic BCTs to receive GEMOX (gemcitabine 1000mg/m2 on days 1 and 8, and oxaliplatin 100mg/m2 on day 1) or XELOX (capecitabine 1000mg/m2, twice daily, on days 1–14 and oxaliplatin 130mg/m2 on day 1) as first-line treatment, given every 3weeks, totaling eight cycles. The primary end point was to prove the noninferiority of XELOX to GEMOX in terms of 6-month progression-free survival (PFS) rate.
In total, 114 patients randomly received GEMOX and 108 randomly received XELOX. The median PFS was 5.3months for the GEMOX group and 5.8months for the XELOX group. The 6-month PFS rate was 44.5% for the GEMOX group and 46.7% for the XELOX group. The 95% confidence interval of the 6-month PFS rate difference between both groups was −12% to 16%, meeting the criteria for noninferiority of XELOX to GEMOX. There was no difference in objective response (P=0.171) and median overall survival (P=0.131) between both groups. The most common grade three to four adverse events were neutropenia and thrombocytopenia. No patient died of treatment-related causes. The XELOX group had significantly lower frequencies of hospital visits than the GEMOX group (P<0.001).
XELOX showed significant noninferiority to GEMOX in terms of 6-month PFS rate. Thus, XELOX could be an alternative first-line treatment of BCTs.
This study was registered in ClinicalTrials.gov (number NCT01470443).
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