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BACKGROUND: Recurrence after resection of metastatic sarcoma is common. The gangliosides GM2, GD2 and GD3 are strongly expressed across sarcoma subtypes. We hypothesised that generation of anti-ganglioside antibodies would control micrometastases and improve outcomes in sarcoma patients who were disease-free after metastasectomy. METHODS: We conducted a randomised phase II trial of the immunological adjuvant OPT-821 with a KLH-conjugated ganglioside vaccine targeting GM2, GD2 and GD3, versus OPT-821 alone in patients with metastatic sarcoma following complete metastasectomy. Patients received 10 subcutaneous injections at Weeks 1, 2, 3, 8, 16, 28, 40, 52, 68 and 84 and were followed for evidence of recurrent disease. The primary end-point was relapse-free survival. Secondary end-points included overall survival and serologic response. RESULTS: A total of 136 patients were randomised, 68 to each arm. The mean age was 51.2, 52.2% were male, 90.4% had relapsed disease, 86.8% had high-grade tumours and 14% had ≥4 metastases resected. Histologies included leiomyosarcoma (33%), spindle cell sarcoma (14%), undifferentiated pleomorphic sarcoma (13%), osteosarcoma (10%), synovial sarcoma (9%), liposarcoma (9%) and others (12%). Most adverse events were Grade ≤2 (83.8% and 70.6% in the vaccine and adjuvant arms, respectively). The most common (≥20% of patients) were injection site reaction (89.7%), fatigue (44.1%) and pyrexia (27.9%) on the vaccine arm, and injection site reaction (69.1%) on the adjuvant only arm. The 1-year relapse-free survival rate (34.5% and 34.8% in the vaccine and OPT-821 monotherapy arm, respectively) did not differ between arms (P = 0.725). One-year overall survival rates were 93.1% and 91.5% in the vaccine and OPT-821 monotherapy arm, respectively (P = 0.578). Serologic responses at week 9 were more frequent on the vaccine arm (96.5% of patients) than in the adjuvant arm (32.8%), and the difference between groups was durable. CONCLUSIONS: A sustained serologic response to vaccination was induced with the vaccine, but no difference in recurrence-free or overall survival was observed between treatment arms. CLINICALTRIALS: gov identifier: NCT01141491.

We analyze tropical ozone (O3) and carbon monoxide (CO) distributions in the upper troposphere (UT) and their temporal changes for 2005–2020 using Aura Microwave Limb Sounder (MLS) observations and chemistry climate models. The models are the Whole Atmosphere Community Climate Model (WACCM6) and two variants of the Community Atmosphere Model with Chemistry (CAM-chem), each variant using different anthropogenic emissions. Upper tropospheric trends and variability diagnostics are obtained from multiple linear regression analyses. We compare the model and MLS annual climatologies, focusing on 147 and 215 hPa pressure levels; climatological values generally fall within 10–20 % of each other, with both positive and negative differences for O3, and with models generally underestimating observed CO. In the northern hemisphere tropics, we find significantly poorer model fits to the observed phasing of CO seasonal changes at 215 hPa than at 147 hPa. This discrepancy is much smaller for the comparison of modeled and Measurements of Pollution in the Troposphere (MOPITT) V9J CO columns. We also find that the sensitivity of UT CO to El Niño / Southern Oscillation (ENSO) is positive at all tropical longitudes, in contrast to the dipolar longitudinal structure that exists for UT O3 ENSO sensitivity. MLS O3 has a zonal mean trend at 20° S–20° N of +0.39 ± 0.28 % yr-1; CAM-chem and WACCM have similar trends, though the WACCM trend is somewhat smaller. Our analyses for specific latitude/longitude bins yield positive trends up to 1.4 % yr-1 over Indonesia and East of that region, as well as over tropical Africa and the tropical Atlantic. We find broad similarities between the mapped MLS-derived UT O3 trends and corresponding mapped trends of tropospheric column ozone. Positive tropical UT mapped O3 trends are generally captured by the models, although in a more muted way. There is room for improvements in modeled tropical UT CO trends. Indeed, the MLS zonal mean CO trend is -0.25 ± 0.30 % yr-1, whereas the corresponding modeled CO trends are near zero (0.0 ± 0.14 % yr-1) when the anthropogenic emissions used in CAM-chem and WACCM are taken from Community Emissions Data System (CEDS) version 2. The non-CEDS version of CAM-chem yields CO UT trends of 0.22 ± 0.19 % yr-1, in contrast to the negative MLS CO trends throughout the tropics. The negative MLS tropical UT CO trends for 2005–2020 agree with (but tend to be smaller in magnitude than) previously published total column CO trends. Decreasing CO emissions from anthropogenic and biomass burning sources have previously been suggested as the main causes of tropospheric CO decreases, although significant regional emission trend variations exist. [ABSTRACT FROM AUTHOR]

We report the successful use of RADPLAT to treat a patient with an unresectable T4N0 sinonasal undifferentiated carcinoma. This patient received 4 cycles of weekly intra-arterial cisplatin together with thiosulfate infusion with concurrent radiation therapy. Radiation therapy was given in 28 daily fractions to 54 Gy using intensity-modulated radiation therapy followed by a hypofractionated stereotactic boost of 3 fractions to 13 Gy to a total dose of 67 Gy in 31 fractions to the nasal sinus and bilateral neck. Intra-arterial cisplatin was administered using a bilateral approach due to the midline site of this tumor. Within days of the first intra-arterial cisplatin, there was an obvious decrease in tumor size. She has been followed with magnetic resonance imaging and positron emission tomography, and remains disease-free 47 mo post-treatment. Centers with expertise in intra-arterial chemotherapy could consider the RADPLAT approach for patients with unresectable sinonasal undifferentiated carcinoma.

We use Aura Microwave Limb Sounder (MLS) trace gas measurements to investigate whether water vapor (H2O) injected into the stratosphere by the Hunga Tonga‐Hunga Ha'apai (HTHH) eruption affected the 2022 Antarctic stratospheric vortex. Other MLS‐measured long‐lived species are used to distinguish high HTHH H2O from that descending in the vortex from the upper‐stratospheric H2O peak. HTHH H2O reached high southern latitudes in June–July but was effectively excluded from the vortex by the strong transport barrier at its edge. MLS H2O, nitric acid, chlorine species, and ozone within the 2022 Antarctic polar vortex were near average; the vortex was large, strong, and long‐lived, but not exceptionally so. There is thus no clear evidence of HTHH influence on the 2022 Antarctic vortex or its composition. Substantial impacts on the stratospheric polar vortices are expected in succeeding years since the H2O injected by HTHH has spread globally. Plain Language Summary: The 2022 Hunga Tonga‐Hunga Ha'apai eruption injected vast amounts of water vapor into the stratosphere. Concern arose that this excess water vapor could affect the 2022 Antarctic stratospheric polar vortex and ozone hole: Water vapor plays a crucial role in forming polar stratospheric clouds, which provide surfaces upon which chemical reactions that destroy ozone take place. Enhanced water vapor also affects temperatures, which in turn affect the powerful winds defining the polar vortex boundary. Antarctic polar vortex development began in April–May; by June the intense vortex‐edge winds presented a formidable obstacle to transport. Satellite trace‐gas measurements show that when water vapor from the Hunga Tonga eruption reached the vortex edge in June, it faced an impenetrable barrier and "besieged" the vortex, building up exceptionally strong water vapor gradients across the vortex edge. Water vapor, ozone, and chemicals involved in ozone destruction remained near historical average levels within the vortex through spring 2022. Because excess water vapor spread throughout the south polar regions after vortex breakup, much larger effects on the Antarctic vortex and chemical processing within it are expected in 2023 and beyond, when high water vapor will be entrained into the vortex as it develops. Key Points: Microwave Limb Sounder (MLS) trace gas data show that the Hunga Tonga‐Hunga Ha'apai H2O plume was effectively excluded from the 2022 Antarctic polar vortexAntarctic lower stratospheric vortex strength, size, and longevity were among the largest on record, but within the range of previous yearsAntarctic chemical ozone loss in 2022 was unexceptional, with MLS ozone and related trace gases observed to be near average [ABSTRACT FROM AUTHOR]

A new algorithm to derive near-real-time (NRT) data products for the Aura Microwave Limb Sounder (MLS) is presented. The old approach was based on a simplified optimal estimation retrieval algorithm (OE-NRT) to reduce computational demands and latency. This paper describes the setup, training, and evaluation of a redesigned approach based on artificial neural networks (ANN-NRT), which is trained on >17 years of MLS radiance observations and composition profile retrievals. Comparisons of joint histograms and performance metrics derived between the two NRT results and the operational MLS products demonstrate a noticeable statistical improvement from ANN-NRT. This new approach results in higher correlation coefficients, in addition to lower root-mean-square deviations and biases at almost all retrieval levels compared to OE-NRT. The exceptions are pressure levels with concentrations close to 0 ppbv (parts per billion by volume), where the ANN models fail to establish a functional relationship and tend to predict 0. Depending on the application, this behavior might be advantageous. While the developed models can take advantage of the extended MLS data record, this study demonstrates that training ANN-NRT on just a single year of MLS observations is sufficient to improve upon OE-NRT. This confirms the potential of applying machine learning to the NRT efforts of other current and future mission concepts. [ABSTRACT FROM AUTHOR]