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Background Given the young age of patients with CNS WHO grade 2 and 3 oligodendrogliomas and the relevant risk of neurocognitive, functional, and quality-of-life impairment with the current aggressive standard of care treatment, chemoradiation with PCV, of the tumour located in the brain optimizing care is the major challenge. Methods NOA-18 aims at improving qualified overall survival (qOS) for adult patients with CNS WHO grade 2 and 3 oligodendrogliomas by randomizing between standard chemoradiation with up to six six-weekly cycles with PCV and six six-weekly cycles with lomustine and temozolomide (CETEG) ( n  = 182 patients per group accrued over 4 years) thereby delaying radiotherapy and adding the chemoradiotherapy concept at progression after initial radiation-free chemotherapy, allowing for effective salvage treatment and delaying potentially deleterious side effects. QOS represents a new concept and is defined as OS without functional and/or cognitive and/or quality of life deterioration regardless of whether tumour progression or toxicity is the main cause. The primary objective is to show superiority of an initial CETEG treatment followed by partial brain radiotherapy (RT) plus PCV (RT-PCV) at progression over partial brain radiotherapy (RT) followed by procarbazine, lomustine, and vincristine (PCV) chemotherapy (RT-PCV) and best investigators choice (BIC) at progression for sustained qOS. An event concerning a sustained qOS is then defined as a functional and/or cognitive and/or quality of life deterioration after completion of primary therapy on two consecutive study visits with an interval of 3 months, tolerating a deviation of at most 1 month. Assessments are done with a 3-monthly MRI, assessment of the NANO scale, HRQoL, and KPS, and annual cognitive testing. Secondary objectives are evaluation and comparison of the two groups regarding secondary endpoints (short-term qOS, PFS, OS, complete and partial response rate). The trial is planned to be conducted at a minimum of 18 NOA study sites in Germany. Discussion qOS represents a new concept. The present NOA trial aims at showing the superiority of CETEG plus RT-PCV over RT-PCV plus BIC as determined at the level of OS without sustained functional deterioration for all patients with oligodendroglioma diagnosed according to the most recent WHO classification. Trial registration Clinicaltrials.gov NCT05331521 . EudraCT 2018–005027-16.

Due to advances in sequencing technology, somatically mutated cancer antigens, or neoantigens, are now readily identifiable and have become compelling targets for immunotherapy. In particular, neoantigen-targeted vaccines have shown promise in several pre-clinical and clinical studies. However, to date, neoantigen-targeted vaccine studies have involved tumors with exceptionally high mutation burdens. It remains unclear whether neoantigen-targeted vaccines will be broadly applicable to cancers with intermediate to low mutation burdens, such as ovarian cancer. To address this, we assessed whether a derivative of the murine ovarian tumor model ID8 could be targeted with neoantigen vaccines. We performed whole exome and transcriptome sequencing on ID8-G7 cells. We identified 92 somatic mutations, 39 of which were transcribed, missense mutations. For the 17 top predicted MHC class I binding mutations, we immunized mice subcutaneously with synthetic long peptide vaccines encoding the relevant mutation. Seven of 17 vaccines induced robust mutation-specific CD4 and/or CD8 T cell responses. However, none of the vaccines prolonged survival of tumor-bearing mice in either the prophylactic or therapeutic setting. Moreover, none of the neoantigen-specific T cell lines recognized ID8-G7 tumor cells in vitro, indicating that the corresponding mutations did not give rise to bonafide MHC-presented epitopes. Additionally, bioinformatic analysis of The Cancer Genome Atlas data revealed that only 12% (26/220) of HGSC cases had a ≥90% likelihood of harboring at least one authentic, naturally processed and presented neoantigen versus 51% (80/158) of lung cancers. Our findings highlight the limitations of applying neoantigen-targeted vaccines to tumor types with intermediate/low mutation burdens.

This study utilizes multiple decades of daily streamflow data gathered in four major watersheds in western Washington to determine the meteorological conditions most likely to cause flooding in those watersheds. Two are located in the Olympic Mountains and the other two in the western Cascades; and each has uniquely different topographic characteristics. The flood analysis is based on the maximum daily flow observed during each water year (WY) at each site [i.e., the annual peak daily flow (APDF)], with an initial emphasis on the 12 most recent water years between WY1998 and 2009, and then focusing on a 30-year interval between WY1980 and 2009. The shorter time period coincides with relatively complete passive microwave satellite coverage of integrated water vapor (IWV) over the Pacific basin. The combination of IWV imagery and streamflow data highlights a close link between landfalling atmospheric rivers (ARs) and APDFs (i.e., 46 of the 48 APDFs occurred with landfalling ARs). To complement this approach, the three-decade time series of APDFs, which correspond to the availability of the North American Regional Reanalysis (NARR) dataset, are examined. The APDFs occur most often, and are typically largest in magnitude, from November to January. The NARR is used to assess the composite meteorological conditions associated with the 10 largest APDFs at each site during this 30-year period. Heavy precipitation fell during the top 10 APDFs, and anomalously high composite NARR melting levels averaged ~1.9 km MSL, which is primarily above the four basins of interest. Hence, on average, mostly rain rather than snow fell within these basins, leading to enhanced runoff. The flooding on the four watersheds shared common meteorological attributes, including the presence of land-falling ARs with anomalous warmth, strong low-level water vapor fluxes, and weak static stability. There were also key differences that modulated the orographic control of precipitation. Notably, two watersheds experienced their top 10 APDFs when the low-level flow was southwesterly, while the other two basins had their largest APDFs with west–southwesterly flow. These differences arose because of the region’s complex topography, basin orientations, and related rain shadowing.

Ralph et al use a unique combination of airborne and satellite observations to characterize narrow regions of strong horizontal water vapor flux associated with polar cold fronts that occurred over the eastern North Pacific Ocean during the winter of 1997-1998. Observations of these \"atmospheric rivers\" are compared with past numerical modeling studies to confirm that such narrow features account for most of the instantaneous meridional water vapor transport at midlatitudes.

The ability of five operational ensemble forecast systems to accurately represent and predict atmospheric rivers (ARs) is evaluated as a function of lead time out to 10 days over the northeastern Pacific Ocean and west coast of North America. The study employs the recently developed Atmospheric River Detection Tool to compare the distinctive signature of ARs in integrated water vapor (IWV) fields from model forecasts and corresponding satellite-derived observations. The model forecast characteristics evaluated include the prediction of occurrence of ARs, the width of the IWV signature of ARs, their core strength as represented by the IWV content along the AR axis, and the occurrence and location of AR landfall. Analysis of three cool seasons shows that while the overall occurrence of ARs is well forecast out to a 10-day lead, forecasts of landfall occurrence are poorer, and skill degrades with increasing lead time. Average errors in the position of landfall are significant, increasing to over 800 km at 10-day lead time. Also, there is a 1°–2° southward position bias at 7-day lead time. The forecast IWV content along the AR axis possesses a slight moist bias averaged over the entire AR but little bias near landfall. The IWV biases are nearly independent of forecast lead time. Model spatial resolution is a factor in forecast skill and model differences are greatest for forecasts of AR width. This width error is greatest for coarser-resolution models that have positive width biases that increase with forecast lead time.

The pre-cold-frontal low-level jet within oceanic extratropical cyclones represents the lower-tropospheric component of a deeper corridor of concentrated water vapor transport in the cyclone warm sector. These corridors are referred to as atmospheric rivers (ARs) because they are narrow relative to their length scale and are responsible for most of the poleward water vapor transport at midlatitudes. This paper investigates landfalling ARs along adjacent north- and south-coast regions of western North America. Special Sensor Microwave Imager (SSM/I) satellite observations of long, narrow plumes of enhanced integrated water vapor (IWV) were used to detect ARs just offshore over the eastern Pacific from 1997 to 2005. The north coast experienced 301 AR days, while the south coast had only 115. Most ARs occurred during the warm season in the north and cool season in the south, despite the fact that the cool season is climatologically wettest for both regions. Composite SSM/I IWV analyses showed landfalling wintertime ARs extending northeastward from the tropical eastern Pacific, whereas the summertime composites were zonally oriented and, thus, did not originate from this region of the tropics. Companion SSM/I composites of daily rainfall showed significant orographic enhancement during the landfall of winter (but not summer) ARs. The NCEP–NCAR global reanalysis dataset and regional precipitation networks were used to assess composite synoptic characteristics and overland impacts of landfalling ARs. The ARs possess strong vertically integrated horizontal water vapor fluxes that, on average, impinge on the West Coast in the pre-cold-frontal environment in winter and post-cold-frontal environment in summer. Even though the IWV in the ARs is greater in summer, the vapor flux is stronger in winter due to much stronger flows associated with more intense storms. The landfall of ARs in winter and north-coast summer coincides with anomalous warmth, a trough offshore, and ridging over the Intermountain West, whereas the south-coast summer ARs coincide with relatively cold conditions and a near-coast trough. ARs have a much more profound impact on near-coast precipitation in winter than summer, because the terrain-normal vapor flux is stronger and the air more nearly saturated in winter. During winter, ARs produce roughly twice as much precipitation as all storms. In addition, wintertime ARs with the largest SSM/I IWV are tied to more intense storms with stronger flows and vapor fluxes, and more precipitation. ARs generally increase snow water equivalent (SWE) in autumn/winter and decrease SWE in spring. On average, wintertime SWE exhibits normal gains during north-coast AR storms and above-normal gains during the south-coast AR storms. The north-coast sites are mostly lower in altitude, where warmer-than-normal conditions more frequently yield rain. During those events when heavy rain from a warm AR storm falls on a preexisting snowpack, flooding is more likely to occur.

We evaluate the reliability and basic characteristics of observations of extreme DW events from current operational geostationary satellite sea surface temperature (SST) products through examination of three months of diurnal warming (DW) estimates derived by different methodologies from the Spinning Enhanced Visible and Infrared Imager on Meteosat-11, Advanced Himawari Imager on Himawari-8, and Advanced Baseline Imager on the Geostationary Operational Environmental Satellite (GOES)-16. This work primarily focuses on the following research questions: (1) Can these operational SST products accurately characterize extreme DW events? (2) What are the amplitudes and frequencies of these events? To answer these, we compute distributions of DW and DW exceedance and compare them amongst the different methods and geostationary sensors. Examination of the DW estimates demonstrates several challenges in accurately deriving distributions of the DW amplitude, particularly associated with estimating the “foundation” temperature and uncertainties in cloud screening. Overall, the results suggest that current geostationary sensors can reliably assess extreme DW, but the estimates are sensitive to the computational methods applied. We thus suggest careful processing/screening of the SST retrievals. We find a value of 3 K, corresponding to the 99th percentile, provides a potential practical threshold for extreme warming, but events of at least 6 K were reliably observed. Warming in excess of 6 K occurred somewhere an average of 47% of the time, and its probability at a given location was of O(10−6).

There is a lack of evidence regarding how patients with malignant brain tumor and their relatives experience participation in neurooncological clinical trials. Similarly, insights from the perspective of trial staff caring for this group of patients are missing. This study aims to investigate patient, relative and trial staff experiences regarding participation in clinical neurooncological trials. Within a qualitative exploratory study, 29 semi-structured interviews with brain tumor patients, relatives and trial staff were conducted and analyzed using reflexive thematic analysis (RTA) by Braun and Clarke. A patient researcher and patient council were involved in data analysis and interpretation. Four themes were developed reflecting significant aspects of the trial experience: 1. \"It all revolves around hope\"; 2. \"Trial participation: experiencing unique medical care\"; 3. \"Everyone's roles are changing\"; 4. \"Communication as a possible area of conflict\". Experiencing trial participation and general medical treatment were found to be interconnected to such a degree that they were often not meaningfully distinguished by patients and relatives. In addition to assessing traditional endpoints for patient outcomes, we recommend increased emphasis on investigating the impact of the \"soft\" components constituting trial participation. Due to the interconnectedness of medical treatment and trial participation, we recommend further investigation in comparison to experiences in regular care. A deeper understanding of trial participation is needed to inform improvements for patient experiences and staff satisfaction alongside medical and scientific progress.

N-Acyl-homoserine lactones (AHL) play a major role in the communication of Gram-negative bacteria. They influence processes such as biofilm formation, swarming motility, and bioluminescence in the aquatic environment. A comprehensive analytical method was developed to elucidate the “chemical communication” in pure bacterial cultures as well as in the aquatic environment and engineered environments with biofilms. Due to the high diversity of AHLs and their low concentrations in water, a sensitive and selective LC-ESI-MS/MS method combined with solid-phase extraction was developed for 34 AHLs, optimized and validated to quantify AHLs in bacterial conditioned medium, river water, and treated wastewater. Furthermore, the developed method was optimized in terms of enrichment volume, internal standards, limits of detection, and limits of quantification in several matrices. An unanticipated variety of AHLs was detected in the culture media of Pseudomonas aeruginosa (in total 8 AHLs), Phaeobacter gallaeciensis (in total 6 AHLs), and Methylobacterium mesophilicum (in total 15 AHLs), which to our knowledge have not been described for these bacterial cultures so far. Furthermore, AHLs were detected in river water (in total 5 AHLs) and treated wastewater (in total 3 AHLs). Several detected AHLs were quantified (in total 24) using a standard addition method up to 7.3±1.0 µg/L 3-Oxo-C12-AHL (culture media of P. aeruginosa).

Earlier studies of spatial variability in sea surface temperature (SST) using ship-based radiometric data suggested that variability at scales smaller than 1 km is significant and affects the perceived uncertainty of satellite-derived SSTs. Here, we compare data from the Ball Experimental Sea Surface Temperature (BESST) thermal infrared radiometer flown over the Arctic Ocean against coincident Moderate Resolution Imaging Spectroradiometer (MODIS) measurements to assess the spatial variability of skin SSTs within 1-km pixels. By taking the standard deviation, σ, of the BESST measurements within individual MODIS pixels, we show that significant spatial variability of the skin temperature exists. The distribution of the surface variability measured by BESST shows a peak value of O(0.1) K, with 95% of the pixels showing σ < 0.45 K. Significantly, high-variability pixels are located at density fronts in the marginal ice zone, which are a primary source of submesoscale intermittency near the surface. SST wavenumber spectra indicate a spectral slope of −2, which is consistent with the presence of submesoscale processes at the ocean surface. Furthermore, the BESST wavenumber spectra not only match the energy distribution of MODIS SST spectra at the satellite-resolved wavelengths, they also span the spectral slope of −2 by ~3 decades, from wavelengths of 8 km to <0.08 km.