Experimental study of radiative shocks at PALS facility

We report on the investigation of strong radiative shocks generated with the high energy, sub-nanosecond iodine laser at PALS. These shock waves are characterized by a developed radiative precursor and their dynamics is analyzed over long time scales (~50 ns), approaching a quasi-stationary limit. We present the first preliminary results on the rear side XUV spectroscopy. These studies are relevant to the understanding of the spectroscopic signatures of accretion shocks in Classical T Tauri Stars.Comment: 21 pages, 1 table, 7 figure

The impact of tumor metabolic activity assessed by 18^{18}F-FET amino acid PET imaging in particle radiotherapy of high-grade glioma patients

Selective uptake of (18)F-fluoro-ethyl-tyrosine ($^{18}$F-FET) is used in high-grade glioma (HGG) to assess tumor metabolic activity via positron emission tomography (PET). We aim to investigate its value for target volume definition, as a prognosticator, and associations with whole-blood transcriptome liquid biopsy (WBT lbx) for which we recently reported feasibility to mirror tumor characteristics and response to particle irradiation in recurrent HGG (rHGG)

Genetic polymorphisms of the RAS-cytokine pathway and chronic kidney disease

Chronic kidney disease (CKD) in children is irreversible. It is associated with renal failure progression and atherosclerotic cardiovascular (CV) abnormalities. Nearly 60% of children with CKD are affected since birth with congenital or inherited kidney disorders. Preliminary evidence primarily from adult CKD studies indicates common genetic risk factors for CKD and atherosclerotic CV disease. Although multiple physiologic pathways share common genes for CKD and CV disease, substantial evidence supports our attention to the renin angiotensin system (RAS) and the interlinked inflammatory cascade because they modulate the progressions of renal and CV disease. Gene polymorphisms in the RAS-cytokine pathway, through altered gene expression of inflammatory cytokines, are potential factors that modulate the rate of CKD progression and CV abnormalities in patients with CKD. For studying such hypotheses, the cooperative efforts among scientific groups and the availability of robust and affordable technologies to genotype thousands of single nucleotide polymorphisms (SNPs) across the genome make genome-wide association studies an attractive paradigm for studying polygenic diseases such as CKD. Although attractive, such studies should be interpreted carefully, with a fundamental understanding of their potential weaknesses. Nevertheless, whole-genome association studies for diabetic nephropathy and future studies pertaining to other types of CKD will offer further insight for the development of targeted interventions to treat CKD and associated atherosclerotic CV abnormalities in the pediatric CKD population

MR Intensity Normalization Methods Impact Sequence Specific Radiomics Prognostic Model Performance in Primary and Recurrent High-Grade Glioma

Purpose: This study investigates the impact of different intensity normalization (IN) methods on the overall survival (OS) radiomics models’ performance of MR sequences in primary (pHGG) and recurrent high-grade glioma (rHGG). Methods: MR scans acquired before radiotherapy were retrieved from two independent cohorts (rHGG C1: 197, pHGG C2: 141) from multiple scanners (15, 14). The sequences are T1 weighted (w), contrast-enhanced T1w (T1wce), T2w, and T2w-FLAIR. Sequence-specific significant features (SF) associated with OS, extracted from the tumour volume, were derived after applying 15 different IN methods. Survival analyses were conducted using Cox proportional hazard (CPH) and Poisson regression (POI) models. A ranking score was assigned based on the 10-fold cross-validated (CV) concordance index (C-I), mean square error (MSE), and the Akaike information criterion (AICs), to evaluate the methods’ performance. Results: Scatter plots of the 10-CV C-I and MSE against the AIC showed an impact on the survival predictions between the IN methods and MR sequences (C1/C2 C-I range: 0.62–0.71/0.61–0.72, MSE range: 0.20–0.42/0.13–0.22). White stripe showed stable results for T1wce (C1/C2 C-I: 0.71/0.65, MSE: 0.21/0.14). Combat (0.68/0.62, 0.22/0.15) and histogram matching (HM, 0.67/0.64, 0.22/0.15) showed consistent prediction results for T2w models. They were also the top-performing methods for T1w in C2 (Combat: 0.67, 0.13; HM: 0.67, 0.13); however, only HM achieved high predictions in C1 (0.66, 0.22). After eliminating IN impacted SF using Spearman’s rank-order correlation coefficient, a mean decrease in the C-I and MSE of 0.05 and 0.03 was observed in all four sequences. Conclusion: The IN method impacted the predictive power of survival models; thus, performance is sequence-dependent

Emission rates of C8-C15 VOCs from seaweed and sand in the inter-tidal zone at Mace Head, Ireland.

Emission fluxes for a range of C8–C15 volatile organic compounds (VOCs) were determined from the seaweed Fucus spiralis (spiral wrack) and an adjacent sand surface during low tide on the coastline of Mace Head, Ireland. These two surface types, assessed using dynamic flux chamber systems, are typical of the Mace Head inter-tidal zone. A range of n-alkanes and oxygenates were routinely identified in the measurement of chamber air. Examination of the odd/even n-alkane ratios and use of the carbon preference index (CPI) suggested a biogenic source for these compounds (CPIs >2 in for all samples). Fluxes of n-pentadecane, the most predominant n-alkane, ranged from 0.2 to 5.1 μg m−2 h−1 (0.9–24 nmol m−2 h−1), while oxygenates such as nonanal and decanal had fluxes ranging from <0.1 to 4.4 μg m−2 h−1 (<0.1–31 nmol m−2 h−1) and <0.1 to 4.6 μg m−2 h−1 (<0.1–30 nmol m−2 h−1), respectively. Seaweed emission rates for n-pentadecane were correlated with photosynthetically active radiation (PAR) (rs=0.94) while emissions from sand showed correlation with temperature (rs=0.85). This suggests a possible biochemical route controlling the release of n-pentadecane from spiral wrack, and temperature-driven volatilisation from sand. Volatilisation from residual seawater trapped in the sand may explain the comparable flux of both n-alkanes and oxygenates from this surface. Unlike the n-alkanes, oxygenate fluxes from sand correlate with PAR, suggesting a photodependent production from organic carbon residues present in seawater. Comparison with previous flux estimates from coastal seawater indicates that the two source types (Fucus spiralis and bare sand) are significant but not dominant sources of these VOCs

A rigorous inter-comparison of ground-level ozone predictions

Novel statistical approaches to prediction have recently been shown to perform well in several scientific fields but have not, until now, been comprehensively evaluated for predicting air pollution. In this paper we report on a model inter-comparison exercise in which 15 different statistical techniques for ozone forecasting were applied to ten data sets representing different meteorological and emission conditions throughout Europe. We also attempt to compare the performance of the statistical techniques with a deterministic chemical trajectory model. Likewise, our exercise includes comparisons of sites, performance indices, forecasting horizons, etc. The comparative evaluation of forecasting performance (benchmarking) produced 1340 yearly time series of daily predictions and the results are described in terms of predefined performance indices. Through analysing associations between the performance indices, we found that the success index is of outstanding significance. For models that are excellent in predicting threshold exceedances and have a high success index, we also observe high performance in the overall goodness of fit. The 8-h average ozone concentration forecast accuracy was found to be superior to the 1-h mean ozone concentration forecast, which makes the former very significant for operational forecasting. The best forecasts were achieved for sites located in rural and suburban areas in Central Europe unaffected by extreme emissions (e.g. from industries). Our results demonstrate that a particular technique is often excellent in some respects but poor in others. For most situations, we recommend neural network and generalised additive models as the best compromise, as these can handle nonlinear associations and can be easily adapted to site specific conditions. In contrast, nonlinear modelling of the dynamical development of univariate ozone time-series was not profitable

Image_3_The impact of tumor metabolic activity assessed by 18F-FET amino acid PET imaging in particle radiotherapy of high-grade glioma patients.jpeg

BackgroundSelective uptake of (18)F-fluoro-ethyl-tyrosine (18F-FET) is used in high-grade glioma (HGG) to assess tumor metabolic activity via positron emission tomography (PET). We aim to investigate its value for target volume definition, as a prognosticator, and associations with whole-blood transcriptome liquid biopsy (WBT lbx) for which we recently reported feasibility to mirror tumor characteristics and response to particle irradiation in recurrent HGG (rHGG).Methods18F-FET-PET data from n = 43 patients with primary glioblastoma (pGBM) and n = 33 patients with rHGG were assessed. pGBM patients were irradiated with photons and sequential proton/carbon boost, and rHGG patients were treated with carbon re-irradiation (CIR). WBT (Illumina HumanHT-12 Expression BeadChips) lbx was available for n = 9 patients from the rHGG cohort. PET isocontours (40%–70% SUVmax, 10% steps) and MRI-based treatment volumes (MRIvol) were compared using the conformity index (CI) (pGBM, n = 16; rHGG, n = 27). Associations with WBT lbx data were tested on gene expression level and inferred pathways activity scores (PROGENy) and from transcriptome estimated cell fractions (CIBERSORT, xCell).ResultsIn pGBM, median SUVmax was higher in PET acquired pre-radiotherapy (4.1, range (R) 1.5–7.8; n = 20) vs. during radiotherapy (3.3, R 1.5–5.7, n = 23; p = 0.03) and in non-resected (4.7, R 2.9–7.9; n = 11) vs. resected tumors (3.3, R 1.5–7.8, n = 32; p = 0.01). In rHGG, a trend toward higher SUVmax values in grade IV tumors was observed (p = 0.13). Median MRIvol was 32.34 (R 8.75–108.77) cm3 in pGBM (n = 16) and 20.77 (R 0.63–128.44) cm3 in rHGG patients (n = 27). The highest median CI was observed for 40% (pGBM, 0.31) and 50% (rHGG, 0.43, all tumors) isodose, with 70% (40%) isodose in grade III (IV) rHGG tumors (median CI, 0.38 and 0.49). High SUVmax was linked to shorter survival in pGBM (>3.3, p = 0.001, OR 6.0 [2.1–17.4]) and rHGG (>2.8, p = 0.02, OR 4.1 [1.2–13.9]). SUVmax showed associations with inferred monocyte fractions, hypoxia, and TGFbeta pathway activity and links to immune checkpoint gene expression from WBT lbx.ConclusionThe benefits of 18F-FET-PET imaging on gross tumor volume (GTV) definition for particle radiotherapy warrant further evaluation. SUVmax might assist in prognostic stratification of HGG patients for particle radiotherapy, highlights heterogeneity in rHGG, and is positively associated with unfavorable signatures in peripheral whole-blood transcriptomes.</p

Image_1_The impact of tumor metabolic activity assessed by 18F-FET amino acid PET imaging in particle radiotherapy of high-grade glioma patients.jpeg

BackgroundSelective uptake of (18)F-fluoro-ethyl-tyrosine (18F-FET) is used in high-grade glioma (HGG) to assess tumor metabolic activity via positron emission tomography (PET). We aim to investigate its value for target volume definition, as a prognosticator, and associations with whole-blood transcriptome liquid biopsy (WBT lbx) for which we recently reported feasibility to mirror tumor characteristics and response to particle irradiation in recurrent HGG (rHGG).Methods18F-FET-PET data from n = 43 patients with primary glioblastoma (pGBM) and n = 33 patients with rHGG were assessed. pGBM patients were irradiated with photons and sequential proton/carbon boost, and rHGG patients were treated with carbon re-irradiation (CIR). WBT (Illumina HumanHT-12 Expression BeadChips) lbx was available for n = 9 patients from the rHGG cohort. PET isocontours (40%–70% SUVmax, 10% steps) and MRI-based treatment volumes (MRIvol) were compared using the conformity index (CI) (pGBM, n = 16; rHGG, n = 27). Associations with WBT lbx data were tested on gene expression level and inferred pathways activity scores (PROGENy) and from transcriptome estimated cell fractions (CIBERSORT, xCell).ResultsIn pGBM, median SUVmax was higher in PET acquired pre-radiotherapy (4.1, range (R) 1.5–7.8; n = 20) vs. during radiotherapy (3.3, R 1.5–5.7, n = 23; p = 0.03) and in non-resected (4.7, R 2.9–7.9; n = 11) vs. resected tumors (3.3, R 1.5–7.8, n = 32; p = 0.01). In rHGG, a trend toward higher SUVmax values in grade IV tumors was observed (p = 0.13). Median MRIvol was 32.34 (R 8.75–108.77) cm3 in pGBM (n = 16) and 20.77 (R 0.63–128.44) cm3 in rHGG patients (n = 27). The highest median CI was observed for 40% (pGBM, 0.31) and 50% (rHGG, 0.43, all tumors) isodose, with 70% (40%) isodose in grade III (IV) rHGG tumors (median CI, 0.38 and 0.49). High SUVmax was linked to shorter survival in pGBM (>3.3, p = 0.001, OR 6.0 [2.1–17.4]) and rHGG (>2.8, p = 0.02, OR 4.1 [1.2–13.9]). SUVmax showed associations with inferred monocyte fractions, hypoxia, and TGFbeta pathway activity and links to immune checkpoint gene expression from WBT lbx.ConclusionThe benefits of 18F-FET-PET imaging on gross tumor volume (GTV) definition for particle radiotherapy warrant further evaluation. SUVmax might assist in prognostic stratification of HGG patients for particle radiotherapy, highlights heterogeneity in rHGG, and is positively associated with unfavorable signatures in peripheral whole-blood transcriptomes.</p

Image_4_The impact of tumor metabolic activity assessed by 18F-FET amino acid PET imaging in particle radiotherapy of high-grade glioma patients.jpeg

BackgroundSelective uptake of (18)F-fluoro-ethyl-tyrosine (18F-FET) is used in high-grade glioma (HGG) to assess tumor metabolic activity via positron emission tomography (PET). We aim to investigate its value for target volume definition, as a prognosticator, and associations with whole-blood transcriptome liquid biopsy (WBT lbx) for which we recently reported feasibility to mirror tumor characteristics and response to particle irradiation in recurrent HGG (rHGG).Methods18F-FET-PET data from n = 43 patients with primary glioblastoma (pGBM) and n = 33 patients with rHGG were assessed. pGBM patients were irradiated with photons and sequential proton/carbon boost, and rHGG patients were treated with carbon re-irradiation (CIR). WBT (Illumina HumanHT-12 Expression BeadChips) lbx was available for n = 9 patients from the rHGG cohort. PET isocontours (40%–70% SUVmax, 10% steps) and MRI-based treatment volumes (MRIvol) were compared using the conformity index (CI) (pGBM, n = 16; rHGG, n = 27). Associations with WBT lbx data were tested on gene expression level and inferred pathways activity scores (PROGENy) and from transcriptome estimated cell fractions (CIBERSORT, xCell).ResultsIn pGBM, median SUVmax was higher in PET acquired pre-radiotherapy (4.1, range (R) 1.5–7.8; n = 20) vs. during radiotherapy (3.3, R 1.5–5.7, n = 23; p = 0.03) and in non-resected (4.7, R 2.9–7.9; n = 11) vs. resected tumors (3.3, R 1.5–7.8, n = 32; p = 0.01). In rHGG, a trend toward higher SUVmax values in grade IV tumors was observed (p = 0.13). Median MRIvol was 32.34 (R 8.75–108.77) cm3 in pGBM (n = 16) and 20.77 (R 0.63–128.44) cm3 in rHGG patients (n = 27). The highest median CI was observed for 40% (pGBM, 0.31) and 50% (rHGG, 0.43, all tumors) isodose, with 70% (40%) isodose in grade III (IV) rHGG tumors (median CI, 0.38 and 0.49). High SUVmax was linked to shorter survival in pGBM (>3.3, p = 0.001, OR 6.0 [2.1–17.4]) and rHGG (>2.8, p = 0.02, OR 4.1 [1.2–13.9]). SUVmax showed associations with inferred monocyte fractions, hypoxia, and TGFbeta pathway activity and links to immune checkpoint gene expression from WBT lbx.ConclusionThe benefits of 18F-FET-PET imaging on gross tumor volume (GTV) definition for particle radiotherapy warrant further evaluation. SUVmax might assist in prognostic stratification of HGG patients for particle radiotherapy, highlights heterogeneity in rHGG, and is positively associated with unfavorable signatures in peripheral whole-blood transcriptomes.</p

Table_1_The impact of tumor metabolic activity assessed by 18F-FET amino acid PET imaging in particle radiotherapy of high-grade glioma patients.docx

BackgroundSelective uptake of (18)F-fluoro-ethyl-tyrosine (18F-FET) is used in high-grade glioma (HGG) to assess tumor metabolic activity via positron emission tomography (PET). We aim to investigate its value for target volume definition, as a prognosticator, and associations with whole-blood transcriptome liquid biopsy (WBT lbx) for which we recently reported feasibility to mirror tumor characteristics and response to particle irradiation in recurrent HGG (rHGG).Methods18F-FET-PET data from n = 43 patients with primary glioblastoma (pGBM) and n = 33 patients with rHGG were assessed. pGBM patients were irradiated with photons and sequential proton/carbon boost, and rHGG patients were treated with carbon re-irradiation (CIR). WBT (Illumina HumanHT-12 Expression BeadChips) lbx was available for n = 9 patients from the rHGG cohort. PET isocontours (40%–70% SUVmax, 10% steps) and MRI-based treatment volumes (MRIvol) were compared using the conformity index (CI) (pGBM, n = 16; rHGG, n = 27). Associations with WBT lbx data were tested on gene expression level and inferred pathways activity scores (PROGENy) and from transcriptome estimated cell fractions (CIBERSORT, xCell).ResultsIn pGBM, median SUVmax was higher in PET acquired pre-radiotherapy (4.1, range (R) 1.5–7.8; n = 20) vs. during radiotherapy (3.3, R 1.5–5.7, n = 23; p = 0.03) and in non-resected (4.7, R 2.9–7.9; n = 11) vs. resected tumors (3.3, R 1.5–7.8, n = 32; p = 0.01). In rHGG, a trend toward higher SUVmax values in grade IV tumors was observed (p = 0.13). Median MRIvol was 32.34 (R 8.75–108.77) cm3 in pGBM (n = 16) and 20.77 (R 0.63–128.44) cm3 in rHGG patients (n = 27). The highest median CI was observed for 40% (pGBM, 0.31) and 50% (rHGG, 0.43, all tumors) isodose, with 70% (40%) isodose in grade III (IV) rHGG tumors (median CI, 0.38 and 0.49). High SUVmax was linked to shorter survival in pGBM (>3.3, p = 0.001, OR 6.0 [2.1–17.4]) and rHGG (>2.8, p = 0.02, OR 4.1 [1.2–13.9]). SUVmax showed associations with inferred monocyte fractions, hypoxia, and TGFbeta pathway activity and links to immune checkpoint gene expression from WBT lbx.ConclusionThe benefits of 18F-FET-PET imaging on gross tumor volume (GTV) definition for particle radiotherapy warrant further evaluation. SUVmax might assist in prognostic stratification of HGG patients for particle radiotherapy, highlights heterogeneity in rHGG, and is positively associated with unfavorable signatures in peripheral whole-blood transcriptomes.</p