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Background: Yttrium‐90 (90Y) positron emission tomography (PET)/computed tomography (CT) imaging is increasingly being used to perform tumor (T) and normal liver (NL) voxel dosimetry after 90Y‐radioembolization (90Y‐RE). Yet, the accuracy of in vivo 90Y‐PET/CT imaging, subject to motion blur and co‐registration inaccuracies, and 90Y‐PET/CT dose quantification, subject to availability of different voxel dosimetry algorithms, are not well understood. Purpose: The purpose of this study was to investigate the accuracy of 90Y‐PET/CT‐based activity estimates following 90Y‐RE and characterize differences between 90Y‐PET/CT‐based voxel dosimetry algorithms. Methods: Thirty‐five patients underwent 90Y‐PET/CT imaging after 90Y‐RE with TheraSphere. The net administered 90Y activity (Aadmin) was determined using a dose calibrator and pre‐ and post‐procedure exposure rate measurements. The summation of image‐based activity (Aimage) was extracted from perfused volume (PV) and 3D‐isotropically 2‐cm expanded PV contour (PV+2 cm). Absorbed doses were calculated using voxel S‐value (VSV), local deposition method (LDM), and LDM with known activity (LDMKA) dosimetry algorithms. Linear regression and Bland‐Altman analysis quantified the relationship between Aimage and Aadmin and between mean dose estimates (DLDM, DVSV, DLDM‐KA) for PV, T, and perfused NL volumes. Results: While Aadmin and Aimage in PV were highly correlated (R2 > 0.95), the mean bias ± standard error (SE) and (95% limits of agreement, LOA) was significantly non‐zero with −22.7 ± 4.7% (± 28.4%). In PV+2 cm, the mean bias ± SE (± LOA) decreased to 1.3 ± 3.4% (± 18.0%) consistent with zero mean error. DLDM and DVSV were highly correlated (R2 > 0.99) for all volumes of interest (VOIs) and the mean bias ± SE (± LOA) was 2.2 ± 0.2% (± 1.0%), 0.7 ± 0.4% (± 2.8%), and 3.2 ± 0.5% (± 2.8%) for PV, T, and NL, respectively. DLDM‐KA and DVSV were correlated with R2 = 0.86, 0.80, and 0.86 for PV, T, and NL, respectively. The mean bias ± SE (± LOA) between DLDM‐KA and DVSV was significantly non‐zero with −19.6 ± 5.1% (± 31.0%), −20.8 ± 4.4% (± 29.0%), and −18.1 ± 5.3% (± 31.1%) for PV, T, and NL, respectively. Conclusions: The summation of Aimage in PV was underestimated relative to Aadmin. Only by accounting for respiratory motion, limited spatial resolution, and PET/CT co‐registration errors through VOI expansion was Aimage, on average, equal to Aadmin. The differences between DLDM and DVSV were not clinically relevant, though DLDM‐KA was approximately 20% greater than DVSV. Given the high quantitative accuracy of dose calibrators and challenges associated with accurate 90Y‐PET/CT quantification, LDMKA is the preferred algorithm for accurate 90Y‐PET/CT‐based dosimetry following 90Y‐RE. [ABSTRACT FROM AUTHOR]

Background: Following yttrium‐90 radioembolization (90Y‐RE), 90Y‐PET/CT and 90Y‐SPECT/CT imaging provide the means to calculate the voxelized absorbed dose distribution. Given the widespread use of the two imaging modalities and lack of well‐established standardized dosimetry protocols for 90Y‐RE, there is a clinical need to systematically investigate and evaluate differences in the performance of voxel‐based dosimetry between 90Y‐PET/CT and 90Y‐SPECT/CT. Purpose: To quantitatively analyze and compare 90Y‐PET/CT and 90Y‐SPECT/CT‐based dosimetry following 90Y‐RE. Methods: 90Y‐PET/CT and 90Y‐SPECT/CT imaging was acquired for 35 patients following 90Y‐RE with TheraSphere for the treatment of unresectable hepatocellular carcinoma. Dosimetry was performed using the local deposition method with known activity and the mean dose (Dmean) was calculated for perfused liver volumes (PV), tumors (T), and perfused normal livers (NL). Additionally, the absorbed dose to x% of the volume (Dx, x ∈$ \in $ [5%, 10%, ..., 90%, 95%]) and the volume receiving y Gy (Vy, y ∈$ \in $ [10 Gy, 20 Gy, ..., 190 Gy, 200 Gy]) were calculated for T and NL, respectively. Dose metrics were compared using linear regression, Bland‐Altman analysis, and statistical testing. Results: Both 90Y‐SPECT/CT and 90Y‐PET/CT‐based tumor Dmean were strongly correlated (R2 ≥ 0.90) with Dx, excluding metrics on the extrema. Intra‐modality comparisons of various Dx and Vy metrics yielded statistically significant differences (ANOVA, p < 0.001) for both90Y‐PET/CT and 90Y‐SPECT/CT. Based on statistical testing, only Dx metrics separated by greater than 20%–30% coverage, and only Vy metrics separated by greater than 40–70 Gy, reported significant differences. For PV, there was a strong correlation (R2 ≥ 0.99) between Dmean derived separately from 90Y‐PET/CT and 90Y‐SPECT/CT imaging. The strength of the correlation was slightly reduced for T and NL with R2 = 0.91 and R2 = 0.95, respectively. For PV, the mean bias ± standard error (SE) and 95% limits of agreement (LOA) between Dmean from the two modalities was effectively zero with ‐0.8 ± 0.4% (± 2.5%). For T and NL, the mean bias ± SE (± LOA) was ‐14.5 ± 3.7% (± 24%) and 9.4 ± 4.7% (± 27%), respectively. Conclusion: The strong correlation between Dmean and Dx suggests information from multiple dose metrics (e.g., D70 and Dmean) is largely redundant when establishing dose‐response relationships in 90Y‐RE. Dmean is highly correlated between 90Y‐PET/CT and 90Y‐SPECT/CT‐based dosimetry, for all liver VOIs. Relative to 90Y‐SPECT/CT, 90Y‐PET/CT, on average, yielded higher Dmean to tumors (14%) and lower Dmean to perfused normal livers (9%). Absorbed dose differences for perfused liver volumes between 90Y‐SPECT/CT and 90Y‐PET/CT were negligible. [ABSTRACT FROM AUTHOR]

Wheat is used for making many food products due to its diverse quality profile among different wheat classes. Since laboratory analysis of these end-use quality traits is costly and time-consuming, genetic dissection of the traits is preferential. This study used a genome-wide association study (GWAS) of ten end-use quality traits, including kernel protein, flour protein, flour yield, softness equivalence, solvent's retention capacity, cookie diameter, and top-grain, in soft red winter wheat (SRWW) adapted to US southeast. The GWAS included 266 SRWW genotypes that were evaluated in two locations over two years (2020–2022). A total of 27,466 single nucleotide markers were used, and a total of 80 significant marker-trait associations were identified. There were 13 major-effect quantitative trait loci (QTLs) explaining >10% phenotypic variance, out of which, 12 were considered to be novel. Five of the major-effect QTLs were found to be stably expressed across multiple datasets, and four showed associations with multiple traits. Candidate genes were identified for eight of the major-effect QTLs, including genes associated with starch biosynthesis and nutritional homeostasis in plants. These findings increase genetic comprehension of these end-use quality traits and could potentially be used for improving the quality of SRWW. [ABSTRACT FROM AUTHOR]

A new 90Y SIR-Spheres delivery kit (SIROS D-vial and shield) has been introduced with a different physical form from the legacy V-Vial kit. Here, we establish the dose calibrator settings and exposure-rate–to–activity conversion factor to assay 90Y SIR-Spheres activity in the new SIROS kit. Methods: Eight D-vials with initial 90Y activities from 1.2 to 6.6 GBq within acrylic shields were assayed with dose calibrators and exposure-rate meters until activities decayed to approximately 0.1 GBq. The dose calibrator settings resulting in the lowest median activity errors and the best-fit slope of exposure rate versus activity were identified. Results: SIROS D-vial 90Y activity can be accurately and reliably estimated directly using setting 51 × 10 on both the CRC-15R and the CRC-55tR dose calibrators (errors within ±0.5%) and indirectly with an exposure-rate reading at 30 cm using conversion factor 0.664 ± 0.003 GBq/(mR/h) (R2 = 0.985). Conclusion: Dose calibrator settings and exposure-rate–to–activity conversion factor for 90Y activity assays with new SIROS kit should be updated from legacy V-Vial parameters to avoid an approximately 10% underestimation. [ABSTRACT FROM AUTHOR]

Agro‐morphological traits play a significant role in the adaptation of wheat to diverse agroecosystems. Genetic understanding of these traits is crucial to develop cultivars adapted to specific environments and maximize their productivity. This is a comprehensive genome‐wide association study (GWAS) of 230 diverse lines of soft red winter wheat for identifying quantitative trait loci (QTLs) related to eight key agro‐morphological traits. The diversity panel was evaluated in two locations for three consecutive years (2020–2023). A total of 150 significant marker–trait associations were detected, including 65 for three flag leaf traits, 35 for peduncle length, 33 for plant height, 16 for heading date, and one for plant vigor using 27,466 single nucleotide polymorphism (SNP) markers. Eleven high‐confidence major‐effect QTLs explaining greater than 10% phenotypic variance were detected, of which seven were stable, and one showed an association with plant height and peduncle length. QTLs possibly allelic for important dwarfing (Rht23) and vernalization (Vrn‐B1) genes were identified. Six QTLs, QFlw.uga‐1A, QPdl.uga‐1A, QFlw.uga‐2B.2, QPdl.uga‐5A, QPdl.uga‐7A, and QPht.uga‐7B, are presumed to be novel, and nearby candidate gene(s) were identified for all except QPdl.uga‐1A. The pyramiding of favorable alleles from major‐effect QTLs was found to have significant improvement in peduncle length (shortened by 5 cm), flag leaf width (increased by 0.18 cm), and plant height (shortened by 11 cm). This study has improved our genetic understanding of important agro‐morphological traits. These results, upon further validation, can be used in breeding for desirable plant architecture to improve wheat yield potential. Core Ideas: Genome‐wide association study (GWAS) was conducted using 230 wheat lines evaluated for eight agro‐morphological traits.One hundred fifty significant marker–trait associations were found using 27,466 single nucleotide polymorphism (SNP) markers.Eleven major‐effect quantitative trait loci (QTLs) including seven stable QTLs were identified.Six major‐effect QTLs were presumed to be novel, and candidate genes were identified for five of them.Pyramiding favorable alleles from these QTLs led to significant improvement in traits. [ABSTRACT FROM AUTHOR]

A new 90Y SIR-Spheres delivery kit (SIROS D-vial and shield) has been introduced with a different physical form from the legacy V-Vial kit. Here, we establish the dose calibrator settings and exposure-rate–to–activity conversion factor to assay 90Y SIR-Spheres activity in the new SIROS kit. Methods: Eight D-vials with initial 90Y activities from 1.2 to 6.6 GBq within acrylic shields were assayed with dose calibrators and exposure-rate meters until activities decayed to approximately 0.1 GBq. The dose calibrator settings resulting in the lowest median activity errors and the best-fit slope of exposure rate versus activity were identified. Results: SIROS D-vial 90Y activity can be accurately and reliably estimated directly using setting 51 × 10 on both the CRC-15R and the CRC-55tR dose calibrators (errors within ±0.5%) and indirectly with an exposure-rate reading at 30 cm using conversion factor 0.664 ± 0.003 GBq/(mR/h) (R2 = 0.985). Conclusion: Dose calibrator settings and exposure-rate–to–activity conversion factor for 90Y activity assays with new SIROS kit should be updated from legacy V-Vial parameters to avoid an approximately 10% underestimation. [ABSTRACT FROM AUTHOR]

Because of the importance of potassium efflux in inflammasome activation, we investigated the role of the two-pore potassium (K2P) channel TREK-1 in macrophage inflammasome activity. Using primary alveolar macrophages (AMs) and bone marrow-derived macrophages (BMDMs) from wild-type (wt) and TREK-1–/– mice, we measured responses to inflammasome priming [using lipopolysaccharide (LPS)] and activation (LPS + ATP). We measured IL-1β, caspase-1, and NLRP3 via ELISA and Western blot. A membrane-permeable potassium indicator was used to measure potassium efflux during ATP exposure, and a fluorescencebased assay was used to assess changes in membrane potential. Inflammasome activation induced by LPS + ATP increased IL-1β secretion in wt AMs, whereas activation was significantly reduced in TREK-1–/– AMs. Priming of BMDMs using LPS was not affected by either genetic deficiency or pharmacological inhibition of TREK-1 with Spadin. Cleavage of caspase-1 following LPS + ATP treatment was significantly reduced in TREK-1–/– BMDMs. The intracellular potassium concentration in LPS-primed wt BMDMs was significant[ly lower compared with TREK-1–/– BMDMs or wt BMDMs treated with Spadin. Conversely, activation of TREK-1 with BL1249 caused a decrease in intracellular potassium in wt BMDMs. Treatment of LPS-primed BMDMs with ATP caused a rapid reduction in intracellular potassium levels, with the largest change observed in TREK-1–/– BMDMs. Intracellular K+ changes were associated with changes in the plasma membrane potential (Em), as evidenced by a more depolarized Em in TREK-1–/– BMDMs compared with wt, and Em hyperpolarization upon TREK-1 channel opening with BL1249. These results suggest that TREK-1 is an important regulator of NLRP3 inflammasome activation in macrophages. NEW & NOTEWORTHY Because of the importance of potassium efflux in inflammasome activation, we investigated the role of the two-pore potassium (K2P) channel TREK-1 in macrophage inflammasome activity. Using primary alveolar macrophages and bone marrow-derived macrophages from wild-type and TREK-1–/– mice, we measured responses to inflammasome priming (using LPS) and activation (LPS + ATP). Our results suggest that TREK-1 is an important regulator of NLRP3 inflammasome activation in macrophages. [ABSTRACT FROM AUTHOR]

Background: The calculation of the net administered activity (Aadmin) in patients undergoing 90Y‐radioembolization is essential for dosimetry and radiation safety, yet current methods for measuring residual 90Y activity are often associated with high uncertainty. Therefore, an accurate, robust, and clinically viable method for the determination of Aadmin across approved 90Y microsphere devices is desirable. Purpose: We report on a novel method to determine Aadmin by leveraging the quantitative capabilities of SPECT/CT to measure 90Y‐emission in vivo from patients following 90Y‐radioembolization with glass or resin microspheres. Methods: 90Y‐SPECT/CT attenuation‐corrected count data from 147 sequential 90Y‐radioembolization patients was used for this analysis. Aadmin was calculated as part of routine clinical practice via the exposure rate differences between the initial 90Y‐vial and the 90Y‐residual jar. This served as our gold standard measure of Aadmin. Patient data for each microsphere device were separated into training and testing cohorts to first develop regression models and then to independently assess model performance. The training cohorts were divided into four groups: first, based on the microsphere device (glass or resin), and second, based on the SPECT volume used to calculate counts (the full SPECT field of view (FOV) or liver only (VOIliver)). Univariate linear regression models were generated for each group to predict Aadmin based on 90Y‐SPECT data from the training cohorts. Leave‐one‐out cross validation was implemented to estimate variability in model parameters. To assess performance, linear models derived from the training cohort were applied to 90Y‐SPECT data from the testing cohort. A comparison of the models between microspheres devices was also performed. Results: Linear models derived from the glass and resin training cohorts demonstrated a strong, positive correlation between 90Y‐SPECT image counts and Aadmin for VOIliver and FOV with R2 > 0.98 in all cases. In the glass training cohort, model accuracy (100%—absolute mean prediction error) and precision (95% prediction intervals of mean prediction error) were 99.0% and 15.4% for the VOIliver and 99.7% and 17.5% for the FOV models, respectively. In the resin training cohort, the corresponding values were 98.6% and 16.7% for VOIliver and > 99.9% and 11.4% for the FOV models, respectively. The application of these linear models to 90Y‐SPECT data from the testing cohort showed Aadmin prediction errors to have high accuracy and precision for both microsphere devices. For the glass testing cohort, accuracy (precision) was 96.9% (19.6%) and 98.8% (21.1%) for the VOIliver and FOV models, respectively. The corresponding values for the resin training cohort were 97.3% (26.2%) and 98.5% (25.7%) for the VOIliver and FOV models, respectively. The slope of the linear models between the two microsphere devices was observed to be significantly different with resin microspheres generating 48%–49% more SPECT counts for equivalent 90Y activity based on each device manufacturer's activity calibration process. Conclusion: 90Y‐SPECT image counts can reliably predict (accuracy > 95% and precision < 18%) Aadmin after 90Y‐radioembolization, with performance characteristics essentially equivalent for both glass and resin microspheres. There is a clear indication that activity calibrations are fundamentally different between the two microsphere devices. [ABSTRACT FROM AUTHOR]

The Hessian fly (HF) is an invasive insect that has caused millions of dollars in yield losses to southeastern US wheat farms. Genetic resistance is the most sustainable solution to control HF. However, emerging biotypes are quickly overcoming resistance genes in the southeast; therefore, identifying novel sources of resistance is critical. The resistant line "UGA 111729" and susceptible variety "AGS 2038" were crossbred to generate a population of 225 recombinant inbred lines. This population was phenotyped in the growth chamber (GC) during 2019 and 2021 and in field (F) trials in Georgia during the 2021–2022 growing seasons. Visual scoring was utilized in GC studies. The percentage of infested tillers and number of pupae/larvae per tiller, and infested tiller per sample were measured in studies from 2021 to 2022. Averaging across all traits, a major QTL on chromosome 3D explained 42.27% (GC) and 10.43% (F) phenotypic variance within 9.86 centimorgans (cM). SNP marker IWB65911 was associated with the quantitative trait locus (QTL) peak with logarithm of odds (LOD) values of 14.98 (F) and 62.22 (GC). IWB65911 colocalized with resistance gene H32. KASP marker validation verified that UGA 111729 and KS89WGRC06 express H32. IWB65911 may be used for marker-assisted selection. [ABSTRACT FROM AUTHOR]

Background: Current molecular breast imaging (MBI) images are limited to qualitative evaluation, not absolute measurement, of 99mTc uptake in benign and malignant breast tissues. Purpose: This work assesses the accuracy of previously‐published and newly‐proposed tumor and normal breast tissue 99mTc uptake MBI measurements using simulations of a commercial dual‐headed planar MBI system under typical clinical and acquisition protocols. Methods: Quantification techniques were tested in over 4000 simulated acquisitions of spherical and ellipsoid tumors with clinically relevant uptake conditions using a validated Monte Carlo application of the GE Discovery NM750b system. The evaluated techniques consisted of four tumor total activity methodologies (two single‐detector‐based and two geometric‐mean‐based), two tumor MBI volume methodologies (diameter‐based and ROI‐based), and two normal tissue activity concentration methodologies (single‐detector‐based and geometric‐mean‐based). The most accurate of these techniques were then used to estimate tumor activity concentrations and tumor to normal tissue relative activity concentrations (RC). Results: Single‐detector techniques for tumor total activity quantification achieved mean (standard deviation) relative errors of 0.2% (4.3%) and 1.6% (4.4%) when using the near and far detector images, respectively and were more accurate and precise than the measured 8.1% (5.8%) errors of a previously published geometric‐mean technique. Using these activity estimates and the true tumor volumes resulted in tumor activity concentration and RC errors within 10% of simulated values. The precision of tumor activity concentration and RC when using only MBI measurements were largely driven by the errors in estimating tumor MBI volume using planar images (± 30% inter‐quartile range). Conclusions: Planar MBI images were shown to accurately and reliably be used to estimate tumor total activities and normal tissue activity concentrations in this simulation study. However, volumetric tumor uptake measurements (i.e., absolute and relative concentrations) are limited by inaccuracies in MBI volume estimation using two‐dimensional images, highlighting the need for either tomographic MBI acquisitions or anatomical volume estimates for accurate three‐dimensional tumor uptake estimates. [ABSTRACT FROM AUTHOR]

Background: Yttrium-90 (90Y) radioembolization is increasingly being utilized with curative intent. While single-compartment doses with respect to the perfused volume for the complete pathologic necrosis (CPN) of tumors have been reported, the actual doses delivered to the tumor and at-risk margins that leads to CPN have hitherto not been estimated. We present an ablative dosimetry model that calculates the dose distribution for tumors and at-risk margins based on numerical mm-scale dose modeling and the available clinical CPN evidence and report on the necessary dose metrics needed to achieve CPN following 90Y-radioembolization. Methods: Three-dimensional (3D) activity distributions (MBq/voxel) simulating spherical tumors were modeled with a 121 × 121 × 121 mm3 soft tissue volume (1 mm3 voxels). Then, 3D dose distributions (Gy/voxel) were estimated by convolving 3D activity distributions with a 90Y 3D dose kernel (Gy/MBq) sized 61 × 61 × 61 mm3 (1 mm3 voxels). Based on the published data on single-compartment segmental doses for the resected liver samples of HCC tumors showing CPN after radiation segmentectomy, the nominal voxel-based mean tumor dose ( D m e a n C P N ), point dose at tumor rim ( D r i m C P N ), and point dose 2 mm beyond the tumor boundary ( D 2 m m C P N ), which are necessary to achieve CPN, were calculated. The single-compartment dose prescriptions to required achieve CPN were then analytically modeled for more general cases of tumors with diameters d t = 2, 3, 4, 5, 6, and 7 cm and with tumor-to-normal-liver uptake ratios T : N = 1:1, 2:1, 3:1, 4:1, and 5:1. Results: The nominal case defined to estimate the doses needed for CPN, based on the previously published clinical data, was a single hyperperfused tumor with a diameter of 2.5 cm and T : N = 3:1, treated with a single-compartment segmental dose of 400 Gy. The voxel-level doses necessary to achieve CPN were 1053 Gy for the mean tumor dose, 860 Gy for the point dose at the tumor boundary, and 561 Gy for the point dose at 2 mm beyond the tumor edge. The single-compartment segmental doses necessary to satisfy the criteria for CPN in terms of the mean tumor dose, point dose at the tumor boundary, and the point dose at 2 mm beyond the tumor edge were tabulated for a range of tumor diameters and tumor-to-normal-liver uptake ratios. Conclusions: The analytical functions that describe the relevant dose metrics for CPN and, more importantly, the single-compartment dose prescriptions for the perfused volume needed to achieve CPN are reported for a large range of conditions in terms of tumor diameters (1–7 cm) and T : N uptake ratios (2:1–5:1). [ABSTRACT FROM AUTHOR]

Background: Molecular breast imaging (MBI) of 99mTc‐sestamibi is an emerging adjunct qualitative tool in the detection and diagnosis of breast cancer. Purpose: This work outlines the development and performance evaluation of a methodology to absolutely quantify tumor 99mTc activity uptake using a commercially available dual‐headed MBI system by implementing corrections for background, scatter, attenuation, and detector characteristics. Methods: A validated Monte Carlo application of a commercial MBI system was used to simulate over 7000 unique acquisitions of spherical and ellipsoidal tumors in breast tissue. Tumor absolute activity was calculated following background, scatter, and attenuation corrections of tumor region of interest counts. The methodology was first optimized using a set of high‐uptake spherical tumors, and its accuracy and precision was then assessed in a set of spherical tumors with clinical uptake conditions. Finally, the performance of the activity methodology was evaluated under various bias and uncertainty conditions to better characterize the technique under expected clinical measurement conditions. Results: In a test set of images with clinically relevant contrast and noise conditions, the mean ± standard deviation relative error in total tumor activity was 0.5% ± 6.5% (n = 2363) under ideal measurement conditions. Allowing for variability in tumor and background contours and in estimated tumor depths, the expected accuracy of the methodology in clinical practice was 0.5% ± 11.1% (n = 2363), with minimal loss of accuracy for ellipsoidal tumors. Conclusions: Planar MBI photopeak images acquired with standard‐of‐care protocols can be used to accurately quantify absolute tumor 99mTc activity with an accuracy and precision of 0.5% ± 11.1%. The reported precision was based on a comprehensive evaluation of random errors and systematic biases. [ABSTRACT FROM AUTHOR]

Elevated TNF-α levels in serum and broncho-alveolar lavage fluid of acute lung injury patients correlate with mortality rates. We hypothesized that pharmacological plasma membrane potential (Em) hyperpolarization protects against TNF-α-induced CCL-2 and IL-6 secretion from human pulmonary endothelial cells through inhibition of inflammatory Ca2+-dependent MAPK pathways. Since the role of Ca2+ influx in TNF-α-mediated inflammation remains poorly understood, we explored the role of L-type voltage-gated Ca2+ (CaV) channels in TNF-α-induced CCL-2 and IL-6 secretion from human pulmonary endothelial cells. The CaV channel blocker, Nifedipine, decreased both CCL-2 and IL-6 secretion, suggesting that a fraction of CaV channels is open at the significantly depolarized resting Em of human microvascular pulmonary endothelial cells (−6 ± 1.9 mV), as shown by whole-cell patch-clamp measurements. To further explore the role of CaV channels in cytokine secretion, we demonstrated that the beneficial effects of Nifedipine could also be achieved by Em hyperpolarization via the pharmacological activation of large conductance K+ (BK) channels with NS1619, which elicited a similar decrease in CCL-2 but not IL-6 secretion. Using functional gene enrichment analysis tools, we predicted and validated that known Ca2+-dependent kinases, JNK-1/2 and p38, are the most likely pathways to mediate the decrease in CCL-2 secretion. [ABSTRACT FROM AUTHOR]

Influenza-A virus (IAV) infects yearly an estimated one billion people worldwide, resulting in 300,000-650,000 deaths. Preventive vaccination programs and antiviral medications represent the mainstay of therapy, but with unacceptably high morbidity and mortality rates, new targeted therapeutic approaches are urgently needed. Since inflammatory processes are commonly associated with measurable changes in the cell membrane potential (Em), we investigated whether Em hyperpolarization via TREK-1 (K2P2.1) K+ channel activation can protect against influenza-A virus (IAV)-induced pneumonia. We infected mice with IAV, which after 5 days caused 10-15% weight loss and a decrease in spontaneous activity, representing a clinically relevant infection. We then started a 3-day intratracheal treatment course with the novel TREK-1 activating compounds BL1249 or ML335. We confirmed TREK-1 activation with both compounds in untreated and IAV-infected primary human alveolar epithelial cells (HAECs) using high-throughput fluorescent imaging plate reader (FLIPR) assays. In mice, TREK-1 activation with BL1249 and ML335 counteracted IAV-induced histological lung injury and decrease in lung compliance and improved BAL fluid total protein levels, cell counts, and inflammatory IL-6, IP-10/CXCL-10, MIP-1α, and TNF-α levels. To determine whether these anti-inflammatory effects were mediated by activation of alveolar epithelial TREK-1 channels, we studied the effects of BL1249 and ML335 in IAV-infected HAEC, and found that TREK-1 activation decreased IAV-induced inflammatory IL-6, IP-10/CXCL10, and CCL-2 secretion. Dissection of TREK-1 downstream signaling pathways and construction of protein-protein interaction (PPI) networks revealed NF-κB1 and retinoic acid-inducible gene-1 (RIG-1) cascades as the most likely targets for TREK-1 protection. Therefore, TREK-1 activation may represent a novel therapeutic approach against IAV-induced lung injury. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the accuracy and biases of predicted lung shunt fraction (LSF) and lung dose (LD) calculations via 99mTc‐macro‐aggregated albumin (99mTc‐MAA) planar imaging for treatment planning of 90Y‐microsphere radioembolization. Methods and materials: LSFs in 52 planning and LDs in 44 treatment procedures were retrospectively calculated, in consecutive radioembolization patients over a 2 year interval, using 99mTc‐MAA planar and SPECT/CT imaging. For each procedure, multiple planar LSFs and LDs were calculated using different: (1) contours, (2) views, (3) liver 99mTc‐MAA shine‐through compensations, and (4) lung mass estimations. The accuracy of each planar‐based LSF and LD methodology was determined by calculating the median (range) absolute difference from SPECT/CT‐based LSF and LD values, which have been demonstrated in phantom and patient studies to more accurately and reliably quantify the true LSF and LD values. Results: Standard‐of‐care LSF using geometric mean of lung and liver contours had median (range) absolute over‐estimation of 4.4 percentage points (pp) (0.9 to 11.9 pp) from SPECT/CT LSF. Using anterior views only decreased LSF errors (2.4 pp median, −1.1 to +5.7 pp range). Planar LD over‐estimations decreased when using single‐view versus geometric‐mean LSF (1.3 vs. 2.6 Gy median and 7.2 vs. 18.5 Gy maximum using 1000 g lung mass) but increased when using patient‐specific versus standard‐man lung mass (2.4 vs. 1.3 Gy median and 11.8 vs. 7.2 Gy maximum using single‐view LSF). Conclusions: Calculating planar LSF from lung and liver contours of a single view and planar LD using that same LSF and 1000 g lung mass was found to improve accuracy and minimize bias in planar lung dosimetry. [ABSTRACT FROM AUTHOR]

Soft red winter wheat (SRWW) (Triticum aestivum L.) production in the southeastern United States is affected by biotic and abiotic stresses that can result in yield losses and reduced acreage. Developing new cultivars with high yield, good resistance to predominant pests, and acceptable quality to maximize value in regional markets is needed. The University of Georgia (UGA) SRWW breeding program, in collaboration with institutions in the region including the Southern UNiversities GRAINS (SUNGRAINS) programs, is responding to these challenges by developing and releasing superior cultivars adapted to the region. 'GA 08535‐15LE29' (Reg. no. CV‐1191, PI 693269) SRWW cultivar was developed and released by the UGA College of Agricultural and Environmental Sciences and licensed to Uni South Genetics seed company in 2018 as USG 3640. GA 08535‐15LE29 is well adapted to Georgia and the U.S. southeast region with high yield and good resistance to leaf (Puccinia triticina Erikss.) and stripe (P. striiformis Westend.) rusts, Fusarium head blight (caused by Fusarium graminearum Schwabe), powdery mildew (Erisyphe graminis), and Soil‐borne wheat mosaic virus (SBWMV) diseases. GA 08535‐15LE29 showed moderate field resistance to Hessian fly [Mayetiola destructor (Say)]. GA 08535‐15LE29 has Sbm1 and Yr17/Lr37/Sr38 for resistance to SBWMV and rust diseases and has good grain volume weight and acceptable milling and baking qualities. Core Ideas: GA 08535‐15LE29 was developed by the University of Georgia in collaboration with SUNGRAINS.GA 08535‐15LE29 is well adapted to Georgia and the U.S. Southeast.GA 08535‐15LE29 is resistant to prevalent diseases (e.g., rusts) and insects (e.g., Hessian fly).GA 08535‐15LE29 possesses Sbm1 and Yr17/Lr37/Sr38 genes/QTL. [ABSTRACT FROM AUTHOR]

Purpose: There are no published data on organ doses following intra‐hepatic‐arterial administration of 99mTc‐macroaggregated‐albumin (IHA 99mTc‐MAA) routinely used in 90Y‐radioembolization treatment planning to assess intra‐ and extra‐hepatic depositions and calculate lung‐shunt‐fraction (LSF). We propose a method to model the organ doses following IHA 99mTc‐MAA that incorporates three in vivo constituent biodistributions, the 99mTc‐MAA that escape the liver due to LSF, and the 99mTc‐MAA dissociation fraction (DF). Methods: The potential in vivo biodistributions for IHA 99mTc‐MAA are: Liver‐Only MAA with all activity sequestered in the liver (LSF = 0&DF = 0), Intravenous MAA with all activity transferred intravenously as 99mTc‐MAA (LSF = 1&DF = 0), and Intravenous Pertechnetate with all activity is transferred intravenously as 99mTc‐pertechnetate (LSF = 0&DF = 1). Organ doses for Liver‐Only MAA were determined using OLINDA/EXM 2.2, where liver was modeled as the source organ containing 99mTc‐MAA, while those for Intravenous MAA and Intravenous Pertechnetate were from ICRP 128. Organ doses for the general case can be determined as a weighted‐linear‐combination of the three constituent biodistributions depending on the LSF and DF. The maximum‐dose scenario was modeled by selecting the highest dose rate for each organ amongst the three constituent cases. Results: For Liver‐Only MAA, the liver as source organ received the highest dose at 98.6 and 126 mGy/GBq for the adult male and adult female phantoms, respectively; all remaining organs received <27 and <32 mGy/GBq. For Intravenous MAA, the lung as source organ received the highest dose at 66 and 97 mGy/GBq; all remaining organs received <16 and <21 mGy/GBq. The organ with the highest dose for Intravenous Pertechnetate was the upper‐large‐intestinal wall at 56 and 73 mGy/GBq; all remaining organs received <26 and <34 mGy/GBq. The liver and lung doses for the maximum‐dose scenario with 5 mCi (185 MBq) 99mTc‐MAA were estimated at 18.2 and 12.2 mGy, and 23.3 and 17.9 mGy, for the adult male and adult female phantoms, respectively. Conclusion: Organ dose estimates following IHA 99mTc‐MAA based on constituent biodistribution models and patient‐specific LSF and DF values have been derived. Liver and lung were the organs with highest dose, receiving at most 15–25 mGy in the maximum‐dose scenario, following 5 mCi IHA 99mTc‐MAA. [ABSTRACT FROM AUTHOR]

The association between blood transfusion and the occurrence of de novo HLA donor specific antibodies (DSA) after kidney transplantation remains controversial. In this singlecenter observational study, we examined the association between early blood transfusion, i.e. before 1-month post-transplantation, and the risk of DSA occurrence, using Luminex based-methods. In total, 1,424 patients with a minimum of 1-month follow-up were evaluated between January 2007 and December 2018. During a median time of follow-up of 4.52 years, we observed 258 recipients who had at least one blood transfusion during the first month post-transplantation. At baseline, recipients in the transfused group were significant older, more sensitized against HLA class I and class II antibodies and had a higher 1-month serum creatinine. Cox proportional hazards regression analyses did not show any significant association between blood transfusion and the risk of de novo DSA occurrence (1.35 [0.86-2.11], p = 0.19), the risk of rejection (HR = 1.33 [0.94-1.89], p = 0.11), or the risk of graft loss (HR = 1.04 [0.73-1.50], p = 0.82). These data suggest then that blood transfusion may not be limited when required in the early phase of transplantation, and may not impact long-term outcomes. [ABSTRACT FROM AUTHOR]

In Georgia and the southeast region of the United States, acreage of soft red winter wheat (SRWW) (Triticum aestivum L.) has decreased in recent years. There is an urgent need to release new cultivars with high yield potential, resistance to yield‐limiting diseases and insects, and good baking quality to maximize value in regional markets. To address this, the SRWW breeding program at the University of Georgia (UGA), in collaboration with the SUNGRAINS breeding programs, developed 'GA JT141‐14E45' (Reg. no. CV‐1183, PI 689519), a SRWW cultivar released by the UGA College of Agricultural and Environmental Sciences and licensed to AGSouth (AGS) Genetics as AGS 3030. GA JT141‐14E45 is widely adapted to the U.S. Southeast, having high yield, good resistance to diseases such as leaf rust, stripe rust, powdery mildew, and Soil‐borne wheat mosaic virus (SBWMV) and to current biotypes of Hessian fly (Mayetiola destructor Say). It has good resistance to Fusarium head blight (FHB) or scab. GA JT141‐14E45 has good grain volume weight and acceptable milling and baking quality. GA JT141‐14E45 was derived from the cross of 'AGS 2026'/'Jamestown'. Jamestown was used in the cross mainly for its resistance to FHB (FHB QTL 1A‐Neuse and 1B‐Jamestown). AGS 2026 is a UGA cultivar released in 2007 with very good disease resistance to rusts (Yr17/Lr37/Sr38), Hessian fly resistance (H13), and excellent yield. [ABSTRACT FROM AUTHOR]

Purpose. Molecular breast imaging (MBI) of 99mTc-sestamibi with dual-headed, pixelated, cadmium–zinc–telluride (CZT) detectors is increasingly used in breast cancer care for screening/detecting lesions, monitoring response to therapy, and predicting risk of cancer. MBI as a truly quantitative tool in these applications, however, is limited due the lack of absolute 99mTc-sestamibi uptake quantification. To help advance the field of quantitative MBI, we have developed a Monte Carlo simulation application of the GE Discovery NM 750b system. Methods. Our simulation consists of a two-step process using the Geant4 toolkit to model the detector and source geometry and to track photon interactions and a MATLAB script to model the charge transport within the pixelated CZT detector. Simulated detector and detector response model parameters were selected to match measured and simulated standard performance characteristics using various 99mTc point-, line-, and film-sources in air. The final model parameters were verified by comparing the count profiles, energy spectra, and region of interest counts between simulated and measured images of a breast phantom with two spherical lesions in 5 cm thick medium of air or water. Results. Final performance characteristics with 99mTc sources in air were: (1) energy resolution: 6.1% measured versus 5.9% simulated photopeak full-width at half-maximum (FWHM), (2) spatial resolution: mean error between measured and simulated FWHM of 0.08 mm across 4.4–14.0 mm FWHM range, and (3) sensitivity: 572 cpm/μCi measured versus 567 cpm/μCi simulated (<1% error). Good agreement was observed in the breast phantom line profiles through the spherical lesions and overall energy spectra, with <5% difference in sphere counts between simulated and measured data. Conclusion. A pixelated CZT charge transport and induction model was successfully implemented and validated to simulate imaging with the GE Discovery NM 750b system. This work will enable investigations improving MBI image quality and developing algorithms for uptake quantification. [ABSTRACT FROM AUTHOR]

Soft red winter wheat (SRWW) (Triticum aestivum L.), historically a major crop in Georgia and the U.S. Southeast (SE) region, has been challenged by numerous biotic and abiotic constraints resulting in decreased hectarage in recent years. Hence, an urgent need exists to release new cultivars with high yield potential, good resistance to predominant diseases and insects, and acceptable quality attributes to capture and maximize value in regional markets. The SRWW breeding program at the University of Georgia (UGA), in collaboration with the Southeastern University GRAINS (SUNGRAINS) breeding programs, is responding to these challenges by developing and releasing superior SRWW cultivars adapted to Georgia and the SE wheat region. 'GA 07353‐14E19' (Reg. no. CV‐1179, PI 689520), a SRWW cultivar developed by the UGA small grains breeding program, was released by the UGA College of Agricultural and Environmental Sciences and licensed to Stratton Seed Company in 2017 as GO WHEAT 2032. GA 07353‐14E19 is adapted to the SE region with high yield, good resistance to prevalent diseases, including leaf and stripe rusts, Fusarium head blight, powdery mildew, and Soil‐borne wheat mosaic virus. GA 07353‐14E19 also showed good resistance to current biotypes of Hessian fly. GA 07353‐14E19 possesses the H13, Sbm1, and Yr17–Lr37–Sr38 genes that protect it against the above pests. It has very good grain volume weight and good milling and baking quality as a SRWW. [ABSTRACT FROM AUTHOR]

Purpose: A Positron Emission Tomography/Computed Tomography quality assurance program is necessary to ensure that patients receive optimal imaging and care. We summarize the AAPM Task Group (TG) 126 report on acceptance and quality assurance (QA) testing of PET/CT systems. Methods: TG 126 was charged with developing PET/CT acceptance testing and QA procedures. The TG aimed to develop procedures that would allow for standardized evaluation of existing short‐axis cylindrical‐bore PET/CT systems in the spirit of NEMA NU 2 standards without requiring specialized phantoms or proprietary software tools. Results: We outline eight performance evaluations using common phantoms and freely available software whereby the clinical physicist monitors each PET/CT system by comparing periodic Follow‐Up Measurements to Baseline Measurements acquired during acceptance testing. For each of the eight evaluations, we also summarize the expected testing time and materials necessary and the recommended pass/fail criteria. Conclusion: Our report provides a guideline for periodic evaluations of most clinical PET/CT systems that simplifies procedures and requirements outlined by other agencies and will facilitate performance comparisons across vendors, models, and institutions. [ABSTRACT FROM AUTHOR]

We recently established a role for the stretch-activated two-poredomain K1 (K2P) channel TREK-1 (K2P2.1) in inflammatory cytokine secretion using models of hyperoxia-, mechanical stretch-, and TNF-a-induced acute lung injury. We have now discovered the expression of large conductance, Ca21-activated K1 (BK) channels in human pulmonary microvascular endothelial cells and primary human alveolar epithelial cells using semiquantitative real-time PCR, IP and Western blot, and investigated their role in inflammatory cytokine secretion using an LPS-induced acute lung injury model. As expected, LPS induced IL-6 and CCL-2 secretion from pulmonary endothelial and epithelial cells. BK activation with NS1619 decreased LPS-induced CCL-2 but not IL-6 secretion from endothelial cells and had no effect on epithelial cells, although fluorometric assays revealed that BK activation hyperpolarized the plasma membrane potential (Em) of both cell types. Interestingly, BK inhibition (Paxilline) did not alter cytokine secretion or theEmin either cell type. Furthermore, LPS treatment by itself did not affect the Em or intracellular Ca21 concentrations. Therefore, we propose BK channel activation as a novel targeted approach to counteract LPS-induced CCL-2 secretion from endothelial cells. This protective effect appears to occur via Em hyperpolarization but independent of intracellular Ca21 concentrations. [ABSTRACT FROM AUTHOR]

Soft red winter wheat (SRWW) (Triticum aestivum L.) is a major crop in Georgia and the U.S. Southeast (SE) region. Hence, new cultivars with high yield potential, high resistance levels to predominant pests, and adequate quality parameters are required to capture and maximize regional market values. Therefore, the University of Georgia SRWW breeding program in collaboration with the SUNGRAINS breeding programs, aims to develop and release SRWW cultivars adapted to Georgia and the SE wheat region with high yield, quality, and pest resistance. 'GA 051207‐14E53' SRWW (Reg. no. CV‐1168, PI 689518) was developed and released by the University of Georgia and licensed to AGSouth Genetics Company in 2017 under the name AGS 3040. GA 051207‐14E53 is well adapted to Georgia and the SE region. It has high yield and high resistance to leaf rust, stripe rust, and Soil‐borne wheat mosaic virus. It has medium resistance to powdery mildew and to biotypes C and O of Hessian fly and is resistant to biotypes B and L. GA 051207‐14E53 has good Fusarium head blight resistance. GA 051207‐14E53 possesses H9, Sbm1, and the 2NS:2AS alien introgression from Aegilops ventricosa Tausch, having the Yr17/Lr37/Sr38 genes that protect it against these pests. Grain volume weight and milling and baking qualities of GA 051207‐14E53 are good and meet the SRWW grade standards. [ABSTRACT FROM AUTHOR]

We report the observation of a 75-year-old patient referred for cervical lymphadenopathies. A pre-lymphadenectomy blood work revealed an asymptomatic elevation of aPTT with low factor VIII (FVIII) levels and high anti-FVIII antibodies titers, consistent with acquired hemophilia A (AHA). Histological work-up of a cervical lymphadenopathy revealed benign follicular hyperplasia with IgG4+ lymphoplasmacytic infiltration; and serum IgG4 levels were markedly elevated, compatible with IgG4-related disease (IgG4-RD). He was successfully treated with a 9-month course of prednisone, secondarily associated with rituximab when an AHA relapse occurred. As this patient presented with an unusual association of rare diseases, we wondered whether there was a link between the two conditions. Our first hypothesis was that the anti-FVIII autoantibodies could be directly produced by the proliferating IgG4+ plasma cells as a result of broken tolerance to autologous FVIII. To test this assumption, we determined the anti-FVIII IgG subclasses in our patient and in a control group of 11 AHA patients without IgG4-RD. The FVIII inhibitor was mostly IgG4, with an anti-FVIII IgG4/IgG1 ratio of 42 at diagnosis and 268 at relapse in our patient; similar values were observed in non-IgG4-RD AHA patients. As a second hypothesis, we considered whether the anti-FVIII activity could be the result of a non-specific autoantibody production due to polyclonal IgG4+ plasma cell proliferation. To test this hypothesis, we measured the anti-FVIII IgG4/total IgG4 ratio in our patient, as well as in several control groups: 11 AHA patients without IgG4-RD, 8 IgG4-RD patients without AHA, and 11 healthy controls. We found that the median [min-max] ratio was higher in AHA-only controls (2.4 10-2 [5.7 10-4-1.79 10-1]), an oligoclonal setting in which only anti-FVIII plasma cells proliferate, than in IgG4-RD-only controls (3.0 10-5 [2.0 10-5-6.0 10-5]), a polyclonal setting in which all IgG4+ plasma cells proliferate equally. Our patient had intermediate ratio values (2.7 10-3 at diagnosis and 1.0 10-3 at relapse), which could plead for a combination of both mechanisms. Although no definitive conclusion can be drawn, we hypothesized that the anti-FVIII autoantibody production in our IgG4-RD AHA patient could be the result of both broken tolerance to FVIII and bystander polyclonal IgG4+ plasma cell proliferation. [ABSTRACT FROM AUTHOR]

No targeted therapies exist to counteract Hyperoxia (HO)-induced Acute Lung Injury (HALI). We previously found that HO downregulates alveolar K2P2.1 (TREK-1) K+ channels, which results in worsening lung injury. This decrease in TREK-1 levels leaves a subset of channels amendable to pharmacological intervention. Therefore, we hypothesized that TREK-1 activation protects against HALI. We treated HO-exposed mice and primary alveolar epithelial cells (AECs) with the novel TREK-1 activators ML335 and BL1249, and quantified physiological, histological, and biochemical lung injury markers. We determined the effects of these drugs on epithelial TREK-1 currents, plasma membrane potential (Em), and intracellular Ca2+ (iCa) concentrations using fluorometric assays, and blocked voltage-gated Ca2+ channels (CaV) as a downstream mechanism of cytokine secretion. Once-daily, intra-tracheal injections of HO-exposed mice with ML335 or BL1249 improved lung compliance, histological lung injury scores, broncho-alveolar lavage protein levels and cell counts, and IL-6 and IP-10 concentrations. TREK-1 activation also decreased IL-6, IP-10, and CCL-2 secretion from primary AECs. Mechanistically, ML335 and BL1249 induced TREK-1 currents in AECs, counteracted HO-induced cell depolarization, and lowered iCa2+ concentrations. In addition, CCL-2 secretion was decreased after L-type CaV inhibition. Therefore, Em stabilization with TREK-1 activators may represent a novel approach to counteract HALI. [ABSTRACT FROM AUTHOR]

A pilot project was conducted to determine the effect of common construction dusts as interferences in a new portable end-of-shift (EoS), direct-on-filter (DoF) sampling and analysis method for respirable crystalline silica (RCS), in this case, quartz. Construction dusts were prepared from plaster, drywall, cement and brick by grinding, aerosolizing, and collecting respirable dust with high flow rate cyclones. Filters were loaded with different levels of commercial α-quartz powder Min-u-Sil 5, and different levels of interfering dusts, singly and in combination. Samples were analyzed by Fourier Transform Infrared Spectroscopy (FTIR). Good correlations were found between nominal quartz loading (0 µg, 25 µg, 50 µg, and 100 µg) adjusted for quartz in the interfering dust and FTIR absorbance alone and in the presence of all interfering dusts. The slopes of the correlations were similar whether the loading was quartz without interference, or with plaster, drywall, and cement dusts, regardless of quantity. The results show that (a) plaster and drywall dusts do not interfere substantially; (b) cement does not interfere, but a change in the intercept suggests an effect on the background absorbance of the filter; and (c) in addition to having a substantial quartz content, brick dust contains an additional material, probably a silicate mineral, which interferes with the quartz peak. Thus, the presence of cement leads to lower quartz values and brick leads to higher values, but overall, 83% of the quartz contents predicted from the calibration data agreed within 50% of the adjusted nominal loadings within the range 20–110 µg. This result is encouraging given the high levels of interfering dusts. Nine samples loaded with smaller amounts of all four dusts together gave results within 25% of the adjusted nominal loadings. A single mixture addition of the dusts to the filter gave tighter variance in results than sequential additions. Unexpectedly, the two Certified Reference Materials (CRMs) 1878a and 1878b, gave different results when used to calibrate XRD analysis of Min-u-Sil 5. [ABSTRACT FROM AUTHOR]

Climate simulations for the North Atlantic and Europe for recent and future conditions simulated with the regionally coupled ROM model are analyzed and compared to the results from the MPI‐ESM. The ROM simulations also include a biogeochemistry and ocean tides. For recent climate conditions, ROM generally improves the simulations compared to the driving model MPI‐ESM. Reduced oceanic biases in the Northern Atlantic are found, as well as a better simulation of the atmospheric circulation, notably storm tracks and blocking. Regarding future climate projections for the 21st century following the RCP 4.5 and 8.5 scenarios, MPI‐ESM and ROM largely agree qualitatively on the climate change signal over Europe. However, many important differences are identified. For example, ROM shows an SST cooling in the Subpolar Gyre, which is not present in MPI‐ESM. Under the RCP8.5 scenario, ROM Arctic sea ice cover is thinner and reaches the seasonally ice‐free state by 2055, well before MPI‐ESM. This shows the decisive importance of higher ocean resolution and regional coupling for determining the regional responses to global warming trends. Regarding biogeochemistry, both ROM and MPI‐ESM simulate a widespread decline in winter nutrient concentration in the North Atlantic of up to ~35%. On the other hand, the phytoplankton spring bloom in the Arctic and in the North‐Western Atlantic starts earlier, and the yearly primary production is enhanced in the Arctic in the late 21st century. These results clearly demonstrate the added value of ROM to determine more detailed and more reliable climate projections at the regional scale. Plain Language Summary: We downscale present climate and future climate change projections for the North Atlantic and Europe using a regionally coupled Earth System Model including atmosphere, ocean, river runoff, and ocean biogeochemistry components. This approach allows us to attain higher spatial resolution and to a more accurate representation of key physical processes, yielding a better simulation of present climate at regional and local scales when compared to the driving global climate model. Future climate change projections show more detail at regional and local scale, mostly related to the improvement in the representation of orography and bathymetry. These improvements along with a better representation of the interactive ocean‐atmosphere coupling lead to other remarkable differences with the driving global climate model: (1) colder Sea Surface Temperature in the Subpolar Gyre region, indicating a local convection collapse and a Atlantic Meridional Overturning Circulation slowdown; (2) a seasonal free‐ice Arctic is reached by 2055 under RCP8.5 scenario, well before projected by the driving global climate model; and (3) stronger reduction in nutrients in the North Atlantic by the end of the 21st century. These results clearly demonstrate the added value of the regionally coupled model system to determine more reliable climate projections at the regional scale. Key Points: The regionally coupled model shows reduced oceanic biases in the North Atlantic and a better simulation of the atmospheric circulationThe Arctic reaches a seasonally ice‐free state by 2055 with the regionally coupled model under RCP8.5 scenarioChanges in biogeochemistry are generally stronger and show enhanced details in the regionally coupled model [ABSTRACT FROM AUTHOR]

Purpose: Current treatment planning for 90Y radioembolization estimates lung mean dose (LMD) by measuring the lung shunt fraction (LSF) from 99mTc‐macroaggregated albumin (MAA) planar imaging and assuming a 1‐kg lung mass. This methodology, however, overestimates LSF and LMD and could therefore unnecessarily limit the dose to target volume(s). We propose an improved LMD calculation that derives LSF from 99mTc‐MAA SPECT/CT and the patient‐specific lung mass from diagnostic chest CT. Furthermore, we investigated the errors in lung mass, LSF, and LMD arising from contour variability in patient data in order to estimate the precision of our proposed methodology. Methods: Our proposed LMD (LMDnew) calculation consisted of the following steps: (a) estimate liver counts from the MAA SPECT/CT liver contour; (b) estimate total lung counts by multiplying density (counts/g) from the MAA SPECT/CT left‐lung contour by the total lung mass (g) from the diagnostic CT lung contours; (c) compute LSFnew from liver and lung counts; (d) calculate LMDnew using LSFnew and the total lung mass from the diagnostic CT (Mnew). LMDnew, LSFnew, and Mnew estimates were compared to standard model values (LMDclin, LSFclin, and 1 kg, respectively) in 52 consecutive patients with hepatocellular carcinoma who underwent radioembolization using 90Y glass microspheres. The precision of our methodology was quantified by varying lung and liver contours in the same patient population and calculating the resulting relative errors in the liver count, lung count, and lung mass measurements. Results: The median Mnew was 839 g (range, 550–1178 g) for men and 731 g (range, 548–869 g) for women. The median LSFnew was 0.02 (range, 0.01–0.11), while the median LMDnew was 4.9 Gy (range, 0.3–25.5 Gy). Mnew, LSFnew, and LMDnew were significantly lower than Mclin, LSFclin, and LMDclin, with respective relative mean (±SD) differences of −20% (±16%) for Mnew, −63% (±15%) for LSFnew, and −53% (±23%) for LMDnew. The estimated 1‐sigma uncertainties in Mnew, LSFnew, and LMDnew were 9%, 10%, and 13%, respectively. Conclusions: We derived a method to calculate lung mass and LSF using routinely available diagnostic chest CT and 99mTc‐MAA SPECT/CT. More importantly, we systematically quantified the errors in our measurements to establish the precision of the estimated lung dose (13%). The proposed methodology provides a more accurate LMD and an estimate of its precision, which will improve treatment and retreatment planning for 90Y radioembolizations. [ABSTRACT FROM AUTHOR]

This qualitative study investigated the lived experiences of six community college dance students. The theoretical framework of social cognitive career theory was used but was modified to include only the tenets most frequently cited in the literature that directly influenced the career identity of dancers particularly in relation to their motivation to academically persist and graduate. The research provides insight into the individual experiences of the participants in their dance journey. The goal was to obtain current data on the student experience so that dance programs can further enhance the student experience. The phenomenological analysis produced an early thematic matrix of 18 codes that were reduced to six major themes. Of those six themes, this study will focus on academic commitment, dance identification, and challenges. [ABSTRACT FROM AUTHOR]

Objectives: Antiphospholipid antibodies (aPL) can be present in the sera of systemic sclerosis (SSc) patients. This study aimed to determine the prevalence of aPL in a cross-sectional study of SSc patients, to assess their clinical associations, to perform a systematic review of published reports and a meta-analysis to estimate the worldwide prevalence of aPL in SSc. Methods: Two-hundred and forty-nine SSc patients were consecutively tested once for lupus anticoagulant (LA), anticardiolipin (aCL), and anti-β2glycoprotein I (anti-β2GpI) antibodies. Clinical associations with aPL positivity were studied using a logistic regression model. A systematic review of the literature was carried out in PubMed and Embase. Meta-analysis was performed using number of aPL positive (at least one of the three antibodies positive) and negative patients. Meta-regression was used to study potential factors explaining the heterogeneity between studies. Results: In our cross-sectional study, aPL positivity was found in 16 patients (prevalence 6.4%; 95%CI [3.8–10.4]). In multivariate analysis, there was a significant association between aPL positivity and venous thrombosis (VT) (OR 6.25 [1.18–33.00]; p = 0.028) and miscarriage (OR 5.43; 95%CI [1.31–22.13]; p = 0.017). Twenty-four studies were included in the meta-analysis, representing a total population of 3036 SSc patients. The overall pooled prevalence of aPL in SSc was 16% (10–22) with a high degree of heterogeneity among studies. Conclusion: This study found a prevalence of aPL positivity in our SSc population of 6.4% (3.8–10.4) and an overall worldwide pooled prevalence of 14% (9–20). In our SSc population, aPL positivity was associated with VT and miscarriage. These data provide additional insights into the role of aPL in the vasculopathy observed in SSc. [ABSTRACT FROM AUTHOR]

The attenuation of 511 keV photons by the structure of a PET/MR scanner was measured prior to energizing the magnet. The exposure rate from a source of fluorine‐18 was measured in air and, with the source placed at the isocenter of the instrument, at various points outside of the scanner. In an arc from 45 to 135 degrees relative to the long axis of the scanner and at a distance of 1.5 m from the isocenter, the attenuation by the scanner is at least 5.6 half‐value layers from the MR component alone and at least 6.6 half‐value layers with the PET insert installed. This information could inform better design of the radiation shielding for PET/MR scanners. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin G (IgG) and IgG subclass assays are indicated in patients with suspected primary immunodeficiency (PID). Commercially available assays for IgG subclass determination are calibrated against various preparations, and so specific reference values are required for each of them. Using Optilite® reagents from The Binding Site Group Ltd., we sought to determine the pediatric IgG and IgG subclass reference intervals with respect to the ERM-DA470k certified reference material. Methods: Levels of IgG and IgG subclasses were analyzed in serum samples collected from a large cohort of PID-free children and adolescents. Reference intervals were calculated for previously published age groups (6-12 months, 12-18 months, 18 months-2 years, 2-3 years, 3-4 years, 4-6 years, 6-9 years, 9-12 years and 12-18 years), according to the Clinical and Laboratory Standards Institute's C28-A3c protocol. Results: A total of 456 serum samples were analyzed. The correlation between the total IgG and the sum of the IgG subclasses was good (r² = 0.96). No statistically significant gender-specific differences were observed. Our results for the changes over time in IgG and IgG subclass levels are consistent with previous reports. The differences between our lower/upper reference limits and those in the literature are probably due to variations in calibration. Conclusions: Our present results provide a reliable basis for the diagnosis of PIDs in childhood and for the accreditation of laboratories using Optilite® immunoturbidimetric reagents for IgG subclass measurement. Laboratory scientists and clinicians should be aware of the need for manufacturer-specific IgG subclass reference intervals. [ABSTRACT FROM AUTHOR]

Background: An overall response assay [OVA, based on a 23-valent pneumococcal polysaccharide vaccine (PPV23)] is widely used to screen for anti-pneumococcal antibodies. Given the heterogeneity of response from one polysaccharide (PS) to another, a World Health Organization-standardized serotype-specific enzyme-linked immunosorbent assay (SSA) is considered to be the only reliable method for testing anti-PS antibody responses in individuals with suspected primary immunodeficiencies (PIDs). Objective: To evaluate the OVA relative to the reference SSA. Methods: Serum samples of adult patients referred for a suspected PID were collected before and then 4-8 weeks after immunization with PPV23. The anti-pneumococcal response was systematically assessed with an SSA (7-16 serotypes) and interpreted according to the American Academy of Asthma, Allergy and Immunology's current guidelines. We used receiver operating characteristic curves and agreement indices to assess the OVA's diagnostic value in a first cohort. In order to validate these findings, a second (validation) cohort was then prospectively included. Results: Sixty-two adult patients were included, and 42 (67.7%) were defined as poor responders according to the SSA. Only the post-immunization titer in the OVA was able to correctly identify poor responders; a titer below 110 mg/L gave a positive predictive value of 100% [identifying 24 (57.1%) of the 42 poor responders], and similar levels of diagnostic performance were observed in the validation cohort. The pre-vaccination antibody titer, the post/pre-vaccination antibody titer ratio and a post-vaccination titer above 110 mg/L in the OVA were not predictive of the response in the SSA. Conclusion: A post-vaccination antibody titer below 110 mg/L in the OVA was constantly associated with a poor PPV23 response using the SSA. In all other cases, SSA is the only reliable method for assessing diagnostic vaccination with PPV23. [ABSTRACT FROM AUTHOR]

We previously proposed a role for the two-pore domain potassium (K2P) channel TREK-1 in hyperoxia (HO)-induced lung injury. To determine whether redundancy among the three TREK isoforms (TREK-1, TREK-2, and TRAAK) could protect from HO-induced injury, we now examined the effect of deletion of all three TREK isoforms in a clinically relevant scenario of prolonged HO exposure and mechanical ventilation (MV). We exposed WT and TREK-1/TREK-2/TRAAK-deficient [triple knockout (KO)] mice to either room air, 72-h HO, MV [high and low tidal volume (TV)], or a combination of HO + MV and measured quasistatic lung compliance, bronchoalveolar lavage (BAL) protein concentration, histologic lung injury scores (LIS), cellular apoptosis, and cytokine levels. We determined surfactant gene and protein expression and attempted to prevent HO-induced lung injury by prophylactically administering an exogenous surfactant (Curosurf). HO treatment increased lung injury in triple KO but not WT mice, including an elevated LIS, BAL protein concentration, and markers of apoptosis, decreased lung compliance, and a more proinflammatory cytokine phenotype. MV alone had no effect on lung injury markers. Exposure to HO + MV (low TV) further decreased lung compliance in triple KO but not WT mice, and HO + MV (high TV) was lethal for triple KO mice. In triple KO mice, the HO-induced lung injury was associated with decreased surfactant protein (SP) A and SPC but not SPB and SPD expression. However, these changes could not be explained by alterations in the transcription factors nuclear factor-1 (NF-1), NKX2.1/thyroid transcription factor-1 (TTF-1) or c-jun, or lamellar body levels. Prophylactic Curosurf administration did not improve lung injury scores or compliance in triple KO mice. [ABSTRACT FROM AUTHOR]

Background: Solitary pulmonary nodules (SPN) are frequently detected in cancer patients. These lesions are often considered as pulmonary metastases and increasingly treated by non-surgical techniques without histological confirmation. The aim of this study is to determine the histological nature of SPN resected by thoracoscopy and to identify risk factors of malignancy.Methods: Single-institution retrospective analysis of all consecutive patients with previously known malignancies who underwent thoracoscopic resection of SPN with unknown diagnosis between 2001 and 2014.Results: One hundred and forty cancer patients underwent thoracoscopic resection of a SPN. The resected SPN was benign in 34 patients (24.3%) and malignant in 106 patients. The latter were metastasis in 70 patients (50%) and a primary lung cancer in 36 patients (25.7%). Upon univariate analysis, malignancy was significantly associated with age >60 years, disease-free interval ≥24 months, SPN size >8 mm, upper lobe localization and SUVmax > 2.5 on PET-CT. Upon multivariate analysis, upper lobe localization and SUVmax > 2.5 were associated with malignancy. Smoking was significantly associated with SPN containing primary lung cancer.Conclusion: In this series, only 50% of SPN in patients with known malignant disease were pulmonary metastases and 25% had a newly diagnosed NSCLC. Smoking was associated with primary lung cancer but no other predictor was found to allow the distinction between pulmonary metastasis and lung cancer. These results endorse the need of histological confirmation of SPN in patients with previous malignancies to avoid diagnostic uncertainty and suboptimal treatments. [ABSTRACT FROM AUTHOR]

Background: Dengue is a major public health problem worldwide. Assessment of adaptive immunity is important to understanding immunopathology and to define correlates of protection against dengue virus (DENV). To enable global assessment of CD4+ T cell responses, we mapped HLA-DRB1-restricted DENV-specific CD4+ T cell epitopes in individuals previously exposed to DENV in the general population of the dengue-endemic region of Managua, Nicaragua. Methods: HLA class II epitopes in the population of Managua were identified by an in vitro IFNγ ELISPOT assay. CD4+ T cells purified by magnetic bead negative selection were stimulated with HLA-matched epitope pools in the presence of autologous antigen-presenting cells, followed by pool deconvolution to identify specific epitopes. The epitopes identified in this study were combined with those previously identified in the DENV endemic region of Sri Lanka, to generate a "megapool" (MP) consisting of 180 peptides specifically designed to achieve balanced HLA and DENV serotype coverage. The DENV CD4MP180 was validated by intracellular cytokine staining assays. Results: We detected responses directed against a total of 431 epitopes, representing all 4 DENV serotypes, restricted by 15 different HLA-DRB1 alleles. The responses were associated with a similar pattern of protein immunodominance, overall higher magnitude of responses, as compared to what was observed previously in the Sri Lanka region. Based on these epitope mapping studies, we designed a DENV CD4 MP180 with higher and more consistent coverage, which allowed the detection of CD4+ T cell DENV responses ex vivo in various cohorts of DENV exposed donors worldwide, including donors from Nicaragua, Brazil, Singapore, Sri Lanka, and U.S. domestic flavivirus-naïve subjects immunized with Tetravalent Dengue Live-Attenuated Vaccine (TV005). This broad reactivity reflects that the 21 HLA-DRB1 alleles analyzed in this and previous studies account for more than 80% of alleles present with a phenotypic frequency ≥5% worldwide, corresponding to 92% phenotypic coverage of the general population (i.e., 92% of individuals express at least one of these alleles). Conclusion: The DENV CD4 MP180 can be utilized to measure ex vivo responses to DENV irrespective of geographical location. [ABSTRACT FROM AUTHOR]

We report on 11 cases of specific polysaccharide antibody deficiency (SPAD) revealed in adulthood by severe infections with encapsulated bacteria. Given that immunoglobulin replacement therapy can effectively prevent the recurrence of bacterial infections in this context, SPAD should be considered once other antibody deficiencies have been ruled out. [ABSTRACT FROM AUTHOR]

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The recent discoveries of deeply buried Cretaceous reservoir bodies in the Atlantic Ocean revealed that relationships between the distribution of spring carbonate deposits and faults are poorly understood. The well-exposed Quaternary deposits at Obruktepe (Denizli Basin, Turkey) provide an opportunity to reconstruct the three-dimensional sedimentary architecture of such a system. Integration of sedimentological, lithofacies and geochemical analyses reveals complexity in the lateral relationships between sedimentary environments, faults and geothermal spring carbonates. Five environmental systems are distinguished based on the lithofacies analysis: (i) vent; (ii) smooth slope; (iii) travertine-terrace; (iv) tufa-barrage; and (v) flood systems. Encrusting, baffling and settling sedimentary processes are reflected in data acquired at several scales, from lithofacies observations to the morphology and arrangement of geobodies, together with microfabrics and stable carbon and oxygen isotope data. Mean values of +4·9‰ δ13C and −8·74‰ δ18O Vienna PeeDee Belemnite reflect geothermal circulation of springwaters. The environmental distribution and lithofacies indicate a lateral continuum between travertine and tufa deposits within this hot spring system. This finding supports two depositional models in which water flow variation is the main control on both Ca CO3 precipitation and the resulting formation of travertine and tufa. The proposed models address the factors responsible for the development of these complex mound-shaped carbonate spring deposits, and how they are related to fluid circulation at depth and in association with faults. [ABSTRACT FROM AUTHOR]

Background: Lung maturation can be disrupted through pro-inflammatory processes including intra-uterine amniotic infection, mechanical ventilation, or oxidative stress. Lincr, originally identified as a gene induced in the lung by lipopolysaccharide (LPS), is also expressed in the developing lung. The Lung- inducible Neuralized-related C3HC4 RING domain (LINCR) protein is structurally related to Drosophila Neuralized, a regulator of the developmentally important Notch signaling pathway. LINCR is expressed in alveolar epithelial type II cells in the mature lung, and its expression is markedly increased by LPS and inflammatory cytokines. To test the hypothesis that targeted overexpression of LINCR in lung epithelium would interfere with normal lung development, we generated double transgenic mice that conditionally overexpress LINCR in lung epithelium under the control of doxycycline. Results: Single transgenic controls and double transgenic mice not treated with doxycycline were unaffected, but double transgenic mice exposed to doxycycline starting at embryonic day 6 developed markedly hypoplastic lungs with decreased numbers of alveoli and large cysts lined with a proximalized and poorly differentiated epithelium expressing Hairy/Enhancer of Split 1, an effector of Notch signaling. The phenotype was similar to that caused by overexpression of activated Notch1 in lung epithelium. Conclusions: LINCR may exert its effects on distal lung development in this model through activation of the Notch signaling pathway. Developmental Dynamics 244:827-838, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: Lung maturation can be disrupted through pro-inflammatory processes including intra-uterine amniotic infection, mechanical ventilation, or oxidative stress. Lincr, originally identified as a gene induced in the lung by lipopolysaccharide (LPS), is also expressed in the developing lung. The Lung- inducible Neuralized-related C3HC4 RING domain (LINCR) protein is structurally related to Drosophila Neuralized, a regulator of the developmentally important Notch signaling pathway. LINCR is expressed in alveolar epithelial type II cells in the mature lung, and its expression is markedly increased by LPS and inflammatory cytokines. To test the hypothesis that targeted overexpression of LINCR in lung epithelium would interfere with normal lung development, we generated double transgenic mice that conditionally overexpress LINCR in lung epithelium under the control of doxycycline. Results: Single transgenic controls and double transgenic mice not treated with doxycycline were unaffected, but double transgenic mice exposed to doxycycline starting at embryonic day 6 developed markedly hypoplastic lungs with decreased numbers of alveoli and large cysts lined with a proximalized and poorly differentiated epithelium expressing Hairy/Enhancer of Split 1, an effector of Notch signaling. The phenotype was similar to that caused by overexpression of activated Notch1 in lung epithelium. Conclusions: LINCR may exert its effects on distal lung development in this model through activation of the Notch signaling pathway. Developmental Dynamics 244:827-838, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]