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Objectives To investigate whether the increased soft tissue contrast of virtual monoenergetic images (VMIs) obtained from a spectral detector computed tomography (SDCT) system improves washout assessment of arterially hyper-enhancing liver lesions. Methods Fifty-nine arterially hyper-enhancing lesions in 31 patients (age 65 ± 9 years, M/W 20/11) were included in this IRB-approved study. All patients underwent multi-phase SDCT for HCC screening. MRI, CEUS or biopsy within 3 months served as standard of reference to classify lesions as LiRADS 3 or 4/5. VMIs and conventional images (CIs) were reconstructed. Visual analysis was performed on 40, 60, and 80 kiloelectronvolt (keV) and CIs by 3 radiologists. Presence and visibility of washout were assessed; image quality and confidence of washout evaluation were evaluated on 5-point Likert scales. Signal-to-noise ratio (SNR), lesion-to-liver contrast-to-noise ratio (CNR) (|HU lesion –HU liver |/SD liver ) and washout (|HU lesion –HU liver |) were calculated. Statistical assessment was performed using ANOVA and Wilcoxon test. Results On subjective lesion analysis, the highest level of diagnostic confidence and highest sensitivity for the detection of lesion washout were found for 40-keV VMIs (40 keV vs. CI, 81.3 vs. 71.3%). Image quality parameters were significantly better in low-kiloelectronvolt VMIs than in CIs ( p  < 0.05; e.g. SNR liver : 40 keV vs. CIs, 12.5 ± 4.1 vs. 5.6 ± 1.6). In LiRADS 4/5 lesions, CNR and quantitative washout values were significantly higher in 40-keV VMIs compared to CIs ( p  < 0.05; e.g. CNR and washout in 40 keV vs. CIs, 2.3 ± 1.6 vs. 0.8 ± 0.5 and 29.0 ± 19.1 vs. 12.9 ± 6.9 HU, respectively). Conclusion By increasing lesion contrast, low-kiloelectronvolt VMIs obtained from SDCT improve washout assessment of hyper-enhancing liver lesions with respect to washout visibility and diagnostic confidence. Key Points • Low-kiloelectronvolt virtual monoenergetic images from spectral detector CT facilitate washout assessment in arterially hyper-enhancing liver lesions. • Image quality and quantitative washout parameters as well as subjective washout visibility and diagnostic confidence benefit from low-kiloelectronvolt virtual monoenergetic images.

Objectives To systematically investigate the usability of virtual non-contrast reconstructions (VNC) derived from dual-layer CT (DLCT) for detection and size measurements of kidney stones with regards to different degrees of surrounding iodine-induced attenuation and radiation dose. Methods Ninety-two kidney stones of varying size (3–14 mm) and composition were placed in a phantom filled with different contrast media/water mixtures exhibiting specific iodine-induced attenuation (0–1500 HU). DLCT-scans were acquired using CTDI vol of 2 mGy and 10 mGy. Conventional images (CI) and VNC 0H-1500HU were reconstructed. Reference stone size was determined using a digital caliper (Man-M). Visibility and stone size were assessed. Statistical analysis was performed using the McNemar test, Wilcoxon test, and the coefficient of determination. Results All stones were visible on CI 0HU and VNC 200HU . Starting at VNC 400 HU , the detection rate decreased with increasing HU and was significantly lower as compared to CI 0HU on VNC ≥ 600HU (100.0 vs. 94.0%, p < 0.05). The overall detection rate was higher using 10 mGy as compared to 2 mGy protocol (87.9 vs. 81.8%; p < 0.001). Stone size was significantly overestimated on all VNC compared to Man-M (7.0 ± 3.5 vs. 6.6 ± 2.8 mm, p < 0.001). Again, the 10 mGy protocol tended to show a better correlation with Man-M as compared to 2 mGy protocol ( R 2 = 0.39–0.68 vs. R 2 = 0.31–0.57). Conclusions Detection and size measurements of kidney stones surrounded by contrast media on VNC are feasible. The detection rate of kidney stones decreases with increasing iodine-induced attenuation and with decreasing radiation dose as well as stone size, while remaining comparable to CI 0HU on VNC ≤ 400 HU . Key Points • The detection rate of kidney stones on VNC depends on the surrounding iodine-induced attenuation, the used radiation dose, and the stone size. • The detection rate of kidney stones on VNC decreases with greater iodine-induced attenuation and with lower radiation dose, particularly in small stones. • The visibility of kidney stones on VNC ≤ 400 HU remains comparable to true-non-contrast scans even when using a low-dose technique.

Objectives The blood of patients with anemia demonstrates distinctly lower attenuation in unenhanced CT images. However, the frequent usage of intravenous contrast hampers evaluation of anemia. Spectral detector computed tomography (SDCT) allows for reconstruction of virtual non-contrast images (VNC) from contrast-enhanced data (CE). The purpose of this study was to evaluate whether VNC allow for prediction of anemia. Methods Five hundred twenty-two patients with CE-SDCT of the chest and accessible serum hemoglobin (HbS) were retrospectively included. Patients were assigned to three groups (severe anemia, moderate/mild anemia, and healthy) based on recent lab tests (≤ 7 days) for HbS following gender and the WHO definition of anemia. CT attenuation was determined using two ROI in the left ventricular lumen and one ROI in the descending thoracic aorta. ROI were placed on CE and copied to VNC. ANOVA, linear regression, and receiver operating characteristics were used for statistic evaluation. Results Average HbS was 11.6 ± 2.4 g/dl. Attenuation on VNC showed significant differences between healthy patients, patients with mild/moderate anemia, and severely anemic patients (all p ≤ 0.05). Applying cutoffs of 39.2/37.6 HU and 33.6/32.7 HU allowed to differentiate between healthy, mild/moderately, and severely anemic men/women (AUC 0.857/0.833 and 0.879/0.932). A linear relationship between HbS and attenuation on VNC was established ( r 2 = 0.54, HbS = − 0.875 + 0.329 × HU). Conclusions An approximation of HbS and presence of anemia can be conducted based on simple attenuation measurements in contrast-enhanced SDCT examinations enabled by VNC imaging. Key Points • While the attenuation of blood is a previously described biomarker for anemia in non-contrast images, virtual non-contrast images from spectral detector CT circumvent this limitation and allow for diagnosis of anemia in contrast-enhanced scans. • Attenuation of blood in virtual non-contrast images derived from spectral detector CT shows a moderate correlation to serum hemoglobin levels. • Presence of anemia be estimated in virtual non-contrast images using proposed cutoffs of 39.2 HU and 37.6 HU for men and women, respectively, to differentiate between healthy and anemic patients.

The objective of this study was to evaluate the effectiveness of a streamlined interfacility referral protocol in reducing door-to-balloon (D2B) times for patients experiencing acute ST-segment elevation myocardial infarction (STEMI). In a retrospective database review, we compared D2B times for patients requiring interfacility transfer after the implementation of a streamlined referral protocol. All patients undergoing interfacility transport with a referring diagnosis of STEMI were eligible for inclusion. Quality management databases were reviewed by trained abstractors using standardized data entry forms for D2B times from July 2009 through June 2010. Median D2B times with interquartile ranges are reported. A total of 133 patients exhibited complete data and were included in the analysis, 54 of which were transferred via the streamlined referral protocol. Streamlined referral patients exhibited a median D2B time of 101 minutes (interquartile range, 88-128) vs a median D2B time of 122 minutes (interquartile range, 99-157) for the traditional referral group (P = .001). Door-to-balloon times of 90 minutes or less were achieved in 13% of the traditional referral patients and in 30% of the streamlined protocol group (odds ratio, 2.9; 95% confidence interval, 1.2-7). The implementation of a streamlined referral protocol has significantly reduced D2B times for patients diagnosed with STEMI that required interfacility transport for intervention.

Radiocarbon (14C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric 14C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable 14C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the 14C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine 14C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.

In May 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened a panel of nutritionists, physiologists and microbiologists to review the definition and scope of synbiotics. The panel updated the definition of a synbiotic to “a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host”. The panel concluded that defining synbiotics as simply a mixture of probiotics and prebiotics could suppress the innovation of synbiotics that are designed to function cooperatively. Requiring that each component must meet the evidence and dose requirements for probiotics and prebiotics individually could also present an obstacle. Rather, the panel clarified that a complementary synbiotic, which has not been designed so that its component parts function cooperatively, must be composed of a probiotic plus a prebiotic, whereas a synergistic synbiotic does not need to be so. A synergistic synbiotic is a synbiotic for which the substrate is designed to be selectively utilized by the co-administered microorganisms. This Consensus Statement further explores the levels of evidence (existing and required), safety, effects upon targets and implications for stakeholders of the synbiotic concept.Gut microbiota can be manipulated to benefit host health, including the use of probiotics, prebiotics and synbiotics. This Consensus Statement outlines the definition and scope of the term ‘synbiotics’ as determined by an expert panel convened by the International Scientific Association for Probiotics and Prebiotics in May 2019.

Background/objectives: A diet rich in dairy and calcium (Ca) has been variably associated with improvements in body composition and decreased risk of type 2 diabetes. Our objective was to determine if a dietary pattern high in dairy and Ca improves weight loss and subjective appetite to a greater extent than a low dairy/Ca diet during energy restriction in overweight and obese adults with metabolic syndrome. Subjects/methods: A total of 49 participants were randomized to one of two treatment groups: Control (low dairy, ∼700 mg/day Ca, −500 kcal/day) or Dairy/Ca (high dairy, ∼1400 mg/day Ca, −500 kcal/day) for 12 weeks. Body composition, subjective ratings of appetite, food intake, plasma satiety hormones, glycemic response and inflammatory cytokines were measured. Results: Control (−2.2±0.5 kg) and Dairy/Ca (−3.3±0.6 kg) had similar weight loss. Based on self-reported energy intake, the percentage of expected weight loss achieved was higher with Dairy/Ca (82.1±19.4%) than Control (32.2±7.7%; P =0.03). Subjects in the Dairy/Ca group reported feeling more satisfied ( P =0.01) and had lower dietary fat intake ( P =0.02) over 12 weeks compared with Control. Compared with Control, Dairy/Ca had higher plasma levels of peptide tyrosine tyrosine (PYY, P =0.01) during the meal tolerance test at week 12. Monocyte chemoattractant protein-1 was reduced at 30 min with Dairy/Ca compared with Control ( P =0.04). Conclusions: In conclusion, a dairy- and Ca-rich diet was not associated with greater weight loss than control. Modest increases in plasma PYY concentrations with increased dairy/Ca intake, however, may contribute to enhanced sensations of satisfaction and reduced dietary fat intake during energy restriction.

The proton is one of the main building blocks of all visible matter in the Universe 1 . Among its intrinsic properties are its electric charge, mass and spin 2 . These properties emerge from the complex dynamics of its fundamental constituents—quarks and gluons—described by the theory of quantum chromodynamics 3 – 5 . The electric charge and spin of protons, which are shared among the quarks, have been investigated previously using electron scattering 2 . An example is the highly precise measurement of the electric charge radius of the proton 6 . By contrast, little is known about the inner mass density of the proton, which is dominated by the energy carried by gluons. Gluons are hard to access using electron scattering because they do not carry an electromagnetic charge. Here we investigated the gravitational density of gluons using a small colour dipole, through the threshold photoproduction of the J / ψ particle. We determined the gluonic gravitational form factors of the proton 7 , 8  from our measurement. We used a variety of models 9 – 11 and determined, in all cases, a mass radius that is notably smaller than the electric charge radius. In some, but not all cases, depending on the model, the determined radius agrees well with first-principle predictions from lattice quantum chromodynamics 12 . This work paves the way for a deeper understanding of the salient role of gluons in providing gravitational mass to visible matter. The gluonic gravitational form factor of the proton was determined using various models, and these analyses showed that the mass radius of the proton was smaller than the electric charge radius.

PurposeIn obesity and diabetes the liver is highly susceptible to abnormal uptake and storage of fat. In certain individuals hepatic steatosis predisposes to the development of non-alcoholic steatohepatitis (NASH), a disease marked by hepatic inflammation and fibrosis. Although the precise pathophysiology of NASH is unknown, it is believed that the gut microbiota-liver axis influences the development of this disease. With few treatment strategies available for NASH, exploration of gut microbiota-targeted interventions is warranted. We investigated the therapeutic potential of a prebiotic supplement to improve histological parameters of NASH.MethodsIn a placebo-controlled, randomized pilot trial, 14 individuals with liver-biopsy-confirmed NASH [non-alcoholic fatty liver activity score (NAS) ≥ 5] were randomized to receive oligofructose (8 g/day for 12 weeks followed by 16 g/day for 24 weeks) or isocaloric placebo for 9 months. The primary outcome measure was the change in liver biopsy NAS score and the secondary outcomes included changes in body weight, body composition, glucose tolerance, inflammatory markers, and gut microbiota.ResultsIndependent of weight loss, oligofructose improved liver steatosis relative to placebo and improved overall NAS score (P = 0.016). Bifidobacterium was enhanced by oligofructose, whereas bacteria within Clostridium cluster XI and I were reduced with oligofructose (P < 0.05). There were no adverse side effects that deterred individuals from consuming oligofructose for treatment of this disease.ConclusionsIndependent of other lifestyle changes, prebiotic supplementation reduced histologically-confirmed steatosis in patients with NASH. Larger follow-up studies are warranted.Clinical TrialThis trial was registered at Clinicaltrials.com as NCT03184376.

Patch-seq reveals new neuronal subtypes by combining electrophysiological and RNA-seq data on single neurons in situ . Despite the importance of the mammalian neocortex for complex cognitive processes, we still lack a comprehensive description of its cellular components. To improve the classification of neuronal cell types and the functional characterization of single neurons, we present Patch-seq, a method that combines whole-cell electrophysiological patch-clamp recordings, single-cell RNA-sequencing and morphological characterization. Following electrophysiological characterization, cell contents are aspirated through the patch-clamp pipette and prepared for RNA-sequencing. Using this approach, we generate electrophysiological and molecular profiles of 58 neocortical cells and show that gene expression patterns can be used to infer the morphological and physiological properties such as axonal arborization and action potential amplitude of individual neurons. Our results shed light on the molecular underpinnings of neuronal diversity and suggest that Patch-seq can facilitate the classification of cell types in the nervous system.