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Objectives To investigate photon-counting CT (PCCT)–derived virtual monoenergetic images (VMI) for artifact reduction in patients with unilateral total hip replacements (THR). Methods Forty-two patients with THR and portal-venous phase PCCT of the abdomen and pelvis were retrospectively included. For the quantitative analysis, region of interest (ROI)–based measurements of hypodense and hyperdense artifacts, as well as of artifact-impaired bone and the urinary bladder, were conducted, and corrected attenuation and image noise were calculated as the difference of attenuation and noise between artifact-impaired and normal tissue. Two radiologists qualitatively evaluated artifact extent, bone assessment, organ assessment, and iliac vessel assessment using 5-point Likert scales. Results VMI 110keV yielded a significant reduction of hypo- and hyperdense artifacts compared to conventional polyenergetic images (CI) and the corrected attenuation closest to 0, indicating best possible artifact reduction (hypodense artifacts: CI: 237.8 ± 71.4 HU, VMI 110keV : 8.5 ± 122.5 HU; p  < 0.05; hyperdense artifacts: CI: 240.6 ± 40.8 HU vs. VMI 110keV : 13.0 ± 110.4 HU; p  < 0.05). VMI 110keV concordantly provided best artifact reduction in the bone and bladder as well as the lowest corrected image noise. In the qualitative assessment, VMI 110keV received the best ratings for artifact extent (CI: 2 (1–3), VMI 110keV : 3 (2–4); p  < 0.05) and bone assessment (CI: 3 (1–4), VMI 110keV : 4 (2–5); p  < 0.05), whereas organ and iliac vessel assessments were rated highest in CI and VMI 70keV . Conclusions PCCT-derived VMI effectively reduce artifacts from THR and thereby improve assessability of circumjacent bone tissue. VMI 110keV yielded optimal artifact reduction without overcorrection, yet organ and vessel assessments at that energy level and higher were impaired by loss of contrast. Clinical relevance statement PCCT-enabled artifact reduction is a feasible method for improving assessability of the pelvis in patients with total hip replacements at clinical routine imaging. Key Points • Photon-counting CT-derived virtual monoenergetic images at 110 keV yielded best reduction of hyper- and hypodense artifacts, whereas higher energy levels resulted in artifact overcorrection. • The qualitative artifact extent was reduced best in virtual monoenergetic images at 110 keV, facilitating an improved assessment of the circumjacent bone. • Despite significant artifact reduction, assessment of pelvic organs as well as vessels did not profit from energy levels higher than 70 keV, due to the decline in image contrast.

Objectives The aim of this study was to evaluate whether simple 2D measurements in axial slices of head and neck CT examinations correlate with generally established measurements of body composition in abdominal CT at the height of the third lumbar vertebra and thus allow for an estimation of muscle and fat masses. Methods One hundred twenty-two patients who underwent concurrent CT of the head and neck and the abdomen between July 2016 and July 2020 were retrospectively included. For a subset of 30 patients, additional bioelectrical impedance analysis (BIA) was available. Areas of paraspinal muscles at the height of the third (C3) and fifth cervical vertebrae (C5) as well as the total cross-sectional area at the height of C3 and at the submandibular level were correlated with the results of abdominal measurements and BIA. Furthermore, intra- and interreader variabilities of all measurements were assessed. Results Regarding adipose tissue, good correlations were found between the total cross-sectional area of the patient’s body at the submandibular level and at the height of C3 between both abdominal measurements and BIA results ( r = 0.8–0.92; all p < 0.001). Regarding muscle, the total paraspinal muscle area at the height of C3 and C5 showed strong correlations with abdominal measurements and moderate to strong correlations with BIA results ( r = 0.44–0.80; all p < 0.001), with the muscle area on C5 yielding slightly higher correlations. Conclusions Body composition information can be obtained with comparable reliability from head and neck CT using simple biplanar measurements as from abdominal CT. Key Points • The total paraspinal muscle area at the height of C3 and C5 correlates strongly with abdominal muscle mass. • The total cross-sectional area at the submandibular level and at the height of C3 shows good correlations with abdominal fat mass. • The described measurements facilitate a rapid, opportunistic assessment of relevant body composition parameters.

IntroductionTo determine whether post-treatment magnetic resonance imaging (MRI)-based texture analysis of liver metastases (LM) may be suited predicting therapy response to transarterial radioembolization (TARE) during follow-up.Materials and MethodsThirty-seven patients with LM treated by TARE (mean age 63.4 years) between January 2006 and December 2014 were identified in this retrospective feasibility study. They underwent dynamic contrast-enhanced and hepatocellular phase MRI after TARE (mean 2.2 days). Response was evaluated on follow-up imaging scheduled in intervals of 3 months (median follow-up, 7.3 months) based on response evaluation criteria in solid tumors 1.1 (RECIST 1.1). Results of texture analysis [mean, standard deviation, skewness (s), kurtosis (k), entropy and uniformity] were compared between patients with progressive disease (PD) and patients with stable disease (SD), partial or complete response (PR/CR). Receiver operating characteristics including the area under the curve (AUC) and cutoff values including the sensitivity and specificity were calculated.ResultsAccording to RECIST 1.1, 24 patients (64.9%) had PD, 8 SD (21.6%) and 5 PR (13.5%). MRI-based texture analysis showed an earlier differentiation between patients with and without PD when compared with RECIST 1.1. Median k (2.88 vs. 2.35) in arterial phase MRI and median s (0.48 vs. 0.25) and k (2.85 vs. 2.25) in venous phase MRI were significantly different (p < 0.05). The AUC for k derived from arterial phase MRI was 0.73 (cutoff = 2.55, sensitivity = 0.83, specificity = 0.62) (p < 0.05). The AUC for s and k in venous phase MRI was 0.76 (cutoff = 0.35, sensitivity = 0.71, specificity = 0.85) (p > 0.05) and 0.83 (cutoff = 2.50, sensitivity = 0.75, specificity = 0.85) (p < 0.05).ConclusionThis study indicates the potential of MRI-based texture analysis at arterial and venous phase MRI for the early prediction of PD after TARE.Level of EvidenceIV.

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.

To investigate the impact of short summers and long summer solar periods at high latitudes on the behavior of a nocturnal, hibernating mammal, we recorded the phenology of Myotis lucifugus (little brown myotis) at 60° N in the Northwest Territories (NWT), Canada. In particular, we assessed the timing of spring emergence from, and autumn entry into, hibernation, reproduction, and seasonal mass fluctuations. We used a combination of acoustic monitoring and capture surveys at two hibernacula and two maternity roosts during 2011 and 2012. Myotis spp. were active at the hibernacula from late April to late September/early October, suggesting that the “active” season length is similar to that of populations farther south. At maternity colonies, we detected M. lucifugus activity from early May to early October, with peaks during mid‐July in both years. Lactation, fledging, and weaning all occurred later in the NWT than at more southern locations, and reproductive rates were significantly lower than rates observed farther south. The average mass of individuals fluctuated throughout the season, with an initial decline immediately following emergence from hibernation likely reflecting increased energy expenditure due to flight and decreased use of torpor, coupled with relatively low prey intake due to low prey abundance associated with cool temperatures. Females did not appear to have lower pre‐hibernation masses than those in more southern populations, suggesting that despite the cool spring and autumn temperatures, and short summer nights, bats are able to obtain enough energy for reproduction and mass accumulation for hibernation. However, the lower reproductive rates may indicate that there are limitations to life at the northern limits of the species' range.

Theoretical, laboratory, and chamber studies have shown fast regeneration of the hydroxyl radical (OH) in the photochemistry of isoprene, largely due to unimolecular reactions which were previously thought not to be important under atmospheric conditions. Based on early field measurements, nearly complete regeneration was hypothesized for a wide range of tropospheric conditions, including areas such as the rainforest where slow regeneration of OH radicals is expected due to low concentrations of nitric oxide (NO). In this work the OH regeneration in isoprene oxidation is directly quantified for the first time through experiments covering a wide range of atmospherically relevant NO levels (between 0.15 and 2 ppbv – parts per billion by volume) in the atmospheric simulation chamber SAPHIR. These conditions cover remote areas partially influenced by anthropogenic NO emissions, giving a regeneration efficiency of OH close to 1, and areas like the Amazonian rainforest with very low NO, resulting in a surprisingly high regeneration efficiency of 0.5, i.e. a factor of 2 to 3 higher than explainable in the absence of unimolecular reactions. The measured radical concentrations were compared to model calculations, and the best agreement was observed when at least 50 % of the total loss of isoprene peroxy radicals conformers (weighted by their abundance) occurs via isomerization reactions for NO lower than 0.2 ppbv. For these levels of NO, up to 50 % of the OH radicals are regenerated from the products of the 1,6 α-hydroxy-hydrogen shift (1,6-H shift) of Z-δ-RO2 radicals through the photolysis of an unsaturated hydroperoxy aldehyde (HPALD) and/or through the fast aldehydic hydrogen shift (rate constant ∼10 s−1 at 300 K) in di-hydroperoxy carbonyl peroxy radicals (di-HPCARP-RO2), depending on their relative yield. The agreement between all measured and modelled trace gases (hydroxyl, hydroperoxy, and organic peroxy radicals, carbon monoxide, and the sum of methyl vinyl ketone, methacrolein, and hydroxyl hydroperoxides) is nearly independent of the adopted yield of HPALD and di-HPCARP-RO2 as both degrade relatively fast (<1 h), forming the OH radical and CO among other products. Taking into consideration this and earlier isoprene studies, considerable uncertainties remain on the distribution of oxygenated products, which affect radical levels and organic aerosol downwind of unpolluted isoprene-dominated regions.

The ProteomeTools project provides the proteomics community with a physical synthetic tryptic peptide resource and a digital LC-MS/MS data resource covering all human proteins. We describe ProteomeTools, a project building molecular and digital tools from the human proteome to facilitate biomedical research. Here we report the generation and multimodal liquid chromatography–tandem mass spectrometry analysis of >330,000 synthetic tryptic peptides representing essentially all canonical human gene products, and we exemplify the utility of these data in several applications. The resource (available at http://www.proteometools.org ) will be extended to >1 million peptides, and all data will be shared with the community via ProteomicsDB and ProteomeXchange.

In luminal breast cancer, adjuvant CDK4/6 inhibitors (eg, abemaciclib) improve invasive disease-free survival. In patients with T1–2, grade 1–2 tumours, and one or two sentinel lymph node metastases, completion axillary lymph node dissection (cALND) is the only prognostic tool available that can reveal four or more nodal metastases (pN2–3), which is the only indication for adjuvant abemaciclib in this setting. However, this technique can lead to substantial arm morbidity in patients. We aimed to pragmatically describe the potential benefit and harm of this strategy on the individual patient level in patients from the ongoing SENOMAC trial. In the randomised, phase 3, SENOMAC trial, patients aged 18 years or older, of any performance status, with clinically node-negative T1–T3 breast cancer and one or two sentinel node macrometastases from 67 sites in five European countries (Denmark, Germany, Greece, Italy, and Sweden) were randomly assigned (1:1), via permutated block randomisation (random block size of 2 and 4) stratified by country, to either cALND or its omission (ie, they had a sentinel lymph node biopsy only). The primary outcome is overall survival, which is yet to be reported. In this post-hoc analysis, patients from the SENOMAC per-protocol population, with luminal oestrogen-receptor positive, HER2-negative, T1–2, histological grade 1–2 breast cancer, with tumour size of 5 cm or smaller were selected to match the characteristics of cohort 1 of the monarchE trial who would only have an indication for adjuvant abemaciclib if found to have 4 or more nodal metastases. The primary study objective was to determine the number of patients who developed patient-reported severe or very severe impairment of physical arm function after cALND (as measured by the Lymphedema Functioning, Disability, and Health [Lymph-ICF] Questionnaire) 1 year after surgery to avoid one invasive disease-free survival event at 5 years with 2 years of adjuvant abemaciclib, using invasive disease-free survival event data from cohort 1 of the monarchE trial. The SENOMAC trial is registered with ClincialTrials.gov, NCT02240472, and is closed to accrual and ongoing. Between Jan 31, 2015, and Dec 31, 2021, 2766 patients were enrolled in SENOMAC and randomly assigned to cALND (n=1384) or sentinel node biopsy only (n=1382), of whom 2540 were included in the per-protocol population. 1705 (67%) of 2540 patients met this post-hoc study's eligibility criteria, of whom 802 (47%) had a cALND and 903 (53%) had a sentinel lymph node biopsy only. Median age at randomisation was 62 years (IQR 52–71), 1699 (>99%) of 1705 patients were female, and six (<1%) were male. Among 1342 patients who responded to questionnaires, after a median follow-up of 45·2 months (IQR 25·6–59·8; data cutoff Nov 17, 2023), patient-reported severe or very severe impairment of physical arm function was reported in 84 (13%) of 634 patients who had cALND versus 30 (4%) of 708 who had sentinel lymph node biopsy only (χ2 test p<0·0001). To avoid one invasive disease-free survival event at 5 years with adjuvant abemaciclib, cALND would need to be performed in 104 patients, and would result in nine patients having severe or very severe impairment of physical arm function 1 year after surgery. As a method to potentially identify an indication for abemaciclib, and subsequently avoid invasive disease-free survival events at 5 years with 2 years of adjuvant abemaciclib, cALND carries a substantial risk of severe or very severe arm morbidity and so cALND should be discouraged for this purpose. Swedish Research Council, the Swedish Cancer Society, the Nordic Cancer Union, and the Swedish Breast Cancer Association.

The oxidation of limonene by the hydroxyl (OH) radical and ozone (O3) was investigated in the atmospheric simulation chamber SAPHIR (Simulation of Atmospheric PHotochemistry In a large Reaction Chamber) in experiments performed at different nitric oxide (NO) mixing ratios from nearly 0 up to 10 ppbv. For the experiments dominated by OH oxidation, the formaldehyde (HCHO) yield was experimentally determined and found to be (12 ± 3), (13 ± 3), and (32 ± 5) % for experiments with low (∼ 0.1 ppbv), medium (∼ 0.3 ppbv), and high NO (5 to 10 ppbv), respectively. The yield in an ozonolysis-only experiment was (10 ± 1) %, which agrees with previous laboratory studies. The experimental yield of the first-generation organic nitrates from limonene–OH oxidation is calculated as (34 ± 5) %, about 11 % higher than the value in the Master Chemical Mechanism (MCM), which is derived from structure–activity relationships (SARs). Time series of measured radicals, trace-gas concentrations, and OH reactivity are compared to results from zero-dimensional chemical box model calculations applying MCM v3.3.1. Modeled OH reactivity is 5 to 10 s−1 (25 % to 33 % of the OH reactivity at the start of the experiment) higher than measured values at the end of the experiments under all chemical conditions investigated, suggesting either that there are unaccounted loss processes of limonene oxidation products or that products are less reactive toward OH. In addition, model calculations underestimate measured hydroperoxyl radical (HO2) concentrations by 20 % to 90 % and overestimate organic peroxyl radical (RO2) concentrations by 50 % to 300 %. The largest deviations are found in low-NO experiments and in the ozonolysis experiment. An OH radical budget analysis, which uses only measured quantities, shows that the budget is closed in most of the experiments. A similar budget analysis for RO2 radicals suggests that an additional RO2 loss rate constant of about (1–6) × 10−2 s−1 for first-generation RO2 is required to match the measured RO2 concentrations in all experiments. Sensitivity model runs indicate that additional reactions converting RO2 to HO2 at a rate constant of about (1.7–3.0) × 10−2 s−1 would improve the model–measurement agreement of NOx, HO2, and RO2 concentrations and OH reactivity. Reaction pathways that could lead to the production of additional OH and HO2 are discussed, which include isomerization reactions of RO2 from the oxidation of limonene, different branching ratios for the reaction of RO2 with HO2, and a faster rate constant for RO2 recombination reactions. As the exact chemical mechanisms of the additional HO2 and OH sources could not be identified, further work needs to focus on quantifying organic product species and organic peroxy radicals from limonene oxidation.

Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere – the global carbon budget – is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and methodology to quantify the five major components of the global carbon budget and their uncertainties. CO2 emissions from fossil fuels and industry (EFF) are based on energy statistics and cement production data, respectively, while emissions from land-use change (ELUC), mainly deforestation, are based on land-cover change data and bookkeeping models. The global atmospheric CO2 concentration is measured directly and its rate of growth (GATM) is computed from the annual changes in concentration. The ocean CO2 sink (SOCEAN) and terrestrial CO2 sink (SLAND) are estimated with global process models constrained by observations. The resulting carbon budget imbalance (BIM), the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere, is a measure of imperfect data and understanding of the contemporary carbon cycle. All uncertainties are reported as ±1σ. For the last decade available (2007–2016), EFF was 9.4 ± 0.5 GtC yr−1, ELUC 1.3 ± 0.7 GtC yr−1, GATM 4.7 ± 0.1 GtC yr−1, SOCEAN 2.4 ± 0.5 GtC yr−1, and SLAND 3.0 ± 0.8 GtC yr−1, with a budget imbalance BIM of 0.6 GtC yr−1 indicating overestimated emissions and/or underestimated sinks. For year 2016 alone, the growth in EFF was approximately zero and emissions remained at 9.9 ± 0.5 GtC yr−1. Also for 2016, ELUC was 1.3 ± 0.7 GtC yr−1, GATM was 6.1 ± 0.2 GtC yr−1, SOCEAN was 2.6 ± 0.5 GtC yr−1, and SLAND was 2.7 ± 1.0 GtC yr−1, with a small BIM of −0.3 GtC. GATM continued to be higher in 2016 compared to the past decade (2007–2016), reflecting in part the high fossil emissions and the small SLAND consistent with El Niño conditions. The global atmospheric CO2 concentration reached 402.8 ± 0.1 ppm averaged over 2016. For 2017, preliminary data for the first 6–9 months indicate a renewed growth in EFF of +2.0 % (range of 0.8 to 3.0 %) based on national emissions projections for China, USA, and India, and projections of gross domestic product (GDP) corrected for recent changes in the carbon intensity of the economy for the rest of the world. This living data update documents changes in the methods and data sets used in this new global carbon budget compared with previous publications of this data set (Le Quéré et al., 2016, 2015b, a, 2014, 2013). All results presented here can be downloaded from https://doi.org/10.18160/GCP-2017 (GCP, 2017).