Inflammatory bowel disease (IBD)-related colorectal cancer (CRC) is responsible for approximately 2% of the annual mortality from CRC overall, but 10–15% of the annual deaths in IBD patients. ...IBD-related CRC patients are also affected at a younger age than sporadic CRC patients, and have a 5-year survival rate of 50%. Despite optimal medical treatment, the chronic inflammatory state inherent in IBD increases the risk for high-grade dysplasia and CRC, with additional input from genetic and environmental risk factors and the microbiome. Recognizing risk factors, implementing appropriate surveillance, and identifying high-risk patients are key to managing the CRC risk in IBD patients. Chemoprevention strategies exist, and studies evaluating their efficacy are underway. Once dysplasia or invasive cancer is diagnosed, appropriate surgical resection and postoperative treatment and surveillance are necessary. Here, we discuss the current state of IBD-related CRC, prevalence, risk factors, and evidence for surveillance, prophylaxis, and treatment recommendations.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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A model of dynamic orientation using optimized radiofrequency (RF) irradiation produced perpendicular to the holding field is developed for the spin-1 system required for tensor-polarized ...fixed-target experiments. The derivation applies to RF produced close to the Larmor frequency of the nucleus and requires the electron spin-resonance linewidth to be much smaller than the nuclear magnetic resonance frequency. The rate equations are solved numerically to study a semi-saturated steady-state resulting from the two sources of irradiation: microwave from the DNP process and the additional RF used to manipulate the tensor polarization. The steady-state condition and continuous-wave NMR lineshape are found that optimize the spin-1 alignment in the polycrystalline materials used as solid polarized targets in charged-beam nuclear and particle physics experiments.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The environment receives antibiotics through a combination of direct application (e.g., aquaculture and fruit production), as well as indirect release through pharmaceutical manufacturing, sewage and ...animal manure. Antibiotic concentrations in many sewage-impacted rivers are thought to be sufficient to select for antibiotic resistance genes. Yet, because antibiotics are nearly always found associated with antibiotic-resistant faecal bacteria in wastewater, it is difficult to distinguish the selective role of effluent antibiotics within a 'sea' of gut-derived resistance genes. Here we examine the potential for macrolide and fluoroquinolone prescribing in England to select for resistance in the River Thames catchment, England. We show that 64% and 74% of the length of the modelled catchment is chronically exposed to putative resistance-selecting concentrations (PNEC) of macrolides and fluoroquinolones, respectively. Under current macrolide usage, 115 km of the modelled River Thames catchment (8% of total length) exceeds the PNEC by 5-fold. Similarly, under current fluoroquinolone usage, 223 km of the modelled River Thames catchment (16% of total length) exceeds the PNEC by 5-fold. Our results reveal that if reduced prescribing was the sole mitigating measure, that macrolide and fluoroquinolone prescribing would need to decline by 77% and 85%, respectively, to limit resistance selection in the catchment. Significant reductions in antibiotic prescribing are feasible, but innovation in sewage-treatment will be necessary for achieving substantially-reduced antibiotic loads and inactivation of DNA-pollution from resistant bacteria. Greater confidence is needed in current risk-based targets for antibiotics, particularly in mixtures, to better inform environmental risk assessments and mitigation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
VALUE is an open European collaboration to intercompare downscaling approaches for climate change research, focusing on different validation aspects (marginal, temporal, extremes, spatial, ...process‐based, etc.). Here we describe the participating methods and first results from the first experiment, using “perfect” reanalysis (and reanalysis‐driven regional climate model (RCM)) predictors to assess the intrinsic performance of the methods for downscaling precipitation and temperatures over a set of 86 stations representative of the main climatic regions in Europe. This study constitutes the largest and most comprehensive to date intercomparison of statistical downscaling methods, covering the three common downscaling approaches (perfect prognosis, model output statistics—including bias correction—and weather generators) with a total of over 50 downscaling methods representative of the most common techniques.
Overall, most of the downscaling methods greatly improve (reanalysis or RCM) raw model biases and no approach or technique seems to be superior in general, because there is a large method‐to‐method variability. The main factors most influencing the results are the seasonal calibration of the methods (e.g., using a moving window) and their stochastic nature. The particular predictors used also play an important role in cases where the comparison was possible, both for the validation results and for the strength of the predictor–predictand link, indicating the local variability explained. However, the present study cannot give a conclusive assessment of the skill of the methods to simulate regional future climates, and further experiments will be soon performed in the framework of the EURO‐CORDEX initiative (where VALUE activities have merged and follow on).
Finally, research transparency and reproducibility has been a major concern and substantive steps have been taken. In particular, the necessary data to run the experiments are provided at http://www.value‐cost.eu/data and data and validation results are available from the VALUE validation portal for further investigation: http://www.value‐cost.eu/validationportal.
The largest and most comprehensive to date intercomparison of statistical downscaling methods is presented, with a total of over 50 downscaling methods representative of the most common approaches and techniques. Overall, most of the downscaling methods greatly improve raw model biases and no approach is superior in general, due to the large method‐to‐method variability. The main factors influencing the results are the seasonal calibration of the methods and their stochastic nature, for biases in the mean and variance.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Multiscale cardiac modeling has made great advances over the last decade. Highly detailed atrial models were created and used for the investigation of initiation and perpetuation of atrial ...fibrillation. The next challenge is the use of personalized atrial models in clinical practice. In this study, a framework of simple and robust tools is presented, which enables the generation and validation of patient-specific anatomical and electrophysiological atrial models. Introduction of rule-based atrial fiber orientation produced a realistic excitation sequence and a better correlation to the measured electrocardiograms. Personalization of the global conduction velocity lead to a precise match of the measured P-wave duration. The use of a virtual cohort of nine patient and volunteer models averaged out possible model-specific errors. Intra-atrial excitation conduction was personalized manually from left atrial local activation time maps. Inclusion of LE-MRI data into the simulations revealed possible gaps in ablation lesions. A fast marching level set approach to compute atrial depolarization was extended to incorporate anisotropy and conduction velocity heterogeneities and reproduced the monodomain solution. The presented chain of tools is an important step towards the use of atrial models for the patient-specific AF diagnosis and ablation therapy planing.
Aims
. We present the design and pre-launch performance of the Solar Orbiter Heliospheric Imager (SoloHI) which is an instrument prepared for inclusion in the ESA/NASA Solar Orbiter mission, ...currently scheduled for launch in 2020.
Methods
. The goal of this paper is to provide details of the SoloHI instrument concept, design, and pre-flight performance to give the potential user of the data a better understanding of how the observations are collected and the sources that contribute to the signal.
Results
. The paper discusses the science objectives, including the SoloHI-specific aspects, before presenting the design concepts, which include the optics, mechanical, thermal, electrical, and ground processing. Finally, a list of planned data products is also presented.
Conclusions
. The performance measurements of the various instrument parameters meet or exceed the requirements derived from the mission science objectives. SoloHI is poised to take its place as a vital contributor to the science success of the Solar Orbiter mission.
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FMFMET, NUK, UL, UM, UPUK
The scope of the paper is to present the results of a RANS-based aerodynamic high-lift design for a natural laminar flow wing with negative sweep. The chosen high-lift system consists of a Krueger ...leading edge flap with shielding function and a fixed-vane trailing edge flap. The design was first optimized in two main wing sections and then verified by 3D RANS simulations of a wing-body model. Finally, engines were added to the geometric model to estimate the high-lift performance of the landing configuration. With a maximum lift coefficient of
C
L
=
2.85
for the wing-body model with engine, the target from the preliminary aircraft design was reached. Further potential for improvement was found in the optimization strategy and the shape of the fuselage–wing junction.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Ostracism, excluding and ignoring others, results from a variety of factors. Here, we investigate the effect of personality on the likelihood of becoming a target of ostracism. Theorizing that ...individuals low in conscientiousness or agreeableness are at risk of getting ostracized, we tested our hypotheses within 5 preregistered studies: Four experiments investigating participants' willingness to ostracize targets characterized by different personality traits and a reverse correlation face modeling study where we determined and subsequently validated the stereotypical face of an ostracized person. A survey study within a representative German data panel further corroborated our findings. In line with our hypotheses, persons low in conscientiousness or agreeableness provoke more ostracism intentions (Studies 1, 2, and 4), are more likely to be actually ostracized by others (Study 3), represent the stereotype of an "ostracizable" person (Study 5), and report experiencing more ostracism (Study 6). Effects remained stable even after controlling for likability of the target (Study 2 and 4). Moreover, being described as negative on 1 personality dimension could not be compensated by being described as positive on the other (Study 4). In exploratory analyses, we further investigated the effects of openness to experience, neuroticism, and extraversion. In sum, we find evidence that personality affects the likelihood of becoming a target of ostracism, and that especially low agreeableness and conscientiousness represent risk factors.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
Advances in high-throughput materials fabrication and characterization techniques have resulted in faster rates of data collection and rapidly growing volumes of experimental data. To convert this ...mass of information into actionable knowledge of material process-structure-property relationships requires high-throughput data analysis techniques. This work explores the use of the Graph-based endmember extraction and labeling (GRENDEL) algorithm as a high-throughput method for analyzing structural data from combinatorial libraries, specifically, to determine phase diagrams and constituent phases from both x-ray diffraction and Raman spectral data. The GRENDEL algorithm utilizes a set of physical constraints to optimize results and provides a framework by which additional physics-based constraints can be easily incorporated. GRENDEL also permits the integration of database data as shown by the use of critically evaluated data from the Inorganic Crystal Structure Database in the x-ray diffraction data analysis. Also the Sunburst radial tree map is demonstrated as a tool to visualize material structure-property relationships found through graph based analysis.
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