Purpose
PET using radiolabelled amino acids has become a promising tool in the diagnostics of gliomas and brain metastasis. Current research is focused on the evaluation of amide proton transfer ...(APT) chemical exchange saturation transfer (CEST) MR imaging for brain tumour imaging. In this hybrid MR-PET study, brain tumours were compared using 3D data derived from APT-CEST MRI and amino acid PET using O-(2-
18
F-fluoroethyl)-L-tyrosine (
18
F-FET).
Methods
Eight patients with gliomas were investigated simultaneously with
18
F-FET PET and APT-CEST MRI using a 3-T MR-BrainPET scanner. CEST imaging was based on a steady-state approach using a B
1
average power of 1μT. B
0
field inhomogeneities were corrected a Prametric images of magnetisation transfer ratio asymmetry (MTR
asym
) and differences to the extrapolated semi-solid magnetisation transfer reference method, APT# and nuclear Overhauser effect (NOE#), were calculated. Statistical analysis of the tumour-to-brain ratio of the CEST data was performed against PET data using the non-parametric Wilcoxon test.
Results
A tumour-to-brain ratio derived from APT# and
18
F-FET presented no significant differences, and no correlation was found between APT# and
18
F-FET PET data. The distance between local hot spot APT# and
18
F-FET were different (average 20 ± 13 mm, range 4–45 mm).
Conclusion
For the first time, CEST images were compared with
18
F-FET in a simultaneous MR-PET measurement. Imaging findings derived from
18
F-FET PET and APT CEST MRI seem to provide different biological information. The validation of these imaging findings by histological confirmation is necessary, ideally using stereotactic biopsy.
Air pollution, in particular high concentrations of particulate matter smaller than 1 µm in diameter (PM1), continues to be a major health problem, and meteorology is known to substantially influence ...atmospheric PM concentrations. However, the scientific understanding of the ways in which complex interactions of meteorological factors lead to high-pollution episodes is inconclusive. In this study, a novel, data-driven approach based on empirical relationships is used to characterize and better understand the meteorology-driven component of PM1 variability. A tree-based machine learning model is set up to reproduce concentrations of speciated PM1 at a suburban site southwest of Paris, France, using meteorological variables as input features. The model is able to capture the majority of occurring variance of mean afternoon total PM1 concentrations (coefficient of determination (R2) of 0.58), with model performance depending on the individual PM1 species predicted.
Based on the models, an isolation and quantification of individual, season-specific meteorological influences for process understanding at the measurement site is achieved using SHapley Additive exPlanation (SHAP) regression values.
Model results suggest that winter pollution episodes are often driven by a combination of shallow mixed layer heights (MLHs), low temperatures, low wind speeds, or inflow from northeastern wind directions. Contributions of MLHs to the winter pollution episodes are quantified to be on average ∼5 µg/m3 for MLHs below <500 m a.g.l. Temperatures below freezing initiate formation processes and increase local emissions related to residential heating, amounting to a contribution to predicted PM1 concentrations of as much as ∼9 µg/m3. Northeasterly winds are found to contribute ∼5 µg/m3 to predicted PM1 concentrations (combined effects of u- and v-wind components), by advecting particles from source regions, e.g. central Europe or the Paris region.
Meteorological drivers of unusually high PM1 concentrations in summer are temperatures above ∼25 ∘C (contributions of up to ∼2.5 µg/m3), dry spells of several days (maximum contributions of ∼1.5 µg/m3), and wind speeds below ∼2 m/s (maximum contributions of ∼3 µg/m3), which cause a lack of dispersion.
High-resolution case studies are conducted showing a large variability of processes that can lead to high-pollution episodes.
The identification of these meteorological conditions that increase air pollution could help policy makers to adapt policy measures, issue warnings to the public, or assess the effectiveness of air pollution measures.
To increase granularity in human neuroimaging science, we designed and built a next-generation 7 Tesla magnetic resonance imaging scanner to reach ultra-high resolution by implementing several ...advances in hardware. To improve spatial encoding and increase the image signal-to-noise ratio, we developed a head-only asymmetric gradient coil (200 mT m
, 900 T m
s
) with an additional third layer of windings. We integrated a 128-channel receiver system with 64- and 96-channel receiver coil arrays to boost signal in the cerebral cortex while reducing g-factor noise to enable higher accelerations. A 16-channel transmit system reduced power deposition and improved image uniformity. The scanner routinely performs functional imaging studies at 0.35-0.45 mm isotropic spatial resolution to reveal cortical layer functional activity, achieves high angular resolution in diffusion imaging and reduces acquisition time for both functional and structural imaging.
Head motion reduces data quality of neuroimaging data. In three functional magnetic resonance imaging (MRI) experiments we demonstrate that people make less head movements under task than ...resting-state conditions. In Experiment 1, we observed less head motion during a memory encoding task than during the resting-state condition. In Experiment 2, using publicly shared data from the UCLA Consortium for Neuropsychiatric Phenomics LA5c Study, we again found less head motion during several active task conditions than during a resting-state condition, although some task conditions also showed comparable motion. In the healthy controls, we found more head motion in men than in women and more motion with increasing age. When comparing clinical groups, we found that patients with a clinical diagnosis of bipolar disorder, or schizophrenia, move more compared to healthy controls or patients with ADHD. Both these experiments had a fixed acquisition order across participants, and we could not rule out that a first or last scan during a session might be particularly prone to more head motion. Therefore, we conducted Experiment 3, in which we collected several task and resting-state fMRI runs with an acquisition order counter-balanced. The results of Experiment 3 show again less head motion during several task conditions than during rest. Together these experiments demonstrate that small head motions occur during MRI even with careful instruction to remain still and fixation with foam pillows, but that head motion is lower when participants are engaged in a cognitive task. These finding may inform the choice of functional runs when studying difficult-to-scan populations, such as children or certain patient populations. Our findings also indicate that differences in head motion complicate direct comparisons of measures of functional neuronal networks between task and resting-state fMRI because of potential differences in data quality. In practice, a task to reduce head motion might be especially useful when acquiring structural MRI data such as T1/T2-weighted and diffusion MRI in research and clinical settings.
•Resting-state conditions are associated with more head motion.•Task conditions are associated with less head motion.•Older adults and men move more during MRI acquisition.•Bipolar or schizophrenia patients move more than healthy controls.•Cognitive tasks can reduce head motion for improved MRI data quality.
The host metalloprotease meprin β is required for mucin 2 (MUC2) cleavage, which drives intestinal mucus detachment and prevents bacterial overgrowth. To gain access to the cleavage site in MUC2, ...meprin β must be proteolytically shed from epithelial cells. Hence, regulation of meprin β shedding and activation is important for physiological and pathophysiological conditions. Here, we demonstrate that meprin β activation and shedding are mutually exclusive events. Employing ex vivo small intestinal organoid and cell culture experiments, we found that ADAM-mediated shedding is restricted to the inactive pro-form of meprin β and is completely inhibited upon its conversion to the active form at the cell surface. This strict regulation of meprin β activity can be overridden by pathogens, as demonstrated for the bacterial protease Arg-gingipain (RgpB). This secreted cysteine protease potently converts membrane-bound meprin β into its active form, impairing meprin β shedding and its function as a mucus-detaching protease.
Display omitted
•Meprin β activation and shedding are mutually exclusive events•ADAM-mediated pro-meprin β shedding is required for proper mucus integrity•Pathogenic secreted cysteine protease RgpB activates host metalloprotease meprin β•Activation of membrane-bound meprin β prevents its shedding and mucus detachment
ADAM-mediated meprin β shedding is required for mucus detachment, regulating intestinal integrity. This work by Wichert et al. demonstrates that meprin β is exclusively shed in its pro-form. Activation of meprin β by the serine protease MT-2 or the bacterial virulence factor RgpB abrogates its shedding, resulting in a disturbed mucus barrier.
Agrobacterium-mediated transformation is the most widely used technique for generating transgenic plants. However, many crops remain recalcitrant. We found that an Arabidopsis myb family ...transcription factor (MTF1) inhibited plant transformation susceptibility. Mutating MTF1 increased attachment of several Agrobacterium strains to roots and increased both stable and transient transformation in both susceptible and transformation-resistant Arabidopsis ecotypes. Cytokinins from Agrobacterium tumefaciens decreased the expression of MTF1 through activation of the cytokinin response regulator ARR3. Mutating AHK3 and AHK4, genes that encode cytokinin-responsive kinases, increased the expression of MTF1 and impaired plant transformation. Mutant mtf1 plants also had increased expression of AT14A, which encodes a putative transmembrane receptor for cell adhesion molecules. Plants overexpressing AT14A exhibited increased susceptibility to transformation, whereas at14a mutant plants exhibited decreased attachment of bacteria to roots and decreased transformation, suggesting that AT14A may serve as an anchor point for Agrobacteria. Thus, by promoting bacterial attachment and transformation of resistant plants and increasing such processes in susceptible plants, treating roots with cytokinins may help engineer crops with improved features or yield.
Guidelines for prehospital emergency care within the chain of rescue are recommended. At the scene, information about the patient and therapeutical tools are limited. Accidents and emergencies happen ...outside of hospitals and doctor's offices, while environmental factors and logistic problems strongly determine the rescue process. The sequence of interventions or the choice of the right hospital with specific triage criterias are only examples for these problems. There is only limited scientific evidence for therapies performed prehospitally. However, scientific material for the preparation of guidelines should be evaluated by using standardized criteria. The rules of evidence based medicine according to Cook are a practical way to evaluate and classify scientific material and to establish practical guidelines. In this paper, an 8-step-program is introduced to develop practical guidelines for the Emergency Medical Services Cologne.
PDF
