Speed in Clinical Magnetic Resonance Runge, Val M; Richter, Johannes K; Heverhagen, Johannes T
Investigative radiology
52, Issue:
1
Journal Article
Peer reviewed
Open access
The relevant clinical accelerated magnetic resonance techniques that are available currently for routine patient examinations are reviewed, presenting and discussing the benefits therein when ...compared with more conventional scans. The focus is on clinical use and practicality, with the review divided into 3 sections. Improvements in 3-dimensional acquisition are first discussed, specifically controlled aliasing in parallel imaging results in higher acceleration, related radial techniques, and CAIPI-Dixon-TWIST-VIBE. Simultaneous multislice imaging is then reviewed, focusing on current implementation for 2-dimensional imaging, including both echo-planar and fast spin echo techniques. The final topic is that of sparse reconstruction (data sparsity), discussing the principles therein, challenges, and current applications. Guidance in terms of clinical use for accelerated techniques is provided, focusing on enabling faster and improved clinical scan results.
A
bstract
We initiate the study of transverse momentum-dependent (TMD) fragmentation functions for heavy quarks, demonstrate their factorization in terms of novel nonperturbative matrix elements in ...heavy-quark effective theory (HQET), and prove new TMD sum rules that arise from heavy-quark spin symmetry. We discuss the phenomenology of heavy-quark TMD FFs at
B
factories and find that the Collins effect, in contrast to claims in the literature, is not parametrically suppressed by the heavy-quark mass. We further calculate all TMD parton distribution functions for the production of heavy quarks from polarized gluons within the nucleon and use our results to demonstrate the potential of the future EIC to resolve TMD heavy-quark fragmentation in semi-inclusive DIS, complementing the planned EIC program to use heavy quarks as probes of gluon distributions.
Jet veto resummation with jet rapidity cuts Michel, Johannes K. L.; Pietrulewicz, Piotr; Tackmann, Frank J.
The journal of high energy physics,
04/2019, Volume:
2019, Issue:
4
Journal Article
Peer reviewed
Open access
A
bstract
Jet vetoes are widely used in experimental analyses at the LHC to distinguish different hard-interaction processes. Experimental jet selections require a cut on the (pseudo)rapidity of ...reconstructed jets, |
η
jet
| ≤
η
cut
. We extend the standard jet-
p
T
(jet-veto) resummation, which implicitly works in the limit
η
cut
→ ∞, by incorporating a finite jet rapidity cut. We also consider the case of a step in the required
p
T
cut
at an intermediate value of |
η
| ≃ 2.5, which is of experimental relevance to avoid the increased pile-up contamination beyond the reach of the tracking detectors. We identify all relevant parametric regimes, discuss their factorization and resummation as well as the relations between them, and show that the phenomenologically relevant regimes are free of large nonglobal logarithms. The
η
cut
dependence of all resummation ingredients is computed to the same order to which they are currently known for
η
cut
→ ∞. Our results pave the way for carrying out the jet-veto resummation including a sharp cut or a step at
η
cut
to the same order as is currently available in the
η
cut
→ ∞ limit. The numerical impact of the jet rapidity cut is illustrated for benchmark
q
q
¯
and
gg
initiated color-singlet processes at NLL′+NLO. We find that a rapidity cut at high
η
cut
= 4.5 is safe to use and has little effect on the cross section. A sharp cut at
η
cut
= 2.5 can in some cases lead to a substantial increase in the perturbative uncertainties, which can be mitigated by instead using a step in the veto.
A
bstract
The extraction of nonperturbative TMD physics is made challenging by prescriptions that shield the Landau pole, which entangle long- and short-distance contributions in momentum space. The ...use of different prescriptions then makes the comparison of fit results for underlying nonperturbative contributions not meaningful on their own. We propose a model-independent method to restrict momentum-space observables to the perturbative domain. This method is based on a set of integral functionals that act linearly on terms in the conventional position-space operator product expansion (OPE). Artifacts from the truncation of the integral can be systematically pushed to higher powers in Λ
QCD
/
k
T
. We demonstrate that this method can be used to compute the cumulative integral of TMD PDFs over
k
T
≤
k
T
cut
in terms of collinear PDFs, accounting for both radiative corrections and evolution effects. This yields a systematic way of correcting the naive picture where the TMD PDF integrates to a collinear PDF, and for unpolarized quark distributions we find that when renormalization scales are chosen near
k
T
cut
, such corrections are a percent-level effect. We also show that, when supplemented with experimental data and improved perturbative inputs, our integral functionals will enable model-independent limits to be put on the non-perturbative OPE contributions to the Collins-Soper kernel and intrinsic TMD distributions.
Abstract Nosocomial staphylococcal foreign-body infections related to biofilm formation are a serious threat, demanding new therapeutic and preventive strategies. As the use of biofilm-associated ...factors as vaccines is critically restricted by their prevalence in natural staphylococcal populations we studied the distribution of genes involved in biofilm formation, the biofilm phenotype and production of polysaccharide intercellular adhesin (PIA) in clonally independent Staphylococcus aureus and Staphylococcus epidermidis strains isolated from prosthetic joint infections after total hip or total knee arthroplasty. Biofilm formation was detected in all S. aureus and 69.2% of S. epidermidis strains. Importantly, 27% of biofilm-positive S. epidermidis produced PIA-independent biofilms, in part mediated by the accumulation associated protein (Aap). Protein-dependent biofilms were exclusively found in S. epidermidis strains from total hip arthroplasty (THA). In S. aureus PIA and proteins act cooperatively in biofilm formation regardless of the infection site. PIA and protein factors like Aap are of differential importance for the pathogenesis of S. epidermidis in prosthetic joint infections (PJI) after THA and total knee arthroplasty (TKA), implicating that icaADBC cannot serve as a general virulence marker in this species. In S. aureus biofilm formation proteins are of overall importance and future work should focus on the identification of functionally active molecules.
This preclinical study was devised to investigate potential cellular toxicity in human neurons induced by gadolinium-based contrast agents (GBCAs) used for contrast-enhanced magnetic resonance ...imaging (MRI). Neurons modeling a subset of those in the basal ganglia were tested, because the basal ganglia region is 1 of 2 brain regions that displays the greatest T1-dependent signal hyperintensity changes.
Eight GBCAs were tested. Dopaminergic neurons modeling a subset of those in the basal ganglia were differentiated from an established human neuroblastoma cell line and exposed to increasing concentrations of each agent for 7 days. The tested dosages ranged from clinically relevant concentrations measured in some autopsy patients who had received repeated injections of contrast for MRI, to higher concentrations to reveal dose-dependent toxicity trends. Cell death, mitochondrial membrane potential, mitochondrial oxidative capacity, and mitochondrial function measured by oxygen consumption were quantified in cells treated with each GBCA or the osmolality control mannitol and compared to untreated cells which served as a negative control.
Mannitol caused no change from negative controls in any of the tests, at any concentration tested. For all GBCAs, cell death increased with exposure dose, with toxicity at clinically relevant doses for agents with lower kinetic stability. Reduction of mitochondrial membrane potential and oxidative respiratory function also generally mirrored the agents' structural kinetic stabilities, with greater impairment at lower concentration for the less stable agents.
In human neurons modeling a subset of those in the basal ganglia, these results demonstrate a toxic effect of gadolinium-containing MRI contrast agents on mitochondrial respiratory function and cell viability. Toxicity increases as agent concentration increases and as the kinetic stability of the agent decreases.
Protein aggregation is a phenomenon that has attracted considerable attention within the pharmaceutical industry from both a developability standpoint (to ensure stability of protein formulations) ...and from a research perspective for neurodegenerative diseases. Experimental identification of aggregation behavior in proteins can be expensive; and hence, the development of accurate computational approaches is crucial. The existing methods for predicting protein aggregation rely mostly on the primary sequence and are typically trained on amyloid‐like proteins. However, the training bias toward beta amyloid peptides may worsen prediction accuracy of such models when applied to larger protein systems. Here, we present a novel algorithm to identify aggregation‐prone regions in proteins termed “AggScore” that is based entirely on three‐dimensional structure input. The method uses the distribution of hydrophobic and electrostatic patches on the surface of the protein, factoring in the intensity and relative orientation of the respective surface patches into an aggregation propensity function that has been trained on a benchmark set of 31 adnectin proteins. AggScore can accurately identify aggregation‐prone regions in several well‐studied proteins and also reliably predict changes in aggregation behavior upon residue mutation. The method is agnostic to an amyloid‐specific aggregation context and thus may be applied to globular proteins, small peptides and antibodies.
Abstract
Aims
Long-term sequelae may occur after SARS-CoV-2 infection. We comprehensively assessed organ-specific functions in individuals after mild to moderate SARS-CoV-2 infection compared with ...controls from the general population.
Methods and results
Four hundred and forty-three mainly non-hospitalized individuals were examined in median 9.6 months after the first positive SARS-CoV-2 test and matched for age, sex, and education with 1328 controls from a population-based German cohort. We assessed pulmonary, cardiac, vascular, renal, and neurological status, as well as patient-related outcomes. Bodyplethysmography documented mildly lower total lung volume (regression coefficient −3.24, adjusted P = 0.014) and higher specific airway resistance (regression coefficient 8.11, adjusted P = 0.001) after SARS-CoV-2 infection. Cardiac assessment revealed slightly lower measures of left (regression coefficient for left ventricular ejection fraction on transthoracic echocardiography −0.93, adjusted P = 0.015) and right ventricular function and higher concentrations of cardiac biomarkers (factor 1.14 for high-sensitivity troponin, 1.41 for N-terminal pro-B-type natriuretic peptide, adjusted P ≤ 0.01) in post-SARS-CoV-2 patients compared with matched controls, but no significant differences in cardiac magnetic resonance imaging findings. Sonographically non-compressible femoral veins, suggesting deep vein thrombosis, were substantially more frequent after SARS-CoV-2 infection (odds ratio 2.68, adjusted P < 0.001). Glomerular filtration rate (regression coefficient −2.35, adjusted P = 0.019) was lower in post-SARS-CoV-2 cases. Relative brain volume, prevalence of cerebral microbleeds, and infarct residuals were similar, while the mean cortical thickness was higher in post-SARS-CoV-2 cases. Cognitive function was not impaired. Similarly, patient-related outcomes did not differ.
Conclusion
Subjects who apparently recovered from mild to moderate SARS-CoV-2 infection show signs of subclinical multi-organ affection related to pulmonary, cardiac, thrombotic, and renal function without signs of structural brain damage, neurocognitive, or quality-of-life impairment. Respective screening may guide further patient management.
Graphical Abstract
Graphical Abstract
The key question is: How does a mild to moderate course of SARS-CoV-2 infection in mainly non-hospitalized individuals impact intermediate-term organ-specific functions in comparison to the general population? The key findings are (i) a mild to moderate course of SARS-CoV-2 infection is associated with subsequent signs of subclinical multi-organ affection; (ii) associations mainly affect the pulmonary, cardiac, coagulation, and renal system; and (iii) no systematic associations with structural brain damage, neurocognition, or quality of life were observed. The take-home message is systematic screening of multi-organ function even after mild to moderate SARS-CoV-2 infection is recommended to identify individuals at risk and initiate appropriate preventive therapies.
An outbreak of Shiga toxin-producing enteroaggregative Escherichia coli (STEC O104:H4) infection with a high incidence of hemolytic uremic syndrome (HUS) occurred in Germany in May 2011. Antibiotic ...treatment of STEC infection is discouraged because it might increase the risk of HUS development. However, antibiotic therapy is widely used to treat enteroaggregative E coli infection. In the German outbreak, a substantial number of patients received prophylactic azithromycin treatment as part of a therapeutic regimen with the C5 antibody eculizumab.
To analyze the duration of bacterial shedding in patients with STEC infection who did and did not receive oral azithromycin therapy.
At a single center in Lübeck, Germany, 65 patients with STEC infection, including patients with HUS as well as STEC-infected outpatients without manifestation of HUS, were investigated between May 15 and July 26, 2011, and were monitored for a mean of 39.3 days after onset of clinical symptoms.
Carriage of STEC after azithromycin therapy.
Twenty-two patients received oral azithromycin and 43 patients did not receive antibiotic treatment. Among antibiotic-treated patients, long-term STEC carriage (>28 days) was observed in 1 of 22 patients (4.5%; 95% CI, 0%-13.3%) compared with 35 of 43 patients (81.4%; 95% CI, 69.8%-93.0%) who were not treated with antibiotics (P < .001). All 22 patients receiving azithromycin treatment had at least 3 STEC-negative stool specimens after the completion of treatment, and no recurrence of STEC was observed in these patients. As proof of principle, 15 patients who initially were not treated with antibiotics and were long-term STEC carriers were treated with oral azithromycin given for 3 days and subsequently had negative stool specimens.
Treatment with azithromycin was associated with a lower frequency of long-term STEC O104:H4 carriage.
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