The Standard Model (SM) is known to be incomplete (it cannot explain dark matter, dark energy, gravitational waves, matter-antimatter asymmetry, etc). The introduction of a Dark Sector via an ...additional U(1)d gauge symmetry added to the SM Lagrangian could be the long-awaited solution. In this model there is a dark vector boson Zd which can mix with the SM hypercharge gauge boson. This opens the Hypercharge Portal which can mediate the fluctuation of a Z to a Zd, or the decay of the Zd to SM leptons. If a dark Higgs singlet also exists, then this breaks the U(1)d symmetry, allowing for Higgs mixing (parametrised by ) between the SM and dark sector Higgs bosons, and thereby opening the Higgs portal as a discovery channel. Including dark fermionic fields in the Lagrangian allows for long-lived cold Dark Matter candidates. The various connections between the Dark and SM sectors allow descriptions of many key astro-physical phenomena. This contribution discusses an ATLAS search for the dark force boson Zd using its production via the Higgs Portal and its decay back to SM leptons: H → Z d Z d → 4 ℓ . The biggest deviation from the Standard Model expectation is from a single event at 〈 m ℓ ℓ 〉 ≈ 20 GeV , with a local significance of 3.2 σ in the 2e2µ channel, and the corresponding global significance is approximately 1.9 σ.
Proton therapy with active scanning beam delivery has significant advantages compared to conventional radiotherapy. However, so far only static targets have been treated in this way, since moving ...targets potentially lead to interplay effects. For 4D treatment planning, information on the target motion is needed to calculate time-resolved dose distributions. In this study, respiratory liver motion has been extracted from 4D CT data using two deformable image registration algorithms. In moderately moving patient cases (mean motion range around 6 mm), the registration error was no more than 3 mm, while it reached 7 mm for larger motions (range around 13 mm). The obtained deformation fields have then been used to calculate different time-resolved 4D treatment plans. Averaged over both motion estimations, interplay effects can increase the D₅-D₉₅ value for the clinical target volume (CTV) from 8.8% in a static plan to 23.4% when motion is considered. It has also been found that the different deformable registration algorithms can provide different motion estimations despite performing similarly for the selected landmarks, which in turn can lead to differing 4D dose distributions. Especially for single-field treatments where no motion mitigation is used, a maximum (mean) dose difference (averaged over three cases) of 32.8% (2.9%) can be observed. However, this registration ambiguity-induced uncertainty can be reduced if rescanning is applied or if the treatment plan consists of multiple fields, where the maximum (mean) difference can decrease to 15.2% (0.57%). Our results indicate the necessity to interpret 4D dose distributions for scanned proton therapy with some caution or with error bars to reflect the uncertainties resulting from the motion estimation. On the other hand, rescanning has been found to be an appropriate motion mitigation technique and, furthermore, has been shown to be a robust approach to also deal with these motion estimation uncertainties.
Organ motion is a major problem for any dynamic radiotherapy delivery technique, and is particularly so for spot scanned proton therapy. On the other hand, the use of narrow, magnetically deflected ...proton pencil beams is potentially an ideal delivery technique for tracking tumour motion on-line. At PSI, our new Gantry is equipped with a Beams Eye View (BEV) imaging system which will be able to acquire 2D x-ray images in fluoroscopy mode during treatment delivery. However, besides precisely tracking motion from BEVs, it is also essential to obtain information on the 3D motion vector throughout the whole region of interest, and any sparsely acquired surrogate motion is generally not sufficient to describe the deformable behaviour of the whole volume in three dimensions. In this study, we propose a method by which 3D deformable motions can be estimated from surrogate motions obtained using this monoscopic imaging system. The method assumes that example motions over a number of breathing cycles can be acquired before treatment for each patient using 4DMRI. In this study, for each of 11 different subjects, 100 continuous breathing cycles have been extracted from extended 4DMRI studies in the liver and then subject specific motion models have been built using principle component analysis (PCA). To simulate treatment conditions, a different set of 30 continuous breathing cycles from the same subjects have then been used to generate a set of simulated 4DCT data sets (so-called 4DCT(MRI) data sets), from which time-resolved digitally reconstructed radiographs (DRRs) were calculated using the BEV geometry for three treatment fields respectively. From these DRRs, surrogate motions from fiducial markers or the diaphragm have been used as a predictor to estimate 3D motions in the liver region for each subject. The prediction results have been directly compared to the 'ground truth' motions extracted from the same 30 breath cycles of the originating 4DMRI data set. Averaged over all 11 subjects, and for three field directions, for 99% of predicted positions, median (max) error magnitudes of better than 2.63(5.67) mm can be achieved when fiducial markers was chosen as predictor. Furthermore, three single fields, 4D dose calculations have been performed as a verification tool to evaluate the prediction performance of such a model in the context of scanned proton beam therapy. These show a high similarity between plans considering either PCA predicted motion or ground truth motion, where absolute dose differences of more than 5% (V(dosediff = 5%)) occur for the worst field scenarios in only 3.61% (median) or 15.13% (max) of dose calculation points in the irradiated volume. The magnitude of these dose differences were insignificantly dependent on whether surrogate motions were tracked by monoscopic or stereoscopic imaging systems, or whether fiducial markers or diaphragm were chosen as surrogate. This study has demonstrated that on-line deformable motion reconstruction from sparse surrogate motions is feasible, even when using only a monoscopic imaging system. In addition, it has also been found that diaphragm motion can be considered as a good predictor for respiratory deformable liver motion prediction, implying that fiducial markers might not be compulsory if used in conjunction with a patient specific PCA based model.
Abstract
Background/Introduction
Most patients with atrial fibrillation (AF) report symptoms, while around one-third are asymptomatic. We hypothesized that sensory processing, in particular pain, ...differs in patients with symptomatic and asymptomatic AF.
Purpose
To assess differences in pain sensitisation in patients with symptomatic and asymptomatic AF.
Methods
Thirty individuals with permanent AF (15 symptomatic, 15 asymptomatic) completed the AF6 and SF-36 questionnaires and underwent quantitative pain sensitisation testing using pressure algometry at the sternum (referred pain area) and the tibialis anterior muscle (generalized pain area). The primary objective was to assess differences in pressure pain thresholds (PPT), temporal summation of pain (TSP), and conditioned pain modulation (CPM) in the two groups. The secondary objective was to determine association of demographic and clinical parameters to quantitative measures of pain sensitisation.
Results
The symptomatic group had lower PPTs at both tibialis (p=0.004) and sternum (p=0.01), as well as impaired CPM (p=0.025) and facilitated TSP (p=0.008) at the tibialis but not sternum, compared to the asymptomatic group. The AF6 sum score was negatively correlated to PPT on both tibialis (r=−0.50, p=0.005) and sternum (r=−0.42, p=0.02) and positively correlated to TSP of both tibialis (r=0.57, p=0.001) and sternum (r=0.45, p=0.01), but not to CPM. The physical component summary score was positively correlated to the PPT on both tibialis (r=0.52, p=0.003) and sternum (r=0.40, p=0.03) and negatively to TSP on the tibialis (r=−0.53, p=0.003) but not sternum.
Conclusions
Patients with symptomatic AF exhibit lower pain tolerance than patients with asymptomatic AF, as well as impaired pain inhibitory control and facilitated summation of pain, indicating that pain sensitisation may be of importance in symptomatic AF.
Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): Department of Cardiology, Örebro University, Sweden
PPTs tibialis anterior musclePPTs sternum
We report the synthesis of a new nanocrystal (NC) mesophase through self-assembly of water-soluble NC micelles with soluble silica. The mesophase comprises gold nanocrystals arranged within a silica ...matrix in a face-centered cubic lattice with cell dimensions that are adjustable through control of the nanocrystal diameter and/or the alkane chain lengths of the primary alkanethiol stabilizing ligands or the surrounding secondary surfactants. Under kinetically controlled silica polymerization conditions, evaporation drives self-assembly of NC micelles into ordered NC/silica thin-film mesophases during spin coating. The intermediate NC micelles are water soluble and of interest for biolabeling. Initial experiments on a metal-insulator-metal capacitor fabricated with an ordered three-dimensional gold nanocrystal/silica array as the "insulator" demonstrated collective Coulomb blockade behavior below 100 kelvin and established the current-voltage scaling relationship for a well-defined three-dimensional array of Coulomb islands.
Airway hyperresponsiveness leading to subepithelial fibrosis is mediated by inflammatory cells activated by T helper (Th) 2-derived cytokines such as IL-4 and IL-5. By analyzing the phenotype and ...response of human lung fibroblasts derived from either fetal (ICIG7) or adult (CCL202) tissue as well as from a Th2-type stromal reaction (FPA) to IL-4 and IL-13, we provide evidence that human lung fibroblasts may behave as inflammatory cells upon activation by IL-4 and IL-13. We show that the three types of fibroblasts constitute different populations that display a distinct pattern in cell surface molecule expression and proinflammatory cytokine and chemokine release. All fibroblasts express functional but different IL-4/IL-13 receptors. Thus, while IL-4 receptor (R) alpha and IL-13Ralpha1 chains are present in all the cells, CCL202 and FPA fibroblasts coexpress the IL-13Ralpha2 and the IL-2Rgamma chain, respectively, suggesting the existence of a heterotrimeric receptor (IL-4Ralpha/IL-13Ralpha/IL-2Rgamma) able to bind IL-4 and IL-13. Stimulation with IL-4 or IL-13 triggers in the fibroblasts a differential signal transduction and upregulation in the expression of beta1 integrin and vascular cell adhesion molecule 1 and in the production of IL-6 and monocyte chemoattractant protein 1, two inflammatory cytokines important in the pathogenesis of allergic inflammation. Our results suggest that when activated by IL-4 and IL-13, different subsets of lung fibroblasts may act as effector cells not only in the pathogenesis of asthma but also in lung remodeling processes. They may also differentially contribute to trigger and maintain the recruitment, homing, and activation of inflammatory cells.
Abstract
The Standard Model (SM) is known to be incomplete (it cannot explain dark matter, dark energy, gravitational waves, matter-antimatter asymmetry, etc). The introduction of a Dark Sector via ...an additional
U
(1)
d
gauge symmetry added to the SM Lagrangian could be the long-awaited solution. In this model there is a dark vector boson
Z
d
which can mix with the SM hypercharge gauge boson. This opens the Hypercharge Portal which can mediate the fluctuation of a
Z
to a
Z
d
, or the decay of the
Z
d
to SM leptons. If a dark Higgs singlet also exists, then this breaks the
U
(1)
d
symmetry, allowing for Higgs mixing (parametrised by ) between the SM and dark sector Higgs bosons, and thereby opening the Higgs portal as a discovery channel. Including dark fermionic fields in the Lagrangian allows for long-lived cold Dark Matter candidates. The various connections between the Dark and SM sectors allow descriptions of many key astro-physical phenomena. This contribution discusses an ATLAS search for the dark force boson
Z
d
using its production via the Higgs Portal and its decay back to SM leptons:
H
→
Z
d
Z
d
→
4
ℓ
. The biggest deviation from the Standard Model expectation is from a single event at
〈
m
ℓ
ℓ
〉
≈
20
GeV
, with a local significance of 3.2
σ
in the 2
e
2
µ
channel, and the corresponding global significance is approximately 1.9
σ
.
Objectives. To evaluate the inflammatory status and the cartilage regenerative potential of pathological synovial fibroblasts from patients with osteoarthritis (OA) compared with non-inflamed ...synovium (NS)-derived cells from patients with chondropathy. Methods. The inflammatory cell phenotype was investigated based on the constitutive and inducible surface expression and secretion of various effector molecules using flow cytometry or ELISA assays. The capacity of cells to produce cartilage-like extracellular matrix was assessed using acid Alcian blue staining and type II collagen immunostaining after treatment with transforming growth factor β1 (TGF-β1). Results. OA and NS fibroblasts consistently expressed CD29, CD44, CD49e, CD54, CD90 and CD106. Expression of high-affinity receptors for IL-4, IL-15, CXCL8 and CXCL12 was also detected but only intracellularly. All types of fibroblasts spontaneously released abundant amounts of CXCL12, CCL2, IL-6 and tissue inhibitor of metalloproteinase 1, while the production of IL-11, TGF-β1, matrix metalloproteinase 1 (MMP-1) and MMP-9 was detected at moderate levels. Several other secreted factors remained undetectable. No statistically significant differences were noted between the two groups of fibroblasts. Treatment with the proinflammatory cytokine tumour necrosis factor α (TNF-α) up-regulated the same set of surface and secreted molecules, including CD54, CD106, membrane IL-15, CCL2 and CCL5. Under TGF-β1 treatment and adipogenic culture conditions, both OA and NS fibroblasts displayed chondrogenic and adipocytic activities that were reduced in OA compared with NS cells. Conclusions. OA synovial fibroblasts did not display a distinct activated inflammatory phenotype compared with NS cells. However, they did differ in their reduced ability to produce cartilage-like matrix. This difference may be an additional important factor contributing to OA pathogenesis.
A novel technique is introduced for studying how rare earth ions are incorporated into the matrix of porous materials. Tb
3+-doped silica sol–gel is annealed to form porous glass and immersed in an ...aqueous Gd(NO
3)
3 solution. Re-heating removes the liquid and deposits Gd
3+ ions on the internal pore surfaces. Spectroscopic investigation of Gd
3+→Tb
3+ energy transfer yields information about the location of Tb
3+ dopant ions relative to pore surfaces. Results from post-annealing immersion experiments indicate that most Tb
3+ dopant ions are close to pore surfaces when sol–gel glass is annealed to 700
°C. The observed energy transfer decreases with higher annealing temperatures, indicating that Tb
3+ dopants in densified regions are isolated from Gd
3+ ions deposited on pore surfaces. Al
3+ co-doping affects both the overall sample density and the degree of Gd
3+→Tb
3+ interaction in post-annealing immersion samples.
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