•4DCT and 4DCBCT under-predict treatment lung target motion ranges.•4DCT under-predicts target motion by factors of 1.7–1.9 and 4DCBCT by factors of 1.5–1.6.•4DCBCT shows higher correlations with ...target motion than 4DCT.•4DCT and 4DCBCT motion measurements should be interpreted carefully.
To test the hypothesis that 4DCT and 4DCBCT-measured target motion ranges predict target motion ranges during lung cancer SABR.
Ten lung SABR patients were implanted with Calypso beacons. 4DCBCT was reconstructed for 29 fractions (1–4fx/patient) from a 1 min CBCT scan. The beacon centroid motion segmented for all 4DCT and 4DCBCT bins was compared with the real-time imaging and treatment beacon centroid (“target”) motion range (4SDs) for each fraction. We tested the hypotheses that (1) 4DCT and 4CBCT predict treatment motion range and (2) there is no difference between 4DCT and 4DCBCT for predicting treatment motion range. Phase-wise root-mean-square errors (RMSEs) between imaging and treatment motion and reconstructed motion (4DCT, 4DCBCT) were calculated. Relationships between motion ranges in 4DCT and 4DCBCT and imaging and treatment motion ranges were investigated for the superior–inferior (SI), left–right (LR) and anterior–posterior (AP) directions. Baseline drifts and amplitude variability were investigated as potential factors leading to motion misrepresentation.
SI 4DCT, 4DCBCT, imaging and treatment motion ranges were 6.3 ± 3.6 mm, 7.1 ± 4.5 mm, 11.1 ± 7.5 mm and 10.9 ± 6.9 mm, respectively. Similar 4DCT and 4DCBCT under-predictions were observed in the LR and AP directions. Hypothesis (1) was rejected (p < 0.0001). Treatment target motion range was under-predicted in 4DCT by factors of 1.7, 1.9 and 1.7 and in 4DCBCT by factors of 1.5, 1.6 and 1.6 in the SI, LR, and AP directions, respectively. RMSEs were generally lower for end-exhale than inhale. 4DCBCT showed higher correlations with the imaging and treatment target motion than 4DCT and testing hypothesis (2) a statistically significant difference between 4DCT and 4DCBCT was shown in the SI direction (p = 0.03).
For lung SABR patients both 4DCT and 4DCBCT significantly under-predict treatment target motion ranges.
it contains macromolecules such as proteins, nucleic acids, polysaccharides and lipids. Proteins influence the entire brewing process with regard to enzymes, which degrade starch, beta-glucans and ...proteins; with protein-protein linkages that stabilize foam and are responsible for mouthfeel and flavour stability; and in combination with polyphenols, thought to form haze. With this complexity, problems in processability are as various as the constituents. Several substances in beer are responsible for haze formation. Organic components such as proteins, polyphenols and carbohydrates (alpha-glucans, beta-glucans) are known to form haze. In addition, inorganic particles such as filter aids and label remains can cause increased turbidity. In this article only nonmicrobiological induced hazes are described. Many studies have been conducted on the identification of haze and foam active components in beer. Hence the aim of this work was to survey the different possibilities of haze formation and for haze identification. A summary is provided on methods for haze identification including dyeing methods, microscopic analyses and size exclusion chromatography.
Deep inspiration breath hold (DIBH) reduces radiotherapy cardiac dose for left-sided breast cancer patients. The primary aim of the BRAVEHeart (Breast Radiotherapy Audio Visual Enhancement for ...sparing the Heart) trial is to assess the accuracy and usability of a novel device, Breathe Well, for DIBH guidance for left-sided breast cancer patients. Breathe Well will be compared to an adapted widely available monitoring system, the Real-time Position Management system (RPM).
BRAVEHeart is a single institution prospective randomised trial of two DIBH devices. BRAVEHeart will assess the DIBH accuracy for Breathe Well and RPM during left-sided breast cancer radiotherapy. After informed consent has been obtained, 40 patients will be randomised into two equal groups, the experimental arm (Breathe Well) and the control arm (RPM with in-house modification of an added patient screen). The primary hypothesis of BRAVEHeart is that the accuracy of Breathe Well in maintaining the position of the chest during DIBH is superior to the RPM system. Accuracy will be measured by comparing chest wall motion extracted from images acquired of the treatment field during breast radiotherapy for patients treated using the Breathe Well system and those using the RPM system.
The Breathe Well device uses a depth camera to monitor the chest surface while the RPM system monitors a block on the patient's abdomen. The hypothesis of this trial is that the chest surface is a better surrogate for the internal chest wall motion used as a measure of treatment accuracy. The Breathe Well device aims to deliver an easy-to-use implementation of surface monitoring. The findings from the study will help inform the technology choice for other centres performing DIBH.
ClinicalTrials.gov NCT02881203 . Registered on 26 August 2016.
Abstract
Intra-fractional respiratory motion during radiotherapy leads to a larger planning target volume (PTV). Real-time tumor motion tracking by two-dimensional (2D)/3D registration using on-board ...kilo-voltage (kV) imaging can allow for a reduction of the PTV though motion along the imaging beam axis cannot be resolved using only one projection image. We present a retrospective patient study investigating the impact of paired portal mega-voltage (MV) and kV images on registration accuracy. Material and methods. We used data from 10 patients suffering from non-small cell lung cancer (NSCLC) undergoing stereotactic body radiation therapy (SBRT) lung treatment. For each patient we acquired a planning computed tomography (CT) and sequences of kV and MV images during treatment. We compared the accuracy of motion tracking in six degrees-of-freedom (DOF) using the anterior-posterior (AP) kV sequence or the sequence of kV-MV image pairs. Results. Motion along cranial-caudal direction could accurately be extracted when using only the kV sequence but in AP direction we obtained large errors. When using kV-MV pairs, the average error was reduced from 2.9 mm to 1.5 mm and the motion along AP was successfully extracted. Mean registration time was 188 ms. Conclusion. Our evaluation shows that using kV-MV image pairs leads to improved motion extraction in six DOF and is suitable for real-time tumor motion tracking with a conventional LINAC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Simple heuristics can be efficient ways of decision making and literature has shown that they are widely used in actual decision situations. Although many types of heuristics have been found and ...analyzed, there is only scarce research on factors that lead to the use of a particular heuristic. In the present paper, we describe an experiment to analyze whether the usage of a particular heuristic like recognition or take-the-best depends on individual decision making styles as identified by Scott and Bruce (Educ Psychol Meas 55(5):818–831,
1995
). The experiment is based on a choice problem, in which different heuristics are likely to lead to different choices. Analyzing experimental data from two replications of the experiment in two different countries, we find some evidence that decision making styles influence the use of heuristics. However, considerable differences between the two experiments indicate that other, perhaps cultural, factors might also be important.
Research data repositories and data centres are becoming more and more important as infrastructures in academic research. The article introduces the Humanities’ research data repository GAMS, ...starting with the system architecture to preservation policy and content policy. Challenges of data centres and repositories and the general and domain-specific approaches and solutions are outlined. Special emphasis lies on the sustainability and long-term perspective of such infrastructures, not only on the technical but above all on the organisational and financial level.
To investigate intrafraction prostate and patient motion during different radiation therapy treatments as a function of treatment time; included were prostate patients with an endorectal balloon ...(ERB). Margins accounting for setup uncertainties and intrafraction motion were determined.
The study included 17 patients undergoing prostate cancer radiation therapy. All patients received 3 fiducial gold markers implanted in the prostate and were then immobilized in the supine position with a knee support and treated with an ERB. Twelve patients with intermediate risk for pelvic lymph node metastases received intensity modulated radiation therapy (IMRT), and 5 patients at low risk received a 4-field box treatment. After setup based on skin marks, patients were imaged with a stereoscopic imaging system. If the marker displacement exceeded a 3-mm tolerance relative to planning computed tomography, patients were shifted and verification images were taken. All patients underwent additional imaging after treatment; IMRT patients also received additional imaging at halftime of treatment. Prostate and bone drifts were evaluated as a function of treatment time for more than 600 fractions, and margins were extracted.
Patient motion evaluated by bone match was strongly patient dependent but in general was smallest in the superior-inferior (SI) direction. Prostate drifts were less patient dependent, showing an increase with treatment time in the SI and anterior-posterior (AP) directions. In the lateral (LAT) direction, the prostate stayed rather stable. Mean treatment times were 5.5 minutes for 4-field box, 10 minutes for 5-field boost IMRT, and 15 minutes or more for 9-field boost and 9-field pelvic IMRT treatments. Margins resulted in 2.2 mm, 3.9 mm, and 4.3 mm for 4-field box; 3.7 mm, 2.6 mm, and 3.6 mm for 5-field boost IMRT; 2.3 mm, 3.9 mm, and 6.2 mm for 9-field boost IMRT; and 4.2 mm, 5.1 mm, and 6.6 mm for 9-field pelvic IMRT in the LAT, SI, and AP directions, respectively.
Intrafraction prostate and patient displacement increased with treatment time, showing different behaviors for the single directions of movement. Repositioning of the patients during long treatments or shorter treatment times will be necessary to further reduce the treatment margin.
Abstract
The polysaccharide Bep is essential for in vitro biofilm formation of the opportunistic pathogen
Burkholderia cenocepacia
. We found that the
Burkholderia
diffusible signaling factor (BDSF) ...quorum sensing receptor RpfR is a negative regulator of the
bep
gene cluster in
B. cenocepacia
. An
rpfR
mutant formed wrinkled colonies, whereas additional mutations in the
bep
genes or known
bep
regulators like
berA
and
berB
restored the wild-type smooth colony morphology. We found that there is a good correlation between intracellular c-di-GMP levels and
bep
expression when the c-di-GMP level is increased or decreased through ectopic expression of a diguanylate cyclase or a c-di-GMP phosphodiesterase, respectively. However, when the intracellular c-di-GMP level is changed by site directed mutagenesis of the EAL or GGDEF domain of RpfR there is no correlation between intracellular c-di-GMP levels and
bep
expression. Except for
rpfR,
deletion mutants of all 25 c-di-GMP phosphodiesterase and diguanylate cyclase genes encoded by
B. cenocepacia
showed no change to
berA
and
bep
gene expression. Moreover, bacterial two-hybrid assays provided evidence that RpfR and BerB physically interact and give specificity to the regulation of the
bep
genes. We suggest a model where RpfR binds BerB at low c-di-GMP levels to sequester this RpoN-dependent activator to an RpfR/RpfF complex. If the c-di-GMP levels rise, possibly by the enzymatic action of RpfR, BerB binds c-di-GMP and is released from the RpfR/RpfF complex and associates with RpoN to activate transcription of
berA
, and the BerA protein subsequently activates transcription of the
bep
genes.
The bone morphogenetic protein (BMP) signaling pathway plays a central role during vasculature development. Mutations or dysregulation of the BMP pathway members have been linked to arteriovenous ...malformations. In the present study, we investigated the effect of the BMP modulators bone morphogenetic protein endothelial precursor‐derived regulator (BMPER) and twisted gastrulation protein homolog 1 (TWSG1) on arteriovenous specification during zebrafish development and analyzed downstream Notch signaling pathway in human endothelial cells. Silencing of bmper and twsg1b in zebrafish embryos by morpholinos resulted in a pronounced enhancement of venous ephrinB4a marker expression and concomitant dysregulated arterial ephrinb2a marker expression detected by in situ hybridization. As arteriovenous specification was disturbed, we assessed the impact of BMPER and TWSG1 protein stimulation on the Notch signaling pathway on endothelial cells from different origin. Quantitative real‐time PCR (qRT‐PCR) and western blot analysis showed increased expression of Notch target gene hairy and enhancer of split, HEY1/2 and EPHRINB2. Consistently, silencing of BMPER in endothelial cells by siRNAs decreased Notch signaling and downstream effectors. BMP receptor antagonist DMH1 abolished BMPER and BMP4 induced Notch signaling pathway activation. In conclusion, we found that in endothelial cells, BMPER and TWSG1 are necessary for regular Notch signaling activity and in zebrafish embryos BMPER and TWSG1 preserve arteriovenous specification to prevent malformations.
The bone morphogenetic protein (BMP) signaling pathway plays a central role during vasculature development. Silencing of bmper and twsg1b in zebrafish embryos by morpholinos resulted in increased venous ephrinB4a and concomitant dysregulated arterial ephrinb2a marker expression, which was confirmed in human endothelial cells. Silencing of bone morphogenetic protein endothelial precursor‐derived regulator or application of BMP inhibitor dorsomorphin homolog 1 prevented Notch pathway activation and increased ephrin receptor b4a expression.
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