Multi-Institutional Study of End-to-End Dose Delivery Quality Assurance Testing for Image-Guided Brachytherapy Using a Gel Dosimeter.

PURPOSE: To quantify dose delivery errors for high-dose-rate image-guided brachytherapy (HDR-IGBT) using an independent end-to-end dose delivery quality assurance test at multiple institutions. The novelty of our study is that this is the first multi-institutional end-to-end dose delivery study in the world. MATERIALS AND METHODS: The postal audit used a polymer gel dosimeter in a cylindrical acrylic container for the afterloading system. Image acquisition using computed tomography, treatment planning, and irradiation were performed at each institution. Dose distribution comparison between the plan and gel measurement was performed. The percentage of pixels satisfying the absolute-dose gamma criterion was reviewed. RESULTS: Thirty-five institutions participated in this study. The dose uncertainty was 3.6% ± 2.3% (mean ± 1.96σ). The geometric uncertainty with a coverage factor of k = 2 was 3.5 mm. The tolerance level was set to the gamma passing rate of 95% with the agreement criterion of 5% (global)/3 mm, which was determined from the uncertainty estimation. The percentage of pixels satisfying the gamma criterion was 90.4% ± 32.2% (mean ± 1.96σ). Sixty-six percent (23/35) of the institutions passed the verification. Of the institutions that failed the verification, 75% (9/12) had incorrect inputs of the offset between the catheter tip and indexer length in treatment planning and 17% (2/12) had incorrect catheter reconstruction in treatment planning. CONCLUSIONS: The methodology should be useful for comprehensively checking the accuracy of HDR-IGBT dose delivery and credentialing clinical studies. The results of our study highlight the high risk of large source positional errors while delivering dose for HDR-IGBT in clinical practices.

Development of alveolar and airway cells from human iPS cells: toward SARS-CoV-2 research and drug toxicity testing.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). SARS-CoV-2 enters host cells by binding with the receptor angiotensin-converting enzyme 2 (ACE2). While ACE2 is expressed in multiple cell types, it has been implicated in the clinical progression of COVID-19 as an entry point for SARS-CoV-2 into respiratory cells. Human respiratory cells, such as airway and alveolar epithelial type II (ATII) cells, are considered essential for COVID-19 research; however, primary human respiratory cells are difficult to obtain. In the present study, we generated ATII and club cells from human induced pluripotent stem cells (hiPSCs) for SARS-CoV-2 infection and drug testing. The differentiated cells expressed ATII markers (SFTPB, SFTPC, ABCA3, SLC34A2) or club cell markers (SCGB1A1 and SCGB3A2). Differentiated cells, which express ACE2 and TMPRSS2, were infected with SARS-CoV-2. Remdesivir treatment decreased intracellular SARS-CoV-2 viral replication and, furthermore, treatment with bleomycin showed cytotoxicity in a concentration-dependent manner. These data suggest that hiPSC-derived AT2 and club cells provide a useful in vitro model for drug development.

A childhood-onset intestinal toxemia botulism during chemotherapy for relapsed acute leukemia.

BACKGROUND: Botulism is a potentially fatal infection characterized by progressive muscle weakness, bulbar paralysis, constipation and other autonomic dysfunctions. A recent report suggested that cancer chemotherapy might increase the risk for the intestinal toxemia botulism in both adults and children. CASE PRESENTATION: We report a 5-year-old boy, who developed general muscle weakness, constipation, ptosis and mydriasis during the third induction therapy for relapsed acute myeloid leukemia. He had recent histories of multiple antibiotic therapy for bacteremia and intake of well water at home. Repeated bacterial cultures identified Clostridium botulinum producing botulinum neurotoxin A. Botulinum toxin A was isolated from his stools at 17, 21, and 23 days after the onset. Symptoms were self-limiting, and were fully recovered without anti-botulinum toxin globulin therapy. CONCLUSION: This is the second report of a pediatric case with cancer chemotherapy-associated intestinal toxemia botulism. Our case provides further evidence that the immunocompromised status due to anti-cancer treatments increases the risk for the development of botulism at all ages in childhood.

Helicobacter pylori outer membrane protein HopQ identified as a novel T4SS-associated virulence factor.

Helicobacter pylori is a bacterial pathogen that colonizes the gastric niche of ∼ 50% of the human population worldwide and is known to cause peptic ulceration and gastric cancer. Pathology of infection strongly depends on a cag pathogenicity island (cagPAI)-encoded type IV secretion system (T4SS). Here, we aimed to identify as yet unknown bacterial factors involved in cagPAI effector function and performed a large-scale screen of an H. pylori transposon mutant library using activation of the pro-inflammatory transcription factor NF-κB in human gastric epithelial cells as a measure of T4SS function. Analysis of ∼ 3000 H. pylori mutants revealed three non-cagPAI genes that affected NF-κB nuclear translocation. Of these, the outer membrane protein HopQ from H. pylori strain P12 was essential for CagA translocation and for CagA-mediated host cell responses such as formation of the hummingbird phenotype and cell scattering. Besides that, deletion of hopQ reduced T4SS-dependent activation of NF-κB, induction of MAPK signalling and secretion of interleukin 8 (IL-8) in the host cells, but did not affect motility or the quantity of bacteria attached to host cells. Hence, we identified HopQ as a non-cagPAI-encoded cofactor of T4SS function.

Intrahost passage alters SigB-dependent acid resistance and host cell-associated kinetics of Listeria monocytogenes.

Listeria monocytogenes is a foodborne pathogen that causes gastroenteritis, maternofetal infections and meningoencephalitis in humans. Here we report that an intrahost genome mutation alters bacterial acid resistance and the abilities for replication/invasion in tissue cell culture. Among the L. monocytogenes isolates from the recent outbreak in Japan, we found that one food strain, 668, exhibited the greatest acid resistance, whereas one human clinical strain, 690, sharing identical pulsed-field gel electrophoresis (PFGE) and ribotyping patterns, exhibited an acid-sensitive phenotype. Passage of the 668 food strain through the mouse intestine increased its acid sensitivity without altering the macrogenotypes, indicating intrahost alteration of the bacterial acid-resistant phenotype. Genetic and proteomic analyses revealed a link between acid resistance and SigB (RNA polymerase SigmaB subunit) activity. Compared with the strain 668, the clinical and 4 of 5 mice-passaged strains showed a mutation in the rsbW locus, whose product controls the regulation of SigB activity. Corresponding to the SigB activity, the host-passaged strains had reduced abilities to survive inside macrophages and to invade Caco-2 cells, compared with the food strain 668. Overall, we have demonstrated the first example of a host environment promoting the alteration of SigB-dependent acid resistance and host cell-associated actions of L. monocytogenes. Our study provides new insight into the potential role of intrahost environment in the process of bacterial evolution.

Antimicrobial susceptibilities of Listeria monocytogenes isolated in Japan.

The antimicrobial susceptibility of 201 Listeria monocytogenes isolates from foods, environments, animals and human patients in Japan was determined. All isolates were susceptible to ampicillin, the first choice of drug for listeriosis treatment, chloramphenicol, dihydrostreptomycin, erythromycin, enrofloxacin, gentamicin, kanamycin, lincomycin, nosiheptide, salinomycin, vancomycin, and virginiamycin. A human strain was resistant to oxytetracycline. The Minimum Inhibitory Concentration (MIC) for 50% of the strains and the MIC for 90% of the strains were comparable in all the isolates. This is the first investigation to compare antibiotic resistances between isolates from foods and isolates from human patients in Japan. The result showed that most of the isolates were susceptible to antibiotics used in this study.

Intrafractional respiratory motion for charged particle lung therapy with immobilization assessed by four-dimensional computed tomography.

The aim of this study was to quantify the magnitude of intrafractional lung tumor motion under free-breathing conditions with an immobilization device using four-dimensional computed tomography (4DCT). 4DCT data sets were acquired for 17 patients with lung tumors receiving carbon ion beam therapy. A single respiratory cycle was subdivided into 10 phases, and intrafractional tumor motion was calculated by identifying the gross tumor volume (GTV) center of mass (COM) in two scenarios; respiratory-ungated and -gated treatments, which were based on a whole respiratory cycle and a 30% duty cycle around peak exhalation, respectively. For the respiratory-ungated case, the mean (± standard deviation) GTV-COM displacements from the peak exhalation position over the 17 patients were 0.6 (± 0.8) / 0.9 (± 1.2) mm, 2.0 (± 1.4) / 0.4 (± 0.7) mm, and 0.2 (± 0.5) / 7.8 (± 6.9) mm in left/right, anterior/posterior and superior/inferior directions, respectively, while these were reduced for the respiratory-gated case to 0.3 (± 0.4) / 0.4 (± 0.6) mm (left/right), 0.8 (± 0.7) / 0.3 (± 0.5) mm (anterior/posterior), and 0.1 (± 0.2) / 2.8 (± 2.9) mm (superior/inferior). Quantitative analysis of tumor motion with immobilization is valuable not only for particle beam therapy but also for photon beam therapy.

Four-dimensional lung treatment planning in layer-stacking carbon ion beam treatment: comparison of layer-stacking and conventional ungated/gated irradiation.

PURPOSE: We compared four-dimensional (4D) layer-stacking and conventional carbon ion beam distribution in the treatment of lung cancer between ungated and gated respiratory strategies using 4DCT data sets. METHODS AND MATERIALS: Twenty lung patients underwent 4DCT imaging under free-breathing conditions. Using planning target volumes (PTVs) at respective respiratory phases, two types of compensating bolus were designed, a full single respiratory cycle for the ungated strategy and an approximately 30% duty cycle for the exhalation-gated strategy. Beams were delivered to the PTVs for the ungated and gated strategies, PTV(ungated) and PTV(gated), respectively, which were calculated by combining the respective PTV(Tn)s by layer-stacking and conventional irradiation. Carbon ion beam dose distribution was calculated as a function of respiratory phase by applying a compensating bolus to 4DCT. Accumulated dose distributions were calculated by applying deformable registration. RESULTS: With the ungated strategy, accumulated dose distributions were satisfactorily provided to the PTV, with D95 values for layer-stacking and conventional irradiation of 94.0% and 96.2%, respectively. V20 for the lung and Dmax for the spinal cord were lower with layer-stacking than with conventional irradiation, whereas Dmax for the skin (14.1 GyE) was significantly lower (21.9 GyE). In addition, dose conformation to the GTV/PTV with layer-stacking irradiation was better with the gated than with the ungated strategy. CONCLUSIONS: Gated layer-stacking irradiation allows the delivery of a carbon ion beam to a moving target without significant degradation of dose conformity or the development of hot spots.

Helicobacter pylori HP0518 affects flagellin glycosylation to alter bacterial motility.

Helicobacter pylori is a human gastric pathogen associated with gastric and duodenal ulcers as well as gastric cancer. Mounting evidence suggests this pathogen's motility is prerequisite for successful colonization of human gastric tissues. Here, we isolated an H. pylori G27 HP0518 mutant exhibiting altered motility in comparison to its parental strain. We show that the mutant's modulated motility is linked to increased levels of O-linked glycosylation on flagellin A (FlaA) protein. Recombinant HP0518 protein decreased glycosylation levels of H. pylori flagellin in vitro, indicating that HP0518 functions in deglycosylation of FlaA protein. Furthermore, mass spectrometric analysis revealed increased glycosylation of HP0518 FlaA was due to a change in pseudaminic acid (Pse) levels on FlaA; HP0518 mutant-derived flagellin contained approximately threefold more Pse than the parental strain. Further phenotypic and molecular characterization demonstrated that the hyper-motile HP0518 mutant exhibits superior colonization capabilities and subsequently triggers enhanced CagA phosphorylation and NF-κB activation in AGS cells. Our study shows that HP0518 is involved in the deglycosylation of flagellin, thereby regulating pathogen motility. These findings corroborate the prominent function of H. pylori flagella in pathogen-host cell interactions and modulation of host cell responses, likely influencing the pathogenesis process.

A treatment planning strategy for heavy-charged-particle radiotherapy of lung cancer by the use of computed tomography with projection data-based temporal maximum-intensity projection.

To design a range-compensating bolus for heavy-charged-particle radiotherapy of lung cancer, we propose an image-processing method that uses CT projection data for treatment planning. We studied six lung cancer patients in 4DCT mode. Three types of range-compensating bolus were designed with use of (1) each bolus for 4DCT images, (2) image-based maximum-intensity projection data (4DIM), and (3) CT images reconstructed by the use of maximum-attenuation projection data (4DPM) along the time axis around exhale (=respiratory-gated treatment). Carbon-ion dose distributions were calculated by the use of these designed range-compensating boluses and were compared. The dose distribution with 4DIM caused overdosing beyond the target. However, the dose distribution with 4DPM was similar to that with a composite of the range-compensating bolus (CCB) designed for the respiratory phases. Furthermore, the volume of the receiving dose for >95% (D95) for CTV and the volume of the lung receiving dose for >20 GyE (V20) with 4DPM were similar to that with the CCB. The range-compensating bolus with 4DPM provides dose distributions similar to that with the CCB in peripheral lung cancer and improves the calculating efficiency over CCB.

Comparison of respiratory-gated and respiratory-ungated planning in scattered carbon ion beam treatment of the pancreas using four-dimensional computed tomography.

PURPOSE: We compared respiratory-gated and respiratory-ungated treatment strategies using four-dimensional (4D) scattered carbon ion beam distribution in pancreatic 4D computed tomography (CT) datasets. METHODS AND MATERIALS: Seven inpatients with pancreatic tumors underwent 4DCT scanning under free-breathing conditions using a rapidly rotating cone-beam CT, which was integrated with a 256-slice detector, in cine mode. Two types of bolus for gated and ungated treatment were designed to cover the planning target volume (PTV) using 4DCT datasets in a 30% duty cycle around exhalation and a single respiratory cycle, respectively. Carbon ion beam distribution for each strategy was calculated as a function of respiratory phase by applying the compensating bolus to 4DCT at the respective phases. Smearing was not applied to the bolus, but consideration was given to drill diameter. The accumulated dose distributions were calculated by applying deformable registration and calculating the dose-volume histogram. RESULTS: Doses to normal tissues in gated treatment were minimized mainly on the inferior aspect, which thereby minimized excessive doses to normal tissues. Over 95% of the dose, however, was delivered to the clinical target volume at all phases for both treatment strategies. Maximum doses to the duodenum and pancreas averaged across all patients were 43.1/43.1 GyE (ungated/gated) and 43.2/43.2 GyE (ungated/gated), respectively. CONCLUSIONS: Although gated treatment minimized excessive dosing to normal tissue, the difference between treatment strategies was small. Respiratory gating may not always be required in pancreatic treatment as long as dose distribution is assessed. Any application of our results to clinical use should be undertaken only after discussion with oncologists, particularly with regard to radiotherapy combined with chemotherapy.

Dosimetric variation due to CT inter-slice spacing in four-dimensional carbon beam lung therapy.

When CT data with thick slice thickness are used in treatment planning, geometrical uncertainty may induce dosimetric errors. We evaluated carbon ion dose variations due to different CT slice thicknesses using a four-dimensional (4D) carbon ion beam dose calculation, and compared results between ungated and gated respiratory strategies. Seven lung patients were scanned in 4D mode with a 0.5 mm slice thickness using a 256-multi-slice CT scanner. CT images were averaged with various numbers of images to simulate reconstructed images with various slice thicknesses (0.5-5.0 mm). Two scenarios were studied (respiratory-ungated and -gated strategies). Range compensators were designed for each of the CT volumes with coarse inter-slice spacing to cover the internal target volume (ITV), as defined from 4DCT. Carbon ion dose distribution was computed for each resulting ITV on the 0.5 mm slice 4DCT data. The accumulated dose distribution was then calculated using deformable registration for 4D dose assessment. The magnitude of over- and under-dosage was found to be larger with the use of range compensators designed with a coarser inter-slice spacing than those obtained with a 0.5 mm slice thickness. Although no under-dosage was observed within the clinical target volume (CTV) region, D95 remained at over 97% of the prescribed dose for the ungated strategy and 95% for the gated strategy for all slice thicknesses. An inter-slice spacing of less than 3 mm may be able to minimize dose variation between the ungated and gated strategies. Although volumes with increased inter-slice spacing may reduce geometrical accuracy at a certain respiratory phase, this does not significantly affect delivery of the accumulated dose to the target during the treatment course.

Impact of intrafractional bowel gas movement on carbon ion beam dose distribution in pancreatic radiotherapy.

PURPOSE: To assess carbon ion beam dose variation due to bowel gas movement in pancreatic radiotherapy. METHODS AND MATERIALS: Ten pancreatic cancer inpatients were subject to diagnostic contrast-enhanced dynamic helical CT examination under breath-holding conditions, which included multiple-phase dynamic CT with arterial, venous, and delayed phases. The arterial-venous phase and arterial-delayed phase intervals were 35 and 145 s, respectively. A compensating bolus was designed to cover the target obtained at the arterial phase. Carbon ion dose distribution was calculated by applying the bolus to the CT data sets at the other two phases. RESULTS: Dose conformation to the clinical target volume was degraded by beam overshoot/undershoot due to bowel gas movement. The D95 for clinical target volume was degraded from 98.2% (range, 98.0-99.1%) of the prescribed dose to 94.7% (range, 88.0-99.0%) at 145 s. Excessive dosing to normal tissues varied among tissues and was, for example, 12.2 GyE/13.1 GyE (0 s/145 s) for the cord and 38.8 GyE/39.8 GyE (0 s/145 s) for the duodenum. The magnitude of beam overshoot/undershoot was particularly exacerbated from the anterior and left directions. CONCLUSIONS: Bowel gas movement causes dosimetric variation to the target during treatment for radiotherapy. The effect of bowel gas movement varies with beam angle, with greatest influence on the anterior-posterior and left-right beams.

Four-dimensional measurement of intrafractional respiratory motion of pancreatic tumors using a 256 multi-slice CT scanner.

PURPOSE: To quantify pancreas and pancreatic tumor movement due to respiratory motion using volumetric cine CT images. MATERIALS AND METHODS: Six patients with pancreatic tumors were scanned in cine mode with a 256 multi-slice CT scanner under free breathing conditions. Gross tumor volume (GTV) and pancreas were manually contoured on the CT data set by a radiation oncologist. Intrafractional respiratory movement of the GTV and pancreas was calculated, and the results were compared between the respiratory ungated and gated phases, which is a 30% duty cycle around exhalation. RESULTS: Respiratory-induced organ motion was observed mainly in the anterior abdominal side than the posterior side. Average GTV displacement (ungated/gated phases) was 0.7 mm/0.2mm in both the left and right directions, and 2.5mm/0.9 mm in the anterior, 0.1 mm/0mm in the posterior, and 8.9 mm/2.6mm in the inferior directions. Average pancreas center of mass displacement relative to that at peak exhalation was mainly in the inferior direction, at 9.6mm in the ungated phase and 2.3mm in the gated phase. CONCLUSIONS: By allowing accurate determination of the margin, quantitative analysis of tumor and pancreas displacement provides useful information in treatment planning in all radiation approaches for pancreatic tumors.

Water-equivalent pathlength reproducibility due to respiratory pattern variation in charged-particle pancreatic radiotherapy.

We evaluated the water-equivalent length (WEL) reproducibility due to variation in the external respiratory marker position when using a 4DCT scan in respiratory-gated charged-particle treatment. Two sets of pancreatic 4DCT data from two patients were acquired under free breathing conditions with 256-slice CT. The 4DCT data included two exhalation phases and the respiratory patterns in each patient differed, one being regular and the other irregular. The WEL calculation region is defined in the first respiratory cycle by two planes, one at the patient entrance surface and the other behind the target in the anterior-posterior (AP) and posterior-anterior (PA) directions. In the regular respiratory pattern, the WEL variation within the target region was less than 1.7 mm between the first and second exhalations in both AP and PA calculation directions. However, in the irregular breathing pattern, the respiratory amplitude at the second exhalation was 20% lower than that at the first exhalation; therefore, WEL variations from 8.1 to -9.1 mm and from 3.1 to -3.4 mm were observed within the target region in the AP and PA calculation directions, respectively. The WEL variation in the PA direction was smaller than that in the AP direction because the abdominal thickness is affected more in the AP direction. Respiratory pattern variation even affects WEL values in the respiratory-gated phase. This variation should be considered in treatment planning, and necessary improvements in respiratory reproducibility should be made.

Magnitude of residual internal anatomy motion on heavy charged particle dose distribution in respiratory gated lung therapy.

PURPOSE: To assess the variation in carbon beam dose distribution due to residual motion in lung cancer patients undergoing respiratory-gated radiotherapy. METHODS AND MATERIALS: A total of 11 lung cancer patients underwent four-dimensional computed tomography with a 256-multislice computed tomography scanner under free-breathing conditions. A compensating bolus was designed to cover the treatment beam for all planning target volumes during a 30% duty cycle centered on exhalation (gating window). This bolus was applied to the four-dimensional computed tomography data for one respiratory cycle, and then the carbon beam dose distribution was calculated. RESULTS: A water equivalent pathlength variation of <5 mm was observed in the gating window, but this increased to 95% volume irradiation is dependent on the respiratory phase but not the gating window. However, the dose for >95% volume irradiation correlated well with the tumor displacement distance. More than 90% of the dose for >95% volume irradiation could be delivered in the gating window with <4-mm tumor displacement resulting from exhalation. CONCLUSION: The results of our study have shown that even when the treatment beam delivery occurs outside the gating window, the prescribed dose to the target is not affected in patients with a tumor displacement of <4 mm. Thus, respiratory gating is not required in radiotherapy for patients with <4-mm tumor displacement in a respiratory cycle.

Design of a compensating bolus by use of exhalation CT data for covering residual motion in respiratory-gated charged-particle lung therapy: four-dimensional carbon beam dose calculation.

We developed an algorithm which we used to design a compensating bolus by using respiratory-gated CT data for respiratory-gated carbon beam lung therapy and evaluated it by calculating dose distributions as a function of time. Four-dimensional CT (4DCT) images were obtained for seven lung cancer patients under free breathing conditions. The internal target volume (ITV) was calculated by maximum intensity projection processing which use of three types of gross tumor volumes (GTVs): at peak exhalation and with a 5 mm shift of the GTV to both superior and inferior sides. Then a compensating bolus was designed which use of the ITV and applied to 4DCT data at the gating window (around exhalation phase). The carbon beam distribution was calculated by a pencil-beam algorithm as a function of time. The compensating bolus provides a sufficient prescribed dose to the target in the gating window and minimizes any excessive dose to the normal tissues. The metric of dosimetric assessment metrics of D95 in all patients is greater than 96% of the prescribed dose in the gating window. Our results will be beneficial for improving the accuracy of charged-particle radiotherapy for hospitals where 4DCT cannot be used.

Projection-data based temporal maximum attenuation computed tomography: determination of internal target volume for lung cancer against intra-fraction motion.

The concept of internal target volume (ITV) is highly significant in radiotherapy for the lung, an organ which is hampered by organ motion. To date, different methods to obtain the ITV have been published and are therefore available. To define ITV, we developed a new method by adapting a time filter to the four-dimensional CT scan technique (4DCT) which is projection-data processing (4D projection data maximum attenuation (4DPM)), and compared it with reconstructed image processing (4D image maximum intensity projection (4DIM)) using a phantom and clinical evaluations. 4DIM and 4DPM captured accurate maximum intensity volume (MIV), that is tumour encompassing volume, easily. Although 4DIM increased the CT number 1.8 times higher than 4DPM, 4DPM provided the original tumour CT number for MIV via a reconstruction algorithm. In the patient with lung fibrosis honeycomb, the MIV with 4DIM is 0.7 cm larger than that for cine imaging in the cranio-caudal direction. 4DPM therefore provided an accurate MIV independent of patient characteristics and reconstruction conditions. These findings indicate the usefulness of 4DPM in determining ITV in radiotherapy.

Improvement in banding artefacts in four-dimensional computed tomography for radiotherapy planning.

Respiratory-gated CT (RGCT) and four-dimensional CT (4DCT) scan techniques cover consecutive segments of the respiratory cycle. However, motion artefacts may occur in fast respiratory phases such as mid-inhalation and -exhalation. CT imaging involves the use of a number of x-ray tube positions for each couch position. We investigated the fundamental nature of motion artefacts using a constant-velocity moving phantom in motion in the CT plane or perpendicular to the CT plane, and in pigs to simulate a human model. Artefacts and movement distance were evaluated in a moving phantom and artificially ventilated pigs with a 256-multi-detector row CT (256MDCT). The phantom moved in the CT plane or perpendicular to the CT plane with a constant velocity. Backprojection used variable initial backprojection angles (IBAs). The phantom length for motion perpendicular to the CT plane was independent of IBA but was represented by phantom diameter plus the distance of movement per gantry rotation. In contrast, that for the motion in the CT plane was dependent on IBA, as represented by phantom diameter plus the distance of movement per rotation for IBA perpendicular to the phantom movement direction, and phantom diameter plus half the distance of movement per gantry rotation for other IBAs. Results for volumetric CT images with different IBAs showed the presence of banding artefacts. Similar findings were seen in artificially ventilated pigs. Motion artefacts are unavoidable in both conventional CT and 256MDCT. Banding artefacts will be improved if the same IBAs at each couch position are accounted for during image reconstruction. This improvement will be beneficial in respiratory gated and 4D radiation therapies.

The sigma factor RpoN (sigma54) is involved in osmotolerance in Listeria monocytogenes.

Listeria monocytogenes is able to grow under conditions of high osmolarity. We constructed a deletion mutant of rpoN, encoding the alternative sigma factor RpoN, and analyzed its response to osmotic stress. In a minimal medium with 4% NaCl and 1 mM betaine, the mutant showed a similar growth to that of the parental strain, EGD. In the same medium with 4% NaCl and 1 M carnitine, the growth rate of the mutant was greatly reduced, when the optical density at 600 nm (OD600) at the starting point of growth, was 0.15. However, when growth of the culture was started at an OD600 of 0.025, the growth of the mutant was similar to that of EGD. The mutant's expression of two betaine transporter genes, betL and gbuB, and the carnitine transporter gene opuCA, was osmotically induced at a level similar to EGD, and its rate of carnitine uptake was similar to that of EGD. These results suggest that the growth defect from the rpoN mutant is caused not by the transcriptional regulation of opuCA or by a decrease in carnitine uptake, but possibly by larger amounts of carnitine being needed for growth of the mutant in minimal medium when NaCl is present.