bluuebunny/crossref_metadata_2025 huggingface dataset:
Poster — Wed Eve—23: Electron Energy Spectral Analyses on Electron Backscatter in Solid Water Using Low‐Energy Electron Beams
Authors: Chow J , Grigorov G
Published: December 2012

Electron energy spectral analyses were carried out to evaluate the dosimetric performance of electron backscatter, when Solid Water was used to substitute water as phantom in electron radiotherapy using low‐energy electron beams (≤ 6 MeV). Monte Carlo simulation (EGSnrc‐based code) was used to predict electron energy spectra of Solid Water and water slabs above 0.3 mm of lead (Pb) layers, using the 4 and 6 MeV electron beams produced by a Varian 21 EX linear accelerator. For the simulation geometry, slabs of Solid Water and water on top of a piece of Pb layer were irradiated by electron beams ( applicator and cutout) with the source‐to‐surface distance equal to 100 cm. The thickness of Solid Water or water above the Pb layer was equal to 0.5 and 1 cm. Electron energy spectra were determined at scoring planes at depths of 0, 0.5 and 1 cm of the phantoms. For comparison, Monte Carlo simulations were repeated with Pb layers taken out from the phantoms with the same experimental configuration. Analyses of the electron energy spectra at different depths showed that deviation of energy spectra between Solid Water and water was more significant in the high‐energy range (i.e. close to the maximal electron energy) than lower range corresponding to the electron backscatter. The good agreement for the parts of the spectra representing the electron backscatter in Solid Water and water indicated that Solid Water performed well as a substitute of water for the electron backscatter when using low‐energy electron beams.
Poster — Wed Eve—24: Dosimetry of Lead Shield in Electron Radiotherapy: A Monte Carlo Evaluation
Authors: Chow J , Grigorov G
Published: December 2012

We investigated the dosimetric characteristics of the beam profile, relative dose at the central beam axis (CAX) and penumbra width at the depth of maximum dose (), varying with different sizes and thicknesses of a piece of lead (Pb) layer using different clinical electron beams. Monte Carlo simulations (EGSnrc‐based code) validated by measurements were used to calculate beam profiles at for different Pb shields and electron beams with energies of 4, 9 and 16 MeV. Pb layers with different thicknesses (2–8 mm) and sizes () were placed at the center of an electron field on a Solid Water phantom. Beam profiles were determined at , and dosimetry under the Pb layer was studied. We found that 2 mm of Pb layer is adequate to provide 5 half‐value‐layer attenuation for the 4 MeV electron beams. However, for the 9 and 16 MeV electron beams, the relative dose at CAX and depends on the thickness and size of the Pb layer. The dosimetry of the beam profile under the Pb layer at depends on the penumbra at the edge of the layer, and beam attenuation varies with the thickness of the layer. The dosimetry of the profile also depends on the electron side‐scatter contributing to the CAX, and photon contamination produced by the Pb layer. The dosimetric data calculated by Monte Carlo simulations in this study provides useful information in selecting the Pb shield suitable for the protection of critical tissue in electron radiotherapy.
Poster — Wed Eve—25: Comparison of Dose Calculation Algorithms with Monte Carlo Simulation for Surface Dosimetry
Authors: Chow J , Jiang R
Published: December 2012

The aim of this study is to compare the surface dosimetry calculated by the analytical anisotropic algorithm (AAA) and collapsed cone convolution (CCC) algorithm with Monte Carlo (MC) simulation. The MC simulations are verified by measurements. In this study, tangential photon beams (6 and 15 MV; 4 × 4 and ), produced by a Varian 21 EX linear accelerator, with central beam axis (CAX) parallel to the water phantom surface were used. In addition, the photon beam was tilted clockwise 3 and 5 degrees around the isocenter located at a distance of 2 mm from the phantom surface to represent the skin thickness. Relative dose profiles (2 mm from the phantom surface) corresponding to the above experimental configuration were calculated using the AAA, CCC and MC methods based on the Eclipse, Pinnacle3 treatment planning system and the EGSnrc code. It is found that both the AAA and CCC methods agreed with uncertainty < ±3% compared to the MC, in calculating the relative surface dose profiles, when the CAXs of the photon beams were overlapped along the profiles. However, when the photon beams (6 and 15 MV; 4 × 4 and ) were tilted clockwise, the AAA and CCC methods underestimated the dose in the relative surface profile as compared to the MC. The deviation of the calculated relative surface dose profile among the AAA, CCC and MC methods depends on the energy, angle and field size of the photon beam.
Poster — Wed Eve—27: Feasibility of Using Amorphous Silicon EPIDs for QC of MLCs
Authors: Hobson M , Khan R , Dunscombe P
Published: December 2012

The correct delivery of dynamic IMRT treatments is dependent on proper functioning of the MLCs. Recent publications suggest that an error of 0.3 mm in leaf position could lead to a 2% error in absolute dose to the target volume. QC tests that allow quick checks of the reproducibility of leaf positions and speeds would provide additional confidence in the correct functioning of the MLCs on a frequent basis. The feasibility of utilizing amorphous silicon EPIDs for QC of MLCs was evaluated with aS1000 EPIDs. Portal images of the MLC test patterns were acquired and analyzed in Matlab. Portal images of a picket fence pattern (1 cm steps separated by standard gaps between leaf ends) were acquired at different times and collimator and gantry angles (0° and 90°). The consistency in MLC leaf positions was evaluated by calculating the second derivative of image intensity profiles, allowing analysis of an image in 1–2 minutes. The measured standard gap was consistent within 0.5 mm, indicating reproducibility over time, and at gantry angles of 0° and 90°, indicating no measurable gravitational effects. Portal images of a wedge intensity pattern were acquired at various MUs to investigate effects of MLC acceleration/deceleration. Analysis of the wedge intensity pattern demonstrated a linear relationship between dose delivered and response of the EPID indicating consistency in leaf speed. QC tests developed will allow for daily robust evaluation of the performance of MLCs at different gantry and collimator angles without using films.
Poster — Wed Eve—28: Monte Carlo Study of the Influence of a Novel Transmission Detector on 6 MV Photon Beam
Authors: Asuni G , McCurdy B , Jensen M
Published: December 2012

The Monte Carlo technique is used to investigate the influence of a novel transmission detector (IBA Dosimetry, Germany) on a 6MV photon beam. The transmission detector may be used as an in vivo IMRT quality assurance tool, and therefore will be a source of contaminant electrons. This could potentially affect prescribed dose to patients. The linear accelerator together with the transmission detector and a plastic block tray for comparison, were modeled using BEAMnrc/EGSnrc. Electron fluence at different SSDs (70, 80, 90, 100 cm), electron energy spectra, electron angular distributions, and surface doses were calculated. Calculated data were validated against measurements using a fixed parallel plate chamber. Calculated surface dose for both open field and non‐open fields (i.e. TRD and block tray) agree within 3% of measurement. The fluence of contaminant electrons produced in the TRD and block tray fields increases at shorter SSD, but most electrons at shorter SSD are low energy electrons with large angular spread. These electrons contribute less to surface dose at larger SSD because they are either out‐scattered or absorbed in air. Surface doses at different SSDs for the block tray are higher than those of the TRD. Contribution of contaminant electrons to dose in the buildup region increases with increasing field size. For a field, the contribution of electrons is 9.8 % and 8.6% for block tray and TRD respectively, while for a smaller field is 0.35% and 0.75% for TRD and block tray respectively.
Poster — Wed Eve—29: Validation of VMAT Delivery Using a Commercial 2D Diode Array
Authors: Nielsen M , Wilson J , McCabe R , Khan F , MacPherson M
Published: December 2012

Volumetric modulated arc therapy (VMAT) is a new modality that combines IMRT with rotational delivery. RapidArc (Varian Medical Systems) incorporates the capability to vary dose rate, gantry speed and dynamic multileaf collimators to optimize dose and delivery efficiency. While new systems are being developed for VMAT verification, diode arrays are efficient and convenient tools for beam‐wise verification of IMRT delivery, and also have been employed in composite rotational delivery verification. Mapcheck2 (Sun Nuclear Corporation) is a new diode array with 1527 detectors. In this study, we investigate the use of Mapchekc2 in the MapPhan solid water phantom to validate VMAT delivery. 5 VMAT plans were generated in Eclipse using the RapidArc optimizer. All plans were delivered several times to verify consistency of delivery and measurement. Gamma analysis was used to verify the results compared to calculated dose distributions. The system was found to be sensitive to small changes in position or orientation. RapidArc beam delivery has been verified to correspond well with calculated dose distributions. Gamma values were below 1 in greater than 90% of measured points for all treatment plans. Delivery was found to be insensitive to initial dose rate. The MapPhan, with Mapcheck2 2D array in solidwater is a convenient way to verify VMAT plans. MapPhan results showed that RapidArc delivery is stable and reproducible.
Poster — Wed Eve—30: Routine QA and Re‐Commissioning of Linacs, TomoTherapy, and Treatment Planning Systems with MapCHECK™
Authors: Mosalaei H , Muligan M , Chen J
Published: December 2012

Recent developments in radiation delivery and treatment planning systems require more complicated quality assurance (QA) procedures. There are various QA test tools and specialized equipment for performing linear accelerator (Linac) and treatment delivery QA tests. However in order to have an effective QA program and ensure execution of the program, QA procedures should be simple and yet tailored so that each procedure checks as many facets as possible, while keeping the operating cost reasonable. At our center we use a 2D detector array, MapCHECK™ from SUN NUCLEAR Corporation, not only for its intended filmless IMRT QA but also for routine Linac and TomoTherapy machine QA as well as QA and commissioning of radiation treatment planning system. Using MapCHECK™ has improved our QA program feasibility and accuracy and has brought us one step closer to a paperless QA program.
Poster — Wed Eve—32: Internal Target Volume Dose Coverage Measurement for Respiratory Tumor Motion
Authors: Jiang R , Gopaul D , Osei E , Barnett R
Published: December 2012

The purpose of this study was to evaluate the difference between planned and delivered doses within the ITV generated by the co‐alignment of the standard and slow CT scan. A QUASAR™ phantom with a cedar insert (to simulate the lung) and an ionization chamber with buildup cap was scanned twice using modified slow CT scan technique. The respiratory cycle used for CT scan was 4 seconds/cycle and 10.0 mm amplitude along the longitudinal axis of the phantom. The two image sets were co‐aligned using the same reference points. The volume of the ionization chamber was used as a gross tumor volume (GTV) and was contoured on each scan. The ITV was generated by enveloping two GTVs from the two CT scans. The PTV was created by adding a 5mm margin around the ITV. If the chamber movement is within 1 cm, the minimum ITV dose coverage is 98.5%. The ITV dose coverage drops dramatically when the movement is larger than 1cm. The ITV dose coverage drops from 96.3% in 1.1cm motion to 90.7% in 1.5 cm motion. This study evaluated the difference between planned and delivered dose to the GTV using an ITV generated by the co‐alignment of the standard and slow CT scan. Co‐alignment of a slow CT and a standard CT underestimates the amplitude of GTV motion by 6mm. This results in under‐dosing of the ITV by 1.5%. The discrepancy between the TPS and measurement was 0.8%, for a total discrepancy of 2.3 %.
Poster — Wed Eve—33: Respiratory Internal Target Volume Assessment Using a Modified Slow CT Scan and CBCT
Authors: Jiang R , Gopaul D , Osei E , Barnett R
Published: December 2012

The purpose of this study was to investigate the volume of the ITV generated by a modified slow CT scan and CBCT using a QUASAR™ phantom. The standard CT scan (CTstandard) was acquired with pitch 1.7 and scan time 1 second followed by the slow CT scan (CTslow) limited to the tumor region with pitch 1 and scan time 3 seconds. The two image sets were co‐aligned using the same reference point, which was independent of bony anatomy changes with respiration. A gross tumor volume was contoured on each scan; Volume A is for CTstandard and Volume B is for CTslow; The ITV was generated from A∪B in Pinnacle TPS. Nine data sets of CTstandard and CTslow plus CBCT were acquired under free‐breathing. The ITV generated from the CTstandard is smaller than that from the CTslow (80% vs. 93% for 3 cm cube); however, the ITV generated from the co‐alignment of two image sets are improved compared to the sing CT alone. The ITV generated from the co‐alignment of CTstandard and CTslow is 98% for the 3cm cube and acceptable as depicted extent of motion. Modified slow CT scan provides complimentary information for the respiratory tumor motion. It compares favorably with the ITV generated with a cone beam CT. Modified slow CT scan and CBCT with tighter margin were used for lung radiosurgery with daily twice CBCT. It is a useful technique for optimizing the ITV resulting in tighter margins which may reduce toxicity and facilitate dose escalation.
Poster — Wed Eve—36: Preliminary Results of Patient Scatter Model for EPID Dosimetry
Authors: Chytyk K , McCurdy BMC
Published: December 2012

Complex radiotherapy techniques, such as intensity modulated radiation therapy (IMRT) or volumetric modulated radiation therapy (VMAT), have greatly increased the motivation for dosimetric verification of radiation therapy treatments. Pretreatment dosimetry is typically carried out prior to a patient's treatment but verification of the actual delivered treatment is not usually performed. Amorphous silicon electronic portal imaging devices (a‐Si EPIDs) have been established for IMRT verification, with one method involving the comparison of a predicted image to a measured image to determine whether the treatment field was delivered correctly. In this work, a comprehensive physics‐based parameter fluence model is interfaced with a patient scatter model to predict portal dose images. The patient scatter algorithm consists of a library of Monte Carlo calculated, scattered photon fluence kernels which predict scattered energy fluence exiting the patient or phantom. Images were acquired with an a‐Si EPID using a 6 MV beam and slab material in the beam path to test the model. Field size ranged from 1×1 to , with solid water thicknesses extending from 1 cm to 25 cm and an air gap of 40 cm. A prostate IMRT field was acquired during a patient treatment for prediction as well. Smaller fields were found to be accurately predicted within 2% and 2 mm, while larger fields were over‐predicted. The prostate field agreed within 2%, 3 mm. The model is able to accurately predict most MLC‐defined fields to within 2% and 2 mm; a prostate IMRT field has also been accurately predicted.
Poster — Wed Eve—37: Phantom Study Comparing Image Quality of Slow‐CT and Average CT Dataset from 4DCT Radiotherapy Planning Acquisitions
Authors: Basran PS , Karotki A
Published: December 2012

The purpose of this work was to compare slow‐CT () and average CT () datasets with free‐breathing helical CT () for contouring of organs at risk (OAR) and radiation treatment planning in patients receiving stereotactic body radiation therapy in lung. A quantitative examination of image quality parameters obtained from 4DCT‐derived datasets was performed using a mobile image quality phantom. The rigid phantom was translated in the superior‐inferior and anterior‐posterior directions through the CT scanning plane. Measurements of noise, low and high‐contrast resolution, spatial linearity, sensitometry, and observation of image artifacts resulting from phantom motion were recorded. In addition to these measurements, we computed the mean CT image () by increasing the number of breathing phases in the average CT calculation, and compared those image quality parameters with , and . While the image quality parameters were statistically the same in the phantom study, datasets had fewer image artifacts than the datasets. The image quality of the datasets improved greatly when the number of datasets used to generate the CTN was larger than the maximum permissible bins on the 4DCT reconstruction software (10 phases). or datasets may be used in place of for OAR contouring and potentially dose calculations, without significant compromise in image quality. This work demonstrates that when 4DCT is available, it may not be necessary to acquire a separate scan for OAR contouring.
Poster — Wed Eve—38: Comparison of IMRT Plan Quality from Two Different Linear Accelerator
Authors: Basran PS , MacKenzie R , Poon I , Balogh J , Chan T
Published: December 2012

The purpose of this work was to determine whether two different types of linear accelerators manufacturers with similar MLC leaf widths deliver equivalent IMRT dose distributions for head and neck radiotherapy patients. In the first study, a retrospective analysis of 197 head and neck IMRT patients delivered on Siemens Primus and Elekta Synergy machines was undertaken to test statistical differences in machine type, monitor units, maximum target dose, and number of target doses. Both machines have 1 cm MLC leaves but have different linac head geometries. Plan were created using the direct machine parameter optimization (DMPO) routine on Philips' Pinnacle treatment planning system (TPS) system, in step and shoot mode. A multi‐variate analysis was used to test for significance, Pearson's correlations, and coefficients of determination. In the second study, a replanning exercise was conducted where deliverable plans from a Siemens machine was re‐optimized with an Elekta machine and vice‐versa. In the first study, there was no evidence of any significant difference in the IMRT plans. Elekta machines delivered more MUs than the Siemens units but the difference was not significant (). In the second study, the presentation of the dose distributions, DVHs, and mean dose to target and normal tissue structures were equivalent. However, approximately 15% more monitor units were delivered when plans were planned or re‐planned on the Elekta machine. This work suggests that for plans of comparable quality, Elekta machines deliver more monitor units than Siemens machines, likely due to differences in the geometric properties of the machines.
Poster — Wed Eve—39: Using DOSRZnrc to Study the SFD Si‐Diode for Small Field Relative Dosimetry
Authors: Cranmer‐Sargison G , Babcock K
Published: December 2012

Purpose: The goal of this work was to study the SFD Si‐diode (IBA Dosimetry, previously Scanditronix/Wellhofer) for small field dosimetry. Methods and Materials: The EGSnrc user code DOSRZnrc was used to construct a geometrically accurate model of the detector. The active volume was modelled as pure silicon () and 6HSiC (). For field sizes between 0.5 and 5.0 cm, water tank simulations were run and validated experimentally for isocentric detector placement at depths of 1.5, 5.0 and 10.0 cm. Detector response was investigated and correction factors calculated according to Capote et al (Med. Phys. 31 2416–22) and Alfonso et al (Med. Phys. 35 5179–86). Results: The SFDSi simulated ROFs were generally higher than the experimental values yet still within the statistical uncertainty of 1.3 to 1.5%. However, for the two smallest field sizes the data was high by as much as 3.0%. The simulated ROFs revealed no such disagreement with experiment and were statistically equivalent to the measured data. Conclusion: The active volume of the SFD detector is most likely a substrate very similar to 6HSiC and should not be modelled as pure silicon, modelling the detector as a “chip in water” may be considered a reasonable approximation but does hinge on the correct choice of material for the active volume and it appears no correction factor is required for small field relative output factors measured with the SFD Si‐diode detector, however a reduction in the statistical uncertainty would be desirable.
Poster — Wed Eve—42: IMRT Dosimetry for Prostate, Breast and Head‐and‐Neck: Comparing Biologically Based Step‐and‐Shoot IMRT with Dynamic Helical Tomotherapy
Authors: Ploquin N , Belec J , Clark B
Published: December 2012

We have dosimetrically compared two treatment planning systems used in our clinic to create intensity‐modulated radiation therapy (IMRT) plans. A new commercial inverse treatment planning system (Monaco, CMS, Inc, St. Louis, Missouri) allowing Monte‐Carlo calculations, aperture based optimization, and biological cost functions was compared to the TomoTherapy Hi‐ART (Tomo‐Therapy, Madison, WI) planning system. Six clinical test cases (head and neck, prostate, and breast) were planned and compared using DVHs and dosimetric parameters (maximum dose, mean dose, conformity and homogeneity indexes). Both treatment planning systems provided adequate deliverable plans. Overall, tomotherapy plans provided a better conformality and dose homogeneity in most of the clinical cases also with improved sparing of major organs at risk. The dosimetric analysis shows that although the treatment planning systems have differences, they are each capable of producing substantially equivalent treatment plans in term of target coverage and normal tissue sparing.
Poster — Wed Eve—43: A Maximum Likelihood/ Simulated Annealing‐Based Validation Method for Tumor Segmentation Techniques
Authors: Yu H , Caldwell C , Mah K
Published: December 2012

Introduction: The performance of tumor segmentation methods can only be evaluated by comparison with observers' contours when the true pathologic extent is unknown. All observers' contours contain bias and it is unclear how to best combine segmentations to estimate “truth”. Objective: To develop a method that optimally combines observers' contours to estimate a “true” reference for evaluating tumor segmentation techniques. Methods: A probabilistic “truth” was estimated from multiple observers' segmentations via maximum‐likelihood analysis using the simulated‐annealing (SA) and Expectation‐Maximum optimization algorithms. A qualitative ranking of the performance levels of observers' segmentations, was introduced to steer the method when the relative qualities of input contours are known. The SA‐based method was evaluated first using digital phantoms which were “true” tumors and simulated observers' contours by shifting, shrinking and expanding the “true” tumors. It, secondly, was evaluated using clinical data. The tumor volumes of 12 head and neck cancer (HNC) patients were contoured by three radiation oncologists using CT alone and subsequently, using PET/CT. Results: The SA‐based method exactly determined the “truth” in digital phantom studies. In the clinical study of HNC patients the mean and the range of sensitivity of the SA method were 0.90 and 0.70–0.98, respectively, when compared to a pre‐defined “probabilistic” reference. Conclusions: This work suggests that the SA method can accurately estimate a “truth” to validate image segmentation methods. It also provides a logical means of combining segmentations from different sources, which could potentially improve accuracy of radiation therapy or surgical target localization.
Poster — Wed Eve—44: CO‐Registered Multi‐Modality Pattern Analysis Segmentation System (COMPASS) for Radiation Targeting of Head and Neck Cancer Using FDG PET/CT
Authors: Yu H , Caldwell C , Mah K , Poon I , Balogh J , MacKenzie R
Published: December 2012

Introduction: Previous attempts to segment tumours for radiation therapy targeting based on FDG‐PET image thresholds have had little success. However, if the texture information available in PET and CT images is used, more accurate and reliable differentiation of abnormal and normal tissues may be possible. Objective: To develop an automated image segmentation method for head and neck cancer (HNC) using texture analysis of co‐registered FDG‐PET/CT images. Methods: CO‐registered Multi‐modality Pattern Analysis Segmentation System (COMPASS) was developed using a region‐of‐interest‐based Decision Tree K‐Nearest‐Neighbors (DTKNN) classifier. 14 PET and 13 CT texture features such as coarseness, busyness and Left/right symmetrical ratio were calculated for each voxel from corresponding PET and CT images within a window centered on the voxel. Then the voxel was classified as “tumor” or “non‐tumor” using the DTKNN classifier. PET/CT images of 10 patients with HNC who had their primary tumors and positive nodes manually segmented by three radiation oncologists were used for evaluation. Results: The sensitivity per patient was 83%±19% when “true positive voxels” were defined as those voxels identified by at least two physicians as tumor. The specificity was 95%±2% when “true negative” voxels were all soft tissue voxels not identified by any of three physicians as tumor. Results of COMPASS were significantly better than those of three previously published PET threshold‐based methods. Conclusions: This work suggests that an automated segmentation method based on texture classification of FDG‐PET/CT images has the potential to provide accurate delineation of HNC.
Poster — Wed Eve—46: Quantitative Evaluation on the Accuracy of Image Registration Methods in SPECT Guided Radiation Therapy for Lung Cancer Patients
Authors: Yin L , Tang L , Hamarneh G , Moiseenko V , Celler A , Shcherbinin S , Fua T‐F , Thompson A , Liu M , Duzenli C , Gill B , Sheehan F , Powe J , Worsley D
Published: December 2012

Purpose: To quantitatively evaluate the accuracy of several SPECT/CT image registration methods in recent studies and its impact on the functional lung volume segmentation in SPECT guided radiation therapy (RT) treatment planning. Methods and Materials: Five lung cancer patients were consented to have a perfusion SPECT scan with 99mTc‐macroaggregated albumin. During the scan, a low resolution CT image was acquired using the SPECT/CT scanner. This CT scan was co‐registered to the patient's planning CT scan through four rigid and deformable image registration programs (rigid registration, skin/lung control points based registration and B‐spline deformable registration). After the CT to CT co‐registration, original SPECT reconstructions were warped and co‐registered to the planning CT scan. The functional lung volumes were segmented from each deformed SPECT using 10, 20, …, 90% of maximum pixel value as a threshold. The differences in the size and contours of each functional volume were calculated. Results: Based on the evaluation of registered CT images, the result from B‐spline registration demonstrated the smallest intensity difference. Using the warped SPECT images obtained from this registration method as a reference, the smallest difference in the size and contour of functional volumes was found using rigid registration. In the point‐based registrations, a better result was found when the control points were placed on lung volume instead of body contour. Conclusion: Apply B‐spline based image registration method in SPECT‐guided RT studies was shown to be accurate. Point‐based image registration using skin markers with a standalone SPECT scanner was found least accurate.
Poster — Wed Eve—47: IMRT Beam Angle Optimization Using a Hot‐Scripted Learning Algorithm for a Commercial Planning System
Authors: Sak M , Richer J , Rangan C
Published: December 2012

Traditionally, beam angle selection for intensity‐modulated radiation therapy (IMRT) plans has been left up to the experienced dosimetrist. However, the large number of potential angle orientations suggests that the human plan may not be ideal. A learning algorithm (a variation of a genetic algorithm) was written to select beam angles to produce plans with more desirable dose‐volume histograms (DVH). The algorithm is used in parallel with the commercial Pinnacle3 Radiation Therapy Planning System. Starting with a generation of randomly chosen beam angles, the algorithm uses Pinnacle's built‐in hot scripting to call on the P3 IMRT portion of the software to perform dose calculations on each individual. Each set of angles is then ranked using a dosimetric fitness function that uses the same constraints that are used during the IMRT calculations. A new generation of beam angles is then constructed using both biologically and non‐biologically relevant operators. Operator weights are also adjusted each generation based on the dosimetric fitness function as well. Once completed, the algorithm was tested on several IMRT prostate cases. In each case, the DVH for the algorithm‐selected plan fit the dose constraints better than the human‐designed IMRT plan. A major drawback was the long running time of the algorithm (up to 11 hours), which was constrained almost entirely by the speed of Pinnacle's IMRT calculations. The ideal use of the code would be for overnight applications, with the human planner then using the optimized beam angles to plan as normal. This research was supported by the Graduate Internship program of the MITACS Network of Centres of Excellence and the Local Investigator Research Fund of the Windsor Regional Cancer Centre.
Serodiagnosis of Human Cutaneous Anthrax in India Using an Indirect Anti-Lethal Factor IgG Enzyme-Linked Immunosorbent Assay
Authors: Ghosh N. , Tomar I. , Lukka H. , Goel A. K.
Published: December 2012

Anthrax, caused by
Bacillus anthracis
, is primarily a zoonotic disease. Being a public health problem also in several developing countries, its early diagnosis is very important in human cases. In this study, we describe the use of an indirect enzyme-linked immunosorbent assay (ELISA) for detection of anti-lethal factor (anti-LF) IgG in human serum samples. A panel of 203 human serum samples consisting of 50 samples from patients with confirmed cutaneous anthrax, 93 samples from healthy controls from areas of India where anthrax is nonendemic, 44 samples from controls from an area of India where anthrax is endemic, and 16 patients with a disease confirmed not to be anthrax were evaluated with an anti-LF ELISA. The combined mean anti-LF ELISA titer for the three control groups was 0.136 ELISA unit (EU), with a 95% confidence interval (CI) of 0.120 to 0.151 EU. The observed sensitivity and specificity of the ELISA were 100% (95% CI, 92.89 to 100%) and 97.39% (95% CI, 93.44 to 99.28%), respectively, at a cutoff value of 0.375 EU, as decided by receiver operating characteristic (ROC) curve analysis. The likelihood ratio was found to be 49.98. The positive predictive value (PPV), negative predictive value (NPV), efficiency, and Youden's index (
J
) for reliability of the assay were 92.5%, 100%, 98.02%, and 0.97, respectively. The false-positive predictive rate and false-negative predictive rate of the assay were 2.61% and 0%. The assay could be a very useful tool for early diagnosis of cutaneous anthrax cases, as antibodies against LF appear much earlier than those against other anthrax toxins in human serum samples.
Serodiagnostic Potential of Mycobacterium avium MAV2054 and MAV5183 Proteins
Authors: Shin A-Rum , Lee Kil-Soo , Lee Kang In , Shim Tae Sun , Koh Won-Jung , Jeon Haet Sal , Son Yeo-Jin , Shin Sung-Jae , Kim Hwa-Jung
Published: December 2012

The
Mycobacterium avium
-
M. intracellulare
complex (MAC) causes a pulmonary disease (PD) similar to tuberculosis (TB). Diagnosis of MAC-PD is complicated and time-consuming. In this study, the serodiagnostic potential of the newly identified MAV2054 and MAV5183 proteins was evaluated in subjects with MAC-PD, pulmonary TB, or latent TB and in noninfected healthy controls (HC), together with HspX and the 38-kDa antigen, well-known serodiagnostic
M. tuberculosis
antigens. All four antigens evoked significantly higher IgG responses in MAC-PD and active TB than in latent TB and HC subjects. Among the antigens, MAV2054 elicited the highest antibody responses in pulmonary TB and MAC-PD patients. IgG titers against MAV2054 and MAV5183 were significantly higher in MAC-PD than in pulmonary TB subjects. In addition, the levels of IgG against all antigens in the
M. intracellulare
and fibrocavitary forms were higher than those in the
M. avium
and nodular bronchiectatic forms, respectively. Based on sensitivity and receiver operator characteristic curve analysis, the best candidates for detection of MAC-PD and pulmonary TB were MAV2054 and the 38-kDa antigen, respectively. In total, 76.0% of MAC-PD and 65.0% of active TB patients were reactive to at least two antigens. In contrast, only 2.8% of HC subjects were reactive with two or more antigens. Our findings suggest that an enzyme-linked immunosorbent assay (ELISA) using the four antigens would be valuable for screening for mycobacterial lung disease, including MAC-PD and pulmonary TB, although it does not provide good discrimination of the disease-causing pathogens.
Mechanisms of Linezolid Resistance among Staphylococci in a Tertiary Hospital
Authors: Quiles-Melero Inmaculada , Gómez-Gil Rosa , Romero-Gómez María Pilar , Sánchez-Díaz Ana María , de Pablos Manuela , García-Rodriguez Julio , Gutiérrez Avelino , Mingorance Jesús
Published: December 2012

The mechanisms of linezolid resistance among 86 staphylococcal isolates from two intensive care units were investigated. The most frequent was the G2576T mutation in the 23S rRNA (82%). The
cfr
gene was found in 17% of the isolates, seven
S. aureus
and eight
S. epidermidis
isolates. Four of the
S. epidermidis
isolates had the G2576T mutation and the
cfr
gene. In four
S. haemolyticus
isolates, the mechanism could not be identified.
Changes in Molecular Epidemiology of Streptococcus pneumoniae Causing Meningitis following Introduction of Pneumococcal Conjugate Vaccination in England and Wales
Authors: Pichon Bruno , Ladhani Shamez N. , Slack Mary P. E. , Segonds-Pichon Anne , Andrews Nick J. , Waight Pauline A. , Miller Elizabeth , George Robert
Published: December 2012

The introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in September 2006 has markedly reduced the burden of invasive pneumococcal disease (IPD) including meningitis in England and Wales. This study examined changes in the molecular epidemiology of pneumococcal isolates causing meningitis from July 2004 to June 2009. The Health Protection Agency conducts enhanced pneumococcal surveillance in England and Wales. In addition to serotyping, pneumococcal isolates causing meningitis were genotyped by multilocus sequence typing (MLST). A total of 1,030 isolates were both serotyped and genotyped over the 5-year period. Fifty-two serotypes, 238 sequence types (STs), and 87 clonal complexes were identified, with no significant difference in the yearly Simpson's diversity index values (range, 0.974 to 0.984). STs commonly associated with PCV7 serotypes declined following PCV implementation, with a proportionally greater decline in ST124 (commonly associated with serotype 14). No other ST showed significant changes in distribution, even within individual serotypes. Replacement disease following PCV7 introduction was mainly due to serotypes 1, 3, 7F, 19A, 22F, and 33F through clonal expansion. A single instance of possible capsule switching was identified where one ST4327 clone expressed a serotype 14 capsule in 2005 and a serotype 28A capsule in 2009. In 2008 to 2009, ST191 (7F) became the most prevalent clone causing meningitis (10.3%). Case fatality (145 fatalities/1,030 cases; 14.1%) was high across all age groups and serotype groups. Thus, the introduction of PCV7 resulted in an increase in non-PCV7 serotypes, including some not covered by the 13-valent vaccine, such as serotypes 22F and 33F, emphasizing the importance of long-term epidemiological and molecular surveillance.
Multiplex Real-Time PCR Assay for Detection of Methicillin-Resistant Staphylococcus aureus (MRSA) Strains Suitable in Regions of High MRSA Endemicity
Authors: Kim Jeong-Uk , Cha Choong-Hwan , An Hae-Kyong , Lee Ho-Jun , Kim Mi-Na
Published: December 2012

A multiplex real-time PCR assay that simultaneously detects the
mecA
, staphylococcal cassette chromosome (SCC
mec
)-open reading frame X (
orfX
) junction, and staphylococcal 16S rRNA genes was developed and evaluated using 444 staphylococcal strains. We demonstrated that this assay resulted in fewer false-positive results than a single-locus real-time PCR assay that amplified the SCC
mec-orfX
junction. This assay would be useful in a clinical laboratory in a region of high endemicity for methicillin-resistant
Staphylococcus aureus
(MRSA) infections.
Nationwide Study of Candidemia, Antifungal Use, and Antifungal Drug Resistance in Iceland, 2000 to 2011
Authors: Asmundsdottir Lena Ros , Erlendsdottir Helga , Gottfredsson Magnus
Published: December 2012

Candidemia is often a life-threatening infection, with highly variable incidence among countries. We conducted a nationwide study of candidemia in Iceland from 2000 to 2011, in order to determine recent trends in incidence rates, fungal species distribution, antifungal susceptibility patterns, and concurrent antifungal consumption. A total of 208 infection episodes in 199 patients were identified. The average incidence during the 12 years was 5.7 cases/100,000 population/year, which was significantly higher than that from 1990 to 1999 (4.3/100,000/year;
P
= 0.02). A significant reduction in the use of blood cultures was noted in the last 3 years of the study, coinciding with the economic crisis in the country (
P
< 0.001). Age-specific incidence rates were highest among patients at the extremes of age, 20.7/100,000 for <1 year of age and 18.1/100,000 for >60 years, and varied by gender. Age-specific incidence among males >80 years old was 28.6/100,000/year, and it was 8.3/100,000/year for females in this age group (
P
= 0.028). The 30-day survival rate among adult patients remained unchanged compared to that from 1990 to 1999 (70.4% versus 69.5%,
P
= 0.97).
Candida albicans
was the predominant species (56%), followed by
C. glabrata
(16%) and
C. tropicalis
(13%). The species distribution remained stable compared to that from previous decades. Fluconazole use increased 2.4-fold from 2000 to 2011, with no increase in resistance. In summary, the incidence of candidemia in Iceland has continued to increase but may have reached a steady state, and no increase in antifungal drug resistance has been noted. Decreased use of blood cultures toward the end of the study may have influenced detection rates.
Genetic Analysis of Glycopeptide-Resistant Staphylococcus epidermidis Strains from Bone and Joint Infections
Authors: Cremniter Julie , Sivadon-Tardy Valérie , Caulliez Charlotte , Bauer Thomas , Porcher Raphaël , Lortat-Jacob Alain , Piriou Philippe , Judet Thierry , Aegerter Philippe , Herrmann Jean-Louis , Gaillard Jean-Louis , Rottman Martin
Published: December 2012

Glycopeptide-resistant
Staphylococcus epidermidis
(GRSE) strains are of increasing concern in bone and joint infections (BJIs). Using multilocus sequence typing and multilocus variable-number tandem repeat analysis, we show that BJI-associated GRSE strains are genetically diverse but arise from related, multiresistant hospital sequence types (STs), mostly ST2, ST5, and ST23.
Vascular Endothelial Growth Factor A Promotes Vaccinia Virus Entry into Host Cells via Activation of the Akt Pathway
Authors: Hiley Crispin T. , Chard Louisa S. , Gangeswaran Rathi , Tysome James R. , Briat Arnaud , Lemoine Nicholas R. , Wang Yaohe
Published: December 2012

Vaccinia virus (VV) is an enveloped DNA virus from the poxvirus family and has played a crucial role in the eradication of smallpox. It continues to be used in immunotherapy for the prevention of infectious diseases and treatment of cancer. However, the mechanisms of poxvirus entry, the host factors that affect viral virulence, and the reasons for its natural tropism for tumor cells are incompletely understood. By studying the effect of hypoxia on VV infection, we found that vascular endothelial growth factor A (VEGF-A) augments oncolytic VV cytotoxicity. VEGF derived from tumor cells acts to increase VV internalization, resulting in increased replication and cytotoxicity in an AKT-dependent manner in both tumor cells and normal respiratory epithelial cells. Overexpression of VEGF also enhances VV infection within tumor tissue
in vivo
after systemic delivery. These results highlight the importance of VEGF expression in VV infection and have potential implications for the design of new strategies to prevent poxvirus infection and the development of future generations of oncolytic VV in combination with conventional or biological therapies.
A Vesicular Stomatitis Virus-Based Therapeutic Vaccine Generates a Functional CD8 T Cell Response to Hepatitis B Virus in Transgenic Mice
Authors: Cobleigh Melissa A. , Wei Xin , Robek Michael D.
Published: December 2012

Recombinant vesicular stomatitis virus (VSV) is a promising therapeutic vaccine platform. Using a transgenic mouse model of chronic hepatitis B virus (HBV) infection, we evaluated the therapeutic potential of a VSV vector expressing the HBV middle surface envelope glycoprotein (MS). VSV-MS immunization generated HBV-specific CD8 T cell and antibody responses in transgenic mice that express low HBV antigen levels. These findings support the further development of VSV as a therapeutic vaccine vector for chronic HBV.
Enhancement of Antiviral Activity of Human Alpha-Defensin 5 against Herpes Simplex Virus 2 by Arginine Mutagenesis at Adaptive Evolution Sites
Authors: Wang Aiping , Chen Fang , Wang Yingjie , Shen Mingqiang , Xu Yang , Hu Jian , Wang Song , Geng Fang , Wang Cheng , Ran Xinze , Su Yongping , Cheng Tianmin , Wang Junping
Published: December 2012

Herpes simplex virus 2 (HSV-2) infection is still one of the common causes of sexually transmitted diseases worldwide. The prevalence of HSV strains resistant to traditional nucleoside antiviral agents has led to the development of novel antiviral drugs. Human alpha-defensin 5 (HD5), a kind of endogenous antimicrobial peptide expressed in the epithelia of the small intestine and urogenital tract, displays natural antiviral activity. Based on arginine-rich features and adaptive evolution characteristics of vertebrate defensins, we conducted a screen for HD5 derivatives with enhanced anti-HSV-2 activity by a single arginine substitution at the adaptive evolution sites. Cell protection assay and temporal antiviral studies showed that HD5 and its mutants displayed affirmatory but differential anti-HSV-2 effects
in vitro
by inhibiting viral adhesion and entry. Inspiringly, the E21R-HD5 mutant had significantly higher antiviral activity than natural HD5, which is possibly attributed to the stronger binding affinity of the E21R-HD5 mutant with HSV-2 capsid protein gD, indicating that E21R mutation can increase the anti-HSV-2 potency of HD5. In a mouse model of lethal HSV-2 infection, prophylactic and/or therapeutic treatment with E21R-HD5 via intravaginal instillation remarkably alleviated the symptoms and delayed disease progress and resulted in about a 1.5-fold-higher survival rate than in the HD5 group. Furthermore, the E21R variant exhibited a 2-fold-higher antiviral potency against HIV-1 over parental HD5
in vitro
. This study demonstrates that arginine mutagenesis at appropriate evolution sites may significantly enhance the antiviral activity of HD5, which also paves a facile way to search for potent antiviral drugs based on natural antimicrobial peptides.
Low Oxygen Tension Enhances Hepatitis C Virus Replication
Authors: Vassilaki N. , Kalliampakou K. I. , Kotta-Loizou I. , Befani C. , Liakos P. , Simos G. , Mentis A. F. , Kalliaropoulos A. , Doumba P. P. , Smirlis D. , Foka P. , Bauhofer O. , Poenisch M. , Windisch M. P. , Lee M. E. , Koskinas J. , Bartenschlager R. , Mavromara P.
Published: December 2012

Low oxygen tension exerts a significant effect on the replication of several DNA and RNA viruses in cultured cells.In vitropropagation of hepatitis C virus (HCV) has thus far been studied under atmospheric oxygen levels despite the fact that the liver tissue microenvironment is hypoxic. In this study, we investigated the efficiency of HCV production in actively dividing or differentiating human hepatoma cells cultured under low or atmospheric oxygen tensions. By using both HCV replicons and infection-based assays, low oxygen was found to enhance HCV RNA replication whereas virus entry and RNA translation were not affected. Hypoxia signaling pathway-focused DNA microarray and real-time quantitative reverse transcription-PCR (qRT-PCR) analyses revealed an upregulation of genes related to hypoxic stress, glycolytic metabolism, cell growth, and proliferation when cells were kept under low (3% [vol/vol]) oxygen tension, likely reflecting cell adaptation to anaerobic conditions. Interestingly, hypoxia-mediated enhancement of HCV replication correlated directly with the increase in anaerobic glycolysis and creatine kinase B (CKB) activity that leads to elevated ATP production. Surprisingly, activation of hypoxia-inducible factor alpha (HIF-α) was not involved in the elevation of HCV replication. Instead, a number of oncogenes known to be associated with glycolysis were upregulated and evidence that these oncogenes contribute to hypoxia-mediated enhancement of HCV replication was obtained. Finally, in liver biopsy specimens of HCV-infected patients, the levels of hypoxia and anaerobic metabolism markers correlated with HCV RNA levels. These results provide new insights into the impact of oxygen tension on the intricate HCV-host cell interaction.
Analysis of the Costructure of the Simian Virus 40 T-Antigen Origin Binding Domain with Site I Reveals a Correlation between GAGGC Spacing and Spiral Assembly
Authors: Meinke Gretchen , Phelan Paul J. , Harrison Celia J. , Bullock Peter A.
Published: December 2012

Polyomavirus origins of replication contain multiple occurrences of G(A/G)GGC, the high-affinity binding element for the viral initiator T-antigen (T-ag). The site I regulatory region of simian virus 40, involved in the repression of transcription and the enhancement of DNA replication initiation, contains two GAGGC sequences arranged head to tail and separated by a 7-bp AT-rich sequence. We have solved a 3.2-Å costructure of the SV40 origin-binding domain (OBD) bound to site I. We have also established that T-ag assembly on site I is limited to the formation of a single hexamer. These observations have enabled an analysis of the role(s) of the OBDs bound to the site I pentanucleotides in hexamer formation. Of interest, they reveal a correlation between the OBDs bound to site I and a pair of OBD subunits in the previously described hexameric spiral structure. Based on these findings, we propose that spiral assembly is promoted by pentanucleotide pairs arranged in a head-to-tail manner. Finally, the possibility that spiral assembly by OBD subunits accounts for the heterogeneous distribution of pentanucleotides found in the origins of replication of polyomaviruses is discussed.