bluuebunny/crossref_metadata_2025 huggingface dataset:
Presumed primary immune‐mediated neutropenia in 35 dogs: a retrospective study
Authors: Devine L. , Armstrong P. J. , Whittemore J. C. , Sharkey L. , Bailiff N. , Huang A. , Rishniw M.
Published: February 2017

Objectives

To describe, in a cohort of dogs with presumed primary immune‐mediated neutropenia, the presenting clinical characteristics, haematology results, bone marrow characteristics, therapies used (drugs and doses), clinical response to treatment, relapse and outcome at six months and one year.

Methods

Multi‐institutional recruited retrospective descriptive case series with voluntary submissions. Presumed immune‐mediated neutropenia was diagnosed based on a neutrophil concentration <1·5×109 cells/L on a minimum of two complete blood counts, exclusion of other causes of neutropenia based on a diagnostic bone marrow aspirate or biopsy, and exclusion of secondary immune‐mediated neutropenia. Dogs meeting these diagnostic criteria between 2006 and 2013, and that had a haematocrit of ≥29% and minimum of two complete blood clounts performed after initiation of therapy, were included.

Results

Information on 35 dogs was included. Neutropenia was less than 0·5×109 cells/L in most cases (21 dogs), 0·5 to ·99×109 cells/L in 11, and 1.0 to 1·49×109 cells/L in three. Eight dogs had thrombocytopenia, which was severe (<49·9×109 cells/L) in three. [Correction added on 23 May 2017, after first online publication: the cell numbers were incorrect due to errors in the conversion of cell measurements to international units. The numbers have been corrected throughout the article and Table 2.] Twenty‐three dogs had myeloid hyperplasia, 10 dogs had myeloid hypoplasia and two dogs had normal myelopoiesis. Neutropenia resolved in 32 of 33 dogs within two weeks of starting corticosteroid therapy and in all dogs within one month. Relapse of neutropenia occurred in 12 cases within one year.

Clinical Significance

Initial response of presumed primary immune‐mediated neutropenia cases to corticosteroid therapy can be excellent. Long‐term monitoring for relapse is warranted because 34% of cases relapsed during or after taper of immunosuppressive medications.
Early evolution of the land plant circadian clock
Authors: Linde Anna‐Malin , Eklund D. Magnus , Kubota Akane , Pederson Eric R. A. , Holm Karl , Gyllenstrand Niclas , Nishihama Ryuichi , Cronberg Nils , Muranaka Tomoaki , Oyama Tokitaka , Kohchi Takayuki , Lagercrantz Ulf
Published: February 2017

While angiosperm clocks can be described as an intricate network of interlocked transcriptional feedback loops, clocks of green algae have been modelled as a loop of only two genes. To investigate the transition from a simple clock in algae to a complex one in angiosperms, we performed an inventory of circadian clock genes in bryophytes and charophytes. Additionally, we performed functional characterization of putative core clock genes in the liverwort Marchantia polymorpha and the hornwort Anthoceros agrestis.

Phylogenetic construction was combined with studies of spatiotemporal expression patterns and analysis of M. polymorpha clock gene mutants.

Homologues to core clock genes identified in Arabidopsis were found not only in bryophytes but also in charophytes, albeit in fewer copies. Circadian rhythms were detected for most identified genes in M. polymorpha and A. agrestis, and mutant analysis supports a role for putative clock genes in M. polymorpha.

Our data are in line with a recent hypothesis that adaptation to terrestrial life occurred earlier than previously expected in the evolutionary history of charophyte algae. Both gene duplication and acquisition of new genes was important in the evolution of the plant circadian clock, but gene loss has also contributed to shaping the clock of bryophytes.
Deletion‐bias in DNA double‐strand break repair differentially contributes to plant genome shrinkage
Authors: Vu Giang T. H. , Cao Hieu X. , Reiss Bernd , Schubert Ingo
Published: February 2017

In order to prevent genome instability, cells need to be protected by a number of repair mechanisms, including DNA double‐strand break (DSB) repair. The extent to which DSB repair, biased towards deletions or insertions, contributes to evolutionary diversification of genome size is still under debate.

We analyzed mutation spectra in Arabidopsis thaliana and in barley (Hordeum vulgare) by PacBio sequencing of three DSB‐targeted loci each, uncovering repair via gene conversion, single strand annealing (SSA) or nonhomologous end‐joining (NHEJ). Furthermore, phylogenomic comparisons between A. thaliana and two related species were used to detect naturally occurring deletions during Arabidopsis evolution.

Arabidopsis thaliana revealed significantly more and larger deletions after DSB repair than barley, and barley displayed more and larger insertions. Arabidopsis displayed a clear net loss of DNA after DSB repair, mainly via SSA and NHEJ. Barley revealed a very weak net loss of DNA, apparently due to less active break‐end resection and easier copying of template sequences into breaks. Comparative phylogenomics revealed several footprints of SSA in the A. thaliana genome.

Quantitative assessment of DNA gain and loss through DSB repair processes suggests deletion‐biased DSB repair causing ongoing genome shrinking in A. thaliana, whereas genome size in barley remains nearly constant.
Overexpression of OsERF48 causes regulation of OsCML16, a calmodulin‐like protein gene that enhances root growth and drought tolerance
Authors: Jung Harin , Chung Pil Joong , Park Su‐Hyun , Redillas Mark Christian Felipe Reveche , Kim Youn Shic , Suh Joo‐Won , Kim Ju‐Kon
Published: February 2017

The AP2/ERF family is a plant‐specific transcription factor family whose members have been associated with various developmental processes and stress tolerance. Here, we functionally characterized the drought‐inducible OsERF48, a group Ib member of the rice ERF family with four conserved motifs, CMI‐1, ‐2, ‐3 and ‐4. A transactivation assay in yeast revealed that the C‐terminal CMI‐1 motif was essential for OsERF48 transcriptional activity. When OsERF48 was overexpressed in an either a root‐specific (ROXOsERF48) or whole‐body (OXOsERF48) manner, transgenic plants showed a longer and denser root phenotype compared to the nontransgenic (NT) controls. When plants were grown on a 40% polyethylene glycol‐infused medium under in vitro drought conditions, ROXOsERF48 plants showed a more vigorous root growth than OXOsERF48 and NT plants. In addition, the ROXOsERF48 plants exhibited higher grain yield than OXOsERF48 and NT plants under field‐drought conditions. We constructed a putative OsERF48 regulatory network by cross‐referencing ROXOsERF48 root‐specific RNA‐seq data with a co‐expression network database, from which we inferred the involvement of 20 drought‐related genes in OsERF48‐mediated responses. These included genes annotated as being involved in stress signalling, carbohydrate metabolism, cell‐wall proteins and drought responses. They included, OsCML16, a key gene in calcium signalling during abiotic stress, which was shown to be a direct target of OsERF48 by chromatin immunoprecipitation‐qPCR analysis and a transient protoplast expression assay. Our results demonstrated that OsERF48 regulates OsCML16, a calmodulin‐like protein gene that enhances root growth and drought tolerance.
Unravelling early events in the Taphrina deformans–Prunus persica interaction: an insight into the differential responses in resistant and susceptible genotypes
Authors: Svetaz Laura A. , Bustamante Claudia A. , Goldy Camila , Rivero Nery , Müller Gabriela L. , Valentini Gabriel H. , Fernie Alisdair R. , Drincovich María F. , Lara María V.
Published: February 2017

Leaf peach curl is a devastating disease affecting leaves, flowers and fruits, caused by the dimorphic fungus Taphrina deformans. To gain insight into the mechanisms of fungus pathogenesis and plant responses, leaves of a resistant and two susceptible Prunus persica genotypes were inoculated with blastospores (yeast), and the infection was monitored during 120 h post inoculation (h.p.i.). Fungal dimorphism to the filamentous form and induction of reactive oxygen species (ROS), callose synthesis, cell death and defence compound production were observed independently of the genotype. Fungal load significantly decreased after 120 h.p.i. in the resistant genotype, while the pathogen tended to grow in the susceptible genotypes. Metabolic profiling revealed a biphasic re‐programming of plant tissue in susceptible genotypes, with an initial stage co‐incident with the yeast form of the fungus and a second when the hypha is developed. Transcriptional analysis of PRs and plant hormone‐related genes indicated that pathogenesis‐related (PR) proteins are involved in P. persica defence responses against T. deformans and that salicylic acid is induced in the resistant genotype. Conducted experiments allowed the elucidation of common and differential responses in susceptible versus resistant genotypes and thus allow us to construct a picture of early events during T. deformans infection.
Effects of diabetes mellitus on the clinical presentation and treatment response in tuberculosis
Authors: Leung Chi C. , Yew Wing W. , Mok Thomas Y.W. , Lau Kam S. , Wong Chi F. , Chau Chi H. , Chan Chi K. , Chang Kwok C. , Tam Greta , Tam Cheuk M.
Published: February 2017

Background and objective

With the colliding global epidemics of diabetes mellitus (DM) and tuberculosis (TB), we studied the effects of DM on the presentation of TB and its response to treatment.

Methods

Consecutive TB patients from 2006 to 2010 in a territory‐wide treatment programme offering 9‐month extended treatment for TB patients with DM were examined and followed up prospectively to assess their treatment response. Successful treatment completers were tracked through the TB registry and death registry for relapse, death or till 31 December 2014, whichever was the earliest.

Results

DM was independently associated with more chest symptoms (adjusted OR (AOR): 1.13) and systemic symptoms (AOR: 1.30) but less with other site‐specific symptoms (AOR: 0.58) at TB presentation. There was more frequent pulmonary involvement (AOR: 1.69), with more extensive lung lesion (AOR: 1.25), lung cavity (AOR: 2.00) and positive sputum smear (AOR: 1.83) and culture (AOR: 1.38), but no difference in the proportion of retreatment cases or isoniazid and/or rifampicin resistance. After treatment initiation, there was higher overall incidence (AOR: 1.38) of adverse effects (mainly gastrointestinal symptoms, renal impairment and peripheral neuropathy but less fever and skin hypersensitivity reactions), more smear non‐conversion (AOR: 1.59) and culture non‐conversion (AOR: 1.40) at 2 months, and lower combined cure/treatment completion rate at 12 months (AOR: 0.79), but no difference in the relapse rate after having successfully completed treatment.

Conclusion

DM adversely affected the clinical presentation and treatment response of TB, but there was no difference in the drug resistance and relapse rates.
Fully General Chao and Zelterman Estimators with Application to a Whale Shark Population
Authors: Farcomeni Alessio
Published: February 2017

We introduce generalized Chao and generalized Zelterman estimators which include individual, time varying and behavioural effects. Under mild assumptions in the presence of unobserved heterogeneity, the generalized Chao estimator asymptotically provides a lower bound for the population size and is unbiased otherwise. Corrected versions guarantee bounded estimates. To include the best set of predictors we propose the biased empirical focused information criterion bFIC. Simulations indicate that bFIC might give considerable improvements over other selection criteria in our context. We illustrate with an original application to size estimation of a whale shark (Rhincodon typus) population in South Ari Atoll, in the Maldives.
A mathematical model for estimating residual transmission risk of occult hepatitis B virus infection with different blood safety scenarios
Authors: Weusten Jos , van Drimmelen Harry , Vermeulen Marion , Lelie Nico
Published: February 2017

BACKGROUND

If anti‐hepatitis B core antibody testing is not mandated blood donors with occult hepatitis B infection (OBI) may transmit hepatitis B virus (HBV) to a recipient in spite of the use of nucleic acid amplification technology (NAT) or pathogen inactivation (PI).

STUDY DESIGN AND METHODS

We developed a model to estimate OBI transmission risk based on three components: the probability distribution of the viral load (VL) in a randomly selected OBI donor, the probability that a given VL remains undetected, and the probability that this VL causes infection in the recipient. A subset of 217 South African OBI samples identified by individual donation (ID)‐NAT screening were quantified by replicate testing using an ID‐NAT assay (Ultrio Plus) against HBV DNA standard dilution series. The observed log VLs could be described by a Gumbel distribution. A correction was included to compensate for OBI samples missed by initial ID‐NAT screening.

RESULTS

The model estimates that 3.3% of all OBI donations are undetected by ID‐NAT (Ultrio Plus) and cause infection by a blood component containing 20 mL plasma, going up to 8.7% when using minipools of 6 (MP6)‐NAT. For 200‐mL plasma transfusion these risks were estimated at 14 and 28%, respectively, while PI with modest (2 log) reduction capacity would reach 4.8% without NAT and 1.3 or 0.4% when combined with MP6‐ or ID‐NAT.

CONCLUSION

The model can be used to compare different screening and/or PI strategies in reducing viral transmission risk and could serve as a tool in evaluating efficacy of alternative blood safety scenarios.
Prevalence of herbicide‐resistant weed species in Malaysian rice fields: A review
Authors: Ruzmi Rabiatuladawiyah , Ahmad‐Hamdani Muhammad S. , Bakar Baki B.
Published: February 2017

The management of weeds in Malaysian rice fields is very much herbicide‐based. The heavy reliance on herbicide for weed control by many rice‐growers arguably eventually has led to the development and evolution of herbicide‐resistant biotypes in Malaysian rice fields over the years. The continuous use of synthetic auxin (phenoxy group) herbicides and acetohydroxyacid synthase‐inhibiting herbicides to control rice weeds was consequential in leading to the emergence and prevalence of resistant weed biotypes. This review discusses the history and confirmed cases and incidence of herbicide‐resistant weeds in Malaysian rice fields. It also reviews the Clearfield Production System and its impact on the evolution of herbicide resistance among rice weed species and biotypes. This review also emphasizes the strategies and management options for herbicide‐resistant rice field weeds within the framework of herbicide‐based integrated weed management. These include the use of optimum tillage practices, certified clean seeds, increased crop competition through high seeding rates, crop rotation, the application of multiple modes of action of herbicides in annual rotations, tank mixtures and sequential applications to enable a broad spectrum of weed control, increase the selective control of noxious weed species in a field and help to delay the resistance evolution by reducing the selection pressure that is forced on those weed populations by a specific herbicidal mode of action.
Recovery Efficiency in Hydraulically Fractured Shale Gas Reservoirs
Authors: Seales Maxian B. , Ertekin Turgay , Yilin Wang John
Published: February 2017

At the end of 2015 the U.S. held 5.6% or approximately 369 Tcf of worldwide conventional natural gas proved reserves (British Petroleum Company, 2016, “BP Statistical Review of World Energy June 2016,” British Petroleum Co., London). If unconventional gas sources are considered, natural gas reserves rise steeply to 2276 Tcf. Shale gas alone accounts for approximately 750 Tcf of the technically recoverable gas reserves in the U.S. (U.S. Energy Information Administration, 2011, “Review of Emerging Resources: U.S. Shale Gas and Shale Oil plays,” U.S. Department of Energy, Washington, DC). However, this represents only a very small fraction of the gas associated with shale formations and is indicative of current technological limits. This manuscript addresses the question of recovery efficiency/recovery factor (RF) in fractured gas shales. Predictions of gas RF in fractured shale gas reservoirs are presented as a function of operating conditions, non-Darcy flow, gas slippage, proppant crushing, and proppant diagenesis. Recovery factors are simulated using a fully implicit, three-dimensional, two-phase, dual-porosity finite difference model that was developed specifically for this purpose. The results presented in this article provide clear insight into the range of recovery factors one can expect from a fractured shale gas formation, the impact that operation procedures and other phenomena have on these recovery factors, and the efficiency or inefficiency of contemporary shale gas production technology.
A phantom study investigating the relationship between ground‐glass opacity visibility and physical detectability index in low‐dose chest computed tomography
Authors: Ichikawa Katsuhiro , Kobayashi Takeshi , Sagawa Motoyasu , Katagiri Ayako , Uno Yukiko , Nishioka Ryo , Matsuyama Jun
Published: February 2017

In this study, the relationship between ground‐glass opacity (GGO) visibility and physical detectability index in low‐dose computed tomography (LDCT) for lung cancer screening was investigated. An anthropomorphic chest phantom that included synthetic GGOs with CT numbers of Hounsfield units (HU; high attenuation GGO: HGGO) and HU (low attenuation GGO: LGGO), and three phantoms for physical measurements were employed. The phantoms were scanned using 12 CT systems located in 11 screening centers in Japan. The slice thicknesses and CT dose indices () varied over 1.0–5.0 mm and 0.85–3.30 mGy, respectively, and several reconstruction kernels were used. Physical detectability index values were calculated from measurements of resolution, noise, and slice thickness properties for all image sets. Five radiologists and one thoracic surgeon, blind to one another's observations, evaluated GGO visibility using a five‐point scoring system. The physical detectability index correlated reasonably well with the GGO visibility ( for 6 mm HGGO and for 10 mm LGGO), and was nearly proportional to the CTDIvol. Consequently, the also correlated reasonably well with the GGO visibility ( for 6 mm HGGO and for 10 mm LGGO). As a result, the was nearly dominant in the GGO visibility for image sets with different reconstruction kernels and slice thicknesses, used in this study.

PACS numbers: 81.70.Tx, 87.57.Q‐
Determining the optimal dosimetric leaf gap setting for rounded leaf‐end multileaf collimator systems by simple test fields
Authors: Yao Weiguang , Farr Jonathan B.
Published: February 2017

Individual QA for IMRT/VMAT plans is required by protocols. Sometimes plans cannot pass the institute's QA criteria. For the Eclipse treatment planning system (TPS) with rounded leaf‐end multileaf collimator (MLC), one practical way to improve the agreement of planned and delivered doses is to tune the value of dosimetric leaf gap (DLG) in the TPS from the measured DLG. We propose that this step may be necessary due to the complexity of the MLC system, including dosimetry of small fields and the tongue‐and‐groove (T&G) effects, and report our use of test fields to obtain linac‐specific optimal DLGs in TPSs. More than 20 original patient plans were reoptimized with the linac‐specific optimal DLG value. We examined the distribution of gaps and T&G extensions in typical patient plans and the effect of using the optimal DLG on the distribution. The QA pass rate of patient plans using the optimal DLG was investigated. The dose‐volume histograms (DVHs) of targets and organs at risk were checked. We tested three MLC systems (Varian millennium 120 MLC, high‐definition 120 MLC, and Siemens 160 MLC) installed in four Varian linear accelerators (linacs) (TrueBEAM STx, Trilogy, Clinac 2300 iX, and Clinac 21 EX) and 1 Siemens linac (Artiste). With an optimal DLG, the individual QA for all those patient plans passed the institute's criteria (95% in DTA test or gamma test with ), even though most of these plans had failed to pass QA when using original DLGs optimized from typical patient plans or from the optimization process (automodeler) of Pinnacle TPS. Using either our optimal DLG or one optimized from typical patient plans or from the Pinnacle optimization process yielded similar DVHs.

PACS number: 87.55Qr
Dosimetric effect due to the motion during deep inspiration breath hold for left‐sided breast cancer radiotherapy
Authors: Tang Xiaoli , Cullip Tim , Dooley John , Zagar Timothy , Jones Ellen , Chang Sha , Zhu Xiaofeng , Lian Jun , Marks Lawrence
Published: February 2017

Deep inspiration breath‐hold (DIBH) radiotherapy for left‐sided breast cancer can reduce cardiac exposure and internal motion. We modified our in‐house treatment planning system (TPS) to retrospectively analyze breath‐hold motion log files to calculate the dosimetric effect of the motion during breath hold. Thirty left‐sided supine DIBH breast patients treated using AlignRT were studied. Breath‐hold motion was recorded — three translational and three rotational displacements of the treatment surface — the Real Time Deltas (RTD). The corresponding delivered dose was estimated using the beam‐on portions of the RTDs. Each motion was used to calculate dose, and the final estimated dose was the equally weighted average of the multiple resultant doses. Ten of thirty patients had internal mammary nodes (IMN) purposefully included in the tangential fields, and we evaluated the percentage of IMN covered by 40 Gy. The planned and delivered heart mean dose, lungs V20 (volume of the lungs receiving ), percentage of IMN covered by 40 Gy, and IMN mean dose were compared. The averaged mean and standard deviation of the beam‐on portions of the absolute RTDs were , , , , and , for vertical, longitudinal, lateral, yaw, roll, and pitch, respectively. The averaged planned and delivered mean heart dose were 99 and 101 cGy. Lungs V20 were 6.59% and 6.74%. IMN 40 Gy coverage was 83% and 77%, and mean IMN dose was 4642 and 4518 cGy. The averaged mean motion during DIBH was smaller than 1 mm and 1°, which reflects the relative reproducibility of the patient breath hold. On average, the mean heart dose and lungs V20 were reasonably close to what have been planned. IMN 40 Gy coverage might be modestly reduced for certain cases.

PACS number: 87.55.km, 87.55.N
Implementation of an efficient Monte Carlo calculation for CBCT scatter correction: phantom study
Authors: Watson Peter G.F. , Mainegra‐Hing Ernesto , Tomic Nada , Seuntjens Jan
Published: February 2017

Cone‐beam computed tomography (CBCT) images suffer from poor image quality, in a large part due to contamination from scattered X‐rays. In this work, a Monte Carlo (MC)‐based iterative scatter correction algorithm was implemented on measured phantom data acquired from a clinical on‐board CBCT scanner. An efficient EGSnrc user code (egs_cbct) was used to transport photons through an uncorrected CBCT scan of a Catphan 600 phantom. From the simulation output, the contribution from primary and scattered photons was estimated in each projection image. From these estimates, an iterative scatter correction was performed on the raw CBCT projection data. The results of the scatter correction were compared with the default vendor reconstruction. The scatter correction was found to reduce the error in CT number for selected regions of interest, while improving contrast‐to‐noise ratio (CNR) by 18%. These results demonstrate the performance of the proposed scatter correction algorithm in improving image quality for clinical CBCT images.

PACS numbers: 87.10.Rt, 87.57.Q‐
Is 5 mm MMLC suitable for VMAT‐based lung SBRT? A dosimetric comparison with 2.5 mm HDMLC using RTOG‐0813 treatment planning criteria for both conventional and high‐dose flattening filter‐free photon beams
Authors: Subramanian Shanmuga V. , Subramani Vellaiyan , Swamy Shanmugam Thirumalai , Gandhi Arun , Chilukuri Srinivas , Kathirvel Murugesan
Published: February 2017

The aim of this study is to assess the suitability of 5 mm millennium multileaf collimator (MMLC) for volumetric‐modulated arc therapy (VMAT)‐based lung stereotactic body radiotherapy (SBRT). Thirty lung SBRT patient treatment plans along with their planning target volumes (ranging from 2.01 cc to 150.11 cc) were transferred to an inhomogeneous lung phantom and retrospectively planned using VMAT technique, along with the high definition multileaf collimator (HDMLC) and MMLC systems. The plans were evaluated using Radiation Therapy Oncology Group (RTOG‐0813) treatment planning criteria for target coverage, normal tissue sparing, and treatment efficiency for both the MMLC and HDMLC systems using flat and flattening filter‐free (FFF) photon beams. Irrespective of the target volumes, both the MLC systems were able to satisfy the RTOG‐0813 treatment planning criteria without having any major deviation. Dose conformity was marginally better with HDMLC. The average conformity index (CI) value was found to be and for HDMLC and MMLC plans, respectively. For the 6 MV FFF beams, the plan was slightly more conformal, with the average CI values of and for the HDMLC and MMLC plans, respectively. The high dose spillage was the maximum for 2 cc volume set (3% for HDMLC and 3.1% for MMLC). In the case of low dose spillage, both the MLCs were within the protocol of no deviation, except for the 2 cc volume set. The results from this study revealed that VMAT‐based lung SBRT using 5 mm MMLC satisfies the RTOG‐0813 treatment planning criteria for the studied target size and shapes.

PACS numbers: 87.53.Ly, 87.53D, 87.56.jk
Clinical implementation and error sensitivity of a 3D quality assurance protocol for prostate and thoracic IMRT
Authors: Gueorguiev Gueorgui , Cotter Christopher , Turcotte Julie Catherine , Crawford Bruce , Sharp Gregory , Mah'D Mufeed
Published: February 2017

This work aims at three goals: first, to define a set of statistical parameters and plan structures for a 3D pretreatment thoracic and prostate intensity‐modulated radiation therapy (IMRT) quality assurance (QA) protocol; secondly, to test if the 3D QA protocol is able to detect certain clinical errors; and third, to compare the 3D QA method with QA performed with single ion chamber and 2D gamma test in detecting those errors. The 3D QA protocol measurements were performed on 13 prostate and 25 thoracic IMRT patients using IBA's COMPASS system. For each treatment planning structure included in the protocol, the following statistical parameters were evaluated: average absolute dose difference (AADD), percent structure volume with absolute dose difference greater than 6% (ADD6), and 3D gamma test. To test the 3D QA protocol error sensitivity, two prostate and two thoracic step‐and‐shoot IMRT patients were investigated. Errors introduced to each of the treatment plans included energy switched from 6 MV to 10 MV, multileaf collimator (MLC) leaf errors, linac jaws errors, monitor unit (MU) errors, MLC and gantry angle errors, and detector shift errors. QA was performed on each plan using a single ion chamber and 2D array of ion chambers for 2D and 3D QA. Based on the measurements performed, we established a uniform set of tolerance levels to determine if QA passes for each IMRT treatment plan structure: maximum allowed AADD is 6%; maximum 4% of any structure volume can be with ADD6 greater than 6%, and maximum 4% of any structure volume may fail 3D gamma test with test parameters DTA. Out of the three QA methods tested the single ion chamber performed the worst by detecting 4 out of 18 introduced errors, 2D QA detected 11 out of 18 errors, and 3D QA detected 14 out of 18 errors.

PACS number: 87.56.Fc
A new transmission methodology for quality assurance in radiotherapy based on radiochromic film measurements
Authors: do Amaral Leonardo L. , de Oliveira Harley F. , Pavoni Juliana F. , Sampaio Francisco , Netto Thomaz Ghilardi
Published: February 2017

Despite individual quality assurance (QA) being recommended for complex techniques in radiotherapy (RT) treatment, the possibility of errors in dose delivery during therapeutic application has been verified. Therefore, it is fundamentally important to conduct in vivo QA during treatment. This work presents an in vivo transmission quality control methodology, using radiochromic film (RCF) coupled to the linear accelerator (linac) accessory holder. This QA methodology compares the dose distribution measured by the film in the linac accessory holder with the dose distribution expected by the treatment planning software. The calculated dose distribution is obtained in the coronal and central plane of a phantom with the same dimensions of the acrylic support used for positioning the film but in a source‐to‐detector distance (SDD) of 100 cm, as a result of transferring the IMRT plan in question with all the fields positioned with the gantry vertically, that is, perpendicular to the phantom. To validate this procedure, first of all a Monte Carlo simulation using PENELOPE code was done to evaluate the differences between the dose distributions measured by the film in a SDD of 56.8 cm and 100 cm. After that, several simple dose distribution tests were evaluated using the proposed methodology, and finally a study using IMRT treatments was done. In the Monte Carlo simulation, the mean percentage of points approved in the gamma function comparing the dose distribution acquired in the two SDDs were . In the simple dose distribution tests, the mean percentage of points approved in the gamma function were and the mean percentage differences in the normalization point doses were . The transmission methodology was approved in 24 of 25 IMRT test irradiations. Based on these results, it can be concluded that the proposed methodology using RCFs can be applied for in vivo QA in RT treatments.

PACS number: 87.55.Qr, 87.55.km, 87.55.N‐
Investigating the clinical advantages of a robotic linac equipped with a multileaf collimator in the treatment of brain and prostate cancer patients
Authors: McGuinness Christopher M. , Gottschalk Alexander R. , Lessard Etienne , Nakamura Jean L. , Pinnaduwage Dilini , Pouliot Jean , Sims Colin , Descovich Martina
Published: February 2017

The purpose of this study was to evaluate the performance of a commercially available CyberKnife system with a multileaf collimator (CK‐MLC) for stereotactic body radiotherapy (SBRT) and standard fractionated intensity‐modulated radiotherapy (IMRT) applications. Ten prostate and ten intracranial cases were planned for the CK‐MLC. Half of these cases were compared with clinically approved SBRT plans generated for the CyberKnife with circular collimators, and the other half were compared with clinically approved standard fractionated IMRT plans generated for conventional linacs. The plans were compared on target coverage, conformity, homogeneity, dose to organs at risk (OAR), low dose to the surrounding tissue, total monitor units (MU), and treatment time. CK‐MLC plans generated for the SBRT cases achieved more homogeneous dose to the target than the CK plans with the circular collimators, for equivalent coverage, conformity, and dose to OARs. Total monitor units were reduced by 40% to 70% and treatment time was reduced by half. The CK‐MLC plans generated for the standard fractionated cases achieved prescription isodose lines between 86% and 93%, which was 2%–3% below the plans generated for conventional linacs. Compared to standard IMRT plans, the total MU were up to three times greater for the prostate (whole pelvis) plans and up to 1.4 times greater for the intracranial plans. Average treatment time was 25 min for the whole pelvis plans and 19 min for the intracranial cases. The CK‐MLC system provides significant improvements in treatment time and target homogeneity compared to the CK system with circular collimators, while maintaining high conformity and dose sparing to critical organs. Standard fractionated plans for large target volumes were generated that achieved high prescription isodose levels. The CK‐MLC system provides more efficient SRS and SBRT treatments and, in select clinical cases, might be a potential alternative for standard fractionated treatments.

PACS numbers: 87.56.nk, 87.56.bd
Optimizing the MLC model parameters for IMRT in the RayStation treatment planning system
Authors: Chen Shifeng , Yi Byong Yong , Yang Xiaocheng , Xu Huijun , Prado Karl L. , D'Souza Warren D.
Published: February 2017

Unlike other commercial treatment planning systems (TPS) which model the rounded leaf end differently (such as the MLC dosimetric leaf gap (DLG) or rounded leaf‐tip radius), the RayStation TPS (RaySearch Laboratories, Stockholm, Sweden) models transmission through the rounded leaf end of the MLC with a step function, in which the radiation transmission through the leaf end is the square root of the average MLC transmission factor. We report on the optimization of MLC model parameters for the RayStation planning system. This (TPS) models the rounded leaf end of the MLC with the following parameters: leaf‐tip offset, leaf‐tip width, average transmission factor, and tongue and groove. We optimized the MLC model parameters for IMRT in the RayStation v. 4.0 planning system and for a Varian C‐series linac with a 120‐leaf Millennium MLC, and validated the model using measured data. The leaf‐tip offset is the geometric offset due to the rounded leaf‐end design and resulting divergence of the light/radiation field. The offset value is a function of the leaf‐tip position, and tabulated data are available from the vendor. The leaf‐tip width was iteratively evaluated by comparing computed and measured transverse dose profiles of MLC defined fields at in water. In‐water profile comparisons were also used to verify the MLC leaf position (leaf‐tip offset). The average transmission factor and leaf tongue‐and‐groove width were derived iteratively by maximizing the agreement between measurements and RayStation TPS calculations for five clinical IMRT QA plans. Plan verifications were performed by comparing MapCHECK2 measurements and Monte Carlo calculations. The MLC model was validated using five test IMRT cases from the AAPM Task Group 119 report. Absolute gamma analyses ( and ) were applied. In addition, computed output factors for MLC‐defined small fields () of both 6 MV and 18 MV photons were compared to those independently measured by the Imaging and Radiation Oncology Core (IROC), Houston, TX. 6 MV and 18 MV models were both determined to have the same MLC parameters: leaf‐tip transmission, and leaf tongue‐and‐groove . IMRT QA analysis for five test cases in TG‐119 resulted in a 100% passing rate with gamma analysis for 6 MV, and for 18 MV. The passing rate was for 6 MV and for 18 MV when the gamma analysis criteria was applied. These results compared favorably with those published in AAPM Task Group 119. The reported MLC model parameters serve as a reference for other users.

PACS number(s): 87.55.D, 87.56.nk
Surface dose measurements with commonly used detectors: a consistent thickness correction method
Authors: Reynolds Tatsiana A. , Higgins Patrick
Published: February 2017

The purpose of this study was to review application of a consistent correction method for the solid state detectors, such as thermoluminescent dosimeters (chips (cTLD) and powder (pTLD)), optically stimulated detectors (both closed (OSL) and open (eOSL)), and radiochromic (EBT2) and radiographic (EDR2) films. In addition, to compare measured surface dose using an extrapolation ionization chamber (PTW 30‐360) with other parallel plate chambers RMI‐449 (Attix), Capintec PS‐033, PTW 30‐329 (Markus) and Memorial. Measurements of surface dose for 6 MV photons with parallel plate chambers were used to establish a baseline. cTLD, OSLs, EDR2, and EBT2 measurements were corrected using a method which involved irradiation of three dosimeter stacks, followed by linear extrapolation of individual dosimeter measurements to zero thickness. We determined the magnitude of correction for each detector and compared our results against an alternative correction method based on effective thickness. All uncorrected surface dose measurements exhibited overresponse, compared with the extrapolation chamber data, except for the Attix chamber. The closest match was obtained with the Attix chamber (), followed by pTLD (0.5%), Capintec (4.5%), Memorial (7.3%), Markus (10%), cTLD (11.8%), eOSL (12.8%), EBT2 (14%), EDR2 (14.8%), and OSL (26%). Application of published ionization chamber corrections brought all the parallel plate results to within 1% of the extrapolation chamber. The extrapolation method corrected all solid‐state detector results to within 2% of baseline, except the OSLs. Extrapolation of dose using a simple three‐detector stack has been demonstrated to provide thickness corrections for cTLD, eOSLs, EBT2, and EDR2 which can then be used for surface dose measurements. Standard OSLs are not recommended for surface dose measurement. The effective thickness method suffers from the subjectivity inherent in the inclusion of measured percentage depth‐dose curves and is not recommended for these types of measurements.

PACS number: 87.56.‐v
Monte Carlo calculation based on hydrogen composition of the tissue for MV photon radiotherapy
Authors: Demol Benjamin , Viard Romain , Reynaert Nick
Published: February 2017

The purpose of this study was to demonstrate that Monte Carlo treatment planning systems require tissue characterization (density and composition) as a function of CT number. A discrete set of tissue classes with a specific composition is introduced. In the current work we demonstrate that, for megavoltage photon radiotherapy, only the hydrogen content of the different tissues is of interest. This conclusion might have an impact on MRI‐based dose calculations and on MVCT calibration using tissue substitutes. A stoichiometric calibration was performed, grouping tissues with similar atomic composition into 15 dosimetrically equivalent subsets. To demonstrate the importance of hydrogen, a new scheme was derived, with correct hydrogen content, complemented by oxygen (all elements differing from hydrogen are replaced by oxygen). Mass attenuation coefficients and mass stopping powers for this scheme were calculated and compared to the original scheme. Twenty‐five CyberKnife treatment plans were recalculated by an in‐house developed Monte Carlo system using tissue density and hydrogen content derived from the CT images. The results were compared to Monte Carlo simulations using the original stoichiometric calibration. Between 300 keV and 3 MeV, the relative difference of mass attenuation coefficients is under 1% within all subsets. Between 10 keV and 20 MeV, the relative difference of mass stopping powers goes up to 5% in hard bone and remains below 2% for all other tissue subsets. Dose‐volume histograms (DVHs) of the treatment plans present no visual difference between the two schemes. Relative differences of dose indexes , and were analyzed and a distribution centered around zero and of standard deviation below 2% () was established. On the other hand, once the hydrogen content is slightly modified, important dose differences are obtained. Monte Carlo dose planning in the field of megavoltage photon radiotherapy is fully achievable using only hydrogen content of tissues, a conclusion that might impact MRI dose calculation, but can also help selecting the optimal tissue substitutes when calibrating MVCT devices.

PACS numbers: 87.55.D‐, 87.55.dk, 87.55.K‐, 87.57.Q‐
High‐density dental implants and radiotherapy planning: evaluation of effects on dose distribution using pencil beam convolution algorithm and Monte Carlo method
Authors: Çatli Serap
Published: February 2017

High atomic number and density of dental implants leads to major problems at providing an accurate dose distribution in radiotherapy and contouring tumors and organs caused by the artifact in head and neck tumors. The limits and deficiencies of the algorithms using in the treatment planning systems can lead to large errors in dose calculation, and this may adversely affect the patient's treatment. In the present study, four commercial dental implants were used: pure titanium, titanium alloy (Ti‐6Al‐4V), amalgam, and crown. The effects of dental implants on dose distribution are determined with two methods: pencil beam convolution (PBC) algorithm and Monte Carlo code for 6 MV photon beam. The central axis depth doses were calculated on the phantom for a source–skin distance (SSD) of 100 cm and a field using both of algorithms. The results of Monte Carlo method and Eclipse TPS were compared to each other and to those previously reported. In the present study, dose increases in tissue at a distance of 2 mm in front of the dental implants were seen due to the backscatter of electrons for dental implants at 6 MV using the Monte Carlo method. The Eclipse treatment planning system (TPS) couldn't precisely account for the backscatter radiation caused by the dental prostheses. TPS underestimated the back scatter dose and overestimated the dose after the dental implants. The large errors found for TPS in this study are due to the limits and deficiencies of the algorithms. The accuracy of the PBC algorithm of Eclipse TPS was evaluated in comparison to Monte Carlo calculations in consideration of the recommendations of the American Association of Physicists in Medicine Radiation Therapy Committee Task Group 65. From the comparisons of the TPS and Monte Carlo calculations, it is verified that the Monte Carlo simulation is a good approach to derive the dose distribution in heterogeneous media.

PACS numbers: 87.55.K‐
Using CBCT for pretreatment range check in proton therapy: a phantom study for prostate treatment by anterior–posterior beam
Authors: Bentefour El Hassane , Both Stefan , Tang Shikui , Lu Hsiao‐Ming
Published: February 2017

This study explores the potential of cone‐beam computed tomography (CBCT) for monitoring relative beam range variations due to daily changes in patient anatomy for prostate treatment by anterior proton beams. CBCT was used to image an anthropomorphic pelvic phantom, in eight sessions on eight different days. In each session, the phantom was scanned twice, first at a standard position as determined by the room lasers, and then after it was shifted by 10 mm translation randomly along one of the X, Y, or Z directions. The filling of the phantom bladder with water was not refreshed from day to day, inducing gradual change of the water‐equivalent path length (WEPL) across the bladder. MIMvista (MIM) software was used to perform image registration and re‐alignment of all the scans with the scan from the first session. The XiO treatment planning system was used to perform data analysis. It was found that, although the Hounsfield unit numbers in CBCT have substantially larger fluctuations than those in diagnostic CT, CBCT datasets taken for daily patient positioning could potentially be used to monitor changes in patient anatomy. The reproducibility of the WEPL, computed using CBCT along anterior–posterior (AP) paths across and around the phantom prostate, over a volume of 360 cc, is sufficient for detecting daily WEPL variations that are equal to or larger than 3 mm. This result also applies to CBCT scans of the phantom after it is randomly shifted from the treatment position by 10 mm. limiting the interest to WEPL variation over a specific path within the same CBCT slice, one can detect WEPL variation smaller than 1 mm. That is the case when using CBCT for tracking daily change of the WEPL across the phantom bladder that was induced by spontaneous change in the bladder filling due to evaporation. In summary, the phantom study suggests that CBCT can be used for monitoring day to day WEPL variations in a patient. The method can detect WEPL variation equal to or greater than 3 mm. The study calls for further investigation using the CBCT data from real patients. If confirmed with real patients' data, CBCT could become, in addition to patient setup, a standard tool for proton therapy pretreatment beam range check.

PACS number: 87.55.Tm
A measurement‐based X‐ray source model characterization for CT dosimetry computations
Authors: Sommerville Mitchell , Poirier Yannick , Tambasco Mauro
Published: February 2017

The purpose of this study was to show that the nominal peak tube voltage potential (kVp) and measured half‐value layer (HVL) can be used to generate energy spectra and fluence profiles for characterizing a computed tomography (CT) X‐ray source, and to validate the source model and an in‐house kV X‐ray dose computation algorithm (kVDoseCalc) for computing machine‐ and patient‐specific CT dose. Spatial variation of the X‐ray source spectra of a Philips Brilliance and a GE Optima Big Bore CT scanner were found by measuring the HVL along the direction of the internal bow‐tie filter axes. Third‐party software, Spektr, and the nominal kVp settings were used to generate the energy spectra. Beam fluence was calculated by dividing the integral product of the spectra and the in‐air NIST mass‐energy attenuation coefficients by in‐air dose measurements along the filter axis. The authors found the optimal number of photons to seed in kVDoseCalc to achieve dose convergence. The Philips Brilliance beams were modeled for 90, 120, and 140 kVp tube settings. The GE Optima beams were modeled for 80, 100, 120, and 140 kVp tube settings. Relative doses measured using a Capintec Farmer‐type ionization chamber (0.65 cc) placed in a cylindrical polymethyl methacrylate (PMMA) phantom and irradiated by the Philips Brilliance, were compared to those computed with kVDoseCalc. Relative doses in an anthropomorphic thorax phantom (E2E SBRT Phantom) irradiated by the GE Optima were measured using a (0.015 cc) PTW Freiburg ionization chamber and compared to computations from kVDoseCalc. The number of photons required to reduce the average statistical uncertainty in dose to was . The average percent difference between calculation and measurement over all 12 PMMA phantom positions was found to be 1.44%, 1.47%, and 1.41% for 90, 120, and 140 kVp, respectively. The maximum percent difference between calculation and measurement for all energies, measurement positions, and phantoms was less than 3.50%. Thirty‐five out of a total of 36 simulation conditions were within the experimental uncertainties associated with measurement reproducibility and chamber volume effects for the PMMA phantom. The agreement between calculation and measurement was within experimental uncertainty for 19 out of 20 simulation conditions at five points of interest in the anthropomorphic thorax phantom for the four beam energies modeled. The source model and characterization technique based on HVL measurements and nominal kVp can be used to accurately compute CT dose. This accuracy provides experimental validation of kVDoseCalc for computing CT dose.

PACS numbers: 87.57.Q‐, 87.57.uq, 87.10.Rt