bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermal structure and tectonic evolution of the Scandian orogenic wedge, Scottish Caledonides: integrating geothermometry, deformation temperatures and conceptual kinematic‐thermal models
Authors: Thigpen J.R. , Law R.D. , Loehn C.L. , Strachan R. A. , Tracy R.J. , Lloyd G.E. , Roth B.L. , Brown S.J.
Published: July 2013

In the Caledonides of northwest Scotland, two independent geothermometers (Fe‐Mg exchange and quartz c‐axis fabric opening angle) are used to characterize the thermal structure of the lower part of the Scandian (435–420 Ma) orogenic wedge within the Moine, Ben Hope and Naver‐Sgurr Beag thrust sheets. Traced from west (foreland) to east (hinterland), Fe‐Mg exchange thermometry yields peak or near‐peak temperatures ranging from 484 ± 50 °C to 524 ± 50 °C in the immediate hangingwall of the Moine thrust to 601 ± 50 °C in the immediate hangingwall of the Ben Hope thrust, to 630 ± 50 °C in the Naver thrust sheet. Preserved metamorphic facies and textural relationships are consistent with thermometric estimates. Deformation temperatures calculated from quartz c‐axis fabric opening angles across two similar orogen‐perpendicular transects also yield systematic increases (Glen Golly – Ben Klibreck, 520–630 °C; Ullapool‐Contin, 465–632 °C) traced towards the Naver and Sgurr Beag thrusts. In addition, deformation temperatures show a pronounced increase along the leading edge of the Moine thrust sheet moving south towards the Assynt window, which is interpreted to reflect deeper exhumation of the thrust plane above the Assynt footwall imbricate stack. Because temperatures calculated from metamorphic assemblages are within error of the quartz fabric‐derived deformation temperatures that are of demonstrably Scandian age, the metamorphic sequence between the Moine and Naver‐Sgurr Beag thrusts is interpreted to have developed during the Scandian orogeny. Integration of our results with previous 2D thermal‐mechanical studies allows development of new conceptual thermal‐kinematic models of Scandian orogenesis that may be broadly applicable to other collisional systems. Furthermore, it highlights the critical nature of coupling between orogen kinematic and thermal evolution.
Efficacy of Three Strategies Based on Insecticide, Oil and Elicitor Treatments in Controlling Aphid Populations and Potato virus Y Epidemics in Potato Fields
Authors: Dupuis Brice , Schwaerzel Ruedi , Derron Jacques
Published: July 2013

Potato virus Y (PVY), the potato virus with the highest economic impact in Europe, is transmitted by aphids in a non‐persistent manner. A two‐year field experiment was conducted in Switzerland to evaluate the efficacy of three strategies for controlling aphid populations and the spread of PVY, consisting of treatment with one insecticide (Karate Zeon®), one elicitor (Bion®) and one oil (Telmion®), respectively. The elicitor strategy proved to be ineffective for controlling aphid populations and inadequate for controlling PVY spread. The insecticide strategy gave incomplete protection from aphid infestations, owing to the selection of aphid‐resistant clones. The insecticide gave too little protection against PVY spread for it to be considered a suitable candidate for the purpose. The oil strategy had no effect on aphid populations, but was the best option to reduce PVY spread.
Blockade of the human ether-a-go-go-related gene potassium channel by ketamine
Authors: Zhang Peihua , Xing Junlian , Luo Antao , Feng Juan , Liu Zhipei , Gao Chenghao , Ma Jihua
Published: July 2013

Objectives

The inhibition of the cardiac rapid delayed rectifier potassium current (IKr) and its cloned equivalent human ether-a-go-go-related gene (hERG) channel illustrate QT interval prolonging effects of a wide range of clinically used drugs. In this study, the direct interaction of the intravenous anaesthetic ketamine with wild-type (WT) and mutation hERG currents (IhERG) was investigated.

Methods

The hERG channel (WT, Y652A and F656A) was expressed in Xenopus oocytes and studied using standard two-microelectrode voltage-clamp techniques.

Key findings

WT hERG is blocked in a concentration-dependent manner with IC50 = 12.05 ± 1.38 μm by ketamine, and the steady-state inactivation curves are shifted to more negative potentials (about −27 mV). The mutation to Ala of Y652 and F656 located on the S6 domain attenuate IhERG blockade by ketamine, and produced approximately 9-fold and 2.5-fold increases in IC50 compared with that of WT hERG channel, respectively.

Conclusions

Ketamine blocks WT IhERG expressed in Xenopus oocytes in a concentration-dependent manner and predominantly interacts with the open hERG channels. The interaction of ketamine with hERG channel may involve the aromatic residues Tyr652 and Phe656.
Finding chemo: the search for marine-based pharmaceutical drugs active against cancer
Authors: Indumathy Sivanjah , Dass Crispin R
Published: July 2013

Objectives

Cancer affects the health of many people globally. The most common treatment that is used for cancer is chemotherapy, which has shown promising results but not without side effects. Some of these side effects jeopardise further treatment, and this eventually leads to advanced stages of malignancy and mortality. As a result, there is a need for better and safer anticancer compounds such as those found naturally. One of the most abundant natural environments to find such compounds is the sea, and this vast resource has been biomined since the 1950s.

Key findings

There are currently three marine anticancer agents marketed (Yondelis, Cytosar-U and Halaven), with several others undergoing clinical trials. This review discusses marine-derived products in clinical use and in clinical trials, and discusses available literature on the growth suppression or pro-apoptotic properties of these compounds, and the molecular mechanisms underpinning these cell biological phenomena.

The marine environment may hold promising anticancer compounds within its depths, warranting further research to be performed in this area, albeit with respect for the natural ecosystems that are being explored for drug discover and subsequently used for drug development.
A comparative study of the effect of spray drying and hot-melt extrusion on the properties of amorphous solid dispersions containing felodipine
Authors: Mahmah Osama , Tabbakh Rami , Kelly Adrian , Paradkar Anant
Published: July 2013

Objectives

To compare the properties of solid dispersions of felodipine for oral bioavailability enhancement using two different polymers, polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose acetate succinate (HPMCAS), by hot-melt extrusion (HME) and spray drying.

Methods

Felodipine solid dispersions were prepared by HME and spray drying techniques. PVP and HPMCAS were used as polymer matrices at different drug : polymer ratios (1 : 1, 1 : 2 and 1 : 3). Detailed characterization was performed using differential scanning calorimetry, powder X-ray diffractometry, scanning electron microscopy and in-vitro dissolution testing. Dissolution profiles were evaluated in the presence of sodium dodecyl sulphate. Stability of different solid dispersions was studied under accelerated conditions (40°C/75% RH) over 8 weeks.

Key findings

Spray-dried formulations were found to release felodipine faster than melt extruded formulations for both polymer matrices. Solid dispersions containing HMPCAS exhibited higher drug release rates and better wettability than those produced with a PVP matrix. No significant differences in stability were observed except with HPMCAS at a 1 : 1 ratio, where crystallization was detected in spray-dried formulations.

Conclusions

Solid dispersions of felodipine produced by spray drying exhibited more rapid drug release than corresponding melt extruded formulations, although in some cases improved stability was observed for melt extruded formulations.
Cellular distribution studies of the nitric oxide-generating antineoplastic prodrug O2-(2,4-dinitrophenyl)1-((4-ethoxycarbonyl)piperazin-1-yl)diazen-1-ium-1,2-diolate formulated in Pluronic P123 micelles
Authors: Kaur Imit , Terrazas Moises , Kosak Ken M , Kern Steven E , Boucher Kenneth M , Shami Paul J
Published: July 2013

Objective

Nitric oxide (NO) possesses antitumour activity. It induces differentiation and apoptosis in acute myeloid leukaemia (AML) cells. The NO prodrug O2-(2,4-dinitrophenyl)1-((4-ethoxycarbonyl)piperazin-1-yl)diazen-1-ium-1,2-diolate, or JS-K, has potent antileukaemic activity. JS-K is also active in vitro and in vivo against multiple myeloma, prostate cancer, non-small-cell lung cancer, glioma and liver cancer. Using the Pluronic P123 polymer, we have developed a micelle formulation for JS-K to increase its solubility and stability. The goal of the current study was to investigate the cellular distribution of JS-K in AML cells.

Methods

We investigated the intracellular distribution of JS-K (free drug) and JS-K formulated in P123 micelles (P123/JS-K) using HL-60 AML cells. We also studied the S-glutathionylating effects of JS-K on proteins in the cytoplasmic and nuclear cellular fractions.

Key findings

Both free JS-K and P123/JS-K accumulate primarily in the nucleus. Both free JS-K and P123/JS-K induced S-glutathionylation of nuclear proteins, although the effect produced was more pronounced with P123/JS-K. Minimal S-glutathionylation of cytoplasmic proteins was observed.

Conclusions

We conclude that a micelle formulation of JS-K increases its accumulation in the nucleus. Post-translational protein modification through S-glutathionylation may contribute to JS-K's antileukaemic properties.
Gualou Xiebai Decoction prevents myocardial fibrosis by blocking TGF-beta/Smad signalling
Authors: Ding Yong-fang , Peng Yun-ru , Li Juan , Shen Hong , Shen Ming-qin , Fang Tai-hui
Published: July 2013

Objectives

The present study is aimed to investigate the effect of Gualou Xiebai Decoction (GXD) ethanol extract on myocardial fibrosis and clarify the possible mechanism.

Methods

Rats with ligated left anterior descending coronary artery were treated with GXD ethanol extract (1.14 g/kg, 2.27 g/kg, 4.53 g/kg) daily via gavage for 4 weeks. Histopathological changes and collagen distribution were evaluated by haematoxylin and eosin and Masson staining. The mRNA levels of Collagen I and Collagen III were detected by real-time PCR. The expressions of TGF-β1, TGFβ receptor (TGFβR)I, TGFβRII, P-Smad2/3 and Smad7 were determined by Western blot.

Results

GXD treatment was significantly reduced the heart weight/body weight ratio (P < 0.05) as well as the left ventricle weight/body weight ratio (P < 0.05). It also significantly alleviated the degree of inflammation, decreased myocardial collagen volume fraction (P < 0.05 ∼ 0.01), together with markedly prevented the upregulations of Collagen I and Collagen III (P < 0.05 ∼ 0.01). Moreover, GXD downregulated expressions of TGF-β1, TGFβRI, TGFβRII, Smad2/3 whereas improved Smad7 expression in the myocardial fibrosis rats.

Conclusions

GXD ameliorates myocardial fibrosis induced by cardiac infarction with ligated left anterior descending coronary artery, the mechanism maybe involve in inhibiting the TGF-β1 signalling pathway.
Assessment of the regenerative potential of allogeneic periodontal ligament stem cells in a rodent periodontal defect model
Authors: Han J. , Menicanin D. , Marino V. , Ge S. , Mrozik K. , Gronthos S. , Bartold P. M.
Published: July 2013

Background and Objective

The complex microenvironment of the periodontal wound creates many challenges associated with multitissue regeneration of periodontal lesions. Recent characterization of mesenchymal stem cell‐like populations residing in periodontal ligament tissues has shown that these cells exhibit features of postnatal stem cells. Despite these advances, a lack of consistency in design of preclinical studies and a limited study of allogeneic transplantation applications has restricted our understanding of their clinical utility in the treatment of periodontal disease. The aim of this study was to assess the regenerative potential of allogeneic periodontal ligament stem cells (PDLSCs) in a rat periodontal fenestration defect mode and to identify an optimal end time‐point suitable for quantitative assessment of tissue regeneration.

Material and Methods

Periodontal fenestration defects, created in Sprague Dawley rats, were treated with allogeneic PDLSCs seeded onto Gelfoam® (Absorbable gelatin sponge; Pharmacia Corporation, Kalamazoo, MI, USA) or with Gelfoam® alone, or remained untreated. Experimental rats were killed at 7, 14, 21 or 28 d after surgery and the tissues were processed for immunohistochemical and histomorphometric examination.

Results

Defects treated with PDLSCs showed significantly greater percentage bone fill and length of new bone bridge compared with the untreated group or the group treated withGelfoam® alone on days 14 and 21. Similarly, a statistically significant difference was achieved within specimens retrieved on day 21 for analysis of regeneration of cementum/periodontal ligament (PDL)‐like structures.

Conclusion

The present investigation shows that allogeneic PDLSCs have a marked ability to repair periodontal defects by forming bone, PDL and cementum‐like tissue in vivo. The results suggest that treatment periods of 14 and 21 d are optimal end time‐points for quantitative assessment of periodontal regeneration within the rodent fenestration‐defect model utilized in the present study.
Variation in habitat connectivity generates positive correlations between species and genetic diversity in a metacommunity
Authors: Lamy T. , Jarne P. , Laroche F. , Pointier J.‐P. , Huth G. , Segard A. , David P.
Published: July 2013

An increasing number of studies are simultaneously investigating species diversity (SD) and genetic diversity (GD) in the same systems, looking for ‘species–genetic diversitycorrelations’ (SGDCs). From negative to positiveSGDCs have been reported, but studies have generally not quantified the processes underlying these correlations. They were also mostly conducted at large biogeographical scales or in recently degraded habitats. Such correlations have not been looked for in natural networks of connected habitat fragments (metacommunities), and the underlying processes remain elusive in most systems. We investigated these issues by studying freshwater snails in a pond network inGuadeloupe (LesserAntilles). We recordedSDand habitat characteristics in 232 ponds and assessedGDin 75 populations of two species. Strongly significant and positiveSGDCs were detected in both species. Based on a decomposition ofSGDCas a function of variance–covariance of habitat characteristics, we showed that connectivity (opportunity of water flow between a site and the nearest watershed during the rainy season) has the strongest contribution onSGDCs. More connective sites received both more alleles and more species through immigration resulting in both higherGDand higherSD. Other habitat characteristics did not contribute, or contributed negatively, toSGDCs. This is true of the desiccation frequency of ponds during the dry season, presumably because species markedly differ in their ability to tolerate desiccation. Our study shows that variation in environmental characteristics of habitat patches can promoteSGDCs at metacommunity scale when the studied species respond homogeneously to these environmental characteristics.
Developmental hypothyroxinaemia and hypothyroidism limit dendritic growth of cerebellar Purkinje cells in rat offspring: involvement of microtubule‐associated protein 2 (MAP2) and stathmin
Authors: Wang Yuan , Wang Yi , Dong Jing , Wei Wei , Song Binbin , Min Hui , Teng Weiping , Chen Jie
Published: July 2013

Aims

Iodine is essential for the synthesis of thyroid hormone. Iodine deficiency (ID)‐induced hypothyroxinaemia and hypothyroidism during developmental period contribute to impairments of function in the brain, such as psychomotor and motor alterations. However, the mechanisms are still unclear. Therefore, the present research is to study the effects of developmental hypothyroxinaemia caused by mild ID and developmental hypothyroidism caused by severe ID or methimazole (MMZ) on dendritic growth in filial cerebellar Purkinje cells (PCs) and the underlying mechanisms.

Methods

A maternal hypothyroxinaemia model was established in Wistar rats using a mild ID diet, and two maternal hypothyroidism models were developed with either severe ID diet or MMZ water. We examined the total dendritic length using immunofluorescence, and Western blot analysis was conducted to investigate the activity of microtubule‐associated protein 2 (MAP2), stathmin and calcium/calmodulin‐dependent protein kinase II (CaMKII).

Results

Hypothyroxinaemia and hypothyroidism reduced the total dendritic length of cerebellar PCs, decreased MAP2 and its phosphorylation, increased stathmin but reduced its phosphorylation and down‐regulated the activity of CaMKII and its phosphorylation in cerebellar PCs on postnatal day (PN) 7, PN14 and PN21.

Conclusion

Developmental hypothyroxinaemia induced by mild ID and hypothyroidism induced by severe ID or MMZ limit PCs dendritic growth, which may involve in the disturbance of MAP2 and stathmin in a CaMKII‐dependent manner. It suggests a potential mechanism of motor coordination impairments caused by developmental hypothyroxinaemia and hypothyroidism.
Uric acid‐induced endoplasmic reticulum stress triggers phenotypic change in rat glomerular mesangial cells
Authors: Li Shasha , Zhao Fei , Cheng Shaoli , Wang Xinyang , Hao Yaning
Published: July 2013

Aim

The aim of this study was to explore the contribution and the mechanism of uric acid (UA) to phenotypic change in rat glomerular mesangial cells.

Methods

Rat glomerular mesangial cells (HBZY‐1) were exposed to UA (0.05 mmol/L to 0.4 mmol/L) for 24 h to 48 h. Subsequently, 4‐phenyl butyric acid (4‐PBA) (5 mg/dL) was added and 48 h incubation was performed. HBZY‐1 cells exposed to UA (0.4 mmol/L) were incubated for 48 h. After incubation, the cells were examined under an inverted microscope and transmission electron microscope to observe their morphologies and the expressions of α‐smooth muscle actin (α‐SMA), transforming growth factor‐β1 (TGF‐β1), fibronectin (FN), glucose regulated protein 78 (GRP78), and the protein disulfide isomerase (PDI) proteins and mRNA in the HBZY‐1 cells were measured by Western blot and reversed transcription‐polymerase chain reaction.

Results

HBZY‐1 cultured in UA showed evident morphological changes under transmission electron microscopy. The soluble UA stimulated the upregulation of the α‐SMA, TGF‐β1 and FN mRNA and proteins in a concentration‐ and time‐dependent manner. UA‐induced endoplasmic reticulum (ER) stress, as evidenced by the upregulation of the mRNA and protein expressions of GRP78 and PDI. However, the upregulation was reverted by 4‐PBA, an inhibitor of ER stress.

Conclusions

Uric acid induces phenotypic change in HBZY‐1 cells. ER stress plays a central role in UA‐induced phenotypic transformation in vitro. 4‐PBA may be beneficial in attenuating UA‐induced glomerular injury.
Risk Factors and Prognosis for Clot Formation on Cardiac Device Leads
Authors: RAHBAR ATA SOLEIMANI , AZADANI PEYMAN N. , THATIPELLI SINDHURA , FLEISCHMANN KIRSTEN E. , NGUYEN NHUNHU , LEE BYRON K.
Published: July 2013

Background

Clot formation on cardiac device leads is poorly understood. We sought to determine how often clot is seen on device leads by transthoracic echo (TTE), identify risk factors, and to describe the natural history of this phenomenon.

Methods

We reviewed 71,888 echocardiographic studies performed at the University of California, San Francisco from 2005 to 2011. We searched for cases where clot was found adhered to a device lead with no diagnosis of endocarditis. For every case, three age‐matched controls with a device but no clot were selected from the echo database.

Results

We found 15 cases with clot adhered to a device lead among 1,086 patients with devices who had TTE (1.4%). In univariate analysis, females had more than four times greater odds of having a clot on their device lead and patients with a history of atrial fibrillation (AF) had an eight times greater odds. Percentage mode switch was also associated with clot formation. Only AF was still associated with clot formation after multivariate analysis. Follow‐up data were available for nine of 15 patients. All nine patients had intensification of their anticoagulant/antiplatelet regimen following clot discovery. Complete resolution or shrinkage of clot was observed in eight of nine patients. The one case with no change was a patient who continued taking only aspirin (higher dose) after clot discovery. None of the nine patients had embolic phenomenon.

Conclusion

Patients with AF are at higher risk for clot formation on device leads. After clot detection, treatment with anticoagulants usually results in resolution of the clot without embolic phenomenon.
Women, Infant and Children (WIC) Peer Counselor Contact with First Time Breastfeeding Mothers
Authors: Campbell Lisa A. , Wan Jim , Speck Patricia M. , Hartig Margaret T.
Published: July 2013

Objective

This study was designed to determine whether singleton women who had not previously breastfed and who had a women, infant and children (WIC) peer counselor were more likely to initiate breastfeeding than women not exposed to the WIC peer counselor.

Design and Sample

The retrospective cross‐sectional study used data from the 2009 Texas Department of State Health Services (DSHS) WIC Infant Feeding Practices Survey (IFPS) administered through 73 local WIC agencies. Of the 5,427 responses to the 2009 Texas DSHS WIC IFP Survey, 56.6% (N = 3,070) were included in this study.

Measures

The Texas DSHS WIC IFPS, a 55‐item survey with multiple‐choice and two open‐ended questions, was used to evaluate breastfeeding beliefs, attitudes, and practices among women receiving WIC services.

Results

Women who had peer counselor contact during pregnancy, in the hospital, and after delivery were more likely to initiate breastfeeding than women without such contacts, OR = 1.36, 2.06, 1.85, respectively.

Conclusion

Women's decision to initiate breastfeeding is significantly associated with WIC peer counselor contacts. Continued WIC peer counselor program services may increase breastfeeding initiation rates among WIC participants.
Numerical modelling of the late stage of subduction zone transference after an accretion event
Authors: Simakin Alexander G.
Published: July 2013

The resumption of subduction of an oceanic plate at a contact with a docked island (continental) margin is modelled numerically in 2D. The mechanical properties of the crustal and mantle rock masses are treated with visco‐plastic rheologies where the viscosities are described by a dynamic power law phenomenologically accounting for the transient texture evolution of the deforming rock masses. The study is limited to the extreme case of a fluid weakened lithosphere characterized by a uniform effective yield stress. At a constant push of 8 cm a−1, the shear zones split the oceanic slab into blocks at the contact with the island. At a moderate yield stress (σY < 80 MPa) and normal relaxation rate of viscosity, subduction resumes in less than ca 1 Ma. High σY = 100 MPa leads to the island edge bending. A detached block of the island is subducted after the plunge of the oceanic plate reverses.
Nanocarrier Hydrodynamics and Binding in Targeted Drug Delivery: Challenges in Numerical Modeling and Experimental Validation
Authors: Ayyaswamy Portonovo S. , Muzykantov Vladimir , Eckmann David M. , Radhakrishnan Ravi
Published: July 2013

This review discusses current progress and future challenges in the numerical modeling of targeted drug delivery using functionalized nanocarriers (NC). Antibody coated nanocarriers of various size and shapes, also called functionalized nanocarriers, are designed to be injected in the vasculature, whereby they undergo translational and rotational motion governed by hydrodynamic interaction with blood particulates as well as adhesive interactions mediated by the surface antibody binding to target antigens/receptors on cell surfaces. We review current multiscale modeling approaches rooted in computational fluid dynamics and nonequilibrium statistical mechanics to accurately resolve fluid, thermal, as well as adhesive interactions governing nanocarrier motion and their binding to endothelial cells lining the vasculature. We also outline current challenges and unresolved issues surrounding the modeling methods. Experimental approaches in pharmacology and bioengineering are discussed briefly from the perspective of model validation.
Influence of Space-Varying Surface Heat Flux on the Heat Transfer Due to a Moving Fluid Over a Moving Surface
Authors: Mukhopadhyay Swati , Mondal Iswar Chandra , Vajravelu Kuppalapalle , Van Gorder Robert A.
Published: July 2013

Boundary-layer forced convective heat transfer at a moving flat surface parallel to a moving stream is presented for the case where the plate is subjected to a variable heat flux. In particular, we assume that the surface heat flux varies with spatial variable x according to a power-law rule. The similarity solutions for the problem are obtained by solving the reduced ordinary differential equations numerically, while exact solutions are provided for certain parametric values. It is noted that even in the case of prescribed surface heat flux, dual solutions exist when the surface and the fluid move in opposite directions.
SU‐C‐105‐02: Real‐Time Treatment Guidance Using An IR Navigation System for Pleural PDT
Authors: Kim M , Liang X , Zhu T
Published: July 2013

Purpose: Pleural photodynamic therapy (PDT) has been used in conjunction with surgical debulking of the tumorous tissue in treatment for mesothelioma. Uniform light fluence distribution is critical for effective and predictable PDT outcome. Current treatment methods involve monitoring the light dose delivered with 8 detectors that are located at various locations inside the pleural cavity. A tracking and real‐time feedback system can be utilized to improve the uniformity of light. Methods: An infrared (IR) tracking camera to monitor the movement of the light source. The same system is used to determine the pleural contour geometry of the treatment area. This study examines the fluence (rate) delivered between measurement and calibration in phantom studies. Isotropic detectors were used for in‐vivo light dosimetry. The tracking data for the light source was used to calculate the light fluence rate delivered which was then compared with the in‐vivo measurement. The real‐time feedback software developed shows the tracking data and calculations during treatment time, enabling more uniform treatment of the pleural cavity. Results: Using the real‐time feedback system, we are able to match the calculated fluence rate with the in‐vivo measurements. Furthermore, we are able to treat more effectively and uniformly with the feedback software. The light fluence rate can have up to 50% deviation compared to the prescription in phantom experiments. With the navigation system, we are able to collect more data regarding the light delivered and the location to which the light was delivered. Conclusion: The IR camera has been used successfully during pleural PDT patient treatment to track the motion of the light source. It is possible to use the feedback system to deliver a more uniform dose of light throughout the pleural cavity.
SU‐C‐137‐01: Out‐Of‐Field Fetal Dose Measurement From a Head‐And‐Neck Treatment with VMAT: An Anthropomorphic Phantom Study
Authors: Roa D , Lin Y , Hanna N , Al‐Ghazi M , Kuo J
Published: July 2013

Purpose: The irradiation of pregnant patients is an uncommon occurrence but if discovered requires accurate fetal dose estimates. For this purpose, we measured the out‐of‐field dose to the fetal region from the primary dose given to a head‐and‐neck tumor(s) irradiated with a volumetric‐modulated arc therapy (VMAT) technique. Methods: A VMAT‐RapidArc plan was generated in ECLIPSE for a head‐and‐neck case extrapolated to an anthropomorphic phantom. The clinical plan, including target and OAR contours was co‐registered to the phantom CT study. The phantom received a total dose of 60 Gy in 2 Gy/fx using a 6 MV photon beam from a Varian Trilogy irradiated using two 358o axial arcs. 108 TLDs and 6 Gafchromic films were mounted outside and inside the phantom to measure the out‐of‐field surface and internal scatter dose. Films were mounted axially in the phantom so that ∼60% of the area provided internal scatter and ∼40% leakage dose data. Results: At 9 cm inferior to the primary treatment site, the leakage dose (∼150 cGy) was about two times higher than internal scattering (∼80 cGy). At 30 cm, the leakage (∼40 cGy) was 2–3 times higher than the internal scatter dose (∼15cGy). The highest dose measured by TLDs at 25 cm away from the target was 20 cGy (0.3 % of total). Although, the data showed higher dose contribution from leakage than internal scattering, the combined amount was small with respect to the primary dose. The estimated fetal dose from these measurements amounted to 0.1–0.3 cGy (at 45–60 cm from the target) which could be slightly higher compared to the established NCRP #91 recommendation (0.5 mSv). Conclusion: Fetal dose measurements at different stages of pregnancy using a VMAT‐RapidArc technique are underway. This data should provide updated and comprehensive information to complement TG‐36.
SU‐C‐137‐04: Effective Control Limits for Predictive Maintenance (PdM) of Accelerator Beam Uniformity
Authors: Able C , Baydush A
Published: July 2013

Purpose: Predictive maintenance programs employ non‐invasive methods to monitor the performance of systems to determine when preemptive intervention is required to maintain high quality performance. The focus of this study is to evaluate the effectiveness of a modified calculation method for the control limits of process control charts (PCC) that will reduce false positive alarms but detect clinically relevant changes in beam uniformity (flatness and symmetry). Methods: Steering coil currents (SCC) for the transverse and radial planes are adjusted such that a reproducibly useful photon or electron beam is available. Performing controlled experiments varying a single SCC, we were able to determine the magnitude of change required to produce a 1% change in beam uniformity. The average and range (Xbar/R) control chart limit calculation was reformulated incorporating a scaling factor (Cm). After monitoring the SCC of 3 accelerators for several months, without detecting any PCC alarms, we intentionally changed the transverse angle and position SCC independently until the beam symmetry differed by ∼1.1% from baseline as confirmed by computerized beam profile scan in water using an ion chamber. These experimental SCC values were plotted in the PCC to determine if they would exceed the modified control limits. Results: The experimental SCC value exceeded the PCC limit for each of the steering coils. Additionally, the capability of the new control limit calculation method was confirmed when an anomaly was detected in the operation of an accelerator in clinical use. Instability in the operation of the 18 MV photon beam was predicted by SPC analysis prior to it being confirmed by service and daily check devices. If the analysis had been performed using the original methodology, a number of false positives would have been reported. Conclusion: Reformulated X‐bar/R chart control limits of SCC can provide an effective predictive maintenance tool for accelerator beam uniformity. This project is supported by a grant from Varian Medical Systems.
SU‐C‐137‐05: Reference Dosimetry for An 80 MeV/n Carbon Ion Beam Based On Graphite Calorimetry
Authors: Rossomme S , Palmans H , Thomas R , Lee N , Shipley D , Bailey M , Duane S , Bertrand D , Vynckier S
Published: July 2013

Purpose: Comparison between the response of a primary standard graphite calorimeter and the response of an ionization chamber (IC) allows the estimations of values of the beam quality correction factor, kQ,Q0, for the IC. This factor is used in the IAEA TRS‐398 dosimetric protocol to derive the absorbed dose‐to‐water using an IC. It depends on three parameters, one of which is the average energy required to produce an ion pair in dry air (Wair). The aim of this work is the experimental determination of the Wair‐value for an 80 MeV/A carbon ion beam. Methods: The dose measured with a graphite calorimeter, after correction for heat transfer between different parts of the calorimeter, must be converted to dose‐to‐water. This conversion needs knowledge of the water‐to‐graphite stopping power ratio and the fluence correction factor. These have been determined experimentally and numerically using Geant4 Monte Carlo simulations. In addition to these calorimetric corrections, the determination of kQ,Q0‐values needs the IC reading to be corrected for ion recombination. Results: The water‐to‐graphite stopping power ratio has been determined numerically to be 1.115 while the fluence correction factor has been determined experimentally and numerically to vary linearly between 0.9996 at the phantom surface and 1.0063 before the Bragg peak. The analysis of the ion recombination correction measurements is still ongoing. Two experimental campaigns with the graphite calorimeter and several IC's have been performed. Based on recommended data from TRS‐398, we derived preliminary Wair‐values of 36. J/C and 34.85 J/C for each campaign. These results are under investigation. Conclusion: These results demonstrate the feasibility of graphite calorimetry in an 80 MeV/A carbon ion beam and are encouraging for our future work: a direct comparison between water and graphite calorimetry in a clinical carbon ion beam. Funding support for Severine Rossomme: BioWin program of the Walloon Government (Belgium); Funding support for NPL people: Acoustics and Ionising Radiation Metrology Programme of the National Measurement System (UK)
SU‐C‐108‐02: Dosimetric Impact of VMAT Delivery and Target Motion: MIP‐Based ITV Vs. ITV From Contoured Phases of 4DCT
Authors: Chan M , Li J , Burman C , Schupak K , Parhar P
Published: July 2013

Purpose: It has been a concern that the interplay effect in dynamic radiation treatments of moving targets may compromise dose coverage. In this work we study the interplay‐induced dosimetric impact to moving targets in VMAT delivery. Methods: A new patient‐specific QA system with ArcCHECK/3DVH v3 (Sun Nuclear Corp) was utilized to estimate “true” dose to a moving target during VMAT delivery. A set of 4DCT scans was acquired for an SBRT lung patient and a VMAT plan was generated using an in‐house TPS with ITV (internal‐target‐volume) generated from the MIPs (maximum‐intensity‐projections) of 4DCT. The prescribed dose to the PTV (ITV+5mm) was 45Gy in 5 fractions. The motion trajectory was obtained based on the GTVs (gross‐tumor‐volume) from the 10 phases of 4DCT. The QA system was first used to measure the dose distribution delivered according to the plan. Then, the motion trajectory was incorporated into the QA algorithm to derive the “true” dose coverage, with the virtual motion simulation. Results: The MIP‐based ITV had measurable difference from the ITV generated with contoured phases of 4DCT. The dose differences for targets and critical structures between measurements and TPS were: −1.9%, PTV(D95); −3.5%, ITV(D95); 3.0%, max cord; −1%, mean heart; −1.2%, mean esophagus; 1.6%, mean right lung; −0.9%, mean left lung. After accounting for the statistical mean of motion‐simulated dose for 5 fractions, the dose differences for the ITV(D95) became −4.1%. However, the dose coverage of the moving GTV itself is nearly unchanged from the plan PTV coverage (<0.2%), indicating that the 5mm margin was adequate to compensate for dose perturbation due to motion. Conclusion: The interplay between organ motion and dynamic radiation delivery leads to dose coverage differences between treatment delivery and the static ITV based treatment plan. The new patient‐specific QA device may be a useful tool to estimate the differences.
SU‐C‐108‐04: To Better Understand IMRT and Planned Dose Distributions: A Measure of Entropy
Authors: Veres A , Snyder M
Published: July 2013

Purpose: Traditional IMRT QA procedures yield close approximations to the patients planned dose distribution. However, the relationship between QA data and the patients planned distribution is difficult to quantify. This study presents an approach to investigate the relationship between a planar QA distribution and the same doseplane within the patient using complexity analysis. Methods: Shannon entropy was the decided metric to quantify the complexity of three calculated dose distributions: 1) the IMRT QA distribution, 2) the in‐patient dose distributions with heterogeneity correction on, and 3) the in‐patient dose distribution without heterogeneity correction. Varian Eclipse treatment planning system was used to construct the plans and calculate dose. MapCheck 1175 diode array was used for the IMRT QA acquisition. Global entropy was calculated without threshold for each distribution, and local entropies were found for low dose thresholds ranging from 0% to 100% of both prescribed and maximum dose. All calculations were done using MATLAB. Results: The QA data proved to have the highest global entropy of the three dose distributions analyzed. Local entropies, calculated using subsets of all dose points, converged at a low dose threshold of >∼70% of maximum dose. For low dose thresholds <∼70%, the entropies of both patient distributions remained similar, while the entropy for the QA distribution diverged, increasing in value. Conclusion: The greater entropy values for the QA distribution at low dose thresholds <∼70% suggests a more disordered dose distribution than the two planned dose distributions. This is thought to be due to the larger phantom size with respect to the patient, which tends to spread out the dose gradient outside the target. This Result is suggestive that an optimal threshold for meaningful gamma analysis could be >70% of maximum dose, or where the QA and planned dose distributions entropies, or complexities, are accurately matched.
SU‐C‐108‐06: Monte Carlo Simulations for Trajectory‐Based Beam Delivery in Varian TrueBeam Developer Mode
Authors: Teke T , Gete E , Duzenli C , McAvoy S , Popescu I
Published: July 2013

Purpose: Varian experimental trajectory based beam delivery mode on the TrueBeam linac comes well in advance of treatment planning software capable of managing the range of trajectories the linac is able to deliver. The goal of this study is to present a Monte Carlo based dose calculation system for trajectory based treatment delivered using Varian TrueBeam Developer Mode. Methods: The Varian TrueBeam linear accelerator advanced control features are designed to allow complex three dimensional trajectory beam delivery. In Developer Mode, the machine is capable of dynamically moving all its components simultaneously while the beam is on. Dose delivery is executed via a set of instructions written in XML which use the “Trajectory Model”, a central concept of the TrueBeam control system. In this model all beams are characterized by the relationship between monitor units (MU) and position of the moving components of the linear accelerator. A trajectory based beam was created which includes simultaneous collimator rotation, couch translation and rotation. An in‐house C++ code converts the XML file into DOSXYZnrc input file for source 20. This source supports all of the degrees of freedom available in Developer Mode. Therefore, it is possible to simulate any complex trajectory‐based beam delivery continuously, in a single run. The trajectory beam was delivered on a Varian TrueBeam linac in developer mode using a 6XFFF photon beam with a 1.5cm2 field size defined by the MLC. Monte Carlo dose distribution was compared to Gafchromic film measurement using FilmQA Pro. Results: Good agreement is observed between Monte Carlo and film measurement with over 90% of the points passing the 3%/3mm Gamma test. Conclusion: This work created a tool that can be employed by any user of the TrueBeam Developer Mode to calculate the dose for complex trajectory‐based beam delivery with the accuracy of Monte Carlo simulations. This work is supported by the Varian Master Research Agreement
SU‐C‐108‐07: Possible Implications for Skin Toxicity in Large Breasted Women with the Use of Enhance Dynamic‐Wedged (EDW) Tangential Fields
Authors: Amro H , Gulam M , Chetty I , Walker E
Published: July 2013

Purpose: It has been reported that women with large breast sizes (>300 cc) may experience increased skin toxicity when undergoing post‐lumpectomy radiation therapy. Studies have shown that skin dose increases with the use of dynamic wedges during chest wall irradiations. This study will evaluate the increase in skin dose due to using hard‐vs. dynamic‐wedged fields for various breast volumes. We hypothesize the use of enhanced dynamic‐wedged tangential radiation fields will Result in clinically important changes in skin toxicity. Methods: Three phantoms were build with breast volumes 300, 400, and 500 cc. The phantoms were CT scanned and the scans were imported to the TPS for planning. For each phantom, two dosimetrically matched plans were created, one with hard wedged tangential fields and the other using enhanced dynamic‐wedges (EDW). EBT film pieces were placed on various areas on the breast surface for dose measurements. The plans were delivered to each phantom using 6x photon beams. Results: The film data showed an increase of 151%, 22%, and 26% in skin dose due to the use of EDW for 300, 400, and 500 cc breast volumes, respectively. This increase in skin dose was between 9% – 13% of the total prescription dose for EDW and 8% – 10% for HW system. The increased skin dose was evaluated by our clinicians. An increase of 26% was deemed too large and likely to Result in clinically relevant implications for skin toxicity. Conclusion: Based on these results the use of EDW for tangential field radiation therapy of patients with large breasts may increase skin toxicity
SU‐C‐500‐05: CT‐Based Treatment Planning for 4Pi Non‐Coplanar Converging (4PiNC) Beams in An External‐Beam Treatment Planning System
Authors: Wang S , Chao K , Chang J
Published: July 2013

Purpose: A 4‐Pi non‐coplanar converging (4PiNC) modality has been actively developed in our institution, in which the radiation beams are delivered along conic trajectories and rotate around the midline of a patient. The proposed design eliminates the potential gantry‐couch collision, a major concern of non‐coplanar beam delivery. This study introduces a method to implement the 4PiNC planning in the public‐domain treatment planning system (TPS) PLUNC. Methods: The cone angle of a 4PiNC delivery is defined as the angle between the cone edge and the transverse iso‐plane. The beam angle defines its relative position on the cone. We have mathematically proved that there is a one‐to‐one correspondence between a 4PiNC beam specification (cone and beam angle) and a LINAC beam specification (gantry and couch angle). Therefore, a graphic interface was written in PLUNC to design a 4PiNC RT plan using existing commissioned LINAC machines. The method was validated visually on a spherical phantom of 15cm radius with 12 beams evenly distributed on a cone, and with cone angle 40, ‐ 30, 20, ‐ 10 and 0 degree respectively. A 4PiNC RT plan was made for a prostate SBRT case with the afore‐mentioned 5 cones (20 beams on each cone) and was compared with the conventional five‐beam IMRT plan. Results: In the phantom study, the transverse planes at −3, 0 and 3 cm from the iso‐plane as well as the sagittal iso‐plane were examined; the beam separations and cone angles were consistent with those specified. The prostate study suggested that the OAR mean dose can be reduced by up to 44.5% by the 4PiNC RT plan with comparable PTV coverage. Conclusion: The RT planning for the proposed 4PiNC delivery system can be implemented in a TPS for conventional LINAC beams. This allows dosimetric investigation of the proposed system even before finalizing the hardware design. This work was partially supported by a DoD grant DoD W81XWH1010862
SU‐C‐500‐07: Material Interface Behavior of the Eclipse Modulated Spot Scanning Proton Algorithm
Authors: Mundy D , Beltran C , Herman M
Published: July 2013

Purpose: Evaluate the accuracy of the Eclipse proton dose calculation at high and low density material interfaces. Methods: A phantom designed to test the Eclipse algorithm accuracy at material interfaces was developed. The phantom is a 40‐cm water cube with two slab heterogeneities (dense bone and air). The materials abut at the central‐axis and dose from a single 144.7‐MeV beam spot along and spanning the interface was calculated. Depth and thickness of the slabs were varied to examine effects on beam termination and penetration of the bone. The dose distributions were compared using a variety of metrics. Results: The most notable observed difference was the presence of three Bragg peaks in Eclipse versus two in Geant4. The proximal peak corresponds to the range associated with the presence of the bone and the distal to that of the air. Eclipse calculates an intermediate peak of substantial intensity. The depth of this peak scales linearly with the thickness of the slabs, but is independent of the slab depth. Intensity of the peak decreases with increasing thickness, but is constant with depth. The energy loss associated with this peak causes a decrease (∼45%) in the intensity of the distal peak. The distal peak locations agree to within 2‐mm, while the proximal peaks are deeper in Eclipse by ∼5‐mm for all shallow slabs and 1.6‐mm for the deep slab. Intensity of the proximal peaks differed by 2–5% with the greatest difference observed with the deep slab. Conclusions: Large discrepancies were identified in the Eclipse spot scanning proton dose calculation algorithm relative to Monte Carlo calculations in the presence of a material interface. These differences are much greater than those observed in a homogenous phantom. Further investigation is necessary to determine the impact of these discrepancies on patient dose calculations under clinical conditions.
SU‐C‐141‐02: Evaluation of Dosimetric and Geometric Accuracy of Gated Lung SBRT with CIRS Lung Motion Phantom
Authors: Yu S , Han B , Wang L , Mok E
Published: July 2013

Purpose: To evaluate the dosimetric and geometric accuracy of the gated SBRT delivery using film measurements and intra‐fractional kV images with predefined software‐markers. Methods: End‐to‐end tests of gated SBRT delivery were performed using a Varian TrueBeam™ linac and a CIRS lung motion phantom with targets of 1 and 2 cm in diameter and implanted fiducials. 4DCT images of the phantom were acquired with 1 mm slice thickness. RapidArc plans were created in Eclipse TPS with software‐markers placed on the fiducials at maximal expiration. SBRT plans were delivered to the phantom in stationary and in gating mode (2 mm and 5 mm‐gating window). Plans were also delivered with 5 mm targets shift with respect to the boney anatomy in stationary mode and 10% phase shift in 2 mm‐gating mode. To investigate the dosimetric accuracy, dose was measured by EBT3 film and compared with the TPS calculation (AcurosXB algorithm) using γ‐index criteria (3mm distance‐to‐agreement and 3% dose‐difference). The geometric accuracy was evaluated using kV intra‐fraction images of the fiducials relative to the predefined software‐markers. Results: Comparing with the stationary mode, the percentage passing γ‐index (%γ) for 1 cm target decreased significantly from 98.0% to 94.8% (2 mm‐gating window) and 84.3% (5 mm‐gating window) while for 2 cm target %y decreased from 99.5% to 99.2% (2 mm‐gating window) and 86.6% (5 mm‐gating window). The %γ for the conditions of target shift and phase shift for the 2 cm target were 89.0% and 89.9%, respectively. Geometric deviation was less than 0.05 mm, except for the phase shift condition (0.45 mm). Conclusion: Higher dosimetric impact from motion was found for the smaller target. With a proper gating window the planned dose can be accurately delivered with the use of kV intra‐fraction image and software‐maker to ensure the geometric accuracy during treatment.