Comparison of dose volume parameters evaluated using three forward planning – optimization techniques in cervical cancer brachytherapy involving two applicators

PubMed Central

Basu-Roy, Somapriya; Kar, Sanjay Kumar; Das, Sounik; Lahiri, Annesha

2017-01-01

Purpose This study is intended to compare dose-volume parameters evaluated using different forward planning- optimization techniques, involving two applicator systems in intracavitary brachytherapy for cervical cancer. It looks for the best applicator-optimization combination to fulfill recommended dose-volume objectives in different high-dose-rate (HDR) fractionation schedules. Material and methods We used tandem-ring and Fletcher-style tandem-ovoid applicator in same patients in two fractions of brachytherapy. Six plans were generated for each patient utilizing 3 forward optimization techniques for each applicator used: equal dwell weight/times (‘no optimization’), ‘manual dwell weight/times’, and ‘graphical’. Plans were normalized to left point A and dose of 8 Gy was prescribed. Dose volume and dose point parameters were compared. Results Without graphical optimization, maximum width and thickness of volume enclosed by 100% isodose line, dose to 90%, and 100% of clinical target volume (CTV); minimum, maximum, median, and average dose to both rectum and bladder are significantly higher with Fletcher applicator. Even if it is done, dose to both points B, minimum dose to CTV, and treatment time; dose to 2 cc (D2cc) rectum and rectal point etc.; D2cc, minimum, maximum, median, and average dose to sigmoid colon; D2cc of bladder remain significantly higher with this applicator. Dose to bladder point is similar (p > 0.05) between two applicators, after all optimization techniques. Conclusions Fletcher applicator generates higher dose to both CTV and organs at risk (2 cc volumes) after all optimization techniques. Dose restriction to rectum is possible using graphical optimization only during selected HDR fractionation schedules. Bladder always receives dose higher than recommended, and 2 cc sigmoid colon always gets permissible dose. Contrarily, graphical optimization with ring applicators fulfills all dose volume objectives in all HDR fractionations practiced. PMID:29204164

WE-AB-207B-04: A Preliminary Investigation of Indicators for Treatment Outcomes of CT Guided Cervical Cancer Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meerschaert, R; Paul, A; Chen, W

Purpose: To identify indicators for recurrence in cervical cancer patients treated with high-dose-rate brachytherapy (HDR-BT). Methods: A total of 37 biopsy proven uterine cervical cancer patients of stage IB-IVA treated between 2011 and 2015 were included in this study. All patients were treated with 37.8–52.2Gy of external beam radiotherapy (EBRT) plus 5 × 5.0–6.5Gy of HDR-BT. Patient age, standard deviation of high-risk clinical tumor volume (HR-CTVSD) collected throughout HDR-BT, and D90 (EQD2, α/β=10Gy) of the HR-CTV were investigated as potential indicators for local/distant recurrence using ROC analysis. The optimal cutoff value was identified through the Youden index and was subsequentlymore » used to obtain a group assignment for all patients. Another two comparing groups were defined per evidence of post-EBRT tumor shrinkage based on the pre-HDR MR scan. Kaplan-Meier curves were generated for recurrence-free proportions for comparing groups where time was measured from the final HDR treatment date to the date of the final follow-up exam and compared through Cox regression. Results: Patients had a median follow-up of 12 months, where 16% had local pelvic recurrence and 16% had distant recurrence. HR-CTVSD was identified as a statistically significant indicator for recurrence (AUC=0.802, p=0.007) compared to D90 (AUC=0.655, p=0.167) and patient age (AUC=0.683, p=0.103). HR-CTVSD of 6.26cc was chosen as the optimal cutoff value, which was used as the basis for patient group assignment. Patients with HR-CTVSD>6.26cc had a hazard ratio of 3.92 (95% CI-1.37, 11.24; p=0.011) for recurrence compared to HRCTVSD≤ 6.26cc. Patients without evidence of post-EBRT tumor shrinkage compared to those with had a hazard ratio of 4.28 (95% CI-1.14, 16.15; p=0.032) for recurrence. Conclusion: HR-CTVSD was identified as an indicator for recurrence and an optimal value of 6.26cc was established in our study. In addition, patients without evidence of post-EBRT tumor shrinkage demonstrated an increased recurrence rate.« less

A novel applicator design for intracavitary brachytherapy of the nasopharynx: Simulated reconstruction, image-guided adaptive brachytherapy planning, and dosimetry.

PubMed

Bacorro, Warren R; Agas, Ryan Anthony F; Cabrera, Stellar Marie R; Bojador, Maureen R; Sogono, Paolo G; Mejia, Michael Benedict A; Sy Ortin, Teresa T

2018-05-11

In nasopharyngeal cancer, brachytherapy is given as boost in primary treatment or as salvage for recurrent or persistent disease. The Rotterdam nasopharyngeal applicator (RNA) allows for suboptimal reduction of soft palate radiation dose, based on image-guided brachytherapy plans. Building on the RNA, we propose a novel design, the Benavides nasopharyngeal applicator (BNA). The virtual BNA was reconstructed on two cases (one T1, one T2) previously treated with intracavitary brachytherapy using the RNA. Dose was prescribed to the high-risk clinical target volumes (CTVs) and optimization was such that high-risk CTV D90 ≥ 100% of prescribed dose (PD), intermediate-risk-CTV D90 ≥ 75% PD, and soft palate D2cc ≤ 120% PD. The optimized RNA and BNA image-guided brachytherapy plans were compared in terms of CTV coverage and organs-at-risk sparing. Optimization objectives were more easily met with the BNA. For the T1 case, all three planning objectives were easily achieved in both the RNA and BNA, but with 18-19% lower soft palate doses with the BNA. For the T2 case, the CTV planning objectives were achieved in both the RNA and BNA, but the soft palate constraint was only achieved with the BNA, with 38-41% lower soft palate doses. Compared to the RNA, the BNA permits easier optimization and improves therapeutic ratio by a significant reduction of soft palate doses, based on simulation using a proposed system for CTV/organs-at-risk delineation, prescription, and optimization for image-guided adaptive brachytherapy. Clinical piloting using a prototype is necessary to evaluate its feasibility and utility. Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

TH-AB-BRA-04: Dosimetric Evaluation of MR-Guided HDR Brachytherapy Planning for Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kamio, Y; Barkati, M; Beliveau-Nadeau, D

2016-06-15

Purpose: To perform a retrospective study on 16 patients that had both CT and T2-weighted MR scans done at first fraction using the Utrecht CT/MR applicator (Elekta Brachytherapy) in order to evaluate uncertainties associated with an MR-only planning workflow. Methods: MR-workflow uncertainties were classified in three categories: reconstruction, registration and contouring. A systematic comparison of the CT and MR contouring, manual reconstruction and optimization process was performed to evaluate the impact of these uncertainties on the recommended GEC ESTRO DVH parameters: D90% and V100% for HR-CTV as well as D2cc for bladder, rectum, sigmoid colon and small bowel. This comparisonmore » was done using the following four steps: 1. Catheter reconstruction done on MR images with original CT-plan contours and dwell times. 2. OAR contours adjusted on MR images with original CT-plan reconstruction and dwell times. 3. Both reconstruction and contours done on MR images with original CT-plan dwell times. 4. Entire MR-based workflow optimized dwell times reimported to the original CT-plan. Results: The MR-based reconstruction process showed average D2cc deviations of 4.5 ± 3.0%, 1.5 ± 2.0%, 2.5 ± 2.0% and 2.0 ± 1.0% for the bladder, rectum, sigmoid colon and small bowels respectively with a maximum of 10%, 6%, 6% and 4%. The HR-CTV’s D90% and V100% average deviations was found to be 4.0 ± 3.0%, and 2.0 ± 2.0% respectively with a maximum of 10% and 6%. Adjusting contours on MR-images was found to have a similar impact. Finally, the optimized MR-based workflow dwell times were found to still give acceptable plans when re-imported to the original CT-plan which validated the entire workflow. Conclusion: This work illustrates a systematic validation method for centers wanting to move towards an MR-only workflow. This work will be expanded to model based reconstruction, PD-weighted images and other types of applicators.« less

Novel use of ViewRay MRI guidance for high-dose-rate brachytherapy in the treatment of cervical cancer.

PubMed

Ko, Huaising C; Huang, Jessie Y; Miller, Jessica R; Das, Rupak K; Wallace, Charles R; De Costa, Anna-Maria A; Francis, David M; Straub, Margaret R; Anderson, Bethany M; Bradley, Kristin A

To characterize image quality and feasibility of using ViewRay MRI (VR)-guided brachytherapy planning for cervical cancer. Cervical cancer patients receiving intracavitary brachytherapy with tandem and ovoids, planned using 0.35T VR MRI at our institution, were included in this series. The high-risk clinical target volume (HR-CTV), visible gross tumor volume, bladder, sigmoid, bowel, and rectum contours for each fraction of brachytherapy were evaluated for dosimetric parameters. Typically, five brachytherapy treatments were planned using the T2 sequence on diagnostic MRI for the first and third fractions, and a noncontrast true fast imaging with steady-state precession sequence on VR or CT scan for the remaining fractions. Most patients received 5.5 Gy × 5 fractions using high-dose-rate Ir-192 following 45 Gy of whole-pelvis radiotherapy. The plan was initiated at 5.5 Gy to point A and subsequently optimized and prescribed to the HR-CTV. The goal equivalent dose in 2 Gy fractions for the combined external beam and brachytherapy dose was 85 Gy. Soft-tissue visualization using contrast-to-noise ratios to distinguish normal tissues from tumor at their interface was compared between diagnostic MRI, CT, and VR. One hundred and forty-two fractions of intracavitary brachytherapy were performed from April 2015 to January 2017 on 29 cervical cancer patients, ranging from stages IB1 to IVA. The median HR-CTV was 27.78 cc, with median D 90 HR-CTV of 6.1 Gy. The median time from instrument placement to start of treatment using VR was 65 min (scan time 2 min), compared to 105 min using diagnostic MRI (scan time 11 min) (t-test, p < 0.01). The contrast-to-noise ratio of tumor to cervix in both diagnostic MRI and VR had significantly higher values compared to CT (ANOVA and t-tests, p < 0.01). We report the first clinical use of VR-guided brachytherapy. Time to treatment using this approach was shorter compared to diagnostic MRI. VR also provided significant advantage in visualizing the tumor and cervix compared to CT. This presents a feasible and reliable manner to image and plan gynecologic brachytherapy. Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

SU-E-T-232: Custom High-Dose-Rate Brachytherapy Surface Mold Applicators: The Importance Source to Skin Distance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, S; Demanes, J; Kamrava, M

2015-06-15

Purpose: Surface mold applicators can be customized to fit irregular skin surfaces that are difficult to treat with other radiation therapy techniques. Optimal design of customized HDR skin brachytherapy is not well-established. We evaluated the impact of applicator thickness (source to skin distance) on target dosimetry. Methods: 27 patients had 34 treated sites: scalp 4, face 13, extremity 13, and torso 4. Custom applicators were constructed from 5–15 mm thick thermoplastic bolus molded over the skin lesion. A planar array of plastic brachytherapy catheters spaced 5–10 mm apart was affixed to the bolus. CT simulation was used to contour themore » target volume and to determine the prescription depth. Inverse planning simulated annealing followed by graphical optimization was used to plan and deliver 40–56 Gy in 8–16 fractions. Target coverage parameters (D90, Dmean, and V100) and dose uniformity (V110–200, D0.1cc, D1cc, and D2cc) were studied according to target depth (<5mm vs. ≥5mm) and applicator thickness (5–10mm vs. ≥10mm). Results: The average prescription depth was 4.2±1.5mm. The average bolus thickness was 9.2±2.4mm. The median CTV volume was 10.0 cc (0.2–212.4 cc). Similar target coverage was achieved with prescription depths of <5mm and ≥5mm (Dmean = 113.8% vs. 112.4% and D90 = 100.2% vs. 98.3%). The <5mm prescription depth plans were more uniform (D0.1cc = 131.8% vs. 151.8%). Bolus thickness <10mm vs. ≥10mm plans also had similar target coverage (Dmean = 118.2% vs. 110.7% and D90 = 100.1% vs. 99.0%). Applicators ≥10mm thick, however, provide more uniform target dosimetry (D0.1cc = 146.9% vs. 139.5%). Conclusion: Prescription depth is based upon the thickness of the lesion and upon the clinical needs of the patient. Applicators ≥10mm thick provide more dose uniformity than 5–10mm thick applicators. Applicator thickness is an important variable that should be considered during treatment planning to achieve optimal dose uniformity.« less

Isobio software: biological dose distribution and biological dose volume histogram from physical dose conversion using linear-quadratic-linear model.

PubMed

Jaikuna, Tanwiwat; Khadsiri, Phatchareewan; Chawapun, Nisa; Saekho, Suwit; Tharavichitkul, Ekkasit

2017-02-01

To develop an in-house software program that is able to calculate and generate the biological dose distribution and biological dose volume histogram by physical dose conversion using the linear-quadratic-linear (LQL) model. The Isobio software was developed using MATLAB version 2014b to calculate and generate the biological dose distribution and biological dose volume histograms. The physical dose from each voxel in treatment planning was extracted through Computational Environment for Radiotherapy Research (CERR), and the accuracy was verified by the differentiation between the dose volume histogram from CERR and the treatment planning system. An equivalent dose in 2 Gy fraction (EQD 2 ) was calculated using biological effective dose (BED) based on the LQL model. The software calculation and the manual calculation were compared for EQD 2 verification with pair t -test statistical analysis using IBM SPSS Statistics version 22 (64-bit). Two and three-dimensional biological dose distribution and biological dose volume histogram were displayed correctly by the Isobio software. Different physical doses were found between CERR and treatment planning system (TPS) in Oncentra, with 3.33% in high-risk clinical target volume (HR-CTV) determined by D 90% , 0.56% in the bladder, 1.74% in the rectum when determined by D 2cc , and less than 1% in Pinnacle. The difference in the EQD 2 between the software calculation and the manual calculation was not significantly different with 0.00% at p -values 0.820, 0.095, and 0.593 for external beam radiation therapy (EBRT) and 0.240, 0.320, and 0.849 for brachytherapy (BT) in HR-CTV, bladder, and rectum, respectively. The Isobio software is a feasible tool to generate the biological dose distribution and biological dose volume histogram for treatment plan evaluation in both EBRT and BT.

SU-E-T-10: A Clinical Implementation and the Dosimetric Evidence in High Dose Rate Vaginal Multichannel Applicator Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Syh, J; Syh, J; Patel, B

2015-06-15

Purpose: The multichannel cylindrical applicator has a distinctive modification of the traditional single channel cylindrical applicator. The novel multichannel applicator has additional peripheral channels that provide more flexibility both in treatment planning process and outcomes. To protect by reducing doses to adjacent organ at risk (OAR) while maintaining target coverage with inverse plan optimization are the goals for such novel Brachytherapy device. Through a series of comparison and analysis of reults in more than forty patients who received HDR Brachytherapy using multichannel vaginal applicator, this procedure has been implemented in our institution. Methods: Multichannel planning was CT image based. Themore » CTV of 5mm vaginal cuff rind with prescribed length was well reconstructed as well as bladder and rectum. At least D95 of CTV coverage is 95% of prescribed dose. Multichannel inverse plan optimization algorithm not only shapes target dose cloud but set dose avoids to OAR’s exclusively. The doses of D2cc, D5cc and D5; volume of V2Gy in OAR’s were selected to compare with single channel results when sole central channel is only possibility. Results: Study demonstrates plan superiorly in OAR’s doe reduction in multi-channel plan. The D2cc of the rectum and bladder were showing a little lower for multichannel vs. single channel. The V2Gy of the rectum was 93.72% vs. 83.79% (p=0.007) for single channel vs. multichannel respectively. Absolute reduced mean dose of D5 by multichannel was 17 cGy (s.d.=6.4) and 44 cGy (s.d.=15.2) in bladder and rectum respectively. Conclusion: The optimization solution in multichannel was to maintain D95 CTV coverage while reducing the dose to OAR’s. Dosimetric advantage in sparing critical organs by using a multichannel applicator in HDR Brachytherapy treatment of the vaginal cuff is so promising and has been implemented clinically.« less

Tumor dose-volume response in image-guided adaptive brachytherapy for cervical cancer: A meta-regression analysis.

PubMed

Mazeron, Renaud; Castelnau-Marchand, Pauline; Escande, Alexandre; Rivin Del Campo, Eleonor; Maroun, Pierre; Lefkopoulos, Dimitri; Chargari, Cyrus; Haie-Meder, Christine

2016-01-01

Image-guided adaptive brachytherapy is a high precision technique that allows dose escalation and adaptation to tumor response. Two monocentric studies reported continuous dose-volume response relationships, however, burdened by large confidence intervals. The aim was to refine these estimations by performing a meta-regression analysis based on published series. Eligibility was limited to series reporting dosimetric parameters according to the Groupe Européen de Curiethérapie-European SocieTy for Radiation Oncology recommendations. The local control rates reported at 2-3 years were confronted to the mean D90 clinical target volume (CTV) in 2-Gy equivalent using the probit model. The impact of each series on the relationships was pondered according to the number of patients reported. An exhaustive literature search retrieved 13 series reporting on 1299 patients. D90 high-risk CTV ranged from 70.9 to 93.1 Gy. The probit model showed a significant correlation between the D90 and the probability of achieving local control (p < 0.0001). The D90 associated to a 90% probability of achieving local control was 81.4 Gy (78.3-83.8 Gy). The planning aim of 90 Gy corresponded to a 95.0% probability (92.8-96.3%). For the intermediate-risk CTV, less data were available, with 873 patients from eight institutions. Reported mean D90 intermediate-risk CTV ranged from 61.7 to 69.1 Gy. A significant dose-volume effect was observed (p = 0.009). The D90 of 60 Gy was associated to a 79.4% (60.2-86.0%) local control probability. Based on published data from a high number of patients, significant dose-volume effect relationships were confirmed and refined between the D90 of both CTV and the probability of achieving local control. Further studies based on individual data are required to develop nomograms including nondosimetric prognostic criteria. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

SU-C-202-02: A Comprehensive Evaluation of Adaptive Daily Planning for Cervical Cancer HDR Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meerschaert, R; Paul, A; Zhuang, L

Purpose: To evaluate adaptive daily planning for cervical cancer patients who underwent high-dose-rate intra-cavitary brachytherapy (HDR-ICBT). Methods: This study included 22 cervical cancer patients who underwent 5 fractions of HDR ICBT. Regions of interest (ROIs) including high-risk clinical tumor volume (HR-CTV) and organs-at-risk (OARs) were manually contoured on daily CT images. All patients were treated with adaptive daily plans, which involved ROI delineation and dose optimization at each treatment fraction. Single treatment plans were retrospectively generated by applying the first treatment fraction’s dwell times adjusted for decay and dwell positions of the applicator to subsequent treatment fractions. Various existing similaritymore » metrics were calculated for the ROIs to quantify interfractional organ variations. A novel similarity score (JRARM) was established, which combined both volumetric overlap metrics (DSC, JSC, and RVD) and distance metrics (ASD, MSD, and RMSD). Linear regression was performed to determine a relationship between inter-fractional organ variations of various similarity metrics and D2cc variations from both plans. Wilcoxon Signed Rank Tests were used to assess adaptive daily plans and single plans by comparing EQD2 D2cc (α/β=3) for OARs. Results: For inter-fractional organ variations, the sigmoid demonstrated the greatest variations based on the JRARM and DSC similarity metrics. Comparisons between paired ROIs showed differences in JRARM scores and DSCs at each treatment fraction. RVD, MSD, and RMSD were found to be significantly correlated to D2cc variations for bladder and sigmoid. The comparison between plans found that adaptive daily planning provided lower EQD2 D2cc of OARs than single planning, specifically for the sigmoid (p=0.015). Conclusion: Substantial inter-fractional organ motion can occur during HDR-BT, which may significantly affect D2cc of OARs. Adaptive daily planning provides improved dose sparing for OARs compared to single planning.« less

SU-E-T-564: Multi-Helix Rotating Shield Brachytherapy for Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dadkhah, H; Wu, X; Flynn, R

Purpose: To present a novel and practical brachytherapy technique, called multi-helix rotating shield brachytherapy (H-RSBT), for the precise positioning of a partial shield in a curved applicator. H-RSBT enables RSBT delivery using only translational motion of the radiation source/shield combination. H-RSBT overcomes the challenges associated with previously proposed RSBT approaches based on a serial (S-RSBT) step-and-shoot delivery technique, which required independent translational and rotational motion. Methods: A Fletcher-type applicator, compatible with the combination of a Xoft Axxent™ electronic brachytherapy source and a 0.5 mm thick tungsten shield, is proposed. The wall of the applicator contains six evenly-spaced helical keyways thatmore » rigidly define the emission direction of the shield as a function of depth. The shield contains three protruding keys and is attached to the source such that it rotates freely. S-RSBT and H-RSBT treatment plans with 180° and 45° azimuthal emission angles were generated for five cervical cancer patients representative of a wide range of high-risk clinical target volume (HR-CTV) shapes and applicator positions. The number of beamlets used in the treatment planning process was nearly constant for S-RSBT and H-RSBT by using dwell positions separated by 5 and 1.7 mm, respectively, and emission directions separated by 22.5° and 60°, respectively. For all the treatment plans the EQD2 of the HR-CTV was escalated until the EQD{sub 2cc} tolerance of either the bladder, rectum, or sigmoid colon was reached. Results: Treatment times for H-RSBT tended to be shorter than for S-RSBT, with changes of −38.47% to 1.12% with an average of −8.34%. The HR-CTV D{sub 90} changed by −8.81% to 2.08% with an average of −2.46%. Conclusion: H-RSBT is a mechanically feasible technique in the curved applicators needed for cervical cancer brachytherapy. S-RSBT and H-RSBT dose distributions were clinically equivalent for all patients considered, with the H-RSBT deliveries tending to be faster. Ryan Flynn has ownership interest in pxAlpha, LLC, which is a startup company developing a rotating shield brachytherapy system.« less

Intermediate-term results of image-guided brachytherapy and high-technology external beam radiotherapy in cervical cancer: Chiang Mai University experience.

PubMed

Tharavichitkul, Ekkasit; Chakrabandhu, Somvilai; Wanwilairat, Somsak; Tippanya, Damrongsak; Nobnop, Wannapha; Pukanhaphan, Nantaka; Galalae, Razvan M; Chitapanarux, Imjai

2013-07-01

To evaluate the outcomes of image-guided brachytherapy combined with 3D conformal or intensity modulated external beam radiotherapy (3D CRT/IMRT) in cervical cancer at Chiang Mai University. From 2008 to 2011, forty-seven patients with locally advanced cervical cancer were enrolled in this study. All patients received high-technology (3D CRT/IMRT) whole pelvic radiotherapy with a total dose of 45-46 Gy plus image-guided High-Dose-Rate intracavitary brachytherapy 6.5-7 Gy × 4 fractions to a High-Risk Clinical Target Volume (HR-CTV) according to GEC-ESTRO recommendations. The dose parameters of the HR-CTV for bladder, rectum and sigmoid colon were recorded, as well as toxicity profiles. In addition, the endpoints for local control, disease-free, metastasis-free survival and overall survival were calculated. At the median follow-up time of 26 months, the local control, disease-free survival, and overall survival rates were 97.9%, 85.1%, and 93.6%, respectively. The mean dose of HR-CTV, bladder, rectum and sigmoid were 93.1, 88.2, 69.6, and 72 Gy, respectively. In terms of late toxicity, the incidence of grade 3-4 bladder and rectum morbidity was 2.1% and 2.1%, respectively. A combination of image-guided brachytherapy and IMRT/3D CRT showed very promising results of local control, disease-free survival, metastasis-free survival and overall survival rates. It also caused a low incidence of grade 3-4 toxicity in treated study patients. Copyright © 2013 Elsevier Inc. All rights reserved.

Fast CSF MRI for brain segmentation; Cross-validation by comparison with 3D T1-based brain segmentation methods

PubMed Central

de Bresser, Jeroen; Hendrikse, Jeroen; Siero, Jeroen C. W.; Petersen, Esben T.; De Vis, Jill B.

2018-01-01

Objective In previous work we have developed a fast sequence that focusses on cerebrospinal fluid (CSF) based on the long T2 of CSF. By processing the data obtained with this CSF MRI sequence, brain parenchymal volume (BPV) and intracranial volume (ICV) can be automatically obtained. The aim of this study was to assess the precision of the BPV and ICV measurements of the CSF MRI sequence and to validate the CSF MRI sequence by comparison with 3D T1-based brain segmentation methods. Materials and methods Ten healthy volunteers (2 females; median age 28 years) were scanned (3T MRI) twice with repositioning in between. The scan protocol consisted of a low resolution (LR) CSF sequence (0:57min), a high resolution (HR) CSF sequence (3:21min) and a 3D T1-weighted sequence (6:47min). Data of the HR 3D-T1-weighted images were downsampled to obtain LR T1-weighted images (reconstructed imaging time: 1:59 min). Data of the CSF MRI sequences was automatically segmented using in-house software. The 3D T1-weighted images were segmented using FSL (5.0), SPM12 and FreeSurfer (5.3.0). Results The mean absolute differences for BPV and ICV between the first and second scan for CSF LR (BPV/ICV: 12±9/7±4cc) and CSF HR (5±5/4±2cc) were comparable to FSL HR (9±11/19±23cc), FSL LR (7±4, 6±5cc), FreeSurfer HR (5±3/14±8cc), FreeSurfer LR (9±8, 12±10cc), and SPM HR (5±3/4±7cc), and SPM LR (5±4, 5±3cc). The correlation between the measured volumes of the CSF sequences and that measured by FSL, FreeSurfer and SPM HR and LR was very good (all Pearson’s correlation coefficients >0.83, R2 .67–.97). The results from the downsampled data and the high-resolution data were similar. Conclusion Both CSF MRI sequences have a precision comparable to, and a very good correlation with established 3D T1-based automated segmentations methods for the segmentation of BPV and ICV. However, the short imaging time of the fast CSF MRI sequence is superior to the 3D T1 sequence on which segmentation with established methods is performed. PMID:29672584

Fast CSF MRI for brain segmentation; Cross-validation by comparison with 3D T1-based brain segmentation methods.

PubMed

van der Kleij, Lisa A; de Bresser, Jeroen; Hendrikse, Jeroen; Siero, Jeroen C W; Petersen, Esben T; De Vis, Jill B

2018-01-01

In previous work we have developed a fast sequence that focusses on cerebrospinal fluid (CSF) based on the long T2 of CSF. By processing the data obtained with this CSF MRI sequence, brain parenchymal volume (BPV) and intracranial volume (ICV) can be automatically obtained. The aim of this study was to assess the precision of the BPV and ICV measurements of the CSF MRI sequence and to validate the CSF MRI sequence by comparison with 3D T1-based brain segmentation methods. Ten healthy volunteers (2 females; median age 28 years) were scanned (3T MRI) twice with repositioning in between. The scan protocol consisted of a low resolution (LR) CSF sequence (0:57min), a high resolution (HR) CSF sequence (3:21min) and a 3D T1-weighted sequence (6:47min). Data of the HR 3D-T1-weighted images were downsampled to obtain LR T1-weighted images (reconstructed imaging time: 1:59 min). Data of the CSF MRI sequences was automatically segmented using in-house software. The 3D T1-weighted images were segmented using FSL (5.0), SPM12 and FreeSurfer (5.3.0). The mean absolute differences for BPV and ICV between the first and second scan for CSF LR (BPV/ICV: 12±9/7±4cc) and CSF HR (5±5/4±2cc) were comparable to FSL HR (9±11/19±23cc), FSL LR (7±4, 6±5cc), FreeSurfer HR (5±3/14±8cc), FreeSurfer LR (9±8, 12±10cc), and SPM HR (5±3/4±7cc), and SPM LR (5±4, 5±3cc). The correlation between the measured volumes of the CSF sequences and that measured by FSL, FreeSurfer and SPM HR and LR was very good (all Pearson's correlation coefficients >0.83, R2 .67-.97). The results from the downsampled data and the high-resolution data were similar. Both CSF MRI sequences have a precision comparable to, and a very good correlation with established 3D T1-based automated segmentations methods for the segmentation of BPV and ICV. However, the short imaging time of the fast CSF MRI sequence is superior to the 3D T1 sequence on which segmentation with established methods is performed.

SU-E-J-226: Efficient Use of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) for Cervical-Cancer Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Damato, A; Bhagwat, M; Buzurovic, I

Purpose: To investigate image modality selection in an environment with limited access to interventional MRI for image-guided high-dose-rate cervical-cancer brachytherapy. Methods: Records of all cervical-cancer patients treated with brachytherapy between 1/2013 and 8/2014 were analyzed. Insertions were performed under CT guidance (CT group) or with >1 fraction under 3T MR guidance (MRI group; subMRI includes only patients who also had a CT-guided insertion). Differences between groups in clinical target volume (CTV), disease stage (I/II or III/IV), number of patients with or without interstitial needles, and CTV D90 were investigated. Statistical significance was evaluated with the Student T test and Fishermore » test (p <0.05). Results: 46 cervical-cancer patients were included (16 MRI [3 subMRI], 30 CT). CTV: overall, 55±53 cm3; MRI, 81±61 cm3; CT, 42±44 cm3 (p = 0.017). Stage: overall, 24 I/II and 22 III/IV; MRI, 3 I/II and 13 III/IV; CT, 21 I/II and 9 III/IV (p = 0.002). Use of needles: overall, 26 without and 20 with; MRI, 5 without and 11 with; CT, 21 without and 9 with (p = 0.015). CTV D90: overall, 82±5 Gy; MRI, 81±6 Gy; CT, 82±5 Gy (p = 0.78). SubMRI: CTV and D90 (as % of nominal fraction dose) were 23±6 cm3 and 124±3% for MRI-guided insertions and 21±5 cm3 (p = 0.83) and 106±12% (p = 0.15) for CT-guided insertions. Conclusion: Statistically significant differences in patient population indicate preferential use of MRI for patients with high-stage disease and large residual CTVs requiring the use of interstitial needles. CTV D90 was similar between groups, despite the difference in patient selection. For patients who underwent both CT and MRI insertions, a larger MR CTV D90 and similar CTVs between insertions were observed. While MRI is generally preferable to CT, MRI selection can be optimized in environments without a dedicated MRI brachytherapy suite. This work was partially funded by the NIH R21 CA167800 (PI: Viswanathan; aviswanathan@partners.org)« less

SU-F-T-36: Dosimetric Comparison of Point Based Vs. Target Based Prescription for Intracavitary Brachytherapy in Cancer of the Cervix

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ashenafi, M; McDonald, D; Peng, J

Purpose: Improved patient imaging used for planning the treatment of cervical cancer with Tandem and Ovoid (T&O) Intracavitary high-dose-rate brachytherapy (HDR) now allows for 3D delineation of target volumes and organs-at-risk. However, historical data relies on the conventional point A-based planning technique. A comparative dosimetric study was performed by generating both target-based (TBP) and point-based (PBP) plans for ten clinical patients. Methods: Treatment plans created using Elekta Oncentra v. 4.3 for ten consecutive cervical cancer patients were analyzed. All patients were treated with HDR using the Utrecht T&O applicator. Both CT and MRI imaging modalities were utilized to delineate clinicalmore » target volume (CTV) and organs-at-risk (rectum, sigmoid, bladder, and small bowel). Point A (left and right), vaginal mucosa, and ICRU rectum and bladder points were defined on CT. Two plans were generated for each patient using two prescription methods (PBP and TBP). 7Gy was prescribed to each point A for each PBP plan and to the target D90% for each TBP plan. Target V90%, V100%, and V200% were evaluated. In addition, D0.1cc and D2cc were analyzed for each organ-at-risk. Differences were assessed for statistical significance (p<0.05) by use of Student’s t-test. Results: Target coverage was comparable for both planning methods, with each method providing adequate target coverage. TBP showed lower absolute dose to the target volume than PBP (D90% = 7.0Gy vs. 7.4Gy, p=0.028), (V200% = 10.9cc vs. 12.8cc, p=0.014), (ALeft = 6.4Gy vs. 7Gy, p=0.009), and (ARight = 6.4Gy vs. 7Gy, p=0.013). TBP also showed a statistically significant reduction in bladder, rectum, small bowel, and sigmoid doses compared to PBP. There was no statistically significant difference in vaginal mucosa or ICRU-defined rectum and bladder dose. Conclusion: Target based prescription resulted in substantially lower dose to delineated organs-at-risk compared to point based prescription, while maintaining similar target coverage.« less

Comparative evaluation of two-dimensional radiography and three dimensional computed tomography based dose-volume parameters for high-dose-rate intracavitary brachytherapy of cervical cancer: a prospective study.

PubMed

Madan, Renu; Pathy, Sushmita; Subramani, Vellaiyan; Sharma, Seema; Mohanti, Bidhu Kalyan; Chander, Subhash; Thulkar, Sanjay; Kumar, Lalit; Dadhwal, Vatsla

2014-01-01

Dosimetric comparison of two dimensional (2D) radiography and three-dimensional computed tomography (3D-CT) based dose distributions with high-dose-rate (HDR) intracavitry radiotherapy (ICRT) for carcinoma cervix, in terms of target coverage and doses to bladder and rectum. Sixty four sessions of HDR ICRT were performed in 22 patients. External beam radiotherapy to pelvis at a dose of 50 Gray in 27 fractions followed by HDR ICRT, 21 Grays to point A in 3 sessions, one week apart was planned . All patients underwent 2D-orthogonal and 3D-CT simulation for each session. Treatment plans were generated using 2D-orthogonal images and dose prescription was made at point A. 3D plans were generated using 3D-CT images after delineating target volume and organs at risk. Comparative evaluation of 2D and 3D treatment planning was made for each session in terms of target coverage (dose received by 90%, 95% and 100% of the target volume: D90, D95 and D100 respectively) and doses to bladder and rectum: ICRU-38 bladder and rectum point dose in 2D planning and dose to 0.1cc, 1cc, 2cc, 5cc, and 10cc of bladder and rectum in 3D planning. Mean doses received by 100% and 90% of the target volume were 4.24 ± 0.63 and 4.9 ± 0.56 Gy respectively. Doses received by 0.1cc, 1cc and 2cc volume of bladder were 2.88 ± 0.72, 2.5 ± 0.65 and 2.2 ± 0.57 times more than the ICRU bladder reference point. Similarly, doses received by 0.1cc, 1cc and 2cc of rectum were 1.80 ± 0.5, 1.48 ± 0.41 and 1.35 ± 0.37 times higher than ICRU rectal reference point. Dosimetric comparative evaluation of 2D and 3D CT based treatment planning for the same brachytherapy session demonstrates underestimation of OAR doses and overestimation of target coverage in 2D treatment planning.

Respiratory gating based on internal electromagnetic motion monitoring during stereotactic liver radiation therapy: First results.

PubMed

Poulsen, Per Rugaard; Worm, Esben Schjødt; Hansen, Rune; Larsen, Lars Peter; Grau, Cai; Høyer, Morten

2015-01-01

Intrafraction motion may compromise the target dose in stereotactic body radiation therapy (SBRT) of tumors in the liver. Respiratory gating can improve the treatment delivery, but gating based on an external surrogate signal may be inaccurate. This is the first paper reporting on respiratory gating based on internal electromagnetic monitoring during liver SBRT. Two patients with solitary liver metastases were treated with respiratory-gated SBRT guided by three implanted electromagnetic transponders. The treatment was delivered in end-exhale with beam-on when the centroid of the three transponders deviated less than 3 mm [left-right (LR) and anterior-posterior (AP) directions] and 4mm [cranio-caudal (CC)] from the planned position. For each treatment fraction, log files were used to determine the transponder motion during beam-on in the actual gated treatments and in simulated treatments without gating. The motion was used to reconstruct the dose to the clinical target volume (CTV) with and without gating. The reduction in D95 (minimum dose to 95% of the CTV) relative to the plan was calculated for both treatment courses. With gating the maximum course mean (standard deviation) geometrical error in any direction was 1.2 mm (1.8 mm). Without gating the course mean error would mainly increase for Patient 1 [to -2.8 mm (1.6 mm) (LR), 7.1 mm (5.8 mm) (CC), -2.6 mm (2.8mm) (AP)] due to a large systematic cranial baseline drift at each fraction. The errors without gating increased only slightly for Patient 2. The reduction in CTV D95 was 0.5% (gating) and 12.1% (non-gating) for Patient 1 and 0.3% (gating) and 1.7% (non-gating) for Patient 2. The mean duty cycle was 55%. Respiratory gating based on internal electromagnetic motion monitoring was performed for two liver SBRT patients. The gating added robustness to the dose delivery and ensured a high CTV dose even in the presence of large intrafraction motion.

SU-F-T-27: A Comparative Case Study Among Four Modalities for the Superficial Treatment of Squamous Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ashenafi, M; Koch, N; Peng, J

Purpose: We performed a comparative planning study among High Dose Rate (HDR) brachytherapy, superficial electrons, Volume Modulated Arc Therapy (VMAT), and Helical IMRT (Tomotherapy) for squamous cell carcinoma of the abdominal wall with consideration for the underlining bowel. Methods: A 69-year old female presented with squamous cell carcinoma protruding 8mm beyond the anterior skin surface of the midabdomen was considered for treatment. The patient had a ventral hernia which resulted in the reduction of the abdominal wall thickness and the adjacent small bowel being the dose limiting structure. Four plans were generated using different treatment modalities: a) an enface electronmore » field (eMC, Eclipse v. 11), b) Tomotherapy (HI-Art II v.5.0.5), c) VMAT (Acuros, Eclipse v. 11), and d) HDR using a Freiburg applicator (Oncentra v. 4.3). The following plan objectives were used for all four plans: for the CTV target, V90% ≥90% (61.8Gy2/2).For the small bowel, D0.1cc < 56.2 Gy2/2 was a hard constraint and expressed as a percentage of the prescription for comparison to demonstrate the dose fall-off achieved among the modalities.For HDR, V200% <0.1cc was an additional constraint. Multiple dosimetric parameters, including those listed above, were compared among the four modalities. Results: The HDR plan showed comparable target coverage compared to the Tomotherapy plan and better coverage compared to the electron plan. Small bowel doses (D0.1cc) were lower in HDR plan compared to Tomotherapy, electron, & VMAT plans (88.8%, 89.6%, 90.9%, & 96.6%). Integral dose to the whole body (V5%) was much higher for HDR, VMAT, and Tomotherapy when compared to electron plan by factors of seven, eight, and ten, respectively. After reviewing all treatment modalities, the physician selected HDR owing to better control of the small bowel dose while maintaining adequate target coverage. Conclusion: This case study demonstrated HDR can successfully treat superficial lesions with superior sparing of underlying structures.« less

Dose to the Bladder Neck Is the Most Important Predictor for Acute and Late Toxicity After Low-Dose-Rate Prostate Brachytherapy: Implications for Establishing New Dose Constraints for Treatment Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hathout, Lara; Folkert, Michael R.; Kollmeier, Marisa A.

2014-10-01

Purpose: To identify an anatomic structure predictive for acute (AUT) and late (LUT) urinary toxicity in patients with prostate cancer treated with low-dose-rate brachytherapy (LDR) with or without external beam radiation therapy (EBRT). Methods and Materials: From July 2002 to January 2013, 927 patients with prostate cancer (median age, 66 years) underwent LDR brachytherapy with Iodine 125 (n=753) or Palladium 103 (n=174) as definitive treatment (n=478) and as a boost (n=449) followed by supplemental EBRT (median dose, 50.4 Gy). Structures contoured on the computed tomographic (CT) scan on day 0 after implantation included prostate, urethra, bladder, and the bladder neck, defined asmore » 5 mm around the urethra between the catheter balloon and the prostatic urethra. AUT and LUT were assessed with the Common Terminology Criteria for Adverse Events, version4. Clinical and dosimetric factors associated with AUT and LUT were analyzed with Cox regression and receiver operating characteristic analysis to calculate area under the receiver operator curve (ROC) (AUC). Results: Grade ≥2 AUT and grade ≥2 LUT occurred in 520 patients (56%) and 154 patients (20%), respectively. No grade 4 toxicities were observed. Bladder neck D2cc retained a significant association with AUT (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.03-1.04; P<.0001) and LUT (HR, 1.01; 95% CI, 1.00-1.03; P=.014) on multivariable analysis. In a comparison of bladder neck with the standard dosimetric variables by use of ROC analysis (prostate V100 >90%, D90 >100%, V150 >60%, urethra D20 >130%), bladder neck D2cc >50% was shown to have the strongest prognostic power for AUT (AUC, 0.697; P<.0001) and LUT (AUC, 0.620; P<.001). Conclusions: Bladder neck D2cc >50% was the strongest predictor for grade ≥2 AUT and LUT in patients treated with LDR brachytherapy. These data support inclusion of bladder neck constraints into brachytherapy planning to decrease urinary toxicity.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr; Udrescu, Corina; Department of Medical Physics, Centre Hospitalier Lyon Sud, Pierre Benite

Purpose: The aim of this study was to evaluate the contribution of an injection of hyaluronic acid (HA) between the rectum and the prostate for reducing the dose to the rectal wall in a hypofractionated irradiation for prostate cancer. Methods and Materials: In a phase 2 study, 10 cc of HA was injected between the rectum and prostate. For 16 patients, the same intensity modulated radiation therapy plan (62 Gy in 20 fractions) was optimized on 2 computed tomography scans: CT1 (before injection) and CT2 (after injection). Rectal parameters were compared: dose to 2.5 cc (D2.5), 5 cc (D5), 10more » cc (D10), 15 cc (D15), and 20 cc (D20) of rectal wall and volume of rectum covered by the 90% isodose line (V90), 80% (V80), 70% (V70), 60% (V60), and 50% (V50). Results: The mean V90, V80, V70, V60, and V50 values were reduced by 73.8% (P<.0001), 55.7% (P=.0003), 43.0% (P=.007), 34% (P=.002), and 25% (P=.036), respectively. The average values of D2.5, D5, D10, D15, and D20 were reduced by 8.5 Gy (P<.0001), 12.3 Gy (P<.0001), 8.4 Gy (P=.005), 3.7 Gy (P=.026), and 1.2 Gy (P=.25), respectively. Conclusions: The injection of HA significantly limited radiation doses to the rectal wall.« less

Technical aspects of the integration of three-dimensional treatment planning dose parameters (GEC-ESTRO Working Group) into pre-implant planning for LDR gynecological interstitial brachytherapy.

PubMed

Chi, A; Gao, M; Nguyen, N P; Albuquerque, K

2009-06-01

This study investigates the technical feasibility of pre-implant image-based treatment planning for LDR GYN interstitial brachytherapy(IB) based on the GEC-ESTRO guidelines. Initially, a virtual plan is generated based on the prescription dose and GEC-ESTRO defined OAR dose constraints with a pre-implant CT. After the actual implant, a regular diagnostic CT was obtained and fused with our pre-implant scan/initial treatment plan in our planning software. The Flexi-needle position changes, and treatment plan modifications were made if needed. Dose values were normalized to equivalent doses in 2 Gy fractions (LQED 2 Gy) derived from the linear-quadratic model with alpha/beta of 3 for late responding tissues and alpha/beta of 10 for early responding tissues. D(90) to the CTV, which was gross tumor (GTV) at the time of brachytherapy with a margin to count for microscopic disease, was 84.7 +/- 4.9% of the prescribed dose. The OAR doses were evaluated by D(2cc) (EBRT+IB). Mean D(2cc) values (LQED(2Gy)) for the rectum, bladder, sigmoid, and small bowel were the following: 63.7 +/- 8.4 Gy, 61.2 +/- 6.9 Gy, 48.0 +/- 3.5 Gy, and 49.9 +/- 4.2 Gy. This study confirms the feasibility of applying the GEC-ESTRO recommended dose parameters in pre-implant CT-based treatment planning in GYN IB. In the process, this pre-implant technique also demonstrates a good approximation of the target volume dose coverage, and doses to the OARs.

Exploratory Study of 4D Versus 3D Robust Optimization in Intensity-Modulated Proton Therapy for Lung Cancer

PubMed Central

Liu, Wei; Schild, Steven E.; Chang, Joe Y.; Liao, Zhongxing; Chang, Yu-Hui; Wen, Zhifei; Shen, Jiajian; Stoker, Joshua B.; Ding, Xiaoning; Hu, Yanle; Sahoo, Narayan; Herman, Michael G.; Vargas, Carlos; Keole, Sameer; Wong, William; Bues, Martin

2015-01-01

Background To compare the impact of uncertainties and interplay effect on 3D and 4D robustly optimized intensity-modulated proton therapy (IMPT) plans for lung cancer in an exploratory methodology study. Methods IMPT plans were created for 11 non-randomly selected non-small-cell lung cancer (NSCLC) cases: 3D robustly optimized plans on average CTs with internal gross tumor volume density overridden to irradiate internal target volume, and 4D robustly optimized plans on 4D CTs to irradiate clinical target volume (CTV). Regular fractionation (66 Gy[RBE] in 33 fractions) were considered. In 4D optimization, the CTV of individual phases received non-uniform doses to achieve a uniform cumulative dose. The root-mean-square-dose volume histograms (RVH) measured the sensitivity of the dose to uncertainties, and the areas under the RVH curve (AUCs) were used to evaluate plan robustness. Dose evaluation software modeled time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Dose-volume histogram indices comparing CTV coverage, homogeneity, and normal tissue sparing were evaluated using Wilcoxon signed-rank test. Results 4D robust optimization plans led to smaller AUC for CTV (14.26 vs. 18.61 (p=0.001), better CTV coverage (Gy[RBE]) [D95% CTV: 60.6 vs 55.2 (p=0.001)], and better CTV homogeneity [D5%–D95% CTV: 10.3 vs 17.7 (p=0.002)] in the face of uncertainties. With interplay effect considered, 4D robust optimization produced plans with better target coverage [D95% CTV: 64.5 vs 63.8 (p=0.0068)], comparable target homogeneity, and comparable normal tissue protection. The benefits from 4D robust optimization were most obvious for the 2 typical stage III lung cancer patients. Conclusions Our exploratory methodology study showed that, compared to 3D robust optimization, 4D robust optimization produced significantly more robust and interplay-effect-resistant plans for targets with comparable dose distributions for normal tissues. A further study with a larger and more realistic patient population is warranted to generalize the conclusions. PMID:26725727

Exploratory Study of 4D versus 3D Robust Optimization in Intensity Modulated Proton Therapy for Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Wei, E-mail: Liu.Wei@mayo.edu; Schild, Steven E.; Chang, Joe Y.

Purpose: The purpose of this study was to compare the impact of uncertainties and interplay on 3-dimensional (3D) and 4D robustly optimized intensity modulated proton therapy (IMPT) plans for lung cancer in an exploratory methodology study. Methods and Materials: IMPT plans were created for 11 nonrandomly selected non-small cell lung cancer (NSCLC) cases: 3D robustly optimized plans on average CTs with internal gross tumor volume density overridden to irradiate internal target volume, and 4D robustly optimized plans on 4D computed tomography (CT) to irradiate clinical target volume (CTV). Regular fractionation (66 Gy [relative biological effectiveness; RBE] in 33 fractions) was considered.more » In 4D optimization, the CTV of individual phases received nonuniform doses to achieve a uniform cumulative dose. The root-mean-square dose-volume histograms (RVH) measured the sensitivity of the dose to uncertainties, and the areas under the RVH curve (AUCs) were used to evaluate plan robustness. Dose evaluation software modeled time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Dose-volume histogram (DVH) indices comparing CTV coverage, homogeneity, and normal tissue sparing were evaluated using Wilcoxon signed rank test. Results: 4D robust optimization plans led to smaller AUC for CTV (14.26 vs 18.61, respectively; P=.001), better CTV coverage (Gy [RBE]) (D{sub 95%} CTV: 60.6 vs 55.2, respectively; P=.001), and better CTV homogeneity (D{sub 5%}-D{sub 95%} CTV: 10.3 vs 17.7, resspectively; P=.002) in the face of uncertainties. With interplay effect considered, 4D robust optimization produced plans with better target coverage (D{sub 95%} CTV: 64.5 vs 63.8, respectively; P=.0068), comparable target homogeneity, and comparable normal tissue protection. The benefits from 4D robust optimization were most obvious for the 2 typical stage III lung cancer patients. Conclusions: Our exploratory methodology study showed that, compared to 3D robust optimization, 4D robust optimization produced significantly more robust and interplay-effect-resistant plans for targets with comparable dose distributions for normal tissues. A further study with a larger and more realistic patient population is warranted to generalize the conclusions.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pötter, Richard; Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna; Federico, Mario

Purpose: To define, in the setting of cervical cancer, to what extent information from additional pretreatment magnetic resonance imaging (MRI) without the brachytherapy applicator improves conformity of CT-based high-risk clinical target volume (CTV{sub HR}) contours, compared with the MRI for various tumor stages (International Federation of Gynecology and Obstetrics [FIGO] stages I-IVA). Methods and Materials: The CTV{sub HR} was contoured in 39 patients with cervical cancer (FIGO stages I-IVA) (1) on CT images based on clinical information (CTV{sub HR}-CT{sub Clinical}) alone; and (2) using an additional MRI before brachytherapy, without the applicator (CTV{sub HR}-CT{sub pre-BT} {sub MRI}). The CT contours were compared withmore » reference contours on MRI with the applicator in place (CTV{sub HR}-MRI{sub ref}). Width, height, thickness, volumes, and topography were analyzed. Results: The CT-MRI{sub ref} differences hardly varied in stage I tumors (n=8). In limited-volume stage IIB and IIIB tumors (n=19), CTV{sub HR}-CT{sub pre-BT} {sub MRI}–MRI{sub ref} volume differences (2.6 cm{sup 3} [IIB], 7.3 cm{sup 3} [IIIB]) were superior to CTV{sub HR}-CT{sub Clinical}–MRI{sub ref} (11.8 cm{sup 3} [IIB], 22.9 cm{sup 3} [IIIB]), owing to significant improvement of height and width (P<.05). In advanced disease (n=12), improved agreement with MR volume, width, and height was achieved for CTV{sub HR}-CT{sub pre-BT} {sub MRI}. In 5 of 12 cases, MRI{sub ref} contours were partly missed on CT. Conclusions: Pre-BT MRI helps to define CTV{sub HR} before BT implantation appropriately, if only CT images with the applicator in place are available for BT planning. Significant improvement is achievable in limited-volume stage IIB and IIIB tumors. In more advanced disease (extensive IIB to IVA), improvement of conformity is possible but may be associated with geographic misses. Limited impact on precision of CTV{sub HR}-CT is expected in stage IB tumors.« less

WE-D-17A-03: Improvement of Accuracy of Spot-Scanning Proton Beam Delivery for Liver Tumor by Real-Time Tumor-Monitoring and Gating System: A Simulation Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsuura, T; Shimizu, S; Miyamoto, N

2014-06-15

Purpose: To improve the accuracy of spot-scanning proton beam delivery for target in motion, a real-time tumor-monitoring and gating system using fluoroscopy images was developed. This study investigates the efficacy of this method for treatment of liver tumors using simulation. Methods: Three-dimensional position of a fiducial marker inserted close to the tumor is calculated in real time and proton beam is gated according to the marker's distance from the planned position (Shirato, 2012). The efficient beam delivery is realized even for the irregular and sporadic motion signals, by employing the multiple-gated irradiations per operation cycle (Umezawa, 2012). For each ofmore » two breath-hold CTs (CTV=14.6cc, 63.1cc), dose distributions were calculated with internal margins corresponding to freebreathing (FB) and real-time gating (RG) with a 2-mm gating window. We applied 8 trajectories of liver tumor recorded during the treatment of RTRT in X-ray therapy and 6 initial timings. Dmax/Dmin in CTV, mean liver dose (MLD), and irradiation time to administer 3 Gy (RBE) dose were estimated assuming rigid motion of targets by using in-house simulation tools and VQA treatment planning system (Hitachi, Ltd., Tokyo). Results: Dmax/Dmin was degraded by less than 5% compared to the prescribed dose with all motion parameters for smaller CTV and less than 7% for larger CTV with one exception. Irradiation time showed only a modest increase if RG was used instead of FB; the average value over motion parameters was 113 (FB) and 138 s (RG) for smaller CTV and 120 (FB) and 207 s (RG) for larger CTV. In RG, it was within 5 min for all but one trajectory. MLD was markedly decreased by 14% and 5–6% for smaller and larger CTVs respectively, if RG was applied. Conclusions: Spot-scanning proton beam was shown to be delivered successfully to liver tumor without much lengthening of treatment time. This research was supported by the Cabinet Office, Government of Japan and the Japan Society for the Promotion of Science (JSPS) through the Funding Program for World-Leading Innovative R and D on Science and Technology (FIRST Program), initiated by the Council for Science and Technology Policy (CSTP)« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swanick, Cameron W.; Castle, Katherine O.; Vedam, Sastry

Purpose: We prospectively compared computed tomography (CT)– and magnetic resonance imaging (MRI)–based high-risk clinical target volume (HR-CTV) contours at the time of brachytherapy for cervical cancer in an effort to identify patients who might benefit most from MRI-based planning. Methods and Materials: Thirty-seven patients who had undergone a pretreatment diagnostic MRI scan were included in the analysis. We delineated the HR-CTV on the brachytherapy CT and brachytherapy MRI scans independently for each patient. We then calculated the absolute volumes for each HR-CTV and the Dice coefficient of similarity (DC, a measure of spatial agreement) for the HR-CTV contours. We identifiedmore » the clinical and tumor factors associated with (1) a discrepancy in volume between the CT HR-CTV and MRI HR-CTV contours; and (2) DC. The mean values were compared using 1-way analysis of variance or paired or unpaired t tests, as appropriate. Simple and multivariable linear regression analyses were used to model the effects of covariates on the outcomes. Results: Patients with International Federation of Gynecology and Obstetrics stage IB to IVA cervical cancer were treated with intracavitary brachytherapy using tandem and ovoid (n=33) or tandem and cylinder (n=4) applicators. The mean CT HR-CTV volume (44.1 cm{sup 3}) was larger than the mean MRI HR-CTV volume (35.1 cm{sup 3}; P<.0001, paired t test). On multivariable analysis, a higher body mass index (BMI) and tumor size ≥5 cm with parametrial invasion on the MRI scan at diagnosis were associated with an increased discrepancy in volume between the HR-CTV contours (P<.02 for both). In addition, the spatial agreement (as measured by DC) between the HR-CTV contours decreased with an increasing BMI (P=.013). Conclusions: We recommend MRI-based brachytherapy planning for patients with tumors >5 cm and parametrial invasion on MRI at diagnosis and for those with a high BMI.« less

Search for the rare decays J / ψ → D 0 e + e − + c . c . and ψ ( 3686 ) → D 0 e + e − + c . c .

DOE PAGES

Ablikim, M.; Achasov, M. N.; Ahmed, S.; ...

2017-12-01

Using the data samples of (1310.6 ± 7.2) × 10 6 J / ψ events and (448.1 ± 2.9) × 106 (3686) events collected with the BESIII detector, we search for the rare decays J / ψ → D 0e +e - + c.c. and (3686) → D 0e +e - + c.c.. No significant signals are observed and the corresponding upper limits on the branching fractions at the 90% confidence level are determined to be B( J /more » ψ → D0e+e- + c.c.) < 8.5 × 10 -8 and B( (3686) → D0e+e- + c.c.) < 1.4 × 10 -7, respectively. Our limit on B( J / ψ → D 0e +e - + c.c.) is more stringent by two orders of magnitude than the previous results, and the B( (3686) → D 0e +e - + c.c.) is measured for the first time. « less

Search for the rare decays J / ψ → D 0 e + e − + c . c . and ψ ( 3686 ) → D 0 e + e − + c . c .

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ablikim, M.; Achasov, M. N.; Ahmed, S.

Using the data samples of (1310.6 ± 7.2) × 10 6 J / ψ events and (448.1 ± 2.9) × 106 (3686) events collected with the BESIII detector, we search for the rare decays J / ψ → D 0e +e - + c.c. and (3686) → D 0e +e - + c.c.. No significant signals are observed and the corresponding upper limits on the branching fractions at the 90% confidence level are determined to be B( J /more » ψ → D0e+e- + c.c.) < 8.5 × 10 -8 and B( (3686) → D0e+e- + c.c.) < 1.4 × 10 -7, respectively. Our limit on B( J / ψ → D 0e +e - + c.c.) is more stringent by two orders of magnitude than the previous results, and the B( (3686) → D 0e +e - + c.c.) is measured for the first time. « less

SU-F-P-46: Comparative Study Between Two Normalization Prescriptions for Accelerated Partial Breast Irradiation: A Dosimetric Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agarwal, P; Sharma, D; Gandhi, A

2016-06-15

Purpose: To compare the Accelerated Partial Breast Irradiation (APBI) plan with the normalized basal dose points and 5mm box prescription. Methods: Five patients of APBI were planned twice in Oncentra Master planning TPS (Version 4.3) using TG-43 algorithm. The number of catheters for all the patients was 10 to 16 and implant plane 2 to 3. For planning all catheters were reconstructed. Source loading was done as per HR-CTV contoured. The HR-CTV volume range was from 75cc to 182cc. Plans were normalized in two methods. First all plans were normalized on Basal dose points (PlanA) and second all the planmore » were normalized on 5mm box (PlanB). The prescription dose (PD) was 35Gy in 10 fractions. All the plans were completely based on normalization and without optimization. Plan evaluation was based on certain parameters coverage Index (CI), dose homogeneity index (DHI), conformity index (COIN), over dose volume index (OI). Results: The average and median of CI for planA was 0.835 and 0.8154, for planB 0.82 and 0.799 respectively. The median and average of DHI for planA was 0.66 and 0.6062, for planB 0.67 and 0.62 respectively. The range of COIN for planA and planB was from 0.58 to 0.65 respectively. The range of OI was from 0.083 to 0.169 for planA and planB. The treatment time in planA was in average 1.13 times more than planB as V150% of HR-CTV in planA was 4–6% more. The ipsilateral lung was getting 30% of PD which was 0.6% to 3.5%. Conclusion: Treatment Planning should be individualized based on implants characteristics. Planning with prescription to basal dose points should be preferred to 5mm box prescription, in order to achieve better DHI and less treatment time.« less

TH-CD-202-12: Online Inter-Beam Replanning Based On Real-Time Dose Reconstruction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kamerling, CP; Fast, MF; Ziegenhein, P

Purpose: This work provides a proof-of-concept study for online replanning during treatment delivery for step-and-shoot prostate SBRT, based on real-time dose reconstruction. Online replanning is expected to improve the trade-off between target coverage and organ-at-risk dose in the presence of intra-fractional motion. Methods: We have implemented an online replanning workflow on top of our previously reported real-time dose reconstruction software which connects to an Elekta research linac. The treatment planning system DynaPlan was extended to (1) re-optimize and sequence treatment plans (in clockwise beam order) before each beam, based on actual delivered dose, in a timeframe limited by the gantrymore » rotation between subsequent beams, and (2) send the respective segments to the delivery control software DynaTrack which starts/continues treatment immediately.To investigate the impact of a reduced safety margin, we have created and delivered (on a linac emulator) a conventional CTV+5/3mm (I) and a reduced CTV+1mm margin (II) treatment plan for a prostate patient. We have assessed CTV coverage with and without inter-beam replanning, all exposed to a gradual target shift of 0–5mm in posterior and inferior direction from start until the end of delivery. Results: For the reconstructed conventional plan (I), D98 for CTV was 100% of D98 of the planned dose. For the reconstructed margin-reduced plan (II), D98 for CTV was 95% of the planned D98 without replanning, but could be recovered to 99% by replanning for each beam. Plan (II) with replanning resulted in a decrease for bladder V90% by 88% and an increase to rectum V90% by 9% compared to the conventional plan (I). Dose calculation/accumulation was performed in <15ms per MLC aperture, replanning in <15s per beam. Conclusion: We have shown that online inter-beam replanning is technically feasible and potentially allows for a margin reduction. Future investigation considering motion-robust replanning optimization parameters is in progress. We acknowledge support of the MLC research from Elekta AB. This work is supported by Cancer Research UK under Programme C33589/A19908. Research at ICR is also supported by Cancer Research UK under Programme C33589/A19727 and NHS funding to the NIHR Biomedical Research Centre at RMH and ICR.« less

Neuropsychological Functioning in Adolescents and Young Adults at Genetic Risk for Schizophrenia and Affective Psychoses: Results from the Harvard and Hillside Adolescent High Risk Studies

PubMed Central

Seidman, Larry J.; Giuliano, Anthony J.; Smith, Christopher W.; Stone, William S.; Glatt, Stephen J.; Meyer, Eric; Faraone, Stephen V.; Tsuang, Ming T.; Cornblatt, Barbara

2006-01-01

Siblings and offspring of persons with schizophrenia carry elevated genetic risk for the illness and manifest attentional and memory impairments. Because less is known about other neuropsychological functions and their specificity in adolescents, we conducted a genetic high-risk (HR) study of schizophrenia (HR-SCZ) and affective psychosis (HR-AFF). Participants (ages 12–25) were from the Harvard Adolescent High-Risk and Hillside Family studies, including 73 HR-SCZ, 18 HR-AFF, and 84 community controls (CCs) recruited in metropolitan Boston and New York. Groups were compared on overall neurocognitive functioning, 6 domains, and 13 test scores, controlling for age, parental education, and correlated data within families. The HR-SCZ group was significantly impaired overall, while the HR-AFF group demonstrated a trend toward overall impairment. HR-SCZ subjects showed significantly lower Verbal Ability (d = .73) and Executive Functioning/Working Memory (d = .47) than CCs. HR-AFF subjects showed reduced Verbal Ability (d = .64) compared to CCs. Excluding 12 CCs with a parental history of depression (without psychosis) led to larger differences between HR and CC groups across domains. Moreover, HR-SCZ and CC group differences in Verbal Memory (d = .39) and Visual-Spatial (d = .34) became statistically significant. There were no significant differences between HR-SCZ and HR-AFF groups. Data support a modest neuropsychological deficit in persons at genetic HR for psychosis, with a broader range of deficits in HR-SCZ. Future work should assess the relationship of neurocognition to adaptive functioning and possible onset of psychosis in HR samples. Ascertainment criteria for controls may markedly influence results and interpretation of group differences. PMID:16707777

MO-C-17A-10: Comparison of Dose Deformable Accumulation by Using Parallel and Serial Approaches

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Z; Li, M; Wong, J

Purpose: The uncertainty of dose accumulation over multiple CT datasets with deformable fusion may have significant impact on clinical decisions. In this study, we investigate the difference of two dose summation approaches involving deformable fusion. Methods: Five patients, four external beam and one brachytherapy(BT), were chosen for the study. The BT patient was treated with CT-based HDR. The CT image sets acquired in the imageguidance process (8-11 CTs/patient) were used to determine the dose delivered to the four external beam patients. (prostate, pelvis, lung and head and neck). For the HDR patient (cervix), five CT image sets and the correspondingmore » BT plans were used. In total 44 CT datasets and RT dose/plans were imported into the image fusion software MiM (6.0.4) for analysis.For each of the five clinical cases, the dose from each fraction was accumulated into the primary CT dataset by using both Parallel and Serial approaches. The dose-volume histogram (DVH) for CTV and selected organs-at-risks (OAR) were generated. The D95(CTV), OAR(mean) and OAR(max) for the four external beam cases the D90(CTV), and the max dose to bladder and rectum for the BT case were compared. Results: For the four external beam patients, the difference in D95(CTV) were <1.2% PD between the parallel and the serial approaches. The differences of the OAR(mean) and the OAR(max ) range from 0 to 3.7% and <1% PD respectively. For the HDR patient, the dose difference for D90 is 11% PD while that of the max dose to bladder and rectum were 11.5% and 23.3% respectively. Conclusion: For external beam treatments, the parallel and serial approaches have <5% difference probably because tumor volume and OAR have less changes from fraction to fraction. For the brachytherapy case, >10% dose difference between the two approaches was observed as significant volume changes of tumor and OAR were observed among treatment fractions.« less

TU-H-BRC-08: Use and Validation of Flexible 3D Printed Tissue Compensators for Post-Mastectomy Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Craft, D; Kry, S; Salehpour, M

Purpose: Patient-specific tissue equivalent compensators can be used for post-mastectomy radiation therapy (PMRT) to achieve homogenous dose distributions with single-field treatments. However, current fabrication methods are time consuming and expensive. 3D-printing technology could overcome these limitations. The purposes of this study were to [1] evaluate materials for 3D-printed compensators [2] design and print a compensator to achieve a uniform thickness to a clinical target volume (CTV), and [3] demonstrate that a single-field electron compensator plan is a clinically feasible treatment option for PMRT. Methods: Blocks were printed with three materials; print accuracy, density, Hounsfield units (HU), and percent depth dosesmore » (PDD) were evaluated. For a CT scan of an anthropomorphic phantom, we used a ray-tracing method to design a compensator that achieved uniform thickness from compensator surface to CTV. The compensator was printed with flexible tissue equivalent material whose physical and radiological properties were most similar to soft tissue. A single-field electron compensator plan was designed and compared with two standard-of-care techniques. The compensator plan was validated with thermoluminescent dosimeter (TLD) measurements. Results: We identified an appropriate material for 3D-printed compensators that had high print accuracy (99.6%) and was similar to soft tissue; density was 1.04, HU was - 45 ± 43, and PDD curves agreed with clinical curves within 3 mm. We designed and printed a compensator that conformed well to the phantom surface and created a uniform thickness to the CTV. In-house fabrication was simple and inexpensive (<$75). Compared with the two standard plans, the compensator plan resulted in overall more homogeneous dose distributions and performed similarly in terms of lung/heart doses and 90% isodose coverage of the CTV. TLD measurements agreed well with planned doses (within 5 %). Conclusions: We have demonstrated that 3D-printed compensators make single-field electron therapy a clinically feasible treatment option for PMRT.« less

TH-A-BRF-04: Intra-Fraction Motion Characterization for Early Stage Rectal Cancer Using Cine-MRI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kleijnen, J; Asselen, B; Burbach, M

2014-06-15

Purpose: To investigate the intra-fraction motion in patients with early stage rectal cancer using cine-MRI. Methods: Sixteen patient diagnosed with early stage rectal cancer underwent 1.5 T MR imaging prior to each treatment fraction of their short course radiotherapy (n=76). During each scan session, three 2D sagittal cine-MRIs were performed: at the beginning (Start), after 9:30 minutes (Mid), and after 18 minutes (End). Each cine-MRI has a duration of one minute at 2Hz temporal resolution, resulting in a total of 3:48 hours of cine-MRI. Additionally, standard T2-weighted (T2w) imaging was performed. Clinical target volume (CTV) an tumor (GTV) were delineatedmore » on the T2w scan and transferred to the first time-point of each cine-MRI scan. Within each cine-MRI, the first frame was registered to the remaining frames of the scan, using a non-rigid B-spline registration. To investigate potential drifts, a similar registration was performed between the first frame of the Start and End scans.To evaluate the motion, the distances by which the edge pixels of the delineations move in anterior-posterior (AP) and cranial-caudal (CC) direction, were determined using the deformation field of the registrations. The distance which incorporated 95% of these edge pixels (dist95%) was determined within each cine-MRI, and between Start- End scans, respectively. Results: Within a cine-MRI, we observed an average dist95% for the CTV of 1.3mm/1.5mm (SD=0.7mm/0.6mm) and for the GTV of 1.2mm/1.5mm (SD=0.8mm/0.9mm), in respectively AP/CC. For the CTV motion between the Start and End scan, an average dist95% of 5.5mm/5.3mm (SD=3.1mm/2.5mm) was found, in respectively AP/CC. For the GTV motion, an average dist95% of 3.6mm/3.9mm (SD=2.2mm/2.5mm) was found in AP/CC, respectively. Conclusion: Although intra-fraction motion within a one minute cine-MRI is limited, substantial intra-fraction motion was observed within the 18 minute time period between the Start and End cine-MRI.« less

SU-E-T-527: Is CTV-Based Robust Optimized IMPT in Non-Small-Cell Lung Cancer Robust Against Respiratory Motion?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anetai, Y; Mizuno, H; Sumida, I

2015-06-15

Purpose: To determine which proton planning technique on average-CT is more vulnerable to respiratory motion induced density changes and interplay effect among (a) IMPT of CTV-based minimax robust optimization with 5mm set-up error considered, (b, c) IMPT/SFUD of 5mm-expanded PTV optimization. Methods: Three planning techniques were optimized in Raystation with a prescription of 60/25 (Gy/fractions) and almost the same OAR constraints/objectives for each of 10 NSCLC patients. 4D dose without/with interplay effect was recalculated on eight 4D-CT phases and accumulated after deforming the dose of each phase to a reference (exhalation phase). The change of D98% of each CTV causedmore » by density changes and interplay was determined. In addition, evaluation of the DVH information vector (D99%, D98%, D95%, Dave, D50%, D2%, D1%) which compares the whole DVH by η score = (cosine similarity × Pearson correlation coefficient − 0.9) × 1000 quantified the degree of DVH change: score below 100 indicates changed DVH. Results: Three 3D plans of each technique satisfied our clinical goals. D98% shift mean±SD (Gy) due to density changes was largest in (c): −0.78±1.1 while (a): −0.11±0.65 and (b): − 0.59±0.93. Also the shift due to interplay effect most was (c): −.54±0.70 whereas (a): −0.25±0.93 and (b): −0.12±0.13. Moreover lowest η score caused by density change was also (c): 69, while (a) and (b) kept around 90. η score also indicated less effect of interplay than density changes. Note that generally the changed DVH were still acceptable clinically. Paired T-tests showed a significantly smaller density change effect in (a) (p<0.05) than in (b) or (c) and no significant difference in interplay effect. Conclusion: CTV-based robust optimized IMPT was more robust against respiratory motion induced density changes than PTV-based IMPT and SFUD. The interplay effect was smaller than the effect of density changes and similar among the three techniques. The JSPS Core-to-Core Program (No. 23003), Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research (No. 23390300), Grant-in-Aid for Young Scientists (B) (No. 21791194) and Grant-in-Aid for Cancer Research (H22-3rd Term Cancer Control-General-043)« less

[CT guidance 125I seed implantation for pelvic recurrent rectal cancer assisted by 3D printing individual non-coplanar template].

PubMed

Wang, H; Wang, J J; Jiang, Y L; Tian, S Q; Ji, Z; Guo, F X; Sun, H T; Fan, J H; Xu, Y P

2016-12-20

Objective: To analyze the difference of dosimetric parameters between pre-plan and post-plan of 125 I radioactive seed implantation assisted by 3D printing individual non-coplanar template (3D printing template) for locally recurrent rectal cancer (LRRC). Methods: From February 2016 to April 2016, a total of 10 patients with locally recurrent rectal cancer received 125 I seeds implantation under CT guidance assisted by 3D printing template in Department of Radiation Oncology, Peking University Third Hospital.Each patient underwent CT simulation, three-dimentional treatment planning pre-implantation, 3D printing template design, radioactive seed implantation assisted by 3D printing template and dosimetric verification post implantation. The median activity of seed was 0.63 mCi (0.58 to 0.7 mCi) (2.15- 2.59×10 7 Bq), and the median number of seeds was 80 (19 to 192). D 90 , D 100 , V 100 , V 150 , CI, EI, HI, D 5cc , D 2cc of bladder and bowel of pre-plan and post-plan were calculated, respectively.Paired t test was used to evaluate the difference of dosimetric parameters between pre-plan and post-plan. Results: The median D 90 of pre-plan and post-plan were 13 761.0 and 12 798.8 cGy, respectively.The median D 100 of pre-plan and post-plan were 5 293.6 and 5 397.9 cGy, respectively.The median V 100 of pre-plan and post-plan were 90.0% and 90.0%, respectively.The median V 150 of pre-plan and post-plan were 63.8% and 62.4%, respectively.The median CI of pre-plan and post-plan were 0.73 and 0.67.The median EI of pre-plan and post-plan were 0.22 and 0.30, respectively. The median HI of pre-plan and post-plan were 0.29 and 0.31.The median bladder D 2cc of pre-plan and post-plan were 3 088.8 and 4 240.4 cGy, respectively.The median bowel D 2cc of pre-plan and post-plan were 7 051.6 and 7 903.9 cGy, respectively. Conclusions: 3D printing template might be helpful for locally recurrent rectal cancer patients who received 125 I radioactive seed implantation assisted by 3D printing individual template.Seed implantation might have more chances to achieve prescription dose and dose limitation of organs at risk of pre-plan, which is important for precise implantation and quality control.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loupot, S; Han, T; Salehpour, M

Purpose: To quantify the difference in dose to PTV-EVAL and OARs (skin and rib) as calculated by (TG43) and heterogeneous calculations (CCC). Methods: 25 patient plans (5 Contura and 20 SAVI) were selected for analysis. Clinical dose distributions were computed with a commercially available treatment planning algorithm (TG43-D-(w,w)) and then recomputed with a pre-clinical collapsed cone convolution algorithm (CCCD-( m,m)). PTV-EVAL coverage (V90%, V95%), and rib and skin maximum dose were compared via percent difference. Differences in dose to normal tissue (V150cc, V200cc of PTV-EVAL) were also compared. Changes in coverage and maximum dose to organs at risk are reportedmore » in percent change, (100*(TG43 − CCC) / TG43)), and changes in maximum dose to normal tissue are absolute change in cc (TG43 − CCC). Results: Mean differences in V90, V95, V150, and V200 for the SAVI cases were −0.2%, −0.4%, −0.03cc, and −0.14cc, respectively, with maximum differences of −0.78%, −1.7%, 1.28cc, and 1.01cc, respectively. Mean differences in the 0.1cc dose to the rib and skin were −1.4% and −0.22%, respectively, with maximum differences of −4.5% and 16%, respectively. Mean differences in V90, V95, V150, and V200 for the Contura cases were −1.2%, −2.1%, −1.8cc, and −0.59cc, respectively, with maximum differences of −2.0%, −3.16%, −2.9cc, and −0.76cc, respectively. Mean differences in the 0.1cc dose to the rib and skin were −2.6% and −3.9%, respectively, with maximum differences of −3.2% and −5.7%, respectively. Conclusion: The effects of translating clinical knowledge based on D-(w,w) to plans reported in D-(m,m) are minimal (2% or less) on average, but vary based on the type and placement of the device, source, and heterogeneity information.« less

Citrus tristeza virus-based RNAi in citrus plants induces gene silencing in Diaphorina citri, a phloem-sap sucking insect vector of citrus greening disease (Huanglongbing).

PubMed

Hajeri, Subhas; Killiny, Nabil; El-Mohtar, Choaa; Dawson, William O; Gowda, Siddarame

2014-04-20

A transient expression vector based on Citrus tristeza virus (CTV) is unusually stable. Because of its stability it is being considered for use in the field to control Huanglongbing (HLB), which is caused by Candidatus Liberibacter asiaticus (CLas) and vectored by Asian citrus psyllid, Diaphorina citri. In the absence of effective control strategies for CLas, emphasis has been on control of D. citri. Coincident cohabitation in phloem tissue by CLas, D. citri and CTV was exploited to develop a novel method to mitigate HLB through RNA interference (RNAi). Since CTV has three RNA silencing suppressors, it was not known if CTV-based vector could induce RNAi in citrus. Yet, expression of sequences targeting citrus phytoene desaturase gene by CTV-RNAi resulted in photo-bleaching phenotype. CTV-RNAi vector, engineered with truncated abnormal wing disc (Awd) gene of D. citri, induced altered Awd expression when silencing triggers ingested by feeding D. citri nymphs. Decreased Awd in nymphs resulted in malformed-wing phenotype in adults and increased adult mortality. This impaired ability of D. citri to fly would potentially limit the successful vectoring of CLas bacteria between citrus trees in the grove. CTV-RNAi vector would be relevant for fast-track screening of candidate sequences for RNAi-mediated pest control. Copyright © 2014. Published by Elsevier B.V.

SU-F-J-148: A Collapsed Cone Algorithm Can Be Used for Quality Assurance for Monaco Treatment Plans for the MR-Linac

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hackett, S; Asselen, B van; Wolthaus, J

2016-06-15

Purpose: Treatment plans for the MR-linac, calculated in Monaco v5.19, include direct simulation of the effects of the 1.5T B{sub 0}-field. We tested the feasibility of using a collapsed-cone (CC) algorithm in Oncentra, which does not account for effects of the B{sub 0}-field, as a fast online, independent 3D check of dose calculations. Methods: Treatment plans for six patients were generated in Monaco with a 6 MV FFF beam and the B{sub 0}-field. All plans were recalculated with a CC model of the same beam. Plans for the same patients were also generated in Monaco without the B{sub 0}-field. Themore » mean dose (Dmean) and doses to 10% (D10%) and 90% (D90%) of the volume were determined, as percentages of the prescribed dose, for target volumes and OARs in each calculated dose distribution. Student’s t-tests between paired parameters from Monaco plans and corresponding CC calculations were performed. Results: Figure 1 shows an example of the difference between dose distributions calculated in Monaco, with the B{sub 0}-field, and the CC algorithm. Figure 2 shows distributions of (absolute) difference between parameters for Monaco plans, with the B{sub 0}-field, and CC calculations. The Dmean and D90% values for the CTVs and PTVs were significantly different, but differences in dose distributions arose predominantly at the edges of the target volumes. Inclusion of the B{sub 0}-field had little effect on agreement of the Dmean values, as illustrated by Figure 3, nor on agreement of the D10% and D90% values. Conclusion: Dose distributions recalculated with a CC algorithm show good agreement with those calculated with Monaco, for plans both with and without the B{sub 0}-field, indicating that the CC algorithm could be used to check online treatment planning for the MRlinac. Agreement for a wider range of treatment sites, and the feasibility of using the γ-test as a simple pass/fail criterion, will be investigated.« less

Response of shortgrass plains vegetation to gamma radiation. I. Chronic irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fraley, L. Jr.; Whicker, F.W.

1973-12-01

Native shortgrass plains vegetation was exposed to chronic gamma radiation with exposure rates varying from 0.01 to 650 R/hr starting in April 1969. The dominant species in the plant community was Bouteloua gracilis (blue grama). Density and frequency were recorded and these data were converted into community indices of coefficient of community (CC) and diversity (D). The results indicated that the shortgrass vegetation was very resistant to ionizing radiation. 50% effects of CC and D resulted from exposure of 15 and 12 R/hr, respectively and had not significantly decreased further by June 1972. Community changes took place within constant CCmore » and D values that resulted in the development of new communities and indicated a lack of sensitivity of these parameters for measuring community change and stability. One of the most resistant species was Lepidium densiflorum which became dominant at exposure rates of 12 to 28 R/hr. L. densiflorum was able to germinate, develop, and complete seed set at exposure rates greater than 28 R/hr. (auth)« less

Response of shortgrass Plains vegetation to chronic and seasonally administered gamma radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fraley, Jr., Leslie

1971-08-01

In order to determine the effect of radiation on the structure of native shortgrass plains vegetation, an 8750 Ci 137Cs source was installed on the Central Plains Experimental Range near Nunn, Colorado; The experimental area was divided into 6 treatment sectors, a control, 2 sectors for chronic exposure (irradiation initiated April 1969 and continuing as of August 1971), and one each for spring, summer and late fall seasonal semi-acute (30 day), exposures which were administered during April, July and December, 1969, respectively. Community structure was measured by coefficient of community and diversity index. Yield was determined by clipping plots inmore » September 1970 and visual estimates in September 1969 and 1970 for the grass-sedge component of the vegetation. Individual species sensitivity was determined by density data recorded in April, June and September of 1969 and 1970 and by a phenological index recorded at weekly intervals during the 1969 and 1970 growing seasons. The response of the vegetation was similar whether determined by coefficient of community or diversity with diversity being a more sensitive measure of effects. In the chronically exposed sectors, the exposure rate which resulted in a 50 per cent reduction in these 2 parameters (CC50 or D50) was still decreasing the second growing season and was approximately 18 R/hr for the CC50 as of June 1970 and 10 R/hr for the D50 as of September 1970. For the seasonally exposed sectors, the late fall period (December, 1969) was the most sensitive, summer (July, 1969) the least sensitive and spring (April, 1969) intermediate with CC50 and D50 values of 195 and 90, 240 and 222, and 120 and 74 R/hr for the spring, summer and late fall exposed sectors, respectively. Yield and density data indicated a rapid revegetation of the spring and summer exposed sectors during 1970 as a result of an influx of invader species such as Salsola kali tenuifolia, Chenopodium leptophyllum and Lepidium densiflorum and the reappearance of perennials with underground perennating organs such as Lygodesmia juncea, Gaura coccinea and Oenothera coronopifolia. The most sensitive indicator of radiation damage was the phenological index with a chronic exposure rate of 1 R/hr delaying the development of Tradescantia occidentalis and Opuntia polyacantha. The shortgrass plains vegetation appears to be one of the most resistant community types studied to date with semi-acute exposures of 45 to 75 kR necessary to decrease diversity to 50 per cent of the control value.« less

Prostate volume changes during permanent seed brachytherapy: an analysis of intra-operative variations, predictive factors and clinical implication.

PubMed

Chira, Ciprian; Delouya, Guila; Larrivée, Sandra; Carrier, Jean-Francois; Taussky, Daniel

2013-07-09

To determine prostate volume (Pvol) changes at 3 different time points during the course of I¹²⁵ permanent seed brachytherapy (PB). To assess the impact of these changes on acute urinary retention (AUR) and dosimetric outcome. We analyzed 149 hormone-naïve patients. Measurements of the prostate volume were done using three-dimensional transrectal ultrasound (3D-TRUS) in the operating room before insertion of any needle (V1), after the insertion of 2 fixation needles with a harpoon (V2) and upon completion of the implant (V3). The quality of the implant was analyzed with the D90 (minimum dose in Grays received by 90% of the prostate volume) at day 30. Mean baseline prostate volume (V1) was 37.4 ± 9.6 cc. A volume increase of >5% was seen in 51% between V1-V2 (mean = 2.5 cc, p < 0.01), in 42% between V2-V3 (mean = 1.9 cc, p < 0.01) and in 71% between V1-V3 (mean = 4.5 cc, p < 0.01). Pvol changes caused by insertion of the fixation needles were not statistically different than those caused by the implant itself (p = 0.23).In multivariate linear regression analysis, baseline Pvol is predictive of Pvol changes between V2 and V1 and V3 and V1 but not between V3 and V2. The extent of prostate swelling had an influence on D90. An increase of 10% in prostate volume between V1 and V2 results in an increase of D90 at Day 30 by 11.7%. Baseline Pvol (V1) was the only predictor of the duration of urinary retention in both univariate and multivariate (p = 0.04) regression analysis. A large part of intraoperative swelling occurs already after the insertion of the fixation needles. This early prostate swelling predicts for D90 but not for AUR.

SU-C-17A-05: Quantification of Intra-Fraction Motion of Breast Tumors Using Cine-MRI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heijst, T van; Philippens, M; Bongard, D van den

2014-06-01

Purpose: Magnetic resonance imaging (MRI) enables direct characterization of intra-fraction motion ofbreast tumors, due to high softtissue contrast and geometric accuracy. The purpose is to analyzethis motion in early-stage breast-cancer patients using pre-operative supine cine-MRI. Methods: MRI was performed in 12 female early-stage breast-cancer patients on a 1.5-T Ingenia (Philips)wide-bore scanner in supine radiotherapy (RT) position, prior to breast-conserving surgery. Twotwodimensional (2D) T2-weighted balanced fast-field echo (cine-MRI) sequences were added tothe RT protocol, oriented through the tumor. They were alternately acquired in the transverse andsagittal planes, every 0.3 s during 1 min. A radiation oncologist delineated gross target volumes(GTVs) onmore » 3D contrast-enhanced MRI. Clinical target volumes (CTV = GTV + 15 mm isotropic)were generated and transferred onto the fifth time-slice of the time-series, to which subsequents lices were registered using a non-rigid Bspline algorithm; delineations were transformed accordingly. To evaluate intra-fraction CTV motion, deformation fields between the transformed delineations were derived to acquire the distance ensuring 95% surface coverage during scanning(P95%), for all in-plane directions: anteriorposterior (AP), left-right (LR), and caudal-cranial(CC). Information on LR was derived from transverse scans, CC from sagittal scans, AP fromboth sets. Results: Time-series with registration errors - induced by motion artifacts - were excluded by visual inspection. For our analysis, 11 transverse, and 8 sagittal time-series were taken into account. Themedian P95% calculated in AP (19 series), CC (8), and LR (11) was 1.8 mm (range: 0.9–4.8), 1.7mm (0.8–3.6), and 1.0 mm (0.6–3.5), respectively. Conclusion: Intra-fraction motion analysis of breast tumors was achieved using cine-MRI. These first results show that in supine RT position, motion amplitudes are limited. This information can be used for adaptive RT planning, and to develop preoperative partial-breast RT strategies, such asablative RT for early-stage breast-cancer patients.« less

Clinical outcome of protocol based image (MRI) guided adaptive brachytherapy combined with 3D conformal radiotherapy with or without chemotherapy in patients with locally advanced cervical cancer

PubMed Central

Pötter, Richard; Georg, Petra; Dimopoulos, Johannes C.A.; Grimm, Magdalena; Berger, Daniel; Nesvacil, Nicole; Georg, Dietmar; Schmid, Maximilian P.; Reinthaller, Alexander; Sturdza, Alina; Kirisits, Christian

2011-01-01

Background To analyse the overall clinical outcome and benefits by applying protocol based image guided adaptive brachytherapy combined with 3D conformal external beam radiotherapy (EBRT) ± chemotherapy (ChT). Methods Treatment schedule was EBRT with 45–50.4 Gy ± concomitant cisplatin chemotherapy plus 4 × 7 Gy High Dose Rate (HDR) brachytherapy. Patients were treated in the “protocol period” (2001–2008) with the prospective application of the High Risk CTV concept (D90) and dose volume constraints for organs at risk including biological modelling. Dose volume adaptation was performed with the aim of dose escalation in large tumours (prescribed D90 > 85 Gy), often with inserting additional interstitial needles. Dose volume constraints (D2cc) were 70–75 Gy for rectum and sigmoid and 90 Gy for bladder. Late morbidity was prospectively scored, using LENT/SOMA Score. Disease outcome and treatment related late morbidity were evaluated and compared using actuarial analysis. Findings One hundred and fifty-six consecutive patients (median age 58 years) with cervix cancer FIGO stages IB–IVA were treated with definitive radiotherapy in curative intent. Histology was squamous cell cancer in 134 patients (86%), tumour size was >5 cm in 103 patients (66%), lymph node involvement in 75 patients (48%). Median follow-up was 42 months for all patients. Interstitial techniques were used in addition to intracavitary brachytherapy in 69/156 (44%) patients. Total prescribed mean dose (D90) was 93 ± 13 Gy, D2cc 86 ± 17 Gy for bladder, 65 ± 9 Gy for rectum and 64 ± 9 Gy for sigmoid. Complete remission was achieved in 151/156 patients (97%). Overall local control at 3 years was 95%; 98% for tumours 2–5 cm, and 92% for tumours >5 cm (p = 0.04), 100% for IB, 96% for IIB, 86% for IIIB. Cancer specific survival at 3 years was overall 74%, 83% for tumours 2–5 cm, 70% for tumours >5 cm, 83% for IB, 84% for IIB, 52% for IIIB. Overall survival at 3 years was in total 68%, 72% for tumours 2–5 cm, 65% for tumours >5 cm, 74% for IB, 78% for IIB, 45% for IIIB. In regard to late morbidity in total 188 grade 1 + 2 and 11 grade 3 + 4 late events were observed in 143 patients. G1 + 2/G3 + 4 events for bladder were n = 32/3, for rectum n = 14/5, for bowel (including sigmoid) n = 3/0, for vagina n = 128/2, respectively. Interpretation 3D conformal radiotherapy ± chemotherapy plus image (MRI) guided adaptive intracavitary brachytherapy including needle insertion in advanced disease results in local control rates of 95–100% at 3 years in limited/favourable (IB/IIB) and 85–90% in large/poor response (IIB/III/IV) cervix cancer patients associated with a moderate rate of treatment related morbidity. Compared to the historical Vienna series there is relative reduction in pelvic recurrence by 65–70% and reduction in major morbidity. The local control improvement seems to have impact on CSS and OS. Prospective clinical multi-centre studies are mandatory to evaluate these challenging mono-institutional findings. PMID:21821305

CLOCK gene variation is associated with incidence of type-2 diabetes and cardiovascular diseases in type-2 diabetic subjects: dietary modulation in the PREDIMED randomized trial.

PubMed

Corella, Dolores; Asensio, Eva M; Coltell, Oscar; Sorlí, José V; Estruch, Ramón; Martínez-González, Miguel Ángel; Salas-Salvadó, Jordi; Castañer, Olga; Arós, Fernando; Lapetra, José; Serra-Majem, Lluís; Gómez-Gracia, Enrique; Ortega-Azorín, Carolina; Fiol, Miquel; Espino, Javier Díez; Díaz-López, Andrés; Fitó, Montserrat; Ros, Emilio; Ordovás, José M

2016-01-07

Circadian rhythms regulate key biological processes influencing metabolic pathways. Disregulation is associated with type 2 diabetes (T2D) and cardiovascular diseases (CVD). Circadian rhythms are generated by a transcriptional autoregulatory feedback loop involving core clock genes. CLOCK (circadian locomotor output cycles protein kaput), one of those core genes, is known to regulate glucose metabolism in rodent models. Cross-sectional studies in humans have reported associations between this locus and obesity, plasma glucose, hypertension and T2D prevalence, supporting its role in cardiovascular risk. However, no longitudinal study has investigated the association between CLOCK gene variation and T2D or CVD incidence. Moreover, although in a previous work we detected a gene-diet interaction between the CLOCK-rs4580704 (C > G) single nucleotide polymorphism (SNP) and monounsaturated (MUFA) intake on insulin resistance, no interventional study has analyzed gene-diet interactions on T2D or CVD outcomes. We analyzed the association between the CLOCK-rs4580704 SNP and incidence of T2D and CVD longitudinally in 7098 PREDIMED trial (ISRCTN35739639) participants after a median 4.8-year follow-up. We also examined modulation by Mediterranean diet (MedDiet) intervention (high in MUFA) on these associations. We observed a significant association between the CLOCK-rs4580704 SNP and T2D incidence in n = 3671 non-T2D PREDIMED participants, with variant allele (G) carriers showing decreased incidence (dominant model) compared with CC homozygotes (HR: 0.69; 95 % CI 0.54-0.87; P = 0.002). This protection was more significant in the MedDiet intervention group (HR: 0.58; 95 % CI 0.43-0.78; P < 0.001) than in the control group (HR: 0.95; 95 % CI 0.63-1.44; P = 0.818). Moreover, we detected a statistically significant interaction (P = 0.018) between CLOCK-rs4580704 SNP and T2D status on stroke. Thus, only in T2D subjects was CLOCK-rs4580704 SNP associated with stroke risk, G-carriers having decreased risk (HR: 0.61; 95 % CI 0.40-0.94; P = 0.024 versus CC) in the multivariable-adjusted model. In agreement with our previous results showing a protective effect of the G-allele against hyperglycemia, we extended our findings by reporting a novel association with lower T2D incidence and also suggesting a dietary modulation. Moreover, we report for the first time an association between a CLOCK polymorphism and stroke in T2D subjects, suggesting that core clock genes may significantly contribute to increased CVD risk in T2D.

MO-FG-CAMPUS-TeP2-04: Optimizing for a Specified Target Coverage Probability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fredriksson, A

2016-06-15

Purpose: The purpose of this work is to develop a method for inverse planning of radiation therapy margins. When using this method the user specifies a desired target coverage probability and the system optimizes to meet the demand without any explicit specification of margins to handle setup uncertainty. Methods: The method determines which voxels to include in an optimization function promoting target coverage in order to achieve a specified target coverage probability. Voxels are selected in a way that retains the correlation between them: The target is displaced according to the setup errors and the voxels to include are selectedmore » as the union of the displaced target regions under the x% best scenarios according to some quality measure. The quality measure could depend on the dose to the considered structure alone or could depend on the dose to multiple structures in order to take into account correlation between structures. Results: A target coverage function was applied to the CTV of a prostate case with prescription 78 Gy and compared to conventional planning using a DVH function on the PTV. Planning was performed to achieve 90% probability of CTV coverage. The plan optimized using the coverage probability function had P(D98 > 77.95 Gy) = 0.97 for the CTV. The PTV plan using a constraint on minimum DVH 78 Gy at 90% had P(D98 > 77.95) = 0.44 for the CTV. To match the coverage probability optimization, the DVH volume parameter had to be increased to 97% which resulted in 0.5 Gy higher average dose to the rectum. Conclusion: Optimizing a target coverage probability is an easily used method to find a margin that achieves the desired coverage probability. It can lead to reduced OAR doses at the same coverage probability compared to planning with margins and DVH functions.« less

Monte Carlo investigation of I-125 interseed attenuation for standard and thinner seeds in prostate brachytherapy with phantom validation using a MOSFET.

PubMed

Mason, J; Al-Qaisieh, B; Bownes, P; Henry, A; Thwaites, D

2013-03-01

In permanent seed implant prostate brachytherapy the actual dose delivered to the patient may be less than that calculated by TG-43U1 due to interseed attenuation (ISA) and differences between prostate tissue composition and water. In this study the magnitude of the ISA effect is assessed in a phantom and in clinical prostate postimplant cases. Results are compared for seed models 6711 and 9011 with 0.8 and 0.5 mm diameters, respectively. A polymethyl methacrylate (PMMA) phantom was designed to perform ISA measurements in a simple eight-seed arrangement and at the center of an implant of 36 seeds. Monte Carlo (MC) simulation and experimental measurements using a MOSFET dosimeter were used to measure dose rate and the ISA effect. MC simulations of 15 CT-based postimplant prostate treatment plans were performed to compare the clinical impact of ISA on dose to prostate, urethra, rectum, and the volume enclosed by the 100% isodose, for 6711 and 9011 seed models. In the phantom, ISA reduced the dose rate at the MOSFET position by 8.6%-18.3% (6711) and 7.8%-16.7% (9011) depending on the measurement configuration. MOSFET measured dose rates agreed with MC simulation predictions within the MOSFET measurement uncertainty, which ranged from 5.5% to 7.2% depending on the measurement configuration (k = 1, for the mean of four measurements). For 15 clinical implants, the mean ISA effect for 6711 was to reduce prostate D90 by 4.2 Gy (3%), prostate V100 by 0.5 cc (1.4%), urethra D10 by 11.3 Gy (4.4%), rectal D2cc by 5.5 Gy (4.6%), and the 100% isodose volume by 2.3 cc. For the 9011 seed the mean ISA effect reduced prostate D90 by 2.2 Gy (1.6%), prostate V100 by 0.3 cc (0.7%), urethra D10 by 8.0 Gy (3.2%), rectal D2cc by 3.1 Gy (2.7%), and the 100% isodose volume by 1.2 cc. Differences between the MC simulation and TG-43U1 consensus data for the 6711 seed model had a similar impact, reducing mean prostate D90 by 6 Gy (4.2%) and V100 by 0.6 cc (1.8%). ISA causes the delivered dose in prostate seed implant brachytherapy to be lower than the dose calculated by TG-43U1. MC simulation of phantom seed arrangements show that dose at a point can be reduced by up to 18% and this has been validated using a MOSFET dosimeter. Clinical simulations show that ISA reduces DVH parameter values, but the reduction is less for thinner seeds.

Association of CYP2D6*10 (c.100C>T) polymorphisms with clinical outcome of breast cancer after tamoxifen adjuvant endocrine therapy in Chinese population.

PubMed

Lei, Lei; Wang, Xian; Wu, Xiao-Dan; Wang, Zeng; Chen, Zhan-Hong; Zheng, Ya-Bin; Wang, Xiao-Jia

2016-01-01

Tamoxifen is the most widely used adjuvant endocrine therapy for breast cancer. However, the pharmacogenetic effect of CYP2D6 on its efficacy remains unclear. Therefore, this study aimed to evaluate the association of CYP2D6*10 (c.100C>T) polymorphisms with clinical outcome in Chinese breast cancer patients. A total of 72 tamoxifen-treated early breast cancer patients were included in this study. CYP2D6*10 (c.100C>T) polymorphisms (C/C: wild type; T/T: homozygous mutant genotype T; C/T: heterozygote genotype C) were detected by pyrosequencing. The plasma concentrations of tamoxifen and its two major active metabolites were determined by liquid chromatography tandem mass spectrometry (LC-MS). Disease-free survival (DFS) and overall survival (OS) were assessed by Kaplan-Meier analysis, while the Cox proportional hazards model was used in multivariate tests for prognostic significance. We found that T/T carrier showed the lowest serum concentration of endoxifen as compared to C/C and C/T carriers (p<0.01). In the subgroup of patients below 40 years of age, T/T carriers appeared to have the shortest DFS and OS as compared to other genotype carriers (p<0.01). When genotypes (C/C, C/T and T/T carriers) and other clinical characteristics were adjusted, tumor size (>2 cm) and grades were independent prognostic factors for DFS but not OS (tumor size >2 cm: HR: 3.870, 95% CI: 1.045-14.330, P = 0.043; tumor grades: HR: 2.230, 95% CI: 1.090-4.562, P = 0.028). In conclusion, the T/T genotype is a negative prognostic factor in young breast cancer patients using tamoxifen. Tumor size (>2 cm) and grades are independent prognostic factors for DFS, when genotype of CYP2D6*10 (c.100C>T) is adjusted.

Cone-Beam Computed Tomography–Guided Positioning of Laryngeal Cancer Patients with Large Interfraction Time Trends in Setup and Nonrigid Anatomy Variations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gangsaas, Anne, E-mail: a.gangsaas@erasmusmc.nl; Astreinidou, Eleftheria; Quint, Sandra

2013-10-01

Purpose: To investigate interfraction setup variations of the primary tumor, elective nodes, and vertebrae in laryngeal cancer patients and to validate protocols for cone beam computed tomography (CBCT)-guided correction. Methods and Materials: For 30 patients, CBCT-measured displacements in fractionated treatments were used to investigate population setup errors and to simulate residual setup errors for the no action level (NAL) offline protocol, the extended NAL (eNAL) protocol, and daily CBCT acquisition with online analysis and repositioning. Results: Without corrections, 12 of 26 patients treated with radical radiation therapy would have experienced a gradual change (time trend) in primary tumor setup ≥4more » mm in the craniocaudal (CC) direction during the fractionated treatment (11/12 in caudal direction, maximum 11 mm). Due to these trends, correction of primary tumor displacements with NAL resulted in large residual CC errors (required margin 6.7 mm). With the weekly correction vector adjustments in eNAL, the trends could be largely compensated (CC margin 3.5 mm). Correlation between movements of the primary and nodal clinical target volumes (CTVs) in the CC direction was poor (r{sup 2}=0.15). Therefore, even with online setup corrections of the primary CTV, the required CC margin for the nodal CTV was as large as 6.8 mm. Also for the vertebrae, large time trends were observed for some patients. Because of poor CC correlation (r{sup 2}=0.19) between displacements of the primary CTV and the vertebrae, even with daily online repositioning of the vertebrae, the required CC margin around the primary CTV was 6.9 mm. Conclusions: Laryngeal cancer patients showed substantial interfraction setup variations, including large time trends, and poor CC correlation between primary tumor displacements and motion of the nodes and vertebrae (internal tumor motion). These trends and nonrigid anatomy variations have to be considered in the choice of setup verification protocol and planning target volume margins. eNAL could largely compensate time trends with minor prolongation of fraction time.« less

Adjuvant radiation therapy for bladder cancer: A dosimetric comparison of techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baumann, Brian C.; Noa, Kate; Wileyto, E. Paul

Trials of adjuvant radiation after cystectomy are under development. There are no studies comparing radiation techniques to inform trial design. This study assesses the effect on bowel and rectal dose of 3 different modalities treating 2 proposed alternative clinical target volumes (CTVs). Contours of the bowel, rectum, CTV-pelvic sidewall (common/internal/external iliac and obturator nodes), and CTV-comprehensive (CTV-pelvic sidewall plus cystectomy bed and presacral regions) were drawn on simulation images of 7 post-cystectomy patients. We optimized 3-dimensional conformal radiation (3-D), intensity-modulated radiation (IMRT), and single-field uniform dose (SFUD) scanning proton plans for each CTV. Mixed models regression was used to comparemore » plans for bowel and rectal volumes exposed to 35% (V{sub 35%}), 65% (V{sub 65%}), and 95% (V{sub 95%}) of the prescribed dose. For any given treatment modality, treating the larger CTV-comprehensive volume compared with treating only the CTV-pelvic sidewall nodes significantly increased rectal dose (V{sub 35%} {sub rectum}, V{sub 65%} {sub rectum}, and V{sub 95%} {sub rectum}; p < 0.001 for all comparisons), but it did not produce significant differences in bowel dose (V{sub 95%} {sub bowel}, V{sub 65%} {sub bowel}, or V{sub 35%} {sub bowel}). The 3-D plans, compared with both the IMRT and the SFUD plans, had a significantly greater V{sub 65%} {sub bowel} and V{sub 95%} {sub bowel} for each proposed CTV (p < 0.001 for all comparisons). The effect of treatment modality on rectal dosimetry differed by CTV, but it generally favored the IMRT and the SFUD plans over the 3-D plans. Comparison of the IMRT plan vs the SFUD plan yielded mixed results with no consistent advantage for the SFUD plan over the IMRT plan. Targeting a CTV that spares the cystectomy bed and presacral region may marginally improve rectal toxicity but would not be expected to improve the bowel toxicity associated with any given modality of adjuvant radiation. Using the IMRT or the SFUD plans instead of the 3-D conformal plan may improve both bowel and rectal toxicity.« less

Highly Conformal Craniospinal Radiotherapy Techniques Can Underdose the Cranial Clinical Target Volume if Leptomeningeal Extension through Skull Base Exit Foramina is not Contoured.

PubMed

Noble, D J; Ajithkumar, T; Lambert, J; Gleeson, I; Williams, M V; Jefferies, S J

2017-07-01

Craniospinal irradiation (CSI) remains a crucial treatment for patients with medulloblastoma. There is uncertainty about how to manage meningeal surfaces and cerebrospinal fluid (CSF) that follows cranial nerves exiting skull base foramina. The purpose of this study was to assess plan quality and dose coverage of posterior cranial fossa foramina with both photon and proton therapy. We analysed the radiotherapy plans of seven patients treated with CSI for medulloblastoma and primitive neuro-ectodermal tumours and three with ependymoma (total n = 10). Four had been treated with a field-based technique and six with TomoTherapy™. The internal acoustic meatus (IAM), jugular foramen (JF) and hypoglossal canal (HC) were contoured and added to the original treatment clinical target volume (Plan_CTV) to create a Test_CTV. This was grown to a test planning target volume (Test_PTV) for comparison with a Plan_PTV. Using Plan_CTV and Plan_PTV, proton plans were generated for all 10 cases. The following dosimetry data were recorded: conformity (dice similarity coefficient) and homogeneity index (D 2  - D 98 /D 50 ) as well as median and maximum dose (D 2% ) to Plan_PTV, V 95% and minimum dose (D 99.9% ) to Plan_CTV and Test_CTV and Plan_PTV and Test_PTV, V 95% and minimum dose (D 98% ) to foramina PTVs. Proton and TomoTherapy™ plans were more conformal (0.87, 0.86) and homogeneous (0.07, 0.04) than field-photon plans (0.79, 0.17). However, field-photon plans covered the IAM, JF and HC PTVs better than proton plans (P = 0.002, 0.004, 0.003, respectively). TomoTherapy™ plans covered the IAM and JF better than proton plans (P = 0.000, 0.002, respectively) but the result for the HC was not significant. Adding foramen CTVs/PTVs made no difference for field plans. The mean D min dropped 3.4% from Plan_PTV to Test_PTV for TomoTherapy™ (not significant) and 14.8% for protons (P = 0.001). Highly conformal CSI techniques may underdose meninges and CSF in the dural reflections of posterior fossa cranial nerves unless these structures are specifically included in the CTV. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Prime Contractors with Awards Over $25,000 by Name, Location, and Contract Number. Part 6 (KYOWA DENGYO CORP-N D S INC)

DTIC Science & Technology

1990-01-01

czt a.r 1= Lme mi.). L).) 6 A N...U3 aa a a 0 1a a 0 Ca a =0 a 0 a2 1.2 a a ama 4 a 9 aaAU91 z a a a u a UU a ; t Z a U 2 cc aF - 2 -1. : . R. Ra a, Z .4 a I,2 g il a9a a90 a - 12...N 04a 00s 0o 0000 0 ŘW0 -. CW40 41.0 0 W to c 0 (D~4 OW v s C~C.) rii CO.) U3U 9z Di C.) C. .4 cc .4.4 .4 . ZZE ~ E to 40 ) C’) NtD a) M af . )

SU-E-J-80: Interplay Effect Between VMAT Intensity Modulation and Tumor Motion in Hypofractioned Lung Treatment, Investigated with 3D Pressage Dosimeter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Touch, M; Duke University Medical Center, Durham, NC; Wu, Q

2014-06-01

Purpose: To demonstrate an embedded tissue equivalent presage dosimeter for measuring 3D doses in moving tumors and to study the interplay effect between the tumor motion and intensity modulation in hypofractioned Volumetric Modulated Arc Therapy(VMAT) lung treatment. Methods: Motion experiments were performed using cylindrical Presage dosimeters (5cm diameter by 7cm length) mounted inside the lung insert of a CIRS thorax phantom. Two different VMAT treatment plans were created and delivered in three different scenarios with the same prescribed dose of 18 Gy. Plan1, containing a 2 centimeter spherical CTV with an additional 2mm setup margin, was delivered on a stationarymore » phantom. Plan2 used the same CTV except expanded by 1 cm in the Sup-Inf direction to generate ITV and PTV respectively. The dosimeters were irradiated in static and variable motion scenarios on a Truebeam system. After irradiation, high resolution 3D dosimetry was performed using the Duke Large Field-of-view Optical-CT Scanner, and compared to the calculated dose from Eclipse. Results: In the control case (no motion), good agreement was observed between the planned and delivered dose distributions as indicated by 100% 3D Gamma (3% of maximum planned dose and 3mm DTA) passing rates in the CTV. In motion cases gamma passing rates was 99% in CTV. DVH comparisons also showed good agreement between the planned and delivered dose in CTV for both control and motion cases. However, differences of 15% and 5% in dose to PTV were observed in the motion and control cases respectively. Conclusion: With very high dose nature of a hypofraction treatment, significant effect was observed only motion is introduced to the target. This can be resulted from the motion of the moving target and the modulation of the MLC. 3D optical dosimetry can be of great advantage in hypofraction treatment dose validation studies.« less

SU-E-T-493: Analysis of the Impact of Range and Setup Uncertainties On the Dose to Brain Stem and Whole Brain in the Passively Scattered Proton Therapy Plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sahoo, N; Zhu, X; Zhang, X

Purpose: To quantify the impact of range and setup uncertainties on various dosimetric indices that are used to assess normal tissue toxicities of patients receiving passive scattering proton beam therapy (PSPBT). Methods: Robust analysis of sample treatment plans of six brain cancer patients treated with PSPBT at our facility for whom the maximum brain stem dose exceeded 5800 CcGE were performed. The DVH of each plan was calculated in an Eclipse treatment planning system (TPS) version 11 applying ±3.5% range uncertainty and ±3 mm shift of the isocenter in x, y and z directions to account for setup uncertainties. Worst-casemore » dose indices for brain stem and whole brain were compared to their values in the nominal plan to determine the average change in their values. For the brain stem, maximum dose to 1 cc of volume, dose to 10%, 50%, 90% of volume (D10, D50, D90) and volume receiving 6000, 5400, 5000, 4500, 4000 CcGE (V60, V54, V50, V45, V40) were evaluated. For the whole brain, maximum dose to 1 cc of volume, and volume receiving 5400, 5000, 4500, 4000, 3000 CcGE (V54, V50, V45, V40 and V30) were assessed. Results: The average change in the values of these indices in the worst scenario cases from the nominal plan were as follows. Brain stem; Maximum dose to 1 cc of volume: 1.1%, D10: 1.4%, D50: 8.0%, D90:73.3%, V60:116.9%, V54:27.7%, V50: 21.2%, V45:16.2%, V40:13.6%,Whole brain; Maximum dose to 1 cc of volume: 0.3%, V54:11.4%, V50: 13.0%, V45:13.6%, V40:14.1%, V30:13.5%. Conclusion: Large to modest changes in the dosiemtric indices for brain stem and whole brain compared to nominal plan due to range and set up uncertainties were observed. Such potential changes should be taken into account while using any dosimetric parameters for outcome evaluation of patients receiving proton therapy.« less

Retroperitoneal Sarcoma Target Volume and Organ at Risk Contour Delineation Agreement Among NRG Sarcoma Radiation Oncologists

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baldini, Elizabeth H., E-mail: ebaldini@partners.org; Abrams, Ross A.; Bosch, Walter

Purpose: The purpose of this study was to evaluate the variability in target volume and organ at risk (OAR) contour delineation for retroperitoneal sarcoma (RPS) among 12 sarcoma radiation oncologists. Methods and Materials: Radiation planning computed tomography (CT) scans for 2 cases of RPS were distributed among 12 sarcoma radiation oncologists with instructions for contouring gross tumor volume (GTV), clinical target volume (CTV), high-risk CTV (HR CTV: area judged to be at high risk of resulting in positive margins after resection), and OARs: bowel bag, small bowel, colon, stomach, and duodenum. Analysis of contour agreement was performed using the simultaneousmore » truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results: Ten radiation oncologists contoured both RPS cases, 1 contoured only RPS1, and 1 contoured only RPS2 such that each case was contoured by 11 radiation oncologists. The first case (RPS 1) was a patient with a de-differentiated (DD) liposarcoma (LPS) with a predominant well-differentiated (WD) component, and the second case (RPS 2) was a patient with DD LPS made up almost entirely of a DD component. Contouring agreement for GTV and CTV contours was high. However, the agreement for HR CTVs was only moderate. For OARs, agreement for stomach, bowel bag, small bowel, and colon was high, but agreement for duodenum (distorted by tumor in one of these cases) was fair to moderate. Conclusions: For preoperative treatment of RPS, sarcoma radiation oncologists contoured GTV, CTV, and most OARs with a high level of agreement. HR CTV contours were more variable. Further clarification of this volume with the help of sarcoma surgical oncologists is necessary to reach consensus. More attention to delineation of the duodenum is also needed.« less

Retroperitoneal Sarcoma Target Volume and Organ at Risk Contour Delineation Agreement Among NRG Sarcoma Radiation Oncologists

PubMed Central

Baldini, Elizabeth H.; Abrams, Ross A.; Bosch, Walter; Roberge, David; Haas, Rick L.M.; Catton, Charles N.; Indelicato, Daniel J.; Olsen, Jeffrey R.; Deville, Curtiland; Chen, Yen-Lin; Finkelstein, Steven E.; DeLaney, Thomas F.; Wang, Dian

2015-01-01

Purpose The purpose of this study was to evaluate the variability in target volume and organ at risk (OAR) contour delineation for retroperitoneal sarcoma (RPS) among 12 sarcoma radiation oncologists. Methods and Materials Radiation planning computed tomography (CT) scans for 2 cases of RPS were distributed among 12 sarcoma radiation oncologists with instructions for contouring gross tumor volume (GTV), clinical target volume (CTV), high-risk CTV (HR CTV: area judged to be at high risk of resulting in positive margins after resection), and OARs: bowel bag, small bowel, colon, stomach, and duodenum. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results Ten radiation oncologists contoured both RPS cases, 1 contoured only RPS1, and 1 contoured only RPS2 such that each case was contoured by 11 radiation oncologists. The first case (RPS 1) was a patient with a de-differentiated (DD) liposarcoma (LPS) with a predominant well-differentiated (WD) component, and the second case (RPS 2) was a patient with DD LPS made up almost entirely of a DD component. Contouring agreement for GTV and CTV contours was high. However, the agreement for HR CTVs was only moderate. For OARs, agreement for stomach, bowel bag, small bowel, and colon was high, but agreement for duodenum (distorted by tumor in one of these cases) was fair to moderate. Conclusions For preoperative treatment of RPS, sarcoma radiation oncologists contoured GTV, CTV, and most OARs with a high level of agreement. HR CTV contours were more variable. Further clarification of this volume with the help of sarcoma surgical oncologists is necessary to reach consensus. More attention to delineation of the duodenum is also needed. PMID:26194680

Dosimetric and radiobiological consequences of computed tomography-guided adaptive strategies for intensity modulated radiation therapy of the prostate.

PubMed

Battista, Jerry J; Johnson, Carol; Turnbull, David; Kempe, Jeff; Bzdusek, Karl; Van Dyk, Jacob; Bauman, Glenn

2013-12-01

To examine a range of scenarios for image-guided adaptive radiation therapy of prostate cancer, including different schedules for megavoltage CT imaging, patient repositioning, and dose replanning. We simulated multifraction dose distributions with deformable registration using 35 sets of megavoltage CT scans of 13 patients. We computed cumulative dose-volume histograms, from which tumor control probabilities and normal tissue complication probabilities (NTCPs) for rectum were calculated. Five-field intensity modulated radiation therapy (IMRT) with 18-MV x-rays was planned to achieve an isocentric dose of 76 Gy to the clinical target volume (CTV). The differences between D95, tumor control probability, V70Gy, and NTCP for rectum, for accumulated versus planned dose distributions, were compared for different target volume sizes, margins, and adaptive strategies. The CTV D95 for IMRT treatment plans, averaged over 13 patients, was 75.2 Gy. Using the largest CTV margins (10/7 mm), the D95 values accumulated over 35 fractions were within 2% of the planned value, regardless of the adaptive strategy used. For tighter margins (5 mm), the average D95 values dropped to approximately 73.0 Gy even with frequent repositioning, and daily replanning was necessary to correct this deficit. When personalized margins were applied to an adaptive CTV derived from the first 6 treatment fractions using the STAPLE (Simultaneous Truth and Performance Level Estimation) algorithm, target coverage could be maintained using a single replan 1 week into therapy. For all approaches, normal tissue parameters (rectum V(70Gy) and NTCP) remained within acceptable limits. The frequency of adaptive interventions depends on the size of the CTV combined with target margins used during IMRT optimization. The application of adaptive target margins (<5 mm) to an adaptive CTV determined 1 week into therapy minimizes the need for subsequent dose replanning. Copyright © 2013 Elsevier Inc. All rights reserved.

Bathymetric Atlas of the Northcentral Pacific Ocean,

DTIC Science & Technology

1971-03-01

tD - fn O ) .4p coo 10~~ ob, o o -o 10- (0 00" 0% n ... .... x~ T’ CD ZD v aq *V)~ C’ 0O’ 0~ II tD C A 0 CD 7 -0 (CD 00., J...1I 2 I ~ N- * * * - I I I ~ I ci It * 2 At - ~* 0 I -1 o 0~ .................................... N- ’~ .~ __ 0 0 0 0 0 9 90 N - 0 - N 90 0 tD t4 C>C...9 . N- (D if) oo - - ’T~ / 0 7 ~ I ~’ ~.- -~ - j,~l ~ dz (0 I -d 2 09 ~-~-~--~ N -~ ~ JAJ 0 * (0 N ~ 0 -1 (0~ 0 𔃼~ ~q )A

Simvastatin reduces wasting and improves cardiac function as well as outcome in experimental cancer cachexia.

PubMed

Palus, Sandra; von Haehling, Stephan; Flach, Valerie C; Tschirner, Anika; Doehner, Wolfram; Anker, Stefan D; Springer, Jochen

2013-10-09

Chronic inflammation is common in cancer cachexia (CC) and directly involved in the atrophy seen in this condition. Recently, several groups have described a form of cardiomyopathy in CC animal models. Hence, we investigated the effect of simvastatin with its known anti-inflammatory and cardioprotective effects in a rat model of CC. Juvenile Wister Han rats (weight approx. 200 g) were inoculated with Yoshida AH-130 hepatoma cells and treated once daily with 0.1, 1, 10 or 20 mg/kg/d simvastatin or placebo for 14 days. Body weight and body composition (NMR) were assessed at baseline and at the end of the study. Cardiac function was analysed by echocardiography at baseline and day 11. Tumour-bearing, placebo-treated rats lost 47.9±3.8 g of their initial body weight. Treatment with 0.1, 1, 10 or 20 mg/kg/d simvastatin significantly reduced wasting by 39.6%, 47.6%, 28.5% and 35.4%, respectively (all p<0.05 vs. placebo). This was mainly due to reduced atrophy of lean mass, i.e. muscle mass. Cardiac function was significantly improved, e.g. cardiac output (untreated sham: 78.9 mL/min) was severely impaired in tumour-bearing rats (42.4 mL/min) and improved by 1, 10 or 20 mg/kg/d simvastatin (62.2, 59.0 and 57.0 mL/min, respectively, all p<0.05 vs. placebo). Most importantly, 10 or 20 mg/kg/d simvastatin reduced mortality (HR:0.16, 95%CI:0.04-0.76, p=0.021 and HR:0.16, 95%CI:0.03-0.72, p=0.017 vs placebo, respectively). Simvastatin attenuated loss of body weight as well as muscle mass and improved cardiac function leading to improved survival in this CC model. Simvastatin may be beneficial in a clinical setting to treat CC. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muijs, Christina, E-mail: c.t.muijs@umcg.nl; Smit, Justin; Karrenbeld, Arend

Purpose/Objective(s): The aim of this study was to analyze the accuracy of gross tumor volume (GTV) delineation and clinical target volume (CTV) margins for neoadjuvant chemoradiation therapy (neo-CRT) in esophageal carcinoma at pathologic examination and to determine the impact on survival. Methods and Materials: The study population consisted of 63 esophageal cancer patients treated with neo-CRT. GTV and CTV borders were demarcated in situ during surgery on the esophagus, using anatomical reference points to provide accurate information regarding tumor location at pathologic evaluation. To identify prognostic factors for disease-free survival (DFS) and overall survival (OS), a Cox regression analysis wasmore » performed. Results: After resection, macroscopic residual tumor was found outside the GTV in 7 patients (11%). Microscopic residual tumor was located outside the CTV in 9 patients (14%). The median follow-up was 15.6 months. With multivariate analysis, only microscopic tumor outside the CTV (hazard ratio [HR], 4.96; 95% confidence interval [CI], 1.03-15.36), and perineural growth (HR, 5.77; 95% CI, 1.27-26.13) were identified as independent prognostic factors for OS. The 1-year OS was 20% for patients with tumor outside the CTV and 86% for those without (P<.01). For DFS, microscopic tumor outside the CTV (HR, 5.92; 95% CI, 1.89-18.54) and ypN+ (HR, 3.36; 95% CI, 1.33-8.48) were identified as independent adverse prognostic factors. The 1-year DFS was 23% versus 77% for patients with or without tumor outside the CTV (P<.01). Conclusions: Microscopic tumor outside the CTV is associated with markedly worse OS after neo-CRT. This may either stress the importance of accurate tumor delineation or reflect aggressive tumor behavior requiring new adjuvant treatment modalities.« less

SU-F-19A-03: Dosimetric Advantages in Critical Structure Dose Sparing by Using a Multichannel Cylinder in High Dose Rate Brachytherapy to Treat Vaginal Cuff Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Syh, J; Syh, J; Patel, B

2014-06-15

Purpose: The multichannel cylindrical vaginal applicator is a variation of traditional single channel cylindrical vaginal applicator. The multichannel applicator has additional peripheral channels that provide more flexibility in the planning process. The dosimetric advantage is to reduce dose to adjacent organ at risk (OAR) such as bladder and rectum while maintaining target coverage with the dose optimization from additional channels. Methods: Vaginal HDR brachytherapy plans are all CT based. CT images were acquired in 2 mm thickness to keep integrity of cylinder contouring. The CTV of 5mm Rind with prescribed treatment length was reconstructed from 5mm expansion of inserted cylinder.more » The goal was 95% of CTV covered by 95% of prescribed dose in both single channel planning (SCP)and multichannel planning (MCP) before proceeding any further optimization for dose reduction to critical structures with emphasis on D2cc and V2Gy . Results: This study demonstrated noticeable dose reduction to OAR was apparent in multichannel plans. The D2cc of the rectum and bladder were showing the reduced dose for multichannel versus single channel. The V2Gy of the rectum was 93.72% and 83.79% (p=0.007) for single channel and multichannel respectively (Figure 1 and Table 1). To assure adequate coverage to target while reducing the dose to the OAR without any compromise is the main goal in using multichannel vaginal applicator in HDR brachytherapy. Conclusion: Multichannel plans were optimized using anatomical based inverse optimization algorithm of inverse planning simulation annealing. The optimization solution of the algorithm was to improve the clinical target volume dose coverage while reducing the dose to critical organs such as bladder, rectum and bowels. The comparison between SCP and MCP demonstrated MCP is superior to SCP where the dwell positions were based on geometric array only. It concluded that MCP is preferable and is able to provide certain features superior to SCP.« less

Needle migration and dosimetric impact in high-dose-rate brachytherapy for prostate cancer evaluated by repeated MRI.

PubMed

Buus, Simon; Lizondo, Maria; Hokland, Steffen; Rylander, Susanne; Pedersen, Erik M; Tanderup, Kari; Bentzen, Lise

To quantify needle migration and dosimetric impact in high-dose-rate brachytherapy for prostate cancer and propose a threshold for needle migration. Twenty-four high-risk prostate cancer patients treated with an HDR boost of 2 × 8.5 Gy were included. Patients received an MRI for planning (MRI1), before (MRI2), and after treatment (MRI3). Time from needle insertion to MRI3 was ∼3 hours. Needle migration was evaluated from coregistered images: MRI1-MRI2 and MRI1-MRI3. Dose volume histogram parameters from the treatment plan based on MRI1 were related to parameters based on needle positions in MRI2 or MRI3. Regression was used to model the average needle migration per implant and change in D90 clinical target volume, CTV prostate+3mm . The model fit was used for estimating the dosimetric impact in equivalent dose in 2 Gy fractions for dose levels of 6, 8.5, 10, 15, and 19 Gy. Needle migration was on average 2.2 ± 1.8 mm SD from MRI1-MRI2 and 5.0 ± 3.0 mm SD from MRI1-MRI3. D90 CTV prostate+3mm was robust toward average needle migration ≤3 mm, whereas for migration >3 mm D90 decreased by 4.5% per mm. A 3 mm of needle migration resulted in a decrease of 0.9, 1.7, 2.3, 4.8, and 7.6 equivalent dose in 2 Gy fractions for dose levels of 6, 8.5, 10, 15, and 19 Gy, respectively. Substantial needle migration in high-dose-rate brachytherapy occurs frequently in 1-3 hours following needle insertion. A 3-mm threshold of needle migration is proposed, but 2 mm may be considered for dose levels ≥15 Gy. Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Effects of dietary selenium supply and timing of nutrient restriction during gestation on maternal growth and body composition of pregnant adolescent ewes.

PubMed

Carlson, D B; Reed, J J; Borowicz, P P; Taylor, J B; Reynolds, L P; Neville, T L; Redmer, D A; Vonnahme, K A; Caton, J S

2009-02-01

The objectives were to examine effects of dietary Se supplementation and nutrient restriction during defined periods of gestation on maternal adaptations to pregnancy in primigravid sheep. Sixty-four pregnant Western Whiteface ewe lambs were assigned to treatments in a 2 x 4 factorial design. Treatments were dietary Se [adequate Se (ASe; 3.05 microg/kg of BW) vs. high Se (HSe; 70.4 microg/kg of BW)] fed as Se-enriched yeast, and plane of nutrition [control (C; 100% of NRC requirements) vs. restricted (R; 60% of NRC requirements]. Selenium treatments were fed throughout gestation. Plane of nutrition treatments were applied during mid (d 50 to 90) and late gestation (d 90 to 130), which resulted in 4 distinct plane of nutrition treatments [treatment: CC (control from d 50 to 130), RC (restricted from d 50 to 90, and control d 90 to 130), CR (control from d 50 to 90, and restricted from d 90 to 130), and RR (restricted from d 50 to 130)]. All of the pregnant ewes were necropsied on d 132 +/- 0.9 of gestation (length of gestation approximately 145 d). Nutrient restriction treatments decreased ewe ADG and G:F, as a result, RC and CR ewes had similar BW and maternal BW (MBW) at necropsy, whereas RR ewes were lighter than RC and CR ewes. From d 90 to 130, the HSe-CC ewes had greater ADG (Se x nutrition; P = 0.05) than did ASe-CC ewes, whereas ADG and G:F (Se x nutrition; P = 0.08) were less for HSe-RR ewes compared with ASe-RR ewes. The CR and RR treatments decreased total gravid uterus weight (P = 0.01) as well as fetal weight (P = 0.02) compared with RC and CC. High Se decreased total (g; P = 0.09) and relative heart mass (g/kg of MBW; P = 0.10), but increased total and relative mass of liver (P < or = 0.05) and perirenal fat (P < or = 0.06) compared with ASe. Total stomach complex mass was decreased (P < 0.01) by all the nutrient restriction treatments, but was reduced to a greater extent in CR and RR compared with RC. Total small intestine mass was similar between RC and CC ewes, but was markedly reduced (P < 0.01) in CR and RR ewes. The mass of the stomach complex and the small and large intestine relative to MBW was greater (P = 0.01) for RC than for CR ewes. Increased Se decreased jejunal DNA concentration (P = 0.07), total jejunal cell number (P = 0.03), and total proliferating jejunal cell number (P = 0.05) compared with ASe. These data indicate that increased dietary Se affected whole-body and organ growth of pregnant ewes, but the results differed depending on the plane of nutrition. In addition, the timing and duration of nutrient restriction relative to stage of pregnancy affected visceral organ mass in a markedly different fashion.

Development of an adjoint sensitivity field-based treatment-planning technique for the use of newly designed directional LDR sources in brachytherapy.

PubMed

Chaswal, V; Thomadsen, B R; Henderson, D L

2012-02-21

The development and application of an automated 3D greedy heuristic (GH) optimization algorithm utilizing the adjoint sensitivity fields for treatment planning to assess the advantage of directional interstitial prostate brachytherapy is presented. Directional and isotropic dose kernels generated using Monte Carlo simulations based on Best Industries model 2301 I-125 source are utilized for treatment planning. The newly developed GH algorithm is employed for optimization of the treatment plans for seven interstitial prostate brachytherapy cases using mixed sources (directional brachytherapy) and using only isotropic sources (conventional brachytherapy). All treatment plans resulted in V100 > 98% and D90 > 45 Gy for the target prostate region. For the urethra region, the D10(Ur), D90(Ur) and V150(Ur) and for the rectum region the V100cc, D2cc, D90(Re) and V90(Re) all are reduced significantly when mixed sources brachytherapy is used employing directional sources. The simulations demonstrated that the use of directional sources in the low dose-rate (LDR) brachytherapy of the prostate clearly benefits in sparing the urethra and the rectum sensitive structures from overdose. The time taken for a conventional treatment plan is less than three seconds, while the time taken for a mixed source treatment plan is less than nine seconds, as tested on an Intel Core2 Duo 2.2 GHz processor with 1GB RAM. The new 3D GH algorithm is successful in generating a feasible LDR brachytherapy treatment planning solution with an extra degree of freedom, i.e. directionality in very little time.

Development of an adjoint sensitivity field-based treatment-planning technique for the use of newly designed directional LDR sources in brachytherapy

NASA Astrophysics Data System (ADS)

Chaswal, V.; Thomadsen, B. R.; Henderson, D. L.

2012-02-01

The development and application of an automated 3D greedy heuristic (GH) optimization algorithm utilizing the adjoint sensitivity fields for treatment planning to assess the advantage of directional interstitial prostate brachytherapy is presented. Directional and isotropic dose kernels generated using Monte Carlo simulations based on Best Industries model 2301 I-125 source are utilized for treatment planning. The newly developed GH algorithm is employed for optimization of the treatment plans for seven interstitial prostate brachytherapy cases using mixed sources (directional brachytherapy) and using only isotropic sources (conventional brachytherapy). All treatment plans resulted in V100 > 98% and D90 > 45 Gy for the target prostate region. For the urethra region, the D10Ur, D90Ur and V150Ur and for the rectum region the V100cc, D2cc, D90Re and V90Re all are reduced significantly when mixed sources brachytherapy is used employing directional sources. The simulations demonstrated that the use of directional sources in the low dose-rate (LDR) brachytherapy of the prostate clearly benefits in sparing the urethra and the rectum sensitive structures from overdose. The time taken for a conventional treatment plan is less than three seconds, while the time taken for a mixed source treatment plan is less than nine seconds, as tested on an Intel Core2 Duo 2.2 GHz processor with 1GB RAM. The new 3D GH algorithm is successful in generating a feasible LDR brachytherapy treatment planning solution with an extra degree of freedom, i.e. directionality in very little time.

SU-G-201-14: Is Maximum Skin Dose a Reliable Metric for Accelerated Partial Breast Irradiation with Brachytherapy?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, S; Ragab, O; Patel, S

Purpose: To evaluate the reliability of the maximum point dose (Dmax) to the skin surface as a dosimetric constraint, we investigated the correlation between Dmax at the skin surface and dose metrics at various definitions of skin thickness. Methods: 42 patients treated with APBI using a Strut Adjusted Volume Implant (SAVI) applicator between 2010 and 2014 were retrospectively reviewed. Target (PTV-EVAL) and organs at risk (OARs: skin, lung, and ribs) were delineated on a CT following NSABP B-39 guidelines. Six skin structures were contoured: a rind 3cm external to the body surface and 1, 2, 3, 4, and 5mm thickmore » rinds deep to the body surface. Inverse planning simulated annealing optimization was used to deliver 32–34Gy in 8-10 fractions to the target while minimizing OAR doses. Dmax, D0.1cc, D1.0cc, and D2.0cc to the various skin structures were calculated. Linear regressions between the metrics were evaluated using the coefficient of determination (R{sup 2}). Results: The average±SD PTV-EVAL volume and cavity-to-skin distances were 71.1±28.5cc and 6.9±5.0mm. The target V90 and V95 were 97.3±2.3% and 95.1±3.2%. The Dmax to the skin structures were 78.7±10.2% (skin surface), 82.2±10.7% (skin-1mm), 89.4±12.6% (skin-2mm), 97.9±15.4% (skin-3mm), 114.1±32.5% (skin-4mm), and 157.0±85.3% (skin-5mm). Linear regression analysis showed D1.0cc and D2.0cc to the skin 1mm and Dmax to the skin-4mm and 5mm were poorly correlated with other metrics (R{sup 2}=0.413±0.204). Dmax to the skin surface was well correlated (R{sup 2}=0.910±0.047) and D1.0cc to the skin-3mm was strongly correlated with all subsurface skin layers (R{sup 2}=0.935±0.050). Conclusion: Dmax to the skin surface is a relevant metric for breast skin dose. Contouring discontinuities in the skin with a 1mm subsurface rind and the active dwells in the skin 4 and 5mm introduced significant variations in skin DVH. D0.1cc, D1.0cc, and D2.0cc to a 3mm skin rind are more robust metrics in breast brachytherapy.« less

4D-Listmode-PET-CT and 4D-CT for optimizing PTV margins in gastric lymphoma : Determination of intra- and interfractional gastric motion.

PubMed

Reinartz, Gabriele; Haverkamp, Uwe; Wullenkord, Ramona; Lehrich, Philipp; Kriz, Jan; Büther, Florian; Schäfers, Klaus; Schäfers, Michael; Eich, Hans Theodor

2016-05-01

New imaging protocols for radiotherapy in localized gastric lymphoma were evaluated to optimize planning target volume (PTV) margin and determine intra-/interfractional variation of the stomach. Imaging of 6 patients was explored prospectively. Intensity-modulated radiotherapy (IMRT) planning was based on 4D/3D imaging of computed tomography (CT) and positron-emission tomography (PET)-CT. Static and motion gross tumor volume (sGTV and mGTV, respectively) were distinguished by defining GTV (empty stomach), clinical target volume (CTV = GTV + 5 mm margin), PTV (GTV + 10/15/20/25 mm margins)  plus paraaortic lymph nodes and proximal duodenum. Overlap of 4D-Listmode-PET-based mCTV with 3D-CT-based PTV (increasing margins) and V95/D95 of mCTV were evaluated. Gastric shifts were determined using online cone-beam CT. Dose contribution to organs at risk was assessed. The 4D data demonstrate considerable intra-/interfractional variation of the stomach, especially along the vertical axis. Conventional 3D-CT planning utilizing advancing PTV margins of 10/15/20/25 mm resulted in rising dose coverage of mCTV (4D-Listmode-PET-Summation-CT) and rising D95 and V95 of mCTV. A PTV margin of 15 mm was adequate in 3 of 6 patients, a PTV margin of 20 mm was adequate in 4 of 6 patients, and a PTV margin of 25 mm was adequate in 5 of 6 patients. IMRT planning based on 4D-PET-CT/4D-CT together with online cone-beam CT is advisable to individualize the PTV margin and optimize target coverage in gastric lymphoma.

Impact of dosimetric and clinical parameters on clinical side effects in cervix cancer patients treated with 3D pulse-dose-rate intracavitary brachytherapy.

PubMed

Levitchi, Mihai; Charra-Brunaud, Claire; Quetin, Philippe; Haie-Meder, Christine; Kerr, Christine; Castelain, Bernard; Delannes, Martine; Thomas, Laurence; Desandes, Emmanuel; Peiffert, Didier

2012-06-01

To assess the association between dosimetric/clinical parameters and gastrointestinal/urinary grade 2-4 side effects in cervix cancer patients treated with 3D pulse dose rate brachytherapy. Three hundred and fifty-two patients received brachytherapy associated with external-beam radiotherapy (EBRT) for 266 of them; 236 patients underwent surgery. The doses for the most exposed 2, and 0.1 cm(3) (D(2cc) and D(0.1cc)) volumes of the rectum and bladder as well as bladder ICRU point dose (D(ICRU)) were converted into isoeffective doses in 2-Gy fractions. The clinical parameters analyzed were: age, smoking habits, arteritis, diabetes, previous pelvic surgery, FIGO stage, nodal status, pathology, pelvic surgery, EBRT and chemotherapy. Side effects were prospectively assessed using the CTCAEv3.0. Cutoff dose levels were defined separately for patients treated with EBRT and brachytherapy (Group 1) and with preoperative brachytherapy (Group 2). The median follow-up was 23.4months. In Group 1 a significant predictive value of rectum D(0.1cc) and D(2cc), bladder D(0.1cc) and D(ICRU) for gastrointestinal and urinary toxicity was found using as cutoff 83, 68, 109 and 68Gy(α)(/)(β)(3). In Group 2 a significant predictive value of bladder D(0.1cc), D(2cc) and D(ICRU) for urinary toxicity was found using as cutoff 141, 91 and 67Gy(α)(/)(β)(3), but not for the rectum D(0.1cc) and D(2cc); smoking had a significant predictive value on urinary toxicity. For patients treated with brachytherapy and EBRT, rectum D(0.1cc) and D(2cc) and bladder D(0.1cc) and D(ICRU) had a predictive value for toxicity. For patients treated with preoperative brachytherapy, bladder D(0.1cc), D(2cc) and D(ICRU) and smoking had a predictive value for urinary toxicity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Impact of t(11;14)(q13;q32) on the outcome of autologous hematopoietic cell transplantation in multiple myeloma.

PubMed

Sasaki, Koji; Lu, Gary; Saliba, Rima M; Bashir, Qaiser; Hosing, Chitra; Popat, Uday; Shah, Nina; Parmar, Simrit; Dinh, Yvonne; Ahmed, Sairah; Shpall, Elizabeth J; Kebriaei, Partow; Shah, Jatin J; Orlowski, Robert Z; Champlin, Richard; Qazilbash, Muzaffar H

2013-08-01

The t(11;14)(q13;q32) translocation is seen in 15%-20% patients with multiple myeloma (MM). It generally is not associated with worse outcomes. We studied the impact of t(11;14)(q13;q32) on outcome in patients with MM who received high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HCT). Eligible patients underwent high-dose chemotherapy followed by auto-HCT at the M.D. Anderson Cancer Center between February 2000 and August 2010, and had conventional cytogenetic (CC) or fluorescence in situ hybridization (FISH) results available before auto-HCT (n = 993). The cohort was divided into 3 groups of patients: (1) normal (diploid by CC and negative by FISH; n = 869); (2) t(11;14)(q13;q32) by CC or FISH (n = 27); and (3) high-risk (HR) abnormalities by CC or FISH (n = 97). Of the 27 patients with t(11;14)(q13;q32), 18 had isolated t(11;14)(q13;q32) and 9 had concurrent HR abnormalities. The primary objective was to compare outcomes in patients with t(11;14)(q13;q32) and patients with diploid or HR markers detected by CC or FISH studies. The median duration of follow-up in surviving patients was 37 months. The 3-year progression-free survival (PFS) was 47% for the normal group, 27% for the t(11;14)(q13;q32) group, and 13% for the HR group (P < .00001). The 3-year OS was 83% for the normal group, 63% for the t(11;14)(q13;q32) group, and 34% for the HR group (P < .00001). On multivariate analysis, t(11;14)(q13;q32) and HR abnormalities by CC or FISH and relapsed disease at auto-HCT were associated with shorter PFS, whereas t(11;14)(q13;q32) and HR abnormalities by CC or FISH, β2 microglobulin of >3.5, and relapsed disease at the time of auto-HCT were associated with shorter OS. In conclusion, patients with t(11;14)(q13;q32) had worse outcomes than patients with normal CC or FISH studies, but better outcomes than patients with HR markers detected by CC or FISH studies. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Can MRI-only replace MRI-CT planning with a titanium tandem and ovoid applicator?

PubMed

Harkenrider, Matthew M; Patel, Rakesh; Surucu, Murat; Chinsky, Bonnie; Mysz, Michael L; Wood, Abbie; Ryan, Kelly; Shea, Steven M; Small, William; Roeske, John C

2018-06-23

To evaluate dosimetric differences between MRI-only and MRI-CT planning with a titanium tandem and ovoid applicator to determine if all imaging and planning goals can be achieved with MRI only. We evaluated 10 patients who underwent MRI-CT-based cervical brachytherapy with a titanium tandem and ovoid applicator. High-risk clinical target volume and organs at risk were contoured on the 3D T2 MRI, which were transferred to the co-registered CT, where the applicator was identified. Retrospectively, three planners independently delineated the applicator on the axial 3D T2 MRI while blinded to the CT. Identical dwell position times in the delivered plan were loaded. Dose-volume histogram parameters were compared to the previously delivered MRI-CT plan. There were no significant differences in dose to D 90 or D 98 of the high-risk clinical target volume with MRI vs. MRI-CT planning. MRI vs. MRI-CT planning resulted in mean D 0.1cc bladder of 8.8 ± 3.4 Gy vs. 8.5 ± 3.2 Gy (p = 0.29) and D 2cc bladder of 6.2 ± 1.4 Gy vs. 6.0 ± 1.4 Gy (p = 0.33), respectively. Mean D 0.1cc rectum was 5.7 ± 1.2 Gy vs. 5.3 ± 1.2 Gy (p = 0.03) and D 2cc rectum 4.0 ± 0.8 Gy vs. 4.2 ± 1.0 Gy (p = 0.18), respectively. Mean D 0.1cc sigmoid was 5.2 ± 1.3 Gy vs. 5.4 ± 1.6 Gy (p = 0.23) and D 2cc sigmoid 3.9 ± 1.0 Gy vs. 4.0 ± 1.1 Gy (p = 0.18), respectively. There were no clinically significant dosimetric differences between the MRI and MRI-CT plans. This study demonstrates that cervical brachytherapy with a titanium applicator can be planned with MRI alone, which is now our clinical standard. Copyright © 2018. Published by Elsevier Inc.

Robust plan optimization for electromagnetic transponder guided hypo-fractionated prostate treatment using volumetric modulated arc therapy

NASA Astrophysics Data System (ADS)

Zhang, Pengpeng; Hunt, Margie; Happersett, Laura; Yang, Jie; Zelefsky, Michael; Mageras, Gig

2013-11-01

To develop an optimization algorithm for volumetric modulated arc therapy which incorporates an electromagnetic tracking (EMT) guided gating strategy and is robust to residual intra-fractional motion uncertainties. In a computer simulation, intra-fractional motion traces from prior treatments with EMT were converted to a probability distribution function (PDF), truncated using a patient specific action volume that encloses allowed deviations from the planned position, and renormalized to yield a new PDF with EMT-gated interventions. In lieu of a conventional planning target volume (PTV), multiple instances of clinical target volume (CTV) and organs at risk (OARs) were replicated and displaced to extreme positions inside the action volume representing possible delivery scenarios. When optimizing the volumetric modulated arc therapy plan, doses to the CTV and OARs were calculated as a sum of doses to the replicas weighted by the PDF to account for motion. A treatment plan meeting the clinical constraints was produced and compared to the counterpart conventional margin (PTV) plan. EMT traces from a separate testing database served to simulate motion during gated delivery. Dosimetric end points extracted from dose accumulations for each motion trace were utilized to evaluate potential clinical benefit. Five prostate cases from a hypofractionated protocol (42.5 Gy in 5 fractions) were retrospectively investigated. The patient specific gating window resulted in tight anterior and inferior action levels (∼1 mm) to protect rectal wall and bladder wall, and resulted in an average of four beam interruptions per fraction in the simulation. The robust-optimized plans achieved the same average CTV D95 coverage of 40.5 Gy as the PTV-optimized plans, but with reduced patient-averaged rectum wall D1cc by 2.2 Gy (range 0.7 to 4.7 Gy) and bladder wall mean dose by 2.9 Gy (range 2.0 to 3.4 Gy). Integration of an intra-fractional motion management strategy into the robust optimization process is feasible and may yield improved OAR sparing compared to the standard margin approach.

Robust plan optimization for electromagnetic transponder guided hypo-fractionated prostate treatment using volumetric modulated arc therapy.

PubMed

Zhang, Pengpeng; Hunt, Margie; Happersett, Laura; Yang, Jie; Zelefsky, Michael; Mageras, Gig

2013-11-07

To develop an optimization algorithm for volumetric modulated arc therapy which incorporates an electromagnetic tracking (EMT) guided gating strategy and is robust to residual intra-fractional motion uncertainties. In a computer simulation, intra-fractional motion traces from prior treatments with EMT were converted to a probability distribution function (PDF), truncated using a patient specific action volume that encloses allowed deviations from the planned position, and renormalized to yield a new PDF with EMT-gated interventions. In lieu of a conventional planning target volume (PTV), multiple instances of clinical target volume (CTV) and organs at risk (OARs) were replicated and displaced to extreme positions inside the action volume representing possible delivery scenarios. When optimizing the volumetric modulated arc therapy plan, doses to the CTV and OARs were calculated as a sum of doses to the replicas weighted by the PDF to account for motion. A treatment plan meeting the clinical constraints was produced and compared to the counterpart conventional margin (PTV) plan. EMT traces from a separate testing database served to simulate motion during gated delivery. Dosimetric end points extracted from dose accumulations for each motion trace were utilized to evaluate potential clinical benefit. Five prostate cases from a hypofractionated protocol (42.5 Gy in 5 fractions) were retrospectively investigated. The patient specific gating window resulted in tight anterior and inferior action levels (~1 mm) to protect rectal wall and bladder wall, and resulted in an average of four beam interruptions per fraction in the simulation. The robust-optimized plans achieved the same average CTV D95 coverage of 40.5 Gy as the PTV-optimized plans, but with reduced patient-averaged rectum wall D1cc by 2.2 Gy (range 0.7 to 4.7 Gy) and bladder wall mean dose by 2.9 Gy (range 2.0 to 3.4 Gy). Integration of an intra-fractional motion management strategy into the robust optimization process is feasible and may yield improved OAR sparing compared to the standard margin approach.

SU-E-T-12: A Comparative Dosimetric Study of Pre and Post Prostate Iodine-125 Permanent Seed Implants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, X; Rahimian, J; Goy, B

Purpose: Post-implant dosimetry has become the gold standard for prostate implant evaluation. The goal of this research is to compare the dosimetry between pre-plan and post-plan in permanent prostate seed implant brachytherapy. Methods: A retrospective study of 91 patients treated with Iodine-125 prostate seed implant between year 2012∼2014 were performed. All plans were created using a VariSeed 8.0 planning system. Pre-plan ultrasound images were acquired using 0.5 cm slice thickness. Post-plan CT images acquired about 1–4 weeks after implant, fused with the preplan ultrasound images. The prostate and urethra contours were generated using the fusion of ultrasound and CT images.more » Iodine-125 seed source activities varied between 0.382 to 0.414 mCi per seed. The loading patterns varied slightly between patients depending on the prostate size. Statistical analysis of pre and post plans for prostate and urethra volumes, V100%, V150% and D90, and urethra D10 were performed and reported. Results: The pre and post implant average prostate size was 36.90cc vs. 38.58cc; V100% was 98.33% vs. 96.89%; V150% was 47.09% vs. 56.95%; D90 was 116.35Gy vs. 116.12Gy, urethra volume was 1.72cc vs. 1.85cc, urethra D10% was 122.0% vs. 135.35%, respectively. There was no statistically significant difference between the pre and post-plan values for D90(p-value=0.43). However, there are significant differences between other parameters most likely due to post surgical edema; prostate size (p-value= 0.00015); V100% (p-value=3.7803E-07); V150% (p-value=1.49E-09); urethra volume (p-value= 2.77E-06); Urethra D10 (p-value=7.37E-11). Conclusion: The post-plan dosimetry using CT image set showed similar D90 dose coverage to the pre-plan using the ultrasound image dataset. The study showed that our prostate seed implants have consistently delivered adequate therapeutic dose to the prostate while sparing urethra. Future studies to correlate dose versus biochemical response using patients’ PSA values as well as patients’ survival are warranted.« less

Comparison of DVH parameters and loading patterns of standard loading, manual and inverse optimization for intracavitary brachytherapy on a subset of tandem/ovoid cases.

PubMed

Jamema, Swamidas V; Kirisits, Christian; Mahantshetty, Umesh; Trnkova, Petra; Deshpande, Deepak D; Shrivastava, Shyam K; Pötter, Richard

2010-12-01

Comparison of inverse planning with the standard clinical plan and with the manually optimized plan based on dose-volume parameters and loading patterns. Twenty-eight patients who underwent MRI based HDR brachytherapy for cervix cancer were selected for this study. Three plans were calculated for each patient: (1) standard loading, (2) manual optimized, and (3) inverse optimized. Dosimetric outcomes from these plans were compared based on dose-volume parameters. The ratio of Total Reference Air Kerma of ovoid to tandem (TRAK(O/T)) was used to compare the loading patterns. The volume of HR CTV ranged from 9-68 cc with a mean of 41(±16.2) cc. Mean V100 for standard, manual optimized and inverse plans was found to be not significant (p=0.35, 0.38, 0.4). Dose to bladder (7.8±1.6 Gy) and sigmoid (5.6±1.4 Gy) was high for standard plans; Manual optimization reduced the dose to bladder (7.1±1.7 Gy p=0.006) and sigmoid (4.5±1.0 Gy p=0.005) without compromising the HR CTV coverage. The inverse plan resulted in a significant reduction to bladder dose (6.5±1.4 Gy, p=0.002). TRAK was found to be 0.49(±0.02), 0.44(±0.04) and 0.40(±0.04) cGy m(-2) for the standard loading, manual optimized and inverse plans, respectively. It was observed that TRAK(O/T) was 0.82(±0.05), 1.7(±1.04) and 1.41(±0.93) for standard loading, manual optimized and inverse plans, respectively, while this ratio was 1 for the traditional loading pattern. Inverse planning offers good sparing of critical structures without compromising the target coverage. The average loading pattern of the whole patient cohort deviates from the standard Fletcher loading pattern. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Residual tumor after neoadjuvant chemoradiation outside the radiation therapy target volume: a new prognostic factor for survival in esophageal cancer.

PubMed

Muijs, Christina; Smit, Justin; Karrenbeld, Arend; Beukema, Jannet; Mul, Veronique; van Dam, Go; Hospers, Geke; Kluin, Phillip; Langendijk, Johannes; Plukker, John

2014-03-15

The aim of this study was to analyze the accuracy of gross tumor volume (GTV) delineation and clinical target volume (CTV) margins for neoadjuvant chemoradiation therapy (neo-CRT) in esophageal carcinoma at pathologic examination and to determine the impact on survival. The study population consisted of 63 esophageal cancer patients treated with neo-CRT. GTV and CTV borders were demarcated in situ during surgery on the esophagus, using anatomical reference points to provide accurate information regarding tumor location at pathologic evaluation. To identify prognostic factors for disease-free survival (DFS) and overall survival (OS), a Cox regression analysis was performed. After resection, macroscopic residual tumor was found outside the GTV in 7 patients (11%). Microscopic residual tumor was located outside the CTV in 9 patients (14%). The median follow-up was 15.6 months. With multivariate analysis, only microscopic tumor outside the CTV (hazard ratio [HR], 4.96; 95% confidence interval [CI], 1.03-15.36), and perineural growth (HR, 5.77; 95% CI, 1.27-26.13) were identified as independent prognostic factors for OS. The 1-year OS was 20% for patients with tumor outside the CTV and 86% for those without (P<.01). For DFS, microscopic tumor outside the CTV (HR, 5.92; 95% CI, 1.89-18.54) and ypN+ (HR, 3.36; 95% CI, 1.33-8.48) were identified as independent adverse prognostic factors. The 1-year DFS was 23% versus 77% for patients with or without tumor outside the CTV (P<.01). Microscopic tumor outside the CTV is associated with markedly worse OS after neo-CRT. This may either stress the importance of accurate tumor delineation or reflect aggressive tumor behavior requiring new adjuvant treatment modalities. Copyright © 2014 Elsevier Inc. All rights reserved.

SU-E-T-157: Evaluation and Comparison of Doses to Pelvic Lymph Nodes and to Point B with 3D Image Guided Treatment Planning for High Dose Brachytherapy for Treatment of Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhandare, N.

2014-06-01

Purpose: To estimate and compare the doses received by the obturator, external and internal iliac lymph nodes and point Methods: CT-MR fused image sets of 15 patients obtained for each of 5 fractions of HDR brachytherapy using tandem and ring applicator, were used to generate treatment plans optimized to deliver a prescription dose to HRCTV-D90 and to minimize the doses to organs at risk (OARs). For each set of image, target volume (GTV, HRCTV) OARs (Bladder, Rectum, Sigmoid), and both left and right pelvic lymph nodes (obturator, external and internal iliac lymph nodes) were delineated. Dose-volume histograms (DVH) were generatedmore » for pelvic nodal groups (left and right obturator group, internal and external iliac chains) Per fraction DVH parameters used for dose comparison included dose to 100% volume (D100), and dose received by 2cc (D2cc), 1cc (D1cc) and 0.1 cc (D0.1cc) of nodal volume. Dose to point B was compared with each DVH parameter using 2 sided t-test. Pearson correlation were determined to examine relationship of point B dose with nodal DVH parameters. Results: FIGO clinical stage varied from 1B1 to IIIB. The median pretreatment tumor diameter measured on MRI was 4.5 cm (2.7– 6.4cm).The median dose to bilateral point B was 1.20 Gy ± 0.12 or 20% of the prescription dose. The correlation coefficients were all <0.60 for all nodal DVH parameters indicating low degree of correlation. Only 2 cc of obturator nodes was not significantly different from point B dose on t-test. Conclusion: Dose to point B does not adequately represent the dose to any specific pelvic nodal group. When using image guided 3D dose-volume optimized treatment nodal groups should be individually identified and delineated to obtain the doses received by pelvic nodes.« less

Molecular cloning, characterization and expression of immunoglobulin D on pathogen challenge and pathogen associated molecular patterns stimulation in freshwater carp, Catla catla.

PubMed

Banerjee, Rajanya; Patel, Bhakti; Basu, Madhubanti; Lenka, Saswati S; Paicha, Mahismita; Samanta, Mrinal; Das, Surajit

2017-10-01

The primordial immunoglobulin class, IgD, was the first non-IgM isotype discovered in teleosts. The crucial roles of IgM and IgZ in imparting systemic and mucosal immunity, respectively, in various fish species have been widely established. However, the putative function of a unique IgD isotype during pathogenic invasions has not been well explored. The present study reports the existence of an IgD ortholog in freshwater carp, Catla catla, and further evaluates its differential expression profile in response to bacterial, parasitic and viral antigenic exposure and pathogen associated molecular patterns (PAMPs) stimulation. The IgD of C. catla (CcIgD) cDNA sequence was found to encode 226 amino acids and confirmed homology with heavy chain delta region of Cyprinidae family members. Phylogenetic analysis of CcIgD exhibited greatest similarity with Ctenopharyngodon idella. qRT-PCR analysis revealed significant upregulation (P < 0.001) of IgD gene expression in kidney with respect to other tissues at 24 hr post-Aeromonas hydrophila challenge. CcIgD gene expression in skin was enhanced following Streptococcus uberis infection and in blood following Argulus infection and inactivated rhabdoviral antigen stimulation. Further, the treatment of bacterial and viral products (PAMPs) also triggered significant (P < 0.05) increases in CcIgD mRNA expression in kidney. These findings indicate the functional importance of teleost IgD in orchestrating tissue specific neutralization of antigens on stimulation with different pathogens and PAMPs. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

Clinical analysis of speculum-based vaginal packing for high-dose-rate intracavitary tandem and ovoid brachytherapy in cervical cancer

PubMed Central

Sud, Shivani; Roth, Toni

2018-01-01

Purpose Intra-vaginal packing is used to fix the applicator and displace organs at risk (OAR) during high-dose-rate intracavitary tandem and ovoid brachytherapy (HDR-ICB). We retain the speculum from applicator placement as a dual-function bladder and rectum retractor during treatment. Our objective is to review salient techniques for OAR displacement, share our packing technique, and determine the reduction in dose to OAR and inter-fraction variability of dose to OAR, associated with speculum-based vaginal packing (SBVP) in comparison to conventional gauze packing during HDR-ICB. Material and methods We reviewed HDR-ICB treatment plans for 45 patients, including 10 who underwent both conventional gauze packing and SBVP. Due to institutional inter-provider practice differences, patients non-selectively received either packing procedure. Packing was performed under conscious sedation, followed by cone beam computed tomography used for dosimetric planning. Maximum absolute and percent-of-prescription dose to the International Commission of Radiation Units bladder and rectal points in addition to D0.1cc, D1.0cc, and D2.0cc volumes of the bladder and rectum were analyzed and compared for each packing method using an independent sample t-test. Results Of the 179 fractions included, 73% and 27% used SBVP and gauze packing, respectively. For patients prescribed 6 Gy to point A, SBVP was associated with reduced mean D0.1cc bladder dose, inter-fraction variability in D0.1cc bladder dose by 9.3% (p = 0.026) and 9.0%, respectively, and statistically equivalent rectal D0.1cc, D1.0cc, and D2.0cc. Patients prescribed 5.5 Gy or 5 Gy to point A after dose optimization, were less likely to benefit from SBVP. In the intra-patient comparison, 80% of patients had reduction in at least one rectum or bladder parameter. Conclusions In patients with conducive anatomy, SBVP is a cost-efficient packing method that is associated with improved bladder sparing and comparable rectal sparing relative to gauze packing during HDR-ICB without general anesthesia. PMID:29619054

A statistical model for analyzing the rotational error of single isocenter for multiple targets technique.

PubMed

Chang, Jenghwa

2017-06-01

To develop a statistical model that incorporates the treatment uncertainty from the rotational error of the single isocenter for multiple targets technique, and calculates the extra PTV (planning target volume) margin required to compensate for this error. The random vector for modeling the setup (S) error in the three-dimensional (3D) patient coordinate system was assumed to follow a 3D normal distribution with a zero mean, and standard deviations of σ x , σ y , σ z . It was further assumed that the rotation of clinical target volume (CTV) about the isocenter happens randomly and follows a three-dimensional (3D) independent normal distribution with a zero mean and a uniform standard deviation of σ δ . This rotation leads to a rotational random error (R), which also has a 3D independent normal distribution with a zero mean and a uniform standard deviation of σ R equal to the product of σδπ180 and dI⇔T, the distance between the isocenter and CTV. Both (S and R) random vectors were summed, normalized, and transformed to the spherical coordinates to derive the Chi distribution with three degrees of freedom for the radial coordinate of S+R. PTV margin was determined using the critical value of this distribution for a 0.05 significance level so that 95% of the time the treatment target would be covered by the prescription dose. The additional PTV margin required to compensate for the rotational error was calculated as a function of σ R and dI⇔T. The effect of the rotational error is more pronounced for treatments that require high accuracy/precision like stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT). With a uniform 2-mm PTV margin (or σ x = σ y = σ z = 0.715 mm), a σ R = 0.328 mm will decrease the CTV coverage probability from 95.0% to 90.9%, or an additional 0.2-mm PTV margin is needed to prevent this loss of coverage. If we choose 0.2 mm as the threshold, any σ R > 0.328 mm will lead to an extra PTV margin that cannot be ignored, and the maximal σ δ that can be ignored is 0.45° (or 0.0079 rad ) for dI⇔T = 50 mm or 0.23° (or 0.004 rad ) for dI⇔T = 100 mm. The rotational error cannot be ignored for high-accuracy/-precision treatments like SRS/SBRT, particularly when the distance between the isocenter and target is large. © 2017 American Association of Physicists in Medicine.

Comparison of Intraoperatively Built Custom Linked Seeds Versus Loose Seed Gun Applicator Technique Using Real-Time Intraoperative Planning for Permanent Prostate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zauls, A. Jason; Ashenafi, Michael S.; Onicescu, Georgiana

2011-11-15

Purpose: To report our dosimetric results using a novel push-button seed delivery system that constructs custom links of seeds intraoperatively. Methods and Materials: From 2005 to 2007, 43 patients underwent implantation using a gun applicator (GA), and from 2007 to 2008, 48 patientsunderwent implantation with a novel technique allowing creation of intraoperatively built custom links of seeds (IBCL). Specific endpoint analyses were prostate D90% (pD90%), rV100% > 1.3 cc, and overall time under anesthesia. Results: Final analyses included 91 patients, 43 GA and 48 IBCL. Absolute change in pD90% ({Delta}pD90%) between intraoperative and postoperative plans was evaluated. Using GA method,more » the {Delta}pD90% was -8.1Gy and -12.8Gy for I-125 and Pd-103 implants, respectively. Similarly, the IBCL technique resulted in a {Delta}pD90% of -8.7Gy and -9.8Gy for I-125 and Pd-103 implants, respectively. No statistically significant difference in {Delta}pD90% was found comparing methods. The GA method had two intraoperative and 10 postoperative rV100% >1.3 cc. For IBCL, five intraoperative and eight postoperative plans had rV100% >1.3 cc. For GA, the mean time under anesthesia was 75 min and 87 min for Pd-103 and I-125 implants, respectively. For IBCL, the mean time was 86 and 98 min for Pd-103 and I-125. There was a statistical difference between the methods when comparing mean time under anesthesia. Conclusions: Dosimetrically relevant endpoints were equivalent between the two methods. Currently, time under anesthesia is longer using the IBCL technique but has decreased over time. IBCL is a straightforward brachytherapy technique that can be implemented into clinical practice as an alternative to gun applicators.« less

SU-E-T-786: Utility of Gold Wires to Optimize Intensity Modulation Capacity of a Novel Directional Modulated Brachytherapy Tandem Applicator for Image Guided Cervical Cancer Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, D; Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario; Safigholi, H

2015-06-15

Purpose: To evaluate the impact of using gold wires to differentially fill various channels on plan quality compared with conventional T&R applicator, inside a novel directional modulated brachytherapy (DMBT) tandem applicator for cervical cancer brachytherapy. Materials and Methods: The novel DMBT tandem applicator has a 5.4-mm diameter MR-compatible tungsten alloy enclosed in a 0.3-mm thick plastic tubing that wraps around the tandem. To modulate the radiation intensity, 6 symmetric peripheral holes of 1.3-mm diameter are grooved along the tungsten alloy rod. These grooved holes are differentially filled with gold wires to generate various degrees of directional beams. For example, threemore » different fill patterns of 1) all void, 2) all filled except the hole containing the 192-Ir source, and 3) two adjacent holes to the 192-Ir source filled were Monte Carlo simulated. The resulting 3D dose distributions were imported into an in-house-coded inverse optimization planning system to generate HDR brachytherapy clinical plans for 19 patient cases. All plans generated were normalized to the same D90 as the clinical plans and D2cc doses of OARs were evaluated. Prescription ranged between 15 and 17.5Gy. Results: In general, the plans in case 1) resulted in the highest D2cc doses for the OARs with 11.65±2.30Gy, 7.47±3.05Gy, and 9.84±2.48Gy for bladder, rectum, and sigmoid, respectively, although the differences were small. For the case 2), D2cc doses were 11.61±2.29Gy, 7.41±3.07Gy, and 9.75±2.45Gy, respectively. And, for the case 3), D2cc doses were 11.60±2.28Gy, 7.41±3.05Gy, and 9.74±2.45Gy, respectively. Difference between 1) and 2) cases were small with the average D2cc difference of <0.64%. Difference between 1) and 3) cases were even smaller with the average D2cc difference of <0.1%. Conclusions: There is a minimal clinical benefit by differentially filling grooved holes in the novel DMBT tandem applicator for image guided cervical cancer brachytherapy.« less

Efficacy of robust optimization plan with partial-arc VMAT for photon volumetric-modulated arc therapy: A phantom study.

PubMed

Miura, Hideharu; Ozawa, Shuichi; Nagata, Yasushi

2017-09-01

This study investigated position dependence in planning target volume (PTV)-based and robust optimization plans using full-arc and partial-arc volumetric modulated arc therapy (VMAT). The gantry angles at the periphery, intermediate, and center CTV positions were 181°-180° (full-arc VMAT) and 181°-360° (partial-arc VMAT). A PTV-based optimization plan was defined by 5 mm margin expansion of the CTV to a PTV volume, on which the dose constraints were applied. The robust optimization plan consisted of a directly optimized dose to the CTV under a maximum-uncertainties setup of 5 mm. The prescription dose was normalized to the CTV D 99% (the minimum relative dose that covers 99% of the volume of the CTV) as an original plan. The isocenter was rigidly shifted at 1 mm intervals in the anterior-posterior (A-P), superior-inferior (S-I), and right-left (R-L) directions from the original position to the maximum-uncertainties setup of 5 mm in the original plan, yielding recalculated dose distributions. It was found that for the intermediate and center positions, the uncertainties in the D 99% doses to the CTV for all directions did not significantly differ when comparing the PTV-based and robust optimization plans (P > 0.05). For the periphery position, uncertainties in the D 99% doses to the CTV in the R-L direction for the robust optimization plan were found to be lower than those in the PTV-based optimization plan (P < 0.05). Our study demonstrated that a robust optimization plan's efficacy using partial-arc VMAT depends on the periphery CTV position. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

40 CFR 1051.145 - What provisions apply only for a limited time?

Code of Federal Regulations, 2012 CFR

2012-07-01

... nitrogen in g/kW-hr. (ii) For engines below 225 cc, use the following equation: NER = 9.898 × log [(HC+NOX... oxides of nitrogen in g/kW-hr. (c) [Reserved] (d) Phase-in flexibility. For model years before 2014, if... model years, you may have a negative balance of emission credits relative to the permeation emission...

40 CFR 1051.145 - What provisions apply only for a limited time?

Code of Federal Regulations, 2013 CFR

2013-07-01

... nitrogen in g/kW-hr. (ii) For engines below 225 cc, use the following equation: NER = 9.898 × log [(HC+NOX... oxides of nitrogen in g/kW-hr. (c) [Reserved] (d) Phase-in flexibility. For model years before 2014, if... model years, you may have a negative balance of emission credits relative to the permeation emission...

40 CFR 1051.145 - What provisions apply only for a limited time?

Code of Federal Regulations, 2014 CFR

2014-07-01

... nitrogen in g/kW-hr. (ii) For engines below 225 cc, use the following equation: NER = 9.898 × log [(HC+NOX... oxides of nitrogen in g/kW-hr. (c) [Reserved] (d) Phase-in flexibility. For model years before 2014, if... model years, you may have a negative balance of emission credits relative to the permeation emission...

40 CFR 1051.145 - What provisions apply only for a limited time?

Code of Federal Regulations, 2011 CFR

2011-07-01

... nitrogen in g/kW-hr. (ii) For engines below 225 cc, use the following equation: NER = 9.898 × log [(HC+NOX... oxides of nitrogen in g/kW-hr. (c) [Reserved] (d) Phase-in flexibility. For model years before 2014, if... model years, you may have a negative balance of emission credits relative to the permeation emission...

40 CFR 1051.145 - What provisions apply only for a limited time?

Code of Federal Regulations, 2010 CFR

2010-07-01

... nitrogen in g/kW-hr. (ii) For engines below 225 cc, use the following equation: NER = 9.898 × log [(HC+NOX... oxides of nitrogen in g/kW-hr. (c) [Reserved] (d) Phase-in flexibility. For model years before 2014, if... model years, you may have a negative balance of emission credits relative to the permeation emission...

SU-F-T-258: Efficacy of Exit Fluence-Based Dose Calculation for Prostate Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siebers, J; Gardner, J; Neal, B

Purpose: To investigate the efficacy of exit-fluence-based dose computation for prostate radiotherapy by determining if it estimates true dose more accurately than the original planning dose. Methods: Virtual exit-fluencebased dose computation was performed for 19 patients, each with 9–12 repeat CT images. For each patient, a 78 Gy treatment plan was created utilizing 5 mm CTV-to-PTV and OAR-to-PRV margins. A Monte Carlo framework was used to compute dose and exit-fluence images for the planning image and for each repeat CT image based on boney-anatomyaligned and prostate-centroid-aligned CTs. Identical source particles were used for the MC dose-computations on the planning andmore » repeat CTs to maximize correlation. The exit-fluence-based dose and image were computed by multiplying source particle weights by FC(x,y)=FP(x,y)/FT(x,y), where (x,y) are the source particle coordinates projected to the exit-fluence plane and we denote the dose/fluence from the plan by (DP,FP), from the repeat-CT as (DT,FT), and the exit-fluence computation by (DFC,FFC). DFC mimics exit-fluence backprojection through the planning image as FT=FFC. Dose estimates were intercompared to judge the efficacy of exit-fluence-based dose computation. Results: Boney- and prostate-centroid aligned results are combined as there is no statistical difference between them, yielding 420 dose comparisons per dose-volume metric. DFC is more accurate than DP for 46%, 33%, and 44% of cases in estimating CTV D98, D50, and D2 respectively. DFC improved rectum D50 and D2 estimates 54% and 49% respectively and bladder D50 and D2 47 and 49% respectively. While averaged over all patients and images DFC and DP were within 3.1% of DT, they differed from DT by as much as 22% for GTV D98, 71% for the Bladder D50, 17% for Bladder D2, 19% for Rectum D2. Conclusion: Exit-fluence based dose computations infrequently improve CTV or OAR dose estimates and should be used with caution. Research supported in part by Varian Medical Systems.« less

CC2D1A and CC2D1B regulate degradation and signaling of EGFR and TLR4.

PubMed

Deshar, Rakesh; Cho, Eun-Bee; Yoon, Sungjoo Kim; Yoon, Jong-Bok

2016-11-11

Signaling through many transmembrane receptors is terminated by their sorting to the intraluminal vesicles (ILVs) of multivescular bodies (MVBs) and subsequent lysosomal degradation. ILV formation requires the endosomal sorting complex required for transport (ESCRT) machinery. CC2D1A and CC2D1B interact with the CHMP4 family of proteins, the major subunit of the ESCRT-III complex, however, their roles in receptor degradation and signaling are poorly defined. Here, we report that CC2D1A binds to CHMP4B polymers formed on endosomes to regulate the endosomal sorting pathway. We show that depletion of CC2D1A and B accelerates degradation of EGFR and elicits rapid termination of its downstream signaling through ERK1 and 2. Depletion of CC2D1A and B promotes sorting of EGFR to ILV leading to its rapid lysosomal degradation. In addition, we show that knockdown of CC2D1A and B has similar effects on degradation and downstream signaling of another membrane receptor, TLR4. Thus, these findings suggest that CC2D1A and B may have broad effects on transmembrane receptors by preventing premature ILV sorting and termination of signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

Dose calculations accounting for breathing motion in stereotactic lung radiotherapy based on 4D-CT and the internal target volume.

PubMed

Admiraal, Marjan A; Schuring, Danny; Hurkmans, Coen W

2008-01-01

The purpose of this study was to determine the 4D accumulated dose delivered to the CTV in stereotactic radiotherapy of lung tumours, for treatments planned on an average CT using an ITV derived from the Maximum Intensity Projection (MIP) CT. For 10 stage I lung cancer patients, treatment plans were generated based on 4D-CT images. From the 4D-CT scan, 10 time-sorted breathing phases were derived, along with the average CT and the MIP. The ITV with a margin of 0mm was used as a PTV to study a worst case scenario in which the differences between 3D planning and 4D dose accumulation will be largest. Dose calculations were performed on the average CT. Dose prescription was 60Gy to 95% of the PTV, and at least 54Gy should be received by 99% of the PTV. Plans were generated using the inverse planning module of the Pinnacle(3) treatment planning system. The plans consisted of nine coplanar beams with two segments each. After optimisation, the treatment plan was transferred to all breathing phases and the delivered dose per phase was calculated using an elastic body spline model available in our research version of Pinnacle (8.1r). Then, the cumulative dose to the CTV over all breathing phases was calculated and compared to the dose distribution of the original treatment plan. Although location, tumour size and breathing-induced tumour movement varied widely between patients, the PTV planning criteria could always be achieved without compromising organs at risk criteria. After 4D dose calculations, only very small differences between the initial planned PTV coverage and resulting CTV coverage were observed. For all patients, the dose delivered to 99% of the CTV exceeded 54Gy. For nine out of 10 patients also the criterion was met that the volume of the CTV receiving at least the prescribed dose was more than 95%. When the target dose is prescribed to the ITV (PTV=ITV) and dose calculations are performed on the average CT, the cumulative CTV dose compares well to the planned dose to the ITV. Thus, the concept of treatment plan optimisation and evaluation based on the average CT and the ITV is a valid approach in stereotactic lung treatment. Even with a zero ITV to PTV margin, no significantly different dose coverage of the CTV arises from the breathing motion induced dose variation over time.

Molecular and functional analyses of a maize autoactive NB-LRR protein identify precise structural requirements for activity.

PubMed

Wang, Guan-Feng; Ji, Jiabing; El-Kasmi, Farid; Dangl, Jeffery L; Johal, Guri; Balint-Kurti, Peter J

2015-02-01

Plant disease resistance is often mediated by nucleotide binding-leucine rich repeat (NLR) proteins which remain auto-inhibited until recognition of specific pathogen-derived molecules causes their activation, triggering a rapid, localized cell death called a hypersensitive response (HR). Three domains are recognized in one of the major classes of NLR proteins: a coiled-coil (CC), a nucleotide binding (NB-ARC) and a leucine rich repeat (LRR) domains. The maize NLR gene Rp1-D21 derives from an intergenic recombination event between two NLR genes, Rp1-D and Rp1-dp2 and confers an autoactive HR. We report systematic structural and functional analyses of Rp1 proteins in maize and N. benthamiana to characterize the molecular mechanism of NLR activation/auto-inhibition. We derive a model comprising the following three main features: Rp1 proteins appear to self-associate to become competent for activity. The CC domain is signaling-competent and is sufficient to induce HR. This can be suppressed by the NB-ARC domain through direct interaction. In autoactive proteins, the interaction of the LRR domain with the NB-ARC domain causes de-repression and thus disrupts the inhibition of HR. Further, we identify specific amino acids and combinations thereof that are important for the auto-inhibition/activity of Rp1 proteins. We also provide evidence for the function of MHD2, a previously uncharacterized, though widely conserved NLR motif. This work reports several novel insights into the precise structural requirement for NLR function and informs efforts towards utilizing these proteins for engineering disease resistance.

SU-E-T-27: A Dosimetric Evaluation of Boney Anatomy Versus Fiducial Marker Alignment for the Treatment of Prostate Cancer Using Scanned Beam Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Freund, D; Ding, X; Zhang, J

Purpose: In prostate proton radiotherapy, three fiducial markers are used for patient daily alignment. However fiducial alignment can change beamline heterogeneity in proton therapy. The purpose of this study is to determine the difference in fiducial and boney anatomy alignment for patient treatment. Methods and materials: Prostate cancer patients who received proton treatment were included in this study. 3 fiducial markers were implanted before the initial CT. All the patients were re-CT’d every 2 weeks to check the fiducial marker position reproducibility as well as dosimetric consistence of target coverage. In geometry study, re-CT were fused to the initial CTmore » base on the boney anatomy and the average fiducial marker displacement was measured the centers of the fiducials. Dosimetrically, the initial plan was recalculated directly to re-CT image set based on the boney alignment and fiducial alignment to determine the difference from daily treatment. Prostate coverage and hotspots were evaluated using the dose to 98% of the CTV (D98) and dose to 2% (D2), respectively. Results: The shift from the initial 6 patient CT image sets resulted in an average change in the fiducial location of 5.70 +/− 3 mm. Dosimetric comparison from a single patient revealed that differences from the planned dose resulted from both boney and fiducial alignment. Planned clinical treatment volume coverage resulted in a D98 of 70.44Gy and D2 of 70.84Gy compared to a D98 of 70.13Gy and D2 70.94Gy for boney alignment and a D98 of 70.08Gy and D2 71.18Gy for fiducial alignment respectively. Conclusion: This study demonstrates that with boney anatomy alignment there is little change to CTV coverage and only slightly worse CTV coverage and hotspot production with fiducial alignment. An increase patient cohort and further investigation is necessary to determine the whether boney alignment can help better control dose heterogeneity.« less

Prime Contractors with Awards Over $25,000 by Name, Location, and Contract Number, Fiscal Year 87. Part 7. Kinnetic Laboratories, Incorporated-Medical Supplies Manufacturing.

DTIC Science & Technology

1987-01-01

tD -4 00...r-0N oo U) 0 ( t- OD 0 m -~0 S N 4bD ko .10,- - 0 >0 0- 4 ’I’ A-l i 0 c X: 0 to 00 -5 z9 0. c . 4! 0 0a LJ O 4 In -3.4 z 6 w- 0E *i 0 E3 T-). 6 0 0 0...CCH C CC L(U~4r)-. -ccC 13 td cc- C ~00 ~ 121-’CC~~~~A AtL C CU . . rC ~UM I;7 : m u Su ~~,- U. U -p.- N- 10 m99 90 r-- OD0 N 90> - a N m0.- No x w

Evaluation and mitigation of the interplay effects for intensity modulated proton therapy for lung cancer in a clinical setting

PubMed Central

Kardar, Laleh; Li, Yupeng; Li, Xiaoqiang; Li, Heng; Cao, Wenhua; Chang, Joe Y.; Liao, Li; Zhu, Ronald X.; Sahoo, Narayan; Gillin, Michael; Liao, Zhongxing; Komaki, Ritsuko; Cox, James D.; Lim, Gino; Zhang, Xiaodong

2015-01-01

Purpose The primary aim of this study was to evaluate the impact of interplay effects for intensity-modulated proton therapy (IMPT) plans for lung cancer in the clinical setting. The secondary aim was to explore the technique of iso-layered re-scanning for mitigating these interplay effects. Methods and Materials Single-fraction 4D dynamic dose without considering re-scanning (1FX dynamic dose) was used as a metric to determine the magnitude of dosimetric degradation caused by 4D interplay effects. The 1FX dynamic dose was calculated by simulating the machine delivery processes of proton spot scanning on moving patient described by 4D computed tomography (4DCT) during the IMPT delivery. The dose contributed from an individual spot was fully calculated on the respiratory phase corresponding to the life span of that spot, and the final dose was accumulated to a reference CT phase by using deformable image registration. The 1FX dynamic dose was compared with the 4D composite dose. Seven patients with various tumor volumes and motions were selected. Results The CTV prescription coverage for the 7 patients were 95.04%, 95.38%, 95.39%, 95.24%, 95.65%, 95.90%, and 95.53%, calculated with use of the 4D composite dose, and were 89.30%, 94.70%, 85.47%, 94.09%, 79.69%, 91.20%, and 94.19% with use of the 1FX dynamic dose. For the 7 patients, the CTV coverage, calculated by using single-fraction dynamic dose, were 95.52%, 95.32%, 96.36%, 95.28%, 94.32%, 95.53%, and 95.78%, using maximum MU limit value of 0.005. In other words, by increasing the number of delivered spots in each fraction, the degradation of CTV coverage improved up to 14.6%. Conclusions Single-fraction 4D dynamic dose without re-scanning was validated as a surrogate to evaluate the interplay effects for IMPT for lung cancer in the clinical setting. The interplay effects can be potentially mitigated by increasing the number of iso-layered re-scanning in each fraction delivery. PMID:25407877

Evaluation and mitigation of the interplay effects of intensity modulated proton therapy for lung cancer in a clinical setting.

PubMed

Kardar, Laleh; Li, Yupeng; Li, Xiaoqiang; Li, Heng; Cao, Wenhua; Chang, Joe Y; Liao, Li; Zhu, Ronald X; Sahoo, Narayan; Gillin, Michael; Liao, Zhongxing; Komaki, Ritsuko; Cox, James D; Lim, Gino; Zhang, Xiaodong

2014-01-01

The primary aim of this study was to evaluate the impact of the interplay effects of intensity modulated proton therapy (IMPT) plans for lung cancer in the clinical setting. The secondary aim was to explore the technique of isolayered rescanning to mitigate these interplay effects. A single-fraction 4-dimensional (4D) dynamic dose without considering rescanning (1FX dynamic dose) was used as a metric to determine the magnitude of dosimetric degradation caused by 4D interplay effects. The 1FX dynamic dose was calculated by simulating the machine delivery processes of proton spot scanning on a moving patient, described by 4D computed tomography during IMPT delivery. The dose contributed from an individual spot was fully calculated on the respiratory phase that corresponded to the life span of that spot, and the final dose was accumulated to a reference computed tomography phase by use of deformable image registration. The 1FX dynamic dose was compared with the 4D composite dose. Seven patients with various tumor volumes and motions were selected for study. The clinical target volume (CTV) prescription coverage for the 7 patients was 95.04%, 95.38%, 95.39%, 95.24%, 95.65%, 95.90%, and 95.53% when calculated with the 4D composite dose and 89.30%, 94.70%, 85.47%, 94.09%, 79.69%, 91.20%, and 94.19% when calculated with the 1FX dynamic dose. For these 7 patients, the CTV coverage calculated by use of a single-fraction dynamic dose was 95.52%, 95.32%, 96.36%, 95.28%, 94.32%, 95.53%, and 95.78%, with a maximum monitor unit limit value of 0.005. In other words, by increasing the number of delivered spots in each fraction, the degradation of CTV coverage improved up to 14.6%. A single-fraction 4D dynamic dose without rescanning was validated as a surrogate to evaluate the interplay effects of IMPT for lung cancer in the clinical setting. The interplay effects potentially can be mitigated by increasing the amount of isolayered rescanning in each fraction delivery.

Relative plan robustness of step-and-shoot vs rotational intensity–modulated radiotherapy on repeat computed tomographic simulation for weight loss in head and neck cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomson, David J.; The University of Manchester, Manchester Academic Health Science Centre, Institute of Cancer Sciences, Manchester; Beasley, William J.

Introduction: Interfractional anatomical alterations may have a differential effect on the dose delivered by step-and-shoot intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT). The increased degrees of freedom afforded by rotational delivery may increase plan robustness (measured by change in target volume coverage and doses to organs at risk [OARs]). However, this has not been evaluated for head and neck cancer. Materials and methods: A total of 10 patients who required repeat computed tomography (CT) simulation and replanning during head and neck IMRT were included. Step-and-shoot IMRT and VMAT plans were generated from the original planning scan. The initial andmore » second CT simulation scans were fused and targets/OAR contours transferred, reviewed, and modified. The plans were applied to the second CT scan and doses recalculated without repeat optimization. Differences between step-and-shoot IMRT and VMAT for change in target volume coverage and doses to OARs between first and second CT scans were compared by Wilcoxon signed rank test. Results: There were clinically relevant dosimetric changes between the first and the second CT scans for both the techniques (reduction in mean D{sub 95%} for PTV2 and PTV3, D{sub min} for CTV2 and CTV3, and increased mean doses to the parotid glands). However, there were no significant differences between step-and-shoot IMRT and VMAT for change in any target coverage parameter (including D{sub 95%} for PTV2 and PTV3 and D{sub min} for CTV2 and CTV3) or dose to any OARs (including parotid glands) between the first and the second CT scans. Conclusions: For patients with head and neck cancer who required replanning mainly due to weight loss, there were no significant differences in plan robustness between step-and-shoot IMRT and VMAT. This information is useful with increased clinical adoption of VMAT.« less

Motion induced interplay effects for VMAT radiotherapy.

PubMed

Edvardsson, Anneli; Nordström, Fredrik; Ceberg, Crister; Ceberg, Sofie

2018-04-19

The purpose of this study was to develop a method to simulate breathing motion induced interplay effects for volumetric modulated arc therapy (VMAT), to verify the proposed method with measurements, and to use the method to investigate how interplay effects vary with different patient- and machine specific parameters. VMAT treatment plans were created on a virtual phantom in a treatment planning system (TPS). Interplay effects were simulated by dividing each plan into smaller sub-arcs using an in-house developed software and shifting the isocenter for each sub-arc to simulate a sin 6 breathing motion in the superior-inferior direction. The simulations were performed for both flattening-filter (FF) and flattening-filter free (FFF) plans and for different breathing amplitudes, period times, initial breathing phases, dose levels, plan complexities, CTV sizes, and collimator angles. The resulting sub-arcs were calculated in the TPS, generating a dose distribution including the effects of motion. The interplay effects were separated from dose blurring and the relative dose differences to 2% and 98% of the CTV volume (ΔD 98% and ΔD 2% ) were calculated. To verify the simulation method, measurements were carried out, both static and during motion, using a quasi-3D phantom and a motion platform. The results of the verification measurements during motion were comparable to the results of the static measurements. Considerable interplay effects were observed for individual fractions, with the minimum ΔD 98% and maximum ΔD 2% being  -16.7% and 16.2%, respectively. The extent of interplay effects was larger for FFF compared to FF and generally increased for higher breathing amplitudes, larger period times, lower dose levels, and more complex treatment plans. Also, the interplay effects varied considerably with the initial breathing phase, and larger variations were observed for smaller CTV sizes. In conclusion, a method to simulate motion induced interplay effects was developed and verified with measurements, which allowed for a large number of treatment scenarios to be investigated. The simulations showed large interplay effects for individual fractions and that the extent of interplay effects varied with the breathing pattern, FFF/FF, dose level, CTV size, collimator angle, and the complexity of the treatment plan.

Motion induced interplay effects for VMAT radiotherapy

NASA Astrophysics Data System (ADS)

Edvardsson, Anneli; Nordström, Fredrik; Ceberg, Crister; Ceberg, Sofie

2018-04-01

The purpose of this study was to develop a method to simulate breathing motion induced interplay effects for volumetric modulated arc therapy (VMAT), to verify the proposed method with measurements, and to use the method to investigate how interplay effects vary with different patient- and machine specific parameters. VMAT treatment plans were created on a virtual phantom in a treatment planning system (TPS). Interplay effects were simulated by dividing each plan into smaller sub-arcs using an in-house developed software and shifting the isocenter for each sub-arc to simulate a sin6 breathing motion in the superior–inferior direction. The simulations were performed for both flattening-filter (FF) and flattening-filter free (FFF) plans and for different breathing amplitudes, period times, initial breathing phases, dose levels, plan complexities, CTV sizes, and collimator angles. The resulting sub-arcs were calculated in the TPS, generating a dose distribution including the effects of motion. The interplay effects were separated from dose blurring and the relative dose differences to 2% and 98% of the CTV volume (ΔD98% and ΔD2%) were calculated. To verify the simulation method, measurements were carried out, both static and during motion, using a quasi-3D phantom and a motion platform. The results of the verification measurements during motion were comparable to the results of the static measurements. Considerable interplay effects were observed for individual fractions, with the minimum ΔD98% and maximum ΔD2% being  ‑16.7% and 16.2%, respectively. The extent of interplay effects was larger for FFF compared to FF and generally increased for higher breathing amplitudes, larger period times, lower dose levels, and more complex treatment plans. Also, the interplay effects varied considerably with the initial breathing phase, and larger variations were observed for smaller CTV sizes. In conclusion, a method to simulate motion induced interplay effects was developed and verified with measurements, which allowed for a large number of treatment scenarios to be investigated. The simulations showed large interplay effects for individual fractions and that the extent of interplay effects varied with the breathing pattern, FFF/FF, dose level, CTV size, collimator angle, and the complexity of the treatment plan.

SU-E-T-491: Influence of Applicator Dimensions On Doses to Bladder, Rectum and Sigmoid in HDR Brachytherapy for Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dumane, V; Rhome, R; Yuan, Y

2015-06-15

Purpose: To study the influence of dimensions of the tandem and ring applicator on bladder D2cc, rectum D2cc and sigmoid D2cc in HDR treatment planning for cervical cancer. Methods: 53 plans from 13 patients treated at our institution with the tandem and ring applicator were retrospectively reviewed. Prescription doses were one of the following: 8 Gy x 3, 7 Gy x 4 and 5.5 Gy x 5. Doses to the D2ccs of the bladder, rectum and the sigmoid were recorded. These doses were normalized to their relative prescriptions doses. Correlations between the normalized bladder D2cc, rectum D2cc and sigmoid D2ccmore » were investigated and linear regression models were developed to study the dependence of these doses on the ring diameter and the applicator angle. Results: Normalized doses to the D2cc of the bladder, rectum and sigmoid showed statistically significant correlation (P < 0.05) to the applicator angle. Significant correlation was also noted for the normalized D2cc of the rectum and the sigmoid with the ring diameter. The normalized bladder D2cc was found to decrease with applicator angle on an average by 22.65% ± 4.43% while the same for the rectum and sigmoid were found to increase on an average by 14.43% ± 1.65% and 14.01% ± 1.42% respectively. Both the rectum and sigmoid D2cc reduced with increasing ring diameter by 12.93% ± 1.95% and 11.27% ± 1.79%. No correlation was observed between the normalized bladder D2cc and the ring diameter. Conclusion: Preliminary regression models developed in this study can potentially aid in the choice of the appropriate applicator angle and ring diameter for tandem and ring implant so as to optimize doses to the bladder, rectum and sigmoid.« less

Cc2d1a Loss of Function Disrupts Functional and Morphological Development in Forebrain Neurons Leading to Cognitive and Social Deficits.

PubMed

Oaks, Adam W; Zamarbide, Marta; Tambunan, Dimira E; Santini, Emanuela; Di Costanzo, Stefania; Pond, Heather L; Johnson, Mark W; Lin, Jeff; Gonzalez, Dilenny M; Boehler, Jessica F; Wu, Guangying K; Klann, Eric; Walsh, Christopher A; Manzini, M Chiara

2017-02-01

Loss-of-function (LOF) mutations in CC2D1A cause a spectrum of neurodevelopmental disorders, including intellectual disability, autism spectrum disorder, and seizures, identifying a critical role for this gene in cognitive and social development. CC2D1A regulates intracellular signaling processes that are critical for neuronal function, but previous attempts to model the human LOF phenotypes have been prevented by perinatal lethality in Cc2d1a-deficient mice. To overcome this challenge, we generated a floxed Cc2d1a allele for conditional removal of Cc2d1a in the brain using Cre recombinase. While removal of Cc2d1a in neuronal progenitors using Cre expressed from the Nestin promoter still causes death at birth, conditional postnatal removal of Cc2d1a in the forebrain via calcium/calmodulin-dependent protein kinase II-alpha (CamKIIa) promoter-driven Cre generates animals that are viable and fertile with grossly normal anatomy. Analysis of neuronal morphology identified abnormal cortical dendrite organization and a reduction in dendritic spine density. These animals display deficits in neuronal plasticity and in spatial learning and memory that are accompanied by reduced sociability, hyperactivity, anxiety, and excessive grooming. Cc2d1a conditional knockout mice therefore recapitulate features of both cognitive and social impairment caused by human CC2D1A mutation, and represent a model that could provide much needed insights into the developmental mechanisms underlying nonsyndromic neurodevelopmental disorders. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Comparison of anisotropic aperture based intensity modulated radiotherapy with 3D-conformal radiotherapy for the treatment of large lung tumors.

PubMed

Simeonova, Anna; Abo-Madyan, Yasser; El-Haddad, Mostafa; Welzel, Grit; Polednik, Martin; Boggula, Ramesh; Wenz, Frederik; Lohr, Frank

2012-02-01

IMRT allows dose escalation for large lung tumors, but respiratory motion may compromise delivery. A treatment plan that modulates fluence predominantly in the transversal direction and leaves the fluence identical in the direction of the breathing motion may reduce this problem. Planning-CT-datasets of 20 patients with Stage I-IV non small cell lung cancer (NSCLC) formed the basis of this study. A total of two IMRT plans and one 3D plan were created for each patient. Prescription dose was 60 Gy to the CTV and 70 Gy to the GTV. For the 3D plans an energy of 18 MV photons was used. IMRT plans were calculated for 6 MV photons with 13 coplanar and with 17 noncoplanar beams. Robustness of the used method of anisotropic modulation toward breathing motion was tested in a 13-field IMRT plan. As a consequence of identical prescription doses, mean target doses were similar for 3D and IMRT. Differences between 3D and 13- and 17-field IMRT were significant for CTV Dmin (43 Gy vs. 49.1 Gy vs. 48.6 Gy; p<0.001) and CTV D(95) (53.2 Gy vs. 55.0 Gy vs. 55.4 Gy; p=0.001). The D(mean) of the contralateral lung was significantly lower in the 17-field plans (17-field IMRT vs. 13- vs. 3D: 12.5 Gy vs. 14.8 Gy vs. 15.8 Gy: p<0.05). The spinal cord dose limit of 50 Gy was always respected in IMRT plans and only in 17 of 20 3D-plans. Heart D(max) was only marginally reduced with IMRT (3D vs. 13- vs. 17-field IMRT: 38.2 Gy vs. 36.8 Gy vs. 37.8 Gy). Simulated breathing motion caused only minor changes in the IMRT dose distribution (~0.5-1 Gy). Anisotropic modulation of IMRT improves dose delivery over 3D-RT and renders IMRT plans robust toward breathing induced organ motion, effectively preventing interplay effects. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Image-guided brachytherapy for cervical cancer: analysis of D2 cc hot spot in three-dimensional and anatomic factors affecting D2 cc hot spot in organs at risk.

PubMed

Kim, Robert Y; Dragovic, Alek F; Whitley, Alexander C; Shen, Sui

2014-01-01

To analyze the D2 cc hot spot in three-dimensional CT and anatomic factors affecting the D2 cc hot spot in organs at risk (OARs). Thirty-one patients underwent pelvic CT scan after insertion of the applicator. High-dose-rate treatment planning was performed with standard loading patterns. The D2 cc structures in OARs were generated in three dimensional if the total equivalent dose in 2 Gy exceeded our defined dose limits (hot spot). The location of D2 cc hot spot was defined as the center of the largest D2 cc fragment. The relationship between the hot spot and the applicator position was reported in Digital Imaging and Communication in Medicine coordinates. The location of sigmoid, small bowel, and bladder D2 cc hot spots was around the endocervix: The mean location of sigmoid hot spot for lateral view was 1.6 cm posteriorly and 2.3 cm superiorly (Y, 1.6 and Z, 2.3), small bowel was 1.6 cm anteriorly and 2.7 cm superiorly (Y, -1.6 and Z, 2.7). The mean location of bladder hot spot was 1.6 cm anteriorly and 1.6 cm superiorly (Y, -1.6 and Z, 1.6). These hot spots were near the plane of Point A (X, 2.0 or -2.0; Y, 0; and Z, 2.0). The mean location of rectal hot spot was 1.6 cm posteriorly and 1.9 cm inferiorly (Y, 1.6 and Z, -1.9). D2 cc hot spot was affected by uterine wall thickness, uterine tandem position, fibroids, bladder fullness, bowel gas, and vaginal packing. Because of the location of the D2 cc hot spots, larger tumors present a challenge for adequate tumor coverage with a conventional brachytherapy applicator without an interstitial implant. Additionally, anatomic factors were identified which affect the D2 cc hot spot in OARs. Copyright © 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, M; Choi, E; Chuong, M

Purpose: To evaluate weather the current radiobiological models can predict the normal liver complications of radioactive Yttrium-90 ({sup 90}Y) selective-internal-radiation-treatment (SIRT) for metastatic liver lesions based on the post-infusion {sup 90}Y PET images. Methods: A total of 20 patients with metastatic liver tumors treated with SIRT that received a post-infusion {sup 90}Y-PET/CT scan were analyzed in this work. The 3D activity distribution of the PET images was converted into a 3D dose distribution via a kernel convolution process. The physical dose distribution was converted into the equivalent dose (EQ2) delivered at 2 Gy based on the linear-quadratic (LQ) model consideringmore » the dose rate effect. The biological endpoint of this work was radiation-induce liver disease (RILD). The NTCPs were calculated with four different repair-times (T1/2-Liver-Repair= 0,0.5,1.0,2.0 hr) and three published NTCP models (Lyman-external-RT, Lyman 90Y-HCC-SIRT, parallel model) were compared to the incidence of RILD of the recruited patients to evaluate their ability of outcome prediction. Results: The mean normal liver physical dose (avg. 51.9 Gy, range 31.9–69.8 Gy) is higher than the suggested liver dose constraint for external beam treatment (∼30 Gy). However, none of the patients in our study developed RILD after the SIRT. The estimated probability of ‘no patient developing RILD’ obtained from the two Lyman models are 46.3% to 48.3% (T1/2-Liver-Repair= 0hr) and <1% for all other repair times. For the parallel model, the estimated probability is 97.3% (0hr), 51.7% (0.5hr), 2.0% (1.0hr) and <1% (2.0hr). Conclusion: Molecular-images providing the distribution of {sup 90}Y enable the dose-volume based dose/outcome analysis for SIRT. Current NTCP models fail to predict RILD complications in our patient population, unless a very short repair-time for the liver is assumed. The discrepancy between the Lyman {sup 90}Y-HCC-SIRT model predicted and the clinically observed outcomes further demonstrates the need of an NTCP model specific to the metastatic liver SIRT.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liang, X; Li, Z; Zheng, D

Purpose: In the context of evaluating dosimetric impacts of a variety of uncertainties involved in HDR Tandem-and-Ovoid treatment, to study the correlations between conventional point doses and 3D volumetric doses. Methods: For 5 cervical cancer patients treated with HDR T&O, 150 plans were retrospectively created to study dosimetric impacts of the following uncertainties: (1) inter-fractional applicator displacement between two treatment fractions within a single insertion by applying Fraction#1 plan to Fraction#2 CT; (2) positional dwell error simulated from −5mm to 5mm in 1mm steps; (3) simulated temporal dwell error of 0.05s, 0.1s, 0.5s, and 1s. The original plans were basedmore » on point dose prescription, from which the volume covered by the prescription dose was generated as the pseudo target volume to study the 3D target dose effect. OARs were contoured. The point and volumetric dose errors were calculated by taking the differences between original and simulated plans. The correlations between the point and volumetric dose errors were analyzed. Results: For the most clinically relevant positional dwell uncertainty of 1mm, temporal uncertainty of 0.05s, and inter-fractional applicator displacement within the same insertion, the mean target D90 and V100 deviation were within 1%. Among these uncertainties, the applicator displacement showed the largest potential target coverage impact (2.6% on D90) as well as the OAR dose impact (2.5% and 3.4% on bladder D2cc and rectum D2cc). The Spearman correlation analysis shows a correlation coefficient of 0.43 with a p-value of 0.11 between target D90 coverage and H point dose. Conclusion: With the most clinically relevant positional and temporal dwell uncertainties and patient interfractional applicator displacement within the same insertion, the dose error is within clinical acceptable range. The lack of correlation between H point and 3D volumetric dose errors is a motivator for the use of 3D treatment planning in cervical HDR brachytherapy.« less

Study of Three Dimensional Transonic Flow Separations.

DTIC Science & Technology

1988-04-01

22222222222222222222222222222222222222 CD22 2 NN 22 0 2 2 C 22 .2 2 .2 .2 .2 .’ 22 . . . cD( C) DC)C DC D CC 222 2 22 2 2- C 2 22 22 22 - 22 02 N NT NL z...In1.0 INco (N -.- L’ c3 107 :-I--cnr -! - - N N 1 f;CC-7 cD c, 222 c222 cN -) H22 o cc -- -4 0,2222222" (D2 C22 22 D2 220 CD22 CD 2 CD CD N22 22D2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pokhrel, D; Mallory, M; Badkul, R

Purpose: To retrospectively evaluate quality, efficiency and delivery accuracy of intensity modulated arc therapy (IMAT) plans for thoracic-vertebral metastases using stereotactic body radiotherapy (SBRT). Methods: After obtaining approval of RPC-benchmark plan, seven previously treated thoracic-vertebral metastases patients with non-coplanar hybrid arcs(NC-HA)using 1–2 3D-dynamic conformal partial-arcs plus 7–9 IMRT-beams were re-optimized with IMAT using 3 full co-planar arcs. Tumors were located between T2–T7. T1/T2-weighted MRI images were co-registered with planning-CT. PTVs were between 24.3–240.1cc(median=48.1cc). Prescription was 30Gy in 5 fractions with 6-MV beams at Novalis-TX consisting of HD-MLC.Plans were compared for target coverage:conformality index(CI),homogeneity index(HI),PTVD90. Organs-at-risks(OARs)was evaluated for spinal cord(Dmax, D0.35cc,more » and D1.2cc), esophagus(Dmax and D5cc),heart(Dmax, D15cc)and lung(V5 and V10). Dose delivery efficiency and accuracy of each IMAT plan was assessed via quality assurance(QA) plan. Beam-on time was recorded and a gamma index was used to compare agreement between planned and measured doses. Results: SBRT IMAT plans resulted in superior CI(1.02 vs. 1.36, p=0.05) and HI (0.14 vs. 0.27, p=0.01). PTVD90 was improved but statistically insignificant (31.0 vs. 30.4Gy, p=0.38). IMAT resulted in statistically significant improvements in OARs sparing: esophagus max(22.5 vs. 27.0Gy, p=0.03), esophagus 5cc (17.6 vs. 21.5Gy, p=0.02) and heart max(13.1 vs. 15.8Gy, p=0.03). Spinal cord,lung V5 and V10 were lower but statistically insignificant. Average total MU and beam-on time were 2598±354 vs. 3542±495 and 4.7±0.6 min vs. 7.1±1.0min for IMAT vs. NC-HA (without accounting for couch kicks time for NC-HA). IMAT plans demonstrated an accurate dose delivery of 95.5±1.0% for clinical gamma passing-rate of 2%/2mm criteria on MapCHECK, that was comparable to NC-HA plans. Conclusion: IMAT plans provided highly conformal and homogeneous dose distributions to target and reduced OARs doses compared to NC-HA. Total MU was reduced by a factor of 1.4 and subsequently decreased treatment times significantly - potentially minimizing intra-fraction motion error and owing to patient comfort. SBRT using IMAT planning for single fraction thoracic-vertebrae metastases will be investigated.« less

Restricted L1 Estimators and Their Covariances,

DTIC Science & Technology

1980-06-01

CD22 w =e 1-.< l’ -- I -M Ce -=, -2 C 22 CD -. 00 CD LJ L":v, wD .-C >-C CD U., -D -a 22J CD: CD. Vt. U.1 . CD* 31- a UOC CD I" -J zI == CŖ - 1- InCC.J...C 22 CC:.: 2 15Cb In0’C C 4 t’ 3 CD.2-cm I- I.- iC2 CD-3SJ U. cc CDam CC 22 0.-J~ I- iD C Me CC .JJ . A.2 Dt-2C. 2. D ~ 2 CD, Z-i- C -J 2Cn LI CD22 ...22 "I.- bII CD 0.-..CW I -- k- -o. CDCD-c =DDCCC-ce CDI- 22eCCDC.C I-L- 5 2wI-CDUct. I4.CDgCD Ci L., 2=9 E Mm t,2 cm CD22 ,,- D.-.2RCC Ce:CD .Cc n 9

SU-E-T-07: 4DCT Robust Optimization for Esophageal Cancer Using Intensity Modulated Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liao, L; Department of Industrial Engineering, University of Houston, Houston, TX; Yu, J

2015-06-15

Purpose: To develop a 4DCT robust optimization method to reduce the dosimetric impact from respiratory motion in intensity modulated proton therapy (IMPT) for esophageal cancer. Methods: Four esophageal cancer patients were selected for this study. The different phases of CT from a set of 4DCT were incorporated into the worst-case dose distribution robust optimization algorithm. 4DCT robust treatment plans were designed and compared with the conventional non-robust plans. Result doses were calculated on the average and maximum inhale/exhale phases of 4DCT. Dose volume histogram (DVH) band graphic and ΔD95%, ΔD98%, ΔD5%, ΔD2% of CTV between different phases were used tomore » evaluate the robustness of the plans. Results: Compare to the IMPT plans optimized using conventional methods, the 4DCT robust IMPT plans can achieve the same quality in nominal cases, while yield a better robustness to breathing motion. The mean ΔD95%, ΔD98%, ΔD5% and ΔD2% of CTV are 6%, 3.2%, 0.9% and 1% for the robustly optimized plans vs. 16.2%, 11.8%, 1.6% and 3.3% from the conventional non-robust plans. Conclusion: A 4DCT robust optimization method was proposed for esophageal cancer using IMPT. We demonstrate that the 4DCT robust optimization can mitigate the dose deviation caused by the diaphragm motion.« less

Polymorphism of the Transcription Factor 7-Like 2 Gene (TCF7L2) Interacts with Obesity on Type-2 Diabetes in the PREDIMED Study Emphasizing the Heterogeneity of Genetic Variants in Type-2 Diabetes Risk Prediction: Time for Obesity-Specific Genetic Risk Scores.

PubMed

Corella, Dolores; Coltell, Oscar; Sorlí, Jose V; Estruch, Ramón; Quiles, Laura; Martínez-González, Miguel Ángel; Salas-Salvadó, Jordi; Castañer, Olga; Arós, Fernando; Ortega-Calvo, Manuel; Serra-Majem, Lluís; Gómez-Gracia, Enrique; Portolés, Olga; Fiol, Miquel; Díez Espino, Javier; Basora, Josep; Fitó, Montserrat; Ros, Emilio; Ordovás, José M

2016-12-06

Nutrigenetic studies analyzing gene-diet interactions of the TCF7L2-rs7903146 C > T polymorphism on type-2 diabetes (T2D) have shown controversial results. A reason contributing to this may be the additional modulation by obesity. Moreover, TCF7L2-rs7903146 is one of the most influential variants in T2D-genetic risk scores (GRS). Therefore, to increase the predictive value (PV) of GRS it is necessary to first see whether the included polymorphisms have heterogeneous effects. We comprehensively investigated gene-obesity interactions between the TCF7L2-rs7903146 C > T polymorphism on T2D (prevalence and incidence) and analyzed other T2D-polymorphisms in a sub-sample. We studied 7018 PREDIMED participants at baseline and longitudinally (8.7 years maximum follow-up). Obesity significantly interacted with the TCF7L2-rs7903146 on T2D prevalence, associations being greater in non-obese subjects. Accordingly, we prospectively observed in non-T2D subjects ( n = 3607) that its association with T2D incidence was stronger in non-obese (HR: 1.81; 95% CI: 1.13-2.92, p = 0.013 for TT versus CC) than in obese subjects (HR: 1.01; 95% CI: 0.61-1.66; p = 0.979; p -interaction = 0.048). Accordingly, TCF7L2-PV was higher in non-obese subjects. Additionally, we created obesity-specific GRS with ten T2D-polymorphisms and demonstrated for the first time their higher strata-specific PV. In conclusion, we provide strong evidence supporting the need for considering obesity when analyzing the TCF7L2 effects and propose the use of obesity-specific GRS for T2D.

No Interaction with Alcohol Consumption, but Independent Effect of C12orf51 (HECTD4) on Type 2 Diabetes Mellitus in Korean Adults Aged 40-69 Years: The KoGES_Ansan and Ansung Study.

PubMed

Kim, Jihye; Oh, Bermseok; Lim, Ji Eun; Kim, Mi Kyung

2016-01-01

Previously, genetic polymorphisms of C12orf51 (HECTD4) (rs2074356 and/or rs11066280) have been shown to be related to alcohol consumption and type 2 diabetes (T2D). This study aimed to prospectively examine whether C12orf51 had an interaction with or independent effect on alcohol consumption and the risk of T2D. The present study included 3,244 men and 3,629 women aged 40 to 69 years who participated in the Korean Genome and Epidemiology Study (KoGES)_Ansan and Ansung Study. Cox proportional hazards models were used to estimate HRs and 95% CIs for T2D. rs2074356 and rs11066280 were associated with the risk of T2D after adjusting for alcohol consumption (rs2074356 for AA: HR = 0.39 and 95% CI = 0.17-0.87 in men, and HR = 0.36 and 95% CI = 0.13-0.96 in women; rs11066280 for AA: HR = 0.44 and 95% CI = 0.23-0.86 in men, and HR = 0.39 and 95% CI = 0.16-0.94 in women). We identified that the association of each variant (rs2074356 and rs11065756) in C12orf51 was nearly unchanged after adjusted for alcohol consumption. Therefore, the association of 2 SNPs in C12orf51 with diabetes may not be mediated by alcohol use. There was no interaction effect between alcohol consumption and the SNPs with T2D. However, even in never-drinkers, minor allele homozygote strongly influenced T2D risk reduction (rs2074356 for AA: HR = 0.35, 95% CI = 0.14-0.90, and p-trend = 0.0035 in men and HR = 0.34, 95% CI = 0.13-0.93, and p-trend = 0.2348 in women; rs11066280 for AA: HR = 0.36, 95% CI = 0.16-0.82, and p-trend = 0.0014 in men and HR = 0.39, 95% CI = 0.16-0.95, and p-trend = 0.3790 in women), while alcohol consumption did not influence the risk of T2D within each genotype. rs2074356 and rs11066280 in or near C12orf51, which is related to alcohol drinking behavior, may longitudinally decrease the risk of T2D, but not through regulation of alcohol consumption.

Evaluation of the setup margins for cone beam computed tomography–guided cranial radiosurgery: A phantom study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Calvo Ortega, Juan Francisco, E-mail: jfcdrr@yahoo.es; Wunderink, Wouter; Delgado, David

The aim of this study is to evaluate the setup margins from the clinical target volume (CTV) to planning target volume (PTV) for cranial stereotactic radiosurgery (SRS) treatments guided by cone beam computed tomography (CBCT). We designed an end-to-end (E2E) test using a skull phantom with an embedded 6mm tungsten ball (target). A noncoplanar plan was computed (E2E plan) to irradiate the target. The CBCT-guided positioning of the skull phantom on the linac was performed. Megavoltage portal images were acquired after 15 independent deliveries of the E2E plan. The displacement 2-dimensional (2D) vector between the centers of the square fieldmore » and the ball target on each portal image was used to quantify the isocenter accuracy. Geometrical margins on each patient's direction (left-right or LR, anterior-posterior or AP, superior-inferior or SI) were calculated. Dosimetric validation of the margins was performed in 5 real SRS cases: 3-dimesional (3D) isocenter deviations were mimicked, and changes in CTV dose coverage and organs-at-risk (OARs) dosage were analyzed. The CTV-PTV margins of 1.1 mm in LR direction, and 0.7 mm in AP and SI directions were derived from the E2E tests. The dosimetric analysis revealed that a 1-mm uniform margin was sufficient to ensure the CTV dose coverage, without compromising the OAR dose tolerances. The effect of isocenter uncertainty has been estimated to be 1 mm in our CBCT-guided SRS approach.« less

Immobilisation precision in VMAT for oral cancer patients

NASA Astrophysics Data System (ADS)

Norfadilah, M. N.; Ahmad, R.; Heng, S. P.; Lam, K. S.; Radzi, A. B. Ahmad; John, L. S. H.

2017-05-01

A study was conducted to evaluate and quantify a precision of the interfraction setup with different immobilisation devices throughout the treatment time. Local setup accuracy was analysed for 8 oral cancer patients receiving radiotherapy; 4 with HeadFIX® mouthpiece moulded with wax (HFW) and 4 with 10 ml/cc syringe barrel (SYR). Each patients underwent Image Guided Radiotherapy (IGRT) with total of 209 cone-beam computed tomography (CBCT) data sets for position set up errors measurement. The setup variations in the mediolateral (ML), craniocaudal (CC), and anteroposterior (AP) dimensions were measured. Overall mean displacement (M), the population systematic (Σ) and random (σ) errors and the 3D vector length were calculated. Clinical target volume to planning target volume (CTV-PTV) margins were calculated according to the van Herk formula (2.5Σ+0.7σ). The M values for both group were < 1 mm and < 1° in all translational and rotational directions. This indicate there is no significant imprecision in the equipment (lasers) and during procedure. The interfraction translational 3 dimension vector for HFW and SYR were 1.93±0.66mm and 3.84±1.34mm, respectively. The interfraction average rotational error were 0.00°±0.65° and 0.34°±0.59°, respectively. CTV-PTV margins along the 3 translational axis (Right-Left, Superior-Inferior, Anterior-Posterior) calculated were 3.08, 2.22 and 0.81 mm for HFW and 3.76, 6.24 and 5.06 mm for SYR. The results of this study have demonstrated that HFW more precise in reproducing patient position compared to conventionally used SYR (p<0.001). All margin calculated did not exceed hospital protocol (5mm) except S-I and A-P axes using syringe. For this reason, a daily IGRT is highly recommended to improve the immobilisation precision.

The influence of FLiNaK salt impregnation on the mechanical properties of a 2D woven C/C composite

NASA Astrophysics Data System (ADS)

Zhang, Dongsheng; Xia, Huihao; Yang, Xinmei; Feng, Shanglei; Song, Jinliang; Zhou, Xingtai

2017-03-01

Impregnating of molten LiF-NaF-KF salt (LiF-NaF-KF: 46.5-11.5-42 mol%, FLiNaK) into a 2D woven C/C composite was performed at 650 °C under different pressure. The weight gain and mechanical properties change of the 2D woven C/C composite after FLiNaK salt impregnation were measured. The FLiNaK salt distribution into the 2D woven C/C composite was observed by X-ray computed tomography (X-ray CT) and scanning electron microscopy. The results showed that the weight gain of the 2D woven C/C composite increased with increasing impregnating pressure. In X-ray CT images, FLiNaK salt was distributed into the open pores and fissures among fiber bundles and neighboring plies. The interlaminar shear strength, compressive strength, and flexural strength of the 2D woven C/C composite increased with the increase of weight gain. The influence of FLiNaK salt impregnation on the mechanical properties was attributed to the coupling effect of re-densification of FLiNaK salt impregnation and residual stress formed in 2D woven C/C composite.

SU-E-T-548: How To Decrease Spine Dose In Patients Who Underwent Sterotactic Spine Radiosurgery?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Acar, H; Altinok, A; Kucukmorkoc, E

2014-06-01

Purpose: Stereotactic radiosurgery for spine metastases involves irradiation using a single high dose fraction. The purpose of this study was to dosimetrically compare stereotactic spine radiosurgery(SRS) plans using a recently new volumetric modulated arc therapy(VMAT) technique against fix-field intensity-modulated radiotherapy(IMRT). Plans were evaluated for target conformity and spinal cord sparing. Methods: Fifteen previously treated patients were replanned using the Eclipse 10.1 TPS AAA calculation algorithm. IMRT plans with 7 fields were generated. The arc plans used 2 full arc configurations. Arc and IMRT plans were normalized and prescribed to deliver 16.0 Gy in a single fraction to 90% of themore » planning target volume(PTV). PTVs consisted of the vertebral body expanded by 3mm, excluding the PRV-cord, where the cord was expanded by 2mm.RTOG 0631 recommendations were applied for treatment planning. Partial spinal cord volume was defined as 5mm above and below the radiosurgery target volume. Plans were compared for conformity and gradient index as well as spinal cord sparing. Results: The conformity index values of fifteen patients for two different treatment planning techniques were shown in table 1. Conformity index values for 2 full arc planning (average CI=0.84) were higher than that of IMRT planning (average CI=0.79). The gradient index values of fifteen patients for two different treatment planning techniques were shown in table 2. Gradient index values for 2 full arc planning (average GI=3.58) were higher than that of IMRT planning (average GI=2.82).The spinal cord doses of fifteen patients for two different treatment planning techniques were shown in table 3. D0.35cc, D0.03cc and partial spinal cord D10% values in 2 full arc plannings (average D0.35cc=819.3cGy, D0.03cc=965.4cGy, 10%partial spinal=718.1cGy) were lower than IMRT plannings (average D0.35cc=877.4cGy, D0.03c=1071.4cGy, 10%partial spinal=805.1cGy). Conclusions: The two arc VMAT technique is superior to 7 field IMRT technique in terms of both spinal cord sparing and better conformity and gradient indexes.« less

Mediterranean Diet Reduces the Adverse Effect of the TCF7L2-rs7903146 Polymorphism on Cardiovascular Risk Factors and Stroke Incidence

PubMed Central

Corella, Dolores; Carrasco, Paula; Sorlí, Jose V.; Estruch, Ramón; Rico-Sanz, Jesús; Martínez-González, Miguel Ángel; Salas-Salvadó, Jordi; Covas, M. Isabel; Coltell, Oscar; Arós, Fernando; Lapetra, José; Serra-Majem, Lluís; Ruiz-Gutiérrez, Valentina; Warnberg, Julia; Fiol, Miquel; Pintó, Xavier; Ortega-Azorín, Carolina; Muñoz, Miguel Ángel; Martínez, J. Alfredo; Gómez-Gracia, Enrique; González, José I.; Ros, Emilio; Ordovás, José M.

2013-01-01

OBJECTIVE Transcription factor 7-like 2 (TCF7L2) polymorphisms are strongly associated with type 2 diabetes, but controversially with plasma lipids and cardiovascular disease. Interactions of the Mediterranean diet (MedDiet) on these associations are unknown. We investigated whether the TCF7L2-rs7903146 (C>T) polymorphism associations with type 2 diabetes, glucose, lipids, and cardiovascular disease incidence were modulated by MedDiet. RESEARCH DESIGN AND METHODS A randomized trial (two MedDiet intervention groups and a control group) with 7,018 participants in the PREvención con DIetaMEDiterránea study was undertaken and major cardiovascular events assessed. Data were analyzed at baseline and after a median follow-up of 4.8 years. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) for cardiovascular events. RESULTS The TCF7L2-rs7903146 polymorphism was associated with type 2 diabetes (odds ratio 1.87 [95% CI 1.62–2.17] for TT compared with CC). MedDiet interacted significantly with rs7903146 on fasting glucose at baseline (P interaction = 0.004). When adherence to the MedDiet was low, TT had higher fasting glucose concentrations (132.3 ± 3.5 mg/dL) than CC+CT (127.3 ± 3.2 mg/dL) individuals (P = 0.001). Nevertheless, when adherence was high, this increase was not observed (P = 0.605). This modulation was also detected for total cholesterol, LDL cholesterol, and triglycerides (P interaction < 0.05 for all). Likewise, in the randomized trial, TT subjects had a higher stroke incidence in the control group (adjusted HR 2.91 [95% CI 1.36–6.19]; P = 0.006 compared with CC), whereas dietary intervention with MedDiet reduced stroke incidence in TT homozygotes (adjusted HR 0.96 [95% CI 0.49–1.87]; P = 0.892 for TT compared with CC). CONCLUSIONS Our novel results suggest that MedDiet may not only reduce increased fasting glucose and lipids in TT individuals, but also stroke incidence. PMID:23942586

A Population-Based Comparative Effectiveness Study of Radiation Therapy Techniques in Stage III Non-Small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harris, Jeremy P.; Murphy, James D.; Hanlon, Alexandra L.

2014-03-15

Purpose: Concerns have been raised about the potential for worse treatment outcomes because of dosimetric inaccuracies related to tumor motion and increased toxicity caused by the spread of low-dose radiation to normal tissues in patients with locally advanced non-small cell lung cancer (NSCLC) treated with intensity modulated radiation therapy (IMRT). We therefore performed a population-based comparative effectiveness analysis of IMRT, conventional 3-dimensional conformal radiation therapy (3D-CRT), and 2-dimensional radiation therapy (2D-RT) in stage III NSCLC. Methods and Materials: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify a cohort of patients diagnosed with stage III NSCLC frommore » 2002 to 2009 treated with IMRT, 3D-CRT, or 2D-RT. Using Cox regression and propensity score matching, we compared survival and toxicities of these treatments. Results: The proportion of patients treated with IMRT increased from 2% in 2002 to 25% in 2009, and the use of 2D-RT decreased from 32% to 3%. In univariate analysis, IMRT was associated with improved overall survival (OS) (hazard ratio [HR] 0.90, P=.02) and cancer-specific survival (CSS) (HR 0.89, P=.02). After controlling for confounders, IMRT was associated with similar OS (HR 0.94, P=.23) and CSS (HR 0.94, P=.28) compared with 3D-CRT. Both techniques had superior OS compared with 2D-RT. IMRT was associated with similar toxicity risks on multivariate analysis compared with 3D-CRT. Propensity score matched model results were similar to those from adjusted models. Conclusions: In this population-based analysis, IMRT for stage III NSCLC was associated with similar OS and CSS and maintained similar toxicity risks compared with 3D-CRT.« less

Edema worsens target coverage in high-dose-rate interstitial brachytherapy of mobile tongue cancer: a report of two cases.

PubMed

Yoshida, Ken; Yamazaki, Hideya; Kotsuma, Tadayuki; Akiyama, Hironori; Takenaka, Tadashi; Masui, Koji; Yoshioka, Yasuo; Uesugi, Yasuo; Shimbo, Taiju; Yoshikawa, Nobuhiko; Yoshioka, Hiroto; Arika, Takumi; Tanaka, Eiichi; Narumi, Yoshifumi

2017-02-01

We report our study on two patients to highlight the risk of underdosage of the clinical target volume (CTV) due to edema during high-dose-rate interstitial brachytherapy (HDR-ISBT) of mobile tongue cancer. To treat the lateral side of the CTV, flexible applicator tubes were implanted on the mouth floor. Two-dimensional planning was performed using X-ray images for Case 1, and three-dimensional (3D) planning was performed using computed tomography (CT) for Case 2. Prescribed doses for both cases were 54 Gy in nine fractions. Case 1 was treated for cancer of the right lateral border of the tongue in 2005. Tongue edema occurred after implantation, and part of the lateral border of the tongue protruded between the applicator tubes. Acute mucosal reaction abated in the protruded area earlier than in the other parts of the CTV. In this case, the tumor recurred in this area 5 months after the treatment. Case 2 was treated for cancer of the left lateral border of the tongue. Because tongue edema occurred in this case also, plastic splints were inserted between the applicator tubes to push the edematous region into the irradiated area. The mucosal surface of the CTV was covered by the 70% isodose, and 100% isodose line for before and after splint insertion. Local control of the tumor was achieved 4 years after treatment. To ensure sufficient target coverage, 3D image-based planning using CT should be performed, followed by re-planning using repeated CT as needed. Also, the development of devices to prevent protrusion of the edematous tissue outside the target area will help to ensure the full dosing of CTV.

The Association of Resting Heart Rate with the Presence of Diabetes in Korean Adults: The 2010-2013 Korea National Health and Nutrition Examination Survey

PubMed Central

Hong, Jae Won; Noh, Jung Hyun; Kim, Dong-Jun

2016-01-01

Background Previous epidemiologic studies have shown that elevated resting heart rate (HR) is associated with higher cardiovascular disease (CVD) morbidity and mortality. Although the relationship between elevated HR and CVD is well established, the association between resting HR and diabetes has been relatively understudied, particularly in non-Western populations. Objectives We confirmed the association between the presence of type 2 diabetes and resting HR in the Korean adult population using data from the 2010–2013 Korea National Health and Nutrition Examination Survey (KNHANES). Methods Among 25,712 adults (≥ 19 years of age) who participated in the 2010–2013 KNHANES, a total of 22,512 subjects completed laboratory examinations and were included in this analysis. The fasting plasma glucose (FPG) level was categorized into the following five groups: normal fasting glucose (NFG) 1 (<90 mg/dL), NFG 2 (90–99 mg/dL), impaired fasting glucose (IFG) 1 (100–110 mg/dL), IFG 2 (111–125 mg/dL), and diabetes (≥ 126 mg/dL). Results The unadjusted weighted resting HRs were 69.6, 69.4, 69.8, 70.1, and 72.0 beats per minute (bpm) in the NFG 1, NFG 2, IFG 1, IFG 2, and diabetes groups, respectively (P<0.001). We assessed the adjusted weighted resting HR according to the FPG level after adjusting for age, sex, smoking history, high risk alcohol drinking, daily energy intake, waist circumference, serum total cholesterol level, serum triglyceride (TG) level, serum white blood cell (WBC) count, serum hemoglobin (Hb), and the presence of hypertension. The adjusted weighted resting HR significantly increased across the FPG groups (P<0.001). The weighted prevalence rates of diabetes were 6.8% (6.2–7.5%), 7.6% (6.7–8.5%), 8.0% (7.0–9.1%), and 11.8% (10.8–12.7%) in subjects with HR ≤ 64, 65–69, 70–75, and ≥ 76 bpm, respectively (P<0.001), after adjusting for the confounding factors mentioned above. Using resting HR ≤ 64 bpm as the control, resting HR ≥ 76 bpm was correlated with the presence of diabetes (adjusted OR 1.83, 95% CI 1.55–2.16, P<0.001). Each 10 bpm increment of HR increased the risk of the presence of diabetes by 35% (P<0.001). This association of high resting HR with the presence of diabetes was not influenced by the status of blood pressure (BP) medication. Conclusion We demonstrated that higher HR was associated with diabetes in a representative sample of Korean adults. These positive associations were independent of age, sex, current smoking, high risk alcohol drinking, daily energy intake, waist circumference, and the presence of hypertension and other potential confounders. This study suggests that individuals with higher resting HR are at risk of diabetes and that HR might provide an easy and simple surrogate marker for the risk of diabetes. PMID:27992613

Evaluation of litter type and dietary coarse ground corn inclusion on broiler live performance, gastrointestinal tract development, and litter characteristics.

PubMed

Xu, Y; Stark, C R; Ferket, P R; Williams, C M; Nusairat, B; Brake, J

2015-03-01

Two 49 d floor pen studies were conducted to evaluate the effects of litter type and dietary coarse ground corn (CC) inclusion on broiler live performance, gastrointestinal tract (GIT) development, and litter characteristics. Experiment 1 was a 2×2 factorial arrangement of 2 genders (male or female) and 2 CC levels (0 or 50%). From 15 to 35 d, the addition of CC decreased feed intake (P<0.01) and BW gain (P<0.05) of males but not females. The inclusion of CC decreased feed intake (P<0.01) and BW gain (P<0.01) from 0 to 49 d but improved adjusted feed conversion ratio (AdjFCR) from 35 to 49 d (P<0.05). Male broilers exhibited better live performance than females during the study as evidenced by greater feed intake (P<0.01) and BW gain (P<0.01), and improved FCR (P<0.01), but with increased mortality (P<0.05). The inclusion of CC increased relative gizzard weight (P<0.01) and decreased relative proventriculus weight (P<0.01) at 49 d. Experiment 2 was a 2×2 factorial arrangement of 2 CC levels (0 or 50%) and 2 litter types (ground old litter or new wood shavings litter). The inclusion of CC decreased feed intake throughout the experiment without affecting final BW when only males were used and improved FCR after 25 d (P<0.01). New litter improved FCR from 1 to 14 d (P<0.01). At 49 d, the birds fed the CC diet had reduced excreta nitrogen (P<0.05) and litter moisture (P<0.05). In conclusion, 50% CC inclusion initially produced negative effects on live performance that became positive as BW increased. The effects of CC became evident at an earlier age for males. New litter had only a marginal benefit on broiler live performance. © 2015 Poultry Science Association Inc.

Scheduling and Coordination of Multiple Dynamic Systems.

DTIC Science & Technology

1979-12-01

Lemna 9. For C (.) defined in (39), .im C (D) -C (D ) exists V DE(.,D) (42) D-D and him4 C(D) C*(D+) exists V DE[D,D). (43) D-D Proof. For any DEi(,D] a...0[t0 ,1 ] where -to - [t,..., tK ’ (151) With this minor abuse of notation, the gradient of C[(t,V1 is to be K found with respect to t ER This

Tri-Service Literacy and Readability: Workshop Proceedings.

DTIC Science & Technology

1980-03-01

LN zC t’ DC D -2l C CC U CC., r C CzC.C-.C, CC C ~ ., caCQ.. *’UC - -C CL UQC’CC Ci - CT 0 --. . C DJZDCU- CC C C. C C...8217 flCCD.- CC, CCC~4J o zC C-Ca C ,.-C,-.O ,-,- CC CC,.. -- r C C,- -z~~~~~~~~~~~~~~~ (U’~’ C- O’ ,.0 C CCC,.. D Ca D CCCO.C - 0.a l F--Ci E CC CC CDO C C...understanding in problem solving. In Catellan, N. J., Jr., Pisoni, D . B., & Potts G. R . (Eds.), Cognitive theory. Hillsdale, NJ: Lawrence Erlbaum

D* production in deep inelastic scattering at HERA

NASA Astrophysics Data System (ADS)

Breitweg, J.; Derrick, M.; Krakauer, D.; Magill, S.; Mikunas, D.; Musgrave, B.; Repond, J.; Stanek, R.; Talaga, R. L.; Yoshida, R.; Zhang, H.; Mattingly, M. C. K.; Anselmo, F.; Antonioli, P.; Bari, G.; Basile, M.; Bellagamba, L.; Boscherini, D.; Bruni, A.; Bruni, G.; Romeo, G. Cara; Castellini, G.; Cifarelli, L.; Cindolo, F.; Contin, A.; Corradi, M.; de Pasquale, S.; Gialas, I.; Giusti, P.; Iacobucci, G.; Laurenti, G.; Levi, G.; Margotti, A.; Massam, T.; Nania, R.; Palmonari, F.; Pesci, A.; Polini, A.; Sartorelli, G.; Garcia, Y. Zamora; Zichichi, A.; Amelung, C.; Bornheim, A.; Brock, I.; Coböken, K.; Crittenden, J.; Deffner, R.; Eckert, M.; Feld, L.; Grothe, M.; Hartmann, H.; Heinloth, K.; Heinz, L.; Hilger, E.; Jakob, H.-P.; Katz, U. F.; Paul, E.; Pfeiffer, M.; Rembser, Ch.; Stamm, J.; Wedemeyer, R.; Bailey, D. S.; Campbell-Robson, S.; Cottingham, W. N.; Foster, B.; Hall-Wilton, R.; Hayes, M. E.; Heath, G. P.; Heath, H. F.; Piccioni, D.; Roff, D. G.; Tapper, R. J.; Arneodo, M.; Ayad, R.; Capua, M.; Garfagnini, A.; Iannotti, L.; Schioppa, M.; Susinno, G.; Kim, J. Y.; Lee, J. H.; Lim, I. T.; Pac, M. Y.; Caldwell, A.; Cartiglia, N.; Jing, Z.; Liu, W.; Parsons, J. A.; Ritz, S.; Sampson, S.; Sciulli, F.; Straub, P. B.; Zhu, Q.; Borzemski, P.; Chwastowski, J.; Eskreys, A.; Jakubowski, Z.; Przybycień, M. B.; Zachara, M.; Zawiejski, L.; Adamczyk, L.; Bednarek, B.; Jeleń, K.; Kisielewska, D.; Kowalski, T.; Przybycień, M.; Rulikowska-Zarȩbska, E.; Suszycki, L.; Zajac, J.; Duliński, Z.; Kotański, A.; Abbiendi, G.; Bauerdick, L. A. T.; Behrens, U.; Beier, H.; Bienlein, J. K.; Cases, G.; Deppe, O.; Desler, K.; Drews, G.; Fricke, U.; Gilkinson, D. J.; Glasman, C.; Göttlicher, P.; Große-Knetter, J.; Haas, T.; Hain, W.; Hasell, D.; Johnson, K. F.; Kasemann, M.; Koch, W.; Kötz, U.; Kowalski, H.; Labs, J.; Lindemann, L.; Löhr, B.; Löwe, M.; Mańczak, O.; Milewski, J.; Monteiro, T.; Ng, J. S. T.; Notz, D.; Ohrenberg, K.; Park, I. H.; Pellegrino, A.; Pelucchi, F.; Piotrzkowski, K.; Roco, M.; Rohde, M.; Roldán, J.; Ryan, J. J.; Savin, A. A.; Schneekloth, U.; Selonke, F.; Surrow, B.; Tassi, E.; Voß, T.; Westphal, D.; Wolf, G.; Wollmer, U.; Youngman, C.; Żarnecki, A. F.; Zeuner, W.; Burow, B. D.; Grabosch, H. J.; Meyer, A.; Schlenstedt, S.; Barbagli, G.; Gallo, E.; Pelfer, P.; Maccarrone, G.; Votano, L.; Bamberger, A.; Eisenhardt, S.; Markun, P.; Trefzger, T.; Wölfle, S.; Bromley, J. T.; Brook, N. H.; Bussey, P. J.; Doyle, A. T.; Saxon, D. H.; Sinclair, L. E.; Strickland, E.; Utley, M. L.; Waugh, R.; Wilson, A. S.; Bohnet, I.; Gendner, N.; Holm, U.; Meyer-Larsen, A.; Salehi, H.; Wick, K.; Gladilin, L. K.; Horstmann, D.; Kçira, D.; Klanner, R.; Lohrmann, E.; Poelz, G.; Schott, W.; Zetsche, F.; Bacon, T. C.; Butterworth, I.; Cole, J. E.; Harris, V. L.; Howell, G.; Hung, B. H. Y.; Lamberti, L.; Long, K. R.; Miller, D. B.; Pavel, N.; Prinias, A.; Sedgbeer, J. K.; Sideris, D.; Whitfield, A. F.; Mallik, U.; Wang, S. M.; Wu, J. T.; Cloth, P.; Filges, D.; Fleck, J. I.; Ishii, T.; Kuze, M.; Nakao, M.; Tokushuku, K.; Yamada, S.; Yamazaki, Y.; An, S. H.; Lee, S. B.; Nam, S. W.; Park, H. S.; Park, S. K.; Barreiro, F.; Fernández, J. P.; García, G.; Graciani, R.; Hernández, J. M.; Hervás, L.; Labarga, L.; Martínez, M.; del Peso, J.; Puga, J.; Terrón, J.; de Trocóniz, J. F.; Corriveau, F.; Hanna, D. S.; Hartmann, J.; Hung, L. W.; Lim, J. N.; Murray, W. N.; Ochs, A.; Riveline, M.; Stairs, D. G.; St-Laurent, M.; Ullmann, R.; Tsurugai, T.; Bashkirov, V.; Dolgoshein, B. A.; Stifutkin, A.; Bashindzhagyan, G. L.; Ermolov, P. F.; Golubkov, Yu. A.; Khein, L. A.; Korotkova, N. A.; Korzhavina, I. A.; Kuzmin, V. A.; Lukina, O. Yu.; Proskuryakov, A. S.; Shcheglova, L. M.; Shumilin, A. V.; Solomin, A. N.; Zotkin, S. A.; Bokel, C.; Botje, M.; Brümmer, N.; Chlebana, F.; Engelen, J.; Kooijman, P.; Kruse, A.; van Sighem, A.; Tiecke, H.; Verkerke, W.; Vossebeld, J.; Vreeswijk, M.; Wiggers, L.; de Wolf, E.; Acosta, D.; Bylsma, B.; Durkin, L. S.; Gilmore, J.; Ginsburg, C. M.; Kim, C. L.; Ling, T. Y.; Nylander, P.; Romanowski, T. A.; Blaikley, H. E.; Cashmore, R. J.; Cooper-Sarkar, A. M.; Devenish, R. C. E.; Edmonds, J. K.; Harnew, N.; Lancaster, M.; McFall, J. D.; Nath, C.; Noyes, V. A.; Quadt, A.; Ruske, O.; Tickner, J. R.; Uijterwaal, H.; Walczak, R.; Waters, D. S.; Bertolin, A.; Brugnera, R.; Carlin, R.; dal Corso, F.; Dosselli, U.; Limentani, S.; Morandin, M.; Posocco, M.; Stanco, L.; Stroili, R.; Voci, C.; Bulmahn, J.; Feild, R. G.; Oh, B. Y.; Okrasiński, J. R.; Whitmore, J. J.; Iga, Y.; D'Agostini, G.; Marini, G.; Nigro, A.; Raso, M.; Hart, J. C.; McCubbin, N. A.; Shah, T. P.; Barberis, E.; Dubbs, T.; Heusch, C.; van Hook, M.; Lockman, W.; Rahn, J. T.; Sadrozinski, H. F.-W.; Seiden, A.; Williams, D. C.; Schwarzer, O.; Walenta, A. H.; Abramowicz, H.; Briskin, G.; Dagan, S.; Doeker, T.; Kananov, S.; Levy, A.; Abe, T.; Fusayasu, T.; Inuzuka, M.; Nagano, K.; Suzuki, I.; Umemori, K.; Yamashita, T.; Hamatsu, R.; Hirose, T.; Homma, K.; Kitamura, S.; Matsushita, T.; Yamauchi, K.; Cirio, R.; Costa, M.; Ferrero, M. I.; Maselli, S.; Monaco, V.; Peroni, C.; Petrucci, M. C.; Sacchi, R.; Solano, A.; Staiano, A.; Dardo, M.; Bailey, D. C.; Brkic, M.; Fagerstroem, C.-P.; Hartner, G. F.; Joo, K. K.; Levman, G. M.; Martin, J. F.; Orr, R. S.; Polenz, S.; Sampson, C. R.; Simmons, D.; Teuscher, R. J.; Butterworth, J. M.; Catterall, C. D.; Jones, T. W.; Kaziewicz, P. B.; Lane, J. B.; Saunders, R. L.; Shulman, J.; Sutton, M. R.; Lu, B.; Mo, L. W.; Ciborowski, J.; Grzelak, G.; Kasprzak, M.; Muchorowski, K.; Nowak, R. J.; Pawlak, J. M.; Pawlak, R.; Tymieniecka, T.; Wróblewski, A. K.; Zakrzewski, J. A.; Adamus, M.; Coldewey, C.; Eisenberg, Y.; Hochman, D.; Karshon, U.; Revel, D.; Badgett, W. F.; Chapin, D.; Cross, R.; Dasu, S.; Foudas, C.; Loveless, R. J.; Mattingly, S.; Reeder, D. D.; Smith, W. H.; Vaiciulis, A.; Wodarczyk, M.; Bhadra, S.; Frisken, W. R.; Khakzad, M.; Schmidke, W. B.

1997-02-01

This paper presents measurements of D*+/- production in deep inelastic scattering from collisions between 27.5 GeV positrons and 820 GeV protons. The data have been taken with the ZEUS detector at HERA. The decay channel D*+ -> (D0 -> K- π+) π+ (+c.c.) has been used in the study. The e+p cross section for inclusive D*+/- production with 5 < Q2 < 100 GeV2 and y < 0.7 is 5.3 +/- 1.0 +/- 0.8 nb in the kinematic region 1.3 < pT(D*+/-) < 9.0 GeV and η(D*+/-) < 1.5. Differential cross sections as functions of pT(D*+/-), η(D*+/-), W and Q2 are compared with next-to-leading order QCD calculations based on the photon-gluon fusion production mechanism. After an extrapolation of the cross section to the full kinematic region in pT(D*+/-) and η(D*+/-), the charm contribution Fcc2 (x, Q2) to the proton structure function is determined for Bjorken x between 2.10-4 and 5.10-3.

SU-E-T-402: Y-90 Microspheres (SIR Spheres) for Treatment of Liver Metastasis : Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nair, M

2014-06-01

Purpose: The purpose of this presentation is to discuss the radiation safety and dosimetric technique used for the therapeutic procedure using Y-90 microspheres through intra -arterial administration on patients with liver metastasis Methods: The radiation dosimetry, technique and safety aspects of 14 patients with primary and metastatic liver cancer, treated with Y-90 microsphere (SIR spheres) are discussed. The liver and tumor volumes were determined using the CT and MR scans . The images were imported into the treatment planning system and the liver and tumor volumes and the volume of the liver affected were outlined and the volume calculation wasmore » performed using the software. The lung shunt fraction (LSF) and tumor to liver uptake ratio (TLR) were determined using the nuclear medicine SPECT imaging with Tc-99m MAA. The absorbed dose to the target volume in liver was calculated using the following equation:Dose ? (Gy) = C x E? x 5.92 x 10-6 (Gy/s) x T(1/2)(days) x 1.44 x 8.64 x 104 (s) The distribution of activity in the tumor bed was confirmed by post Y-90 administration imaging using the Bremsstrahlung peak at 30% window. The patient and the procedure room were surveyed and radiation safety instructions were given to the patient Results: The tumor volume ranged from 77 cc to 700 cc, tumor to liver uptake ranged from 3 to 12. The lung shunt fraction varied from 1.08% to 9.0%. The activity administered ranged from 1.0GBq to 2.5 GBq, . The radiation survey in contact with the patient ranged from 1.8 mR/hr to 2.5 mR/hr and reading at 1 meter was less than 0.2 mR/hr Conclusion: The technique for radiation dosimetry and radiation safety for Y-90 microsphere therapy is established. The post treatment imaging helped to confirm the distribution of Y-90 microspheres inside the tumor bed.« less

Crystallization and X-ray diffraction analysis of an l-arabinonate dehydratase from Rhizobium leguminosarum bv. trifolii and a d-xylonate dehydratase from Caulobacter crescentus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rahman, Mohammad Mubinur; Andberg, Martina; Koivula, Anu

l-Arabinonate dehydratase and d-xylonate dehydratase from the IlvD/EDD family were crystallized by the vapour-diffusion method. Diffraction data sets were collected to resolutions of 2.40 and 2.66 Å from crystals of l-arabinonate dehydratase and d-xylonate dehydratase, respectively. l-Arabinonate dehydratase (EC 4.2.1.25) and d-xylonate dehydratase (EC 4.2.1.82) are two enzymes that are involved in a nonphosphorylative oxidation pathway of pentose sugars. l-Arabinonate dehydratase converts l-arabinonate into 2-dehydro-3-deoxy-l-arabinonate, and d-xylonate dehydratase catalyzes the dehydration of d-xylonate to 2-dehydro-3-deoxy-d-xylonate. l-Arabinonate and d-xylonate dehydratases belong to the IlvD/EDD family, together with 6-phosphogluconate dehydratases and dihydroxyacid dehydratases. No crystal structure of any l-arabinonate or d-xylonate dehydratasemore » is available in the PDB. In this study, recombinant l-arabinonate dehydratase from Rhizobium leguminosarum bv. trifolii (RlArDHT) and d-xylonate dehydratase from Caulobacter crescentus (CcXyDHT) were heterologously expressed in Escherichia coli and purified by the use of affinity chromatography followed by gel-filtration chromatography. The purified proteins were crystallized using the hanging-drop vapour-diffusion method at 293 K. Crystals of RlArDHT that diffracted to 2.40 Å resolution were obtained using sodium formate as a precipitating agent. They belonged to space group P2{sub 1}, with unit-cell parameters a = 106.07, b = 208.61, c = 147.09 Å, β = 90.43°. Eight RlArDHT molecules (two tetramers) in the asymmetric unit give a V{sub M} value of 3.2 Å{sup 3} Da{sup −1} and a solvent content of 62%. Crystals of CcXyDHT that diffracted to 2.66 Å resolution were obtained using sodium formate and polyethylene glycol 3350. They belonged to space group C2, with unit-cell parameters a = 270.42, b = 236.13, c = 65.17 Å, β = 97.38°. Four CcXyDHT molecules (a tetramer) in the asymmetric unit give a V{sub M} value of 4.0 Å{sup 3} Da{sup −1} and a solvent content of 69%.« less

SU-F-J-203: Retrospective Assessment of Delivered Proton Dose in Prostate Cancer Patients Based On Daily In-Room CT Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stuetzer, K; Paessler, T; Valentini, C

Purpose: Retrospective calculation of the delivered proton dose in prostate cancer patients based on a unique dataset of daily CT images. Methods: Inter-fractional motion in prostate cancer patients treated at our proton facility is counteracted by water-filled endorectal ballon and bladder filling protocol. Typical plans (XiO, Elekta Instruments AB, Stockholm) for 74 Gy(RBE) sequential boost treatment in 37 fractions include two series of opposing lateral double-scattered proton beams covering the respective iCTV. Stability of fiducial markers and anatomy were checked in 12 patients by daily scheduled in-room control CT (cCT) after immobilization and positioning according to bony anatomy utilizing orthogonalmore » X-ray. In RayStation 4.6 (RaySearch Laboritories AB, Stockholm), all cCTs are delineated retrospectively and the treatment plans were recalculated on the planning CT and the registered cCTs. All fraction doses were accumulated on the planning CT after deformable registration. Parameters of delivered dose to iCTV (D98%>95%, D2%<107%), bladder (V75Gy<15%, V70Gy<25%, V65Gy<30%), rectum (V70Gy<10%, V50Gy<40%) and femoral heads (V50Gy<5%) are compared to those in the treatment plan. Intra-therapy variation is represented in DVH bands. Results: No alarming differences were observed between planned and retrospectively accumulated dose: iCTV constraints were met, except for one patient (D98%=94.6% in non-boosted iCTV). Considered bladder and femoral head values were below the limits. Rectum V70Gy was slightly exceeded (<11.3%) in two patients. First intra-therapy variability analysis in 4 patients showed no timedependent parameter drift, revealed strongest variability for bladder dose. In some fractions, iCTV coverage (D98%) and rectum V70Gy was missed. Conclusion: Double scattered proton plans are accurately delivered to prostate cancer patients due to fractionation effects and the applied precise positioning and immobilization protocols. As a result of rare interventions after daily 3D imaging of the first 12 patients, in-room CT frequency for prostate cancer patients was reduced. The presented study supports this decision. The authors acknowledge the German Federal Ministry for Education and Research for funding the High Precision Radiotherapy Group at the OncoRay - National Center for Radiation Research in Oncology (BMBF- 03Z1N51).« less

Inter- and Intrafraction Target Motion in Highly Focused Single Vocal Cord Irradiation of T1a Larynx Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwa, Stefan L.S., E-mail: s.kwa@erasmusmc.nl; Al-Mamgani, Abrahim; Osman, Sarah O.S.

2015-09-01

Purpose: The purpose of this study was to verify clinical target volume–planning target volume (CTV-PTV) margins in single vocal cord irradiation (SVCI) of T1a larynx tumors and characterize inter- and intrafraction target motion. Methods and Materials: For 42 patients, a single vocal cord was irradiated using intensity modulated radiation therapy at a total dose of 58.1 Gy (16 fractions × 3.63 Gy). A daily cone beam computed tomography (CBCT) scan was performed to online correct the setup of the thyroid cartilage after patient positioning with in-room lasers (interfraction motion correction). To monitor intrafraction motion, CBCT scans were also acquired just after patient repositioning and aftermore » dose delivery. A mixed online-offline setup correction protocol (“O2 protocol”) was designed to compensate for both inter- and intrafraction motion. Results: Observed interfraction, systematic (Σ), and random (σ) setup errors in left-right (LR), craniocaudal (CC), and anteroposterior (AP) directions were 0.9, 2.0, and 1.1 mm and 1.0, 1.6, and 1.0 mm, respectively. After correction of these errors, the following intrafraction movements derived from the CBCT acquired after dose delivery were: Σ = 0.4, 1.3, and 0.7 mm, and σ = 0.8, 1.4, and 0.8 mm. More than half of the patients showed a systematic non-zero intrafraction shift in target position, (ie, the mean intrafraction displacement over the treatment fractions was statistically significantly different from zero; P<.05). With the applied CTV-PTV margins (for most patients 3, 5, and 3 mm in LR, CC, and AP directions, respectively), the minimum CTV dose, estimated from the target displacements observed in the last CBCT, was at least 94% of the prescribed dose for all patients and more than 98% for most patients (37 of 42). The proposed O2 protocol could effectively reduce the systematic intrafraction errors observed after dose delivery to almost zero (Σ = 0.1, 0.2, 0.2 mm). Conclusions: With adequate image guidance and CTV-PTV margins in LR, CC, and AP directions of 3, 5, and 3 mm, respectively, excellent target coverage in SVCI could be ensured.« less

SU-F-J-124: Reduction in Dosimetric Impact of Motion Using VMAT Compared to IMRT in Hypofractionated Prostate Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ravindranath, B; Xiong, J; Happersett, L

2016-06-15

Purpose: To quantify and compare the dosimetric impact of motion management correction strategies during VMAT and IMRT for hypofractionated prostate treatment. Methods: Two arc VMAT and 9 field IMRT plans were generated for two prostate cancer patients undergoing hypofractionated radiotherapy (7.5Gy × 5 and 8Gy × 5). 212 motion traces were retrospectively extracted from treatment records of prostate cancer patients with implanted Calypso beacons. Dose to the CTV and normal tissues was reconstructed for each trace and plan taking into account the actual treatment delivery time. Following motion correction scenarios were simulated: (1) VMAT plan – (a) No correction, (b)more » correction between arcs, (c) correction every 20 degrees of gantry rotation and (2) IMRT plan - (a) No correction,(b) correction between fields. Two mm action threshold for position correction was assumed. The 5–95% confidence interval (CI) range was extracted from the family of DVHs for each correction scenario. Results: Treatment duration for 8Gy plan (VMAT vs IMRT) was 3 vs 12 mins and for 7.5Gy plan was 3 vs 9 mins. In the absence of correction, the VMAT 5–−95% CI dose spread was, on average, less than the IMRT dose spread by 2% for CTVD95, 9% for rectalwall (RW) D1cc and 9% for bladderwall (BW) D53. Further, VMAT b/w arcs correction strategy reduced the spread about the planned value compared to IMRT b/w fields correction by: 1% for CTVD95, 2.6% for RW1cc and 2% for BWD53. VMAT 20 degree strategy led to greater reduction in dose spread compared to IMRT by: 2% for CTVD95, 4.5% for RW1cc and 6.7% for BWD53. Conclusion: In the absence of a correction strategy, the limited motion during VMAT’s shorter delivery times translates into less motion-induced dosimetric degradation than IMRT. Performing limited periodic motion correction during VMAT can yield excellent conformity to planned values that is superior to IMRT. This work was partially supported by Varian Medical Systems.« less

SU-F-T-224: Importance of Timely Review of Daily Cone-Beam CTs: Dosimetric Evaluation of Rejected CBCTs for Head and Neck Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andrews, M; Yu, N; Joshi, N

Purpose: To dosimetrically evaluate the importance of timely reviewing daily CBCTs for patients with head and neck cancer. Methods: After each fraction daily cone-beam CT (CBCT) for head and neck patients are reviewed by physicians prior to next treatment. Physician rejected image registrations of CBCT were identified and analyzed for 17 patients. These CBCT images were rigidly fused with planning CT images and the contours from the planning CT were transferred to CBCTs. Because of limited extension in the superior-inferior dimension contours with partial volumes in CBCTs were discarded. The treatment isocenter was placed by applying the clinically recorded shiftsmore » to the volume isocenter of the CBCT. Dose was recalculated at the shifted isocenter using a homogeneous dose calculation algorithm. Dosimetrically relevant changes defined as greater than 5% deviation from the clinically accepted plans but with homogeneous dose calculation were evaluated for the high dose (HD), intermediate dose (ID), and low dose (LD) CTVs, spinal cord, larynx, oropharynx, parotids, and submandibular glands. Results: Among seventeen rejected CBCTS, HD-CTVs, ID-CTVs, and LD-CTVs were completely included in the CBCTs for 17, 1, and 15 patients, respectively. The prescription doses to the HD-CTV, ID-CTV, and LD-CTV were received by < 95% of the CTV volumes in 5/17, 1/1, and 5/15 patients respectively. For the spinal cord, the maximum doses (D0.03cc) were increased > 5% in 13 of 17 patients. For the oropharynx, larynx, parotid, and submandibular glands, the mean dose of these organs at risk was increased > 5% in 7/17, 8/12, 11/16 and 6/16 patients, respectively. Conclusion: Timely review daily CBCTs for head and neck patients under daily CBCT guidance is important, and uncorrected setup errors can translate to dosimetrically relevant dose increases in organsat- risk and dose decreases in the clinical target volumes.« less

A novel method to quantify and compare anatomical shape: application in cervix cancer radiotherapy

NASA Astrophysics Data System (ADS)

Oh, Seungjong; Jaffray, David; Cho, Young-Bin

2014-06-01

Adaptive radiation therapy (ART) had been proposed to restore dosimetric deficiencies during treatment delivery. In this paper, we developed a technique of Geometric reLocation for analyzing anatomical OBjects' Evolution (GLOBE) for a numerical model of tumor evolution under radiation therapy and characterized geometric changes of the target using GLOBE. A total of 174 clinical target volumes (CTVs) obtained from 32 cervical cancer patients were analyzed. GLOBE consists of three main steps; step (1) deforming a 3D surface object to a sphere by parametric active contour (PAC), step (2) sampling a deformed PAC on 642 nodes of icosahedron geodesic dome for reference frame, and step (3) unfolding 3D data to 2D plane for convenient visualization and analysis. The performance was evaluated with respect to (1) convergence of deformation (iteration number and computation time) and (2) accuracy of deformation (residual deformation). Based on deformation vectors from planning CTV to weekly CTVs, target specific (TS) margins were calculated on each sampled node of GLOBE and the systematic (Σ) and random (σ) variations of the vectors were calculated. Population based anisotropic (PBA) margins were generated using van Herk's margin recipe. GLOBE successfully modeled 152 CTVs from 28 patients. Fast convergence was observed for most cases (137/152) with the iteration number of 65 ± 74 (average ± STD) and the computation time of 13.7 ± 18.6 min. Residual deformation of PAC was 0.9 ± 0.7 mm and more than 97% was less than 3 mm. Margin analysis showed random nature of TS-margin. As a consequence, PBA-margins perform similarly to ISO-margins. For example, PBA-margins for 90% patients' coverage with 95% dose level is close to 13 mm ISO-margins in the aspect of target coverage and OAR sparing. GLOBE demonstrates a systematic analysis of tumor motion and deformation of patients with cervix cancer during radiation therapy and numerical modeling of PBA-margin on 642 locations of CTV surface.

Is a Clinical Target Volume (CTV) Necessary in the Treatment of Lung Cancer in the Modern Era Combining 4-D Imaging and Image-guided Radiotherapy (IGRT)?

PubMed

Kilburn, Jeremy M; Lucas, John T; Soike, Michael H; Ayala-Peacock, Diandra N; Blackstock, Arthur W; Hinson, William H; Munley, Michael T; Petty, William J; Urbanic, James J

2016-01-23

We hypothesized that omission of clinical target volumes (CTV) in lung cancer radiotherapy would not compromise control by determining retrospectively if the addition of a CTV would encompass the site of failure. Stage II-III patients were treated from 2009-2012 with daily cone-beam imaging and a 5 mm planning target volume (PTV) without a CTV. PTVs were expanded 1 cm and termed CTVretro. Recurrences were scored as 1) within the PTV, 2) within CTVretro, or 3) outside the PTV. Locoregional control (LRC), distant control (DC), progression-free survival (PFS), and overall survival (OS) were estimated. Among 110 patients, Stage IIIA 57%, IIIB 32%, IIA 4%, and IIB 7%. Eighty-six percent of Stage III patients received chemotherapy. Median dose was 70 Gy (45-74 Gy) and fraction size ranged from 1.5-2.7 Gy. Median follow-up was 12 months, median OS was 22 months (95% CI 19-30 months), and LRC at two years was 69%. Fourteen local and eight regional events were scored with two CTVretro failures equating to a two-year CTV failure-free survival of 98%. Omission of a 1 cm CTV expansion appears feasible based on only two events among 110 patients and should be considered in radiation planning.

Cardiopulmonary Performance During Maximal Exercise in Soccer Players with Alterations in Renal Function.

PubMed

Morales, Anderson Pontes; Sampaio-Jorge, Felipe; da Cruz Rangel, Luiz Felipe; de Souza Menezes, Jackson; Leite, Tiago Costa; Ribeiro, Beatriz Gonçalves

2017-06-01

The aim of this study was to evaluate the curves of cardiorespiratory variables during cardiopulmonary exercise testing (CPET) in soccer players who had acute alterations in the glomerular filtration rate (GFR) after performing the pre-season training protocol. Sixteen male professional soccer players (25 ± 3 years; 179 ± 2 cm; and 77 ± 6 kg) were evaluated for oxygen uptake (VO 2 ), heart rate (HR) and pulse relative oxygen (relative O 2 Pulse) curves with intervals corresponding to 10% of the total duration of CPET. Athletes were grouped according to the GFR and classified as decreased GFR (dGFR; n = 8) and normal GFR (nGFR; n = 8). Athletes from the dGFR group exhibited lower VO 2 values (p < 0.05) when 90% (dGFR 49.8 ± 4.0 vs. nGFR 54.4 ± 6.1 ml·kg -1 ·min -1 ) and 100% (dGFR 52.6 ± 4.1 vs. nGFR 57.4 ± 5.9 ml·kg -1 ·min -1 ) of the test was complete; HR high values (p < 0.05) when 90% (dGFR 183.7 ± 5.1 vs. nGFR 176.6 ± 4.8 bpm-1) and 100% (dGFR 188.1 ± 5.0 vs. nGFR 180.8 ± 4.8 bpm-1) of the test was complete; and lower relative O 2 Pulse values (p < 0.05) when 70% (dGFR 25.6 ± 8.4 vs. nGFR 27.9 ± 9.7 ml·beat -1 ·kg -1 ), 80% (dGFR 26.6 ± 8.8 vs. nGFR 29.1 ± 10.0 ml·beat -1 ·kg -1 ), 90% (dGFR 27.1 ± 9.0 vs. nGFR 30.8 ± 10.6 ml·beat -1 ·kg -1 ) and 100% (dGFR 28 ± 9.2 vs. nGFR 31.8 ± 10.9 ml·beat -1 ·kg -1 ) of the test was complete. A correlation was found (r = -0.66, R 2 = 0.44, p = 0.00) between lower VO 2 peak and elevated levels of urinary protein excretion. In conclusion, soccer players with reduced kidney function after performing the pre-season training protocol also presented alterations in cardiopulmonary variables. We suggest that monitoring of renal function may be used to identify less conditioned soccer players.

The chemokine decoy receptor D6 prevents excessive inflammation and adverse ventricular remodeling after myocardial infarction.

PubMed

Cochain, Clément; Auvynet, Constance; Poupel, Lucie; Vilar, José; Dumeau, Edouard; Richart, Adèle; Récalde, Alice; Zouggari, Yasmine; Yin, Kiave Yune Ho Wang; Bruneval, Patrick; Renault, Gilles; Marchiol, Carmen; Bonnin, Philippe; Lévy, Bernard; Bonecchi, Raffaella; Locati, Massimo; Combadière, Christophe; Silvestre, Jean-Sébastien

2012-09-01

Leukocyte infiltration in ischemic areas is a hallmark of myocardial infarction, and overwhelming infiltration of innate immune cells has been shown to promote adverse remodeling and cardiac rupture. Recruitment of inflammatory cells in the ischemic heart depends highly on the family of CC-chemokines and their receptors. Here, we hypothesized that the chemokine decoy receptor D6, which specifically binds and scavenges inflammatory CC-chemokines, might limit inflammation and adverse cardiac remodeling after infarction. D6 was expressed in human and murine infarcted myocardium. In a murine model of myocardial infarction, D6 deficiency led to increased chemokine (C-C motif) ligand 2 and chemokine (C-C motif) ligand 3 levels in the ischemic heart. D6-deficient (D6(-/-)) infarcts displayed increased infiltration of pathogenic neutrophils and Ly6Chi monocytes, associated with strong matrix metalloproteinase-9 and matrix metalloproteinase-2 activities in the ischemic heart. D6(-/-) mice were cardiac rupture prone after myocardial infarction, and functional analysis revealed that D6(-/-) hearts had features of adverse remodeling with left ventricle dilation and reduced ejection fraction. Bone marrow chimera experiments showed that leukocyte-borne D6 had no role in this setting, and that leukocyte-specific chemokine (C-C motif) receptor 2 deficiency rescued the adverse phenotype observed in D6(-/-) mice. We show for the first time that the chemokine decoy receptor D6 limits CC-chemokine-dependent pathogenic inflammation and is required for adequate cardiac remodeling after myocardial infarction.

SU-E-T-620: Dosimetric Compliance Study for a New Prostate Protocol of Combined High Dose Rate Brachytherapy and Stereotactic Body Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peng, C; Giaddui, T; Den, R

2014-06-15

Purpose: To investigate the adherence of treatment plans of prostate cancer patients with the dosimetric compliance criteria of the new in house phase I trial of high dose rate (HDR) brachytherapy combined with stereotactic body radiotherapy (SBRT) for intermediate risk prostate cancer patients. Methods: Ten prostate cancer patients were treated using this trial. They received one fraction of HDR to 15Gy, followed by external beam(EB) boost of 3.2Gy(Level 1, five patients) or 3.94Gy(level 2, five patients) per fraction for 10 or 7 fractions, respectively, both equivalent to EB treatments of 113.5Gy in 2Gy fractions. The EB plans were either IMRTmore » or VMAT plans. DVH analysis was performed to verify the adherence of treatment plans to the dosimetric criteria of the trial. Results: For Level 1 patients, target coverage were adequate, with CTV V32Gy(%) of 99.0±1.0 (mean ± 1 standard deviation), and PTV V31Gy(%) of 99.6±0.3. PTV V32.9Gy(%) is 1.4±3.1 and PTVmax is 32.9±0.2Gy. Rectum, bladder and femoral heads sparing were well within protocol criteria. For Level 2 patients, CTV V27.6Gy(%) is 98.7±1.8; PTV V26.7Gy(%) is 99.0±1.4. PTV V28.4Gy(%) is 1.3±1.4, with three patients having minor deviation from protocol. Again critical structures were spared compliant to the protocol. The analysis of HDR plans show similar results, with adequate dose coverage to the prostate and sparing of critical structures including urethra and rectum. V100(%) and V90(%) of prostate are 96.0±1.1 and 98.9±0.5. Urethra D10(%) is 113.1±2.9. Rectum V80(cc) is 1.4±0.5. Hotspot in prostate is substantially higher than what the protocol specifies. But the criteria for hotspot are only guidelines, serving to lower the dose to urethra . Conclusion: This new high biological equivalent dose prostate trial has been carried out successfully for ten patients. Based on dosimetric analysis, all HDR and external plans were compliant to the protocol criteria, with only minor deviations.« less

CC2D2A Is Mutated in Joubert Syndrome and Interacts with the Ciliopathy-Associated Basal Body Protein CEP290

PubMed Central

Gorden, Nicholas T.; Arts, Heleen H.; Parisi, Melissa A.; Coene, Karlien L.M.; Letteboer, Stef J.F.; van Beersum, Sylvia E.C.; Mans, Dorus A.; Hikida, Abigail; Eckert, Melissa; Knutzen, Dana; Alswaid, Abdulrahman F.; Özyurek, Hamit; Dibooglu, Sel; Otto, Edgar A.; Liu, Yangfan; Davis, Erica E.; Hutter, Carolyn M.; Bammler, Theo K.; Farin, Frederico M.; Dorschner, Michael; Topçu, Meral; Zackai, Elaine H.; Rosenthal, Phillip; Owens, Kelly N.; Katsanis, Nicholas; Vincent, John B.; Hildebrandt, Friedhelm; Rubel, Edwin W.; Raible, David W.; Knoers, Nine V.A.M.; Chance, Phillip F.; Roepman, Ronald; Moens, Cecilia B.; Glass, Ian A.; Doherty, Dan

2008-01-01

Joubert syndrome and related disorders (JSRD) are primarily autosomal-recessive conditions characterized by hypotonia, ataxia, abnormal eye movements, and intellectual disability with a distinctive mid-hindbrain malformation. Variable features include retinal dystrophy, cystic kidney disease, and liver fibrosis. JSRD are included in the rapidly expanding group of disorders called ciliopathies, because all six gene products implicated in JSRD (NPHP1, AHI1, CEP290, RPGRIP1L, TMEM67, and ARL13B) function in the primary cilium/basal body organelle. By using homozygosity mapping in consanguineous families, we identify loss-of-function mutations in CC2D2A in JSRD patients with and without retinal, kidney, and liver disease. CC2D2A is expressed in all fetal and adult tissues tested. In ciliated cells, we observe localization of recombinant CC2D2A at the basal body and colocalization with CEP290, whose cognate gene is mutated in multiple hereditary ciliopathies. In addition, the proteins can physically interact in vitro, as shown by yeast two-hybrid and GST pull-down experiments. A nonsense mutation in the zebrafish CC2D2A ortholog (sentinel) results in pronephric cysts, a hallmark of ciliary dysfunction analogous to human cystic kidney disease. Knockdown of cep290 function in sentinel fish results in a synergistic pronephric cyst phenotype, revealing a genetic interaction between CC2D2A and CEP290 and implicating CC2D2A in cilium/basal body function. These observations extend the genetic spectrum of JSRD and provide a model system for studying extragenic modifiers in JSRD and other ciliopathies. PMID:18950740

Discrete Analog Processing for Tracking and Guidance Control

DTIC Science & Technology

1980-11-01

be called the multi- sample algorithm, satisfies -4 67 tD (Da - d) 0 (4.2.2.3) Thus, this descent algorithm will determine a coefficient vector a... flJ -TI:-* IS; 7" rR(VI Dr TH~I ("vFP)ALLCj TT$ C_ F 2C OH Til TPACK I! NC SYS TE ! f- 1I3 cc cc *’I cc. CC snUpcF FIL1j: C~T 01C 0 (1 cc CC OEJCT F I LF

Comparison of urethral diameters for calculating the urethral dose after permanent prostate brachytherapy.

PubMed

Tanaka, Osamu; Hayashi, Shinya; Matsuo, Masayuki; Nakano, Masahiro; Kubota, Yasuaki; Maeda, Sunaho; Ohtakara, Kazuhiro; Deguchi, Takashi; Hoshi, Hiroaki

2007-08-01

No studies have yet evaluated the effects of a dosimetric analysis for different urethral volumes. We therefore evaluated the effects of a dosimetric analysis to determine the different urethral volumes. This study was based on computed tomography/magnetic resonance imaging (CT/MRI) combined findings in 30 patients who had undergone prostate brachytherapy. Postimplant CT/MRI scans were performed 30 days after the implant. The urethra was contoured based on its diameter (8, 6, 4, 2, and 0 mm). The total urethral volume-in cubic centimeters [UrV150/200(cc)] and percent (UrV150%/200%), of the urethra receiving 150% or 200% of the prescribed dose-and the doses (UrD90/30/5) in Grays to 90%, 30%, and 5% of the urethral volume were measured based on the urethral diameters. The UrV150(cc) and UrD30 were statistically different between the of 8-, 6-, 4-, 2-, and 0-mm diameters, whereas the UrD5 was statistically different only between the 8-, 6-, and 4-mm diameters. Especially for UrD5, there was an approximately 40-Gy difference between the mean values for the 8- and 0-mm diameters. We recommend that the urethra should be contoured as a 4- to 6-mm diameter circle or one side of a triangle of 5-7 mm. By standardizing the urethral diameter, the urethral dose will be less affected by the total urethral volume.

Effect of patient setup errors on simultaneously integrated boost head and neck IMRT treatment plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siebers, Jeffrey V.; Keall, Paul J.; Wu Qiuwen

2005-10-01

Purpose: The purpose of this study is to determine dose delivery errors that could result from random and systematic setup errors for head-and-neck patients treated using the simultaneous integrated boost (SIB)-intensity-modulated radiation therapy (IMRT) technique. Methods and Materials: Twenty-four patients who participated in an intramural Phase I/II parotid-sparing IMRT dose-escalation protocol using the SIB treatment technique had their dose distributions reevaluated to assess the impact of random and systematic setup errors. The dosimetric effect of random setup error was simulated by convolving the two-dimensional fluence distribution of each beam with the random setup error probability density distribution. Random setup errorsmore » of {sigma} = 1, 3, and 5 mm were simulated. Systematic setup errors were simulated by randomly shifting the patient isocenter along each of the three Cartesian axes, with each shift selected from a normal distribution. Systematic setup error distributions with {sigma} = 1.5 and 3.0 mm along each axis were simulated. Combined systematic and random setup errors were simulated for {sigma} = {sigma} = 1.5 and 3.0 mm along each axis. For each dose calculation, the gross tumor volume (GTV) received by 98% of the volume (D{sub 98}), clinical target volume (CTV) D{sub 90}, nodes D{sub 90}, cord D{sub 2}, and parotid D{sub 50} and parotid mean dose were evaluated with respect to the plan used for treatment for the structure dose and for an effective planning target volume (PTV) with a 3-mm margin. Results: Simultaneous integrated boost-IMRT head-and-neck treatment plans were found to be less sensitive to random setup errors than to systematic setup errors. For random-only errors, errors exceeded 3% only when the random setup error {sigma} exceeded 3 mm. Simulated systematic setup errors with {sigma} = 1.5 mm resulted in approximately 10% of plan having more than a 3% dose error, whereas a {sigma} = 3.0 mm resulted in half of the plans having more than a 3% dose error and 28% with a 5% dose error. Combined random and systematic dose errors with {sigma} = {sigma} = 3.0 mm resulted in more than 50% of plans having at least a 3% dose error and 38% of the plans having at least a 5% dose error. Evaluation with respect to a 3-mm expanded PTV reduced the observed dose deviations greater than 5% for the {sigma} = {sigma} = 3.0 mm simulations to 5.4% of the plans simulated. Conclusions: Head-and-neck SIB-IMRT dosimetric accuracy would benefit from methods to reduce patient systematic setup errors. When GTV, CTV, or nodal volumes are used for dose evaluation, plans simulated including the effects of random and systematic errors deviate substantially from the nominal plan. The use of PTVs for dose evaluation in the nominal plan improves agreement with evaluated GTV, CTV, and nodal dose values under simulated setup errors. PTV concepts should be used for SIB-IMRT head-and-neck squamous cell carcinoma patients, although the size of the margins may be less than those used with three-dimensional conformal radiation therapy.« less

Experimental validation of a deforming grid 4D dose calculation for PBS proton therapy.

PubMed

Krieger, Miriam; Klimpki, Grischa; Fattori, Giovanni; Hrbacek, Jan; Oxley, David; Safai, Sairos; Weber, Damien C; Lomax, Antony J; Zhang, Ye

2018-03-01

The aim of this study was to verify the temporal accuracy of the estimated dose distribution by a 4D dose calculation (4DDC) in comparison to measurements. A single-field plan (0.6 Gy), optimised for a liver patient case (CTV volume: 403cc), was delivered to a homogeneous PMMA phantom and measured by a high resolution scintillating-CCD system at two water equivalent depths. Various motion scenarios (no motion and motions with amplitude of 10 mm and two periods: 3.7 s and 4.4 s) were simulated using a 4D Quasar phantom and logged by an optical tracking system in real-time. Three motion mitigation approaches (single delivery, 6[Formula: see text] layered and volumetric rescanning) were applied, resulting in 10 individual measurements. 4D dose distributions were retrospectively calculated in water by taking into account the delivery log files (retrospective) containing information on the actually delivered spot positions, fluences, and time stamps. Moreover, in order to evaluate the sensitivity of the 4DDC inputs, the corresponding prospective 4DDCs were performed as a comparison, using the estimated time stamps of the spot delivery and repeated periodical motion patterns. 2D gamma analyses and dose-difference-histograms were used to quantify the agreement between measurements and calculations for all pixels with [Formula: see text]5% of the maximum calculated dose. The results show that a mean gamma score of 99.2% with standard deviation 1.0% can be achieved for 3%/3 mm criteria and all scenarios can reach a score of more than 95%. The average area with more than 5% dose difference was 6.2%. Deviations due to input uncertainties were obvious for single scan deliveries but could be smeared out once rescanning was applied. Thus, the deforming grid 4DDC has been demonstrated to be able to predict the complex patterns of 4D dose distributions for PBS proton therapy with high dosimetric and geometric accuracy, and it can be used as a valid clinical tool for 4D treatment planning, motion mitigation selection, and eventually 4D optimisation applications if the correct temporal information is available.

Experimental validation of a deforming grid 4D dose calculation for PBS proton therapy

NASA Astrophysics Data System (ADS)

Krieger, Miriam; Klimpki, Grischa; Fattori, Giovanni; Hrbacek, Jan; Oxley, David; Safai, Sairos; Weber, Damien C.; Lomax, Antony J.; Zhang, Ye

2018-03-01

The aim of this study was to verify the temporal accuracy of the estimated dose distribution by a 4D dose calculation (4DDC) in comparison to measurements. A single-field plan (0.6 Gy), optimised for a liver patient case (CTV volume: 403cc), was delivered to a homogeneous PMMA phantom and measured by a high resolution scintillating-CCD system at two water equivalent depths. Various motion scenarios (no motion and motions with amplitude of 10 mm and two periods: 3.7 s and 4.4 s) were simulated using a 4D Quasar phantom and logged by an optical tracking system in real-time. Three motion mitigation approaches (single delivery, 6× layered and volumetric rescanning) were applied, resulting in 10 individual measurements. 4D dose distributions were retrospectively calculated in water by taking into account the delivery log files (retrospective) containing information on the actually delivered spot positions, fluences, and time stamps. Moreover, in order to evaluate the sensitivity of the 4DDC inputs, the corresponding prospective 4DDCs were performed as a comparison, using the estimated time stamps of the spot delivery and repeated periodical motion patterns. 2D gamma analyses and dose-difference-histograms were used to quantify the agreement between measurements and calculations for all pixels with > 5% of the maximum calculated dose. The results show that a mean gamma score of 99.2% with standard deviation 1.0% can be achieved for 3%/3 mm criteria and all scenarios can reach a score of more than 95%. The average area with more than 5% dose difference was 6.2%. Deviations due to input uncertainties were obvious for single scan deliveries but could be smeared out once rescanning was applied. Thus, the deforming grid 4DDC has been demonstrated to be able to predict the complex patterns of 4D dose distributions for PBS proton therapy with high dosimetric and geometric accuracy, and it can be used as a valid clinical tool for 4D treatment planning, motion mitigation selection, and eventually 4D optimisation applications if the correct temporal information is available.

Role of Type 1 Diabetes-Associated SNPs on Risk of Autoantibody Positivity in the TEDDY Study.

PubMed

Törn, Carina; Hadley, David; Lee, Hye-Seung; Hagopian, William; Lernmark, Åke; Simell, Olli; Rewers, Marian; Ziegler, Anette; Schatz, Desmond; Akolkar, Beena; Onengut-Gumuscu, Suna; Chen, Wei-Min; Toppari, Jorma; Mykkänen, Juha; Ilonen, Jorma; Rich, Stephen S; She, Jin-Xiong; Steck, Andrea K; Krischer, Jeffrey

2015-05-01

The Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively follows 8,677 children enrolled from birth who carry HLA-susceptibility genotypes for development of islet autoantibodies (IA) and type 1 diabetes (T1D). During the median follow-up time of 57 months, 350 children developed at least one persistent IA (GAD antibody, IA-2A, or micro insulin autoantibodies) and 84 of them progressed to T1D. We genotyped 5,164 Caucasian children for 41 non-HLA single nucleotide polymorphisms (SNPs) that achieved genome-wide significance for association with T1D in the genome-wide association scan meta-analysis conducted by the Type 1 Diabetes Genetics Consortium. In TEDDY participants carrying high-risk HLA genotypes, eight SNPs achieved significant association to development of IA using time-to-event analysis (P < 0.05), whereof four were significant after adjustment for multiple testing (P < 0.0012): rs2476601 in PTPN22 (hazard ratio [HR] 1.54 [95% CI 1.27-1.88]), rs2292239 in ERBB3 (HR 1.33 [95% CI 1.14-1.55]), rs3184504 in SH2B3 (HR 1.38 [95% CI 1.19-1.61]), and rs1004446 in INS (HR 0.77 [0.66-0.90]). These SNPs were also significantly associated with T1D in particular: rs2476601 (HR 2.42 [95% CI 1.70-3.44]). Although genes in the HLA region remain the most important genetic risk factors for T1D, other non-HLA genetic factors contribute to IA, a first step in the pathogenesis of T1D, and the progression of the disease. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Evaluation of target coverage and margins adequacy during CyberKnife Lung Optimized Treatment.

PubMed

Ricotti, Rosalinda; Seregni, Matteo; Ciardo, Delia; Vigorito, Sabrina; Rondi, Elena; Piperno, Gaia; Ferrari, Annamaria; Zerella, Maria Alessia; Arculeo, Simona; Francia, Claudia Maria; Sibio, Daniela; Cattani, Federica; De Marinis, Filippo; Spaggiari, Lorenzo; Orecchia, Roberto; Riboldi, Marco; Baroni, Guido; Jereczek-Fossa, Barbara Alicja

2018-04-01

Evaluation of target coverage and verification of safety margins, in motion management strategies implemented by Lung Optimized Treatment (LOT) module in CyberKnife system. Three fiducial-less motion management strategies provided by LOT can be selected according to tumor visibility in the X ray images acquired during treatment. In 2-view modality the tumor is visible in both X ray images and full motion tracking is performed. In 1-view modality the tumor is visible in a single X ray image, therefore, motion tracking is combined with an internal target volume (ITV)-based margin expansion. In 0-view modality the lesion is not visible, consequently the treatment relies entirely on an ITV-based approach. Data from 30 patients treated in 2-view modality were selected providing information on the three-dimensional tumor motion in correspondence to each X ray image. Treatments in 1-view and 0-view modalities were simulated by processing log files and planning volumes. Planning target volume (PTV) margins were defined according to the tracking modality: end-exhale clinical target volume (CTV) + 3 mm in 2-view and ITV + 5 mm in 0-view. In the 1-view scenario, the ITV encompasses only tumor motion along the non-visible direction. Then, non-uniform ITV to PTV margins were applied: 3 mm and 5 mm in the visible and non-visible direction, respectively. We defined the coverage of each voxel of the CTV as the percentage of X ray images where such voxel was included in the PTV. In 2-view modality coverage was calculated as the intersection between the CTV centred on the imaged target position and the PTV centred on the predicted target position, as recorded in log files. In 1-view modality, coverage was calculated as the intersection between the CTV centred on the imaged target position and the PTV centred on the projected predictor data. In 0-view modality coverage was calculated as the intersection between the CTV centred on the imaged target position and the non-moving PTV. Similar to dose-volume histogram, CTV coverage-volume histograms (defined as CVH) were derived for each patient and treatment modality. The geometric coverages of the 90% and 95% of CTV volume (C90, C95, respectively) were evaluated. Patient-specific optimal margins (ensuring C95 ≥ 95%) were computed retrospectively. The median ± interquartile-rage of C90 and C95 for upper lobe lesions was 99.1 ± 0.6% and 99.0 ± 3.1%, whereas they were 98.9 ± 4.2% and 97.8 ± 7.5% for lower and middle lobe tumors. In 2-view, 1-view and 0-view modality, adopted margins ensured C95 ≥ 95% in 70%, 85% and 63% of cases and C95 ≥ 90% in 90%, 88% and 83% of cases, respectively. In 2-view, 1-view and 0-view a reduction in margins still ensured C95 ≥ 95% in 33%, 78% and 59% of cases, respectively. CTV coverage analysis provided an a-posteriori evaluation of the treatment geometric accuracy and allowed a quantitative verification of the adequacy of the PTV margins applied in CyberKnife LOT treatments offering guidance in the selection of CTV margins. © 2018 American Association of Physicists in Medicine.

Cervical brachytherapy technique for locally advanced carcinoma of the cervix in a patient with septate uterus.

PubMed

Platta, Christopher S; Wallace, Charlie; Gondi, Vinai; Das, Rupak; Straub, Margaret; Al-Niaimi, Ahmed; Applegate, Glenn; Bradley, Kristin A

2014-03-01

To describe an approach to cervical brachytherapy in a patient with congenital septate uterus and locally advanced cervical carcinoma. The patient is a 34-year-old female with septate uterus presenting with pelvic pain. Workup demonstrated a stage IIB cervical adenocarcinoma with imaging evidence of an involved right external iliac lymph node. The patient received whole pelvic radiation, with concurrent weekly cisplatin (40 mg/m(2)), to a dose of 45 Gy in 25 fractions followed by a parametrial boost of 5.4 Gy and an additional nodal boost of 9 Gy. The patient was initiated on cervical brachytherapy following fraction 23 of pelvic radiation. To conform to her septated uterus, a Rotte-Y tandem was used. Additionally, 2 CT-compatible ovoids were placed in the vaginal apex to enhance dose distribution and coverage of the target volume. Each fraction of brachytherapy was performed with CT-based planning. A high-risk clinical target volume (HR-CTV) and normal structures were defined and constrained per American Brachytherapy Society (ABS) and Groupe Européen de Curiethérapie/European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) guidelines. The brachytherapy dose was 27.5 Gy in 5 fractions of 5.5 Gy each, prescribed to the HR-CTV. Herein, we report the first documented case of cervical brachytherapy in a patient with septate uterus and locally advanced cervical carcinoma. Using CT-guided planning, in conjunction with the ABS and GEC-ESTRO guidelines, the patient was effectively treated with adapted cervical brachytherapy, meeting criteria for HR-CTV coverage and normal tissue tolerances.

High Latitude Ionospheric Radio Studies.

DTIC Science & Technology

1988-01-01

AL’TOSCI.ED RES.LTS BY A.R.TL!.S.T. LLCAR OCT 83 S11U2, 2393 :1::’L- 𔃽 -1 5 2 42 !) 1 ? 7 2 2 5.1 10* rOF2 70FI bIIF H’F2 103M ~ WIN :OES W’V -- !I 5.6...4C > % V) L C-C) CC) CCC CC) C C CCD C)CD CD C) C)D CD (CDCC) C)D CDC) CD LC DCD (D C ),C C D DA rH H-4H H I I I HCD CD HHH HH IC DC)CDCD C -A - Ir

Advanced proton beam dosimetry part II: Monte Carlo vs. pencil beam-based planning for lung cancer.

PubMed

Maes, Dominic; Saini, Jatinder; Zeng, Jing; Rengan, Ramesh; Wong, Tony; Bowen, Stephen R

2018-04-01

Proton pencil beam (PB) dose calculation algorithms have limited accuracy within heterogeneous tissues of lung cancer patients, which may be addressed by modern commercial Monte Carlo (MC) algorithms. We investigated clinical pencil beam scanning (PBS) dose differences between PB and MC-based treatment planning for lung cancer patients. With IRB approval, a comparative dosimetric analysis between RayStation MC and PB dose engines was performed on ten patient plans. PBS gantry plans were generated using single-field optimization technique to maintain target coverage under range and setup uncertainties. Dose differences between PB-optimized (PBopt), MC-recalculated (MCrecalc), and MC-optimized (MCopt) plans were recorded for the following region-of-interest metrics: clinical target volume (CTV) V95, CTV homogeneity index (HI), total lung V20, total lung V RX (relative lung volume receiving prescribed dose or higher), and global maximum dose. The impact of PB-based and MC-based planning on robustness to systematic perturbation of range (±3% density) and setup (±3 mm isotropic) was assessed. Pairwise differences in dose parameters were evaluated through non-parametric Friedman and Wilcoxon sign-rank testing. In this ten-patient sample, CTV V95 decreased significantly from 99-100% for PBopt to 77-94% for MCrecalc and recovered to 99-100% for MCopt (P<10 -5 ). The median CTV HI (D95/D5) decreased from 0.98 for PBopt to 0.91 for MCrecalc and increased to 0.95 for MCopt (P<10 -3 ). CTV D95 robustness to range and setup errors improved under MCopt (ΔD95 =-1%) compared to MCrecalc (ΔD95 =-6%, P=0.006). No changes in lung dosimetry were observed for large volumes receiving low to intermediate doses (e.g., V20), while differences between PB-based and MC-based planning were noted for small volumes receiving high doses (e.g., V RX ). Global maximum patient dose increased from 106% for PBopt to 109% for MCrecalc and 112% for MCopt (P<10 -3 ). MC dosimetry revealed a reduction in target dose coverage under PB-based planning that was regained under MC-based planning along with improved plan robustness. MC-based optimization and dose calculation should be integrated into clinical planning workflows of lung cancer patients receiving actively scanned proton therapy.

Advanced proton beam dosimetry part II: Monte Carlo vs. pencil beam-based planning for lung cancer

PubMed Central

Maes, Dominic; Saini, Jatinder; Zeng, Jing; Rengan, Ramesh; Wong, Tony

2018-01-01

Background Proton pencil beam (PB) dose calculation algorithms have limited accuracy within heterogeneous tissues of lung cancer patients, which may be addressed by modern commercial Monte Carlo (MC) algorithms. We investigated clinical pencil beam scanning (PBS) dose differences between PB and MC-based treatment planning for lung cancer patients. Methods With IRB approval, a comparative dosimetric analysis between RayStation MC and PB dose engines was performed on ten patient plans. PBS gantry plans were generated using single-field optimization technique to maintain target coverage under range and setup uncertainties. Dose differences between PB-optimized (PBopt), MC-recalculated (MCrecalc), and MC-optimized (MCopt) plans were recorded for the following region-of-interest metrics: clinical target volume (CTV) V95, CTV homogeneity index (HI), total lung V20, total lung VRX (relative lung volume receiving prescribed dose or higher), and global maximum dose. The impact of PB-based and MC-based planning on robustness to systematic perturbation of range (±3% density) and setup (±3 mm isotropic) was assessed. Pairwise differences in dose parameters were evaluated through non-parametric Friedman and Wilcoxon sign-rank testing. Results In this ten-patient sample, CTV V95 decreased significantly from 99–100% for PBopt to 77–94% for MCrecalc and recovered to 99–100% for MCopt (P<10−5). The median CTV HI (D95/D5) decreased from 0.98 for PBopt to 0.91 for MCrecalc and increased to 0.95 for MCopt (P<10−3). CTV D95 robustness to range and setup errors improved under MCopt (ΔD95 =−1%) compared to MCrecalc (ΔD95 =−6%, P=0.006). No changes in lung dosimetry were observed for large volumes receiving low to intermediate doses (e.g., V20), while differences between PB-based and MC-based planning were noted for small volumes receiving high doses (e.g., VRX). Global maximum patient dose increased from 106% for PBopt to 109% for MCrecalc and 112% for MCopt (P<10−3). Conclusions MC dosimetry revealed a reduction in target dose coverage under PB-based planning that was regained under MC-based planning along with improved plan robustness. MC-based optimization and dose calculation should be integrated into clinical planning workflows of lung cancer patients receiving actively scanned proton therapy. PMID:29876310

OSA Is a Risk Factor for Recurrent VTE.

PubMed

Alonso-Fernández, Alberto; Suquia, Angela García; de la Peña, Mónica; Casitas, Raquel; Pierola, Javier; Barceló, Antonia; Soriano, Joan B; Fernández-Capitán, Carmen; Martinez-Ceron, Elizabet; Carrera, Miguel; García-Río, Francisco

2016-12-01

OSA is a risk factor for a first episode of pulmonary embolism (PE), although its impact on the risk of thromboembolism recurring is uncertain. Our objective was to explore the prognostic value of OSA after the discontinuation of oral anticoagulation (OAC) in patients with a first episode of PE. In 120 consecutive patients who had stopped OAC for a first episode of PE, we performed home respiratory polygraphy and recorded sleep characteristics, classic risk factors for PE, blood pressure measurements, spirometric parameters, physical activity, and levels of D-dimer and prothrombin fragment 1+2 (F1+2). Patients were followed for 5 to 8 years, and the main end point was PE recurrence. Restarting OAC for any thromboembolic event was evaluated as a secondary end point. During the follow-up period, 19 patients had a PE recurrence, and 16 of them had an apnea-hypopnea index (AHI) ≥ 10 h -1 . In a multivariate Cox regression model, an AHI ≥ 10 h -1 (hazard ratio [HR], 20.73; 95% CI, 1.71-251.28), mean nocturnal oxygen saturation (nSao 2 ) (HR, 0.39; 95% CI, 0.20-0.78), time with Sao 2  < 90% (CT90%) (HR, 0.90; 95% CI, 0.82-0.98), and D-dimer level (HR, 1.001; 95% CI, 1.00-1.002) were identified as independent risk factors for recurrent PE. Twenty-four patients resumed OAC, and AHI ≥ 10 h -1 (HR, 20.66; 95% CI, 2.27-188.35), mean nSao 2 (HR, 0.54; 95% CI, 0.32-0.94), and Epworth Sleepiness Scale (ESS) (HR, 0.73; 95% CI, 0.56-0.97) were retained as independent risk factors for the resumption of OAC. After a first episode of PE, OSA is an independent risk factor for PE recurrence or restarting OAC for a new thromboembolic event. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

SU-E-T-25: A Dosimetric Comparison of Three-Dimension Conformal and Intensity-Modulated Radiation Therapy in Esophageal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gallardo, N; Maneru, F; Fuentemilla, N

2015-06-15

Purpose: dosimetric comparison of 3DCRT and IMRT in 9 esophageal cancer. The aim of this paper is to know which of these two techniques is dosimetrically more favorable dosimetrically at both the CTV coverage and dose obtained in the relevant organs at risk, in this case, lungs and heart, as the spinal cord received in all cases below 45 Gy. Methods: we chose 9 patients from our center (CHN) with the same type of esophageal cancer and in which the prescribed dose was the same, 54 Gy. For these treatments we have used the same fields and the same anglesmore » (AP (0 °), OPD (225°–240°) and OPI (125°–135°)).All plans have been implemented using Eclipse (version 11.0) with AAA( Analytical Anisotropic Algorithm )(Version 11.0.31). Results: To analyze the coverage of the CTV, we have evaluated the D99% and found that the average dose received by 99% of CTV with IMRT is 53.8 ± 0.4 Gy (99.6% of the prescribed dose) and the mean value obtained with 3DCRT is 52.3 ± 0.6 Gy (96.8% of the prescribed dose).The last data analyzed was the D2% of PTV, a fact that gives us information on the maximum dose received by our PTV. D2% of the PTV for IMRT planning is 55.4 ± 0.4 Gy (102.6% of the prescribed dose) and with 3DCRT is 56.8 ± 0.7 Gy (105.2% of the prescribed dose).All parameters analyzed at risk organs (V30, V40, V45 and V50 for the case of heart and V5, V10, V15 and V20 for the case of the lungs) provide us irradiated volume percentages lower in IMRT than 3DCRT. Conclusion: IMRT provides a considerable improvement in the coverage of the CTV and the doses to organs at risk.« less

Instrument Landing System Critical Area Studies.

DTIC Science & Technology

1983-11-01

0) 0 ) 6IJU: -OJ **D2! -6. .9.. 09 CL 4- L 0l ’-90 CC C~%01 I-IJ4u: WO N 0142b. -72- L. w- ~ Z2 ’*?-.r X -." 7, ’ Itp - - .- - - -~~2 IV - - dii z...Next there is Ms. Rachel Pollard who ran the model extensively on the IBM 370/44 and produced the calculational results basic to the study. Mr. Mark

SU-F-J-57: Effectiveness of Daily CT-Based Three-Dimensional Image Guided and Adaptive Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moriya, S; National Cancer Center, Kashiwa, Chiba; Tachibana, H

Purpose: Daily CT-based three-dimensional image-guided and adaptive (CTIGRT-ART) proton therapy system was designed and developed. We also evaluated the effectiveness of the CTIGRT-ART. Methods: Retrospective analysis was performed in three lung cancer patients: Proton treatment planning was performed using CT image datasets acquired by Toshiba Aquilion ONE. Planning target volume and surrounding organs were contoured by a well-trained radiation oncologist. Dose distribution was optimized using 180-deg. and 270-deg. two fields in passive scattering proton therapy. Well commissioned Simplified Monte Carlo algorithm was used as dose calculation engine. Daily consecutive CT image datasets was acquired by an in-room CT (Toshiba Aquilionmore » LB). In our in-house program, two image registrations for bone and tumor were performed to shift the isocenter using treatment CT image dataset. Subsequently, dose recalculation was performed after the shift of the isocenter. When the dose distribution after the tumor registration exhibits change of dosimetric parameter of CTV D90% compared to the initial plan, an additional process of was performed that the range shifter thickness was optimized. Dose distribution with CTV D90% for the bone registration, the tumor registration only and adaptive plan with the tumor registration was compared to the initial plan. Results: In the bone registration, tumor dose coverage was decreased by 16% on average (Maximum: 56%). The tumor registration shows better coverage than the bone registration, however the coverage was also decreased by 9% (Maximum: 22%) The adaptive plan shows similar dose coverage of the tumor (Average: 2%, Maximum: 7%). Conclusion: There is a high possibility that only image registration for bone and tumor may reduce tumor coverage. Thus, our proposed methodology of image guidance and adaptive planning using the range adaptation after tumor registration would be effective for proton therapy. This research is partially supported by Japan Agency for Medical Research and Development (AMED).« less

SU-C-303-06: Treatment Planning Study for Non-Invasive Cardiac Arrhythmia Ablation with Scanned Carbon Ions in An Animal Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eichhorn, A; Constantinescu, A; Prall, M

Purpose: Scanned carbon ion beams might offer a non-invasive alternative treatment for cardiac arrhythmia, which are a major health-burden. We studied the feasibility of this procedure in an animal model. The underlying treatment planning and motion mitigation strategies will be presented. Methods: The study was carried out in 15 pigs, randomly distributed to 3 target groups: atrioventricular node (AVN, 8 animals with 25, 40, and 55 Gy target dose), left ventricular free-wall (LV, 4 animals with 40 Gy) and superior pulmonary vein (SPV, 3 animals with 40 Gy). Breathing motion was suppressed by repeated enforced breathholds at end exhale. Cardiacmore » motion was mitigated by an inhomogeneous rescanning scheme with up to 15 rescans. The treatment planning was performed using the GSI in-house software TRiP4D on cardiac-gated 4DCTs, applying a range-considering ITV based on an extended CTV. For AVN and SPV isotropic 5 mm margins were applied to the CTV, while for the LV 2mm+2% range margins were used. The opposing fields for AVN and LV targets were optimized independently (SFUD), while SPV treatments were optimized as IMPT deliveries, including dose restrictions to the radiosensitive AVN. Results: Median value of D{sub 95} over all rescanning simulations was 99.1% (AVN), 98.0% (SPV) and 98.3% (LV) for the CTV and 94.7% (AVN) and 92.7% (SPV) for the PTV, respectively. The median D{sub 5}-D{sub 95} was improved with rescanning compared to unmitigated delivery from 13.3 to 6.5% (CTV) and from 23.4 to 11.6% (PTV). ICRP dose limits for aorta, trachea, esophagus and skin were respected. The maximal dose in the coronary arteries was limited to 30 Gy. Conclusion: We demonstrated the feasibility of a homogeneous dose delivery to different cardiac structures in a porcine model using a time-optimized inhomogeneous rescanning scheme. The presented treatment planning strategies were applied in a pig study with the analysis ongoing. Funding: This work was supported in part by the Helmholtz Association, the American Heart Association Midwest Affiliate Postdoctoral Fellowship Grant, the Mayo Clinic Foundation, and the Goldsmith Foundation.« less

Tissue-specific expression of the gene coding for human Clara cell 10-kD protein, a phospholipase A2-inhibitory protein.

PubMed Central

Peri, A; Cordella-Miele, E; Miele, L; Mukherjee, A B

1993-01-01

Clara cell 10-kD protein (cc10kD), a secretory phospholipase A2 inhibitor, is suggested to be the human counterpart of rabbit uteroglobin (UG). Because cc10kD is expressed constitutively at a very high level in the human respiratory epithelium, the 5' region of its gene may be useful in achieving organ-specific expression of recombinant DNA in gene therapy of diseases such as cystic fibrosis. However, it is important to establish the tissue-specific expression of this gene before designing gene transfer experiments. Since the UG gene in the rabbit is expressed in many other organs besides the lung and the endometrium, we investigated the organ and tissue specificity of human cc10kD gene expression using polymerase chain reaction, nucleotide sequence analysis, immunofluorescence, and Northern blotting. Our results indicate that, in addition to the lung, cc10kD is expressed in several nonrespiratory organs, with a distribution pattern very similar, if not identical, to that of UG in the rabbit. These results underscore the necessity for more detailed analyses of the 5' region of the human cc10kD gene before its usefulness in gene therapy could be fully assessed. These data also suggest that cc10kD and UG may have similar physiological function(s). Images PMID:8227325

Differential proteins among normal cervix cells and cervical cancer cells with HPV-16 infection, through mass spectrometry-based Proteomics (2D-DIGE) in women from Southern México.

PubMed

Serafín-Higuera, Idanya; Garibay-Cerdenares, Olga Lilia; Illades-Aguiar, Berenice; Flores-Alfaro, Eugenia; Jiménez-López, Marco Antonio; Sierra-Martínez, Pavel; Alarcón-Romero, Luz Del Carmen

2016-01-01

Cervical cancer (CC) is the fourth most common cancer in women worldwide with an estimated 528,000 new cases in 2012. The same year México had an incidence of 13,960 and a mortality of 4769 cases. There are several diagnosis methods of CC; among the most frequents are the conventional Pap cytology (Pap), colposcopy, and visual inspection with acetic acid (VIA), histopathological examination, tests of imaging and detection of high-risk papilloma virus (HR-HPV) with molecular tests (PCR, hybridization, sequencing). Proteomics is a tool for the detection of new biomarkers that can be associated with clinical stage, histological type, prognosis, and/or response to treatment. In this study we performed a comparative analysis of CC cells with normal cervical cells. The proteomic analysis was carried out with the fluorescent two-dimensional electrophoresis (2D-DIGE) technique to subsequently identify differential protein profiles using Decyder Software, and the selected proteins were identified by Mass Spectrometry (MALDI-TOF). The proteins that showed an increased expression in cervical cancer in comparison with normal cervix cells were: Mimecan, Actin from aortic smooth muscle and Lumican. While Keratin, type II cytoskeletal 5, Peroxiredoxin-1 and 14-3-3 protein sigma showed a decrease in their protein expression level in cervical cancer in comparison with normal cervix cells. Thus, this study was successful in identifying biomarker signatures for cervical cancer, and might provide new insights into the mechanism of CC progression.

TH-CD-209-04: Fuzzy Robust Optimization in Intensity-Modulated Proton Therapy Planning to Account for Range and Patient Setup Uncertainties

DOE Office of Scientific and Technical Information (OSTI.GOV)

An, Y; Bues, M; Schild, S

Purpose: We propose to apply a robust optimization model based on fuzzy-logic constraints in the intensity-modulated proton therapy (IMPT) planning subject to range and patient setup uncertainties. The purpose is to ensure the plan robustness under uncertainty and obtain the best trade-off between tumor dose coverage and organ-at-risk(OAR) sparing. Methods: Two IMPT plans were generated for 3 head-and-neck cancer patients: one used the planning target volume(PTV) method; the other used the fuzzy robust optimization method. In the latter method, nine dose distributions were computed - the nominal one and one each for ±3mm setup uncertainties along three cardinal axes andmore » for ±3.5% range uncertainty. For tumors, these nine dose distributions were explicitly controlled by adding hard constraints with adjustable parameters. For OARs, fuzzy constraints that allow the dose to vary within a certain range were used so that the tumor dose distribution was guaranteed by minimum compromise of that of OARs. We rendered this model tractable by converting the fuzzy constraints to linear constraints. The plan quality was evaluated using dose-volume histogram(DVH) indices such as tumor dose coverage(D95%), homogeneity(D5%-D95%), plan robustness(DVH band at D95%), and OAR sparing like D1% of brain and D1% of brainstem. Results: Our model could yield clinically acceptable plans. The fuzzy-logic robust optimization method produced IMPT plans with comparable target dose coverage and homogeneity compared to the PTV method(unit: Gy[RBE]; average[min, max])(CTV D95%: 59 [52.7, 63.5] vs 53.5[46.4, 60.1], CTV D5% - D95%: 11.1[5.3, 18.6] vs 14.4[9.2, 21.5]). It also generated more robust plans(CTV DVH band at D95%: 3.8[1.2, 5.6] vs 11.5[6.2, 16.7]). The parameters of tumor constraints could be adjusted to control the tradeoff between tumor coverage and OAR sparing. Conclusion: The fuzzy-logic robust optimization generates superior IMPT with minimum compromise of OAR sparing. This research was supported by the National Cancer Institute Career Developmental Award K25CA168984, by the Fraternal Order of Eagles Cancer Research Fund Career Development Award, by The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research, by Mayo Arizona State University Seed Grant, and by The Kemper Marley Foundation. eRA Person ID(s) for the Principal Investigator: 11017970 (Research Supported by National Institutes of Health)« less

Hypovolemia During Early Exposure to 2,800 m Altitude: Effect of Rehydration

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.; Farrell, P. A.; Loomis, J. L.; Fedele, M.; West, J.; Roessler, A.; Hinghofer-Szalkay, H.

1997-01-01

The mechanism for reduction of total body water and plasma volume (PV) during initial exposure to acute attitude (ALT) is not clear. Ten man (25+/-SD 3yr. 1.99+/-0.l9sq m) were confined (sitting) for 12 hr in a chamber a 2800m ALT or at 305m(ground). They ate a controlled breakfast (450 kcal + 3ml/kg H2O) on the ground, and lunch and dinner at ALT for a total daily intake of 2,850 kcal (14%PRO, 67%CHO, 16%FAT, 26gNaCl). At hr 10 they consumed fluid-electrolyte drinks or water (12ml/kg, 948ml/day) with sessions at weekly intervals: (a) 185mEq/L Na, 283mOsm/kg; (b) 21.6Na, 365mOsm: and (c) water at ALT: and (d) water on the ground. After 10 hr at ALT%(Delta)PV(Hb-Hct) decreased (P<0.05) by (a) 9.0+/-SE1.5%, (b) 6.2+/-1.7%, (c) 7.4+/-2.2%. and (d) 9.0+/-2.4%. respectively. After drinking at 1200 hr PV increased by (a) 8.3% (P<0.05), (b) 2.8% (NS), (c) -0.9% (NS). and (d) by 0.8% (NS). respectively. The ground-induced hypovolemia suggests a confinement rather than an ALT effect. The increase in PV after the NaCl-NaCitrate drink (a) indicates that drink composition is mom important than as Osm for restoring PV in these Conditions.

Development of the Ovarian Cancer Cohort Consortium: Risk Factor Associations by Heterogeneity of Disease

DTIC Science & Technology

2016-12-01

Lifestyle, & Health (CSDLH)4 39,618 90 58 B, D Cancer Prevention Study II (CPS2) 65,975 549 62 B, FU, D Campaign Against Cancer & Heart Disease ...stronger positive associations for less aggressive disease phenotypes. Only very aggressive disease was associated with current versus never smoking (HR...history of ovarian cancer with less aggressive disease is supported by reports of better survival in BRCA mutation carriers. The BMI association with

Optimal Patient Positioning (Prone Versus Supine) for VMAT in Gynecologic Cancer: A Dosimetric Study on the Effect of Different Margins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heijkoop, Sabrina T., E-mail: s.heijkoop@erasmusmc.nl; Westerveld, Henrike; Bijker, Nina

Purpose/Objective: It is unknown whether the historically found dosimetric advantages of treating gynecologic cancer with the patient in a prone position with use of a small-bowel displacement device (belly-board) remain when volumetric arc therapy (VMAT) is used and whether these advantages depend on the necessary margin between clinical target volume (CTV) and planning target volume (PTV). The aim of this study is to determine the best patient position (prone or supine) in terms of sparing organs at risk (OAR) for various CTV-to-PTV margins and VMAT dose delivery. Methods and Materials: In an institutional review board—approved study, 26 patients with gynecologicmore » cancer scheduled for primary (9) or postoperative (17) radiation therapy were scanned in a prone position on a belly-board and in a supine position on the same day. The primary tumor CTV, nodal CTV, bladder, bowel, and rectum were delineated on both scans. The PTVs were created each with a different margin for the primary tumor and nodal CTV. The VMAT plans were generated with our in-house system for automated treatment planning. For all margin combinations, the supine and prone plans were compared with consideration of all OAR dose-volume parameters but with highest priority given to bowel cavity V{sub 45Gy} (cm{sup 3}). Results: For both groups, the prone position reduced the bowel cavity V{sub 45Gy}, in particular for nodal margins ≥10 mm (ΔV{sub 45Gy} = 23.9 ± 10.6 cm{sup 3}). However, for smaller margins, the advantage was much less pronounced (ΔV{sub 45Gy} = 6.5 ± 3.0 cm{sup 3}) and did not reach statistical significance. The rectum mean dose (D{sub mean}) was significantly lower (ΔD{sub mean} = 2.5 ± 0.3 Gy) in the prone position for both patient groups and for all margins, and the bladder D{sub mean} was significantly lower in the supine position (ΔD{sub mean} = 2.6 ± 0.4 Gy) only for the postoperative group. The advantage of the prone position was not present if it needed a larger margin than the supine position. Conclusion: For patients with gynecologic cancer, the historically found dosimetric advantages for the prone position remain for modern dose delivery techniques if large margins are needed. However, the advantage is lost for small margins and if the prone position needs a larger margin than the supine position.« less

Enhanced Osteoblast Response to Porosity and Resolution of Additively Manufactured Ti-6Al-4V Constructs with Trabeculae-Inspired Porosity

PubMed Central

Cheng, Alice; Humayun, Aiza; Schwartz, Zvi

2016-01-01

Abstract The addition of porosity to the traditionally used solid titanium metal implants has been suggested to more closely mimic the natural mechanical properties of bone and increase osseointegration in dental and orthopedic implants. The objective of this study was to evaluate cellular response to three-dimensional (3D) porous Ti-6Al-4V constructs fabricated by additive manufacturing using laser sintering with low porosity (LP), medium porosity (MP), and high porosity (HP) with low resolution (LR) and high resolution (HR) based on a computed tomography scan of human trabecular bone. After surface processing, construct porosity ranged from 41.0% to 76.1%, but all possessed micro-/nanoscale surface roughness and similar surface chemistry containing mostly Ti, O, and C. Biological responses (osteoblast differentiation, maturation, and local factor production) by MG63 osteoblast-like cells and normal human osteoblasts favored 3D than two-dimensional (2D) solid constructs. First, MG63 cells were used to assess differences in cell response to 2D compared to LR and HR porous 3D constructs. MG63 cells were sensitive to porosity resolution and exhibited increased osteocalcin (OCN), vascular endothelial growth factor (VEGF), osteoprotegerin (OPG), and bone morphogenetic protein 2 (BMP2) on HR 3D constructs than on 2D and LR 3D constructs. MG63 cells also exhibited porosity-dependent responses on HR constructs, with up to a 6.9-fold increase in factor production on LP-HR and MP-HR constructs than on HP-HR constructs. NHOsts were then used to validate biological response on HR constructs. NHOsts exhibited decreased DNA content and alkaline phosphatase activity and up to a 2.9-fold increase in OCN, OPG, VEGF, BMP2, and BMP4 on 3D HR constructs than on 2D controls. These results indicate that osteoblasts prefer a 3D architecture than a 2D surface and that osteoblasts are sensitive to the resolution of trabecular detail and porosity parameters of laser-sintered 3D Ti-6Al-4V constructs. PMID:28804735

Enhanced Osteoblast Response to Porosity and Resolution of Additively Manufactured Ti-6Al-4V Constructs with Trabeculae-Inspired Porosity.

PubMed

Cheng, Alice; Humayun, Aiza; Boyan, Barbara D; Schwartz, Zvi

2016-03-01

The addition of porosity to the traditionally used solid titanium metal implants has been suggested to more closely mimic the natural mechanical properties of bone and increase osseointegration in dental and orthopedic implants. The objective of this study was to evaluate cellular response to three-dimensional (3D) porous Ti-6Al-4V constructs fabricated by additive manufacturing using laser sintering with low porosity (LP), medium porosity (MP), and high porosity (HP) with low resolution (LR) and high resolution (HR) based on a computed tomography scan of human trabecular bone. After surface processing, construct porosity ranged from 41.0% to 76.1%, but all possessed micro-/nanoscale surface roughness and similar surface chemistry containing mostly Ti, O, and C. Biological responses (osteoblast differentiation, maturation, and local factor production) by MG63 osteoblast-like cells and normal human osteoblasts favored 3D than two-dimensional (2D) solid constructs. First, MG63 cells were used to assess differences in cell response to 2D compared to LR and HR porous 3D constructs. MG63 cells were sensitive to porosity resolution and exhibited increased osteocalcin (OCN), vascular endothelial growth factor (VEGF), osteoprotegerin (OPG), and bone morphogenetic protein 2 (BMP2) on HR 3D constructs than on 2D and LR 3D constructs. MG63 cells also exhibited porosity-dependent responses on HR constructs, with up to a 6.9-fold increase in factor production on LP-HR and MP-HR constructs than on HP-HR constructs. NHOsts were then used to validate biological response on HR constructs. NHOsts exhibited decreased DNA content and alkaline phosphatase activity and up to a 2.9-fold increase in OCN, OPG, VEGF, BMP2, and BMP4 on 3D HR constructs than on 2D controls. These results indicate that osteoblasts prefer a 3D architecture than a 2D surface and that osteoblasts are sensitive to the resolution of trabecular detail and porosity parameters of laser-sintered 3D Ti-6Al-4V constructs.

A three-dimensional cell culture system as an in vitro canine mammary carcinoma model for the expression of connective tissue modulators.

PubMed

Cardoso, T C; Sakamoto, S S; Stockmann, D; Souza, T F B; Ferreira, H L; Gameiro, R; Vieira, F V; Louzada, M J Q; Andrade, A L; Flores, E F

2017-06-01

In this study, derived complex carcinoma (CC) and simple carcinoma (SC) cell lines were established and cultured under two-dimensional (2D) and three-dimensional (3D) conditions. The 3D was performed in six-well AlgiMatrix™ (LifeTechnologies®, Carlsbad, CA, USA) scaffolds, resulting in spheroids sized 50-125 µm for CC and 175-200 µm for SC. Cell viability was demonstrated up to 14 days for both models. Epidermal growth factor receptor (EGFR) was expressed in CC and SC in both systems. However, higher mRNA and protein levels were observed in SC 2D and 3D systems when compared with CC (P < 0.005). The connective tissue modulators, metalloproteinases-1, -2, -9 and -13 (MMPs), relaxin receptors 1 and 2 (RXR1 and RXR2) and E-cadherin (CDH1) were quantitated. All were upregulated similarly when canine mammary tumour (CMT)-derived cell lines were cultured under 3D AlgiMatrix, except CDH1 that was downregulated (P < 0.005). These results are promising towards the used of 3D system to increase a high throughput in vitro canine tumour model. © 2016 John Wiley & Sons Ltd.

Cervical cancer screening in a low-resource setting: a pilot study on an HPV-based screen-and-treat approach.

PubMed

Kunckler, Margot; Schumacher, Fanny; Kenfack, Bruno; Catarino, Rosa; Viviano, Manuela; Tincho, Eveline; Tebeu, Pierre-Marie; Temogne, Liliane; Vassilakos, Pierre; Petignat, Patrick

2017-07-01

Cervical cancer (CC) is the leading cause of cancer-related death among women in sub-Saharan Africa, primarily because of limited access to effective screening and preventive treatment. Our aim was to assess the feasibility of a human papillomavirus (HPV)-based CC screen-and-treat approach in a low-resource context. We recruited 1012 women aged 30-49 years through a CC screening campaign conducted in the District Hospital of Dschang, Cameroon. Participants performed HPV self-sampling, which was tested for high-risk HPV (HR-HPV) DNA using the point-of-care Xpert HPV assay. All HPV-positive women were invited for visual inspection with acetic acid and Lugol's iodine (VIA/VILI) to exclude CC or enable triage. A cervical sample for histological analysis was also collected. Women positive for HPV 16/18/45 and for other HR-HPV with pathological VIA/VILI were selected to undergo treatment with thermocoagulation. The HPV prevalence in the study population was 18.5% (n = 187); of these cases, 20 (10.6%), 42 (22.3%) and 140 (74.9%) were positive for HPV16, HPV18/45 and other HR-HPV types, respectively. Overall, 107/185 (57.8%) VIA/VILI examinations were classified as pathological and 78 (42.2%) as normal. Women positive for HPV16/18/45 were 4.2 times more likely to harbor cervical intraepithelial neoplasia grade 2 or worse (CIN2+) than those with other HPV types. The specificity of HPV 16/18/45 genotypes for detection of high-grade lesions among HR-HPV positive women was higher than that of VIA/VILI in all age groups. The sensitivity and specificity of VIA/VILI in detecting CIN2+ among HPV positive women were 80% and 44%, respectively. Overall, 110/121 screen-positive women (90.9%) were eligible for, and were treated with, thermocoagulation. An HPV-based screen-and-treat approach is feasible in a low-resource context and may contribute to improving the effectiveness of CC prevention programs. Immediate thermocoagulation treatment for women who are HPV16- and/or HPV18/45-positive is a practical approach for the treatment of CIN2+. The combination of HPV-testing and VIA/VILI for CC screening might reduce overtreatment. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Head and Neck Margin Reduction With Adaptive Radiation Therapy: Robustness of Treatment Plans Against Anatomy Changes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kranen, Simon van; Hamming-Vrieze, Olga; Wolf, Annelisa

Purpose: We set out to investigate loss of target coverage from anatomy changes in head and neck cancer patients as a function of applied safety margins and to verify a cone beam computed tomography (CBCT)–based adaptive strategy with an average patient anatomy to overcome possible target underdosage. Methods and Materials: For 19 oropharyngeal cancer patients, volumetric modulated arc therapy treatment plans (2 arcs; simultaneous integrated boost, 70 and 54.25 Gy; 35 fractions) were automatically optimized with uniform clinical target volume (CTV)–to–planning target volume margins of 5, 3, and 0 mm. We applied b-spline CBCT–to–computed tomography (CT) deformable registration to allow recalculation ofmore » the dose on modified CT scans (planning CT deformed to daily CBCT following online positioning) and dose accumulation in the planning CT scan. Patients with deviations in primary or elective CTV coverage >2 Gy were identified as candidates for adaptive replanning. For these patients, a single adaptive intervention was simulated with an average anatomy from the first 10 fractions. Results: Margin reduction from 5 mm to 3 mm to 0 mm generally led to an organ-at-risk (OAR) mean dose (D{sub mean}) sparing of approximately 1 Gy/mm. CTV shrinkage was mainly seen in the elective volumes (up to 10%), likely related to weight loss. Despite online repositioning, substantial systematic errors were present (>3 mm) in lymph node CTV, the parotid glands, and the larynx. Nevertheless, the average increase in OAR dose was small: maximum of 1.2 Gy (parotid glands, D{sub mean}) for all applied margins. Loss of CTV coverage >2 Gy was found in 1, 3, and 7 of 73 CTVs, respectively. Adaptive intervention in 0-mm plans substantially improved coverage: in 5 of 7 CTVs (in 6 patients) to <2 Gy of initially planned. Conclusions: Volumetric modulated arc therapy head and neck cancer treatment plans with 5-mm margins are robust for anatomy changes and show a modest increase in OAR dose. Margin reduction improves OAR sparing with approximately 1 Gy/mm at the expense of target coverage in a subgroup of patients. Patients at risk of CTV underdosage >2 Gy in 0-mm plans may be identified early in treatment using dose accumulation. A single intervention with an average anatomy derived from CBCT effectively mitigates discrepancies.« less

Physical and Physiological Characteristics of Various-Sided Games in Elite Women's Soccer.

PubMed

Mara, Jocelyn K; Thompson, Kevin G; Pumpa, Kate L

2016-10-01

To investigate the physical and physiological response to different formats of various-sided games. Eighteen elite women's soccer players wore 15-Hz global positioning system devices and heart-rate (HR) monitors during various-sided games (small, 4 vs 4 and 5 vs 5; medium, 6 vs 6 and 7 vs 7; large, 8 vs 8 and 9 vs 9). Players covered more relative sprinting distance during large-sided games than in small-sided (P < .001, d = 0.69) and medium-sided (P < .001, d = 0.54) games. In addition, a greater proportion of total acceleration efforts that had a commencement velocity <1 m/s were observed in small-sided games (44.7% ± 5.5%) than in large-sided games (36.7% ± 10.6%) (P = .018, d = 0.94). This was accompanied by a greater proportion of acceleration efforts with a final velocity equivalent to the sprint threshold in large-sided games (15.4% ± 7.7%) than in small-sided games (5.2% ± 2.5%) (P < .001, d = 1.78). The proportion of time spent in HR zone 4 (>85% maximum HR) was greater during small-sided games (69.8% ± 2.5%) than in medium- (62.1% ± 2.8%, d = 2.90) and large-sided games (54.9% ± 3.1%) (P < .001, d = 5.29). The results from this study demonstrate that coaches can use small-sided games as an aerobic conditioning stimulus and to develop players' explosiveness and repeat-sprint ability over short durations. Large-sided games can be used to maintain aerobic capacity and develop maximum speed over longer distances.

[Dosimetry verification of radioactive seed implantation with 3D printing template and CT guidance for paravertebral/retroperitoneal malignant tumor].

PubMed

Ji, Z; Jiang, Y L; Guo, F X; Peng, R; Sun, H T; Fan, J H; Wang, J J

2017-04-04

Objective: To compare the dose distributions of postoperative plans with preoperative plans for seeds implantations of paravertebral/retroperitoneal tumors assisted by 3D printing guide template and CT guidance, explore the effects of the technology for seeds implantations in dosimetry level and provide data support for the optimization and standardization in seeds implantation. Methods: Between December 2015 and July 2016, a total of 10 patients with paravertebral/retroperitoneal tumors (12 lesions) received 3D printing template assist radioactive seeds implantations in department of radiation oncology of Peking University Third Hospital, and included in the study. The diseases included cervical cancer, kidney cancer, abdominal stromal tumor, leiomyosarcoma of kidney, esophageal cancer and carcinoma of ureter. The prescribed doses was 110-150 Gy. All patients received preoperative planning design, individual template design and production, and the dose distribution of postoperative plan was compared with preoperative plan. Dose parameters including D(90), MPD, V(100), V(150,)conformal index(CI), EI of target volume and D(2cc) of organs at risk (spinal cord, aorta, kidney). Statistical software was SPSS 19.0 and statistical method was non-parameters Wilcoxon symbols test. Results: A total of 10 3D printing templates were designed and produced which were including 12 treatment areas.The mean D(90) of postoperative target area (GTV) was 131.1 (97.8-167.4 Gy) Gy. The actual seeds number of post operation increased by 3 to 12 in 5 cases (42.0%). The needle was well distributed. For postoperative plans, the mean D(90,)MPD, V(100,)V(150) was 131.1 Gy, 69.3 Gy, 90.2% and 65.2%, respectively, and which was 140.2 Gy, 65.6 Gy, 91.7% and 26.8%, respectively, in preoperative plans. This meant that the actual dose of target volume was slightly lower than preplanned dose, and the high dose area of target volume was larger than preplanned range, but there was no statistical difference in P value between the two groups except V(150)( P =0.004). The actual dose conformity of target volume was worse than preplanned (CI was 0.58 and 0.62, respectively) and the difference was statistically significant( P =0.019). The actual dose of external target volume was higher than preplanned (EI was 55% and 45.9%, respectively) and the difference had no significance. For organs at risk, the actual mean D(2cc) of spinal cord, aorta and kidney was 24.7, 54.4 and 29.7 Gy, respectively, which was higher than preplanned(20.6, 51.6 and 28.6 Gy, respectively), and there was no significant difference in two groups. Conclusions: Most parameters of postoperative validations for 3D printing template assisted seeds implantation in paravertebral/retroperitoneal are closed to the expectations of preoperative plans which means the improvement of accuracy in treatment.

Effect of dietary coarsely ground corn on broiler live performance, gastrointestinal tract development, apparent ileal digestibility of energy and nitrogen, and digesta particle size distribution and retention time

PubMed Central

Xu, Y.; Stark, C. R.; Ferket, P. R.; Williams, C. M.; Pacheco, W. J.; Brake, J.

2015-01-01

Dietary structural material has been reported to improve broiler live performance and gastrointestinal tract (GIT) function. In this 50 d cage study, the effects of coarsely ground corn (CC) inclusion on broiler live performance, GIT development, apparent ileal digestibility (AID) of energy and nitrogen (N), and digesta particle size distribution and retention time were investigated. This study included 3 CC inclusions (0, 25, and 50% fine corn [FC] replaced by CC), with 6 replicate cages of 10 birds per treatment. The feed conversion ratio (FCR) at 35 and 42 d was improved (P < 0.01) as the dietary inclusion of CC increased without effect on feed intake. The 50% CC diet increased absolute and relative gizzard weight at 42 d of age as compared to diets with 0 and 25% CC (P < 0.01). Dietary CC increased absolute proventriculus weight at 28 d of age (P < 0.05). A numerically lower gizzard digesta pH (P < 0.08) was observed at 28 d but not 42 d of age, and there was no difference in proventriculus, jejunum, or ileum digesta pH at 28 or 42 d of age. The 25 and 50% CC treatments increased the digesta retention time at 30 and 45 d of age (P < 0.05 and P < 0.01, respectively). The 25 and 50% CC treatments improved AID of energy by 7.1 and 8.2%, respectively, when compared with the 0% CC treatment, and they improved AID of N by 12.2 and 12.4%, respectively (P < 0.01). The digesta particles in the jejunum exhibited a similar distribution, with a dgw (geometric mean diameter by mass) of 218, 204, and 181 μm when 0, 25, of 50% CC diets were consumed, respectively. In conclusion, birds fed pelleted and screened diets that contained 25 and 50% CC exhibited increased BW, improved FCR, and increased AID of energy and N, which was probably due to enhanced gizzard development and greater digesta retention time. PMID:25568134

Caffeine Intake, Coffee Consumption, and Risk of Cutaneous Malignant Melanoma

PubMed Central

Wu, Shaowei; Han, Jiali; Song, Fengju; Cho, Eunyoung; Gao, Xiang; Hunter, David J.; Qureshi, Abrar A.

2015-01-01

Background Caffeine has been shown to prevent ultraviolet radiation-induced carcinogenesis and to inhibit growth of melanoma cells in experimental studies. Objectives We evaluated the association between caffeine intake, coffee consumption, and melanoma risk among three large cohort studies. Methods The analysis used data from 163,886 women in the Nurses’ Health Study II (NHS II, 1991–2009) and Nurses’ Health Study (NHS, 1980–2008) and 39,424 men in the Health Professionals Follow-up Study (HPFS, 1986–2008). We used Cox proportional hazards models to estimate the hazard ratios (HR) with 95% confidence intervals (CI) of melanoma associated with dietary intakes. Results We documented 2,254 melanoma cases over 4 million person-years of follow-up. After adjustment for other risk factors, higher total caffeine intake was associated with a lower risk of melanoma (≥393 mg/d vs. <60 mg/d: HR=0.78, 95% CI=0.64–0.96, Ptrend=0.048). The association was more apparent in women (≥393 mg/d vs. <60 mg/d: HR=0.70, 95% CI=0.58–0.85, Ptrend=0.001) than in men (HR=0.94, 95% CI=0.75–1.18, Ptrend=0.81), and more apparent for melanomas occurred on the body sites with higher continuous sun exposure (head, neck and extremities) (≥393 mg/d vs. <60 mg/d: HR=0.71, 95% CI=0.59–0.86, Ptrend=0.001) than for melanomas occurred on the body sites with lower continuous sun exposure (trunk including shoulder, back, hip, abdomen and chest) (HR=0.90, 95% CI=0.70–1.16, Ptrend=0.60). This pattern of association was similar to that for caffeinated coffee consumption, whereas no association was found for decaffeinated coffee consumption and melanoma risk. Conclusions Increasing caffeine intake and caffeinated coffee consumption may be protective against cutaneous malignant melanomas. PMID:26172864

Therapy of prostate cancer using a novel cancer terminator virus and a small molecule BH-3 mimetic.

PubMed

Sarkar, Siddik; Quinn, Bridget A; Shen, Xue-Ning; Dash, Rupesh; Das, Swadesh K; Emdad, Luni; Klibanov, Alexander L; Wang, Xiang-Yang; Pellecchia, Maurizio; Sarkar, Devanand; Fisher, Paul B

2015-05-10

Despite recent advances, treatment options for advanced prostate cancer (CaP) remain limited. We are pioneering approaches to treat advanced CaP that employ conditionally replication-competent oncolytic adenoviruses that simultaneously produce a systemically active cancer-specific therapeutic cytokine, mda-7/IL-24, Cancer Terminator Viruses (CTV). A truncated version of the CCN1/CYR61 gene promoter, tCCN1-Prom, was more active than progression elevated gene-3 promoter (PEG-Prom) in regulating transformation-selective transgene expression in CaP and oncogene-transformed rat embryo cells. Accordingly, we developed a new CTV, Ad.tCCN1-CTV-m7, which displayed dose-dependent killing of CaP without harming normal prostate epithelial cells in vitro with significant anti-cancer activity in vivo in both nude mouse CaP xenograft and transgenic Hi-Myc mice (using ultrasound-targeted microbubble (MB)-destruction, UTMD, with decorated MBs). Resistance to mda-7/IL-24-induced cell death correlated with overexpression of Bcl-2 family proteins. Inhibiting Mcl-1 using an enhanced BH3 mimetic, BI-97D6, sensitized CaP cell lines to mda-7/IL-24-induced apoptosis. Combining BI-97D6 with Ads expressing mda-7/IL-24 promoted ER stress, decreased anti-apoptotic Mcl-1 expression and enhanced mda-7/IL-24 expression through mRNA stabilization selectively in CaP cells. In Hi-myc mice, the combination induced enhanced apoptosis and tumor growth suppression. These studies highlight therapeutic efficacy of combining a BH3 mimetic with a novel CTV, supporting potential clinical applications for treating advanced CaP.

SU-C-BRA-05: Delineating High-Dose Clinical Target Volumes for Head and Neck Tumors Using Machine Learning Algorithms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cardenas, C; The University of Texas Graduate School of Biomedical Sciences, Houston, TX; Wong, A

Purpose: To develop and test population-based machine learning algorithms for delineating high-dose clinical target volumes (CTVs) in H&N tumors. Automating and standardizing the contouring of CTVs can reduce both physician contouring time and inter-physician variability, which is one of the largest sources of uncertainty in H&N radiotherapy. Methods: Twenty-five node-negative patients treated with definitive radiotherapy were selected (6 right base of tongue, 11 left and 9 right tonsil). All patients had GTV and CTVs manually contoured by an experienced radiation oncologist prior to treatment. This contouring process, which is driven by anatomical, pathological, and patient specific information, typically results inmore » non-uniform margin expansions about the GTV. Therefore, we tested two methods to delineate high-dose CTV given a manually-contoured GTV: (1) regression-support vector machines(SVM) and (2) classification-SVM. These models were trained and tested on each patient group using leave-one-out cross-validation. The volume difference(VD) and Dice similarity coefficient(DSC) between the manual and auto-contoured CTV were calculated to evaluate the results. Distances from GTV-to-CTV were computed about each patient’s GTV and these distances, in addition to distances from GTV to surrounding anatomy in the expansion direction, were utilized in the regression-SVM method. The classification-SVM method used categorical voxel-information (GTV, selected anatomical structures, else) from a 3×3×3cm3 ROI centered about the voxel to classify voxels as CTV. Results: Volumes for the auto-contoured CTVs ranged from 17.1 to 149.1cc and 17.4 to 151.9cc; the average(range) VD between manual and auto-contoured CTV were 0.93 (0.48–1.59) and 1.16(0.48–1.97); while average(range) DSC values were 0.75(0.59–0.88) and 0.74(0.59–0.81) for the regression-SVM and classification-SVM methods, respectively. Conclusion: We developed two novel machine learning methods to delineate high-dose CTV for H&N patients. Both methods showed promising results that hint to a solution to the standardization of the contouring process of clinical target volumes. Varian Medical Systems grant.« less

Measurement of Charged and Neutral Current e-p Deep Inelastic Scattering Cross Sections at High Q2

NASA Astrophysics Data System (ADS)

Derrick, M.; Krakauer, D.; Magill, S.; Mikunas, D.; Musgrave, B.; Repond, J.; Stanek, R.; Talaga, R. L.; Zhang, H.; Ayad, R.; Bari, G.; Basile, M.; Bellagamba, L.; Boscherini, D.; Bruni, A.; Bruni, G.; Bruni, P.; Cara Romeo, G.; Castellini, G.; Chiarini, M.; Cifarelli, L.; Cindolo, F.; Contin, A.; Corradi, M.; Gialas, I.; Giusti, P.; Iacobucci, G.; Laurenti, G.; Levi, G.; Margotti, A.; Massam, T.; Nania, R.; Nemoz, C.; Palmonari, F.; Polini, A.; Sartorelli, G.; Timellini, R.; Zamora Garcia, Y.; Zichichi, A.; Bargende, A.; Crittenden, J.; Desch, K.; Diekmann, B.; Doeker, T.; Eckert, M.; Feld, L.; Frey, A.; Geerts, M.; Geitz, G.; Grothe, M.; Haas, T.; Hartmann, H.; Haun, D.; Heinloth, K.; Hilger, E.; Jakob, H.-P.; Katz, U. F.; Mari, S. M.; Mass, A.; Mengel, S.; Mollen, J.; Paul, E.; Rembser, Ch.; Schattevoy, R.; Schramm, D.; Stamm, J.; Wedemeyer, R.; Campbell-Robson, S.; Cassidy, A.; Dyce, N.; Foster, B.; George, S.; Gilmore, R.; Heath, G. P.; Heath, H. F.; Llewellyn, T. J.; Morgado, C. J.; Norman, D. J.; O'Mara, J. A.; Tapper, R. J.; Wilson, S. S.; Yoshida, R.; Rau, R. R.; Arneodo, M.; Iannotti, L.; Schioppa, M.; Susinno, G.; Bernstein, A.; Caldwell, A.; Cartiglia, N.; Parsons, J. A.; Ritz, S.; Sciulli, F.; Straub, P. B.; Wai, L.; Yang, S.; Zhu, Q.; Borzemski, P.; Chwastowski, J.; Eskreys, A.; Piotrzkowski, K.; Zachara, M.; Zawiejski, L.; Adamczyk, L.; Bednarek, B.; Jeleń, K.; Kisielewska, D.; Kowalski, T.; Rulikowska-Zarȩbska, E.; Suszycki, L.; ZajaÇ, J.; Kotański, A.; Przybycień, M.; Bauerdick, L. A.; Behrens, U.; Beier, H.; Bienlein, J. K.; Coldewey, C.; Deppe, O.; Desler, K.; Drews, G.; Flasiński, M.; Gilkinson, D. J.; Glasman, C.; Göttlicher, P.; Grosse-Knetter, J.; Gutjahr, B.; Hain, W.; Hasell, D.; Hessling, H.; Hultschig, H.; Iga, Y.; Joos, P.; Kasemann, M.; Klanner, R.; Koch, W.; Köpke, L.; Kötz, U.; Kowalski, H.; Labs, J.; Ladage, A.; Löhr, B.; Löwe, M.; Lüke, D.; Mańczak, O.; Ng, J. S.; Nickel, S.; Notz, D.; Ohrenberg, K.; Roco, M.; Rohde, M.; Roldán, J.; Schneekloth, U.; Schulz, W.; Selonke, F.; Stiliaris, E.; Surrow, B.; Voss, T.; Westphal, D.; Wolf, G.; Youngman, C.; Zhou, J. F.; Grabosch, H. J.; Kharchilava, A.; Leich, A.; Mattingly, M.; Meyer, A.; Schlenstedt, S.; Wulff, N.; Barbagli, G.; Pelfer, P.; Anzivino, G.; Maccarrone, G.; de Pasquale, S.; Votano, L.; Bamberger, A.; Eisenhardt, S.; Freidhof, A.; Söldner-Rembold, S.; Schroeder, J.; Trefzger, T.; Brook, N. H.; Bussey, P. J.; Doyle, A. T.; Fleck, J. I.; Saxon, D. H.; Utley, M. L.; Wilson, A. S.; Dannemann, A.; Holm, U.; Horstmann, D.; Neumann, T.; Sinkus, R.; Wick, K.; Badura, E.; Burow, B. D.; Hagge, L.; Lohrmann, E.; Mainusch, J.; Milewski, J.; Nakahata, M.; Pavel, N.; Poelz, G.; Schott, W.; Zetsche, F.; Bacon, T. C.; Butterworth, I.; Gallo, E.; Harris, V. L.; Hung, B. Y.; Long, K. R.; Miller, D. B.; Morawitz, P. P.; Prinias, A.; Sedgbeer, J. K.; Whitfield, A. F.; Mallik, U.; McCliment, E.; Wang, M. Z.; Wang, S. M.; Wu, J. T.; Zhang, Y.; Cloth, P.; Filges, D.; An, S. H.; Hong, S. M.; Nam, S. W.; Park, S. K.; Suh, M. H.; Yon, S. H.; Imlay, R.; Kartik, S.; Kim, H.-J.; McNeil, R. R.; Metcalf, W.; Nadendla, V. K.; Barreiro, F.; Cases, G.; Graciani, R.; Hernández, J. M.; Hervás, L.; Labarga, L.; del Peso, J.; Puga, J.; Terron, J.; de Trocóniz, J. F.; Smith, G. R.; Corriveau, F.; Hanna, D. S.; Hartmann, J.; Hung, L. W.; Lim, J. N.; Matthews, C. G.; Patel, P. M.; Sinclair, L. E.; Stairs, D. G.; St. Laurent, M.; Ullmann, R.; Zacek, G.; Bashkirov, V.; Dolgoshein, B. A.; Stifutkin, A.; Bashindzhagyan, G. L.; Ermolov, P. F.; Gladilin, L. K.; Golubkov, Y. A.; Kobrin, V. D.; Kuzmin, V. A.; Proskuryakov, A. S.; Savin, A. A.; Shcheglova, L. M.; Solomin, A. N.; Zotov, N. P.; Botje, M.; Chlebana, F.; Dake, A.; Engelen, J.; de Kamps, M.; Kooijman, P.; Kruse, A.; Tiecke, H.; Verkerke, W.; Vreeswijk, M.; Wiggers, L.; de Wolf, E.; van Woudenberg, R.; Acosta, D.; Bylsma, B.; Durkin, L. S.; Honscheid, K.; Li, C.; Ling, T. Y.; McLean, K. W.; Murray, W. N.; Park, I. H.; Romanowski, T. A.; Seidlein, R.; Bailey, D. S.; Blair, G. A.; Byrne, A.; Cashmore, R. J.; Cooper-Sarkar, A. M.; Daniels, D.; Devenish, R. C.; Harnew, N.; Lancaster, M.; Luffman, P. E.; Lindemann, L.; McFall, J. D.; Nath, C.; Noyes, V. A.; Quadt, A.; Uijterwaal, H.; Walczak, R.; Wilson, F. F.; Yip, T.; Abbiendi, G.; Bertolin, A.; Brugnera, R.; Carlin, R.; dal Corso, F.; de Giorgi, M.; Dosselli, U.; Limentani, S.; Morandin, M.; Posocco, M.; Stanco, L.; Stroili, R.; Voci, C.; Bulmahn, J.; Butterworth, J. M.; Feild, R. G.; Oh, B. Y.; Whitmore, J. J.; D'Agostini, G.; Marini, G.; Nigro, A.; Tassi, E.; Hart, J. C.; McCubbin, N. A.; Prytz, K.; Shah, T. P.; Short, T. L.; Barberis, E.; Dubbs, T.; Heusch, C.; van Hook, M.; Hubbard, B.; Lockman, W.; Rahn, J. T.; Sadrozinski, H. F.-W.; Seiden, A.; Biltzinger, J.; Schwarzer, O.; Seifert, R. J.; Walenta, A. H.; Zech, G.; Abramowicz, H.; Briskin, G.; Dagan, S.; Levy, A.; Hasegawa, T.; Hazumi, M.; Ishii, T.; Kuze, M.; Mine, S.; Nagasawa, Y.; Nakao, M.; Suzuki, I.; Tokushuku, K.; Yamada, S.; Yamazaki, Y.; Chiba, M.; Hamatsu, R.; Hirose, T.; Homma, K.; Kitamura, S.; Nakamitsu, Y.; Yamauchi, K.; Cirio, R.; Costa, M.; Ferrero, M. I.; Lamberti, L.; Maselli, S.; Peroni, C.; Sacchi, R.; Solano, A.; Staiano, A.; Dardo, M.; Bailey, D. C.; Bandyopadhyay, D.; Benard, F.; Brkic, M.; Crombie, M. B.; Gingrich, D. M.; Hartner, G. F.; Joo, K. K.; Levman, G. M.; Martin, J. F.; Orr, R. S.; Sampson, C. R.; Teuscher, R. J.; Catterall, C. D.; Jones, T. W.; Kaziewicz, P. B.; Lane, J. B.; Saunders, R. L.; Shulman, J.; Blankenship, K.; Kochocki, J.; Lu, B.; Mo, L. W.; Bogusz, W.; Charchuła, K.; Ciborowski, J.; Gajewski, J.; Grzelak, G.; Kasprzak, M.; Krzyżanowski, M.; Muchorowski, K.; Nowak, R. J.; Pawlak, J. M.; Tymieniecka, T.; Wróblewski, A. K.; Zakrzewski, J. A.; Żarnecki, A. F.; Adamus, M.; Eisenberg, Y.; Karshon, U.; Revel, D.; Zer-Zion, D.; Ali, I.; Badgett, W. F.; Behrens, B.; Dasu, S.; Fordham, C.; Foudas, C.; Goussiou, A.; Loveless, R. J.; Reeder, D. D.; Silverstein, S.; Smith, W. H.; Vaiciulis, A.; Wodarczyk, M.; Tsurugai, T.; Bhadra, S.; Cardy, M. L.; Fagerstroem, C.-P.; Frisken, W. R.; Furutani, K. M.; Khakzad, M.; Schmidke, W. B.

1995-08-01

Deep inelastic e-p scattering has been studied in both the charged current (CC) and neutral current (NC) reactions at momentum transfers squared Q2 above 400 GeV2 using the ZEUS detector at the HERA ep collider. The CC and NC total cross sections, the NC to CC cross section ratio, and the differential cross sections dσ/dQ2 are presented. From the Q2 dependence of the CC cross section, the mass term in the CC propagator is determined to be MW = 76+/-16+/-13 GeV.

Effects of dietary coarsely ground corn and 3 bedding floor types on broiler live performance, litter characteristics, gizzard and proventriculus weight, and nutrient digestibility.

PubMed

Xu, Y; Lin, Y M; Stark, C R; Ferket, P R; Williams, C M; Brake, J

2017-07-01

The effects of zero or 50% dietary coarsely ground corn (CC) in pelleted and screened grower and finisher diets on broilers reared on 3 bedding floor types (plastic net [NET], new pine wood shavings litter [NEW], or old pine wood shavings litter [OLD]) on broiler live performance, litter characteristics, gizzard and proventriculus weight, and apparent ileal digestibility (AID) were studied in a 2 × 3 factorial arrangement of treatments. Fine corn was produced with a hammermill (271 μm) and CC with a roller mill (1145 μm). Utilization of CC reduced milling cost by 9.47 cents per MT with similar nutrient content of screened pellets. The 50% CC treatment exhibited improved (P ≤ 0.05) feed intake at 42 d (2.5%) and 49 d (3.0%), and BW (5.4%) and FCR from 28 d (1.4%). Birds on NEW litter exhibited improved (P < 0.05) BW at 28 and 35 d and 42 d FCR as compared to NET and 49 d FCR compared to NET and OLD. The 50% CC treatment exhibited increased (P < 0.05) gizzard weight but decreased proventriculus weight at 49 d. NEW litter birds exhibited increased (P ≤ 0.05) gizzard weight at 28 d and 49 d and decreased proventriculus weight as compared to NET at 49 days. The 50% CC treatment exhibited decreased (P ≤ 0.05) litter moisture at 35 and 42 d, litter N at 35 and 49 d, and litter pH at 49 days. OLD litter birds exhibited greater (P < 0.05) litter N at 14, 35, and 49 d, as well as litter moisture, pH, and ammonia concentration at 49 days. The 50% CC group also exhibited improved AID of nitrogen (P < 0.05). Broilers fed pelleted and screened diets containing 50% CC exhibited improved live performance and reduced litter moisture while use of NEW litter resulted in a somewhat similar effect, which indicated that consumption of NEW litter also facilitated gastric development and function. © 2017 Poultry Science Association Inc.

The prevalence of metabolic syndrome in clomiphene citrate resistant polycystic ovary syndrome.

PubMed

Verit, Fatma Ferda

2012-05-01

To investigate the prevalence of metabolic syndrome in clomiphene citrate (CC) resistant polycystic ovary syndrome (PCOS) patients. 58 CC resistant PCOS patients, 52 CC responders, 53 fertile PCOS and 53 age and body mass index-matched normoandrogenic ovulatory fertile women were evaluated for metabolic syndrome. Metabolic syndrome prevalence was 41.4% in CC resistants, in 23.1% of CC responders, in 11.3% of PCOS fertiles and 0% of controls (p < 0.0001). Waist circumference (WC) > 88 cm was 44.8%, systolic blood pressure (BP) ≥ 130 mmHg and diastolic BP ≥85 mmHg were 27.6%, TG (triglyceride) ≥150 mg/dL was 36.2%, HDL(high density lipoprotein) < 50 mg/dL was 63.8%, fasting glucose levels ≥ 100 mg/dL was 20.7% in CC resistant PCOS women. There were positive associations between CC resistance and WC >88 cm, BP ≥ 130 ≥ 85 mmHg, TG ≥ 150 mg/dL, HDL < 50 mg/dL, fasting glucose ≥ 100 mg/dL, and presence of metabolic syndrome (p < 0.05, for all). Moreover, WC > 88 cm, and HDL < 50 mg/dL were independent variables that were associated by CC resistance by multivariate regression analysis. CC resistant PCOS patients have high prevalence of metabolic syndrome. These women have an increased risk of future cardiovascular disease.

Predictors of Toxicity After Image-guided High-dose-rate Interstitial Brachytherapy for Gynecologic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Larissa J.; Viswanathan, Akila N., E-mail: aviswanathan@lroc.harvard.edu

2012-12-01

Purpose: To identify predictors of grade 3-4 complications and grade 2-4 rectal toxicity after three-dimensional image-guided high-dose-rate (HDR) interstitial brachytherapy for gynecologic cancer. Methods and Materials: Records were reviewed for 51 women (22 with primary disease and 29 with recurrence) treated with HDR interstitial brachytherapy. A single interstitial insertion was performed with image guidance by computed tomography (n = 43) or magnetic resonance imaging (n = 8). The median delivered dose in equivalent 2-Gy fractions was 72.0 Gy (45 Gy for external-beam radiation therapy and 24 Gy for brachytherapy). Toxicity was reported according to the Common Toxicity Criteria for Adversemore » Events. Actuarial toxicity estimates were calculated by the Kaplan-Meier method. Results: At diagnosis, the median patient age was 62 years and the median tumor size was 3.8 cm. The median D90 and V100 were 71.4 Gy and 89.5%; the median D2cc for the bladder, rectum, and sigmoid were 64.6 Gy, 61.0 Gy, and 52.7 Gy, respectively. The actuarial rates of all grade 3-4 complications at 2 years were 20% gastrointestinal, 9% vaginal, 6% skin, 3% musculoskeletal, and 2% lymphatic. There were no grade 3-4 genitourinary complications and no grade 5 toxicities. Grade 2-4 rectal toxicity was observed in 10 patients, and grade 3-4 complications in 4; all cases were proctitis with the exception of 1 rectal fistula. D2cc for rectum was higher for patients with grade 2-4 (68 Gy vs 57 Gy for grade 0-1, P=.03) and grade 3-4 (73 Gy vs 58 Gy for grade 0-2, P=.02) rectal toxicity. The estimated dose that resulted in a 10% risk of grade 2-4 rectal toxicity was 61.8 Gy (95% confidence interval, 51.5-72.2 Gy). Discussion: Image-guided HDR interstitial brachytherapy results in acceptable toxicity for women with primary or recurrent gynecologic cancer. D2cc for the rectum is a reliable predictor of late rectal complications. Three-dimensional-based treatment planning should be performed to ensure adequate tumor coverage while minimizing the D2cc to the rectum.« less

SU-E-T-79: Comparison of Doses Received by the Hippocampus in Patients Treated with Single Vs Multiple Isocenter Based Stereotactic Radiation Therapy to the Brain for Multiple Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Algan, O; Giem, J; Young, J

Purpose: To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiotherapy utilizing a single isocenter (SI) versus multiple isocenter (MI) in patients with multiple intracranial metastases. Methods: Seven patients imaged with MRI including SPGR sequence and diagnosed with 2–3 brain metastases were included in this retrospective study. Two sets of stereotactic IMRT treatment plans, (MI vs SI), were generated. The hippocampus was contoured on SPGR sequences and doses received by the hippocampus and whole brain were calculated. The prescribed dose was 25Gy in 5 fractions. The two groups were compared using t-testmore » analysis. Results: There were 17 lesions in 7 patients. The median tumor, right hippocampus, left hippocampus and brain volumes were: 3.37cc, 2.56cc, 3.28cc, and 1417cc respectively. In comparing the two treatment plans, there was no difference in the PTV coverage except in the tail of the DVH curve. All tumors had V95 > 99.5%. The only statistically significant parameter was the V100 (72% vs 45%, p=0.002, favoring MI). All other evaluated parameters including the V95 and V98 did not reveal any statistically significant differences. None of the evaluated dosimetric parameters for the hippocampus (V100, V80, V60, V40, V20, V10, D100, D90, D70, D50, D30, D10) revealed any statistically significant differences (all p-values > 0.31) between MI and SI plans. The total brain dose was slightly higher in the SI plans, especially in the lower dose regions, although this difference was not statistically significant. Utilizing brain-sub-PTV volumes did not change these results. Conclusion: The use of SI treatment planning for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain compared to MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.« less

The Effect of Calcium plus Vitamin D on Risk for Invasive Cancer: Results of the Women’s Health Initiative (WHI) Calcium Plus Vitamin D Randomized Clinical Trial

PubMed Central

Brunner, Robert L.; Wactawski-Wende, Jean; Caan, Bette J.; Cochrane, Barbara B.; Chlebowski, Rowan T.; Gass, Margery L. S.; Jacobs, Elizabeth T.; LaCroix, Andrea Z.; Lane, Dorothy; Larson, Joseph; Margolis, Karen L.; Millen, Amy E.; Sarto, Gloria E.; Vitolins, Mara Z.; Wallace, Robert B.

2011-01-01

In the Women’s Health Initiative (WHI) trial of calcium plus vitamin D (CaD), we examined the treatment effect on incidence and mortality for all invasive cancers. Postmenopausal women (N = 36,282) were randomized to 1,000 mg of elemental calcium with 400 IU vitamin D3 or placebo. Cox models estimated risk of cancer incidence and mortality. After 7.0 yr, 1,306 invasive cancers were diagnosed in the supplement and 1,333 in the placebo group [hazard ratio (HR) = 0.98; CI = 0.90, 1.05, unweighted P = 0.54]. Mortality did not differ between supplement (315, annualized% = .26) and placebo [(347, 0.28%; P = 0.17; HR = 0.90 (0.77, 1.05)]. Significant treatment interactions on incident cancer were found for family history of cancer, personal total intake of vitamin D, smoking, and WHI dietary trial randomized group. Calcium/vitamin D supplementation did not reduce invasive cancer incidence or mortality. Supplementation lowered cancer risk in the WHI healthy diet trial arm and in women without a first-degree relative with cancer. The interactions are only suggestive given multiple testing considerations. The low vitamin D dose provided, limited adherence, and lack of serum 25(OH)D values should be considered when interpreting these findings. PMID:21774589

Introducing Defects in 3D Photonic Crystals: State of the Art

DTIC Science & Technology

2006-01-01

the art 5. FUNDING NUMBERS DAAD190310227 6. AUTHOR(S) P. V. Braun, S. A. Pruzinsky, and F . Garcia-Santamaria 7...microscopy image of a y-splitter defect formed through two-photon polymerization within a CC. – [*] Prof. P. V. Braun, Dr. S. A. Rinne, Dr. F . García...John, O. Toader, Phys. Rev. Lett. 2003, 90, 3901. [15] T. F . Krauss, R. M. De La Rue, S. Brand, Nature 1996, 383, 699. [16] R. D. Meade, K. D. Brommer

Spine Radiosurgery: A Dosimetric Analysis in 124 Patients Who Received 18 Gy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schipani, Stefano; Wen, Winston; Jin, Jain-Yue

2012-12-01

Purpose: To define the safely tolerated doses to organs at risk (OARs) adjacent to the target volume (TV) of spine radiosurgery (SRS) with 18-Gy in a single fraction. Methods and Materials: A total of 124 patient cases with 165 spine metastases were reviewed. An 18-Gy single-fraction regimen was prescribed to the 90% isodose line encompassing the TV. A constraint of 10 Gy to 10% of the spinal cord outlined 6 mm above and below the TV was used. Dosimetric data to OARs were analyzed. Results: A total of 124 patients (100%) were followed-up, and median follow-up time was 7 monthsmore » (1-50 months). Symptoms and local control were achieved in 114 patients (92%). Acute Radiation Therapy Oncology Group (RTOG) grade 1 oral mucositis occurred in 11 of 11 (100%) patients at risk for oropharyngeal toxicity after cervical spine treatment. There were no RTOG grade 2-4 acute or late complications. Median TV was 43.2 cc (5.3-175.4 cc) and 90% of the TV received median dose of 19 Gy (17-19.8 Gy). Median (range) of spinal cord maximum dose (Dmax), dose to spinal cord 0.35 cc (Dsc0.35), and cord volume receiving 10 Gy (Vsc10) were 13.8 Gy (5.4-21 Gy), 8.9 Gy (2.6-11.4 Gy) and 0.33 cc (0-1.6 cc), respectively. Other OARs were evaluated when in proximity to the TV. Esophagus (n=58), trachea (n=28), oropharynx (n=11), and kidneys (n=34) received median (range) V10 and V15 of 3.1 cc (0-5.8 cc) and 1.2 cc (0-2.9 cc), 2.8 cc (0-4.9 cc), and 0.8 cc (0-2.1 cc), 3.4 cc (0-6.2 cc) and 1.6 cc (0-3.2 cc), 0.3 cc (0-0.8 cc) and 0.08 cc (0-0.1 cc), respectively. Conclusions: Cord Dmax of 14 Gy and D0.35 of 10 Gy are safe dose constraints for 18-Gy single-fraction SRS. Esophagus V10 of 3 cc and V15 of 1 cc, trachea V10 of 3 cc, and V15 of 1 cc, oropharynx V10 of 3.5 cc and V15 of 1.5 cc, kidney V10 of 0.3 cc, and V15 of 0.1 cc are planning guidelines when these OARs are in proximity to the TV.« less

Transaction Design Specification Medical Exam Databases System (MED) update Transaction

DTIC Science & Technology

1986-12-01

8217RECOFD IN 51) 73. CORONARY SFAS1 SITE ;CHAR X(6) IN 7:) 74* CORONARY FLAQUES (RECO D IN 51) 75. CCFONARY PLAOUE 3ITE ,CHAR K(60 IN 74) 76* FCT DIAMETER...KETOSTEROIDS YE HYDROXYCARTICOSTEROIDS YO 24 HR URINE TOTAL VOLUME MA URINE OSMOLALITY MB SERUM OSMOLALITY MC 24HR URINE TOTAL VOLUME ZE SERUM COPPER FBS TO...RHEUMATOID FACTOR PA N P -2 2 ANTINUCLEAR ANTIBODY PB N P -2 2 0 FREE FATTY ACIDS QA 5 9 57 200 MG% SERUM COPPER RA 30 70 130 300 JG% URINE COPPER RBM 10 30 90

The CC2D1A, a member of a new gene family with C2 domains, is involved in autosomal recessive non‐syndromic mental retardation

PubMed Central

Basel‐Vanagaite, L; Attia, R; Yahav, M; Ferland, R J; Anteki, L; Walsh, C A; Olender, T; Straussberg, R; Magal, N; Taub, E; Drasinover, V; Alkelai, A; Bercovich, D; Rechavi, G; Simon, A J; Shohat, M

2006-01-01

Background The molecular basis of autosomal recessive non‐syndromic mental retardation (NSMR) is poorly understood, mostly owing to heterogeneity and absence of clinical criteria for grouping families for linkage analysis. Only two autosomal genes, the PRSS12 gene on chromosome 4q26 and the CRBN on chromosome 3p26, have been shown to cause autosomal recessive NSMR, each gene in only one family. Objective To identify the gene causing autosomal recessive NSMR on chromosome 19p13.12. Results The candidate region established by homozygosity mapping was narrowed down from 2.4 Mb to 0.9 Mb on chromosome 19p13.12. A protein truncating mutation was identified in the gene CC2D1A in nine consanguineous families with severe autosomal recessive NSMR. The absence of the wild type protein in the lymphoblastoid cells of the patients was confirmed. CC2D1A is a member of a previously uncharacterised gene family that carries two conserved motifs, a C2 domain and a DM14 domain. The C2 domain is found in proteins which function in calcium dependent phospholipid binding; the DM14 domain is unique to the CC2D1A protein family and its role is unknown. CC2D1A is a putative signal transducer participating in positive regulation of I‐κB kinase/NFκB cascade. Expression of CC2D1A mRNA was shown in the embryonic ventricular zone and developing cortical plate in staged mouse embryos, persisting into adulthood, with highest expression in the cerebral cortex and hippocampus. Conclusions A previously unknown signal transduction pathway is important in human cognitive development. PMID:16033914

The CC2D1A, a member of a new gene family with C2 domains, is involved in autosomal recessive non-syndromic mental retardation.

PubMed

Basel-Vanagaite, L; Attia, R; Yahav, M; Ferland, R J; Anteki, L; Walsh, C A; Olender, T; Straussberg, R; Magal, N; Taub, E; Drasinover, V; Alkelai, A; Bercovich, D; Rechavi, G; Simon, A J; Shohat, M

2006-03-01

The molecular basis of autosomal recessive non-syndromic mental retardation (NSMR) is poorly understood, mostly owing to heterogeneity and absence of clinical criteria for grouping families for linkage analysis. Only two autosomal genes, the PRSS12 gene on chromosome 4q26 and the CRBN on chromosome 3p26, have been shown to cause autosomal recessive NSMR, each gene in only one family. To identify the gene causing autosomal recessive NSMR on chromosome 19p13.12. The candidate region established by homozygosity mapping was narrowed down from 2.4 Mb to 0.9 Mb on chromosome 19p13.12. A protein truncating mutation was identified in the gene CC2D1A in nine consanguineous families with severe autosomal recessive NSMR. The absence of the wild type protein in the lymphoblastoid cells of the patients was confirmed. CC2D1A is a member of a previously uncharacterised gene family that carries two conserved motifs, a C2 domain and a DM14 domain. The C2 domain is found in proteins which function in calcium dependent phospholipid binding; the DM14 domain is unique to the CC2D1A protein family and its role is unknown. CC2D1A is a putative signal transducer participating in positive regulation of I-kappaB kinase/NFkappaB cascade. Expression of CC2D1A mRNA was shown in the embryonic ventricular zone and developing cortical plate in staged mouse embryos, persisting into adulthood, with highest expression in the cerebral cortex and hippocampus. A previously unknown signal transduction pathway is important in human cognitive development.

Under-reported dosimetry errors due to interplay effects during VMAT dose delivery in extreme hypofractionated stereotactic radiotherapy.

PubMed

Gauer, Tobias; Sothmann, Thilo; Blanck, Oliver; Petersen, Cordula; Werner, René

2018-06-01

Radiotherapy of extracranial metastases changed from normofractioned 3D CRT to extreme hypofractionated stereotactic treatment using VMAT beam techniques. Random interaction between tumour motion and dynamically changing beam parameters might result in underdosage of the CTV even for an appropriately dimensioned ITV (interplay effect). This study presents a clinical scenario of extreme hypofractionated stereotactic treatment and analyses the impact of interplay effects on CTV dose coverage. For a thoracic/abdominal phantom with an integrated high-resolution detector array placed on a 4D motion platform, dual-arc treatment plans with homogenous target coverage were created using a common VMAT technique and delivered in a single fraction. CTV underdosage through interplay effects was investigated by comparing dose measurements with and without tumour motion during plan delivery. Our study agrees with previous works that pointed out insignificant interplay effects on target coverage for very regular tumour motion patterns like simple sinusoidal motion. However, we identified and illustrated scenarios that are likely to result in a clinically relevant CTV underdosage. For tumour motion with abnormal variability, target coverage quantified by the CTV area receiving more than 98% of the prescribed dose decreased to 78% compared to 100% at static dose measurement. This study is further proof of considerable influence of interplay effects on VMAT dose delivery in stereotactic radiotherapy. For selected conditions of an exemplary scenario, interplay effects and related motion-induced target underdosage primarily occurred in tumour motion pattern with increased motion variability and VMAT plan delivery using complex MLC dose modulation.

Mini 3D for shallow gas reconnaissance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vallieres, T. des; Enns, D.; Kuehn, H.

1996-12-31

The Mini 3D project was undertaken by TOTAL and ELF with the support of CEPM (Comite d`Etudes Petrolieres et Marines) to define an economical method of obtaining 3D seismic HR data for shallow gas assessment. An experimental 3D survey was carried out with classical site survey techniques in the North Sea. From these data 19 simulations, were produced to compare different acquisition geometries ranging from dual, 600 m long cables to a single receiver. Results show that short offset, low fold and very simple streamer positioning are sufficient to give a reliable 3D image of gas charged bodies. The 3Dmore » data allow a much more accurate risk delineation than 2D HR data. Moreover on financial grounds Mini-3D is comparable in cost to a classical HR 2D survey. In view of these results, such HR 3D should now be the standard for shallow gas surveying.« less

Differential expression of lactic acid isomers, extracellular matrix metalloproteinase inducer, and matrix metalloproteinase-8 in vaginal fluid from women with vaginal disorders.

PubMed

Beghini, J; Linhares, I M; Giraldo, P C; Ledger, W J; Witkin, S S

2015-11-01

Do metabolites in vaginal samples vary between women with different vaginal disorders. Cross-sectional study. Campinas, Brazil. Seventy-seven women (39.9%) with no vaginal disorder, 52 women (26.9%) with vulvovaginal candidiasis (VVC), 43 women (22.3%) with bacterial vaginosis (BV), and 21 women (10.9%) with cytolytic vaginosis (CTV). Concentrations of D- and L-lactic acid, extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinase-8 (MMP-8), and the influence of Candida albicans on EMMPRIN production by cultured vaginal epithelial cells, were determined by enzyme-linked immunosorbent assay (ELISA). Associations were determined by the Mann-Whitney U-test and by Spearman's rank correlation test. Metabolite levels and their correlation with diagnoses. Vaginal concentrations of D- and L-lactic acid were reduced from control levels in BV (P < 0.0001); L-lactic acid levels were elevated in CTV (P = 0.0116). EMMPRIN and MMP-8 concentrations were elevated in VVC (P < 0.0001). EMMPRIN and L-lactic acid concentrations (P ≤ 0.008), but not EMMPRIN and D-lactic acid, were correlated in all groups. EMMPRIN also increased in proportion with the ratio of L- to D-lactic acid in controls and in women with BV (P ≤ 0.009). Concentrations of EMMPRIN and MMP-8 were correlated in controls and women with VVC (P ≤ 0.0002). Candida albicans induced EMMPRIN release from vaginal epithelial cells. Vaginal secretions from women with BV are deficient in D- and L-lactic acid, women with VVC have elevated EMMPRIN and MMP-8 levels, and women with CTV have elevated L-lactic acid levels. These deviations may contribute to the clinical signs, symptoms, and sequelae that are characteristic of these disorders. © 2014 Royal College of Obstetricians and Gynaecologists.

The First 10 Years of Aerobic Exercise Responses to Long-Duration ISS Flights.

PubMed

Moore, Alan D; Lynn, Peggy A; Feiveson, Alan H

2015-12-01

Aerobic deconditioning may occur during International Space Station (ISS) flights. This paper documents findings from exercise testing conducted before, during, and after ISS expeditions. There were 30 male and 7 female astronauts on ISS missions (48 to 219 d, mean 163 d) who performed cycle exercise protocols consisting of 5-min stages eliciting 25%, 50%, and 75% peak oxygen uptake (Vo(2peak)). Tests were conducted 30 to 90 d before missions, on flight day 15 and every 30 flight days thereafter, and on recovery (R) days +5 and +30. During pre- and postflight tests, heart rate (HR) and metabolic gas exchange were measured. During flight, extrapolation of the HR and Vo2 relationship to preflight-measured peak HR provided an estimate of Vo(2peak), referred to as the aerobic capacity index (ACI). HR during each exercise stage was elevated (P < 0.05) and oxygen pulse was reduced (P < 0.05) on R+5 compared to preflight; however, no other metabolic gas analysis values significantly changed. Compared to preflight, the ACI declined (P < 0.001) on R+5, but recovered to levels greater than preflight by R+30 (P = 0.008). During flight, ACI decreased below preflight values, but increased with mission duration (P < 0.001). Aerobic deconditioning likely occurs initially during flight, but ACI recovers toward preflight levels as flight duration increases, presumably due to performance of exercise countermeasures. Elevated HR and lowered oxygen pulse on R+5 likely results from some combination of relative hypovolemia, lowered cardiac stroke volume, reduced cardiac distensibility, and anemia, but recovery occurs by R+30.

Transient and persistent worsening renal function during hospitalization for acute heart failure.

PubMed

Krishnamoorthy, Arun; Greiner, Melissa A; Sharma, Puza P; DeVore, Adam D; Johnson, Katherine Waltman; Fonarow, Gregg C; Curtis, Lesley H; Hernandez, Adrian F

2014-12-01

Transient and persistent worsening renal function (WRF) may be associated with different risks during hospitalization for acute heart failure. We compared outcomes of patients hospitalized for acute heart failure with transient, persistent, or no WRF. We identified patients 65 years or older hospitalized with acute heart failure from a clinical registry linked to Medicare claims data. We defined WRF as an increase in serum creatinine of ≥ 0.3 mg/dL after admission. We further classified patients with WRF by the difference between admission and last recorded serum creatinine levels into transient WRF (< 0.3 mg/dL) or persistent WRF (≥ 0.3 mg/dL). We examined unadjusted rates and adjusted associations between 90-day outcomes and WRF status. Among 27,309 patients, 18,568 (68.0%) had no WRF, 3,205 (11.7%) had transient WRF, and 5,536 (20.3%) had persistent WRF. Patients with WRF had higher observed rates of 90-day postdischarge all-cause readmission and 90-day postadmission mortality (P < .001). After multivariable adjustment, transient WRF (hazard ratio [HR] 1.19, 99% CI 1.05-1.35) and persistent WRF (HR 1.73, 99% CI 1.57-1.91) were associated with higher risks of 90-day postadmission mortality (P < .001 for both). Compared with transient WRF, persistent WRF was associated with a higher risk of 90-day postadmission mortality (HR 1.46, 99% CI 1.28-1.66, P < .001). Transient and persistent WRF during hospitalization for acute heart failure were associated with higher adjusted risks for 90-day all-cause postadmission mortality. Patients with persistent WRF had worse outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Optimizing D'Amico risk groups in radical prostatectomy through the addition of magnetic resonance imaging data.

PubMed

Algarra, R; Zudaire, B; Tienza, A; Velis, J M; Rincón, A; Pascual, I; Zudaire, J

2014-11-01

To improve the predictive efficacy of the D'Amico risk classification system with magnetic resonance imaging (MRI) of the pelvis. We studied 729 patients from a series of 1310 radical prostatectomies for T1-T2 prostate cancer who underwent staging pelvic MRI. Each patient was classified with T2, T3a or T3b MRI, and N (+) patients were excluded. We identified the therapeutic factors that affected the biochemical progression-free survival (BPFS) time (prostate specific antigen [PSA] levels>0.4ng/mL) using a univariate and multivariate study with Cox models. We attempted to improve the predictive power of the D'Amico model (low risk: T1; Gleason 2-6; PSA levels<10ng/mL; intermediate risk: T2 or Gleason 7 or PSA levels 10-20ng/mL; high risk: T3 or Gleason 8-10 or PSA levels>20ng/mL). In the univariate study, the clinical factors that influenced BPFS were the following: Gleason 7 (HR: 1.7); Gleason 8-10 (HR: 2.9); T2 (HR: 1.6); PSA levels 10-20 (HR: 2); PSA levels>20 (HR: 4.3); D'Amico intermediate (HR: 2.1) and high (HR: 4.8) risk; T3a MRI (HR: 2.3) and T3b MRI (HR: 4.5). In the multivariate study, the only variables that affected BPFS were the following: D'Amico intermediate risk (HR: 2; 95% CI 1.2-3.3); D'Amico high risk (HR: 4.1; 95% CI 2.4-6.8); T3a MRI (HR: 1.9; 95% CI 1.2-2.9) and T3b MRI (HR: 3.9; 95% CI 2.5-6.1). Predictive model: Using the multivariate Cox models, we assessed the weight of each variable. A value of 1 was given to D'Amico low risk and T2 MRI; a value of 2 was given to D'Amico intermediate risk and T3a MRI and a value 3 was given to D'Amico high risk and T3b MRI. Each patient had a marker that varied between 2 and 6. The best model included 3 groups, as follows: 494 (67.7%) patients in group 1, with a score of 2-3 points (HR, 1), a BPFS of 86%±2% and 79%±2% at 5 and 10 years, respectively; 179 (24.6%) patients in group 2, with a score of 4 points (HR, 3), a BPFS of 60%±4% and 54%±5% at 5 and 10 years, respectively; and 56 (7.7%) patients in group 3, with a score of 5-6 points (HR, 9.3), a BPFS of 29%±8% and 19%±7% at 5 and 10 years, respectively. The median BPFS time was 1.5 years. MRI data significantly improves the predictive capacity of BPFS when using the D'Amico model data. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Definition of fields margins for palliative radiotherapy of pancreatic carcinoma.

PubMed

Buwenge, Milly; Marinelli, Alfonso; Deodato, Francesco; Macchia, Gabriella; Wondemagegnhu, Tigeneh; Salah, Tareq; Cammelli, Silvia; Uddin, A F M Kamal; Sumon, Mostafa A; Donati, Constanza M; Cilla, Savino; Morganti, Alessio G

2018-06-01

The present study aimed to provide practical guidelines for palliative treatment of advanced carcinoma of the pancreas (CAP) with the 2D technique. Fifteen patients with locally advanced CAP consecutively treated with radiation therapy at the Radiation Oncology Center, Research and Care Foundation 'Giovanni Paolo II' (Campobasso, Italy) underwent computed tomography simulation in supine position. Definition of the clinical target volume (CTV) included the head and body of the pancreas, and the retropancreatic space. The planning target volume was defined by adding a margin of 14 mm to the CTV in the cranio-caudal direction and of 11 mm in radial direction. For each patient, 3 treatment plans were calculated using a cobalt source, 6 MV photons and 15 MV photons (box technique). Beams were drawn using the primary collimators without using multileaf collimators, and progressively optimized in order to respect the minimum dose (D min >90%) constraint. Once the final plan was achieved, distances of the fields edges from a set of reference points (bony or duodenal landmarks) were measured. Using this technique, 15 anterior-posterior and postero-anterior (AP-PA) beams and 15 pairs of lateral-lateral (LL) beams were defined for the different patients. Finally, the single minimal AP-PA and LL beams able to include the 15 sets of AP-PA and LL beams were defined. The results of this analysis are reported in tabular form. Guidelines are provided for treatment based on cobalt unit or Linear accelerator (both 6 and 15 MV photons). This study provides information regarding field size and position. A dosimetric study has been planned to identify the dose to be administered with this technique taking into account current dose-volume constraints.

HPV genotype distribution and anomalous association of HPV33 to cervical neoplastic lesions in San Luis Potosí, Mexico.

PubMed

DelaRosa-Martínez, Raúl; Sánchez-Garza, Mireya; López-Revilla, Rubén

2016-01-01

The association of human papillomavirus (HPV) types to neoplastic lesions increase as a function of their oncogenicity and the duration of the infection since lesion severity progresses from low-grade to high-grade and cancer. In an outbreak, the prevalence of the HPV type involved would increase and the proportion of the associated low-grade lesions would predominate over severe lesions. In this study, the prevalence of HPV types and their association to neoplastic lesions was determined in women subjected to colposcopy in San Luis Potosí, Mexico. DNA from high-risk (HR) and low-risk (LR) HPV types was identified by E6 nested multiplex PCR in cervical scrapes from 700 women with normal cytology, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL) or invasive cervical cancer (CC). Overall HPV-DNA prevalence was 67.7 %, that of HR-HPV was 63.1 %, and that of LR-HPV was 21.3 %. The highest prevalence (78.2 %) occurred in the 15-24 year group, whereas that of single infections was 52 % and that of multiple infections (i.e., by 2-6 HPV types) was 48 %. The most prevalent HR types were HPV33 (33.1 %), HPV16 (16.6 %), HPV18 and HPV51 (6.7 % each). HR-HPV prevalence was 29.6 % in normal cytology, 26.7 % in ASCUS, 63.3 % in LSIL, 68.2 % in HSIL, and 90.5 % in CC. Three prevalence trends for HR-HPV types were found in neoplastic lesions of increasing severity: increasing (LSIL < HSIL < CC) for HPV16, HPV39, HPV18, HPV58, HPV31 and HPV35; asymptotic (LSIL < HSIL ≈ CC) for HPV51 and HPV68; U-shaped (LSIL < HSIL > CC) for HPV33. Two-thirds of the women subjected to colposcopy from 2007 to 2010 in San Luis Potosí have HPV infections which predominate in the 15-24 years group. Around half of the infections are by one viral type and the rest by 2-6 types. HPV33 is the most prevalent type, followed by HPV16. Overall HR-HPV prevalence increases with the severity of neoplastic lesions. HPV33 prevalence is highest in LSIL and its U-shaped trend with progressing neoplastic lesions differs from the growing/asymptotic trends of other HR-HPV types. An ongoing or recent HPV33 outbreak is consistent with its high prevalence and anomalous association to LSIL.

Carbon-ion scanning lung treatment planning with respiratory-gated phase-controlled rescanning: simulation study using 4-dimensional CT data.

PubMed

Takahashi, Wataru; Mori, Shinichiro; Nakajima, Mio; Yamamoto, Naoyoshi; Inaniwa, Taku; Furukawa, Takuji; Shirai, Toshiyuki; Noda, Koji; Nakagawa, Keiichi; Kamada, Tadashi

2014-11-11

To moving lung tumors, we applied a respiratory-gated strategy to carbon-ion pencil beam scanning with multiple phase-controlled rescanning (PCR). In this simulation study, we quantitatively evaluated dose distributions based on 4-dimensional CT (4DCT) treatment planning. Volumetric 4DCTs were acquired for 14 patients with lung tumors. Gross tumor volume, clinical target volume (CTV) and organs at risk (OARs) were delineated. Field-specific target volumes (FTVs) were calculated, and 48Gy(RBE) in a single fraction was prescribed to the FTVs delivered from four beam angles. The dose assessment metrics were quantified by changing the number of PCR and the results for the ungated and gated scenarios were then compared. For the ungated strategy, the mean dose delivered to 95% of the volume of the CTV (CTV-D95) was in average 45.3 ± 0.9 Gy(RBE) even with a single rescanning (1 × PCR). Using 4 × PCR or more achieved adequate target coverage (CTV-D95 = 46.6 ± 0.3 Gy(RBE) for ungated 4 × PCR) and excellent dose homogeneity (homogeneity index =1.0 ± 0.2% for ungated 4 × PCR). Applying respiratory gating, percentage of lung receiving at least 20 Gy(RBE) (lung-V20) and heart maximal dose, averaged over all patients, significantly decreased by 12% (p < 0.05) and 13% (p < 0.05), respectively. Four or more PCR during PBS-CIRT improved dose conformation to moving lung tumors without gating. The use of a respiratory-gated strategy in combination with PCR reduced excessive doses to OARs.

Variation in the Gross Tumor Volume and Clinical Target Volume for Preoperative Radiotherapy of Primary Large High-Grade Soft Tissue Sarcoma of the Extremity Among RTOG Sarcoma Radiation Oncologists

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Dian, E-mail: dwang@mcw.edu; Bosch, Walter; Kirsch, David G.

Purpose: To evaluate variability in the definition of preoperative radiotherapy gross tumor volume (GTV) and clinical target volume (CTV) delineated by sarcoma radiation oncologists. Methods and Materials: Extremity sarcoma planning CT images along with the corresponding diagnostic MRI from two patients were distributed to 10 Radiation Therapy Oncology Group sarcoma radiation oncologists with instructions to define GTV and CTV using standardized guidelines. The CT data with contours were then returned for central analysis. Contours representing statistically corrected 95% (V95) and 100% (V100) agreement were computed for each structure. Results: For the GTV, the minimum, maximum, mean (SD) volumes (mL) weremore » 674, 798, 752 {+-} 35 for the lower extremity case and 383, 543, 447 {+-} 46 for the upper extremity case. The volume (cc) of the union, V95 and V100 were 882, 761, and 752 for the lower, and 587, 461, and 455 for the upper extremity, respectively. The overall GTV agreement was judged to be almost perfect in both lower and upper extremity cases (kappa = 0.9 [p < 0.0001] and kappa = 0.86 [p < 0.0001]). For the CTV, the minimum, maximum, mean (SD) volumes (mL) were 1145, 1911, 1605 {+-} 211 for the lower extremity case and 637, 1246, 1006 {+-} 180 for the upper extremity case. The volume (cc) of the union, V95, and V100 were 2094, 1609, and 1593 for the lower, and 1533, 1020, and 965 for the upper extremity cases, respectively. The overall CTV agreement was judged to be almost perfect in the lower extremity case (kappa = 0.85 [p < 0.0001]) but only substantial in the upper extremity case (kappa = 0.77 [p < 0.0001]). Conclusions: Almost perfect agreement existed in the GTV of these two representative cases. Tshere was no significant disagreement in the CTV of the lower extremity, but variation in the CTV of upper extremity was seen, perhaps related to the positional differences between the planning CT and the diagnostic MRI.« less

Activated Rho Kinase Mediates Diabetes-Induced Elevation of Vascular Arginase Activation and Contributes to Impaired Corpora Cavernosa Relaxation: Possible Involvement of p38 MAPK Activation

PubMed Central

Nunes, Kenia P.; Yao, Lin; Liao, James K.; Webb, R. Clinton; Caldwell, Ruth B.; Caldwell, R. William

2013-01-01

Introduction Activated RhoA/Rho kinase (ROCK) has been implicated in diabetes-induced erectile dysfunction. Earlier studies have demonstrated involvement of ROCK pathway in the activation of arginase in endothelial cells. However, signaling pathways activated by ROCK in the penis remain unclear. Aim We tested whether ROCK and p38 MAPK are involved in the elevation of arginase activity and subsequent impairment of corpora cavernosal (CC) relaxation in diabetes. Methods Eight weeks after streptozotocin-induced diabetes, vascular functional studies, arginase activity assay, and protein expression of RhoA, ROCK, phospho-p38 MAPK, p38 MAPK, phospho-MYPT-1Thr850, MYPT-1 and arginase levels were assessed in CC tissues from nondiabetic wild type (WT), diabetic (D) WT (WT + D), partial ROCK 2+/− knockout (KO), and ROCK 2+/− KO + D mice. Main Outcome Measures The expression of RhoA, ROCK 1 and 2, phosphorylation of MYPT-1Thr850 and p38 MAPK, arginase activity/expression, endothelial- and nitrergic-dependent relaxation of CC was assayed. Results Diabetes significantly reduced maximum relaxation (Emax) to both endothelium-dependent acetylcholine (WT + D: Emax; 61 ± 4% vs. WT: Emax; 75 ± 2%) and nitrergic nerve stimulation. These effects were associated with increased expression of active RhoA, ROCK 2, phospho-MYPT-1Thr850, phospho-p38 MAPK, arginase II, and activity of corporal arginase (1.6-fold) in WT diabetic CC. However, this impairment in CC of WT + D mice was absent in heterozygous ROCK 2+/− KO + D mice for acetylcholine (Emax: 80 ± 5%) and attenuated for nitrergic nerve-induced relaxation. CC of ROCK 2+/− KO + D mice showed much less ROCK activity, did not exhibit p38 MAPK activation, and had reduced arginase activity and arginase II expression. These findings indicate that ROCK 2 mediates diabetes-induced elevation of arginase activity. Additionally, pretreatment of WT diabetic CC with inhibitors of arginase (ABH) or p38 MAPK (SB203580) partially prevented impairment of ACh- and nitrergic nerve-induced relaxation and elevation of arginase activity. Conclusion ROCK 2, p38 MAPK and arginase play key roles in diabetes-induced impairment of CC relaxation. PMID:23566117

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balik, S; Weiss, E; Sleeman, W

Purpose: To evaluate the potential impact of several setup error correction strategies on a proposed image-guided adaptive radiotherapy strategy for locally advanced lung cancer. Methods: Daily 4D cone-beam CT and weekly 4D fan-beam CT images were acquired from 9 lung cancer patients undergoing concurrent chemoradiation therapy. Initial planning CT was deformably registered to daily CBCT images to generate synthetic treatment courses. An adaptive radiation therapy course was simulated using the weekly CT images with replanning twice and a hypofractionated, simultaneous integrated boost to a total dose of 66 Gy to the original PTV and either a 66 Gy (no boost)more » or 82 Gy (boost) dose to the boost PTV (ITV + 3mm) in 33 fractions with IMRT or VMAT. Lymph nodes (LN) were not boosted (prescribed to 66 Gy in both plans). Synthetic images were rigidly, bony (BN) or tumor and carina (TC), registered to the corresponding plan CT, dose was computed on these from adaptive replans (PLAN) and deformably accumulated back to the original planning CT. Cumulative D98% of CTV of PT (ITV for 82Gy) and LN, and normal tissue dose changes were analyzed. Results: Two patients were removed from the study due to large registration errors. For the remaining 7 patients, D98% for CTV-PT (ITV-PT for 82 Gy) and CTV-LN was within 1 Gy of PLAN for both 66 Gy and 82 Gy plans with both setup techniques. Overall, TC based setup provided better results, especially for LN coverage (p = 0.1 for 66Gy plan and p = 0.2 for 82 Gy plan, comparison of BN and TC), though not significant. Normal tissue dose constraints violated for some patients if constraint was barely achieved in PLAN. Conclusion: The hypofractionated adaptive strategy appears to be deliverable with soft tissue alignment for the evaluated margins and planning parameters. Research was supported by NIH P01CA116602.« less

SU-F-T-46: The Effect of Inter-Seed Attenuation and Tissue Composition in Prostate 125I Brachytherapy Dose Calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tamura, K; Araki, F; Ohno, T

Purpose: To investigate the difference of dose distributions with/without the effect of inter-seed attenuation and tissue compositions in prostate {sup 125}I brachytherapy dose calculations, using Monte Carlo simulations of Particle and Heavy Ion Transport code System (PHITS). Methods: The dose distributions in {sup 125}I prostate brachytherapy were calculated using PHITS for non-simultaneous and simultaneous alignments of STM1251 sources in water or prostate phantom for six patients. The PHITS input file was created from DICOM-RT file which includes source coordinates and structures for clinical target volume (CTV) and organs at risk (OARs) of urethra and rectum, using in-house Matlab software. Photonmore » and electron cutoff energies were set to 1 keV and 100 MeV, respectively. The dose distributions were calculated with the kerma approximation and the voxel size of 1 × 1 × 1 mm{sup 3}. The number of incident photon was set to be the statistical uncertainty (1σ) of less than 1%. The effect of inter-seed attenuation and prostate tissue compositions was evaluated from dose volume histograms (DVHs) for each structure, by comparing to results of the AAPM TG-43 dose calculation (without the effect of inter-seed attenuation and prostate tissue compositions). Results: The dose reduction due to the inter-seed attenuation by source capsules was approximately 2% for CTV and OARs compared to those of TG-43. In additions, by considering prostate tissue composition, the D{sub 90} and V{sub 100} of CTV reduced by 6% and 1%, respectively. Conclusion: It needs to consider the dose reduction due to the inter-seed attenuation and tissue composition in prostate {sup 125}I brachytherapy dose calculations.« less

Prime Contract Awards Alphabetically by Contractor, by State or Country, and Place. Part 8 (Electronic Design Inc-Florida North Shipyards)

DTIC Science & Technology

1990-01-01

8217- " -" 0 Li A- (:4 Li DC 0 2- 0 U Lic U) D I-- I: Ia 10N II U) Fd - > 2 .~ H C4 " 0)4 -4 < 1 1 <- w 0 Z II - CON 11 W LiJ w Lij 2 Li z44 0 0 < <. 4CC) < Li...04 0C(1 L a 0-4 40> 0 a0c0𔃺a4(N(N(1(’ -CN n -4 " C -00CI -1 (0 M a - 00 M 1.0 C 0 it cd I CON it .LJO C>O ct)00( ~ CaO (D 0 <!> cc.Cc 0)00 a~ O)CO...11 I 4 C )( DC 4- - CON -1 -1N --010001-N-4 4 n-1- 4 1--- 4 -0-4- 400 1 1- - D( ,Z 11 I CN (I "N )CC 0 (D DC000,0(0C 00 0 0 00 0 0 0 000C.a0D<DD I C000

Quantification of the kV X-ray imaging dose during real-time tumor tracking and from three- and four-dimensional cone-beam computed tomography in lung cancer patients using a Monte Carlo simulation.

PubMed

Nakamura, Mitsuhiro; Ishihara, Yoshitomo; Matsuo, Yukinori; Iizuka, Yusuke; Ueki, Nami; Iramina, Hiraku; Hirashima, Hideaki; Mizowaki, Takashi

2018-03-01

Knowledge of the imaging doses delivered to patients and accurate dosimetry of the radiation to organs from various imaging procedures is becoming increasingly important for clinicians. The purposes of this study were to calculate imaging doses delivered to the organs of lung cancer patients during real-time tumor tracking (RTTT) with three-dimensional (3D), and four-dimensional (4D) cone-beam computed tomography (CBCT), using Monte Carlo techniques to simulate kV X-ray dose distributions delivered using the Vero4DRT. Imaging doses from RTTT, 3D-CBCT and 4D-CBCT were calculated with the planning CT images for nine lung cancer patients who underwent stereotactic body radiotherapy (SBRT) with RTTT. With RTTT, imaging doses from correlation modeling and from monitoring of imaging during beam delivery were calculated. With CBCT, doses from 3D-CBCT and 4D-CBCT were also simulated. The doses covering 2-cc volumes (D2cc) in correlation modeling were up to 9.3 cGy for soft tissues and 48.4 cGy for bone. The values from correlation modeling and monitoring were up to 11.0 cGy for soft tissues and 59.8 cGy for bone. Imaging doses in correlation modeling were larger with RTTT. On a single 4D-CBCT, the skin and bone D2cc values were in the ranges of 7.4-10.5 cGy and 33.5-58.1 cGy, respectively. The D2cc from 4D-CBCT was approximately double that from 3D-CBCT. Clinicians should Figure that the imaging dose increases the cumulative doses to organs.

Quantification of the kV X-ray imaging dose during real-time tumor tracking and from three- and four-dimensional cone-beam computed tomography in lung cancer patients using a Monte Carlo simulation

PubMed Central

Nakamura, Mitsuhiro; Ishihara, Yoshitomo; Matsuo, Yukinori; Iizuka, Yusuke; Ueki, Nami; Iramina, Hiraku; Hirashima, Hideaki; Mizowaki, Takashi

2018-01-01

Abstract Knowledge of the imaging doses delivered to patients and accurate dosimetry of the radiation to organs from various imaging procedures is becoming increasingly important for clinicians. The purposes of this study were to calculate imaging doses delivered to the organs of lung cancer patients during real-time tumor tracking (RTTT) with three-dimensional (3D), and four-dimensional (4D) cone-beam computed tomography (CBCT), using Monte Carlo techniques to simulate kV X-ray dose distributions delivered using the Vero4DRT. Imaging doses from RTTT, 3D-CBCT and 4D-CBCT were calculated with the planning CT images for nine lung cancer patients who underwent stereotactic body radiotherapy (SBRT) with RTTT. With RTTT, imaging doses from correlation modeling and from monitoring of imaging during beam delivery were calculated. With CBCT, doses from 3D-CBCT and 4D-CBCT were also simulated. The doses covering 2-cc volumes (D2cc) in correlation modeling were up to 9.3 cGy for soft tissues and 48.4 cGy for bone. The values from correlation modeling and monitoring were up to 11.0 cGy for soft tissues and 59.8 cGy for bone. Imaging doses in correlation modeling were larger with RTTT. On a single 4D-CBCT, the skin and bone D2cc values were in the ranges of 7.4–10.5 cGy and 33.5–58.1 cGy, respectively. The D2cc from 4D-CBCT was approximately double that from 3D-CBCT. Clinicians should Figure that the imaging dose increases the cumulative doses to organs. PMID:29385514

Monoclonal antibody-based serological methods for detecting Citrus tristeza virus in citrus groves.

PubMed

Liu, Zhen; Chen, Zhe; Hong, Jian; Wang, Xuefeng; Zhou, Changyong; Zhou, Xueping; Wu, Jianxiang

2016-08-01

Citrus tristeza virus (CTV) is one of the most economically important citrus viruses and harms the citrus industry worldwide. To develop reliable and effective serological detection assays of CTV, the major capsid protein (CP) gene of CTV was expressed in Escherichia coli BL21 (DE3) using the expression vector pET-28a and purified through Ni+-NTA affinity chromatography. The recombinant protein was used to immunize BALB/c mice. Four hybridoma cell lines (14B10, 14H11, 20D5, and 20G12) secreting monoclonal antibodies (MAbs) against CTV were obtained through conventional hybridoma technology. The titers of MAb-containing ascitic fluids secreted by the four hybridoma lines ranged from 10(-6) to 10(-7) in indirect enzyme-linked immunosorbent assay (ELISA). Western blots showed that all four MAbs could specifically react with CTV CP. Using the prepared MAbs, dot-ELISA, Tissue print-ELISA, and triple antibody sandwich (TAS)-ELISA were developed to detect CTV in tree nurseries and epidemiological studies. The developed dot-ELISA and TAS-ELISA methods could detect CTV in crude extracts of infected citrus leaves with dilutions of 1:2560 and 1:10, 240 (w/v, g/mL), respectively. Tissue print-ELISA was particularly useful for large-scale field sample detection, mainly owing to its simplicity and lack of sample preparation requirements. The field survey revealed that CTV is prevalent on citrus trees in the Chongqing Municipality, Jiangxi Province, and Zhejiang Province of China. The coincidence rate of serological and RT-PCR test results reached more than 99.5%. The prepared MAbs against CTV and established sensitive and specific serological assays have a significant role in the detection and prevention and control of CTV in our country.

Comparative Effectiveness of Cardiac Resynchronization Therapy Defibrillators Versus Standard Implantable Defibrillators in Medicare Patients.

PubMed

Zusterzeel, Robbert; Caños, Daniel A; Sanders, William E; Silverman, Henry; MaCurdy, Thomas E; Worrall, Christopher M; Kelman, Jeffrey; Marinac-Dabic, Danica; Strauss, David G

2015-07-01

Previous analyses have shown that there is lower mortality with cardiac resynchronization therapy defibrillators (CRT-D) in patients with left bundle branch block (LBBB) but demonstrated mixed results in patients without LBBB. We evaluated the comparative effectiveness of CRT-D versus standard implantable defibrillators (ICDs) separately in patients with LBBB and right bundle branch block (RBBB) using Medicare claims data. Medicare records from CRT-D and ICD recipients from 2002 to 2009 that were followed up for up to 48 months were analyzed. We used propensity scores to match patients with ICD to those with CRT-D. In LBBB, 1:1 matching with replacement resulted in 54,218 patients with CRT-D and 20,763 with ICD, and in RBBB, 1:1 matching resulted in 7,298 patients with CRT-D and 7,298 with ICD. In LBBB, CRT-D had a 12% lower risk of heart failure hospitalization or death (hazard ratio [HR] 0.88, 95% confidence interval 0.86 to 0.90) and 5% lower death risk (HR 0.95, 0.92 to 0.97) compared with ICD. In RBBB, CRT-D had a 15% higher risk of heart failure hospitalization or death (HR 1.15, 1.10 to 1.20) and 13% higher death risk (HR 1.13, 1.07 to 1.18). Sensitivity analysis revealed that accounting for covariates not captured in the Medicare database may lead to increased benefit with CRT-D in LBBB and no difference in RBBB. In conclusion, in a large Medicare population, CRT-D was associated with lower mortality in LBBB but higher mortality in RBBB. The absence of certain covariates, in particular those that determine treatment selection, may affect the results of comparative effectiveness studies using claims data. Published by Elsevier Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Avkshtol, V; Tanny, S; Reddy, K

Purpose: Stereotactic radiation therapy (SRT) provides an excellent alternative to embolization and surgical excision for the management of appropriately selected cerebral arteriovenous malformations (AVMs). The currently accepted standard for delineating AVMs is planar digital subtraction angiography (DSA). DSA can be used to acquire a 3D data set that preserves osseous structures (3D-DA) at the time of the angiography for SRT planning. Magnetic resonance imaging (MRI) provides an alternative noninvasive method of visualizing the AVM nidus with comparable spatial resolution. We utilized 3D-DA and T1 post-contrast MRI data to evaluate the differences in SRT target volumes. Methods: Four patients underwent 3D-DAmore » and high-resolution MRI. 3D T1 post-contrast images were obtained in all three reconstruction planes. A planning CT was fused with MRI and 3D-DA data sets. The AVMs were contoured utilizing one of the image sets at a time. Target volume, centroid, and maximum and minimum dimensions were analyzed for each patient. Results: Targets delineated using post-contrast MRI demonstrated a larger mean volume. AVMs >2 cc were found to have a larger difference between MRI and 3D-DA volumes. Larger AVMs also demonstrated a smaller relative uncertainty in contour centroid position (1 mm). AVM targets <2 cc had smaller absolute differences in volume, but larger differences in contour centroid position (2.5 mm). MRI targets demonstrated a more irregular shape compared to 3D-DA targets. Conclusions: Our preliminary data supports the use of MRI alone to delineate AVM targets >2 cc. The greater centroid stability for AVMs >2 cc ensures accurate target localization during image fusion. The larger MRI target volumes did not result in prohibitively greater volumes of normal brain tissue receiving the prescription dose. The larger centroid instability for AVMs <2 cc precludes the use of MRI alone for target delineation. We recommend incorporating a 3D-DA for these patients.« less

Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis)

PubMed Central

Doherty, D; Parisi, M A; Finn, L S; Gunay-Aygun, M; Al-Mateen, M; Bates, D; Clericuzio, C; Demir, H; Dorschner, M; van Essen, A J; Gahl, W A; Gentile, M; Gorden, N T; Hikida, A; Knutzen, D; Özyurek, H; Phelps, I; Rosenthal, P; Verloes, A; Weigand, H; Chance, P F; Dobyns, W B; Glass, I A

2011-01-01

Objective To identify genetic causes of COACH syndrome Background COACH syndrome is a rare autosomal recessive disorder characterised by Cerebellar vermis hypoplasia, Oligophrenia (developmental delay/mental retardation), Ataxia, Coloboma, and Hepatic fibrosis. The vermis hypoplasia falls in a spectrum of mid-hindbrain malformation called the molar tooth sign (MTS), making COACH a Joubert syndrome related disorder (JSRD). Methods In a cohort of 251 families with JSRD, 26 subjects in 23 families met criteria for COACH syndrome, defined as JSRD plus clinically apparent liver disease. Diagnostic criteria for JSRD were clinical findings (intellectual impairment, hypotonia, ataxia) plus supportive brain imaging findings (MTS or cerebellar vermis hypoplasia). MKS3/TMEM67 was sequenced in all subjects for whom DNA was available. In COACH subjects without MKS3 mutations, CC2D2A, RPGRIP1L and CEP290 were also sequenced. Results 19/23 families (83%) with COACH syndrome carried MKS3 mutations, compared to 2/209 (1%) with JSRD but no liver disease. Two other families with COACH carried CC2D2A mutations, one family carried RPGRIP1L mutations, and one lacked mutations in MKS3, CC2D2A, RPGRIP1L and CEP290. Liver biopsies from three subjects, each with mutations in one of the three genes, revealed changes within the congenital hepatic fibrosis/ductal plate malformation spectrum. In JSRD with and without liver disease, MKS3 mutations account for 21/232 families (9%). Conclusions Mutations in MKS3 are responsible for the majority of COACH syndrome, with minor contributions from CC2D2A and RPGRIP1L; therefore, MKS3 should be the first gene tested in patients with JSRD plus liver disease and/or coloboma, followed by CC2D2A and RPGRIP1L. PMID:19574260

Celiac disease and other autoimmune diseases in patients with collagenous colitis.

PubMed

Vigren, Lina; Tysk, Curt; Ström, Magnus; Kilander, Anders F; Hjortswang, Henrik; Bohr, Johan; Benoni, Cecilia; Larson, Lasse; Sjöberg, Klas

2013-08-01

Collagenous colitis (CC) is associated with autoimmune disorders. The aim of the present study was to investigate the relationship between CC and autoimmune disorders in a Swedish multicenter study. Patients with CC answered questionnaires about demographic data and disease activity. The patient's files were scrutinized for information about autoimmune diseases. A total number of 116 CC patients were included; 92 women, 24 men, median age 62 years (IQR 55-73). In total, 30.2% had one or more autoimmune disorder. Most common were celiac disease (CeD; 12.9%) and autoimmune thyroid disease (ATD, 10.3%), but they also had Sjögren's syndrome (3.4%), diabetes mellitus (1.7%) and conditions in skin and joints (6.0%). Patients with associated autoimmune disease had more often nocturnal stools. The majority of the patients with associated CeD or ATD got these diagnoses before the colitis diagnosis. Autoimmune disorders occurred in one-third of these patients, especially CeD. In classic inflammatory bowel disease (IBD), liver disease is described in contrast to CC where no cases occurred. Instead, CeD was prevalent, a condition not reported in classic IBD. Patients with an associated autoimmune disease had more symptoms. Patients with CC and CeD had an earlier onset of their colitis. The majority of the patients with both CC and CeD were smokers. Associated autoimmune disease should be contemplated in the follow-up of these patients.

Atrazine sorption by hydroxy-interlayered clays and their organic complexes.

PubMed

Indraratne, Srimathie P; Farenhorst, Annemieke; Goh, Tee Boon

2008-01-01

This study examined the sorption of atrazine by hydroxy-Fe interlayered montmorillonite (FeMt) and its hydroquinone (FeMtHQ), citrate (FeMtCt) and catechol (FeMtCC) complexes as well as by hydroxy-Al interlayered montmorillonite (AlMt) and its hydroquinone (AlMtHQ) and citrate (AlMtCt) complexes. Found among the clays were sorption distribution coefficients (K(d)) ranging from 24 to 123 mL g(-1) and maximum sorption (M) ranging from 2.2 to 16.8 microg g(-1). Both K(d) and M decreased in the order of FeMtCC > FeMtHQ > AlMtHQ > (AlMt = FeMt) > (AlMtCt = FeMtCt). The pH was negatively correlated with both K(d) (r = -0.90, p < 0.001) and M (r = -0.81, p < 0.001). When interlayered clays were associated with humified material (FeMtCC, FeMtHQ, AlMtHQ), both K(d) (r > 0.96, p < 0.01) and M (r > 0.94, p < 0.01) were highly positively correlated with total organic C and alkali-soluble C. However, clays with non-humified organic compounds (FeMtCt and AlMtCt) sorbed less atrazine than clays without any organic C (FeMt and AlMt). This suggests that functional groups of Fe-OH and Al-OH in FeMt and AlMt reduced the available sorption sites for atrazine by making complexes with citrate ions while forming FeMtCt and AlMtCt. The atrazine was sorbed through the hydrophobic interactions with organic compound surfaces as well as through H-bonding and ionic bonding with clay-mineral surfaces.

Loss-of-function of the ciliopathy protein Cc2d2a disorganizes the vesicle fusion machinery at the periciliary membrane and indirectly affects Rab8-trafficking in zebrafish photoreceptors

PubMed Central

Gesemann, Matthias; Mateos, José M.; Barmettler, Gery; Forbes, Austin; Ziegler, Urs

2017-01-01

Ciliopathies are human disorders caused by dysfunction of primary cilia, ubiquitous organelles involved in transduction of environmental signals such as light sensation in photoreceptors. Concentration of signal detection proteins such as opsins in the ciliary membrane is achieved by RabGTPase-regulated polarized vesicle trafficking and by a selective barrier at the ciliary base, the transition zone (TZ). Dysfunction of the TZ protein CC2D2A causes Joubert/Meckel syndromes in humans and loss of ciliary protein localization in animal models, including opsins in retinal photoreceptors. The link between the TZ and upstream vesicle trafficking has been little explored to date. Moreover, the role of the small GTPase Rab8 in opsin-carrier vesicle (OCV) trafficking has been recently questioned in a mouse model. Using correlative light and electron microscopy and live imaging in zebrafish photoreceptors, we provide the first live characterization of Rab8-mediated trafficking in photoreceptors in vivo. Our results support a possibly redundant role for both Rab8a/b paralogs in OCV trafficking, based on co-localization of Rab8 and opsins in vesicular structures, and joint movement of Rab8-tagged particles with opsin. We further investigate the role of the TZ protein Cc2d2a in Rab8-mediated trafficking using cc2d2a zebrafish mutants and identify a requirement for Cc2d2a in the latest step of OCV trafficking, namely vesicle fusion. Progressive accumulation of opsin-containing vesicles in the apical portion of photoreceptors lacking Cc2d2a is caused by disorganization of the vesicle fusion machinery at the periciliary membrane with mislocalization and loss of the t-SNAREs SNAP25 and Syntaxin3 and of the exocyst component Exoc4. We further observe secondary defects on upstream Rab8-trafficking with cytoplasmic accumulation of Rab8. Taken together, our results support participation of Rab8 in OCV trafficking and identify a novel role for the TZ protein Cc2d2a in fusion of incoming ciliary-directed vesicles, through organization of the vesicle fusion machinery at the periciliary membrane. PMID:29281629

Loss-of-function of the ciliopathy protein Cc2d2a disorganizes the vesicle fusion machinery at the periciliary membrane and indirectly affects Rab8-trafficking in zebrafish photoreceptors.

PubMed

Ojeda Naharros, Irene; Gesemann, Matthias; Mateos, José M; Barmettler, Gery; Forbes, Austin; Ziegler, Urs; Neuhauss, Stephan C F; Bachmann-Gagescu, Ruxandra

2017-12-01

Ciliopathies are human disorders caused by dysfunction of primary cilia, ubiquitous organelles involved in transduction of environmental signals such as light sensation in photoreceptors. Concentration of signal detection proteins such as opsins in the ciliary membrane is achieved by RabGTPase-regulated polarized vesicle trafficking and by a selective barrier at the ciliary base, the transition zone (TZ). Dysfunction of the TZ protein CC2D2A causes Joubert/Meckel syndromes in humans and loss of ciliary protein localization in animal models, including opsins in retinal photoreceptors. The link between the TZ and upstream vesicle trafficking has been little explored to date. Moreover, the role of the small GTPase Rab8 in opsin-carrier vesicle (OCV) trafficking has been recently questioned in a mouse model. Using correlative light and electron microscopy and live imaging in zebrafish photoreceptors, we provide the first live characterization of Rab8-mediated trafficking in photoreceptors in vivo. Our results support a possibly redundant role for both Rab8a/b paralogs in OCV trafficking, based on co-localization of Rab8 and opsins in vesicular structures, and joint movement of Rab8-tagged particles with opsin. We further investigate the role of the TZ protein Cc2d2a in Rab8-mediated trafficking using cc2d2a zebrafish mutants and identify a requirement for Cc2d2a in the latest step of OCV trafficking, namely vesicle fusion. Progressive accumulation of opsin-containing vesicles in the apical portion of photoreceptors lacking Cc2d2a is caused by disorganization of the vesicle fusion machinery at the periciliary membrane with mislocalization and loss of the t-SNAREs SNAP25 and Syntaxin3 and of the exocyst component Exoc4. We further observe secondary defects on upstream Rab8-trafficking with cytoplasmic accumulation of Rab8. Taken together, our results support participation of Rab8 in OCV trafficking and identify a novel role for the TZ protein Cc2d2a in fusion of incoming ciliary-directed vesicles, through organization of the vesicle fusion machinery at the periciliary membrane.

Cytochrome P450 (CYP2D6) genotype is associated with elevated systolic blood pressure in preterm infants after discharge from the neonatal intensive care unit.

PubMed

Dagle, John M; Fisher, Tyler J; Haynes, Susan E; Berends, Susan K; Brophy, Patrick D; Morriss, Frank H; Murray, Jeffrey C

2011-07-01

To determine genetic and clinical risk factors associated with elevated systolic blood pressure (ESBP) in preterm infants after discharge from the neonatal intensive care unit (NICU). A convenience cohort of infants born at <32 weeks gestational age was followed after NICU discharge. We retrospectively identified a subgroup of subjects with ESBP (systolic blood pressure [SBP] >90th percentile for term infants). Genetic testing identified alleles associated with ESBP. Multivariate logistic regression analysis was performed for the outcome ESBP, with clinical characteristics and genotype as independent variables. Predictors of ESBP were cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) (rs28360521) CC genotype (OR, 2.92; 95% CI, 1.48-5.79), adjusted for outpatient oxygen therapy (OR, 4.53; 95% CI, 2.23-8.81) and history of urinary tract infection (OR, 4.68; 95% CI, 1.47-14.86). Maximum SBP was modeled by multivariate linear regression analysis: maximum SBP=84.8 mm Hg + 6.8 mm Hg if cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) CC genotype + 6.8 mm Hg if discharged on supplemental oxygen + 4.4 mm Hg if received inpatient glucocorticoids (P=.0002). ESBP is common in preterm infants with residual lung disease after discharge from the NICU. This study defines clinical factors associated with ESBP, identifies a candidate gene for further testing, and supports the recommendation to monitor blood pressure before age 3 years, as is suggested for term infants. Copyright © 2011 Mosby, Inc. All rights reserved.

B-vitamin Supplementation Mitigates Effects of Fine Particles on Cardiac Autonomic Dysfunction and Inflammation: A Pilot Human Intervention Trial

NASA Astrophysics Data System (ADS)

Zhong, Jia; Trevisi, Letizia; Urch, Bruce; Lin, Xinyi; Speck, Mary; Coull, Brent A.; Liss, Gary; Thompson, Aaron; Wu, Shaowei; Wilson, Ander; Koutrakis, Petros; Silverman, Frances; Gold, Diane R.; Baccarelli, Andrea A.

2017-04-01

Ambient fine particle (PM2.5) pollution triggers acute cardiovascular events. Individual-level preventions are proposed to complement regulation in reducing the global burden of PM2.5-induced cardiovascular diseases. We determine whether B vitamin supplementation mitigates PM2.5 effects on cardiac autonomic dysfunction and inflammation in a single-blind placebo-controlled crossover pilot trial. Ten healthy adults received two-hour controlled-exposure-experiment to sham under placebo, PM2.5 (250 μg/m3) under placebo, and PM2.5 (250 μg/m3) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B6, and 1 mg/d vitamin B12), respectively. At pre-, post-, 24 h-post-exposure, we measured resting heart rate (HR) and heart rate variability (HRV) with electrocardiogram, and white blood cell (WBC) counts with hematology analyzer. Compared to sham, PM2.5 exposure increased HR (3.8 bpm, 95% CI: 0.3, 7.4; P = 0.04), total WBC count (11.5%, 95% CI: 0.3%, 24.0%; P = 0.04), lymphocyte count (12.9%, 95% CI: 4.4%, 22.1%; P = 0.005), and reduced low-frequency power (57.5%, 95% CI: 2.5%, 81.5%; P = 0.04). B-vitamin supplementation attenuated PM2.5 effect on HR by 150% (P = 0.003), low-frequency power by 90% (P = 0.01), total WBC count by 139% (P = 0.006), and lymphocyte count by 106% (P = 0.02). In healthy adults, two-hour PM2.5 exposure substantially increases HR, reduces HRV, and increases WBC. These effects are reduced by B vitamin supplementation.

Experiments of the origins of optical activity.

PubMed

Bonner, W A; Flores, J J

1975-01-01

Two recent reports claim that (1) aqueous L-aspartic acid polymerizes faster than D-Asp in the presence of kaolin at 90 degrees, and (2) L-phenylalanine is adsorbed by kaolin more extensively than D-Phe at pH 4(the reverse being true at pH2). The novelty of these observations and their potential significance for the origin of optical activity has prompted us to duplicate these experiments using more sensitive methods. L- and D, L-Asp in 0.01 M solution were incubated with kaolin at 90 degrees for 8 days. Careful examination of the aqueous residues from such experiments failed to demonstrate any preferential polymerization of L-Asp over D-Asp, or indeed any significant gross polymerization of Asp at all. In other experiments 0.001 M solutions of D, L-Phe at pH 6 and pH 2 were stirred with large excesses of kaolin for 24 hr, and the aqueous extracts from these mixtures were examined for gross adsorption using the amino acid analyzer. No significant gross adsorption was noted. We then looked for asymmetric adsorption in the aqueous residues using optical rotatory dispersion, gas chromatography and thin layer chromatography. By none of these analytical criteria could we find any evidence whatsoever for the preferential adsorption of D- versus L-Phe from either pH 6 or pH 2 solutions. Finally, in experiments bearing on the origin of optical activity by parity violation during beta-decay, we have irradiated solid samples of D-, L- and D,L-leucine in a 61700 Ci Sr-90 source at Oak Ridge National Lab. for 1.34 yr (total dose: 4.2 x 10(8) rad). Gas chromatographic examination of the (appropriately derivitized) recovered samples showed that the L-Leu was 16.7% decomposed, the D-Leu 11.4% and theD,L-Leu 13.8% decomposed. The recovered D,L-Leu sample had a gas-chromatographically determined enantiomeric composition of 50.8% D-leu and 49.2% L-Leu. These data, though very close to experimental error, may indicate a slight preferential radiolysis of L-Leu compared to D-Leu by the Bremsstrahlung from Sr-90 beta-decay. These high intensity irradiation experiments are being continued on a prolonged basis in order to reach more definitive conclusions.

Hypoglycemic depression of hepatic phagocytosis in vivo and in the in situ perfused rat liver.

PubMed

Kober, P M; Filkins, J P

1981-01-01

Depression of the phagocytic function of the reticuloendothelial system (RES) during endotoxic hypoglycemia has been implicated in the pathogenesis of endotoxin shock. The present study evaluated the in vivo effects of hypoglycemia on RES function and assessed the effects of an vivo bout of hypoglycemia on phagocytosis in the in situ perfused rat liver. Hypoglycemia was produced in male Holtzman rats using either 1 U of regular insulin (RI) (ILETIN, Lilly) or 0.75 U of long-acting insulin (LAI) (85% LENTE/15% ULTRALENTE, Lilly). RES function was quantitated by intravascular clearance of 8 mg/100 gm body weight colloidal carbon (CC). Two hr after RI and 2.5 hr after LAI, the intravascular halftimes of CC clearance were 19 +/- 2 min (N = 22) and 18 +/- 1 min (N = 19), respectively, as compared to control, 11.3 +/- 0.4 min (N = 53, P less than 0.001). The corresponding plasma glucose (PG) levels were 95 +/- 2 mg/dl in control, 14.4 +/- 0.9 for the RI group, and 17 +/- 1 for LAI. Two hr after RI, livers were perfused for 10 min in situ with 50 mg/liter CC in saline 5% rat serum. PG for control liver donors were 90 +/- 3 mg/dl, while those for hypoglycemic liver donors were 15 +/- 2. CC uptake was decreased from 22 micrograms/min/gm liver in the control (+ serum, n = 19) to 11 +/- 2 in hypoglycemia livers (N = 6); no effect of serum on hypoglycemic depression of the RES was seen. There were no differences in flow rates in the 2 groups. These results indicate that hypoglycemia directly impairs RES function and that the in vivo depression of intravascular clearance is not related to either the presence or absence of serum factors or total hepatic blood flow. Thus, the characteristic hypoglycemia of endotoxin shock may contribute to RES depression and the lethal shock syndrome.

Dosimetric advantages of a clinical daily adaptive plan selection strategy compared with a non-adaptive strategy in cervical cancer radiation therapy.

PubMed

van de Schoot, Agustinus J A J; de Boer, Peter; Visser, Jorrit; Stalpers, Lukas J A; Rasch, Coen R N; Bel, Arjan

2017-05-01

Radiation therapy (RT) using a daily plan selection adaptive strategy can be applied to account for interfraction organ motion while limiting organ at risk dose. The aim of this study was to quantify the dosimetric consequences of daily plan selection compared with non-adaptive RT in cervical cancer. Ten consecutive patients who received pelvic irradiation, planning CTs (full and empty bladder), weekly post-fraction CTs and pre-fraction CBCTs were included. Non-adaptive plans were generated based on the PTV defined using the full bladder planning CT. For the adaptive strategy, multiple PTVs were created based on both planning CTs by ITVs of the primary CTVs (i.e., GTV, cervix, corpus-uterus and upper part of the vagina) and corresponding library plans were generated. Daily CBCTs were rigidly aligned to the full bladder planning CT for plan selection. For daily plan recalculation, selected CTs based on initial similarity were deformably registered to CBCTs. Differences in daily target coverage (D 98%  > 95%) and in V 0.5Gy , V 1.5Gy , V 2Gy , D 50% and D 2% for rectum, bladder and bowel were assessed. Non-adaptive RT showed inadequate primary CTV coverage in 17% of the daily fractions. Plan selection compensated for anatomical changes and improved primary CTV coverage significantly (p < 0.01) to 98%. Compared with non-adaptive RT, plan selection decreased the fraction dose to rectum and bowel indicated by significant (p < 0.01) improvements for daily V 0.5Gy , V 1.5Gy , V 2Gy , D 50% and D 2% . However, daily plan selection significantly increased the bladder V 1.5Gy , V 2Gy , D 50% and D 2% . In cervical cancer RT, a non-adaptive strategy led to inadequate target coverage for individual patients. Daily plan selection corrected for day-to-day anatomical variations and resulted in adequate target coverage in all fractions. The dose to bowel and rectum was decreased significantly when applying adaptive RT.

Dosimetric effects of rotational offsets in stereotactic body radiation therapy (SBRT) for lung cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Yun; Catalano, Suzanne; Kelsey, Chris R.

2014-04-01

To quantitatively evaluate dosimetric effects of rotational offsets in stereotactic body radiation therapy (SBRT) for lung cancer. Overall, 11 lung SBRT patients (8 female and 3 male; mean age: 75.0 years) with medially located tumors were included. Treatment plans with simulated rotational offsets of 1°, 3°, and 5° in roll, yaw, and pitch were generated and compared with the original plans. Both clockwise and counterclockwise rotations were investigated. The following dosimetric metrics were quantitatively evaluated: planning target volume coverage (PTV V{sub 100%}), max PTV dose (PTV D{sub max}), percentage prescription dose to 0.35 cc of cord (cord D{sub 0.35} {submore » cc}), percentage prescription dose to 0.35 cc and 5 cc of esophagus (esophagus D{sub 0.35} {sub cc} and D{sub 5} {sub cc}), and volume of the lungs receiving at least 20 Gy (lung V{sub 20}). Statistical significance was tested using Wilcoxon signed rank test at the significance level of 0.05. Overall, small differences were found in all dosimetric matrices at all rotational offsets: 95.6% of differences were < 1% or < 1 Gy. Of all rotational offsets, largest change in PTV V{sub 100%}, PTV D{sub max}, cord D{sub 0.35} {sub cc}, esophagus D{sub 0.35} {sub cc}, esophagus D{sub 5} {sub cc}, and lung V{sub 20} was − 8.36%, − 6.06%, 11.96%, 8.66%, 6.02%, and − 0.69%, respectively. No significant correlation was found between any dosimetric change and tumor-to-cord/esophagus distances (R{sup 2} range: 0 to 0.44). Larger dosimetric changes and intersubject variations were observed at larger rotational offsets. Small dosimetric differences were found owing to rotational offsets up to 5° in lung SBRT for medially located tumors. Larger intersubject variations were observed at larger rotational offsets.« less

Annihilation rates of 3D2(2--) and 3D3(3--) heavy quarkonia

NASA Astrophysics Data System (ADS)

Wang, Tianhong; Fu, Hui-Feng; Jiang, Yue; Li, Qiang; Wang, Guo-Li

2017-03-01

We calculate the annihilation decay rates of the 3D 2(2--) and 3D 3(3--) charmonia and bottomonia by using the instantaneous Bethe-Salpeter (BS) method. The wave functions of states with quantum numbers JPC = 2-- and 3-- are constructed. By solving the corresponding instantaneous BS equations, we obtain the mass spectra and wave functions of the quarkonia. The annihilation amplitude is written within Mandelstam formalism and the relativistic corrections are taken into account properly. This is important, especially for high excited states, since their relativistic corrections are large. The results for the 3g channel are as follows: Γ13D2(cc¯)→ggg = 9.24 keV, Γ13D3(cc¯)→ggg = 25.0 keV, Γ13D2(bb¯)→ggg = 1.87 keV and Γ13D3(bb¯)→ggg = 0.815 keV.

Effects of progressive resistance training combined with a protein-enriched lean red meat diet on health-related quality of life in elderly women: secondary analysis of a 4-month cluster randomised controlled trial.

PubMed

Torres, Susan J; Robinson, Sian; Orellana, Liliana; O'Connell, Stella L; Grimes, Carley A; Mundell, Niamh L; Dunstan, David W; Nowson, Caryl A; Daly, Robin M

2017-06-01

Resistance training (RT) and increased dietary protein are recommended to attenuate age-related muscle loss in the elderly. This study examined the effect of a lean red meat protein-enriched diet combined with progressive resistance training (RT+Meat) on health-related quality of life (HR-QoL) in elderly women. In this 4-month cluster randomised controlled trial, 100 women aged 60-90 years (mean 73 years) from self-care retirement villages participated in RT twice a week and were allocated either 160 g/d (cooked) lean red meat consumed across 2 meals/d, 6 d/week or ≥1 serving/d (25-30 g) carbohydrates (control group, CRT). HR-QoL (SF-36 Health Survey questionnaire), lower limb maximum muscle strength and lean tissue mass (LTM) (dual-energy X-ray absorptiometry) were assessed at baseline and 4 months. In all, ninety-one women (91 %) completed the study (RT+Meat (n 48); CRT (n 43)). Mean protein intake was greater in RT+Meat than CRT throughout the study (1·3 (sd 0·3) v. 1·1 (sd 0·3) g/kg per d, P<0·05). Exercise compliance (74 %) was not different between groups. After 4 months there was a significant net benefit in the RT+Meat compared with CRT group for overall HR-QoL and the physical component summary (PCS) score (P<0·01), but there were no changes in either group in the mental component summary (MCS) score. Changes in lower limb muscle strength, but not LTM, were positively associated with changes in overall HR-QoL (muscle strength, β: 2·2 (95 % CI 0·1, 4·3), P<0·05). In conclusion, a combination of RT and increased dietary protein led to greater net benefits in overall HR-QoL in elderly women compared with RT alone, which was because of greater improvements in PCS rather than MCS.

A class solution for volumetric-modulated arc therapy planning in postprostatectomy radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Forde, Elizabeth, E-mail: eforde@tcd.ie; Bromley, Regina; Institute of Medical Physics, School of Physics, University of Sydney, New South Wales

This study is aimed to test a postprostatectomy volumetric-modulated arc therapy (VMAT) planning class solution. The solution applies to both the progressive resolution optimizer algorithm version 2 (PRO 2) and the algorithm version 3 (PRO 3), addressing the effect of an upgraded algorithm. A total of 10 radical postprostatectomy patients received 68 Gy to 95% of the planning target volume (PTV), which was planned using VMAT. Each case followed a set of planning instructions; including contouring, field setup, and predetermined optimization parameters. Each case was run through both algorithms only once, with no user interaction. Results were averaged and comparedmore » against Radiation Therapy Oncology Group (RTOG) 0534 end points. In addition, the clinical target volume (CTV) D{sub 100}, PTV D{sub 99}, and PTV mean doses were recorded, along with conformity indices (CIs) (95% and 98%) and the homogeneity index. All cases satisfied PTV D{sub 95} of 68 Gy and a maximum dose < 74.8 Gy. The average result for the PTV D{sub 99} was 64.1 Gy for PRO 2 and 62.1 Gy for PRO 3. The average PTV mean dose for PRO 2 was 71.4 Gy and 71.5 Gy for PRO 3. The CTV D{sub 100} average dose was 67.7 and 68.0 Gy for PRO 2 and PRO 3, respectively. The mean homogeneity index for both algorithms was 0.08. The average 95% CI was 1.17 for PRO 2 and 1.19 for PRO 3. For 98%, the average results were 1.08 and 1.12 for PRO 2 and PRO 3, respectively. All cases for each algorithm met the RTOG organs at risk dose constraints. A successful class solution has been established for prostate bed VMAT radiotherapy regardless of the algorithm used.« less

American River Watershed Investigation, California. Volume 2. Appendixes F-L

DTIC Science & Technology

1991-12-01

j ) 0 U~ - T a< a:a LUi -LJ > Wr 0 ww o I - o w zo 00 ww z. L~ cc 6...At 40.’ U . * J ." 466.00_~I IEA A 432. 601111 CAN a t 417.96 4800 0--:-- -f 10"~tfl _ _ _ W O N d ~ i e -w $ SC 1 I N ) T HR U F PL P SC el. 183.00...500 450 SPILLWAY CREST ELEVATION 418.0 FT 400 - J 15- - .. 00 P o --lJ 300 , 0 100 200 300 400 500 CAF/1 AREA, in thousand acres 5 6 7 t 9 10 It 12 I

Late Side Effects After Image Guided Intensity Modulated Radiation Therapy Compared to 3D-Conformal Radiation Therapy for Prostate Cancer: Results From 2 Prospective Cohorts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wortel, Ruud C.; Incrocci, Luca; Pos, Floris J.

Purpose: Technical developments in the field of external beam radiation therapy (RT) enabled the clinical introduction of image guided intensity modulated radiation therapy (IG-IMRT), which improved target conformity and allowed reduction of safety margins. Whether this had an impact on late toxicity levels compared to previously applied three-dimensional conformal radiation therapy (3D-CRT) is currently unknown. We analyzed late side effects after treatment with IG-IMRT or 3D-CRT, evaluating 2 prospective cohorts of men treated for localized prostate cancer to investigate the hypothesized reductions in toxicity. Methods and Materials: Patients treated with 3D-CRT (n=189) or IG-IMRT (n=242) to 78 Gy in 39 fractionsmore » were recruited from 2 Dutch randomized trials with identical toxicity scoring protocols. Late toxicity (>90 days after treatment) was derived from self-assessment questionnaires and case report forms, according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG-EORTC) scoring criteria. Grade ≥2 endpoints included gastrointestinal (GI) rectal bleeding, increased stool frequency, discomfort, rectal incontinence, proctitis, and genitourinary (GU) obstruction, increased urinary frequency, nocturia, urinary incontinence, and dysuria. The Cox proportional hazards regression model was used to compare grade ≥2 toxicities between both techniques, adjusting for other modifying factors. Results: The 5-year cumulative incidence of grade ≥2 GI toxicity was 24.9% for IG-IMRT and 37.6% following 3D-CRT (adjusted hazard ratio [HR]: 0.59, P=.005), with significant reductions in proctitis (HR: 0.37, P=.047) and increased stool frequency (HR: 0.23, P<.001). GU grade ≥2 toxicity levels at 5 years were comparable with 46.2% and 36.4% following IG-IMRT and 3D-CRT, respectively (adjusted HR: 1.19, P=.33). Other strong predictors (P<.01) of grade ≥2 late toxicity were baseline complaints, acute toxicity, and age. Conclusions: Treatment with IG-IMRT reduced the risk of late grade ≥2 complications, whereas GU toxicities remained comparable. This clinically relevant observation demonstrates that IMRT and image-guidance should therefore be the preferred treatment option, provided that margin reduction is implemented with caution.« less

Dental Shade Guide Variability for Hues B, C, and D Using Cross-Polarized Photography.

PubMed

Sampaio, Camila S; Gurrea, Jon; Gurrea, Marta; Bruguera, August; Atria, Pablo J; Janal, Malvin; Bonfante, Estevam A; Coelho, Paulo G; Hirata, Ronaldo

2018-04-20

This study evaluated the color variability of hues B, C, and D between the VITA Classical shade guide (Vita Zahnfabrik) and four other VITA-coded ceramic shade guides using a digital camera (Canon EOS 60D) and computer software (Adobe Photoshop CC). A cross-polarizing filter was used to standardize external light sources influencing color match. A total of 275 pictures were taken, 5 per shade tab, for 11 shades (B1, B2, B3, B4, C1, C2, C3, C4, D2, D3, and D4), from the following shade guides: VITA Classical (control); IPS e.max Ceram (Ivoclar Vivadent); IPS d.SIGN (Ivoclar Vivadent); Initial ZI (GC); and Creation CC (Creation Willi Geller). Pictures were evaluated using Adobe Photoshop CC for standardization of hue, chroma, and value between shade tabs. The VITA-coded shade guides evaluated here showed an overall unmatched shade in all their tabs when compared to the control, suggesting that shade selection should be made with the corresponding manufacturer guide of the ceramic intended for the final restoration.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Safigholi, H; Soliman, A; Song, W

Purpose: To evaluate various shielding materials such as Gold (Au), Osmium (Os), Tantalum (Ta), and Tungsten (W) based alloys for use with a novel intensity modulation capable direction modulated brachytherapy (DMBT) tandem applicator for image guided cervical cancer HDR brachytherapy. Methods: The novel MRI-compatible DMBT tandem, made from nonmagnetic tungsten-alloy rod with diameter of 5.4 mm, has 6 symmetric peripheral holes of 1.3 mm diameter with 2.05 mm distance from the center for a high degree intensity modulation capacity. The 0.3 mm thickness of bio-compatible plastic tubing wraps the tandem. MCNPX was used for Monte Carlo simulations of the shieldsmore » and the mHDR Ir-192 V2 source. MC-generated 3D dose matrices of different shielding materials of Au, Os, Ta, and W with 1 mm3 resolution were imported into an in-house-coded inverse optimization planning system to evaluate 19 clinical patient plans. Prescription dose was 15Gy. All plans were normalized to receive the same HRCTV D90. Results: In general, the plan qualities for various shielding materials were similar. The OAR D2cc for bladder was very similar for Au, Os, and Ta with 11.64±2.30Gy. For W, it was very close 11.65±2.30Gy. The sigmoid D2cc was 9.82±2.46Gy for Au and Os while it was 9.84±2.48Gy for Ta and W. The rectum D2cc was 7.44±3.06Gy for Au, 7.43±3.07Gy for Os, 7.48±3.05Gy for Ta, and 7.47±3.05Gy for W. The HRCTV D98 and V100 were very close with 16.37±1.87 Gy and 97.37±1.93 Gy, on average, respectively. Conclusion: Various MRI-compatible shielding alloys were investigated for the DMBT tandem applicator. The clinical plan qualities were not significantly different among these various alloys, however. Therefore, the candidate metals (or in combination) can be used to select best alloys for MRI image guided cervical cancer brachytherapy using the novel DMBT applicator that is capable of unprecedented level of intensity modulation.« less

SU-F-P-54: Guidelines to Check Image Registration QA of a Clinical Deformation Registration Software: A Single Institution Preliminary Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gill, G; Souri, S; Rea, A

Purpose: The objective of this study is to verify and analyze the accuracy of a clinical deformable image registration (DIR) software. Methods: To test clinical DIR software qualitatively and quantitatively, we focused on lung radiotherapy and analyzed a single (Lung) patient CT scan. Artificial anatomical changes were applied to account for daily variations during the course of treatment including the planning target volume (PTV) and organs at risk (OAR). The primary CT (pCT) and the structure set (pST) was deformed with commercial tool (ImSimQA-Oncology Systems Limited) and after artificial deformation (dCT and dST) sent to another commercial tool (VelocityAI-Varian Medicalmore » Systems). In Velocity, the deformed CT and structures (dCT and dST) were inversely deformed back to original primary CT (dbpCT and dbpST). We compared the dbpST and pST structure sets using similarity metrics. Furthermore, a binary deformation field vector (BDF) was created and sent to ImSimQA software for comparison with known “ground truth” deformation vector fields (DVF). Results: An image similarity comparison was made by using “ground truth” DVF and “deformed output” BDF with an output of normalized “cross correlation (CC)” and “mutual information (MI)” in ImSimQA software. Results for the lung case were MI=0.66 and CC=0.99. The artificial structure deformation in both pST and dbpST was analyzed using DICE coefficient, mean distance to conformity (MDC) and deformation field error volume histogram (DFEVH) by comparing them before and after inverse deformation. We have noticed inadequate structure match for CTV, ITV and PTV due to close proximity of heart and overall affected by lung expansion. Conclusion: We have seen similarity between pCT and dbpCT but not so well between pST and dbpST, because of inadequate structure deformation in clinical DIR system. This system based quality assurance test will prepare us for adopting the guidelines of upcoming AAPM task group 132 protocol.« less

SU-F-BRD-01: A Novel 4D Robust Optimization Mitigates Interplay Effect in Intensity-Modulated Proton Therapy for Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, W; Shen, J; Stoker, J

2015-06-15

Purpose: To compare the impact of interplay effect on 3D and 4D robustly optimized intensity-modulated proton therapy (IMPT) plans to treat lung cancer. Methods: Two IMPT plans were created for 11 non-small-cell-lung-cancer cases with 6–14 mm spots. 3D robust optimization generated plans on average CTs with the internal gross tumor volume density overridden to deliver 66 CGyE in 33 fractions to the internal target volume (ITV). 4D robust optimization generated plans on 4D CTs with the delivery of prescribed dose to the clinical target volume (CTV). In 4D optimization, the CTV of individual 4D CT phases received non-uniform doses tomore » achieve a uniform cumulative dose. Dose evaluation software was developed to model time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Patient anatomy voxels were mapped from phase to phase via deformable image registration to score doses. Indices from dose-volume histograms were used to compare target coverage, dose homogeneity, and normal-tissue sparing. DVH indices were compared using Wilcoxon test. Results: Given the presence of interplay effect, 4D robust optimization produced IMPT plans with better target coverage and homogeneity, but slightly worse normal tissue sparing compared to 3D robust optimization (unit: Gy) [D95% ITV: 63.5 vs 62.0 (p=0.014), D5% - D95% ITV: 6.2 vs 7.3 (p=0.37), D1% spinal cord: 29.0 vs 29.5 (p=0.52), Dmean total lung: 14.8 vs 14.5 (p=0.12), D33% esophagus: 33.6 vs 33.1 (p=0.28)]. The improvement of target coverage (D95%,4D – D95%,3D) was related to the ratio RMA3/(TVx10−4), with RMA and TV being respiratory motion amplitude (RMA) and tumor volume (TV), respectively. Peak benefit was observed at ratios between 2 and 10. This corresponds to 125 – 625 cm3 TV with 0.5-cm RMA. Conclusion: 4D optimization produced more interplay-effect-resistant plans compared to 3D optimization. It is most effective when respiratory motion is modest compared to TV. NIH/NCI K25CA168984; Eagles Cancer Research Career Development; The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research; Mayo ASU Seed Grant; The Kemper Marley Foundation.« less

The relationship between age of onset and risk factors including family history and life style in Korean population with type 2 diabetes mellitus.

PubMed

Noh, Jin-Won; Jung, Jin Hee; Park, Jeong Eun; Lee, Jung Hwa; Sim, Kang Hee; Park, Jumin; Kim, Min Hee; Yoo, Ki-Bong

2018-02-01

[Purpose] The purpose of the present study was to assess the relationship between age of onset and risk factors including family history and life style in Korean population with type 2 diabetes mellitus (T2D). [Subjects and Methods] Subjects with T2D patients who received outpatient care for blood sugar control were randomly sampled at 13 general hospitals and 969 subjects were included. Cox proportional hazard models were used to confirm associations between age of onset and risk factors including family history and life style in Korean population with T2D. [Results] Parent history of T2D was significantly associated with age of onset. Compared to none of family members with T2D, those whose both father and mother had a history showed the highest the risk of early-onset (HR=2.36; 95% CI=1.45-3.85). Mother and father's history of T2D (HR=1.73; 95% CI=1.46-2.05; HR=1.83; 95% CI=1.40-2.37) were associated with the risk of early-onset. Moreover, exercise (HR=1.23, CI=1.08-1.40) smoking status (HR=1.62, CI=1.32-1.99), and drinking (HR=1.32, CI=1.13-1.54) were associated with a higher risk for the early-onset. [Conclusion] Family history as well as life style including exercise, smoking, and drinking are the risk factors for early-onset factor in Korean population with T2D.

The relationship between age of onset and risk factors including family history and life style in Korean population with type 2 diabetes mellitus

PubMed Central

Noh, Jin-Won; Jung, Jin Hee; Park, Jeong Eun; Lee, Jung Hwa; Sim, Kang Hee; Park, Jumin; Kim, Min Hee; Yoo, Ki-Bong

2018-01-01

[Purpose] The purpose of the present study was to assess the relationship between age of onset and risk factors including family history and life style in Korean population with type 2 diabetes mellitus (T2D). [Subjects and Methods] Subjects with T2D patients who received outpatient care for blood sugar control were randomly sampled at 13 general hospitals and 969 subjects were included. Cox proportional hazard models were used to confirm associations between age of onset and risk factors including family history and life style in Korean population with T2D. [Results] Parent history of T2D was significantly associated with age of onset. Compared to none of family members with T2D, those whose both father and mother had a history showed the highest the risk of early-onset (HR=2.36; 95% CI=1.45–3.85). Mother and father’s history of T2D (HR=1.73; 95% CI=1.46–2.05; HR=1.83; 95% CI=1.40–2.37) were associated with the risk of early-onset. Moreover, exercise (HR=1.23, CI=1.08–1.40) smoking status (HR=1.62, CI=1.32–1.99), and drinking (HR=1.32, CI=1.13–1.54) were associated with a higher risk for the early-onset. [Conclusion] Family history as well as life style including exercise, smoking, and drinking are the risk factors for early-onset factor in Korean population with T2D. PMID:29545678

SU-F-T-394: Impact of PTV Margins With Taking Into Account Shape Variation On IMRT Plans For Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hirose, T; Arimura, H; Oga, S

2016-06-15

Purpose: The purpose of this study was to investigate the impact of planning target volume (PTV) margins with taking into consideration clinical target volume (CTV) shape variations on treatment plans of intensity modulated radiation therapy (IMRT) for prostate cancer. Methods: The systematic errors and the random errors for patient setup errors in right-left (RL), anterior-posterior (AP), and superior-inferior (SI) directions were obtained from data of 20 patients, and those for CTV shape variations were calculated from 10 patients, who were weekly scanned using cone beam computed tomography (CBCT). The setup error was defined as the difference in prostate centers betweenmore » planning CT and CBCT images after bone-based registrations. CTV shape variations of high, intermediate and low risk CTVs were calculated for each patient from variances of interfractional shape variations on each vertex of three-dimensional CTV point distributions, which were manually obtained from CTV contours on the CBCT images. PTV margins were calculated using the setup errors with and without CTV shape variations for each risk CTV. Six treatment plans were retrospectively made by using the PTV margins with and without CTV shape variations for the three risk CTVs of 5 test patients. Furthermore, the treatment plans were applied to CBCT images for investigating the impact of shape variations on PTV margins. Results: The percentages of population to cover with the PTV, which satisfies the CTV D98 of 95%, with and without the shape variations were 89.7% and 74.4% for high risk, 89.7% and 76.9% for intermediate risk, 84.6% and 76.9% for low risk, respectively. Conclusion: PTV margins taking into account CTV shape variation provide significant improvement of applicable percentage of population (P < 0.05). This study suggested that CTV shape variation should be taken consideration into determination of the PTV margins.« less

Polar User’s Manual.

DTIC Science & Technology

1985-10-01

elements with BOTTON faces. 5. Thin plates may only intersect each other at the edges or corners. 6. Double points must be assigned TOP and BOTTOM sets...10 ExPONEP4T 1.7� INCNE) 1.7B.CZC (NONE) 11 YIELDC FOR IKEV PROTONS 𔃾.9C-CC! INCNE) N.-’O S(ONE) 12 AX oC/ aw FRa PROTONS ..zz0=2 KEY ±.Z:-CCZ...AEV 13 PHCTOCURPE~t Z.90-C:S Aw ..Z 1.91-,cE 1/"’sZ I& SURFACE RESISTIVITY -i.Z.C *0 OH*PS -6.d5-C1! v-Sic is SPACE DISCHARGE POT’L I.3IC*CC; VCLTS 1.Z

Shipboard Data Recording Instrumentation: Description and Functions.

DTIC Science & Technology

1979-04-26

UNCLASSIFDIED N USC- TD -56600 N Co C h. saw 0 C 4c4 CL 12 ECL -C e 4 ~.2cc Cz I 9 90 vAdO IU CAc aI U LL VV 3 .’ C.)(U 0.0 U 0 a- r "D (U_ 0 c~o EE _8.t3...nOUVIS 3!sV 0 S S 3DNV~I/ OV3M U0H NvMO 0 0 * S13S3Hd iN~muomm Sol l I SONVWIOD 3uV 33N~nios Dz0H DNIN)133 OV3 ul u 20 o- 0..a -0 Z 0i za z -Q cc - - Z0

ESR1 and ESR2 polymorphisms in the BIG 1-98 trial comparing adjuvant letrozole versus tamoxifen or their sequence for early breast cancer.

PubMed

Leyland-Jones, Brian; Gray, Kathryn P; Abramovitz, Mark; Bouzyk, Mark; Young, Brandon; Long, Bradley; Kammler, Roswitha; Dell'Orto, Patrizia; Biasi, Maria Olivia; Thürlimann, Beat; Harvey, Vernon; Neven, Patrick; Arnould, Laurent; Maibach, Rudolf; Price, Karen N; Coates, Alan S; Goldhirsch, Aron; Gelber, Richard D; Pagani, Olivia; Viale, Giuseppe; Rae, James M; Regan, Meredith M

2015-12-01

Estrogen receptor 1 (ESR1) and ESR2 gene polymorphisms have been associated with endocrine-mediated physiological mechanisms, and inconsistently with breast cancer risk and outcomes, bone mineral density changes, and hot flushes/night sweats. DNA was isolated and genotyped for six ESR1 and two ESR2 single-nucleotide polymorphisms (SNPs) from tumor specimens from 3691 postmenopausal women with hormone receptor-positive breast cancer enrolled in the BIG 1-98 trial to receive tamoxifen and/or letrozole for 5 years. Associations with recurrence and adverse events (AEs) were assessed using Cox proportional hazards models. 3401 samples were successfully genotyped for five SNPs. ESR1 rs9340799(XbaI) (T>C) variants CC or TC were associated with reduced breast cancer risk (HR = 0.82,95% CI = 0.67-1.0), and ESR1 rs2077647 (T>C) variants CC or TC was associated with reduced distant recurrence risk (HR = 0.69, 95% CI = 0.53-0.90), both regardless of the treatments. No differential treatment effects (letrozole vs. tamoxifen) were observed for the association of outcome with any of the SNPs. Letrozole-treated patients with rs2077647 (T>C) variants CC and TC had a reduced risk of bone AE (HR = 0.75, 95% CI = 0.58-0.98, P interaction = 0.08), whereas patients with rs4986938 (G>A) genotype variants AA and AG had an increased risk of bone AE (HR = 1.37, 95% CI = 1.01-1.84, P interaction = 0.07). We observed that (1) rare ESR1 homozygous polymorphisms were associated with lower recurrence, and (2) ESR1 and ESR2 SNPs were associated with bone AEs in letrozole-treated patients. Genes that are involved in estrogen signaling and synthesis have the potential to affect both breast cancer recurrence and side effects, suggesting that individual treatment strategies can incorporate not only oncogenic drivers but also SNPs related to estrogen activity.

Dose evaluation of organs at risk (OAR) cervical cancer using dose volume histogram (DVH) on brachytherapy

NASA Astrophysics Data System (ADS)

Arif Wibowo, R.; Haris, Bambang; Inganatul Islamiyah, dan

2017-05-01

Brachytherapy is one way to cure cervical cancer. It works by placing a radioactive source near the tumor. However, there are some healthy tissues or organs at risk (OAR) such as bladder and rectum which received radiation also. This study aims to evaluate the radiation dose of the bladder and rectum. There were 12 total radiation dose data of the bladder and rectum obtained from patients’ brachytherapy. The dose of cervix for all patients was 6 Gy. Two-dimensional calculation of the radiation dose was based on the International Commission on Radiation Units and Measurements (ICRU) points or called DICRU while the 3-dimensional calculation derived from Dose Volume Histogram (DVH) on a volume of 2 cc (D2cc). The radiation dose of bladder and rectum from both methods were analysed using independent t test. The mean DICRU of bladder was 4.33730 Gy and its D2cc was4.78090 Gy. DICRU and D2cc bladder did not differ significantly (p = 0.144). The mean DICRU of rectum was 3.57980 Gy and 4.58670 Gy for D2cc. The mean DICRU of rectum differed significantly from D2cc of rectum (p = 0.000). The three-dimensional method radiation dose of the bladder and rectum was higher than the two-dimensional method with ratios 1.10227 for bladder and 1.28127 for rectum. The radiation dose of the bladder and rectum was still below the tolerance dose. Two-dimensional calculation of the bladder and rectum dose was lower than three-dimension which was more accurate due to its calculation at the whole volume of the organs.

Induction and concurrent chemotherapy with high-dose thoracic conformal radiation therapy in unresectable stage IIIA and IIIB non-small-cell lung cancer: a dose-escalation phase I trial.

PubMed

Socinski, Mark A; Morris, David E; Halle, Jan S; Moore, Dominic T; Hensing, Thomas A; Limentani, Steven A; Fraser, Robert; Tynan, Maureen; Mears, Andrea; Rivera, M Patricia; Detterbeck, Frank C; Rosenman, Julian G

2004-11-01

Local control rates at conventional radiotherapy doses (60 to 66 Gy) are poor in stage III non-small-cell lung cancer (NSCLC). Dose escalation using three-dimensional thoracic conformal radiation therapy (TCRT) is one strategy to improve local control and perhaps survival. Stage III NSCLC patients with a good performance status (PS) were treated with induction chemotherapy (carboplatin area under the curve [AUC] 5, irinotecan 100 mg/m(2), and paclitaxel 175 mg/m(2) days 1 and 22) followed by concurrent chemotherapy (carboplatin AUC 2 and paclitaxel 45 mg/m(2) weekly for 7 to 8 weeks) beginning on day 43. Pre- and postchemotherapy computed tomography scans defined the initial clinical target volume (CTV(I)) and boost clinical target volume (CTV(B)), respectively. The CTV(I) received 40 to 50 Gy; the CTV(B) received escalating doses of TCRT from 78 Gy to 82, 86, and 90 Gy. The primary objective was to escalate the TCRT dose from 78 to 90 Gy or to the maximum-tolerated dose. Twenty-nine patients were enrolled (25 assessable patients; median age, 59 years; 62% male; 45% stage IIIA; 38% PS 0; and 38% > or = 5% weight loss). Induction CIP was well tolerated (with filgrastim support) and active (partial response rate, 46.2%; stable disease, 53.8%; and early progression, 0%). The TCRT dose was escalated from 78 to 90 Gy without dose-limiting toxicity. The primary acute toxicity was esophagitis (16%, all grade 3). Late toxicity consisted of grade 2 esophageal stricture (n = 3), bronchial stenosis (n = 2), and fatal hemoptysis (n = 2). The overall response rate was 60%, with a median survival time and 1-year survival probability of 24 months and 0.73 (95% CI, 0.55 to 0.89), respectively. CONCLUSION Escalation of the TCRT dose from 78 to 90 Gy in the context of induction and concurrent chemotherapy was accomplished safely in stage III NSCLC patients.

Chlorinated pool attendance, airway epithelium defects and the risks of allergic diseases in adolescents: Interrelationships revealed by circulating biomarkers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bernard, Alfred, E-mail: Alfred.bernard@uclouvain.be; Nickmilder, Marc; Dumont, Xavier

It has been suggested that allergic diseases might be epithelial disorders driven by various environmental stressors but the epidemiological evidence supporting this concept is limited. In a cross-sectional study of 835 school adolescents (365 boys; mean age, 15.5 yr), we measured the serum concentrations of Club cell protein (CC16), surfactant-associated protein D (SP-D) and of total and aeroallergen-specific IgE. We used the serum CC16/SP-D concentration ratio as an index integrating changes in the permeability (SP-D) and secretory function (CC16) of the airway epithelium. In both sexes, early swimming in chlorinated pools emerged as the most consistent and strongest predictor ofmore » low CC16 and CC16/SP-D ratio in serum. Among girls, a low CC16/SP-D ratio was associated with increased odds (lowest vs. highest tertile) for pet sensitization (OR 2.97, 95% CI 1.19–8.22) and for hay fever in subjects sensitized to pollen (OR 4.12, 95% CI 1.28–14.4). Among boys, a low CC16/SP-D ratio was associated with increased odds for house-dust mite (HDM) sensitization (OR 2.01, 95% CI 1.11–3.73), for allergic rhinitis in subjects sensitized to HDM (OR 3.52, 95% CI 1.22–11.1) and for asthma in subjects sensitized to any aeroallergen (OR 3.38, 95% CI 1.17–11.0), HDM (OR 5.20, 95% CI 1.40–24.2) or pollen (OR 5.82, 95% CI 1.51–27.4). Odds for allergic sensitization or rhinitis also increased with increasing SP-D or decreasing CC16 in serum. Our findings support the hypothesis linking the development of allergic diseases to epithelial barrier defects due to host factors or environmental stressors such as early swimming in chlorinated pools. - Highlights: • We conducted a cross-sectional study of 835 school adolescents. • The airway epithelium integrity was evaluated by measuring serum pneumoproteins. • The risk of allergic diseases was associated with a defective airway epithelium. • Childhood swimming in chlorinated pools can cause persistent epithelial alterations.« less

Membrane Localization of Human Equilibrative Nucleoside Transporter 1 in Tumor Cells May Predict Response to Adjuvant Gemcitabine in Resected Cholangiocarcinoma Patients.

PubMed

Brandi, Giovanni; Deserti, Marzia; Vasuri, Francesco; Farioli, Andrea; Degiovanni, Alessio; Palloni, Andrea; Frega, Giorgio; Barbera, Maria A; de Lorenzo, Stefania; Garajova, Ingrid; Di Marco, Mariacristina; Pinna, Antonio D; Cescon, Matteo; Cucchetti, Alessandro; Ercolani, Giorgio; D'Errico-Grigioni, Antonietta; Pantaleo, Maria A; Biasco, Guido; Tavolari, Simona

2016-05-01

The use of gemcitabine as an adjuvant modality for cholangiocarcinoma (CC) is increasing, but limited data are available on predictive biomarkers of response. Human equilibrative nucleoside transporter 1 (hENT-1) is the major transporter involved in gemcitabine intracellular uptake. This study investigated the putative predictive role of hENT-1 localization in tumor cells of CC patients undergoing treatment with adjuvant gemcitabine. Seventy-one consecutive patients with resected CC receiving adjuvant gemcitabine at our center were retrospectively analyzed by immunohistochemistry for hENT-1 localization in tumor cells. The main outcome measure was disease-free survival (DFS). Hazard ratios (HRs) of relapse and associated 95% confidence intervals (CIs) were obtained from proportional hazards regression models stratified on quintiles of propensity score. Twenty-three (32.4%) cases were negative for hENT-1, 22 (31.0%) were positive in the cytoplasm only, and 26 (36.6%) showed concomitant cytoplasm/membrane staining. Patients with membrane hENT-1 had a longer DFS (HR 0.49, 95% CI 0.24-0.99, p = .046) than those who were negative or positive only in the cytoplasm of tumor cells. Notably, the association between DFS and membrane hENT-1 was dependent on the number of gemcitabine cycles (one to two cycles: HR 0.96, 95% CI 0.34-2.68; three to four cycles: HR 0.99, 95% CI 0.34-2.90; five to six cycles: HR 0.27, 95% CI 0.10-0.77). hENT-1 localization on tumor cell membrane may predict response to adjuvant gemcitabine in CC patients receiving more than four cycles of chemotherapy. Further prospective randomized trials on larger populations are required to confirm these preliminary results, so that optimal gemcitabine-based chemotherapy may be tailored for CC patients in the adjuvant setting. Gemcitabine is becoming an increasingly used adjuvant modality in cholangiocarcinoma (CC), but limited data are available on predictive biomarkers of response. In this study, patients receiving more than four cycles of adjuvant gemcitabine and harboring Human equilibrative nucleoside transporter 1 (hENT-1, the major transporter involved in gemcitabine intracellular uptake) on tumor cell membrane had a longer disease-free survival compared with patients negative or positive for hENT-1 only in the cytoplasm of tumor cells. Overall these results may lay the basis for further prospective randomized trials based on a larger population of patients and may prove useful for tailoring appropriate gemcitabine-based chemotherapy for CC patients in the adjuvant setting. ©AlphaMed Press.

Planning study for Merkel cell carcinoma based on the relapse pattern.

PubMed

Hoeller, Ulrike; Schubert, Tina; Mueller, Thomas; Budach, Volker; Ghadjar, Pirus; Brenner, Winfried; Kuschke, Wolf

2017-04-01

To develop a technique for radiation (RT) of in-transit path ways (IT) in Merkel cell carcinoma. In the planning study, IT were ink-marked on the skin during sentinel lymphscintigraphy and wire-marked in planning-CT. Pre- and post-operative planning-CTs were acquired. The clinical target volume (CTV) included tumor bed plus safety margin, IT and draining nodes, the planning volume (PTV) the CTV plus 0.5-1cm margin. VMAT plans with 2-3 arcs were analyzed. A planning study was performed for five pts. including two pts. with primary tumor (PT) in head and neck, 1 pt. each with PT of elbow, forearm and upper leg respectively. Plans showed satisfactory PTV coverage: D mean 100%±0%, D 98% 92.4%±2.24%, homogeneity index (HI) 0.095±0.01, conformation number (CN) 0.84±0.01 and conformality index (CI) 0.95±0.01. The planning study confirms feasibility of highly conformal irradiation of IT pathways based on individualized target delineation. Currently, patients referred for non-metastatic MCC are encouraged to enroll in a prospective clinical study that evaluates the feasibility of radiation of IT pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

The dilemma of "to be or not to be": developing electronically e-health & cloud computing documents for overseas transplant patients from Taiwan organ transplant health professionals' perspective.

PubMed

Shih, F-J; Fan, Y-W; Chiu, C-M; Shih, F-Ji; Wang, S-S

2012-05-01

The development of mutually accessible e-health documents (ehD) and cloud computing (CC) for overseas organ transplant health professionals (OTHP) in two medical parties (domestic and overseas) would ensure better quality of care. This project attempted to compare pro and con arguments from the perspective of Taiwan's OTHP. A sample was obtained from three leading medical centers in Taiwan. Eighty subjects including transplant surgeons (n = 20), registered nurses (RN; n = 30), coordinating nurses (OTCN; n = 15), and e-health information and communication technologies experts (ehICTs; n = 15) participated in this research. The pros of developing ehD were: (1) better and continuous care through communication and cooperation in two parties (78%); (2) better collaborative efforts between health professionals, information technology experts in two medical parties is (74%); (3) easier retrieval and communication of personal health documents with the trustworthy OTHP in the different countries (71%); and (4) CC may help develop transplant patients medical cloud based on the collaboration between medical systems in political parties of Taiwan and mainland China (69%). The cons of developing ehD and CC included: (1) inadequate knowledge of benefits and manuals of developing ehD and CC (75%); (2) no reliable communication avenues in developing ehD and CC (73%); (3) increased workload in direct care and documentation in developing new ehD and CC (70%); (4) lack of coaching and accreditation systems in medical, electronic, and law aspects to settle discrepancies in medical diagnosis and treatment protocols between two parties (68%); and (5) lacking systematic ehD and CC plans developed by interdisciplinary teams in two parties (60%). In this initial phase, the establishment of an interdisciplinary team including transplant leaders, transplant surgeon, RN, OTCN, ehICTs, and law experts from two parties might be helpful in working out developing plans with careful monitoring mechanisms. Copyright © 2012 Elsevier Inc. All rights reserved.

$X(3873$ and $Y(4140)$ using diquark-antidiquark operators with lattice QCD

DOE PAGES

Padmanath, M.; Lang, C.  B.; Prelovsek Komelj, Sasa

2015-08-01

We perform a lattice study of charmonium-like mesons withmore » $$J^{PC}=1^{++}$$ and three quark contents $$\\bar cc \\bar du$$, $$\\bar cc(\\bar uu+\\bar dd)$$ and $$\\bar cc \\bar ss$$, where the later two can mix with $$\\bar cc$$. This simulation with $$N_f=2$$ and $$m_\\pi=266$$ MeV aims at the possible signatures of four-quark exotic states. We utilize a large basis of $$\\bar cc$$, two-meson and diquark-antidiquark interpolating fields, with diquarks in both anti-triplet and sextet color representations. A lattice candidate for X(3872) with I=0 is observed very close to the experimental state only if both $$\\bar cc$$ and $$D\\bar D^*$$ interpolators are included; the candidate is not found if diquark-antidiquark and $$D\\bar D^*$$ are used in the absence of $$\\bar cc$$. No candidate for neutral or charged X(3872), or any other exotic candidates are found in the I=1 channel. We also do not find signatures of exotic $$\\bar cc\\bar ss$$ candidates below 4.3 GeV, such as Y(4140). Possible physics and methodology related reasons for that are discussed. Along the way, we present the diquark-antidiquark operators as linear combinations of the two-meson operators via the Fierz transformations.« less

Feasibility and performance of novel software to quantify metabolically active volumes and 3D partial volume corrected SUV and metabolic volumetric products of spinal bone marrow metastases on 18F-FDG-PET/CT.

PubMed

Torigian, Drew A; Lopez, Rosa Fernandez; Alapati, Sridevi; Bodapati, Geetha; Hofheinz, Frank; van den Hoff, Joerg; Saboury, Babak; Alavi, Abass

2011-01-01

Our aim was to assess feasibility and performance of novel semi-automated image analysis software called ROVER to quantify metabolically active volume (MAV), maximum standardized uptake value-maximum (SUV(max)), 3D partial volume corrected mean SUV (cSUV(mean)), and 3D partial volume corrected mean MVP (cMVP(mean)) of spinal bone marrow metastases on fluorine-18 fluorodeoxyglucose-positron emission tomography/computerized tomography ((18)F-FDG-PET/CT). We retrospectively studied 16 subjects with 31 spinal metastases on FDG-PET/CT and MRI. Manual and ROVER determinations of lesional MAV and SUV(max), and repeated ROVER measurements of MAV, SUV(max), cSUV(mean) and cMVP(mean) were made. Bland-Altman and correlation analyses were performed to assess reproducibility and agreement. Our results showed that analyses of repeated ROVER measurements revealed MAV mean difference (D)=-0.03±0.53cc (95% CI(-0.22, 0.16)), lower limit of agreement (LLOA)=-1.07cc, and upper limit of agreement (ULOA)=1.01cc; SUV(max) D=0.00±0.00 with LOAs=0.00; cSUV(mean) D=-0.01±0.39 (95% CI(-0.15, 0.13)), LLOA=-0.76, and ULOA=0.75; cMVP(mean) D=-0.52±4.78cc (95% CI(-2.23, 1.23)), LLOA=-9.89cc, and ULOA=8.86cc. Comparisons between ROVER and manual measurements revealed volume D= -0.39±1.37cc (95% CI (-0.89, 0.11)), LLOA=-3.08cc, and ULOA=2.30cc; SUV(max) D=0.00±0.00 with LOAs=0.00. Mean percent increase in lesional SUV(mean) and MVP(mean) following partial volume correction using ROVER was 84.25±36.00% and 84.45±35.94% , respectively. In conclusion, it is feasible to estimate MAV, SUV(max), cSUV(mean), and cMVP(mean) of spinal bone marrow metastases from (18)F-FDG-PET/CT quickly and easily with good reproducibility via ROVER software. Partial volume correction is imperative, as uncorrected SUV(mean) and MVP(mean) are significantly underestimated, even for large lesions. This novel approach has great potential for practical, accurate, and precise combined structural-functional PET quantification of disease before and after therapeutic intervention.

0–0 Energies Using Hybrid Schemes: Benchmarks of TD-DFT, CIS(D), ADC(2), CC2, and BSE/GW formalisms for 80 Real-Life Compounds

PubMed Central

2015-01-01

The 0–0 energies of 80 medium and large molecules have been computed with a large panel of theoretical formalisms. We have used an approach computationally tractable for large molecules, that is, the structural and vibrational parameters are obtained with TD-DFT, the solvent effects are accounted for with the PCM model, whereas the total and transition energies have been determined with TD-DFT and with five wave function approaches accounting for contributions from double excitations, namely, CIS(D), ADC(2), CC2, SCS-CC2, and SOS-CC2, as well as Green’s function based BSE/GW approach. Atomic basis sets including diffuse functions have been systematically applied, and several variations of the PCM have been evaluated. Using solvent corrections obtained with corrected linear-response approach, we found that three schemes, namely, ADC(2), CC2, and BSE/GW allow one to reach a mean absolute deviation smaller than 0.15 eV compared to the measurements, the two former yielding slightly better correlation with experiments than the latter. CIS(D), SCS-CC2, and SOS-CC2 provide significantly larger deviations, though the latter approach delivers highly consistent transition energies. In addition, we show that (i) ADC(2) and CC2 values are extremely close to each other but for systems absorbing at low energies; (ii) the linear-response PCM scheme tends to overestimate solvation effects; and that (iii) the average impact of nonequilibrium correction on 0–0 energies is negligible. PMID:26574326

Cost-effectiveness analysis of AS04-adjuvanted human papillomavirus 16/18 vaccine compared with human papillomavirus 6/11/16/18 vaccine in the Philippines, with the new 2-dose schedule.

PubMed

Germar, Maria Julieta; Purugganan, Carrie; Bernardino, Ma Socorro; Cuenca, Benjamin; Chen, Y-Chen; Li, Xiao; Van Kriekinge, Georges; Lee, I-Heng

2017-05-04

Cervical cancer (CC) is the second leading cause of cancer death among Filipino women. Human papillomavirus (HPV) vaccination protects against CC. Two vaccines (AS04-HPV-16/18 and 4vHPV) are approved in the Philippines; they were originally developed for a 3-dose (3D) administration and have recently been approved in a 2-dose schedule (2D). This study aims to evaluate the cost-effectiveness of HPV vaccination of 13-year-old Filipino girls, in addition to current screening, in the new 2D schedule. An existing static lifetime, one-year cycle Markov cohort model was adapted to the Philippine settings to simulate the natural history of low-risk and oncogenic HPV infection, the effects of screening and vaccination of a 13-year-old girls cohort vaccinated with either the 2D-AS04-HPV-16/18 or 2D-4vHPV assuming a 100% vaccination coverage. Incremental cost, quality-adjusted life year (QALY) and cost-effectiveness were derived from these estimates. Input data were obtained from published sources and Delphi panel, using country-specific data where possible. Sensitivity analyses were performed to assess the robustness of the model. The model estimated that 2D-AS04-HPV-16/18 prevented 986 additional CC cases and 399 CC deaths (undiscounted), as well as 555 increased QALY (discounted), and save 228.1 million Philippine pesos (PHP) compared with the 2D-4vHPV. In conclusion, AS04-HPV-16/18 is shown to be dominant over 4vHPV in the Philippines, with greater estimated health benefits and lower costs.

Cost-effectiveness analysis of AS04-adjuvanted human papillomavirus 16/18 vaccine compared with human papillomavirus 6/11/16/18 vaccine in the Philippines, with the new 2-dose schedule

PubMed Central

Germar, Maria Julieta; Purugganan, Carrie; Bernardino, Ma. Socorro; Cuenca, Benjamin; Chen, Y-Chen; Li, Xiao; Van Kriekinge, Georges; Lee, I-Heng

2017-01-01

ABSTRACT Cervical cancer (CC) is the second leading cause of cancer death among Filipino women. Human papillomavirus (HPV) vaccination protects against CC. Two vaccines (AS04-HPV-16/18 and 4vHPV) are approved in the Philippines; they were originally developed for a 3-dose (3D) administration and have recently been approved in a 2-dose schedule (2D). This study aims to evaluate the cost-effectiveness of HPV vaccination of 13-year-old Filipino girls, in addition to current screening, in the new 2D schedule. An existing static lifetime, one-year cycle Markov cohort model was adapted to the Philippine settings to simulate the natural history of low-risk and oncogenic HPV infection, the effects of screening and vaccination of a 13-year-old girls cohort vaccinated with either the 2D-AS04-HPV-16/18 or 2D-4vHPV assuming a 100% vaccination coverage. Incremental cost, quality-adjusted life year (QALY) and cost-effectiveness were derived from these estimates. Input data were obtained from published sources and Delphi panel, using country-specific data where possible. Sensitivity analyses were performed to assess the robustness of the model. The model estimated that 2D-AS04-HPV-16/18 prevented 986 additional CC cases and 399 CC deaths (undiscounted), as well as 555 increased QALY (discounted), and save 228.1 million Philippine pesos (PHP) compared with the 2D-4vHPV. In conclusion, AS04-HPV-16/18 is shown to be dominant over 4vHPV in the Philippines, with greater estimated health benefits and lower costs. PMID:28075249

Optical Characterizations of Surface Polished Polycrystalline YAG (Yttrium Aluminum Garnet) Fibers (Postprint)

DTIC Science & Technology

2017-06-02

Ho:YAG fiber. 0 0.5 1 1.5 20 0.01 0.02 0.03 0.04 0.05 0.06 Input Power (W) O ut pu t P ow er (W ) Fresnel+Fresnel HR+Fresnel HR+70% R HR+90% R...1 2 3 4 5 6 7 8 9 10 11 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 Input Power (W) O ut pu t P ow er (W ) y = 0.07*x - 0.011 50% duty cycle CW linear...1979). [4] Aggarwal, R. L ., Ripin, D. J., Ochoa, J. R. and Fan, T. Y., “Measurement of thermos-optic properties of Y3Al5O12, Lu3Al5O12, YAlO3

Three-Dimensional Changes in the Midface Following Malar Calcium Hydroxyapatite Injection in a Cadaver Model.

PubMed

Gatherwright, James R; Brown, Matthew S; Katira, Kristopher M; Rowe, David J

2015-08-01

Three-dimensional (3D) changes in the midface following malar calcium hydroxyapatite (CaHa) injection have not been systematically analyzed. The authors analyzed 3D volume changes in midface and naso-labial fold (NLF) volume, as well as lateral movement in the NLF/naso-labial crease (NLC) junction following malar injection of CaHa in a cadaver model. A single surgeon injected CaHa in the supraperiosteal plane. Sequential images were obtained with the VECTRA 3D system pre- and post-1.5- and 3-cc CaHa injections. All measurements were performed by a single examiner. Injection location was verified anatomically. Injections were performed in 16 fresh cadaver hemi-faces. Maximal increases in projection were centered on the malar injection site, with associated decreases in projection and volume in the infero-medial locations. Relative mean increases in volume of 3.16 cc and 4.94 cc were observed following the 1.5-cc and 3-cc injections, respectively. There was a relative decrease in the volume of the NLF of -0.3 cc and -0.4 cc following the 1.5- and 3-cc injections, respectively. Injection of CaHa was associated with lateral movements of the NLF-NLC junction at the level of the nasal sill, philtral columns, and oral commissure, measuring 2.7, 2.5, and 1.9 mm and 2.8, 2.9, and 2.4 mm following the 1.5- and 3-cc injections, respectively. Anatomical dissection verified the location in the supraperiosteal space and within the middle malar fat pad. Following malar CaHa injection, 3D photographic analysis showed a measureable lifting effect with recruitment of ptotic tissue and lateral movement of the NLF-NLC junction in a cadaver model. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Efficient LBM visual simulation on face-centered cubic lattices.

PubMed

Petkov, Kaloian; Qiu, Feng; Fan, Zhe; Kaufman, Arie E; Mueller, Klaus

2009-01-01

The Lattice Boltzmann method (LBM) for visual simulation of fluid flow generally employs cubic Cartesian (CC) lattices such as the D3Q13 and D3Q19 lattices for the particle transport. However, the CC lattices lead to suboptimal representation of the simulation space. We introduce the face-centered cubic (FCC) lattice, fD3Q13, for LBM simulations. Compared to the CC lattices, the fD3Q13 lattice creates a more isotropic sampling of the simulation domain and its single lattice speed (i.e., link length) simplifies the computations and data storage. Furthermore, the fD3Q13 lattice can be decomposed into two independent interleaved lattices, one of which can be discarded, which doubles the simulation speed. The resulting LBM simulation can be efficiently mapped to the GPU, further increasing the computational performance. We show the numerical advantages of the FCC lattice on channeled flow in 2D and the flow-past-a-sphere benchmark in 3D. In both cases, the comparison is against the corresponding CC lattices using the analytical solutions for the systems as well as velocity field visualizations. We also demonstrate the performance advantages of the fD3Q13 lattice for interactive simulation and rendering of hot smoke in an urban environment using thermal LBM.

Racial disparity in death from colorectal cancer: does vitamin D deficiency contribute?

PubMed

Fiscella, Kevin; Winters, Paul; Tancredi, Daniel; Hendren, Samantha; Franks, Peter

2011-03-01

The reasons blacks have higher mortality rates from colorectal cancer (CRC) than non-Hispanic whites are not fully understood. Blacks have higher rates of vitamin D deficiency than non-Hispanic whites, and vitamin D deficiency has been associated with CRC. The authors of this report investigated the association of vitamin D deficiency with excess risk for CRC mortality for blacks in the Third National Health and Nutrition Examination Survey (NHANES III) that was conducted from 1988 to 1994. The association between serum 25(OH)D levels and CRC mortality and its contribution to elevated risk among blacks were studied using baseline data from NHANES III and CRC mortality data through 2006 from the National Death Index. By using survival models, the adjusted risk of death from CRC for African Americans was examined with and without adjusting for vitamin D deficiency, which was defined as an 25(OH)D level <20 ng/dL. Black race (hazard ratio [HR], 2.03; 95% confidence interval [95% CI], 1.04-3.95), age (HR, 1.12; 95% CI, 1.09-1.15), not having health insurance (HR, 2.45; 95% CI, 1.12-5.36), and a history of CRC (HR, 7.22; 95% CI, 2.12-24.6) predicted CRC mortality. When added to the model, vitamin D deficiency was associated significantly with CRC mortality (HR, 2.11; 95% CI, 1.11-4.00), and the effect of race was decreased (HR, 1.60; 95% CI, 0.87-2.93); the 40% attenuation was statistically significant (F(1) (,49) = 4.85; P = .03). Similar results were observed when participants who had a history of CRC were excluded from the analysis. The current findings were consistent with the hypothesis that vitamin D deficiency contributes to excess African-American mortality from CRC. Cancer 2011. Copyright © 2010 American Cancer Society.

Peak Oxygen Uptake during and after Long-duration Space Flight

NASA Technical Reports Server (NTRS)

Moore, Alan D., Jr.; Downs, Meghan E.; Lee, Stuart M. C.; Feiveson, Alan H.; Knudsen, Poul; Evetts, Simon N.; Ploutz-Snyder, Lori

2014-01-01

Aerobic capacity (VO2peak) previously has not been measured during or after long-duration spaceflight. PURPOSE: To measure VO2peak and submaximal exercise responses during and after International Space Station (ISS) missions. METHODS: Astronauts (9 M, 5 F: 49 +/- 5 yr, 175 +/- 7 cm, 77.2 +/- 15.1 kg, 40.6 +/- 6.4 mL/kg/min [mean +/-SD]) performed graded peak cycle tests 90 days before spaceflight, 15 d (FD15) after launch and every 30 d thereafter during flight, and 1 (R+1), 10 (R+10), and 30 d (R+30) after landing. Oxygen consumption (VO2) and heart rate (HR) were measured from rest to peak exercise, while cardiac output (Q), stroke volume (SV), and arterial-venous oxygen difference (a-vO2diff) were measured only during rest and submaximal exercise. Data were analyzed using mixed-model linear regression. Body mass contributed significantly to statistical models, and thus results are reported as modeled estimates for an average subject. RESULTS: Early inflight (FD15) VO2peak was 17% lower (95% CI = - 22%, -13%) than preflight. VO2peak increased during spaceflight (0.001 L/min/d, P = 0.02) but did not return to preflight levels. On R+1 VO2peak was 15% (95% CI = -19%, -10%) lower than preflight but recovered to within 2% of preflight by R+30 (95% CI = -6%, +3%). Peak HR was not significantly different from preflight at any time. Inflight submaximal VO2 and a-vO2diff were generally lower than preflight, but the Q vs. VO2 slope was unchanged. In contrast, the SV vs. VO2 slope was lower (P < 0.001), primarily due to elevated SV at rest, and the HR vs. VO2 slope was greater (P < 0.001), largely due to elevated HR during more intense exercise. On R+1 although the relationships between VO2 and Q, SV, and HR were not statistically different than preflight, resting and submaximal exercise SV was lower (P < 0.001), resting and submaximal exercise HR was higher (P < 0.002), and a-vO2diff was unchanged. HR and SV returned to preflight levels by R+30. CONCLUSION: In the average astronaut VO2peak was reduced during spaceflight and immediately after landing but factors contributing to lower VO2peak may be different during spaceflight and recovery. Maintaining Q while VO2 is reduced inflight may be suggestive of an elevated blood flow to vascular beds other than exercising muscles, but decreased SV after flight likely reduces Q at peak exertion.

Improved outcome with pulses of vincristine and corticosteroids in continuation therapy of children with average risk acute lymphoblastic leukemia (ALL) and lymphoblastic non-Hodgkin lymphoma (NHL): report of the EORTC randomized phase 3 trial 58951.

PubMed

De Moerloose, Barbara; Suciu, Stefan; Bertrand, Yves; Mazingue, Françoise; Robert, Alain; Uyttebroeck, Anne; Yakouben, Karima; Ferster, Alice; Margueritte, Geneviève; Lutz, Patrick; Munzer, Martine; Sirvent, Nicolas; Norton, Lucilia; Boutard, Patrick; Plantaz, Dominique; Millot, Frederic; Philippet, Pierre; Baila, Liliana; Benoit, Yves; Otten, Jacques

2010-07-08

The European Organisation for Research and Treatment of Cancer 58951 trial for children with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) addressed 3 randomized questions, including the evaluation of dexamethasone (DEX) versus prednisolone (PRED) in induction and, for average-risk patients, the evaluation of vincristine and corticosteroid pulses during continuation therapy. The corticosteroid used in the pulses was that assigned at induction. Overall, 411 patients were randomly assigned: 202 initially randomly assigned to PRED (60 mg/m(2)/d), 201 to DEX (6 mg/m(2)/d), and 8 nonrandomly assigned to PRED. At a median follow-up of 6.3 years, there were 19 versus 34 events for pulses versus no pulses; 6-year disease-free survival (DFS) rate was 90.6% (standard error [SE], 2.1%) and 82.8% (SE, 2.8%), respectively (hazard ratio [HR] = 0.54; 95% confidence interval, 0.31-0.94; P = .027). The effect of pulses was similar in the PRED (HR = 0.56) and DEX groups (HR = 0.59) but more pronounced in girls (HR = 0.24) than in boys (HR = 0.71). Grade 3 to 4 hepatic toxicity was 30% versus 40% in pulses versus no pulses group and grade 2 to 3 osteonecrosis was 4.4% versus 2%. For average-risk patients treated according to Berlin-Frankfurt-Muenster-based protocols, pulses should become a standard component of therapy.

A novel aldose-aldose oxidoreductase for co-production of D-xylonate and xylitol from D-xylose with Saccharomyces cerevisiae.

PubMed

Wiebe, Marilyn G; Nygård, Yvonne; Oja, Merja; Andberg, Martina; Ruohonen, Laura; Koivula, Anu; Penttilä, Merja; Toivari, Mervi

2015-11-01

An open reading frame CC1225 from the Caulobacter crescentus CB15 genome sequence belongs to the Gfo/Idh/MocA protein family and has 47 % amino acid sequence identity with the glucose-fructose oxidoreductase from Zymomonas mobilis (Zm GFOR). We expressed the ORF CC1225 in the yeast Saccharomyces cerevisiae and used a yeast strain expressing the gene coding for Zm GFOR as a reference. Cell extracts of strains overexpressing CC1225 (renamed as Cc aaor) showed some Zm GFOR type of activity, producing D-gluconate and D-sorbitol when a mixture of D-glucose and D-fructose was used as substrate. However, the activity in Cc aaor expressing strain was >100-fold lower compared to strains expressing Zm gfor. Interestingly, C. crescentus AAOR was clearly more efficient than the Zm GFOR in converting in vitro a single sugar substrate D-xylose (10 mM) to xylitol without an added cofactor, whereas this type of activity was very low with Zm GFOR. Furthermore, when cultured in the presence of D-xylose, the S. cerevisiae strain expressing Cc aaor produced nearly equal concentrations of D-xylonate and xylitol (12.5 g D-xylonate l(-1) and 11.5 g D-xylitol l(-1) from 26 g D-xylose l(-1)), whereas the control strain and strain expressing Zm gfor produced only D-xylitol (5 g l(-1)). Deletion of the gene encoding the major aldose reductase, Gre3p, did not affect xylitol production in the strain expressing Cc aaor, but decreased xylitol production in the strain expressing Zm gfor. In addition, expression of Cc aaor together with the D-xylonolactone lactonase encoding the gene xylC from C. crescentus slightly increased the final concentration and initial volumetric production rate of both D-xylonate and D-xylitol. These results suggest that C. crescentus AAOR is a novel type of oxidoreductase able to convert the single aldose substrate D-xylose to both its oxidized and reduced product.

Plant-Based Dietary Patterns and Incidence of Type 2 Diabetes in US Men and Women: Results from Three Prospective Cohort Studies.

PubMed

Satija, Ambika; Bhupathiraju, Shilpa N; Rimm, Eric B; Spiegelman, Donna; Chiuve, Stephanie E; Borgi, Lea; Willett, Walter C; Manson, JoAnn E; Sun, Qi; Hu, Frank B

2016-06-01

Plant-based diets have been recommended to reduce the risk of type 2 diabetes (T2D). However, not all plant foods are necessarily beneficial. We examined the association of an overall plant-based diet and hypothesized healthful and unhealthful versions of a plant-based diet with T2D incidence in three prospective cohort studies in the US. We included 69,949 women from the Nurses' Health Study (1984-2012), 90,239 women from the Nurses' Health Study 2 (1991-2011), and 40,539 men from the Health Professionals Follow-Up Study (1986-2010), free of chronic diseases at baseline. Dietary data were collected every 2-4 y using a semi-quantitative food frequency questionnaire. Using these data, we created an overall plant-based diet index (PDI), where plant foods received positive scores, while animal foods (animal fats, dairy, eggs, fish/seafood, poultry/red meat, miscellaneous animal-based foods) received reverse scores. We also created a healthful plant-based diet index (hPDI), where healthy plant foods (whole grains, fruits, vegetables, nuts, legumes, vegetable oils, tea/coffee) received positive scores, while less healthy plant foods (fruit juices, sweetened beverages, refined grains, potatoes, sweets/desserts) and animal foods received reverse scores. Lastly, we created an unhealthful plant-based diet index (uPDI) by assigning positive scores to less healthy plant foods and reverse scores to healthy plant foods and animal foods. We documented 16,162 incident T2D cases during 4,102,369 person-years of follow-up. In pooled multivariable-adjusted analysis, both PDI and hPDI were inversely associated with T2D (PDI: hazard ratio [HR] for extreme deciles 0.51, 95% CI 0.47-0.55, p trend < 0.001; hPDI: HR for extreme deciles 0.55, 95% CI 0.51-0.59, p trend < 0.001). The association of T2D with PDI was considerably attenuated when we additionally adjusted for body mass index (BMI) categories (HR 0.80, 95% CI 0.74-0.87, p trend < 0.001), while that with hPDI remained largely unchanged (HR 0.66, 95% CI 0.61-0.72, p trend < 0.001). uPDI was positively associated with T2D even after BMI adjustment (HR for extreme deciles 1.16, 95% CI 1.08-1.25, p trend < 0.001). Limitations of the study include self-reported diet assessment, with the possibility of measurement error, and the potential for residual or unmeasured confounding given the observational nature of the study design. Our study suggests that plant-based diets, especially when rich in high-quality plant foods, are associated with substantially lower risk of developing T2D. This supports current recommendations to shift to diets rich in healthy plant foods, with lower intake of less healthy plant and animal foods.

Resistance to densification, tensile strength and capsule-filling performance of some pharmaceutical diluents.

PubMed

Nikolakakis, I; Aragon, O B; Malamataris, S

1998-07-01

The purpose of this study was to compare some indicators of capsule-filling performance, as measured by tapped density under different conditions, and elucidate possible quantitative relationships between variation of capsule fill-weight (%CV) and gravitational and inter-particle forces (attractive or frictional) derived from measurements of particle size, true density, low compression and tensile strength. Five common pharmaceutical diluents (lactose, maize starch, talc, Emcocel and Avicel) were investigated and two capsule-filling methods (pouring powder and dosator nozzle) were employed. It was found that for the pouring-type method the appropriateness of Hausner's ratio (HR), Carr's compressibility index (CC%) and Kawakita's constant (alpha) as indicators of capsule fill-weight variation decreases in the order alpha > CC% > HR; the appropriateness of these indicators also decreases with increasing cylinder size and with impact velocity during tapping. For the dosator-type method the appropriateness of the indicators decreases in the order HR > CC% > alpha, the opposite of that for the pouring-type method; the appropriateness of the indicators increases with decreasing cylinder size and impact velocity. The relationship between %CV and the ratio of inter-particle attractive to gravitational forces calculated from measurements of particle size and true density (Fvdw/Wp) was more significant for the pouring-type capsule-filling method. For the dosator-type method a significant relationship (1% level) was found between %CV and the product of Fvdw/Wp and a function expressing the increase, with packing density (p(f)), in the ratio of frictional to attractive inter-particle forces derived from compression (P) and tensile-strength (T) testing, d(log(P/T))/d(p(f)). The value of tapped density in predictions of capsule-filling performance is affected by the testing conditions in a manner depending on the filling method applied. For the pouring-type method predictions can be based on the ratio of attractive (inter-particle) to gravitational forces, whereas for the dosator-type method the contribution of frictional and attractive forces should, because of packing density change, also be taken into account.

Calcium Plus Vitamin D Supplementation and the Risk of Nonmelanoma and Melanoma Skin Cancer: Post Hoc Analyses of the Women's Health Initiative Randomized Controlled Trial

PubMed Central

Tang, Jean Y.; Fu, Teresa; LeBlanc, Erin; Manson, JoAnn E.; Feldman, David; Linos, Eleni; Vitolins, Mara Z.; Zeitouni, Nathalie C.; Larson, Joseph; Stefanick, Marcia L.

2011-01-01

Purpose In light of inverse relationships reported in observational studies of vitamin D intake and serum 25-hydroxyvitamin D levels with risk of nonmelanoma skin cancer (NMSC) and melanoma, we evaluated the effects of vitamin D combined with calcium supplementation on skin cancer in a randomized placebo-controlled trial. Methods Postmenopausal women age 50 to 79 years (N = 36,282) enrolled onto the Women's Health Initiative (WHI) calcium/vitamin D clinical trial were randomly assigned to receive 1,000 mg of elemental calcium plus 400 IU of vitamin D3 (CaD) daily or placebo for a mean follow-up period of 7.0 years. NMSC and melanoma skin cancers were ascertained by annual self-report; melanoma skin cancers underwent physician adjudication. Results Neither incident NMSC nor melanoma rates differed between treatment (hazard ratio [HR], 1.02; 95% CI, 0.95 to 1.07) and placebo groups (HR, 0.86; 95% CI, 0.64 to 1.16). In subgroup analyses, women with history of NMSC assigned to CaD had a reduced risk of melanoma versus those receiving placebo (HR, 0.43; 95% CI, 0.21 to 0.90; Pinteraction = .038), which was not observed in women without history of NMSC. Conclusion Vitamin D supplementation at a relatively low dose plus calcium did not reduce the overall incidence of NMSC or melanoma. However, in women with history of NMSC, CaD supplementation reduced melanoma risk, suggesting a potential role for calcium and vitamin D supplements in this high-risk group. Results from this post hoc subgroup analysis should be interpreted with caution but warrant additional investigation. PMID:21709199

Molecular cloning, characterization and expression analysis of TLR9, MyD88 and TRAF6 genes in common carp (Cyprinus carpio).

PubMed

Kongchum, Pawapol; Hallerman, Eric M; Hulata, Gideon; David, Lior; Palti, Yniv

2011-01-01

Induction of innate immune pathways is critical for early host defense, but there is limited understanding of how teleost fishes recognize pathogen molecules and activate these pathways. In mammals, cells of the innate immune system detect pathogenic molecular structures using pattern recognition receptors (PRRs). TLR9 functions as a PRR that recognizes CpG motifs in bacterial and viral DNA and requires adaptor molecules MyD88 and TRAF6 for signal transduction. Here we report full-length cDNA isolation, structural characterization and tissue mRNA expression analysis of the common carp (cc) TLR9, MyD88 and TRAF6 gene orthologs. The ccTLR9 open-reading frame (ORF) is predicted to encode a 1064-amino acid (aa) protein. We found that MyD88 and TRAF6 genes are duplicated in common carp. This is the first report of TRAF6 duplication in a vertebrate genome and stronger evidence in support of MyD88 duplication is provided. The ccMyD88a and b ORFs are predicted to encode 288-aa and 284-aa peptides, respectively. They share 91% aa sequence identity between paralogs. The ccTRAF6a and b ORFs are both predicted to encode 543-aa peptides sharing 95% aa sequence identity between paralogs. The ccTLR9 gene is contained in a single large exon. The ccMyD88a and ccMyD88b coding sequences span five exons. The TRAF6b gene spans six exons. PCR amplification to obtain the entire coding sequence of ccTRAF6a gene was not successful. The 2104-bp fragment amplified covers the 3' end of the gene and it contains a partial sequence of one exon and three complete exons. The predicated protein domains of the ccTLR9, ccMyD88 and ccTRAF6 are conserved and resemble orthologs from other vertebrates. Real-time quantitative PCR assays of the ccTLR9, MyD88a and b, and TRAF6a and b gene transcripts in healthy common carp indicated that mRNA expression varied between tissues. Differential expression of duplicate copies were found for ccMyD88 and ccTRAF6 in white and red muscle tissues, suggesting that paralogs may have evolved and attained a new function. The genomic information we describe in this paper provides evidence of sequence and structural conservation of immune response genes in common carp. Published by Elsevier Ltd.

Search at BaBar for D^0--\\overlineD^0 Mixing using Semileptonic Decays.

NASA Astrophysics Data System (ADS)

Flood, Kevin

2004-05-01

Based on a 87 fb-1 dataset acquired by the Babar experiment running on and near the Υ(4S) from 1999-2002, a new upper limit is set on the rate of D^0--\\overlineD^0 mixing using the decay modes D^*+ arrow π^+ D^0, D^0 arrow [K / K^*]eν (+c.c.). These modes offer unambiguous initial and final-state charm flavor tags, and allow the combined use of the D^0 lifetime and D^*+--D^0 mass difference (Δ M) in a global likelihood fit. The high-statistics sample of reconstructed unmixed semileptonic D^0 decays is used to model Δ M and the time-dependence of mixed events directly from the data. Neural networks are used both to select events and to fully reconstruct the D^0. The current world-best published limit on semileptonic charm mixing is 5x10-3 (90% C.L.) (E791).

SU-D-207-03: Development of 4D-CBCT Imaging System with Dual Source KV X-Ray Tubes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakamura, M; Ishihara, Y; Matsuo, Y

Purpose: The purposes of this work are to develop 4D-CBCT imaging system with orthogonal dual source kV X-ray tubes, and to determine the imaging doses from 4D-CBCT scans. Methods: Dual source kV X-ray tubes were used for the 4D-CBCT imaging. The maximum CBCT field of view was 200 mm in diameter and 150 mm in length, and the imaging parameters were 110 kV, 160 mA and 5 ms. The rotational angle was 105°, the rotational speed of the gantry was 1.5°/s, the gantry rotation time was 70 s, and the image acquisition interval was 0.3°. The observed amplitude of infraredmore » marker motion during respiration was used to sort each image into eight respiratory phase bins. The EGSnrc/BEAMnrc and EGSnrc/DOSXYZnrc packages were used to simulate kV X-ray dose distributions of 4D-CBCT imaging. The kV X-ray dose distributions were calculated for 9 lung cancer patients based on the planning CT images with dose calculation grid size of 2.5 x 2.5 x 2.5 mm. The dose covering a 2-cc volume of skin (D2cc), defined as the inner 5 mm of the skin surface with the exception of bone structure, was assessed. Results: A moving object was well identified on 4D-CBCT images in a phantom study. Given a gantry rotational angle of 105° and the configuration of kV X-ray imaging subsystems, both kV X-ray fields overlapped at a part of skin surface. The D2cc for the 4D-CBCT scans was in the range 73.8–105.4 mGy. Linear correlation coefficient between the 1000 minus averaged SSD during CBCT scanning and D2cc was −0.65 (with a slope of −0.17) for the 4D-CBCT scans. Conclusion: We have developed 4D-CBCT imaging system with dual source kV X-ray tubes. The total imaging dose with 4D-CBCT scans was up to 105.4 mGy.« less

A dosimetric phantom study of thoracic radiotherapy based on three-dimensional modeling of mediastinal lymph nodes

PubMed Central

Zhang, Ji-Bin; Zhao, Li-Rong; Cui, Tian-Xiang; Chen, Xie-Wan; Yang, Qiao; Zhou, Yi-Bing; Chen, Zheng-Tang; Zhang, Shao-Xiang; Sun, Jian-Guo

2018-01-01

The aim of the present study was to investigate the optimal strategy and dosimetric measurement of thoracic radiotherapy based on three-dimensional (3D) modeling of mediastinal lymph nodes (MLNs). A 3D model of MLNs was constructed from a Chinese Visible Human female dataset. Image registration and fusion between reconstructed MLNs and original chest computed tomography (CT) images was conducted in the Eclipse™ treatment planning system (TPS). There were three plans, including 3D conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT), which were designed based on 10 cases of simulated lung lesions (SLLs) and MLNs. The quality of these plans was evaluated via examining indexes, including conformity index (CI), homogeneity index and clinical target volume (CTV) coverage. Dose-volume histogram analysis was performed on SLL, MLNs and organs at risk (OARs). A Chengdu Dosimetric Phantom (CDP) was then drilled at specific MLNs according to 20 patients with thoracic tumors and of a medium-build. These plans were repeated on fused MLNs and CDP CT images in the Eclipse™ TPS. Radiation doses at the SLLs and MLNs of the CDP were measured and compared with calculated doses. The established 3D MLN model demonstrated the spatial location of MLNs and adjacent structures. Precise image registration and fusion were conducted between reconstructed MLNs and the original chest CT or CDP CT images. IMRT demonstrated greater values in CI, CTV coverage and OAR (lungs and spinal cord) protection, compared with 3D-CRT and VMAT (P<0.05). The deviation between the measured and calculated doses was within ± 10% at SLL, and at the 2R and 7th MLN stations. In conclusion, the 3D MLN model can benefit plan optimization and dosimetric measurement of thoracic radiotherapy, and when combined with CDP, it may provide a tool for clinical dosimetric monitoring. PMID:29556300

Mechanism-based inhibition of HsaD: a C-C bond hydrolase essential for survival of Mycobacterium tuberculosis in macrophage.

PubMed

Ryan, Ali; Keany, Sebastian; Eleftheriadou, Olga; Ballet, Romain; Cheng, Hung-Yuan; Sim, Edith

2014-01-01

Mycobacterium tuberculosis remains the leading cause of death by a bacterial pathogen worldwide. Increasing prevalence of multidrug-resistant organisms means prioritizing identification of targets for antituberculars. 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate hydrolase (HsaD), part of the cholesterol metabolism operon, is vital for survival within macrophage. The C-C bond hydrolase, HsaD, has a serine protease-like catalytic triad. We tested a range of serine protease and esterase inhibitors for their effects on HsaD activity. As well as providing a potential starting point for drug development, the data provides evidence for the mechanism of C-C bond hydrolysis. This screen also provides a route to initiate development of fragment-based inhibitors. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Influence of water stress on the carbon isotopic composition of modern plants: Implications for C4 plant appearance in Indian subcontinent

NASA Astrophysics Data System (ADS)

Basu, S.; Ghosh, S.; Sanyal, P.

2016-12-01

The carbon isotopic composition (d13C) of modern terrestrial plants (C3 and C4) provides the baseline to understand past vegetation composition, paleodietary changes and animal migration etc. Accuracy of past environment reconstruction is dependent on the end-member d13C values of plants which found to vary in regional scale. For instance, the d13C values of Indian C3 plants (d13CC3) are 1 to 2‰ more negative compared to global mean. As observed, most of the previous database is devoid of samples from tropical monsoon realm (like India) and the difference between global and regional mean may introduce errors in vegetation reconstruction. To constrain end-member d13CC3 value, published and newly generated results from wide range of mean annual precipitation (MAP: 1-11,700 mm) are compiled which is ca. 1.5 higher in sample size (n=2440) compared to previous database. Using logarithmic function, new relationship between d13C value and MAP (d13CC3 (‰) =20.1585(0.3061)-1.1276(0.0489)ln(MAP+700)) is proposed. The modeled mean d13CC3 value (-28.9‰) is close to average d13CC3 value for Indian plants (-29.1‰) and suggests the importance of vegetation from low-latitudinal tropical region in global compilation. It was observed that C3 plants, on a global scale, are less sensitive to wet climate relative to dry condition. This inference is in agreement with the paleoclimatic data from Indian subcontinent for the late Quaternary period. Despite well established correlation between d13CC3 value and MAP, previous investigation from Indian subcontinent used fixed end-member values to reconstruct past vegetation and total change in the d13C value of proxies was attributed to changes in relative abundance of C3 and C4 plants. Using region-specific mean d13C value of plants, after correcting for changing MAP and error propagation, existence of C4 before ca. 11 Ma plant is observed; earlier to previous reported timing.

A developmental approach to dimensional expression of psychopathology in child and adolescent offspring of parents with bipolar disorder.

PubMed

Morón-Nozaleda, María Goretti; Díaz-Caneja, Covadonga M; Rodríguez-Toscano, Elisa; Arango, Celso; Castro-Fornieles, Josefina; de la Serna, Elena; Espliego, Ana; Sanchez-Gistau, Vanessa; Romero, Soledad; Baeza, Immaculada; Sugranyes, Gisela; Moreno, Carmen; Moreno, Dolores

2017-10-01

The aim of this is to describe psychopathology, functioning and symptom dimensions accounting for subthreshold manifestations and developmental status in child and adolescent offspring of parents with bipolar disorder ("high-risk offspring"). The study population comprised 90 high-risk offspring (HR-offspring) and 107 offspring of community control parents (CC-offspring). Direct clinical observations and parental and offspring reports based on selected standardized clinical scales were used to assess offspring threshold and subthreshold diagnoses, symptoms and functioning. All outcomes were compared between the whole HR-offspring and CC-offspring samples and then by developmental status. After controlling for potential confounders, HR-offspring showed significantly poorer adjustment for childhood (r = 0.18, p = 0.014) and adolescence (r = 0.21, p = 0.048) than CC-offspring, as well as more emotional problems (r = 0.24, p = 0.001) and higher depression scores (r = 0.16, p = 0.021). As for differences in lifetime categorical diagnoses (threshold and subthreshold) between HR-offspring and CC-offspring, the prevalence of disruptive disorders was higher in pre-pubertal HR-offspring (OR 12.78 [1.45-112.42]), while prevalence of mood disorders was higher in post-pubertal HR-offspring (OR 3.39 [1.14-10.06]). Post-pubertal HR-offspring presented more prodromal (r = 0.40, p = 0.001), negative (r = 0.38, p = 0.002), manic (r = 0.22, p = 0.035) and depressive (r = 0.23, p = 0.015) symptoms than pre-pubertal HR-offspring, as well as more peer relationship problems (r = 0.31, p = 0.004), poorer childhood adjustment (r = 0.22, p = 0.044) and worse current psychosocial functioning (r = 0.27, p = 0.04). Externalizing psychopathology is more prevalent in pre-pubertal HR-offspring, while depressive and prodromal symptoms leading to functional impairment are more prominent in post-pubertal HR-offspring. Developmental approaches and dimensional measures may be useful for identifying children at high risk of developing bipolar disorder and help guide specific preventive strategies.

Psychological morbidity and facial volume in HIV lipodystrophy: quantification of treatment outcome.

PubMed

Nelson, Lisa; Stewart, Kenneth J

2012-04-01

HIV lipoatrophy is a stigmatizing condition associated with significant psychological morbidity. The aim of this study was to evaluate change in facial volume and psychological morbidity following treatment with autologous fat, Sculptra and Bio-alcamid. HIV LD patients were treated based on a clinical assessment in a prospective, observational study. 3-D images were obtained pre-operatively then at 2, 6 and 12 months post-operatively using the DI3D system. Volume changes were measured using DI3D software. The DAS-24 and HADS were used to assess psychological morbidity at similar time intervals. Forty-eight patients with HIV LD were treated: 16 patients had Bio-alcamid, 20 patients received Sculptra and 12 patients underwent fat transfer. The mean injected volume of Bio-alcamid was 25.5 cc which was comparable to the measured volume change at follow-up. The mean injected volume of fat was 20.1 cc, which did not differ from the measured volumes at 2 months. There was a mean reduction in measured volume change to11.2 cc at 6 months and 10 cc at 12 months. For Sculptra, the mean volume change compared to baseline was 8.7 cc at 2 months, increasing to 12.6 cc at 6 months and 12.3 cc at 12 months. ANOVA tests demonstrated no difference in psychological outcomes between groups. There was a significant improvement in DAS-24 scores compared to baseline for all 3 groups. No correlation between change in facial volume and psychological measures was demonstrated. Change in 3-D measured facial volume for all 3 groups was seen. Treatment was associated with improved body image perception. Copyright © 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Health-related quality of life measured using the EQ-5D-5L: South Australian population norms.

PubMed

McCaffrey, Nikki; Kaambwa, Billingsley; Currow, David C; Ratcliffe, Julie

2016-09-20

Although a five level version of the widely-used EuroQol 5 dimensions (EQ-5D) instrument has been developed, population norms are not yet available for Australia to inform the future valuation of health in economic evaluations. The aim of this study was to estimate HrQOL normative values for the EQ-5D-5L preference-based measure in a large, randomly selected, community sample in South Australia. The EQ-5D-5L instrument was included in the 2013 South Australian Health Omnibus Survey, an interviewer-administered, face-to-face, cross-sectional survey. Respondents rated their level of impairment across dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and global health rating on a visual analogue scale (EQ-VAS). Utility scores were derived using the newly-developed UK general population-based algorithm and relationships between utility and EQ-VAS scores and socio-demographic factors were also explored using multivariate regression analyses. Ultimately, 2,908 adults participated in the survey (63.4 % participation rate). The mean utility and EQ-VAS scores were 0.91 (95 CI 0.90, 0.91) and 78.55 (95 % CI 77.95, 79.15), respectively. Almost half of respondents reported no problems across all dimensions (42.8 %), whereas only 7.2 % rated their health >90 on the EQ-VAS (100 = the best health you can imagine). Younger age, male gender, longer duration of education, higher annual household income, employment and marriage/de facto relationships were all independent, statistically significant predictors of better health status (p < 0.01) measured with the EQ-VAS. Only age and employment status were associated with higher utility scores, indicating fundamental differences between these measures of health status. This is the first Australian study to apply the EQ-5D-5L in a large, community sample. Overall, findings are consistent with EQ-5D-5L utility and VAS scores reported for other countries and indicate that the majority of South Australian adults report themselves in full health. When valuing health in Australian economic evaluations, the utility population norms can be used to estimate HrQOL. More generally, the EQ-VAS score may be a better measure of population health given the smaller ceiling effect and broader coverage of HrQOL dimensions. Further research is recommended to update EQ-5D-5L population norms using the Australian general population specific scoring algorithm once this becomes publically available.

Optical progression characteristics of an interesting natural downward bipolar lightning flash

NASA Astrophysics Data System (ADS)

Chen, Luwen; Lu, Weitao; Zhang, Yijun; Wang, Daohong

2015-01-01

high-speed cameras, Lightning Attachment Process Observation Systems, and fast and slow electrical antennas, we documented a downward bipolar lightning flash that contained one first positive stroke with a peak current of 142 kA and five subsequent negative strokes hitting on a 90 m tall structure on 29 July 2010 in Guangzhou City, China. All the six strokes propagated along the same viewed channel established by the first positive return stroke. The leader which preceded the positive return stroke propagated downward without any branches at a two-dimensional (2-D) speed of 2.5 × 106 m/s. An upward connecting leader with a length of about 80 m was observed in response to the downward positive leader. The 10-90% risetimes of the return strokes' optical pulses ranged from 2.2 µs to 3.2 µs, while the widths from the 10% wavefront to the 50% wave tail ranged from 56.5 µs to 83.1 µs, and the half peak widths ranged from 53.4 µs to 81.6 µs. All the return strokes exhibited similar speeds, ranging from 1.0 × 108 m/s to 1.3 × 108 m/s. Each of the return strokes was followed by a continuing current stage (CC). The first positive stroke CC lasted more than 150 ms, much larger than all the subsequent negative stroke CC, ranging from 13 ms to 70 ms.

24-HOUR DIFFUSIVE SAMPLING OF 1,3-BUTADIENE IN AIR ONTO CARBOPACK X SOLID ADSORBENT FOLLOWED BY THERMAL DESORPTION/GC/MS ANALYSIS - FEASIBILITY STUDY

EPA Science Inventory

Diffusive sampling of 1,3-butadiene for 24 hr onto the graphitic adsorbent Carbopack X packed in a stainless steel tube badge (6.3 mm o.d., 5 mm i.d., and 90 mm in length) with analysis by thermal desorption/gas chromatography (GC)/mass spectrometry (MS) has been evaluated in con...

Range Finding 14-Day and 90-Day Subchronic Feeding Studies with N,N-Dipropylcyclohexanecarboxamide in Rats. Phase 4.

DTIC Science & Technology

1986-12-01

Y CLS$1F-.AT N OF THIS...1 MN cD jO 0 -O Ocn00 ~ c" W) 400’ rno n + a9 .9 .i , vi 4 -W cm C44. y c 000 CD %D 1% CD-. U 4 CnN C! - N ON N N TV o 00 e~. r, ML 4r WL ne 0...to N D N4 ’aN N " Nf Y N Nm 00 1C’ bq D Wc iG f". rC W C4 No N N D On ’-0 0 0 f" .4l cc W.4 LoP doE N 04 In Ins. +. V. 0 0 fn 10 C Go 0D C 00’ 4o

Lymphadenectomy extent and survival of patients with gastric carcinoma: a systematic review and meta-analysis of time-to-event data from randomized trials.

PubMed

Mocellin, Simone; Nitti, Donato

2015-05-01

The extent of lymph node dissection in patients with resectable non-metastatic primary carcinoma of the stomach is still a controversial matter of debate, with special regard to its effect on survival. We conducted a systematic review and meta-analysis of time-to-event data from randomized controlled trials (RCTs) comparing the three main types of lymphadenectomy (D1, D2, and D3) for gastric cancer. Hazard ratio (HR) was considered the effect measure for both overall (OS), disease-specific (DSS) and disease-free survival (DFS). The quality of the available evidence was assessed using the GRADE system. Eight RCTs enrolling 2515 patients were eligible. The meta-analysis of four RCTs (n=1599) showed a significant impact of D2 versus D1 lymphadenectomy on DSS (summary HR=0.807, CI: 0.705-0.924, P=0.002), the corresponding number-to-treat being equal to ten. This effect remained clinically valuable even after adjustment for postoperative mortality. However, the quality of evidence was graded as moderate due to inconsistency issues. When OS and DFS were considered, the meta-analysis of respectively five (n=1653) and three RCTs (n=1332) found no significant difference between D2 and D1 lymph node dissection (summary HR=0.911, CI: 0.708-1.172, P=0.471, and summary HR=0.946, CI: 0.840-1.066, P=0.366, respectively). However, at subgroup analysis D2 type resulted superior to D1 type lymphadenectomy in terms of OS considering the two RCTs carried out in Eastern countries (summary HR=0.627, CI: 0.396-0.994, P=0.047). As regards the D3 vs D2 comparison, the meta-analysis of the three available RCTs (n=862) showed no significant impact of more extended lymphadenectomy on OS (summary HR=0.990, CI: 0.814-1.205, P=0.924). Our findings support the superiority of D2 versus D1 lymphadenectomy in terms of survival benefit. However, this advantage is mainly limited to DSS, the level of evidence is moderate, and the interaction with other factors affecting patient survival (such as complementary medical therapy) remains to be elucidated. Copyright © 2015 Elsevier Ltd. All rights reserved.

MMIC LNA based novel composite-channel Al0.3Ga0.7N/Al0.05Ga0.95N/GaNHEMTs

NASA Astrophysics Data System (ADS)

Cheng, Zhi-Qun; Cai, Yong; Liu, Jie; Zhou, Yu-Gang; Lau Kei, May; Chen, Kevin J.

2007-11-01

A microwave monolithic integrated circuit (MMIC) C-band low noise amplifier (LNA) using 1 μm-gate composite-channel Al0.3Ga0.7N/Al0.05Ga0.95N/GaN high electron mobility transistors (CC-HEMTs) has been designed, fabricated and characterized. The material structure and special channel of CC-HEMT were given and analysed. The MMIC LNA with CC-HEMT showed a noise figure of 2.4 dB, an associated gain of 12.3 dB, an input return loss of -6 dB and an output return loss of -16 dB at 6 GHz. The IIP3 of the LNA is 13 dBm at 6 GHz. The LNA with 1 μm × 100 μm device showed very high-dynamic range with decent gain and noise figure.

Noise exposure levels for musicians during rehearsal and performance times.

PubMed

McIlvaine, Devon; Stewart, Michael; Anderson, Robert

2012-03-01

The purpose of this study was to determine daily noise doses and 8-hour time weighted averages for rock band musicians, crew members, and spectators during a typical rehearsal and performance using both Occupational Safety and Health Administration (OSHA) and National Institute of Occupational Safety and Health (NIOSH) measurement criteria. Personal noise dosimetry was completed on five members of a rock band during one 2-hr rehearsal and one 4-hr performance. Time-weighted averages (TWA) and daily dose values were calculated using both OSHA and NIOSH criteria and compared to industry guidelines for enrollment in hearing conservation programs and the use of hearing protection devices. TWA values ranged from 84.3 to 90.4 dBA (OSHA) and from 90.0 to 96.4 dBA (NIOSH) during the rehearsal. The same values ranged from 91.0 to 99.7 dBA (OSHA) and 94.0 to 102.8 dBA (NIOSH) for the performance. During the rehearsal, daily noise doses ranged from 45.54% to 106.7% (OSHA) and from 317.74% to 1396.07% (NIOSH). During the performance, doses ranged from 114.66% to 382.49% (OSHA) and from 793.31% to 5970.15% (NIOSH). The musicians in this study were exposed to dangerously high levels of noise and should be enrolled in a hearing conservation programs. Hearing protection devices should be worn, especially during performances. The OSHA measurement criteria yielded values significantly more conservative than those produced by NIOSH criteria. Audiologists should counsel musician-patients about the hazards of excessive noise (music) exposure and how to protect their hearing.

Molecular Basis for the Recognition of Higher Fullerenes into Ureidopyrimidinone-Cyclotriveratrylene Self-Assembled Capsules.

PubMed

Huerta, Elisa; Serapian, Stefano Artin; Santos, Eva; Cequier, Enrique; Bo, Carles; de Mendoza, Javier

2016-09-12

Fullerenes C60 , C70 , and C84 may be readily encaged within a hydrogen-bonded dimeric capsule, based on two concave cyclotriveratrylene (CTV) scaffolds, each containing three self-complementary 2-ureido-4-[1H]-pyrimidinone (UPy) subunits. NMR spectroscopy and circular dichroism studies, complemented by dispersion-corrected DFT calculations, are reported with the aim of characterizing such capsule-fullerene complexes both structurally and energetically. Six fullerenes are considered: in agreement with experiments, calculations find that encapsulation is most favorable for C84 (on a par with C90 ), and follows the trend C60

Sci-Thur PM – Brachytherapy 03: Identifying the impact of seroma visualization on permanent breast seed implant brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morton, Daniel; Batchelar, Deidre; Hilts, Michelle

Purpose: Uncertainties in target identification can reduce treatment accuracy in permanent breast seed implant (PBSI) brachytherapy. This study evaluates the relationship between seroma visualization and seed placement accuracy. Methods: Spatially co-registered CT and 3D ultrasound (US) images were acquired for 10 patients receiving PBSI. Seromas were retrospectively contoured independently by 3 radiation oncologists on both CT and US and respective consensus volumes were defined, CTV{sub CT} and CTV{sub US}. The seroma clarity and inter-user conformity index (CI), as well as inter-modality CI, volume, and positional differences were evaluated. Correlations with seed placement accuracy were then assessed. CTVs were expanded bymore » 1.25cm to create PTV{sub CT} and PTV{sub US} and evaluate the conformity with PTV{sub Clinical} (CTV{sub Clinical}+1.25cm) used in treatment planning. The change in PTV coincidence by expanding PTV{sub Clinical} by 0.25cm was determined. Results: CTV{sub US} were a mean 68 ± 12% smaller than CTV{sub CT} and generally had improved clarity and inter-user conformity. No correlations between seed displacement and CTV{sub US}-CTV{sub CT} positional difference or CI were observed. Greater seed displacements were associated with larger CTV{sub US}-CTV{sub CT} volume differences (r=−0.65) and inter-user CT CI (r=−0.74). A median (range) 88% (71–99%) of PTV{sub CT} and 83% (69–100%) of PTV{sub US} were contained within PTV{sub Clinical}. Expanding treatment margins to 1.5cm increased coincidence to 98% (86–100%) and 94% (82–100%), respectively. Conclusions: Differences in seroma visualization impacts seed displacement in PBSI. Reducing dependence on CT by incorporating 3DUS into target identification, or expanding CT-based treatment margins to 1.5cm may reduce or mitigate uncertainties related to seroma visualization.« less

PTV margin definition in hypofractionated IGRT of localized prostate cancer using cone beam CT and orthogonal image pairs with fiducial markers.

PubMed

Oehler, Christoph; Lang, Stephanie; Dimmerling, Peter; Bolesch, Christian; Kloeck, Stephan; Tini, Alessandra; Glanzmann, Christoph; Najafi, Yousef; Studer, Gabriela; Zwahlen, Daniel R

2014-11-11

To evaluate PTV margins for hypofractionated IGRT of prostate comparing kV/kV imaging or CBCT. Between 2009 and 2012, 20 patients with low- (LR), intermediate- (IR) and high-risk (HR) prostate cancer were treated with VMAT in supine position with fiducial markers (FM), endorectal balloon (ERB) and full bladder. CBCT's and kV/kV imaging were performed before and additional CBCT's after treatment assessing intra-fraction motion. CTVP for 5 patients with LR and CTVPSV for 5 patients with IR/HR prostate cancer were contoured independently by 3 radiation oncologists using MRI. The van Hark formula (PTV margin =2.5Σ +0.7σ) was applied to calculate PTV margins of prostate/seminal vesicles (P/PSV) using CBCT or FM. 172 and 52 CBCTs before and after RT and 507 kV/kV images before RT were analysed. Differences between FM in CBCT or in planar kV image pairs were below 1 mm. Accounting for both random and systematic uncertainties anisotropic PTV margins were 5-8 mm for P (LR) and 6-11 mm for PSV (IR/HR). Random uncertainties like intra-fraction and inter-fraction (setup) uncertainties were of similar magnitude (0.9-1.4 mm). Largest uncertainty was introduced by CTV delineation (LR: 1-2 mm, IR/HR: 1.6-3.5 mm). Patient positioning using bone matching or ERB-matching resulted in larger PTV margins. For IGRT CBCT or kV/kV-image pairs with FM are interchangeable in respect of accuracy. Especially for hypofractionated RT, PTV margins can be kept in the range of 5 mm or below if stringent daily IGRT, ideally including prostate tracking, is applied. MR-based CTV delineation optimization is recommended.

Image-Based 3D Treatment Planning for Vaginal Cylinder Brachytherapy: Dosimetric Effects of Bladder Filling on Organs at Risk

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hung, Jennifer; Shen Sui; De Los Santos, Jennifer F.

2012-07-01

Purpose: To investigate the dosimetric effects of bladder filling on organs at risk (OARs) using three-dimensional image-based treatment planning for vaginal cylinder brachytherapy. Methods and Materials: Twelve patients with endometrial or cervical cancer underwent postoperative high-dose rate vaginal cylinder brachytherapy. For three-dimensional planning, patients were simulated by computed tomography with an indwelling catheter in place (empty bladder) and with 180 mL of sterile water instilled into the bladder (full bladder). The bladder, rectum, sigmoid, and small bowel (OARs) were contoured, and a prescription dose was generated for 10 to 35 Gy in 2 to 5 fractions at the surface ormore » at 5 mm depth. For each OAR, the volume dose was defined by use of two different criteria: the minimum dose value in a 2.0-cc volume receiving the highest dose (D{sub 2cc}) and the dose received by 50% of the OAR volume (D{sub 50%}). International Commission on Radiation Units and Measurements (ICRU) bladder and rectum point doses were calculated for comparison. The cylinder-to-bowel distance was measured using the shortest distance from the cylinder apex to the contoured sigmoid or small bowel. Statistical analyses were performed with paired t tests. Results: Mean bladder and rectum D{sub 2cc} values were lower than their respective ICRU doses. However, differences between D{sub 2cc} and ICRU doses were small. Empty vs. full bladder did not significantly affect the mean cylinder-to-bowel distance (0.72 vs. 0.92 cm, p = 0.08). In contrast, bladder distention had appreciable effects on bladder and small bowel volume dosimetry. With a full bladder, the mean small bowel D{sub 2cc} significantly decreased from 677 to 408 cGy (p = 0.004); the mean bladder D{sub 2cc} did not increase significantly (1,179 cGy vs. 1,246 cGy, p = 0.11). Bladder distention decreased the mean D{sub 50%} for both the bladder (441 vs. 279 cGy, p = 0.001) and the small bowel (168 vs. 132 cGy, p = 0.001). Rectum and sigmoid volume doses were not affected by bladder filling. Conclusions: In high-dose rate vaginal cylinder brachytherapy, treatment with a distended bladder preferentially reduces high dose to the small bowel around the vaginal cuff without a significant change in dose to the bladder, rectum, or sigmoid.« less

Levothyroxine dose and fracture risk according to the osteoporosis status in elderly women.

PubMed

Ko, Young-Jin; Kim, Ji Young; Lee, Joongyub; Song, Hong-Ji; Kim, Ju-Young; Choi, Nam-Kyong; Park, Byung-Joo

2014-01-01

To evaluate the association between fracture risk and levothyroxine use in elderly women with hypothyroidism, according to previous osteoporosis history. We conducted a cohort study from the Korean Health Insurance Review and Assessment Service claims database from January 2005 to June 2006. The study population comprised women aged ≥65 years who had been diagnosed with hypothyroidism and prescribed levothyroxine monotherapy. We excluded patients who met any of the following criteria: previous fracture history, hyperthyroidism, thyroid cancer, or pituitary disorder; low levothyroxine adherence; or a follow-up period <90 days. We categorized the daily levothyroxine doses into 4 groups: ≤50 µg/d, 51 to 100 µg/d, 101 to 150 µg/d, and >150 µg/d. The hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with the Cox proportional hazard model, and subgroup analyses were performed according to the osteoporosis history and osteoporosis-specific drug prescription status. Among 11 155 cohort participants, 35.6% had previous histories of osteoporosis. The adjusted HR of fracture for the >150 µg/d group, compared with the 51 to 100 µg/d group, was 1.56 (95% CI, 1.03 to 2.37) in osteoporosis subgroup. In the highly probable osteoporosis subgroup, restricted to patients who were concurrently prescribed osteoporosis-specific drugs, the adjusted HR of fracture for the >150 µg/d group, compared with the 51 to 100 µg/d group, was 1.93 (95% CI, 1.14 to 3.26). While further studies are needed, physicians should be concerned about potential levothyroxine overtreatment in elderly osteoporosis patients.

Survey of Nuclear Activations for Intense Proton and Deuteron Beams

DTIC Science & Technology

1992-12-24

1.115 64Zn(d,t)6𔃽 Zn -5.60 ÷ 38 min 2.34 0.51 64Zn(d,a)’ 2 Cu 7.52 ÷ 9.8 min 2.93 0.51 6’Zn(d,2p) 64Cu -2.01 - 12.8 hr 0.575 - c,o+ 12.8 hr 0.656...and for the activation of 5aCo by deuterons on a natural nickel target. 43 THICK-TARGET YIELDS Copper Target 1000 63Cu(d,p) 64Cu 65Cu(d,p)66Cu o 100 6...activation of 1 5 Zn by deuterons and for the GCZn(d,n)"Ga, ’,IZn(d,p)60 Zn, 6SZn(d,p)69mZn, 6 6 Zn(d,(X) 64Cu , and 68Zn(d,2n)6,8Ga reactions in a natural zinc target. 45

Membrane Localization of Human Equilibrative Nucleoside Transporter 1 in Tumor Cells May Predict Response to Adjuvant Gemcitabine in Resected Cholangiocarcinoma Patients

PubMed Central

Deserti, Marzia; Vasuri, Francesco; Farioli, Andrea; Degiovanni, Alessio; Palloni, Andrea; Frega, Giorgio; Barbera, Maria A.; de Lorenzo, Stefania; Garajova, Ingrid; Di Marco, Mariacristina; Pinna, Antonio D.; Cescon, Matteo; Cucchetti, Alessandro; Ercolani, Giorgio; D’Errico-Grigioni, Antonietta; Pantaleo, Maria A.; Biasco, Guido; Tavolari, Simona

2016-01-01

Background. The use of gemcitabine as an adjuvant modality for cholangiocarcinoma (CC) is increasing, but limited data are available on predictive biomarkers of response. Human equilibrative nucleoside transporter 1 (hENT-1) is the major transporter involved in gemcitabine intracellular uptake. This study investigated the putative predictive role of hENT-1 localization in tumor cells of CC patients undergoing treatment with adjuvant gemcitabine. Methods. Seventy-one consecutive patients with resected CC receiving adjuvant gemcitabine at our center were retrospectively analyzed by immunohistochemistry for hENT-1 localization in tumor cells. The main outcome measure was disease-free survival (DFS). Hazard ratios (HRs) of relapse and associated 95% confidence intervals (CIs) were obtained from proportional hazards regression models stratified on quintiles of propensity score. Results. Twenty-three (32.4%) cases were negative for hENT-1, 22 (31.0%) were positive in the cytoplasm only, and 26 (36.6%) showed concomitant cytoplasm/membrane staining. Patients with membrane hENT-1 had a longer DFS (HR 0.49, 95% CI 0.24–0.99, p = .046) than those who were negative or positive only in the cytoplasm of tumor cells. Notably, the association between DFS and membrane hENT-1 was dependent on the number of gemcitabine cycles (one to two cycles: HR 0.96, 95% CI 0.34–2.68; three to four cycles: HR 0.99, 95% CI 0.34–2.90; five to six cycles: HR 0.27, 95% CI 0.10–0.77). Conclusion. hENT-1 localization on tumor cell membrane may predict response to adjuvant gemcitabine in CC patients receiving more than four cycles of chemotherapy. Further prospective randomized trials on larger populations are required to confirm these preliminary results, so that optimal gemcitabine-based chemotherapy may be tailored for CC patients in the adjuvant setting. Implications for Practice: Gemcitabine is becoming an increasingly used adjuvant modality in cholangiocarcinoma (CC), but limited data are available on predictive biomarkers of response. In this study, patients receiving more than four cycles of adjuvant gemcitabine and harboring Human equilibrative nucleoside transporter 1 (hENT-1, the major transporter involved in gemcitabine intracellular uptake) on tumor cell membrane had a longer disease-free survival compared with patients negative or positive for hENT-1 only in the cytoplasm of tumor cells. Overall these results may lay the basis for further prospective randomized trials based on a larger population of patients and may prove useful for tailoring appropriate gemcitabine-based chemotherapy for CC patients in the adjuvant setting. PMID:27032872

Muscle protein turnover in rats treated with corticosterone (CC) or/and nandrolone decanoate (ND) and fed an adequate or a low-protein diet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Santidrian, S.; Cuevillas, F.; Goena, M.

1986-03-01

In order to investigate the possible antagonistic effect between glucocorticoids and androgens on muscle protein turnover, the authors have measured the fractional rates of gastrocnemius muscle protein synthesis (k/sub s/) and degradation (k/sub d/) by the constant-intravenous-infusion method using L-//sup 14/C/-tyrosine in rats receiving via s.c. per 100 g b.wt. 10 mg of CC, or 2 mg of ND or CC+ND at the indicated doses, and fed either an 18% or 5% protein diets over a period of 5 days. As an additional index of protein synthesis, RNA activity (g of synthesized protein/day/g RNA) was determined as well. Results showedmore » that as compared to vehicle-injected animals fed the adequate diet, CC-treated rats exhibited a reduction of muscle k/sub d/, while ND-treated rats had an outstanding increase of muscle k/sub s/. However, rats receiving CC+ND showed k/sub s/ and k/sub d/ values similar to those displayed by control animals. Nevertheless, when the steroids were injected to rats fed the low-protein diet, CC has a catabolic effect on muscle protein but by reducing k/sub s/, while the anabolic action of ND is still displayed but by a significant reduction of muscle k/sub d/. CC+ND given to these protein-deficient rats caused an increase in muscle k/sub s/ and a reduction in k/sub d/. These results might indicate that, at least in part, ND antagonizes the catabolic action of high doses of CC on muscle protein metabolism.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Susko, Matthew; Craciunescu, Oana; Meltsner, Sheridan

Purpose: To calculate vaginal doses during image guided brachytherapy with volume-based metrics and correlate with long-term vaginal toxicity. Methods and Materials: In this institutional review board–approved study, institutional databases were searched to identify women undergoing computed tomography and/or magnetic resonance–guided brachytherapy at the Duke Cancer Center from 2009 to 2015. All insertions were contoured to include the vagina as a 3-dimensional structure. All contouring was performed on computed tomography or magnetic resonance imaging and used a 0.4-cm fixed brush to outline the applicator and/or packing, expanded to include any grossly visible vagina. The surface of the cervix was specifically excludedmore » from the contour. High-dose-rate (HDR) and low-dose-rate (LDR) doses were converted to the equivalent dose in 2-Gy fractions using an α/β of 3 for late effects. The parameters D0.1cc, D1cc, and D2cc were calculated for all insertions and summed with prior external beam therapy. Late and subacute toxicity to the vagina were determined by the Common Terminology Criteria for Adverse Events version 4.0 and compared by the median and 4th quartile doses, via the log-rank test. Univariate and multivariate hazard ratios were calculated via Cox regression. Results: A total of 258 insertions in 62 women who underwent definitive radiation therapy including brachytherapy for cervical (n=48) and uterine cancer (n=14) were identified. Twenty HDR tandem and ovoid, 32 HDR tandem and ring, and 10 LDR tandem and ovoid insertions were contoured. The median values (interquartile ranges) for vaginal D0.1cc, D1cc, and D2cc were 157.9 (134.4-196.53) Gy, 112.6 (96.7-124.6) Gy, and 100.5 (86.8-108.4) Gy, respectively. At the 4th quartile cutoff of 108 Gy for D2cc, the rate of late grade 1 toxicity at 2 years was 61.2% (95% confidence interval [CI] 43.0%-79.4%) below 108 Gy and 83.9% (63.9%-100%) above (P=.018); grade 2 or greater toxicity was 36.2% (95% CI 15.8%-56.6%) below 108 Gy and 70.7% (95% CI 45.2%-96.2%) above (P=.004); and grade 3 or worse toxicity was 9.9% (95% CI 0.0%-23.6%) below 108 Gy and 30.0% (95% CI 4.7%-55.3%) above (P=.025). This association was maintained on multivariate analysis, independent of covariates such as applicator type, age, and dose rate. Conclusions: Vaginal dose was associated with all grades of vaginal toxicity. Confirmation at other sites using this methodology will be necessary to establish reproducibility; however, the integration of routine calculation of vaginal dose may be warranted.« less

TU-AB-201-01: A Comprehensive Planning Comparison Study Between a Novel Direction Modulated Brachytherapy Tandem Applicator and Conventional T&R Applicator for Image Guided Cervical Cancer Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, D; Liu, Z; University of California, San Diego, La Jolla, CA

2015-06-15

Purpose: To demonstrate that utilization of a novel, intensity modulation capable, direction modulated brachytherapy (DMBT) tandem applicator can improve plan quality compared with conventional T&R applicator during an image guided cervical cancer brachytherapy. Methods: 45 cervical cancer patients treated with PDR brachytherapy were reviewed. Of them, a) 27 were treated using T&R only, b) 9 were treated using T&R with needles attached to the ring, and c) the remaining 9 were treated using T&R with needles attached to the ring (AN) as well as additional free-hand-loaded needles (FN). The DMBT tandem design has 6 peripheral holes of 1.3-mm diameter, groovedmore » along a nonmagnetic tungsten alloy rod, enclosed in a plastic sheath with total 6.0-mm diameter. An in-house-coded inverse planning system was used for planning DMBT and T&R cases. All typical clinical constraints including OAR dose limits, dwell times, and loading patterns were respected. For the DMBT and T&R applicators, the plans were optimized with the same conventional ring in place, but repeatedly planned with and without AN/FN needles. All generated plans were normalized to the same D90 of the clinically treated plans. Results: For the plans in category a), DMBT generally outperformed T&R with average reduction in D2cc of −2.39%, −5.21%, and −2.69% for bladder, rectum, and sigmoid, respectively. For the plans in category b) and c), DMBT generally outperformed T&R if the same needles in AN/FN were utilized in both cases with average reduction in D2cc of −1.82%, −3.40%, and −6.04%, respectively. For the cases where the needles were not utilized for both applicators, an average D2cc reduction of −7.45%, −7.61%, and 17.47% were observed, respectively. Conclusions: Under the same clinical conditions, with/without needles, the DMBT applicator tends to generate more favorable plans compared with the conventional T&R applicator, and hence, is a promising technology.« less

Everolimus Plus Exemestane vs Everolimus or Capecitabine Monotherapy for Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer: The BOLERO-6 Randomized Clinical Trial.

PubMed

Jerusalem, Guy; de Boer, Richard H; Hurvitz, Sara; Yardley, Denise A; Kovalenko, Elena; Ejlertsen, Bent; Blau, Sibel; Özgüroglu, Mustafa; Landherr, László; Ewertz, Marianne; Taran, Tetiana; Fan, Jenna; Noel-Baron, Florence; Louveau, Anne-Laure; Burris, Howard

2018-06-03

Everolimus plus exemestane and capecitabine are approved second-line therapies for advanced breast cancer. A postapproval commitment to health authorities to estimate the clinical benefit of everolimus plus exemestane vs everolimus or capecitabine monotherapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Open-label, randomized, phase 2 trial of treatment effects in postmenopausal women with advanced breast cancer that had progressed during treatment with nonsteroidal aromatase inhibitors. Patients were randomized to 3 treatment regimens: (1) everolimus (10 mg/d) plus exemestane (25 mg/d); (2) everolimus alone (10 mg/d); and (3) capecitabine alone (1250 mg/m2 twice daily). Estimated hazard ratios (HRs) of progression-free survival (PFS) for everolimus plus exemestane vs everolimus alone (primary objective) or capecitabine alone (key secondary objective). Safety was a secondary objective. No formal statistical comparisons were planned. A total of 309 postmenopausal women were enrolled, median age, 61 years (range, 32-88 years). Of these, 104 received everolimus plus exemestane; 103, everolimus alone; and 102, capecitabine alone. Median follow-up from randomization to the analysis cutoff (June 1, 2017) was 37.6 months. Estimated HR of PFS was 0.74 (90% CI, 0.57-0.97) for the primary objective of everolimus plus exemestane vs everolimus alone and 1.26 (90% CI, 0.96-1.66) for everolimus plus exemestane vs capecitabine alone. Between treatment arms, potential informative censoring was noted, and a stratified multivariate Cox regression model was used to account for imbalances in baseline characteristics; a consistent HR was observed for everolimus plus exemestane vs everolimus (0.73; 90% CI, 0.56-0.97), but the HR was closer to 1 for everolimus plus exemestane vs capecitabine (1.15; 90% CI, 0.86-1.52). Grade 3 to 4 adverse events were more frequent with capecitabine (74%; n = 75) vs everolimus plus exemestane (70%; n = 73) or everolimus alone (59%; n = 61). Serious adverse events were more frequent with everolimus plus exemestane (36%; n = 37) vs everolimus alone (29%; n = 30) or capecitabine (29%; n = 30). These findings suggest that everolimus plus exemestane combination therapy offers a PFS benefit vs everolimus alone, and they support continued use of this therapy in this setting. A numerical PFS difference with capecitabine vs everolimus plus exemestane should be interpreted cautiously owing to imbalances among baseline characteristics and potential informative censoring. ClinicalTrials.gov identifier: NCT01783444.

TH-CD-209-11: Simulation Study of Real-Time-Image Gating On Spot Scanning Proton Therapy for Lung Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kanehira, T; Inoue, T; Katoh, N

Purpose: To study the impact of a real-time-image gating on spot scanning proton therapy for lung tumors and to examine the suitable size of the gating window (GW). Methods: We investigated a real-time-image gated proton therapy (RGPT), in which two fluoroscopic units monitor a gold sphere fiducial in real-time, and the proton beam is irradiated only when the marker enters within the pre-assigned GW. We designed 5 treatment plans for 7 lung cancer patients: RGPT with a GW of ±1, 2, 5, and 8 mm and free-breathing proton therapy (FBPT) using the end-exhale and average images of 4-dimensional (4D) CT,more » respectively. 70 Gy(RBE)/10fr was prescribed to 99% of the targets. The time-series data of the three-dimensional marker positions (RTRT data) were grouped into 10 phases to associate with the phases of 4DCT. The 4D dose distributions were calculated using the plan information, RTRT Data, 4DCT, and modeled accelerator pattern. The dose distribution in each respiratory phase was deformed into the end-exhale CT. The D99 and D5-95 of CTV (with a criteria of D99>95% and D5-95<5%), V20 of Lung-GTV, and treatment times were evaluated. Results: GWs ≤ ±2 mm satisfied the criteria of CTV in all cases, whereas GWs ≥ ±5 mm did not satisfy the criteria in some cases. The V20 was reduced by more than 18.9% (relative to FBPT) for GW ≤ ±2 mm, but equaled or even surpassed the FBPT for GWs ≥ ±5 mm. The irradiation times for the ±1, 2, 5, and 8 mm GWs and FBPT were 372.4±208.3, 215.2±51.5, 180.9±31.6, 178.4±21.2, and 140.1±15.2 s, respectively. The GW of ±1 mm caused large variation in irradiation time among the patients. Conclusion: In RGPT for lung cancer, the most suitable GW, in terms of good dose preservation without prolonging the therapeutic beam delivery, is ±2 mm.« less

Vaccinations in early life are not associated with development of islet autoimmunity in type 1 diabetes high-risk children: Results from prospective cohort data.

PubMed

Beyerlein, Andreas; Strobl, Andreas N; Winkler, Christiane; Carpus, Michaela; Knopff, Annette; Donnachie, Ewan; Ankerst, Donna P; Ziegler, Anette-G

2017-03-27

Vaccinations in early childhood potentially stimulate the immune system and may thus be relevant for the pathogenesis of autoimmune diseases such as type 1 diabetes (T1D). We determined the association of vaccination burden with T1D-associated islet autoimmunity in children with high familial risk followed prospectively from birth. A total of 20,570 certified vaccination records from 1918 children were correlated with time to onset of T1D-associated islet autoimmunity using Cox regression, considering multiple time periods up until age two years and vaccination types, and adjusting for HLA genotype, sex, delivery mode, season of birth, preterm delivery and maternal T1D status. Additionally, prospective claims data of 295,420 subjects were used to validate associations for the tick-borne encephalitis (TBE) vaccination. Most vaccinations were not associated with a significantly increased hazard ratio (HR) for islet autoimmunity (e.g. HR [95% confidence interval]: 1.08 [0.96-1.21] per additional vaccination against measles, mumps and rubella at age 0-24months). TBE vaccinations within the first two years of life were nominally associated with a significantly increased autoimmunity risk (HR: 1.44 [1.06-1.96] per additional vaccination at age 0-24months), but this could not be confirmed with respect to outcome T1D in the validation cohort (HR: 1.02 [0.90-1.16]). We found no evidence that early vaccinations increase the risk of T1D-associated islet autoimmunity development. The potential association with early TBE vaccinations could not be confirmed in an independent cohort and appears to be a false positive finding. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Impact of the Grid Size on TomoTherapy for Prostate Cancer

PubMed Central

Kawashima, Motohiro; Kawamura, Hidemasa; Onishi, Masahiro; Takakusagi, Yosuke; Okonogi, Noriyuki; Okazaki, Atsushi; Sekihara, Tetsuo; Ando, Yoshitaka; Nakano, Takashi

2017-01-01

Discretization errors due to the digitization of computed tomography images and the calculation grid are a significant issue in radiation therapy. Such errors have been quantitatively reported for a fixed multifield intensity-modulated radiation therapy using traditional linear accelerators. The aim of this study is to quantify the influence of the calculation grid size on the dose distribution in TomoTherapy. This study used ten treatment plans for prostate cancer. The final dose calculation was performed with “fine” (2.73 mm) and “normal” (5.46 mm) grid sizes. The dose distributions were compared from different points of view: the dose-volume histogram (DVH) parameters for planning target volume (PTV) and organ at risk (OAR), the various indices, and dose differences. The DVH parameters were used Dmax, D2%, D2cc, Dmean, D95%, D98%, and Dmin for PTV and Dmax, D2%, and D2cc for OARs. The various indices used were homogeneity index and equivalent uniform dose for plan evaluation. Almost all of DVH parameters for the “fine” calculations tended to be higher than those for the “normal” calculations. The largest difference of DVH parameters for PTV was Dmax and that for OARs was rectal D2cc. The mean difference of Dmax was 3.5%, and the rectal D2cc was increased up to 6% at the maximum and 2.9% on average. The mean difference of D95% for PTV was the smallest among the differences of the other DVH parameters. For each index, whether there was a significant difference between the two grid sizes was determined through a paired t-test. There were significant differences for most of the indices. The dose difference between the “fine” and “normal” calculations was evaluated. Some points around high-dose regions had differences exceeding 5% of the prescription dose. The influence of the calculation grid size in TomoTherapy is smaller than traditional linear accelerators. However, there was a significant difference. We recommend calculating the final dose using the “fine” grid size. PMID:28974860

49 CFR 178.356-2 - Materials of construction and other requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... bottom section and 0.16 g/cc (10 pcf) minimum for top section, except 0.1 g/cc (6.5 pcf) for the... encapsulated by the foam. (d) Vent holes 5 mm (0.2-inch) diameter must be drilled in the outer shell to provide... fusion welding process in accordance with American Welding Society Codes B-3.0 and D-1.0 (IBR, see § 171...

49 CFR 178.356-2 - Materials of construction and other requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... bottom section and 0.16 g/cc (10 pcf) minimum for top section, except 0.1 g/cc (6.5 pcf) for the... encapsulated by the foam. (d) Vent holes 5 mm (0.2-inch) diameter must be drilled in the outer shell to provide... fusion welding process in accordance with American Welding Society Codes B-3.0 and D-1.0 (IBR, see § 171...

49 CFR 178.356-2 - Materials of construction and other requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... bottom section and 0.16 g/cc (10 pcf) minimum for top section, except 0.1 g/cc (6.5 pcf) for the... encapsulated by the foam. (d) Vent holes 5 mm (0.2-inch) diameter must be drilled in the outer shell to provide... fusion welding process in accordance with American Welding Society Codes B-3.0 and D-1.0 (IBR, see § 171...

[Effects of a recreational general physical activity program with short term and moderate intensity of blood pressure and other cardiovascular risk factors in hypertensive patients over 50 years old].

PubMed

Torija Archilla, Ana; Pérez González, Javier; Sarmiento Ramírez, Álvaro; Fernández Sánchez, Enrique; González Ruiz, Josué Rubén; Guisado Barrilao, Rafael

2017-10-01

To evaluate the effects of a recreational general physical activity program with moderate intensity and short duration on blood pressure and other cardiovascular risk factors (BMI, cholesterol, Rest Heart Rate, HDL, LDL, Triglycerides) in hypertensive patients older than 50years. Non-randomised pre-post design, quasi-experimental study. Íllora, Granada, Spain. A total of 60 subjects aged 50-75years taking part in the Health Hypertensive Program in the Medical Centre were selected. A recreational general physical activity program, mainly aerobic capacity, of 4weeks duration, 3days/week, and an intensity of 45-55% HR Reserve. SBP, DBP, HR, BMI, total cholesterol, HDL, LDL, TG, and Glucose. Statistically significant decreases (P<.05) were observed in BMI (-0.51%; 95%CI: 30.26 to 31.93units), HR (-5.57beats/min; 95%CI: 68.76 to 71.73beats/min), SBP (-14.82mmHg; 95%CI: 131.57 to 137.52mmHg), DBP (-5.33mmHg; 95%CI: 78.94 to 83.68mmHg), Glucose (-7.63mg/dL; 95%CI: 125.06 to 153.73mg/dL) and REGICOR risk (-20.46%; 95%CI: 5.45 to 6.90%). Statistically significant increases were observed in HDL (+2.82mg/dl; 95%CI: 46.78 to 52.11mmHg), and TG (+8.27mg/dl; 95%CI: 133.89 to 152.60mg/dL). Men had a wider variation in HR and DBP, and women in SBP (P<.05). Subjects with baseline SBP≥160mmHg experienced greater declines in HR, SBP, DBP, Glucose and TG (-10.67beats/min, -31mmHg, -8.27mmHg, -10.86mg/dL, and 34.66mg/dL, respectively) than those with an initial SBP<160mmHg, where there was an increase in HDL and a decrease in LDL. After this program, improvements in BP and other cardiovascular risk factors were obtained in hypertensive subjects over 50years. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

The Lawrence D. Dorr Surgical Techniques & Technologies Award: "Running Two Rooms" Does Not Compromise Outcomes or Patient Safety in Joint Arthroplasty.

PubMed

Hamilton, William G; Ho, Henry; Parks, Nancy L; Strait, Alexander V; Hopper, Robert H; McDonald, James F; Goyal, Nitin; Fricka, Kevin B; Engh, C Anderson

2018-07-01

Scrutiny from the federal government and the media regarding the safety of 1 surgeon doing cases in 2 operating rooms (ORs) on the same day, prompted us to examine our own institutional data. Over the past 11 years, surgeons at our facility have operated consecutively in 1 OR on a given day or used 2 alternating ORs. This study compares these cases with a focus on revisions and complications in both groups. Six surgeons performed a total of 16,916 primary hip and knee arthroplasties from 2006-2016. 7002 cases (41%) were consecutive cases (CCs) and 9914 cases (59%) were overlapping cases (OCs). Intraoperative complications, component revisions, and postoperative complications within 90 days of surgery were compared between the CC and OC groups. There was no difference in intraoperative complication rates between the two groups (CC 1.6% vs. OC 1.7%, relative risk 1.082, 95% confidence interval 0.852 to 1.375, P = .52). There was no difference in 90-day component revision rates among the CC and OC groups (0.66% vs. 0.85% respectively, relative risk = 1.290, 95% confidence interval 0.901 to 1.845, P = .19). There was also no difference in 90-day complication rates among the CC and OC groups (1.33% vs. 1.45% respectively, relative risk = 1.094, 95% confidence interval 0.844 to 1.417, P = .54). This large study of a single institution with multiple surgeons over an 11-year period shows no compromise in patient safety or outcomes when comparing cases done in either consecutive or overlapping rooms. Copyright © 2018 Elsevier Inc. All rights reserved.

Behavioral and anatomical correlates of chronic episodic hypoxia during sleep in the rat.

PubMed

Gozal, D; Daniel, J M; Dohanich, G P

2001-04-01

The role played by chronic episodic hypoxia (EHYP) in the neurocognitive morbidity of obstructive sleep apnea (OSA) is unknown. Sleep recordings, Morris water maze experiments, and immunohistochemistry for NMDA NR1 glutamate receptor, c-fos protein, and apoptosis [nuclear immunoreactivity for single-stranded DNA and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling assay] were conducted in EHYP-exposed Sprague Dawley male rats. Exposures consisted of up to14 d in an environmental chamber in which O(2) concentrations were cycled between 10 and 21% every 90 sec or 30 min during 12 hr of daylight. For the remaining 12 hr, EHYP rats breathed room air, while controls spent 14 d in room air. Although EHYP induced significant disruption of sleep architecture during the initial day of exposure, sleep patterns normalized thereafter. Marked increases in apoptosis occurred in the CA1 hippocampal region (sevenfold) and cortex (Cx; eightfold) after 1-2 d of EHYP but not in CA3 and were followed by decreases toward normoxic levels by 14 d. Double labeling for NMDA NR1 and c-fos revealed marked architectural disorganization in CA1 and Cx with increases in c-fos over time. Rats exposed to EHYP displayed significantly longer escape latencies and swim path lengths to escape a hidden platform during 12 training trials given over 2 d. Differences in the performances of EHYP and control rats, although reduced, persisted after 14 d of recovery. We conclude that EHYP is associated with marked cellular changes over time within neural regions associated with cognitive functions. Furthermore, EHYP impaired performance during acquisition of a cognitive spatial task without affecting sensorimotor function. Such changes may underlie components of the learning and memory impairments found in OSA.

Ecological Validity and Reliability of the Rugby Sevens Simulation Protocol.

PubMed

Furlan, Nicola; Waldron, Mark; Osborne, Mark; Gray, Adrian J

2016-09-01

To assess the ecological validity of the Rugby Sevens Simulation Protocol (R7SP) and to evaluate its interday reliability. Ten male participants (20 ± 2 y, 74 ± 11 kg) completed 2 trials of the R7SP, separated by 7 d. The R7SP comprised typical running and collision activities, based on data recorded during international rugby sevens match play. Heart rate (HR) was monitored continuously during the R7SP, and the participants' movements were recorded through a 20-Hz global positioning system unit. Blood lactate and rating of perceived exertion were collected before and immediately after the 1st and 2nd halves of the R7SP. The average activity profile was 117 ± 5 m/min, of which 27 ± 2 m/min was covered at high speed, with a calculated energetic demand of 1037 ± 581 J/kg, of which ~40% was expended at a rate above 19 W/kg. Mean HR was 88% ± 4% of maximal HR. Participants spent ~45% ± 27% of time above 90% of maximal HR (t >90% HRmax ). There were no significant differences between trials, except for lactate between the halves of the R7SP. The majority of the measured variables demonstrated a between-trials coefficient of variation (CV%) lower than 5%. Blood lactate measurements (14-20% CV) and t >90% HRmax (26% CV) were less reliable variables. In most cases, the calculated moderate worthwhile change was higher than the CV%. The R7SP replicates the activity profile and HR responses of rugby sevens match play. It is a reliable simulation protocol that can be used in a research environment to detect systematic worthwhile changes in selected performance variables.

The effect of clomiphene citrate on human preovulatory oocyte maturation in vivo.

PubMed

Seibel, M M; Smith, D M

1989-02-01

Sixty-four infertile women underwent diagnostic laparoscopy in the periovulatory period at time-bracketed intervals following their endogenous luteinizing hormone (LH) surge. Forty-eight of these women were studied during natural cycles and 16 had mild oligoovulation and were administered clomiphene citrate (CC) to regulate their cycles. No patient received human chorionic gonadotropin. No patient was undergoing either in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT). Follicle puncture was performed and the oocytes were observed immediately for stage of maturation. Oocytes obtained from follicles exposed to CC were found to require an increased interval of time to reach metaphase I compared to oocytes obtained from natural cycles (27.75 +/- 2.2 vs 22.5 hr; mean +/- SE). Furthermore, the interval of time required for metaphase I oocytes to achieve metaphase II was statistically significantly shortened for CC cycles (2.4 hr for CC vs 10 hr for natural cycles. Nevertheless, there was no difference between natural and CC cycles in the time interval between LH surge onset and ovulation. These in vivo findings suggest a direct effect of CC on human oocyte maturation and may help explain the well-established discrepancy between the relatively high ovulation rate and the relatively low conception rate in clomiphene-induced cycles.

Milrinone is preferred to levosimendan for mesenteric perfusion in hypoxia-reoxygenated newborn piglets treated with dopamine

PubMed Central

Manouchehri, Namdar; Bigam, David L.; Churchill, Thomas; Joynt, Chloe; Vento, Maximo; Cheung, Po-Yin

2016-01-01

INTRODUCTION There is little information regarding the comparative hemodynamic effects of adding milrinone or levosimendan to dopamine infusion in hypoxia-reoxygenated (H-R) newborns. RESULTS Severely hypoxic piglets had cardiogenic shock with depressed cardiac index (CI) and mean arterial pressure (MAP). The hemodynamics deteriorated gradually after initial recovery upon reoxygenation. Heart rate and CI improved with milrinone (D+M) and levosimendan (D+L) administration (P < 0.05 vs. control). Both regimens improved carotid arterial flow and carotid vascular resistance; D+M additionally improved superior mesentric arterial flow (all P < 0.05 vs. control). No effect was found on renal arterial flow or elevated lactate state with either regimen. D+M piglets also had a lower myocardial oxidized/reduced glutathione ratio (P < 0.05 vs. control). DISCUSSION In conclusion, adding milrinone or levosimendan to dopamine similarly improved systemic hemodynamics in H-R newborn piglets. Milrinone also improved mesenteric perfusion and attenuated myocardial oxidative stress. METHODS Twenty-eight piglets (1–4 d, 1.5–2.5 kg) were instrumented for continuous monitoring of systemic MAP and pulmonary arterial pressure (PAP), CI, and carotid, superior mesenteric, and renal arterial flows. Piglets were randomized with blinding to sham-operated, H-R control (saline), and H-R dopamine (10 μg/kg/min) with D+M or D+L groups. H-R piglets underwent H-R followed by 2 h of drug infusion after reoxygenation. Tissue was collected for biochemical/oxidative stress testing and histological analysis. PMID:22337258

Milrinone is preferred to levosimendan for mesenteric perfusion in hypoxia-reoxygenated newborn piglets treated with dopamine.

PubMed

Manouchehri, Namdar; Bigam, David L; Churchill, Thomas; Joynt, Chloe; Vento, Maximo; Cheung, Po-Yin

2012-03-01

There is little information regarding the comparative hemodynamic effects of adding milrinone or levosimendan to dopamine infusion in hypoxia-reoxygenated (H-R) newborns. Severely hypoxic piglets had cardiogenic shock with depressed cardiac index (CI) and mean arterial pressure (MAP). The hemodynamics deteriorated gradually after initial recovery upon reoxygenation. Heart rate and CI improved with milrinone (D+M) and levosimendan (D+L) administration (P < 0.05 vs. control). Both regimens improved carotid arterial flow and carotid vascular resistance; D+M additionally improved superior mesentric arterial flow (all P < 0.05 vs. control). No effect was found on renal arterial flow or elevated lactate state with either regimen. D+M piglets also had a lower myocardial oxidized/reduced glutathione ratio (P < 0.05 vs. control). In conclusion, adding milrinone or levosimendan to dopamine similarly improved systemic hemodynamics in H-R newborn piglets. Milrinone also improved mesenteric perfusion and attenuated myocardial oxidative stress. Twenty-eight piglets (1-4 d, 1.5-2.5 kg) were instrumented for continuous monitoring of systemic MAP and pulmonary arterial pressure (PAP), CI, and carotid, superior mesenteric, and renal arterial flows. Piglets were randomized with blinding to sham-operated, H-R control (saline), and H-R dopamine (10 μg/kg/min) with D+M or D+L groups. H-R piglets underwent H-R followed by 2 h of drug infusion after reoxygenation. Tissue was collected for biochemical/oxidative stress testing and histological analysis.

Search for neutral D meson mixing using semileptonic decays

NASA Astrophysics Data System (ADS)

Flood, Kevin T.

Based on a 87 fb-1 dataset, a search for D0-D¯0 mixing is made using the semileptonic decay modes D*+ → pi +D0, D0 → [K/K*]enu (+c.c.) at the B-Factory facility at the Stanford Linear Accelerator Center. These modes offer unambiguous initial and final-state charm flavor tags, and allow the combined use of the D0 lifetime and D*+- D0 mass difference (DeltaM) in a global likelihood fit. The high-statistics sample of reconstructed unmixed semileptonic D0 decays is used to model both the DeltaM distribution and the time-dependence of mixed events directly from the data. Neural networks are used both to select events and to fully reconstruct the D0. A result consistent with no charm mixing has been obtained, Rmix = 0.0023 +/- 0.0012(stat) +/- 0.0004(sys ). This corresponds to an upper limit of Rmix < 0.0047 (95% C.L.) and Rmix < 0.0043 (90% C.L.). The lowest current published limit on semileptonic charm mixing is 0.005 (90% C.L.) (E791, E.M. Aitala et al., Phys.Rev.Lett. 77 2384 (1996)). The current best published limit using any analysis technique on the total rate of charm mixing is 0.0016 (95% C.L.) (Babar Kpi mixing, B. Aubert et al., Phys.Rev.Lett. 91 171801 (2003)).

Image-Guided Radiotherapy for Left-Sided Breast Cancer Patients: Geometrical Uncertainty of the Heart

DOE Office of Scientific and Technical Information (OSTI.GOV)

Topolnjak, Rajko; Borst, Gerben R.; Nijkamp, Jasper

Purpose: To quantify the geometrical uncertainties for the heart during radiotherapy treatment of left-sided breast cancer patients and to determine and validate planning organ at risk volume (PRV) margins. Methods and Materials: Twenty-two patients treated in supine position in 28 fractions with regularly acquired cone-beam computed tomography (CBCT) scans for offline setup correction were included. Retrospectively, the CBCT scans were reconstructed into 10-phase respiration correlated four-dimensional scans. The heart was registered in each breathing phase to the planning CT scan to establish the respiratory heart motion during the CBCT scan ({sigma}{sub resp}). The average of the respiratory motion was calculatedmore » as the heart displacement error for a fraction. Subsequently, the systematic ({Sigma}), random ({sigma}), and total random ({sigma}{sub tot}={radical}({sigma}{sup 2}+{sigma}{sub resp}{sup 2})) errors of the heart position were calculated. Based on the errors a PRV margin for the heart was calculated to ensure that the maximum heart dose (D{sub max}) is not underestimated in at least 90% of the cases (M{sub heart} = 1.3{Sigma}-0.5{sigma}{sub tot}). All analysis were performed in left-right (LR), craniocaudal (CC), and anteroposterior (AP) directions with respect to both online and offline bony anatomy setup corrections. The PRV margin was validated by accumulating the dose to the heart based on the heart registrations and comparing the planned PRV D{sub max} to the accumulated heart D{sub max}. Results: For online setup correction, the cardiac geometrical uncertainties and PRV margins were N-Ary-Summation = 2.2/3.2/2.1 mm, {sigma} = 2.1/2.9/1.4 mm, and M{sub heart} = 1.6/2.3/1.3 mm for LR/CC/AP, respectively. For offline setup correction these were N-Ary-Summation = 2.4/3.7/2.2 mm, {sigma} = 2.9/4.1/2.7 mm, and M{sub heart} = 1.6/2.1/1.4 mm. Cardiac motion induced by breathing was {sigma}{sub resp} = 1.4/2.9/1.4 mm for LR/CC/AP. The PRV D{sub max} underestimated the accumulated heart D{sub max} for 9.1% patients using online and 13.6% patients using offline bony anatomy setup correction, which validated that PRV margin size was adequate. Conclusion: Considerable cardiac position variability relative to the bony anatomy was observed in breast cancer patients. A PRV margin can be used during treatment planning to take these uncertainties into account.« less

Postimplant dosimetry using a Monte Carlo dose calculation engine: a new clinical standard.

PubMed

Carrier, Jean-François; D'Amours, Michel; Verhaegen, Frank; Reniers, Brigitte; Martin, André-Guy; Vigneault, Eric; Beaulieu, Luc

2007-07-15

To use the Monte Carlo (MC) method as a dose calculation engine for postimplant dosimetry. To compare the results with clinically approved data for a sample of 28 patients. Two effects not taken into account by the clinical calculation, interseed attenuation and tissue composition, are being specifically investigated. An automated MC program was developed. The dose distributions were calculated for the target volume and organs at risk (OAR) for 28 patients. Additional MC techniques were developed to focus specifically on the interseed attenuation and tissue effects. For the clinical target volume (CTV) D(90) parameter, the mean difference between the clinical technique and the complete MC method is 10.7 Gy, with cases reaching up to 17 Gy. For all cases, the clinical technique overestimates the deposited dose in the CTV. This overestimation is mainly from a combination of two effects: the interseed attenuation (average, 6.8 Gy) and tissue composition (average, 4.1 Gy). The deposited dose in the OARs is also overestimated in the clinical calculation. The clinical technique systematically overestimates the deposited dose in the prostate and in the OARs. To reduce this systematic inaccuracy, the MC method should be considered in establishing a new standard for clinical postimplant dosimetry and dose-outcome studies in a near future.

Four-Dimensional Patient Dose Reconstruction for Scanned Ion Beam Therapy of Moving Liver Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Richter, Daniel; TU Darmstadt, Darmstadt; Saito, Nami

2014-05-01

Purpose: Estimation of the actual delivered 4-dimensional (4D) dose in treatments of patients with mobile hepatocellular cancer with scanned carbon ion beam therapy. Methods and Materials: Six patients were treated with 4 fractions to a total relative biological effectiveness (RBE)–weighted dose of 40 Gy (RBE) using a single field. Respiratory motion was addressed by dedicated margins and abdominal compression (5 patients) or gating (1 patient). 4D treatment dose reconstructions based on the treatment records and the measured motion monitoring data were performed for the single-fraction dose and a total of 17 fractions. To assess the impact of uncertainties in the temporalmore » correlation between motion trajectory and beam delivery sequence, 3 dose distributions for varying temporal correlation were calculated per fraction. For 3 patients, the total treatment dose was formed from the fractional distributions using all possible combinations. Clinical target volume (CTV) coverage was analyzed using the volumes receiving at least 95% (V{sub 95}) and 107% (V{sub 107}) of the planned doses. Results: 4D dose reconstruction based on daily measured data is possible in a clinical setting. V{sub 95} and V{sub 107} values for the single fractions ranged between 72% and 100%, and 0% and 32%, respectively. The estimated total treatment dose to the CTV exhibited improved and more robust dose coverage (mean V{sub 95} > 87%, SD < 3%) and overdose (mean V{sub 107} < 4%, SD < 3%) with respect to the single-fraction dose for all analyzed patients. Conclusions: A considerable impact of interplay effects on the single-fraction CTV dose was found for most of the analyzed patients. However, due to the fractionated treatment, dose heterogeneities were substantially reduced for the total treatment dose. 4D treatment dose reconstruction for scanned ion beam therapy is technically feasible and may evolve into a valuable tool for dose assessment.« less

Impact of diabetes mellitus and chronic liver disease on the incidence of dementia and all-cause mortality among patients with dementia.

PubMed

Kim, Hyun Min; Lee, Yong-Ho; Han, Kyungdo; Lee, Byung-Wan; Kang, Eun Seok; Kim, Jaetaek; Cha, Bong-Soo

2017-11-01

This study investigated the effects of the presence of type 2 diabetes mellitus (T2D) and/or chronic liver disease (CLD) on the incidence and prognosis of dementia during a 10-year period in Korea using a nationwide population-based dataset from the Korea National Health Insurance Service.To assess the impact of T2D and CLD on the incidence of dementia, we included subjects aged ≥60 years without dementia, T2D, and CLD from 2003 to 2005. We created another cohort for evaluating the all-cause mortality in subjects with dementia between 2003 and 2005. The participants were categorized into 4 groups: control (neither CLD nor T2D), CLD-only, T2D-only, and T2D-and-CLD groups, and they were followed up until 2013.The incidence of dementia was higher in the T2D-only group than in the control and CLD-only groups (2.78 vs. 2.04 and 2.00 per 1000 person-years). After adjustment for age, gender, and comorbid conditions, both T2D and CLD increased the risk of any type of dementia; however, the impact of CLD alone was much lower [hazard ratio (HR) 1.07, 95% confidence interval (CI): 1.06-1.08] than that of T2D alone (HR 1.27, 95% CI: 1.27-1.28). The risk of dementia did not significantly change in patients with the co-occurrence of T2D and CLD compared to those with T2D alone. The all-cause mortality rate was the lowest in the control group (2.59 per 1000 person-years) and the highest in the T2D-and-CLD group (3.77 per 1000 person-years). Presence of T2D or CLD alone was associated with higher mortality (HR 1.46 and HR 1.21, respectively) compared with in the absence of both the diseases. Furthermore, the presence of both the diseases further significantly increased the mortality rate compared to the presence of each disease alone (HR 1.67, 95% CI: 1.65-1.69).In conclusion, this study found that the incidence of dementia was much higher in patients with T2D. CLD was associated with a modest increase in risk of dementia; however, there was no additive effect with T2D. In the population with dementia, however, the presence of CLD was associated with high mortality in patients with or without T2D. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Impact of diabetes mellitus and chronic liver disease on the incidence of dementia and all-cause mortality among patients with dementia

PubMed Central

Kim, Hyun Min; Lee, Yong-ho; Han, Kyungdo; Lee, Byung-Wan; Kang, Eun Seok; Kim, Jaetaek; Cha, Bong-Soo

2017-01-01

Abstract This study investigated the effects of the presence of type 2 diabetes mellitus (T2D) and/or chronic liver disease (CLD) on the incidence and prognosis of dementia during a 10-year period in Korea using a nationwide population-based dataset from the Korea National Health Insurance Service. To assess the impact of T2D and CLD on the incidence of dementia, we included subjects aged ≥60 years without dementia, T2D, and CLD from 2003 to 2005. We created another cohort for evaluating the all-cause mortality in subjects with dementia between 2003 and 2005. The participants were categorized into 4 groups: control (neither CLD nor T2D), CLD-only, T2D-only, and T2D-and-CLD groups, and they were followed up until 2013. The incidence of dementia was higher in the T2D-only group than in the control and CLD-only groups (2.78 vs. 2.04 and 2.00 per 1000 person-years). After adjustment for age, gender, and comorbid conditions, both T2D and CLD increased the risk of any type of dementia; however, the impact of CLD alone was much lower [hazard ratio (HR) 1.07, 95% confidence interval (CI): 1.06–1.08] than that of T2D alone (HR 1.27, 95% CI: 1.27–1.28). The risk of dementia did not significantly change in patients with the co-occurrence of T2D and CLD compared to those with T2D alone. The all-cause mortality rate was the lowest in the control group (2.59 per 1000 person-years) and the highest in the T2D-and-CLD group (3.77 per 1000 person-years). Presence of T2D or CLD alone was associated with higher mortality (HR 1.46 and HR 1.21, respectively) compared with in the absence of both the diseases. Furthermore, the presence of both the diseases further significantly increased the mortality rate compared to the presence of each disease alone (HR 1.67, 95% CI: 1.65–1.69). In conclusion, this study found that the incidence of dementia was much higher in patients with T2D. CLD was associated with a modest increase in risk of dementia; however, there was no additive effect with T2D. In the population with dementia, however, the presence of CLD was associated with high mortality in patients with or without T2D. PMID:29381970

Digestible, metabolizable, and net energy of camelina cake fed to growing pigs and additivity of energy in mixed diets.

PubMed

Kim, J W; Koo, B; Nyachoti, C M

2017-09-01

This experiment was conducted to determine the DE, ME, and NE contents of camelina cake (CC) and to test the hypothesis that dietary glucosinolates originating from CC will affect the additivity of energy in mixed diets containing different inclusion levels of corn, soybean meal (SBM), and CC. A total of 30 growing barrows ([Yorkshire × Landrace] × Duroc) with a mean BW of 16.8 kg (SD 1.4) were randomly allotted to 1 of 5 treatments with 6 replicates per treatment. Pigs were fed experimental diets for 16 d, including 10 d for adaptation and 6 d for total collection of feces and urine. The 5 experimental diets consisted of 3 corn-based diets to determine the DE, ME, and NE of the 3 ingredients (corn, SBM, and CC) and 2 mixed diets to test the additivity of DE, ME, and NE. The corn diet contained 97.52% corn; the SBM diet contained 67.52% corn and 30.0% SBM; the CC diet contained 67.52% corn and 30.0% CC; the Mixed diet 1 contained 67.52% corn, 20.0% SBM, and 10.0% CC; and the Mixed diet 2 contained 67.25% corn, 10.0% SBM, and 20.0% CC. Vitamins and minerals were included in the diets to meet or exceed the requirements for growing pigs (). Pigs were fed their assigned diets at 550 kcal ME/kg BW per day on the basis of BW on d 1, 5, and 10, which was close to ad libitum intake. Pigs had free access to water. Determined DE, ME, and NE contents of corn were 3,348, 3,254, and 2,579 kcal/kg, respectively; those of SBM were 3,626, 3,405, and 2,129 kcal/kg, respectively; and those of CC were 3,755, 3,465, and 2,383 kcal/kg, respectively. No differences between the predicted and determined DE, ME, and NE were observed in the 2 mixed diets. In conclusion, DE, ME, and calculated NE content of CC fed to growing pigs were 3,755, 3,465, and 2,383 kcal/kg (as-fed basis), respectively. In addition, additivity of DE, ME, and calculated NE was observed in the mixed diets containing corn, SBM, and CC, which indicates that dietary glucosinolates originating from up to 30% of CC inclusion do not affect DE, ME, and calculated NE of diets.

Introducing a modular activity monitoring system.

PubMed

Reiss, Attila; Stricker, Didier

2011-01-01

In this paper, the idea of a modular activity monitoring system is introduced. By using different combinations of the system's three modules, different functionality becomes available: 1) a coarse intensity estimation of physical activities 2) different features based on HR-data and 3) the recognition of basic activities and postures. 3D-accelerometers--placed on lower arm, chest and foot--and a heart rate monitor were used as sensors. A dataset with 8 subjects and 14 different activities was recorded to evaluate the performance of the system. The overall performance on the intensity estimation task, relying on the chest-worn accelerometer and the HR-monitor, was 94.37%. The overall performance on the activity recognition task, using all three accelerometer placements and the HR-monitor, was 90.65%. This paper also gives an analysis of the importance of different accelerometer placements and the importance of a HR-monitor for both tasks.

MO-G-17A-06: Kernel Based Dosimetry for 90Y Microsphere Liver Therapy Using 90Y Bremsstrahlung SPECT/CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mikell, J; Siman, W; Kappadath, S

2014-06-15

Purpose: 90Y microsphere therapy in liver presents a situation where beta transport is dominant and the tissue is relatively homogenous. We compare voxel-based absorbed doses from a 90Y kernel to Monte Carlo (MC) using quantitative 90Y bremsstrahlung SPECT/CT as source distribution. Methods: Liver, normal liver, and tumors were delineated by an interventional radiologist using contrast-enhanced CT registered with 90Y SPECT/CT scans for 14 therapies. Right lung was segmented via region growing. The kernel was generated with 1.04 g/cc soft tissue for 4.8 mm voxel matching the SPECT. MC simulation materials included air, lung, soft tissue, and bone with varying densities.more » We report percent difference between kernel and MC (%Δ(K,MC)) for mean absorbed dose, D70, and V20Gy in total liver, normal liver, tumors, and right lung. We also report %Δ(K,MC) for heterogeneity metrics: coefficient of variation (COV) and D10/D90. The impact of spatial resolution (0, 10, 20 mm FWHM) and lung shunt fraction (LSF) (1,5,10,20%) on the accuracy of MC and kernel doses near the liver-lung interface was modeled in 1D. We report the distance from the interface where errors become <10% of unblurred MC as d10(side of interface, dose calculation, FWHM blurring, LSF). Results: The %Δ(K,MC) for mean, D70, and V20Gy in tumor and liver was <7% while right lung differences varied from 60–90%. The %Δ(K,MC) for COV was <4.8% for tumor and liver and <54% for the right lung. The %Δ(K,MC) for D10/D90 was <5% for 22/23 tumors. d10(liver,MC,10,1–20) awere <9mm and d10(liver,MC,20,1–20) awere <15mm; both agreed within 3mm to the kernel. d10(lung,MC,10,20), d10(lung,MC,10,1), d10(lung,MC,20,20), and d10(lung,MC,20,1) awere 6, 25, 15, and 34mm, respectively. Kernel calculations on blurred distributions in lung had errors > 10%. Conclusions: Liver and tumor voxel doses with 90Y kernel and MC agree within 7%. Large differences exist between the two methods in right lung. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number R01CA138986. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.« less

Vitamin D insufficiency over 5 years is associated with increased fracture risk-an observational cohort study of elderly women.

PubMed

Buchebner, D; McGuigan, F; Gerdhem, P; Malm, J; Ridderstråle, M; Akesson, K

2014-12-01

This study of elderly Swedish women investigated the association between chronic vitamin D insufficiency and osteoporotic fractures occurring between ages 80-90. The incidence and risk of hip and major osteoporotic fractures was significantly higher in elderly women with low vitamin D levels maintained over 5 years. Vitamin D insufficiency among the elderly is common; however, relatively little is known about the effects of long-term hypovitaminosis D on fracture. We investigated sequential assessment of serum 25(OH)D at age 75 and 80 to determine if continuously low 25(OH)D levels are associated with increased 10-year fracture incidence. One thousand forty-four Swedish women from the population-based OPRA cohort, all 75 years old, attended at baseline (BL); 715 attended at 5 years. S-25(OH)D was available in 987 and 640, respectively and categorized as: <50 (Low), 50-75 (Intermediate), and >75 nmol/L (High). Incident fracture data was collected with maximum follow-up to 90 years of age. Hip fracture incidence between age 80-85 was higher in women who had low 25(OH)D at both baseline and 5 years (22.2 % (Low) vs. 6.6 % (High); p = 0.003). Between age 80-90, hip fracture incidence was more than double that of women in the high category (27.9 vs. 12.3 %; p = 0.006). Within 5-years, 50 % of women in the continuously low group compared to 34 % in the continuously high 25(OH)D group had an osteoporotic fracture (p = 0.004) while 10-year incidence was higher compared to the intermediate (p = 0.020) but not the high category (p = 0.053). The 10-year relative risk of hip fracture was almost three times higher and osteoporotic fracture risk almost doubled for women in the lowest 25(OH)D category compared to the high category (HR 2.7 and 1.7; p = 0.003 and 0.023, respectively). In these elderly women, 25(OH)D insufficiency over 5-years was associated with increased 10-year risk of hip and major osteoporotic fractures.

1,25 Dihydroxyvitamin D circulating levels, calcitriol administration, and incidence of acute rejection, CMV infection, and polyoma virus infection in renal transplant recipients.

PubMed

Moscarelli, Luciano; Antognoli, Giulia; Buti, Elisa; Dervishi, Egrina; Fani, Filippo; Caroti, Leonardo; Tsalouchos, Aris; Romoli, Elena; Ghiandai, Giulia; Minetti, Enrico

2016-10-01

Observation that 1,25-Dihydroxyvitamin-D3 has an immunomodulatory effect on innate and adaptive immunity raises the possible effect on clinical graft outcome. Aim of this study was to evaluate the correlation of biopsy-proven acute rejection, CMV infection, BKV infection, with 1,25-Dihydroxyvitamin-D3 deficiency and the benefit of calcitriol supplementation before and during the transplantation. Risk factors and kidney graft function were also evaluated. All RTRs received induction therapy with basiliximab, cyclosporine, mycophenolic acid, and steroids. During the first year, the incidence of BPAR (4% vs 11%, P=.04), CMV infection (3% vs 9%, P=.04), and BKV infection (6% vs 19%, P=.04) was significantly lower in users compared to controls. By multivariate Cox regression analysis, 1,25-Dihydroxyvitamin-D3 deficiency and no calcitriol exposure were independent risk factors for BPAR (HR=4.30, P<.005 and HR=3.25, P<.05), for CMV infection (HR=2.33, P<.05 and HR=2.31, P=.001), and for BKV infection (HR=2.41, P<.05 and HR=2.45, P=.001). After one year, users had a better renal function: eGFR was 62.5±6.7 mL/min vs 51.4±7.6 mL/min (P<.05). Only one user developed polyomavirus-associated nephropathy vs 15 controls. Two users lost their graft vs 11 controls. 1,25(OH)2-D3 deficiency circulating levels increased the risk of BPAR, CMV infection, BKV infection after kidney transplantation. Administration of calcitriol is a way to obtain adequate 1,25(OH)2-D3 circulating levels. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Plant-Based Dietary Patterns and Incidence of Type 2 Diabetes in US Men and Women: Results from Three Prospective Cohort Studies

PubMed Central

Satija, Ambika; Bhupathiraju, Shilpa N.; Rimm, Eric B.; Spiegelman, Donna; Chiuve, Stephanie E.; Borgi, Lea; Willett, Walter C.; Manson, JoAnn E.; Sun, Qi; Hu, Frank B.

2016-01-01

Background Plant-based diets have been recommended to reduce the risk of type 2 diabetes (T2D). However, not all plant foods are necessarily beneficial. We examined the association of an overall plant-based diet and hypothesized healthful and unhealthful versions of a plant-based diet with T2D incidence in three prospective cohort studies in the US. Methods and Findings We included 69,949 women from the Nurses’ Health Study (1984–2012), 90,239 women from the Nurses’ Health Study 2 (1991–2011), and 40,539 men from the Health Professionals Follow-Up Study (1986–2010), free of chronic diseases at baseline. Dietary data were collected every 2–4 y using a semi-quantitative food frequency questionnaire. Using these data, we created an overall plant-based diet index (PDI), where plant foods received positive scores, while animal foods (animal fats, dairy, eggs, fish/seafood, poultry/red meat, miscellaneous animal-based foods) received reverse scores. We also created a healthful plant-based diet index (hPDI), where healthy plant foods (whole grains, fruits, vegetables, nuts, legumes, vegetable oils, tea/coffee) received positive scores, while less healthy plant foods (fruit juices, sweetened beverages, refined grains, potatoes, sweets/desserts) and animal foods received reverse scores. Lastly, we created an unhealthful plant-based diet index (uPDI) by assigning positive scores to less healthy plant foods and reverse scores to healthy plant foods and animal foods. We documented 16,162 incident T2D cases during 4,102,369 person-years of follow-up. In pooled multivariable-adjusted analysis, both PDI and hPDI were inversely associated with T2D (PDI: hazard ratio [HR] for extreme deciles 0.51, 95% CI 0.47–0.55, p trend < 0.001; hPDI: HR for extreme deciles 0.55, 95% CI 0.51–0.59, p trend < 0.001). The association of T2D with PDI was considerably attenuated when we additionally adjusted for body mass index (BMI) categories (HR 0.80, 95% CI 0.74–0.87, p trend < 0.001), while that with hPDI remained largely unchanged (HR 0.66, 95% CI 0.61–0.72, p trend < 0.001). uPDI was positively associated with T2D even after BMI adjustment (HR for extreme deciles 1.16, 95% CI 1.08–1.25, p trend < 0.001). Limitations of the study include self-reported diet assessment, with the possibility of measurement error, and the potential for residual or unmeasured confounding given the observational nature of the study design. Conclusions Our study suggests that plant-based diets, especially when rich in high-quality plant foods, are associated with substantially lower risk of developing T2D. This supports current recommendations to shift to diets rich in healthy plant foods, with lower intake of less healthy plant and animal foods. PMID:27299701

Report of the Secretary of Defense Task Force on DoD Nuclear Weapons Management. Phase 1. The Air Force’s Nuclear Mission

DTIC Science & Technology

2008-09-01

under- resourced. • Missile transfer vans /warhead transfer vans require upgrades. • ICBM weapon system test sets under-funded; the coding system...Air Force’s Nuclear Mission D-1 Appendix D. Current B-52 Basing Status Barksdale AFB, LA 64 B-52Hs Minot AFB, ND 27 B-52Hs Edwards AFB, CA 3...Barksdale – 64 B-52s 2 BW (ACC) 15 TF; 24 CC; 7 BAI 53 WG (ACC) 2 Test Coded 917 WG (AFRC) 8 CC; 1 BAI 7 Unfunded AR Edwards - 3 B-52s 412 TW 2 Test

Inverse relationship between sleep duration and myopia.

PubMed

Jee, Donghyun; Morgan, Ian G; Kim, Eun Chul

2016-05-01

To investigate the association between sleep duration and myopia. This population-based, cross-sectional study using a nationwide, systemic, stratified, multistage, clustered sampling method included a total of 3625 subjects aged 12-19 years who participated in the Korean National Health and Nutrition Examination Survey 2008-2012. All participants underwent ophthalmic examination and a standardized interview including average sleep duration (hr/day), education, physical activity and economic status (annual household income). Refractive error was measured by autorefraction without cycloplegia. Myopia and high myopia were defined as ≤-0.50 dioptres (D) and ≤-6.0 D, respectively. Sleep durations were classified into 5 categories: <5, 6, 7, 8 and >9 hr. The overall prevalence of myopia and high myopia were 77.8% and 9.4%, respectively, and the overall sleep duration was 7.1 hr/day. The refractive error increased by 0.10 D per 1 hr increase in sleep after adjusting for potential confounders including sex, age, height, education level, economic status and physical activity. The adjusted odds ratio (OR) for refractive error was 0.90 (95% confidence interval [CI], 0.83-0.97) per 1 hr increase in sleep. The adjusted OR for myopia was decreased in those with >9 hr of sleep (OR, 0.59; 95% CI, 0.38-0.93; p for trend = 0.006) than in those with <5 hr of sleep. However, high myopia was not associated with sleep duration. This study provides the population-based, epidemiologic evidence for an inverse relationship between sleep duration and myopia in a representative population of Korean adolescents. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Adaptive radiation therapy for postprostatectomy patients using real-time electromagnetic target motion tracking during external beam radiation therapy.

PubMed

Zhu, Mingyao; Bharat, Shyam; Michalski, Jeff M; Gay, Hiram A; Hou, Wei-Hsien; Parikh, Parag J

2013-03-15

Using real-time electromagnetic (EM) transponder tracking data recorded by the Calypso 4D Localization System, we report inter- and intrafractional target motion of the prostate bed, describe a strategy to evaluate treatment adequacy in postprostatectomy patients receiving intensity modulated radiation therapy (IMRT), and propose an adaptive workflow. Tracking data recorded by Calypso EM transponders was analyzed for postprostatectomy patients that underwent step-and-shoot IMRT. Rigid target motion parameters during beam delivery were calculated from recorded transponder positions in 16 patients with rigid transponder geometry. The delivered doses to the clinical target volume (CTV) were estimated from the planned dose matrix and the target motion for the first 3, 5, 10, and all fractions. Treatment adequacy was determined by comparing the delivered minimum dose (Dmin) with the planned Dmin to the CTV. Treatments were considered adequate if the delivered CTV Dmin is at least 95% of the planned CTV Dmin. Translational target motion was minimal for all 16 patients (mean: 0.02 cm; range: -0.12 cm to 0.07 cm). Rotational motion was patient-specific, and maximum pitch, yaw, and roll were 12.2, 4.1, and 10.5°, respectively. We observed inadequate treatments in 5 patients. In these treatments, we observed greater target rotations along with large distances between the CTV centroid and transponder centroid. The treatment adequacy from the initial 10 fractions successfully predicted the overall adequacy in 4 of 5 inadequate treatments and 10 of 11 adequate treatments. Target rotational motion could cause underdosage to partial volume of the postprostatectomy targets. Our adaptive treatment strategy is applicable to post-prostatectomy patients receiving IMRT to evaluate and improve radiation therapy delivery. Copyright © 2013 Elsevier Inc. All rights reserved.

Lactose Intolerance (LCT-13910C>T) Genotype Is Associated with Plasma 25-Hydroxyvitamin D Concentrations in Caucasians: A Mendelian Randomization Study.

PubMed

Alharbi, Ohood; El-Sohemy, Ahmed

2017-06-01

Background: The LCT -13910C>T gene variant is associated with lactose intolerance (LI) in different ethnic groups. Individuals with LI often limit or avoid dairy consumption, a major dietary source of vitamin D in North America, which may lead to inadequate vitamin D intake. Objective: The objective was to determine the prevalence of genotypes predictive of LI in different ethnic groups living in Canada and to determine whether the LCT genotype is associated with plasma 25(OH)D concentrations. Methods: Blood samples were drawn from a total of 1495 men and women aged 20-29 y from the Toronto Nutrigenomics and Health Study for genotyping and plasma 25(OH)D analysis. Intakes of dairy were assessed by using a 196-item food frequency questionnaire. The prevalence of LCT -13910C>T genotypes was compared by using χ 2 analysis. Using a Mendelian randomization approach, we examined the association between LCT genotypes and 25(OH)D concentrations. Results: Approximately 32% of Caucasians, 99% of East Asians, 74% of South Asians, and 59% of those with other or mixed ethnicities had the CC genotype associated with LI. Compared with those with the TT genotype, those with the CC genotype had a lower mean ± SE total dairy intake (2.15 ± 0.09 compared with 2.67 ± 0.12 servings/d, P = 0.003), a lower skim-milk intake (0.20 ± 0.03 compared with 0.46 ± 0.06 servings/d, P = 0.0004), and a lower plasma 25(OH)D concentration (63 ± 1.9 compared with 75.8 ± 2.4 nmol/L, P < 0.0001). The CT and CC genotypes were associated with a 50% and a 2-fold increased risk, respectively, of a suboptimal plasma 25(OH)D concentration (<75 nmol/L). Conclusions: In Caucasians, the CC genotype that predicts LI is associated with a lower plasma 25(OH)D concentration, which is attributable at least in part to a lower intake of dairy, particularly skim milk. Increased risk of suboptimal concentrations of vitamin D was also observed among those with the CT genotype, suggesting an intermediate effect of the heterozygous genotype. © 2017 American Society for Nutrition.

Reiki improves heart rate homeostasis in laboratory rats.

PubMed

Baldwin, Ann Linda; Wagers, Christina; Schwartz, Gary E

2008-05-01

To determine whether application of Reiki to noise-stressed rats can reduce their heart rates (HRs) and blood pressures. In a previous study, we showed that exposure of rats to 90 dB white noise for 15 minutes caused their HRs and blood pressures to significantly increase. Reiki has been shown to significantly decrease HR and blood pressure in a small group of healthy human subjects. However, use of humans in such studies has the disadvantage that experimental interpretations are encumbered by the variable of belief or skepticism regarding Reiki. For that reason, noise-stressed rats were used as an animal model to test the efficacy of Reiki in reducing elevated HR and blood pressure. Three unrestrained, male Sprague-Dawley rats implanted with radiotelemetric transducers were exposed daily for 8 days to a 15-minute white noise regimen (90 dB). For the last 5 days, the rats received 15 minutes of Reiki immediately before the noise and during the noise period. The experiment was repeated on the same animals but using sham Reiki. The animals were housed in a quiet room in University of Arizona Animal Facility. Mean HRs and blood pressure were determined before Reiki/sham Reiki, during Reiki/sham Reiki, and during the noise in each case. Reiki, but not sham Reiki, significantly reduced HR compared to initial values. With Reiki, there was a high correlation between change in HR and initial HR, suggesting a homeostatic effect. Reiki, but not sham Reiki, significantly reduced the rise in HR produced by exposure of the rats to loud noise. Neither Reiki nor sham Reiki significantly affected blood pressure. Reiki is effective in modulating HR in stressed and unstressed rats, supporting its use as a stress-reducer in humans.

An Exploration of Team Information Processing in a Dynamic Group Choice Task Involving Uncertainty

DTIC Science & Technology

1988-01-01

T7.JA I- TYPE OF REPORT A PERIoD COVERED )•Uo0L¶tio&J pROCISSIOC 10 h Ty3JWk,4C P1D1 F& THESIS GClROUP CH6tCC IASI< h iD)VOL Ih9’J13 UV CCAI.’AWJY 6...praise be to God for His unfailing pi-omises and fr, many answers to prayer . He has always been with me, even carrying -mo over the roughest spots...Events .90 ’TAPLE S.1, TRAP Task Point Values . . . . ........... . . B-5 TAELE C.1, Types of Uncertain Events .......... .... C-I TABL•E 1.1, Coll Means

SU-E-T-551: PTV Is the Worst-Case of CTV in Photon Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harrington, D; Liu, W; Park, P

2014-06-01

Purpose: To examine the supposition of the static dose cloud and adequacy of the planning target volume (PTV) dose distribution as the worst-case representation of clinical target volume (CTV) dose distribution for photon therapy in head and neck (H and N) plans. Methods: Five diverse H and N plans clinically delivered at our institution were selected. Isocenter for each plan was shifted positively and negatively in the three cardinal directions by a displacement equal to the PTV expansion on the CTV (3 mm) for a total of six shifted plans per original plan. The perturbed plan dose was recalculated inmore » Eclipse (AAA v11.0.30) using the same, fixed fluence map as the original plan. The dose distributions for all plans were exported from the treatment planning system to determine the worst-case CTV dose distributions for each nominal plan. Two worst-case distributions, cold and hot, were defined by selecting the minimum or maximum dose per voxel from all the perturbed plans. The resulting dose volume histograms (DVH) were examined to evaluate the worst-case CTV and nominal PTV dose distributions. Results: Inspection demonstrates that the CTV DVH in the nominal dose distribution is indeed bounded by the CTV DVHs in the worst-case dose distributions. Furthermore, comparison of the D95% for the worst-case (cold) CTV and nominal PTV distributions by Pearson's chi-square test shows excellent agreement for all plans. Conclusion: The assumption that the nominal dose distribution for PTV represents the worst-case dose distribution for CTV appears valid for the five plans under examination. Although the worst-case dose distributions are unphysical since the dose per voxel is chosen independently, the cold worst-case distribution serves as a lower bound for the worst-case possible CTV coverage. Minor discrepancies between the nominal PTV dose distribution and worst-case CTV dose distribution are expected since the dose cloud is not strictly static. This research was supported by the NCI through grant K25CA168984, by The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research, and by the Fraternal Order of Eagles Cancer Research Fund, the Career Development Award Program at Mayo Clinic.« less

Flood risk assessment through 1D/2D couple HEC-RAS hydrodynamic modeling- A case study of Surat City, Lower Tapi Basin, India

NASA Astrophysics Data System (ADS)

Patel, Dhruvesh; Ramirez, Jorge; Srivastava, Prashant; Bray, Michaela; Han, Dawei

2017-04-01

Surat, known as the diamond city of Gujart is situated 100 km downstream of Ukai dam and near the mouth of river Tapi and affected by the flood at every alternate year. The city experienced catastrophic floods in 1933, 1959, 1968, 1970, 1994, 1998 and 2006. It is estimated that a single flood event during August 6-12, 2006 in Surat and Hazira twin-city, caused heavy damages, resulted in the death of 300 people and property damage worth € 289 million. The peak discharge of 25768 m3 s-1 release from Ukai dam was responsible for the disastrous flood in Surat city. To identifylow lying areas prone to inundation and reduce the uncertainty in flood mitigation measures, HEC-RAS based 1D/2D Couple hydrodynamic modeling is carried out for Surat city. Release from the Ukai dam and tidal level of the sea are considered for upstream and downstream boundary condition. 299 surveyed cross-sections have been considered for 1D modeling, whereas a topographic map at 0.5 m contour interval was used to produce a 5 m grid and SRTM (30 & 90 m) grid has been considered for Suart and Lower Tapi Basin (LTB). Flow is simulated under unsteady conditions, calibrated for the year 1998 and validated for the year 2006. The simulated result shows that the 9th August 18.00 hr was the worst day for Surat city and maximum 75-77 % area was under inundation. Most of the flooded area experienced 0.25 m/s water velocity with the duration of 90 hr. Due to low velocity and high duration of the flood, a low lying area within the west zone and south-west zone of the city was badly affected by the flood, whereas the south zone and south-east zone was least. Simulated results show good correlation when compared with an observed flood level map. The simulated results will be helpful to improve the flood resilience strategy at Surat city and reduce the uncertainty for flood inundation mapping for future dam releases. The present case study shows the applicability of 1D/2D coupled hydrodynamic modeling for flood inundation mapping and can be applied for flood assessment at locations with similar geographical conditions.

Technical Actions, Heart Rate, and Locomotor Activity in 7v7 and 8v8 Games for Female Youth Soccer Players.

PubMed

Ørntoft, Christina; Larsen, Malte N; Andersen, Thomas B; Rasmussen, Lasse S; Póvoas, Susana C A; Randers, Morten B; Krustrup, Peter

2016-12-01

Ørntoft, C, Larsen, MN, Andersen, TB, Rasmussen, LS, Póvoas, SCA, Randers, MB, and Krustrup, P. Technical actions, heart rate, and locomotor activity in 7v7 and 8v8 games for female youth soccer players. J Strength Cond Res 30(12): 3298-3303, 2016-The purpose of this study was to evaluate technical performance, heart rate (HR), and activity profile in 7v7 and 8v8 soccer games for 9- to 10-year-old girls (U11). A total of 24 female youth players participated in the study, all playing 20-minute 7v7 and 8v8 games with 160 and 223 m per player, respectively. Technical actions, HR, and activity profile were measured during the games using video filming, HR monitors, and 5-Hz Global positioning system (GPS) units. The number of technical actions was higher in 7v7 than in 8v8 games (34 ± 19 vs. 28 ± 14; p = 0.03; d = 0.37), as was the number of successful actions (25 ± 16 vs. 20 ± 12; p = 0.01; d = 0.35), with no difference in success rate for technical actions (70 ± 13 vs. 69 ± 14%; p = 0.63; d = 0.07). No differences were found between 7v7 and 8v8 in total distance covered (1,574 ± 251 and 1,622 ± 281 m; p = 0.66; d = 0.18), peak speed (19.5 ± 2.6 and 20.7 ± 1.5 km·h; p = 0.16; d = 0.56), mean HR values (85 ± 5 and 86 ± 6%HRpeak; p = 0.85; d = 0.18), and time of >90% HRpeak (37 ± 16 and 35 ± 14% of playing time; p = 0.70; d = 0.13). Distance covered at the highest running speeds of >16 km·h was lower in 7v7 than in 8v8 games (34 ± 24 vs. 63 ± 34 m; p = 0.018; d = 0.98), as was the number of entries into this speed zone (8 ± 5 vs. 13 ± 7; p = 0.006; d = 0.82). In conclusion, more technical actions and successful actions were observed in 7v7 than in 8v8 games, but players covered more ground with high-speed running in 8v8 games. This study also revealed that HR values were high in both game formats for U11 adolescent female players, with no difference between formats.

32 CFR Appendix E to Part 57 - DoD-CC on Early Intervention, Special Education, and Related Services

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false DoD-CC on Early Intervention, Special Education... SECRETARY OF DEFENSE PERSONNEL, MILITARY AND CIVILIAN PROVISION OF EARLY INTERVENTION AND SPECIAL EDUCATION..., Special Education, and Related Services A. Committee Membership The DoD-CC shall meet at least yearly to...

32 CFR Appendix E to Part 57 - DoD-CC on Early Intervention, Special Education, and Related Services

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 1 2011-07-01 2011-07-01 false DoD-CC on Early Intervention, Special Education... SECRETARY OF DEFENSE PERSONNEL, MILITARY AND CIVILIAN PROVISION OF EARLY INTERVENTION AND SPECIAL EDUCATION..., Special Education, and Related Services A. Committee Membership The DoD-CC shall meet at least yearly to...

External-Beam Radiation Therapy and High-Dose Rate Brachytherapy Combined With Long-Term Androgen Deprivation Therapy in High and Very High Prostate Cancer: Preliminary Data on Clinical Outcome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martinez-Monge, Rafael, E-mail: rmartinezm@unav.es; Moreno, Marta; Ciervide, Raquel

2012-03-01

Purpose: To determine the feasibility of combined long-term androgen deprivation therapy (ADT) and dose escalation with high-dose-rate (HDR) brachytherapy. Methods and Materials: Between 2001 and 2007, 200 patients with high-risk prostate cancer (32.5%) or very high-risk prostate cancer (67.5%) were prospectively enrolled in this Phase II trial. Tumor characteristics included a median pretreatment prostate-specific antigen of 15.2 ng/mL, a clinical stage of T2c, and a Gleason score of 7. Treatment consisted of 54 Gy of external irradiation (three-dimensional conformal radiotherapy [3DCRT]) followed by 19 Gy of HDR brachytherapy in four twice-daily treatments. ADT started 0-3 months before 3DCRT and continuedmore » for 2 years. Results: One hundred and ninety patients (95%) received 2 years of ADT. After a median follow-up of 3.7 years (range, 2-9), late Grade {>=}2 urinary toxicity was observed in 18% of the patients and Grade {>=}3 was observed in 5%. Prior transurethral resection of the prostate (p = 0.013) and bladder D{sub 50} {>=}1.19 Gy (p = 0.014) were associated with increased Grade {>=}2 urinary complications; age {>=}70 (p = 0.05) was associated with Grade {>=}3 urinary complications. Late Grade {>=}2 gastrointestinal toxicity was observed in 9% of the patients and Grade {>=}3 in 1.5%. CTV size {>=}35.8 cc (p = 0.007) and D{sub 100} {>=}3.05 Gy (p = 0.01) were significant for increased Grade {>=}2 complications. The 5-year and 9-year biochemical relapse-free survival (nadir + 2) rates were 85.1% and 75.7%, respectively. Patients with Gleason score of 7-10 had a decreased biochemical relapse-free survival (p = 0.007). Conclusions: Intermediate-term results at the 5-year time point indicate a favorable outcome without an increase in the rate of late complications.« less

Effects of Weight Loss, Weight Cycling, and Weight Loss Maintenance on Diabetes Incidence and Change in Cardiometabolic Traits in the Diabetes Prevention Program

PubMed Central

Pan, Qing; Jablonski, Kathleen A.; Aroda, Vanita R.; Watson, Karol E.; Bray, George A.; Kahn, Steven E.; Florez, Jose C.; Perreault, Leigh; Franks, Paul W.

2014-01-01

OBJECTIVE This study examined specific measures of weight loss in relation to incident diabetes and improvement in cardiometabolic risk factors. RESEARCH DESIGN AND METHODS This prospective, observational study analyzed nine weight measures, characterizing baseline weight, short- versus long-term weight loss, short- versus long-term weight regain, and weight cycling, within the Diabetes Prevention Program (DPP) lifestyle intervention arm (n = 1,000) for predictors of incident diabetes and improvement in cardiometabolic risk factors over 2 years. RESULTS Although weight loss in the first 6 months was protective of diabetes (hazard ratio [HR] 0.94 per kg, 95% CI 0.90, 0.98; P < 0.01) and cardiometabolic risk factors (P < 0.01), weight loss from 0 to 2 years was the strongest predictor of reduced diabetes incidence (HR 0.90 per kg, 95% CI 0.87, 0.93; P < 0.01) and cardiometabolic risk factor improvement (e.g., fasting glucose: β = −0.57 mg/dL per kg, 95% CI −0.66, −0.48; P < 0.01). Weight cycling (defined as number of 5-lb [2.25-kg] weight cycles) ranged 0–6 times per participant and was positively associated with incident diabetes (HR 1.33, 95% CI 1.12, 1.58; P < 0.01), fasting glucose (β = 0.91 mg/dL per cycle; P = 0.02), HOMA-IR (β = 0.25 units per cycle; P = 0.04), and systolic blood pressure (β = 0.94 mmHg per cycle; P = 0.01). After adjustment for baseline weight, the effect of weight cycling remained statistically significant for diabetes risk (HR 1.22, 95% CI 1.02, 1.47; P = 0.03) but not for cardiometabolic traits. CONCLUSIONS Two-year weight loss was the strongest predictor of reduced diabetes risk and improvements in cardiometabolic traits. PMID:25024396

Role of the chemokine decoy receptor D6 in balancing inflammation, immune activation, and antimicrobial resistance in Mycobacterium tuberculosis infection

PubMed Central

Di Liberto, Diana; Locati, Massimo; Caccamo, Nadia; Vecchi, Annunciata; Meraviglia, Serena; Salerno, Alfredo; Sireci, Guido; Nebuloni, Manuela; Caceres, Neus; Cardona, Pere-Joan; Dieli, Francesco; Mantovani, Alberto

2008-01-01

D6 is a decoy and scavenger receptor for inflammatory CC chemokines. D6-deficient mice were rapidly killed by intranasal administration of low doses of Mycobacterium tuberculosis. The death of D6−/− mice was associated with a dramatic local and systemic inflammatory response with levels of M. tuberculosis colony-forming units similar to control D6-proficient mice. D6-deficient mice showed an increased numbers of mononuclear cells (macrophages, dendritic cells, and CD4 and CD8 T lymphocytes) infiltrating inflamed tissues and lymph nodes, as well as abnormal increased concentrations of CC chemokines (CCL2, CCL3, CCL4, and CCL5) and proinflammatory cytokines (tumor necrosis factor α, interleukin 1β, and interferon γ) in bronchoalveolar lavage and serum. High levels of inflammatory cytokines in D6−/− infected mice were associated with liver and kidney damage, resulting in both liver and renal failure. Blocking inflammatory CC chemokines with a cocktail of antibodies reversed the inflammatory phenotype of D6−/− mice but led to less controlled growth of M. tuberculosis. Thus, the D6 decoy receptor plays a key role in setting the balance between antimicrobial resistance, immune activation, and inflammation in M. tuberculosis infection. PMID:18695004

Puckering transitions in cyclohexane: Revisited

NASA Astrophysics Data System (ADS)

Kang, Young Kee; Park, Hae Sook

2018-06-01

The interconversion pathways along the puckering transitions in cyclohexane were explored on the two-dimensional projection of the Cremer-Pople sphere using DFT methods and the CCSD(T), MP2, and dispersion-corrected DFT methods with various basis sets were assessed for the relative energies of local minima and transition states for the representative puckering transition pathways. The ωB97X-D/cc-pVTZ and ωB97X-D/def2-QZVP levels of theory well reproduced the relative energies with RMSD = 0.13 kcal/mol against the CCSD(T)/CBS-limit energies. The calculated activation parameters for chair to twist-boat interconversion of cyclohexane at the ωB97X-D/cc-pVTZ//(PCM) M06-2X/6-31+G(d) level of theory were consistent with the observed values.

Dosimetric impact of applicator displacement during high dose rate (HDR) Cobalt-60 brachytherapy for cervical cancer: A planning study

NASA Astrophysics Data System (ADS)

Yong, J. S.; Ung, N. M.; Jamalludin, Z.; Malik, R. A.; Wong, J. H. D.; Liew, Y. M.; Ng, K. H.

2016-02-01

We investigated the dosimetric impact of applicator displacement on dose specification during high dose rate (HDR) Cobalt-60 (Co-60) brachytherapy for cervical cancer through a planning study. Eighteen randomly selected HDR full insertion plans were restrospectively studied. The tandem and ovoids were virtually shifted translationally and rotationally in the x-, y- and z-axis directions on the treatment planning system. Doses to reference points and volumes of interest in the plans with shifted applicators were compared with the original plans. The impact of dose displacement on 2D (point-based) and 3D (volume-based) treatment planning techniques was also assessed. A ±2 mm translational y-axis applicator shift and ±4° rotational x-axis applicator shift resulted in dosimetric changes of more than 5% to organs at risk (OAR) reference points. Changes to the maximum doses to 2 cc of the organ (D2cc) in 3D planning were statistically significant and higher than the reference points in 2D planning for both the rectum and bladder (p<0.05). Rectal D2cc was observed to be the most sensitive to applicator displacement among all dose metrics. Applicator displacement that is greater than ±2 mm translational y-axis and ±4° rotational x-axis resulted in significant dose changes to the OAR. Thus, steps must be taken to minimize the possibility of applicator displacement during brachytherapy.

Evaluation of Dose Uncertainty to the Target Associated With Real-Time Tracking Intensity-Modulated Radiation Therapy Using the CyberKnife Synchrony System.

PubMed

Iwata, Hiromitsu; Inoue, Mitsuhiro; Shiomi, Hiroya; Murai, Taro; Tatewaki, Koshi; Ohta, Seiji; Okawa, Kohei; Yokota, Naoki; Shibamoto, Yuta

2016-02-01

We investigated the dose uncertainty caused by errors in real-time tracking intensity-modulated radiation therapy (IMRT) using the CyberKnife Synchrony Respiratory Tracking System (SRTS). Twenty lung tumors that had been treated with non-IMRT real-time tracking using CyberKnife SRTS were used for this study. After validating the tracking error in each case, we did 40 IMRT planning using 8 different collimator sizes for the 20 patients. The collimator size was determined for each planning target volume (PTV); smaller ones were one-half, and larger ones three-quarters, of the PTV diameter. The planned dose was 45 Gy in 4 fractions prescribed at 95% volume border of the PTV. Thereafter, the tracking error in each case was substituted into calculation software developed in house and randomly added in the setting of each beam. The IMRT planning incorporating tracking errors was simulated 1000 times, and various dose data on the clinical target volume (CTV) were compared with the original data. The same simulation was carried out by changing the fraction number from 1 to 6 in each IMRT plan. Finally, a total of 240 000 plans were analyzed. With 4 fractions, the change in the CTV maximum and minimum doses was within 3.0% (median) for each collimator. The change in D99 and D95 was within 2.0%. With decreases in the fraction number, the CTV coverage rate and the minimum dose decreased and varied greatly. The accuracy of real-time tracking IMRT delivered in 4 fractions using CyberKnife SRTS was considered to be clinically acceptable. © The Author(s) 2014.

Does Vitamin D Mediate the Protective Effects of Time Outdoors On Myopia? Findings From a Prospective Birth Cohort

PubMed Central

Guggenheim, Jeremy A.; Williams, Cathy; Northstone, Kate; Howe, Laura D.; Tilling, Kate; St Pourcain, Beate; McMahon, George; Lawlor, Debbie A.

2014-01-01

Purpose. More time outdoors is associated with a lesser risk of myopia, but the underlying mechanism is unclear. We tested the hypothesis that 25-hydroxyvitamin D (vitamin D) mediates the protective effects of time outdoors against myopia. Methods. We analyzed data for children participating in the Avon Longitudinal Study of Parents and Children (ALSPAC) population-based birth cohort: noncycloplegic autorefraction at age 7 to 15 years; maternal report of time outdoors at age 8 years and serum vitamin D2 and D3 at age 10 years. A survival analysis hazard ratio (HR) for incident myopia was calculated for children spending a high- versus low-time outdoors, before and after controlling for vitamin D level (N = 3677). Results. Total vitamin D and D3, but not D2, levels were higher in children who spent more time outdoors (mean [95% confidence interval (CI)] vitamin D in nmol/L: Total, 60.0 [59.4–60.6] vs. 56.9 [55.0–58.8], P = 0.001; D3, 55.4 [54.9–56.0] vs. 53.0 [51.3–54.9], P = 0.014; D2, 5.7 [5.5–5.8] vs. 5.4 [5.1–5.8], P = 0.23). In models including both time outdoors and sunlight-exposure–related vitamin D, there was no independent association between vitamin D and incident myopia (Total, HR = 0.83 [0.66–1.04], P = 0.11; D3, HR = 0.89 [0.72–1.10], P = 0.30), while time outdoors retained the same strong negative association with incident myopia as in unadjusted models (HR = 0.69 [0.55–0.86], P = 0.001). Conclusions. Total vitamin D and D3 were biomarkers for time spent outdoors, however there was no evidence they were independently associated with future myopia. PMID:25406278

Vitamin D-related host genetic variants alter HIV disease progression in children.

PubMed

Moodley, Amaran; Qin, Min; Singh, Kumud K; Spector, Stephen A

2013-11-01

Vitamin D deficiency is common in HIV infection and has been associated with advanced disease. This study investigated whether vitamin D-related genetic variants were associated with disease progression in HIV-infected children. The Fok-I (C/T), Bsm-I (G/A), GC (A/C), DHCR7 (G/T) and CYP2R1 (G/A) genetic variants were detected by real-time polymerase chain reaction in HIV-infected children who participated in the Pediatric AIDS Clinical Trials Group P152 and P300 protocols, which predated the availability of effective combination antiretroviral therapy. The primary endpoints included time to progression to the first HIV-related disease endpoint (≥2 opportunistic infection, weight growth failure) or death, which constituted the progression-free survival. Analyses were performed for age>2 years and ≤2 years separately adjusting for race and treatment effect. Of the 998 children evaluated, 139 experienced HIV disease progression. For children>2 years, rapid disease progression was associated with the DHCR7 G allele compared with the T allele (G/G vs. T/T: hazard ratio [HR]=5.0, P = 0.035; G/T vs. T/T: HR=4.5, P=0.042; G/G+G/T vs. T/T: HR=4.8, P=0.036) and the Bsm-I A allele compared with the G allele (A/G vs. G/G: HR=2.2, P=0.014 and A/G+A/A vs. G/G: HR=2.0, P=0.026). In children≤2 years, the Bsm-I A allele increased the risk of disease progression in Hispanics (A/A vs. G/A+G/G: HR=2.8, P=0.03 and A/A vs. G/G: HR=2.8, P=0.046) and whites (A/A vs. G/G: HR=6.6, P=0.025 and A/A vs. G/A+G/G: HR=3.6, P=0.038). Vitamin D-related host genetic variants that alter the availability and activity of vitamin D are associated with risk of HIV disease progression in children and may vary by age and race.

Low serum insulin-like growth factor-I (IGF-I) level is associated with increased risk of vascular dementia.

PubMed

Quinlan, Patrick; Horvath, Alexandra; Nordlund, Arto; Wallin, Anders; Svensson, Johan

2017-12-01

Insulin-like growth factor-I (IGF-I) is important for the adult brain, but little is known of the role of IGF-I in Alzheimeŕs disease (AD) or vascular dementia (VaD). A prospective study of 342 patients with subjective or objective mild cognitive impairment recruited at a single memory clinic. We determined whether serum IGF-I concentrations at baseline were associated with the risk of all-cause dementia, AD, or VaD. Patients developing mixed forms of AD and VaD were defined as suffering from VaD. The statistical analyses included Cox proportional hazards regression analysis. During the follow-up (mean 3.6 years), 95 (28%) of the patients developed all-cause dementia [AD, n=37 (11%) and VaD, n=42 (12%)]. Low as well as high serum IGF-I (quartile 1 or 4 vs. quartiles 2-3) did not associate with all-cause dementia [crude hazard ratio (HR) 1.30, 95% confidence interval (CI): 0.81-2.08 and crude HR 1.05, 95% CI: 0.63-1.75, respectively] or AD (crude HR 0.79, 95% CI: 0.35-1.79 and crude HR 0.94, 95% CI: 0.43-2.06, respectively]. In contrast, low serum IGF-I concentrations were associated with increased risk of VaD (quartile 1 vs. quartiles 2-3, crude HR 2.22, 95% CI: 1.13-4.36). The latter association remained significant also after adjustment for multiple covariates. In a memory clinic population, low serum IGF-I was a risk marker for subsequent VaD whereas low IGF-I did not associate with the risk of AD. High serum IGF-I was not related to the risk of conversion to dementia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Vaginal Dose Is Associated With Toxicity in Image Guided Tandem Ring or Ovoid-Based Brachytherapy.

PubMed

Susko, Matthew; Craciunescu, Oana; Meltsner, Sheridan; Yang, Yun; Steffey, Beverly; Cai, Jing; Chino, Junzo

2016-04-01

To calculate vaginal doses during image guided brachytherapy with volume-based metrics and correlate with long-term vaginal toxicity. In this institutional review board-approved study, institutional databases were searched to identify women undergoing computed tomography and/or magnetic resonance-guided brachytherapy at the Duke Cancer Center from 2009 to 2015. All insertions were contoured to include the vagina as a 3-dimensional structure. All contouring was performed on computed tomography or magnetic resonance imaging and used a 0.4-cm fixed brush to outline the applicator and/or packing, expanded to include any grossly visible vagina. The surface of the cervix was specifically excluded from the contour. High-dose-rate (HDR) and low-dose-rate (LDR) doses were converted to the equivalent dose in 2-Gy fractions using an α/β of 3 for late effects. The parameters D0.1cc, D1cc, and D2cc were calculated for all insertions and summed with prior external beam therapy. Late and subacute toxicity to the vagina were determined by the Common Terminology Criteria for Adverse Events version 4.0 and compared by the median and 4th quartile doses, via the log-rank test. Univariate and multivariate hazard ratios were calculated via Cox regression. A total of 258 insertions in 62 women who underwent definitive radiation therapy including brachytherapy for cervical (n=48) and uterine cancer (n=14) were identified. Twenty HDR tandem and ovoid, 32 HDR tandem and ring, and 10 LDR tandem and ovoid insertions were contoured. The median values (interquartile ranges) for vaginal D0.1cc, D1cc, and D2cc were 157.9 (134.4-196.53) Gy, 112.6 (96.7-124.6) Gy, and 100.5 (86.8-108.4) Gy, respectively. At the 4th quartile cutoff of 108 Gy for D2cc, the rate of late grade 1 toxicity at 2 years was 61.2% (95% confidence interval [CI] 43.0%-79.4%) below 108 Gy and 83.9% (63.9%-100%) above (P=.018); grade 2 or greater toxicity was 36.2% (95% CI 15.8%-56.6%) below 108 Gy and 70.7% (95% CI 45.2%-96.2%) above (P=.004); and grade 3 or worse toxicity was 9.9% (95% CI 0.0%-23.6%) below 108 Gy and 30.0% (95% CI 4.7%-55.3%) above (P=.025). This association was maintained on multivariate analysis, independent of covariates such as applicator type, age, and dose rate. Vaginal dose was associated with all grades of vaginal toxicity. Confirmation at other sites using this methodology will be necessary to establish reproducibility; however, the integration of routine calculation of vaginal dose may be warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

The optimal number of personnel for good quality of chest compressions: A prospective randomized parallel manikin trial

PubMed Central

Huh, Ji Young; Nishiyama, Kei; Hayashi, Hiroyuki

2017-01-01

Background Long durational chest compression (CC) deteriorates cardiopulmonary resuscitation (CPR) quality. The appropriate number of CC personnel for minimizing rescuer’s fatigue is mostly unknown. Objective We determined the optimal number of personnel needed for 30-min CPR in a rescue-team. Methods We conducted a randomized, manikin trial on healthcare providers. We divided them into Groups A to D according to the assigned different rest period to each group between the 2 min CCs. Groups A, B, C, and D performed CCs at 2, 4, 6, and 8 min rest period. All participants performed CCs for 30 min with a different rest period; participants allocated to Groups A, B, C, and D performed, eight, five, four, and three cycles, respectively. We compared a quality change of CCs among these groups to investigate how the assigned rest period affects the maintenance of CC quality during the 30-min CPR. Results This study involved 143 participants (male 58 [41%]; mean age, 24 years,) for the evaluation. As participants had less rest periods, the quality of their CCs such as sufficient depth ratio declined over 30-min CPR. A significant decrease in the sufficient CC depth ratio was observed in the second to the last cycle as compared to the first cycle. (median changes; A: −4%, B: −3%, C: 0%, and D: 0% p < 0.01). Conclusions A 6 min rest period after 2 min CC is vital in order to sustain the quality of CC during a 30-min CPR cycle. At least four personnel may be needed to reduce rescuer's fatigue for a 30-min CPR cycle when the team consists of men and women. PMID:29267300

Weak decays of triply heavy baryons

NASA Astrophysics Data System (ADS)

Wang, Wei; Xu, Ji

2018-05-01

After the experimental establishment of doubly heavy baryons, baryons with three quarks are the last missing pieces of the lowest-lying baryon multiplets in the quark model. In this work, we study semileptonic and nonleptonic weak decays of triply heavy baryons, Ωcc c ++, Ωcc b +, Ωcb b 0, and Ωbb b -. Decay amplitudes for various channels are parametrized in terms of a few SU(3) irreducible amplitudes. We point out that branching fractions for Cabibbo-allowed processes, Ωcc c ++→(Ξcc ++K¯0,Ξcc ++K-π+,Ωcc +π+,Ξc+D+,Ξc'D+,ΛcD+K¯0,Ξc+D0π+,Ξc0D+π+), may reach a few percent. We suggest our experimental colleagues to perform a search at hadron colliders and the electron and positron collisions in the future, which will presumably lead to discoveries of triply heavy baryons and complete the baryon multiplets. Using the expanded amplitudes, we derive a number of relations for the partial widths that can be examined in the future.

Dose constraints in the rectum and bladder following carbon-ion radiotherapy for uterus carcinoma: a retrospective pooled analysis.

PubMed

Okonogi, Noriyuki; Fukahori, Mai; Wakatsuki, Masaru; Ohkubo, Yu; Kato, Shingo; Miyasaka, Yuhei; Tsuji, Hiroshi; Nakano, Takashi; Kamada, Tadashi

2018-06-25

Carbon-ion radiotherapy (C-ion RT) provides better dose distribution in cancer treatment compared to photons. Additionally, carbon-ion beams provide a higher biological effectiveness, and thus a higher tumor control probability. However, information regarding the dose constraints for organs at risk in C-ion RT is limited. This study aimed to determine the predictive factors for late morbidities in the rectum and bladder after carbon-ion C-ion RT for uterus carcinomas. Between June 1995 and January 2010, 134 patients with uterus carcinomas were treated with C-ion RT with curative intent; prescription doses of 52.8-74.4 Gy (relative biological effectiveness) were delivered in 20-24 fractions. Of these patients, 132 who were followed up for > 6 months were analyzed. We separated the data in two subgroups, a 24 fractions group and a 20 fractions group. Late morbidities, proctitis, and cystitis were assessed according to the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria. The correlations of clinical and dosimetric parameters, V10-V60, D 5cc , D 2cc , and Dmax, with the incidence of ≥grade 1 morbidities were retrospectively analyzed. In the 24 fractions group, the 3-year actuarial occurrence rates of ≥grade 1 rectal and bladder morbidities were 64 and 9%, respectively. In addition, in the 20 fractions group, the 3-year actuarial occurrence rates of ≥grade 1 rectal and bladder morbidities were 32 and 19%, respectively. Regarding the dose-volume histogram data on the rectum, the D 5cc and D 2cc were significantly higher in patients with ≥grade 1 proctitis than in those without morbidity. In addition, the D 5cc for the bladder was significantly higher in patients with ≥grade 1 cystitis than in those without morbidity. Results of univariate analyses showed that D 2cc of the rectum was correlated with the development of ≥grade 1 late proctitis. Moreover, D 5cc of the bladder was correlated with the development of ≥grade 1 late cystitis. The present study identified the dose-volume relationships in C-ion RT regarding the occurrence of late morbidities in the rectum and bladder. Assessment of the factors discussed herein would be beneficial in preventing late morbidities after C-ion RT for pelvic malignancies. Retrospectively registered ( NIRS: 16-040 ).

32 CFR Appendix E to Part 57 - DoD-CC on Early Intervention, Special Education, and Related Services

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 1 2013-07-01 2013-07-01 false DoD-CC on Early Intervention, Special Education... SECRETARY OF DEFENSE PERSONNEL, MILITARY AND CIVILIAN PROVISION OF EARLY INTERVENTION AND SPECIAL EDUCATION SERVICES TO ELIGIBLE DOD DEPENDENTS Pt. 57, App. E Appendix E to Part 57—DoD-CC on Early Intervention...

32 CFR Appendix E to Part 57 - DoD-CC on Early Intervention, Special Education, and Related Services

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 1 2014-07-01 2014-07-01 false DoD-CC on Early Intervention, Special Education... SECRETARY OF DEFENSE PERSONNEL, MILITARY AND CIVILIAN PROVISION OF EARLY INTERVENTION AND SPECIAL EDUCATION SERVICES TO ELIGIBLE DOD DEPENDENTS Pt. 57, App. E Appendix E to Part 57—DoD-CC on Early Intervention...

32 CFR Appendix E to Part 57 - DoD-CC on Early Intervention, Special Education, and Related Services

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 1 2012-07-01 2012-07-01 false DoD-CC on Early Intervention, Special Education... SECRETARY OF DEFENSE PERSONNEL, MILITARY AND CIVILIAN PROVISION OF EARLY INTERVENTION AND SPECIAL EDUCATION SERVICES TO ELIGIBLE DOD DEPENDENTS Pt. 57, App. E Appendix E to Part 57—DoD-CC on Early Intervention...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borot de Battisti, M; Maenhout, M; Lagendijk, J J W

Purpose: To develop adaptive planning with feedback for MRI-guided focal HDR prostate brachytherapy with a single divergent needle robotic implant device. After each needle insertion, the dwell positions for that needle are calculated and the positioning of remaining needles and dosimetry are both updated based on MR imaging. Methods: Errors in needle positioning may occur due to inaccurate needle insertion (caused by e.g. the needle’s bending) and unpredictable changes in patient anatomy. Consequently, the dose plan quality might dramatically decrease compared to the preplan. In this study, a procedure was developed to re-optimize, after each needle insertion, the remaining needlemore » angulations, source positions and dwell times in order to obtain an optimal coverage (D95% PTV>19 Gy) without exceeding the constraints of the organs at risk (OAR) (D10% urethra<21 Gy, D1cc bladder<12 Gy and D1cc rectum<12 Gy). Complete HDR procedures with 6 needle insertions were simulated for a patient MR-image set with PTV, prostate, urethra, bladder and rectum delineated. Random angulation errors, modeled by a Gaussian distribution (standard deviation of 3 mm at the needle’s tip), were generated for each needle insertion. We compared the final dose parameters for the situations (I) without re-optimization and (II) with the automatic feedback. Results: The computation time of replanning was below 100 seconds on a current desk computer. For the patient tested, a clinically acceptable dose plan was achieved while applying the automatic feedback (median(range) in Gy, D95% PTV: 19.9(19.3–20.3), D10% urethra: 13.4(11.9–18.0), D1cc rectum: 11.0(10.7–11.6), D1cc bladder: 4.9(3.6–6.8)). This was not the case without re-optimization (median(range) in Gy, D95% PTV: 19.4(14.9–21.3), D10% urethra: 12.6(11.0–15.7), D1cc rectum: 10.9(8.9–14.1), D1cc bladder: 4.8(4.4–5.2)). Conclusion: An automatic guidance strategy for HDR prostate brachytherapy was developed to compensate errors in needle positioning and improve the dose distribution. Without re-optimization, target coverage and OAR constraints may not be achieved. M. Borot de Battisti is funded by Philips Medical Systems Nederland B.V.; M. Moerland is principal investigator on a contract funded by Philips Medical Systems Nederland B.V.; G. Hautvast and D. Binnekamp are full-time employees of Philips Medical Systems Nederland B.V.« less

Albumin as a prognostic marker for ulcerative colitis

PubMed Central

Khan, Nabeel; Patel, Dhruvan; Shah, Yash; Trivedi, Chinmay; Yang, Yu-Xiao

2017-01-01

AIM To evaluate the role of albumin at the time of ulcerative colitis (UC) diagnosis in predicting the clinical course of disease. METHODS Nationwide cohort of patients with newly diagnosed UC in the Veterans Affairs health care system was identified and divided into two categories: hypoalbuminemia (i.e., ≤ 3.5 gm/dL) or normal albumin levels (i.e., > 3.5 gm/dL) at the time of UC diagnosis. The exposure of interest was presence of hypoalbuminemia defined as albumin level ≤ 3.5 g/dL at the time of UC diagnosis. Patients were then followed over time to identify the use of ≥ 2 courses of corticosteroids (CS), thiopurines, anti-TNF medications and requirement of colectomy for UC management. RESULTS The eligible study cohort included 802 patients, but 92 (11.4%) patients did not have their albumin levels checked at the time of UC diagnosis, and they were excluded. A total of 710 patients, who had albumin levels checked at time of UC diagnosis, were included in our study. Amongst them, 536 patients had a normal albumin level and 174 patients had hypoalbuminemia. Patients with hypoalbuminemia at diagnosis had a higher likelihood of ≥ 2 courses of CS use (adjusted HR = 1.7, 95%CI: 1.3-2.3), higher likelihood of thiopurine or anti- TNF use (adjusted HR = 1.72, 95%CI: 1.23-2.40) than patients with normal albumin level at diagnosis. There was a trend of higher likelihood of colectomy in hypoalbuminemic patients, but it was not statistically significant (Adjusted HR = 1.7, 95%CI: 0.90-3.25). CONCLUSION Hypoalbuminemia at disease diagnosis can serve as a prognostic marker to predict the clinical course of UC at the time of diagnosis. PMID:29259376

Arthroscopic treatment of acute acromioclavicular dislocations using a double button device: Clinical and MRI results.

PubMed

Loriaut, P; Casabianca, L; Alkhaili, J; Dallaudière, B; Desportes, E; Rousseau, R; Massin, P; Boyer, P

2015-12-01

Arthroscopic treatment of acute grade 3 and 4 acromioclavicular dislocation is controversial, due to the risk of recurrence and of postoperative reduction defect. The purpose of the present study was to investigate whether the healing of the acromioclavicular (AC) and coracoclavicular (CC) ligaments and the accurate 3D positioning parameters of the AC joint using MRI were correlated with satisfactory functional outcome. Thirty-nine patients were enrolled from 2009 to 2011 and managed arthroscopically by CC lacing using a double-button device. Clinical assessment included the Shoulder and Hand (QuickDash) score, Constant-Murley score and visual analog scale (VAS) for residual pain. Time and rate to return to work and return to sport were assessed according to type of sport and work. Postoperative complications were recorded. Radiological examination consisted of anteroposterior clavicle and lateral axillary radiographs. AC ligament healing and 3D joint congruency were assessed on MRI and correlated to the clinical results. Mean patient age was 35.7 years (range, 20-55). Mean follow-up was 42.3±10.6 months (range, 24-60). At final follow-up, mean QuickDash score, Constant score and VAS were respectively 1.7±4 (range, 0-11), 94.7±7.3 (range, 82-100) and 0.5±1.4 (range, 0-2). Thirty-five (90%) patients were able to resume work, including heavy manual labor, and sport. Radiology found accurate 3D joint congruency in 34 patients (87%) and CC and AC ligament healing in 36 (93%). Complications included reduction loss at 6 weeks in 3 patients, requiring surgical stabilization. Satisfactory functional results were associated with accurate AC joint congruency in the coronal and axial planes (P<0.05) and good AC and CC ligament healing (P<0.04). An initial 25% reduction defect in the coronal plane was not associated with poor functional results (P=0.07). Arthroscopic treatment by CC lacing satisfactorily restored ligament and joint anatomy in the present series. These satisfactory anatomic results correlated with good clinical outcome encourage continuing with this technique. Level IV, therapeutic case series. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Longterm prognosis of combined hepatocellular carcinoma-cholangiocarcinoma following liver transplantation and resection.

PubMed

Jung, Dong-Hwan; Hwang, Shin; Song, Gi-Won; Ahn, Chul-Soo; Moon, Deok-Bog; Kim, Ki-Hun; Ha, Tae-Yong; Park, Gil-Chun; Hong, Seung-Mo; Kim, Wan-Jun; Kang, Woo-Hyoung; Kim, Seok-Hwan; Yu, Eun Sil; Lee, Sung-Gyu

2017-03-01

Combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CC) is a rare disease. We investigated the clinicopathological features of cHCC-CC and compared the longterm outcomes following liver transplantation (LT) and hepatic resection (HR). We identified 32 LT patients with cHCC-CC through an institutional database search. The HR control group (n = 100) was selected through propensity score-matching. The incidence of cHCC-CC among all adult LT patients was 1.0%. Mean patient age was 53.4 ± 6.7 years, and 26 patients were male. Thirty patients had hepatitis B virus infection. All patients of cHCC-CC were diagnosed incidentally in the explanted livers. Mean tumor diameter was 2.5 ± 1.3 cm, and 28 patients had single tumors. Tumor stage was stage I in 23 and II in 9. Concurrent hepatocellular carcinoma (HCC) was detected in 12 patients with stage I in 5 and II in 7. Mean tumor diameter was 1.9 ± 1.2 cm, and 5 had single tumors. Tumor recurrence and survival rates were 15.6% and 84.4% at 1 year and 32.2% and 65.8% at 5 years, respectively. Patients with very early stage cHCC-CC (1 or 2 tumors ≤ 2.0 cm) showed 13.3% tumor recurrence and 93.3% patient survival rates at 5 years, which were significantly improved than those with advanced tumors (P = 0.002). Tumor recurrence and survival rates did not differ significantly between the LT and HR control groups (P = 0.22 and P = 0.91, respectively); however, postrecurrence patient survival did (P = 0.016). In conclusion, cHCC-CC is rarely diagnosed following LT, and one-third of such patients have concurrent HCC. The longterm posttransplant prognosis was similar following LT and HR. Very early cHCC-CC resulted in favorable posttransplant prognosis, thus this selection condition can be prudently considered for LT indication. Liver Transplantation 23 330-341 2017 AASLD. © 2016 by the American Association for the Study of Liver Diseases.

Vitamin D receptor-mediated control of Soggy, Wise, and Hairless gene expression in keratinocytes.

PubMed

Hsieh, Jui-Cheng; Estess, Rudolf C; Kaneko, Ichiro; Whitfield, G Kerr; Jurutka, Peter W; Haussler, Mark R

2014-02-01

The vitamin D receptor (VDR), but not its hormonal ligand, 1,25-dihydroxyvitamin D3 (1,25D), is required for the progression of the mammalian hair cycle. We studied three genes relevant to hair cycle signaling, DKKL1 (Soggy), SOSTDC1 (Wise), and HR (Hairless), to determine whether their expression is regulated by VDR and/or its 1,25D ligand. DKKL1 mRNA was repressed 49-72% by 1,25D in primary human and CCD-1106 KERTr keratinocytes; a functional vitamin D responsive element (VDRE) was identified at -9590 bp in murine Soggy. Similarly, SOSTDC1 mRNA was repressed 41-59% by 1,25D in KERTr and primary human keratinocytes; a functional VDRE was located at -6215 bp in human Wise. In contrast, HR mRNA was upregulated 1.56- to 2.77-fold by 1,25D in primary human and KERTr keratinocytes; a VDRE (TGGTGAgtgAGGACA) consisting of an imperfect direct repeat separated by three nucleotides (DR3) was identified at -7269 bp in the human Hairless gene that mediated dramatic induction, even in the absence of 1,25D ligand. In parallel, a DR4 thyroid hormone responsive element, TGGTGAggccAGGACA, was identified at +1304 bp in the human HR gene that conferred tri-iodothyronine (T3)-independent transcriptional activation. Because the thyroid hormone receptor controls HR expression in the CNS, whereas VDR functions in concert with the HR corepressor specifically in skin, a model is proposed wherein unliganded VDR upregulates the expression of HR, the gene product of which acts as a downstream comodulator to feedback-repress DKKL1 and SOSTDC1, resulting in integration of bone morphogenic protein and Wnt signaling to drive the mammalian hair cycle and/or influencing epidermal function.

Dosimetric Analysis of Organs at Risk During Expiratory Gating in Stereotactic Body Radiation Therapy for Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taniguchi, Cullen M.; Murphy, James D.; Eclov, Neville

2013-03-15

Purpose: To determine how the respiratory phase impacts dose to normal organs during stereotactic body radiation therapy (SBRT) for pancreatic cancer. Methods and Materials: Eighteen consecutive patients with locally advanced, unresectable pancreatic adenocarcinoma treated with SBRT were included in this study. On the treatment planning 4-dimensional computed tomography (CT) scan, the planning target volume (PTV), defined as the gross tumor volume plus 3-mm margin, the duodenum, and the stomach were contoured on the end-expiration (CT{sub exp}) and end-inspiration (CT{sub insp}) phases for each patient. A separate treatment plan was constructed for both phases with the dose prescription of 33 Gymore » in 5 fractions with 95% coverage of the PTV by the 100% isodose line. The dose-volume histogram (DVH) endpoints, volume of duodenum that received 20 Gy (V{sub 20}), V{sub 25}, and V{sub 30} and maximum dose to 5 cc of contoured organ (D{sub 5cc}), D{sub 1cc}, and D{sub 0.1cc}, were evaluated. Results: Dosimetric parameters for the duodenum, including V{sub 25}, V{sub 30}, D{sub 1cc}, and D{sub 0.1cc} improved by planning on the CT{sub exp} compared to those on the CT{sub insp}. There was a statistically significant overlap of the PTV with the duodenum but not the stomach during the CT{sub insp} compared to the CT{sub exp} (0.38 ± 0.17 cc vs 0.01 ± 0.01 cc, P=.048). A larger expansion of the PTV, in accordance with a Danish phase 2 trial, showed even more overlapping volume of duodenum on the CT{sub insp} compared to that on the CT{sub exp} (5.5 ± 0.9 cc vs 3.0 ± 0.8 cc, P=.0003) but no statistical difference for any stomach dosimetric DVH parameter. Conclusions: Dose to the duodenum was higher when treating on the inspiratory than on the expiratory phase. These data suggest that expiratory gating may be preferable to inspiratory breath-hold and free breathing strategies for minimizing risk of toxicity.« less

Association of History of Gestational Diabetes With Long-term Cardiovascular Disease Risk in a Large Prospective Cohort of US Women.

PubMed

Tobias, Deirdre K; Stuart, Jennifer J; Li, Shanshan; Chavarro, Jorge; Rimm, Eric B; Rich-Edwards, Janet; Hu, Frank B; Manson, JoAnn E; Zhang, Cuilin

2017-12-01

Previous studies identify gestational diabetes (GD) as a risk factor for intermediate markers of cardiovascular disease (CVD) risk; however, few are prospective, evaluate hard CVD end points, or account for shared risk factors including body weight and lifestyle. To prospectively evaluate history of GD in relation to incident CVD risk. The Nurses' Health Study II (NHS II) is an observational cohort study of US female nurses established in 1989, with ongoing follow-up. Biennial questionnaires updated behavioral characteristics, health outcomes, and lifestyle factors. Multivariable Cox models estimated the hazard ratio (HR) and 95% CI for CVD risk. We included 89 479 women who reported at least 1 pregnancy and were free of CVD and cancer at baseline. Follow-up through May 31, 2015, was complete for more than 90% of eligible participants. History of GD was self-reported at baseline (1989) via questionnaire and updated every 2 years. We observed 1161 incident self-reported nonfatal or fatal myocardial infarction or stroke, confirmed via medical records. Participants had a mean (SD) age of 34.9 (4.7) years. Adjusting for age, prepregnancy body mass index, and other covariates, GD vs no GD was associated with subsequent CVD (HR, 1.43; 95% CI, 1.12-1.81). Additional adjustment for weight gain since pregnancy and updated lifestyle factors attenuated the association (HR, 1.29; 95% CI, 1.01-1.65). Classifying GD by progression to T2D in relation to CVD risk indicated a positive association for GD with progression to T2D vs no GD or T2D (HR, 4.02; 95% CI, 1.94-8.31), and an attenuated relationship for GD only (HR, 1.30; 95% CI, 0.99-1.71). Gestational diabetes was positively associated with CVD later in life, although the absolute rate of CVD in this younger cohort of predominantly white women was low. This relationship is possibly mediated in part by subsequent weight gain and lack of healthy lifestyle.

Structure and spectral features of H+(H2O)7: Eigen versus Zundel forms.

PubMed

Shin, Ilgyou; Park, Mina; Min, Seung Kyu; Lee, Eun Cheol; Suh, Seung Bum; Kim, Kwang S

2006-12-21

The two dimensional (2D) to three dimensional (3D) transition for the protonated water cluster has been controversial, in particular, for H(+)(H(2)O)(7). For H(+)(H(2)O)(7) the 3D structure is predicted to be lower in energy than the 2D structure at most levels of theory without zero-point energy (ZPE) correction. On the other hand, with ZPE correction it is predicted to be either 2D or 3D depending on the calculational levels. Although the ZPE correction favors the 3D structure at the level of coupled cluster theory with singles, doubles, and perturbative triples excitations [CCSD(T)] using the aug-cc-pVDZ basis set, the result based on the anharmonic zero-point vibrational energy correction favors the 2D structure. Therefore, the authors investigated the energies based on the complete basis set limit scheme (which we devised in an unbiased way) at the resolution of the identity approximation Moller-Plesset second order perturbation theory and CCSD(T) levels, and found that the 2D structure has the lowest energy for H(+)(H(2)O)(7) [though nearly isoenergetic to the 3D structure for D(+)(D(2)O)(7)]. This structure has the Zundel-type configuration, but it shows the quantum probabilistic distribution including some of the Eigen-type configuration. The vibrational spectra of MP2/aug-cc-pVDZ calculations and Car-Parrinello molecular dynamics simulations, taking into account the thermal and dynamic effects, show that the 2D Zundel-type form is in good agreement with experiments.

Structure and spectral features of H+(H2O)7: Eigen versus Zundel forms

NASA Astrophysics Data System (ADS)

Shin, Ilgyou; Park, Mina; Min, Seung Kyu; Lee, Eun Cheol; Suh, Seung Bum; Kim, Kwang S.

2006-12-01

The two dimensional (2D) to three dimensional (3D) transition for the protonated water cluster has been controversial, in particular, for H+(H2O)7. For H+(H2O)7 the 3D structure is predicted to be lower in energy than the 2D structure at most levels of theory without zero-point energy (ZPE) correction. On the other hand, with ZPE correction it is predicted to be either 2D or 3D depending on the calculational levels. Although the ZPE correction favors the 3D structure at the level of coupled cluster theory with singles, doubles, and perturbative triples excitations [CCSD(T)] using the aug-cc-pVDZ basis set, the result based on the anharmonic zero-point vibrational energy correction favors the 2D structure. Therefore, the authors investigated the energies based on the complete basis set limit scheme (which we devised in an unbiased way) at the resolution of the identity approximation Møller-Plesset second order perturbation theory and CCSD(T) levels, and found that the 2D structure has the lowest energy for H+(H2O)7 [though nearly isoenergetic to the 3D structure for D+(D2O)7]. This structure has the Zundel-type configuration, but it shows the quantum probabilistic distribution including some of the Eigen-type configuration. The vibrational spectra of MP2/aug-cc-pVDZ calculations and Car-Parrinello molecular dynamics simulations, taking into account the thermal and dynamic effects, show that the 2D Zundel-type form is in good agreement with experiments.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Yizhou, E-mail: yizhou.zhao@dal.ca; Moran, Kathryn; Yewondwossen, Mammo

Three-dimensional (3D) printing is suitable for the fabrication of complex radiotherapy bolus. Although investigated from dosimetric and feasibility standpoints, there are few reports to date of its use for actual patient treatment. This study illustrates the versatile applications of 3D printing in clinical radiation oncology through a selection of patient cases, namely, to create bolus for photon and modulated electron radiotherapy (MERT), as well as applicators for surface high-dose rate (HDR) brachytherapy. Photon boluses were 3D-printed to treat a recurrent squamous cell carcinoma (SCC) of the nasal septum and a basal cell carcinoma (BCC) of the posterior pinna. For amore » patient with a mycosis fungoides involving the upper face, a 3D-printed MERT bolus was used. To treat an SCC of the nose, a 3D-printed applicator for surface brachytherapy was made. The structures' fit to the anatomy and the radiotherapy treatment plans were assessed. Based on the treatment planning computed tomography (CT), the size of the largest air gap at the interface of the 3D-printed structure was 3 mm for the SCC of the nasal septum, 3 mm for the BCC of the pinna, 2 mm for the mycosis fungoides of the face, and 2 mm for the SCC of the nose. Acceptable treatment plans were obtained for the SCC of the nasal septum (95% isodose to 99.8% of planning target volume [PTV]), the BCC of the pinna (95% isodose to 97.7% of PTV), and the mycosis fungoides of the face (90% isodose to 92.5% of PTV). For the latter, compared with a plan with a uniform thickness bolus, the one featuring the MERT bolus achieved relative sparing of all the organs at risk (OARs) distal to the target volume, while maintaining similar target volume coverage. The surface brachytherapy plan for the SCC of the nose had adequate coverage (95% isodose to 95.6% of clinical target volume [CTV]), but a relatively high dose to the left eye, owing to its proximity to the tumor. 3D printing can be implemented effectively in the clinical setting to create highly conformal bolus for photon and MERT, as well as applicators for surface brachytherapy.« less

Correlated natural transition orbital framework for low-scaling excitation energy calculations (CorNFLEx).

PubMed

Baudin, Pablo; Kristensen, Kasper

2017-06-07

We present a new framework for calculating coupled cluster (CC) excitation energies at a reduced computational cost. It relies on correlated natural transition orbitals (NTOs), denoted CIS(D')-NTOs, which are obtained by diagonalizing generalized hole and particle density matrices determined from configuration interaction singles (CIS) information and additional terms that represent correlation effects. A transition-specific reduced orbital space is determined based on the eigenvalues of the CIS(D')-NTOs, and a standard CC excitation energy calculation is then performed in that reduced orbital space. The new method is denoted CorNFLEx (Correlated Natural transition orbital Framework for Low-scaling Excitation energy calculations). We calculate second-order approximate CC singles and doubles (CC2) excitation energies for a test set of organic molecules and demonstrate that CorNFLEx yields excitation energies of CC2 quality at a significantly reduced computational cost, even for relatively small systems and delocalized electronic transitions. In order to illustrate the potential of the method for large molecules, we also apply CorNFLEx to calculate CC2 excitation energies for a series of solvated formamide clusters (up to 4836 basis functions).

A Small-Molecule Antagonist of HIF2α Is Efficacious in Preclinical Models of Renal Cell Carcinoma.

PubMed

Wallace, Eli M; Rizzi, James P; Han, Guangzhou; Wehn, Paul M; Cao, Zhaodan; Du, Xinlin; Cheng, Tzuling; Czerwinski, Robert M; Dixon, Darryl D; Goggin, Barry S; Grina, Jonas A; Halfmann, Megan M; Maddie, Melissa A; Olive, Sarah R; Schlachter, Stephen T; Tan, Huiling; Wang, Bin; Wang, Keshi; Xie, Shanhai; Xu, Rui; Yang, Hanbiao; Josey, John A

2016-09-15

More than 90% of clear cell renal cell carcinomas (ccRCC) exhibit inactivation of the von Hippel-Lindau (pVHL) tumor suppressor, establishing it as the major underlying cause of this malignancy. pVHL inactivation results in stabilization of the hypoxia-inducible transcription factors, HIF1α and HIF2α, leading to expression of a genetic program essential for the initiation and progression of ccRCC. Herein, we describe the potent, selective, and orally active small-molecule inhibitor PT2385 as a specific antagonist of HIF2α that allosterically blocks its dimerization with the HIF1α/2α transcriptional dimerization partner ARNT/HIF1β. PT2385 inhibited the expression of HIF2α-dependent genes, including VEGF-A, PAI-1, and cyclin D1 in ccRCC cell lines and tumor xenografts. Treatment of tumor-bearing mice with PT2385 caused dramatic tumor regressions, validating HIF2α as a pivotal oncogenic driver in ccRCC. Notably, unlike other anticancer agents that inhibit VEGF receptor signaling, PT2385 exhibited no adverse effect on cardiovascular performance. Thus, PT2385 represents a novel class of therapeutics for the treatment of RCC with potent preclincal efficacy as well as improved tolerability relative to current agents that target the VEGF pathway. Cancer Res; 76(18); 5491-500. ©2016 AACR. ©2016 American Association for Cancer Research.

Genetic variation in the serotonin pathway and smoking cessation with nicotine replacement therapy: New data from the Patch in Practice trial and pooled analyses

PubMed Central

David, Sean P.; Johnstone, Elaine C.; Murphy, Michael F.G.; Aveyard, Paul; Guo, Boliang; Lerman, Caryn; Munafò, Marcus R.

2015-01-01

The serotonin pathway has been implicated in nicotine dependence and may influence smoking cessation. Therefore, 792 cigarette smokers from the Patch in Practice trial were genotyped for the tryptophan hydroxylase (TPH1 A779C), serotonin transporter (SLC6A4 5-HTTLPR), and 5-HT1A (HTR1A C-1019G) polymorphisms. Cox regression analysis did not demonstrate significant effects of any of the three genotypes on relapse to smoking: TPH1 (Reference AA; AC: hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.78, 1.24, p = 0.90; CC: HR 0.93, 95% CI 0.73, 1.18, p = 0.55); 5-HTTLPR (Reference LL; SL: HR 1.01, 95% CI 0.85, 1.20, p = 0.90; SS: HR 1.13, 95% CI 0.91, 1.39, p = 0.27); HTR1A (Reference CC; CG: HR 1.04, 95% CI 0.86, 1.25, p = 0.70; GG: HR 1.01, 95% CI 0.82, 1.24, p = 0.93). Moreover, pooled analyses of data from all three extant pharmacogenetic NRT trials (N= 1398) found no significant effect of 5-HTTLPR genotype on continuous abstinence at 12-week (Reference LL; SL: odds ratio (OR) = 1.25, 95% CI 0.89, 1.74, p = 0.19; SS: OR= 1.31, 95% CI 0.86, 1.98, p = 0.21) or 26-week follow-up (Reference LL; SL: OR= 0.93, 95% CI 0.64, 1.33, p = 0.68; SS: OR= 1.00, 95% CI 0.63, 1.58, p = 1.00). These data do not support a statistically or clinically significant moderating effect of these specific 5-HT pathway genetic variants on smoking cessation. However, the possibility remains that other variants in these or other 5-HT genes may influence NRT efficacy for smoking cessation in treatment seeking smokers. PMID:18562131

Analysis of the 2-deoxy-D-glucose-induced vagal stimulation of gastric secretion and gastrin release in dogs using methionine-enkephalin, morphine and naloxone.

PubMed

Anderson, W; Molina, E; Rentz, J; Hirschowitz, B I

1982-09-01

Gastric acid and pepsin secreted in 3 hr and antral gastrin released in response to vagal excitation induced by 2-deoxy-D-glucose (2DG), 625 mumol/kg i.v., were studied in six conscious trained gastric fistula dogs. During a 2-hr infusion, Met-enkephalin (96 nmol/kg/hr; delta receptor) reduced the 2DG response by 50%; when the enkephalin was stopped there was a rapid rebound to peak values. Met-enkephalin also blocked the release of gastrin in the first 15 min. By itself, Met-enkephalin did not stimulate secretion and slightly depressed gastrin. By contrast, morphine (96 nmol/kg/hr; mu receptor) augmented and sustained the 2DG gastric acid secretory response. This effect was blocked by naloxone. Morphine alone caused a small rise in serum gastrin after 90 min, followed by a delayed gastric acid secretion of about 30% of the peak 2DG response. Naloxone, a mu opiate antagonist (mu/delta, 27:1), also inhibited the 2DG gastric secretory response by about 50% and augmented the Met-enkephalin inhibition of secretion without blocking either the secretory rebound or the effect on gastrin release. None of the three opiates changed the direct cholinergic gastric secretory or gastrin-releasing effects of bethanechol. Thus, vagal stimulation of the stomach involves pathways which can be influenced by both mu and delta opiates, with apparently opposite effects, proximal to the level of acetylcholine action on the gastric mucosa. The central and peripheral control points in the activation of the stomach via the vagus which are sensitive to opiates have yet to be located and explained.

Copeptin Associates with Cause-Specific Mortality in Patients with Impaired Renal Function: Results from the LURIC and the 4D Study.

PubMed

Krane, Vera; Genser, Bernd; Kleber, Marcus E; Drechsler, Christiane; März, Winfried; Delgado, Graciela; Allolio, Bruno; Wanner, Christoph; Fenske, Wiebke

2017-05-01

In chronic kidney disease (CKD) arginine vasopressin (AVP) cannot efficiently act via renal V2-receptors. AVP is upregulated leading to augmented activation of V1a- and V1b-receptors, which might contribute to the increase in cardiovascular and infectious complications in CKD. Here, we evaluate copeptin, a surrogate of AVP, and its association with cause specific mortality among patients within the whole spectrum of renal function. Copeptin was measured in baseline samples from the LURIC (n = 3131 patients with coronary angiograms) and the 4D-Study (n = 1241 type 2 diabetic hemodialysis patients). Patients were stratified into 4 groups: estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m 2 , 60-89 mL/min/1.73 m 2 , <60 mL/min/1.73 m 2 , and hemodialysis. The association of copeptin with mortality was assessed by Cox proportional hazards regression during 9.9 years of median follow-up in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study and 4 years of median follow-up in the German Diabetes Dialysis Study (4D-Study). Median copeptin increased with decreasing eGFR: 5.6 [interquartile range (IQR), 3.1-8.1] pmol/L (eGFR ≥90 mL/min/1.73 m 2 ), 6.7 (2.9-10.5) pmol/L (eGFR 60-89 mL/min/1.73 m 2 ), 15.3 (6.7-23.9) pmol/L (eGFR <60 mL/min/1.73 m 2 ), and 80.8 (51.2-122) pmol/L (hemodialysis), respectively. Per SD increase in copeptin, the risk of coronary, infectious, and all-cause mortality increased by 25, 30, and 15% [hazard ratios (HR), 1.25; 95% CI, 1.13-1.39; HR, 1.30; 95% CI, 0.98-1.71; and HR, 1.15; 95% CI, 1.05-1.25], respectively, in patients with eGFR 60-89 mL/min/1.73 m 2 . Except for coronary death, results were similar among patients with more advanced renal disease. No significant association was found in patients with normal renal function. Copeptin concentrations were independently associated with coronary, infectious, and all-cause mortality in patients with renal impairment. In patients with normal renal function no significant association was found. © 2017 American Association for Clinical Chemistry.

SU-F-T-29: The Important of Each Fraction Image-Guided Planning for Postoperative HDR-Brachytherapy in Endometrial Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Piriyasang, D; Pattaranutaporn, P; Manokhoon, K

2016-06-15

Purpose: Cylindrical applicators are often used for postoperative HDRbrachytherapy in endometrial carcinoma. It has been considered that dosimetric variation between fractions for this treatment is minimal and might not be necessary to perform treatment planning for every fractions. At our institute, it is traditional to perform treatment planning with CT simulation on the first fraction and uses this plan for the rest of treatment. This study was aim to evaluate the errors of critical structure doses between the fractions when simulation and planning were done for first fraction only. Methods: Treatment plans of 10 endometrial carcinoma patients who received postoperativemore » HDR-brachytherapy and underwent CT-simulation for every HDR-fractions at our department were retrospectively reviewed. All of these patients were treated with cylindrical applicator and prescribed dose 15Gy in 3 fractions to 0.5cm from vaginal surface. The treatment plan from the first fraction was used to simulate in second and third CT-simulation. Radiation dose for critical structures in term of Dose-to-2cc (D2cc) were evaluated and compared between planning CT. Results: The D2cc for bladder and rectum were evaluated. For bladder, the mean error of D2cc estimation for second and third fractions was 7.6% (0.1–20.1%, SD=5.7). And the mean error for D2cc of rectum was 8.5% (0.1–29.4%, SD=8.5). Conclusion: The critical structure doses could be significant difference between fractions which may affects treatment outcomes or toxicities. From our data, image-guided brachytherapy at least with CT-Simulation should be done for every treatment fractions.« less

An Investigation of Multipath Effects on the GPS System During Auto-Rendezvous and Capture

NASA Technical Reports Server (NTRS)

Richie, James E.; Forest, Francis W.

1995-01-01

The proposed use of a Cargo Transport Vehicle (CTV) to carry hardware to the Space Station Freedom (SSF) during the construction phase of the SSF project requires remote maneuvering of the CTV. The CTV is not a manned vehicle. Obtaining the relative positions of the CTV and SSF for remote auto-rendezvous and capture (AR&C) scenarios will rely heavily on the Global Positioning System (GPS). The GPS system is expected to guide the CTV up to a distance of 100 to 300 meters from the SSF. At some point within this range, an optical docking system will take over the remote guidance for capture. During any remote guidance by GPS it is possible that significant multipath signals may be caused by large objects in the vicinity of the module being remotely guided. This could alter the position obtained by the GPS system from the actual position. Due to the nature of the GPS signals, it has been estimated that if the difference in distance between the Line of Sight (LOS) path and the multipath is greater than 300 meters, the GPS system is capable of discriminating between the direct signal and the reflected (or multipath) signal. However, if the path difference is less than 300 meters, one must be concerned. This report details the work accomplished by the Electromagnetic Simulations Laboratory at Marquette University over the period December 1993 to May 1995. This work is an investigation of the strength and phase of a multipath signal arriving at the CTV relative to the direct or line of sight (LOS) signal. The signal originates at a GPS satellite in half geo-stationary orbit and takes two paths to the CTV: (1) the direct or LOS path from the GPS satellite to the CTV; and (2) a scattered path from the GPS satellite to the SSF module and then to the CTV. The scattering from a cylinder has been computed using the physical optics approximation for the current. No other approximations or assumptions have been made including no assumptions regarding the far field or Fresnel field approximations. The integrations required to obtain the scattered field have been computed numerically using an N dimensional Romberg integration. The total scattered electric field is then projected onto the RCP component in the direction of propagation only. The direct or line of sight signal is then used to compute the relative strength and phase of the scattered field. The trajectory of the CTV has been parameterized into 4,214 points that are calculated for each of the geometries investigated. The motion of the CTV between points is small enough for the magnitude data (dB down from direct signal) to appear very smooth; however, because of the distances and wavelengths involved, the phase of the scattered field relative to the direct signal varies very rapidly.

Assessment of TD-DFT methods and of various spin scaled CIS(D) and CC2 versions for the treatment of low-lying valence excitations of large organic dyes

NASA Astrophysics Data System (ADS)

Goerigk, Lars; Grimme, Stefan

2010-05-01

We present an extension of our previously published benchmark set for low-lying valence transitions of large organic dyes [L. Goerigk et al., Phys. Chem. Chem. Phys. 11, 4611 (2009)]. The new set comprises in total 12 molecules, including two charged species and one with a clear charge-transfer transition. Our previous study on TD-DFT methods is repeated for the new test set with a larger basis set. Additionally, we want to shed light on different spin-scaled variants of the configuration interaction singles with perturbative doubles correction [CIS(D)] and the approximate coupled cluster singles and doubles method (CC2). Particularly for CIS(D) we want to clarify, which of the proposed versions can be recommended. Our results indicate that an unpublished SCS-CIS(D) variant, which is implemented into the TURBOMOLE program package, shows worse results than the original CIS(D) method, while other modified versions perform better. An SCS-CIS(D) version with a parameterization, that has already been used in an application by us recently [L. Goerigk and S. Grimme, ChemPhysChem 9, 2467 (2008)], yields the best results. Another SCS-CIS(D) version and the SOS-CIS(D) method [Y. M. Rhee and M. Head-Gordon, J. Phys. Chem. A 111, 5314 (2007)] perform very similar, though. For the electronic transitions considered herein, there is no improvement observed when going from the original CC2 to the SCS-CC2 method but further adjustment of the latter seems to be beneficial. Double-hybrid density functionals belong to best methods tested here. Particularly B2GP-PLYP provides uniformly good results for the complete set and is considered to be close to chemical accuracy within an ab initio theory of color. For conventional hybrid functionals, a Fock-exchange mixing parameter of about 0.4 seems to be optimum in TD-DFT treatments of large chromophores. A range-separated functional such as, e.g., CAM-B3LYP seems also to be promising.

Investigation on Composite Throat Insert For Cryogenic Engines

NASA Astrophysics Data System (ADS)

Ayyappan, G.; Tiwari, S. B.; Praveen, RS; Mohankumar, L.; Jathaveda, M.; Ganesh, P.

2017-02-01

Injector element testing is an important step in the development and qualification of the cryogenic rocket engines. For the purpose of characterising the injectors, sub scale chambers are used. In order to assess the performance of the injectors, different configurations of the injectors are tested using a combustion chamber and a convergent-divergent nozzle. Pressure distribution along the wall of the chamber and throat insert is obtained from the CFD analysis and temperature distribution is obtained from thermal analysis. Thermo-structural analysis is carried out for the sub-scale model of throat inert using temperature dependent material properties. For the experiments a sub-scale model of the thrust chamber is realised. Injector element tests are carried out for the studies. The objective of the present study is to investigate the behaviour of different throat inserts, mainly graphite, 2-D Carbon-Carbon(2D C-C), 4-D Carbon-Carbon (4D C-C) and Silica Phenolic (SP), under pressure and thermal load for repeated operation of the engine. Analytical results are compared with the test results. The paper gives the results of theoretical studies and experiments conducted with all the four type of throat material. It is concluded that 2D C-C is superior in terms of throat erosion being the least under specified combustion environment.

Simplified Syndrome Decoding of (n, 1) Convolutional Codes

NASA Technical Reports Server (NTRS)

Reed, I. S.; Truong, T. K.

1983-01-01

A new syndrome decoding algorithm for the (n, 1) convolutional codes (CC) that is different and simpler than the previous syndrome decoding algorithm of Schalkwijk and Vinck is presented. The new algorithm uses the general solution of the polynomial linear Diophantine equation for the error polynomial vector E(D). This set of Diophantine solutions is a coset of the CC space. A recursive or Viterbi-like algorithm is developed to find the minimum weight error vector cirumflex E(D) in this error coset. An example illustrating the new decoding algorithm is given for the binary nonsymmetric (2,1)CC.

SU-C-213-01: 3D Printed Patient Specific Phantom Composed of Bone and Soft Tissue Substitute Plastics for Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ehler, E; Sterling, D; Higgins, P

Purpose: 3D printed phantoms constructed of multiple tissue approximating materials could be useful in both clinical and research aspects of radiotherapy. This work describes a 3D printed phantom constructed with tissue substitute plastics for both bone and soft tissue; air cavities were included as well. Methods: 3D models of an anonymized nasopharynx patient were generated for air cavities, soft tissues, and bone, which were segmented by Hounsfield Unit (HU) thresholds. HU thresholds were chosen to define air-to-soft tissue boundaries of 0.65 g/cc and soft tissue-to-bone boundaries of 1.18 g/cc based on clinical HU to density tables. After evaluation of severalmore » composite plastics, a bone tissue substitute was identified as an acceptable material for typical radiotherapy x-ray energies, composed of iron and PLA plastic. PET plastic was determined to be an acceptable soft tissue substitute. 3D printing was performed on a consumer grade dual extrusion fused deposition model 3D printer. Results: MVCT scans of the 3D printed heterogeneous phantom were acquired. Rigid image registration of the patient and the 3D printed phantom scans was performed. The average physical density of the soft tissue and bone regions was 1.02 ± 0.08 g/cc and 1.39 ± 0.14 g/cc, respectively, for the patient kVCT scan. In the 3D printed phantom MVCT scan, the average density of the soft tissue and bone was 1.01 ± 0.09 g/cc and 1.44 ± 0.12 g/cc, respectively. Conclusion: A patient specific phantom, constructed of heterogeneous tissue substitute materials was constructed by 3D printing. MVCT of the 3D printed phantom showed realistic tissue densities were recreated by the 3D printing materials. Funding provided by intra-department grant by University of Minnesota Department of Radiation Oncology.« less

Direct Detection and Orbit Analysis of the Exoplanets HR 8799 bcd from Archival 2005 Keck/NIRC2 Data

NASA Technical Reports Server (NTRS)

Currie, Thayne; Fukagawa, Misato; Thalmann, Christian; Matsumura, Soko; Plavchan, Peter

2012-01-01

We present previously unpublished July 2005 H-band coronagraphic data of the young, planet-hosting star HR 8799 from the newly-released Keck/NIRC2 archive. Despite poor observing conditions, we detect three of the planets (HR 8799 bcd), two of them (HR 8799 bc) without advanced image processing. Comparing these data with previously published 1998-2011 astrometry and that from re-reduced October 2010 Keck data constrains the orbits of the planets. Analyzing the planets' astrometry separately, HR 8799 d's orbit is likely inclined at least 25 deg from face-on and the others may be on in inclined orbits. For semimajor axis ratios consistent with a 4:2:1 mean-motion resonance our analysis yields precise values for HR 8799 bcd's orbital parameters and strictly constrains the planets' eccentricities to be less than 0.18-0.3. However, we find no acceptable orbital solutions with this resonance that place the planets in face-on orbits; HR 8799 d shows the largest deviation from such orbits. Moreover, few orbits make HR 8799 d coplanar with b and c, whereas dynamical stability analyses used to constrain the planets' masses typically assume coplanar and/or fare.on orbits. This paper illustrates the significant science gain enabled with the release of the NIRC2 archive.

Factors associated with postoperative complications and 1-year mortality after surgery for colorectal cancer in octogenarians and nonagenarians

PubMed Central

Kim, Young Wan; Kim, Ik Yong

2016-01-01

Purpose To identify the factors affecting 30-day postoperative complications and 1-year mortality after surgery for colorectal cancer in octogenarians and nonagenarians. Methods Between 2005 and 2014, a total of 204 consecutive patients aged ≥80 years who underwent major colorectal surgery were included. Results One hundred patients were male (49%) and 52 patients had American Society of Anesthesiologists (ASA) score ≥3 (25%). Combined surgery was performed in 32 patients (16%). Postoperative complications within 30 days after surgery occurred in 54 patients (26%) and 30-day mortality occurred in five patients (2%). Independent risk factors affecting 30-day postoperative complications were older age (≥90 years, hazard ratio [HR] with 95% confidence interval [CI] =4.95 [1.69−14.47], P=0.004), an ASA score ≥3 (HR with 95% CI =4.19 [1.8−9.74], P=0.001), performance of combined surgery (HR with 95% CI =3.1 [1.13−8.46], P=0.028), lower hemoglobin level (<10 g/dL, HR with 95% CI =7.56 [3.07−18.63], P<0.001), and lower albumin level (<3.4 g/dL, HR with 95% CI =3.72 [1.43−9.69], P=0.007). An ASA score ≥3 (HR with 95% CI =2.72 [1.15−6.46], P=0.023), tumor-node-metastasis (TNM) stage IV (HR with 95% CI =3.47 [1.44−8.39], P=0.006), and occurrence of postoperative complications (HR with 95% CI =4.42 [1.39−14.09], P=0.012) were significant prognostic factors for 1-year mortality. Conclusion Patient-related factors (older age, higher ASA score, presence of anemia, and lower serum albumin) and procedure-related factors (performance of combined surgical procedure) increased postoperative complications. Avoidance of 30-day postoperative complications may decrease 1-year mortality. PMID:27279741

SU-F-J-145: MRI-Guided Interventional Boost Radiotherapy for Rectal Cancer: Investigating the Feasibility of Adapting the Anatomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kleijnen, J J E; Couwenberg, A M; Asselen, B van

Purpose: The recent development of an MRI-linac allows adaptation of treatments to the anatomy of the moment. This anatomy, in turn, could be altered into a more favorable situation for radiotherapy purposes. The purpose of this study is to investigate the potential dosimetric benefits of manipulating rectal anatomy in MRI-guided interventional external-beam radiotherapy for rectal cancer. Methods: For this retrospective analysis, four patients (1M/3F) diagnosed with rectal cancer were included. These underwent MR-imaging using sonography transmission gel as endorectal contrast at time of diagnosis and standard, non-contrast, MR-imaging prior to radiotherapy planning. In the contrast scan, the rectum is inflatedmore » by the inserted contrast gel, thereby potentially increasing the distance between tumor and the organs-at-risk (OAR). Both anatomies were delineated and 7- beam IMRT-plans were calculated for both situations (RT-standard and RT-inflated), using in-house developed treatment planning software. Each plan was aimed to deliver 15Gy to the planning target volume (PTV; tumor+3mm margin) with a D99>95% and Dmax<120% of the planned dose. The D2cc dose to the OAR were then compared for both situations. Results: At equal (or better) target coverage, we found a mean reduction in D2cc of 4.1Gy/237% [range 2.6Gy–6.3Gy/70%–621%] for the bladder and of 2.0Gy/145% [range −0.7Gy–7.9Gy/−73%–442%] for the small-bowel, for the RT-inflated compared to the RT-standard plans. For the three female patients, a reduction in D2cc of 5.2Gy/191% [range 3.2Gy–9.2Gy/44%–475%] for the gynecological organs was found. We found all D2cc doses to be better for the RT-inflated plans, except for one patient for whom the bladder D2cc dose was slightly increased. Conclusion: Reduction of OAR dose by manipulation of anatomy is feasible. Inflation of the rectum results in more distance between OAR and PTV. This leads to a substantial reduction in dose to OAR at equal or better target coverage.« less

Structure and binding energy of the H2S dimer at the CCSD(T) complete basis set limit.

PubMed

Lemke, Kono H

2017-06-21

This study presents results for the binding energy and geometry of the H 2 S dimer which have been computed using Møller-Plesset perturbation theory (MP2, MP4) and coupled cluster (CCSD, CCSD(T)) calculations with basis sets up to aug-cc-pV5Z. Estimates of D e , E ZPE , D o , and dimer geometry have been obtained at each level of theory by taking advantage of the systematic convergence behavior toward the complete basis set (CBS) limit. The CBS limit binding energy values of D e are 1.91 (MP2), 1.75 (MP4), 1.41 (CCSD), and 1.69 kcal/mol (CCSD[T]). The most accurate values for the equilibrium S-S distance r SS (without counterpoise correction) are 4.080 (MP2/aug-cc-pV5Z), 4.131 (MP4/aug-cc-pVQZ), 4.225 (CCSD/aug-cc-pVQZ), and 4.146 Å (CCSD(T)/aug-cc-pVQZ). This study also evaluates the effect of counterpoise correction on the H 2 S dimer geometry and binding energy. As regards the structure of (H 2 S) 2 , MPn, CCSD, and CCSD(T) level values of r SS , obtained by performing geometry optimizations on the counterpoise-corrected potential energy surface, converge systematically to CBS limit values of 4.099 (MP2), 4.146 (MP4), 4.233 (CCSD), and 4.167 Å (CCSD(T)). The corresponding CBS limit values of the equilibrium binding energy D e are 1.88 (MP2), 1.76 (MP4), 1.41 (CCSD), and 1.69 kcal/mol (CCSD(T)), the latter in excellent agreement with the measured binding energy value of 1.68 ± 0.02 kcal/mol reported by Ciaffoni et al. [Appl. Phys. B 92, 627 (2008)]. Combining CBS electronic binding energies D e with E ZPE predicted by CCSD(T) vibrational second-order perturbation theory calculations yields D o = 1.08 kcal/mol, which is around 0.6 kcal/mol smaller than the measured value of 1.7 ± 0.3 kcal/mol. Overall, the results presented here demonstrate that the application of high level calculations, in particular CCSD(T), in combination with augmented correlation consistent basis sets provides valuable insight into the structure and energetics of the hydrogen sulfide dimer.

DoD Statistical Report on the Military Retirement System. Fiscal Year 1983.

DTIC Science & Technology

1983-01-01

Qne 00000a~a cocoa 00000 0=00m obot 0=o- 00000 00000 coa=cc. 0 a w a .4 0aa coo -- a- aCca C.j a. a ... 0000 a-=.. 00000 00000 00000 00000 00000...4rn , c xV Mo NC.~ Mnoio Or m -.Y c 0.K m. f 0;: 1a -a61 W. 42 *K2% ffM W 0" _F Ww~.. 0K#-: =MWVNC 6O𔃺 NK I0 cc~ ID I 0 ,W NK :IW𔃺 C,*ONg u0:o-mo W...CC# N NIN N N ##CC#CCCC4V)4MMM . or zzzrjj-jjJ.Jjj-J 2 N U0 - l l 7C= ffM M 0’-w 2 N4EfW ’ 019.03,0 1 IM -n INIi LrW U,0 lffO6w lbD K 227 ~ 222 .J

A highly efficient 3D level-set grain growth algorithm tailored for ccNUMA architecture

NASA Astrophysics Data System (ADS)

Mießen, C.; Velinov, N.; Gottstein, G.; Barrales-Mora, L. A.

2017-12-01

A highly efficient simulation model for 2D and 3D grain growth was developed based on the level-set method. The model introduces modern computational concepts to achieve excellent performance on parallel computer architectures. Strong scalability was measured on cache-coherent non-uniform memory access (ccNUMA) architectures. To achieve this, the proposed approach considers the application of local level-set functions at the grain level. Ideal and non-ideal grain growth was simulated in 3D with the objective to study the evolution of statistical representative volume elements in polycrystals. In addition, microstructure evolution in an anisotropic magnetic material affected by an external magnetic field was simulated.

Music intervention during daily weaning trials-A 6 day prospective randomized crossover trial.

PubMed

Liang, Zhan; Ren, Dianxu; Choi, JiYeon; Happ, Mary Beth; Hravnak, Marylyn; Hoffman, Leslie A

2016-12-01

To examine the effect of patient-selected music intervention during daily weaning trials for patients on prolonged mechanical ventilation. Using a crossover repeated measures design, patients were randomized to music vs no music on the first intervention day. Provision of music was alternated for 6 days, resulting in 3 music and 3 no music days. During weaning trials on music days, data were obtained for 30min prior to music listening and continued for 60min while patients listened to selected music (total 90min). On no music days, data were collected for 90min. Outcome measures were heart rate (HR), respiratory rate (RR), oxygen saturation (SpO 2 ), blood pressure (BP), dyspnea and anxiety assessed with a visual analog scale (VAS-D, VAS-A) and weaning duration (meanh per day on music and non-music days). Of 31 patients randomized, 23 completed the 6-day intervention. When comparisons were made between the 3 music and 3 no music days, there were significant decreases in RR and VAS-D and a significant increase in daily weaning duration on music days (p<0.05). A multivariate mixed-effects model analysis that included patients who completed ≥2 days of the intervention (n=28) demonstrated significant decreases in HR, RR, VAS-A, and VAS-D and a significant increase in daily weaning duration on music days (p<0.05). Providing patient selected music during daily weaning trials is a simple, low-cost, potentially beneficial intervention for patients on prolonged mechanical ventilation. Further study is indicated to test ability of this intervention to promote weaning success and benefits earlier in the weaning process. Copyright © 2016 Elsevier Ltd. All rights reserved.

The association between physiologic dead-space fraction and mortality in subjects with ARDS enrolled in a prospective multi-center clinical trial.

PubMed

Kallet, Richard H; Zhuo, Hanjing; Liu, Kathleen D; Calfee, Carolyn S; Matthay, Michael A

2014-11-01

We tested the association between pulmonary dead-space fraction (ratio of dead space to tidal volume [V(D)/V(T)]) and mortality in subjects with ARDS (Berlin definition, P(aO2)/F(IO2) ≤ 300 mm Hg; PEEP ≥ 5 cm H2O) enrolled into a clinical trial incorporating lung-protective ventilation. We conducted a prospective, multi-center study at medical-surgical ICUs in the United States. A total of 126 ALI subjects with acute lung injury were enrolled into a phase 3 randomized, placebo-controlled study of aerosolized albuterol. V(D)/V(T) and pulmonary mechanics were measured within 4 h of enrollment and repeated daily on study days 1 and 2 in subjects requiring arterial blood gases for clinical management. At baseline, non-survivors had a trend toward higher V(D)/V(T) compared with survivors (0.62 ± 0.11 vs 0.56 ± 0.11, respectively, P = .08). Differences in V(D)/V(T) between non-survivors and survivors became significant on study days 1 (0.64 ± 0.12 vs 0.55 ± 0.11, respectively, P = .01) and 2 (0.67 ± 0.12 vs 0.56 ± 0.11, respectively, P = .004). Likewise, the association between VD/VT and mortality was significant on study day 1 (odds ratio per 0.10 change in V(D)/V(T) [95% CI]: 6.84 [1.62-28.84] P = .01; and study day 2: 4.90 [1.28-18.73] P = .02) after adjusting for V(D)/V(T), P(aO2)/F(IO2), oxygenation index, vasopressor use, and the primary risk for ARDS. Using a Cox proportional hazard model, V(D)/V(T) was associated with a trend toward higher mortality (HR = 4.37 [CI 0.99-19.32], P = .052) that became significant when the analysis was adjusted for daily oxygenation index (HR = 1.74 [95% CI 1.12-3.35] P = .04). Markedly elevated V(D)/V(T) (≥ 0.60) in early ARDS is associated with higher mortality. Measuring V(D)/V(T) may be useful in identifying ARDS patients at increased risk of death who are enrolled into a therapeutic trial. Copyright © 2014 by Daedalus Enterprises.

SU-E-T-574: Novel Chance-Constrained Optimization in Intensity-Modulated Proton Therapy Planning to Account for Range and Patient Setup Uncertainties

DOE Office of Scientific and Technical Information (OSTI.GOV)

An, Y; Liang, J; Liu, W

2015-06-15

Purpose: We propose to apply a probabilistic framework, namely chanceconstrained optimization, in the intensity-modulated proton therapy (IMPT) planning subject to range and patient setup uncertainties. The purpose is to hedge against the influence of uncertainties and improve robustness of treatment plans. Methods: IMPT plans were generated for a typical prostate patient. Nine dose distributions are computed — the nominal one and one each for ±5mm setup uncertainties along three cardinal axes and for ±3.5% range uncertainty. These nine dose distributions are supplied to the solver CPLEX as chance constraints to explicitly control plan robustness under these representative uncertainty scenarios withmore » certain probability. This probability is determined by the tolerance level. We make the chance-constrained model tractable by converting it to a mixed integer optimization problem. The quality of plans derived from this method is evaluated using dose-volume histogram (DVH) indices such as tumor dose homogeneity (D5% – D95%) and coverage (D95%) and normal tissue sparing like V70 of rectum, V65, and V40 of bladder. We also compare the results from this novel method with the conventional PTV-based method to further demonstrate its effectiveness Results: Our model can yield clinically acceptable plans within 50 seconds. The chance-constrained optimization produces IMPT plans with comparable target coverage, better target dose homogeneity, and better normal tissue sparing compared to the PTV-based optimization [D95% CTV: 67.9 vs 68.7 (Gy), D5% – D95% CTV: 11.9 vs 18 (Gy), V70 rectum: 0.0 % vs 0.33%, V65 bladder: 2.17% vs 9.33%, V40 bladder: 8.83% vs 21.83%]. It also simultaneously makes the plan more robust [Width of DVH band at D50%: 2.0 vs 10.0 (Gy)]. The tolerance level may be varied to control the tradeoff between plan robustness and quality. Conclusion: The chance-constrained optimization generates superior IMPT plan compared to the PTV-based optimization with explicit control of plan robustness. NIH/NCI K25CA168984, Eagles Cancer Research Career Development, The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research, Mayo ASU Seed Grant, and The Kemper Marley Foundation.« less

Validation of the Oncentra Brachy Advanced Collapsed cone Engine for a commercial (192)Ir source using heterogeneous geometries.

PubMed

Ma, Yunzhi; Lacroix, Fréderic; Lavallée, Marie-Claude; Beaulieu, Luc

2015-01-01

To validate the Advanced Collapsed cone Engine (ACE) dose calculation engine of Oncentra Brachy (OcB) treatment planning system using an (192)Ir source. Two levels of validation were performed, conformant to the model-based dose calculation algorithm commissioning guidelines of American Association of Physicists in Medicine TG-186 report. Level 1 uses all-water phantoms, and the validation is against TG-43 methodology. Level 2 uses real-patient cases, and the validation is against Monte Carlo (MC) simulations. For each case, the ACE and TG-43 calculations were performed in the OcB treatment planning system. ALGEBRA MC system was used to perform MC simulations. In Level 1, the ray effect depends on both accuracy mode and the number of dwell positions. The volume fraction with dose error ≥2% quickly reduces from 23% (13%) for a single dwell to 3% (2%) for eight dwell positions in the standard (high) accuracy mode. In Level 2, the 10% and higher isodose lines were observed overlapping between ACE (both standard and high-resolution modes) and MC. Major clinical indices (V100, V150, V200, D90, D50, and D2cc) were investigated and validated by MC. For example, among the Level 2 cases, the maximum deviation in V100 of ACE from MC is 2.75% but up to ~10% for TG-43. Similarly, the maximum deviation in D90 is 0.14 Gy between ACE and MC but up to 0.24 Gy for TG-43. ACE demonstrated good agreement with MC in most clinically relevant regions in the cases tested. Departure from MC is significant for specific situations but limited to low-dose (<10% isodose) regions. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

An Application of Content Analysis to Determine Congressional Behavior in Relation to the Defense Budget

DTIC Science & Technology

1977-06-01

4 (1 4J 4- r 4 JQ) C) wn 03 Z$ 4 1,4 - )t n 0 4H H- J> )- H( (D 00H 4J W0 ) U 44 )w09 ) C 0 HI4 H 0U 0S.Hr4Wa - S-i U00- 4 j )X:a 9. td 04 t 0 4 JJVW...W4E- 0d .04- 0() - 0 CA r Q-sm 4ww0 U000 Cpv to 0 4 0) 0.0 m (a 10-i 00 014 4 3UV u 1)0 0Uc2 0 02- 144 A: 40 9()0 O4’ w 20 C 04149> 0)" w -H u2 0) 04

Coffee consumption and risk of chronic disease in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Germany study.

PubMed

Floegel, Anna; Pischon, Tobias; Bergmann, Manuela M; Teucher, Birgit; Kaaks, Rudolf; Boeing, Heiner

2012-04-01

Early studies suggested that coffee consumption may increase the risk of chronic disease. We investigated prospectively the association between coffee consumption and the risk of chronic diseases, including type 2 diabetes (T2D), myocardial infarction (MI), stroke, and cancer. We used data from 42,659 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Germany study. Coffee consumption was assessed by self-administered food-frequency questionnaire at baseline, and data on medically verified incident chronic diseases were collected by active and passive follow-up procedures. HRs and 95% CIs were calculated with multivariate Cox regression models and compared by competing risk analysis. During 8.9 y of follow-up, we observed 1432 cases of T2D, 394 of MI, 310 of stroke, and 1801 of cancer as first qualifying events. Caffeinated (HR: 0.94; 95% CI: 0.84, 1.05) or decaffeinated (HR: 1.05; 95% CI: 0.84, 1.31) coffee consumption (≥4 cups/d compared with <1 cup/d; 1 cup was defined as 150 mL) was not associated with the overall risk of chronic disease. A lower risk of T2D was associated with caffeinated (HR: 0.77; 95% CI: 0.63, 0.94; P-trend 0.009) and decaffeinated (HR: 0.70; 95% CI: 0.46, 1.06; P-trend: 0.043) coffee consumption (≥4 cups/d compared with <1 cup/d), but cardiovascular disease and cancer risk were not. The competing risk analysis showed no significant differences between the risk associations of individual diseases. Our findings suggest that coffee consumption does not increase the risk of chronic disease, but it may be linked to a lower risk of T2D.

Evaluation of injury criteria for the prediction of commotio cordis from lacrosse ball impacts.

PubMed

Dau, Nathan; Cavanaugh, John; Bir, Cynthia; Link, Mark

2011-11-01

Commotio Cordis (CC) is the second leading cause of mortality in youth sports. Impacts occurring directly over the left ventricle (LV) during a vulnerable period of the cardiac cycle can cause ventricular fibrillation (VF), which results in CC. In order to better understand the pathophysiology of CC, and develop a mechanical model for CC, appropriate injury criteria need to be developed. This effort consisted of impacts to seventeen juvenile porcine specimens (mass 21-45 kg). Impacts were delivered over the cardiac silhouette during the venerable period of the cardiac cycle. Four impact speeds were used: 13.4, 17.9, 22.4, and 26.8 m/s. The impactor was a lacrosse ball on an aluminum shaft instrumented with an accelerometer (mass 188 g-215 g). The impacts were recorded using high-speed video. LV pressure was measured with a catheter. Univariate binary logistic regression analyses were performed to evaluate the predictive ability of ten injury criteria. A total of 187 impacts were used in the analysis. The criteria were evaluated on their predictive ability based on Somers' D (D) and Goodman-Kruskal gamma (γ). Injury risk functions were created for all criteria using a 2-parameter Weibull distribution using survival analysis. The best criteria for predicting CC were impact force (D=0.52, and γ=0.52) force*compression (D=0.49, and γ=0.49), and impact power (D=0.49, and γ=0.49). All of these criteria proved significant in predicting the probability of CC from projectile impacts in youth sports (p<0.01). Force proved to be the most predictive of the ten criteria evaluated.

40 CFR 86.447-2006 - What provisions apply to motorcycle engines below 50 cc that are certified under the Small SI...

Code of Federal Regulations, 2010 CFR

2010-07-01

... to recall them under 40 CFR part 86, 90, or 1068. (d) Specific requirements. If you are an engine or... family's total sales in the United States are used in highway motorcycles. This includes engines used in...'s total sales in the United States are highway motorcycles. Show that you meet the engine-sales...

Serum uric acid, protein intake and mortality in hemodialysis patients.

PubMed

Park, Christina; Obi, Yoshitsugu; Streja, Elani; Rhee, Connie M; Catabay, Christina J; Vaziri, Nosratola D; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar

2017-10-01

The association between serum uric acid (SUA) and mortality has been conflicting among studies using hemodialysis (HD) patients. Given the close link between purine and protein in foods, we hypothesized that normalized protein catabolic rate (nPCR), a dietary protein intake surrogate, modifies the SUA-mortality association in the HD population. We identified 4298 patients who initiated HD and had one or more SUA measurement in a contemporary cohort of HD patients over 5 years (1 January 2007-31 December 2011), and examined survival probability according to the first uric acid measurement, adjusting for dialysis vintage, case-mix and malnutrition-inflammation complex-related variables. Mean SUA concentration was 6.6 ± 1.8 mg/dL. There was a consistent association of higher SUA with better nutritional status and lower all-cause mortality irrespective of adjusted models (Ptrend < 0.001). In the case-mix adjusted model, the highest SUA category (≥8.0 mg/dL) compared with the reference group (>6.0-7.0 mg/dL) showed no significant mortality risk [hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.72-1.13], while the lowest category (<5.0 mg/dL) was associated with higher mortality (HR 1.42, 95% CI 1.16-1.72). The hypouricemia-mortality association was significantly modified by nPCR (Pinteraction = 0.001). Mortality risk of low SUA (<5.0 mg/dL) persisted among patients with low nPCR (<0.9 g/kg/day; HR 1.73, 95% CI 1.42-2.10) but not with high nPCR (≥0.9 g/kg/day; HR 0.99, 95% CI 0.74-1.33). SUA may be a nutritional marker in HD patients. Contrary to the general population, low but not high SUA is associated with higher all-cause mortality in HD patients, especially in those with low protein intake. Nutritional features of SUA warrant additional studies. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Hydrogen peroxide clusters: the role of open book motif in cage and helical structures.

PubMed

Elango, M; Parthasarathi, R; Subramanian, V; Ramachandran, C N; Sathyamurthy, N

2006-05-18

Hartree-Fock (HF) calculations using 6-31G*, 6-311++G(d,p), aug-cc-pVDZ, and aug-cc-pVTZ basis sets show that hydrogen peroxide molecular clusters tend to form hydrogen-bonded cyclic and cage structures along the lines expected of a molecule which can act as a proton donor as well as an acceptor. These results are reiterated by density functional theoretic (DFT) calculations with B3LYP parametrization and also by second-order Møller-Plesset perturbation (MP2) theory using 6-31G* and 6-311++G(d,p) basis sets. Trends in stabilization energies and geometrical parameters obtained at the HF level using 6-311++G(d,p), aug-cc-pVDZ, and aug-cc-pVTZ basis sets are similar to those obtained from HF/6-31G* calculation. In addition, the HF calculations suggest the formation of stable helical structures for larger clusters, provided the neighbors form an open book structure.

Space Stations.

DTIC Science & Technology

1980-04-01

4 C X 0Z C X - . -0 a m -- L ( U -. W 0 t a - a L 0 r 0 5 U w ( U f i C 0 -a- .. s -an 21.Z IZ W 0 *1 0 0 5 a . - C o ag CL W3 Iz, go, Cc’s "X i -J...50 4- a o r.) LU 0 . A9 0 A (A0 - -VZ % AG 0n W.- C-C- ’-O CL N. L) a D > ) InS r -a 0a C 4 C065 E- 04- 0j cv c I- 0 L U) a -- C GD - - L -z Cd ~J C 1...0 0 -C 041 a OC 0. CW0 McL (n. C/C w. &U - 0. a) O : 0 JC O V EW( W WC -’ - C’. 2 0. L U 0- U 0 10---id - ’D 4)c C(C C’d 0. E- aG do il- W WCD C E L C

Benchmark calculations with correlated molecular wavefunctions. XIII. Potential energy curves for He2, Ne2 and Ar2 using correlation consistent basis sets through augmented sextuple zeta

NASA Astrophysics Data System (ADS)

van Mourik, Tanja

1999-02-01

The potential energy curves of the rare gas dimers He2, Ne2, and Ar2 have been computed using correlation consistent basis sets ranging from singly augmented aug-cc-pVDZ sets through triply augmented t-aug-cc-pV6Z sets, with the augmented sextuple basis sets being reported herein. Several methods for including electron correlation were investigated, namely Moller-Plesset perturbation theory (MP2, MP3 and MP4) and coupled cluster theory [CCSD and CCSD(T)]. For He2CCSD(T)/d-aug-cc-pV6Z calculations yield a well depth of 7.35cm-1 (10.58K), with an estimated complete basis set (CBS) limit of 7.40cm-1 (10.65K). The latter is smaller than the 'exact' well depth (Aziz, R. A., Janzen, A. R., and Moldover, M. R., 1995, Phys. Rev. Lett., 74, 1586) by about 0.2cm-1 (0.35K). The Ne well depth, computed with the CCSD(T)/d-aug-cc-pV6Z method, is 28.31cm-1 and the estimated CBS limit is 28.4cm-1, approximately 1cm-1 smaller than the empirical potential of Aziz, R. A., and Slaman, M., J., 1989, Chem. Phys., 130, 187. Inclusion of core and core-valence correlation effects has a negligible effect on the Ne well depth, decreasing it by only 0.04cm-1. For Ar2, CCSD(T)/ d-aug-cc-pV6Z calculations yield a well depth of 96.2cm-1. The corresponding HFDID potential of Aziz, R. A., 1993, J. chem. Phys., 99, 4518 predicts of D of 99.7cm-1. Inclusion of core and core-valence effects in Ar increases the well depth and decreases the discrepancy by approximately 1cm-1.

Lennard-Jones fluids in two-dimensional nano-pores. Multi-phase coexistence and fluid structure

NASA Astrophysics Data System (ADS)

Yatsyshin, Petr; Savva, Nikos; Kalliadasis, Serafim

2014-03-01

We present a number of fundamental findings on the wetting behaviour of nano-pores. A popular model for fluid confinement is a one-dimensional (1D) slit pore formed by two parallel planar walls and it exhibits capillary condensation (CC): a first-order phase transition from vapour to capillary-liquid (Kelvin shift). Capping such a pore at one end by a third orthogonal wall forms a prototypical two-dimensional (2D) pore. We show that 2D pores possess a wetting temperature such that below this temperature CC remains of first order, above it becomes a continuous phase transition manifested by a slab of capillary-liquid filling the pore from the capping wall. Continuous CC exhibits hysteresis and can be preceded by a first-order capillary prewetting transition. Additionally, liquid drops can form in the corners of the 2D pore (remnant of 2D wedge prewetting). The three fluid phases, vapour, capillary-liquid slab and corner drops, can coexist at the pore triple point. Our model is based on the statistical mechanics of fluids in the density functional formulation. The fluid-fluid and fluid-substrate interactions are dispersive. We analyze in detail the microscopic fluid structure, isotherms and full phase diagrams. Our findings also suggest novel ways to control wetting of nano-pores. We are grateful to the European Research Council via Advanced Grant No. 247031 for support.

Circulating Branched-Chain Amino Acids and Incident Cardiovascular Disease in a Prospective Cohort of US Women.

PubMed

Tobias, Deirdre K; Lawler, Patrick R; Harada, Paulo H; Demler, Olga V; Ridker, Paul M; Manson, JoAnn E; Cheng, Susan; Mora, Samia

2018-04-01

Circulating branched-chain amino acids (BCAAs; isoleucine, leucine, and valine) are strong predictors of type 2 diabetes mellitus (T2D), but their association with cardiovascular disease (CVD) is uncertain. We hypothesized that plasma BCAAs are positively associated with CVD risk and evaluated whether this was dependent on an intermediate diagnosis of T2D. Participants in the Women's Health Study prospective cohort were eligible if free of CVD at baseline blood collection (n=27 041). Plasma metabolites were measured via nuclear magnetic resonance spectroscopy. Multivariable Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for BCAAs with incident CVD (myocardial infarction, stroke, and coronary revascularization). We confirmed 2207 CVD events over a mean 18.6 years of follow-up. Adjusting for age, body mass index, and other established CVD risk factors, total BCAAs were positively associated with CVD (per SD: HR, 1.13; 95% CI, 1.08-1.18), comparable to LDL-C (low-density lipoprotein cholesterol) with CVD (per SD: HR, 1.12; 95% CI, 1.07-1.17). BCAAs were associated with coronary events (myocardial infarction: HR, 1.16; 95% CI, 1.06-1.26; revascularization: HR, 1.17; 95% CI, 1.11-1.25), and borderline significant association with stroke (HR, 1.07; 95% CI, 0.99-1.15). The BCAA-CVD association was greater ( P interaction=0.036) among women who developed T2D before CVD (HR, 1.20; 95% CI, 1.08-1.32) versus women without T2D (HR, 1.08; 95% CI, 1.03-1.14). Adjusting for LDL-C, an established CVD risk factor, did not attenuate these findings; however, adjusting for HbA1c and insulin resistance eliminated the associations of BCAAs with CVD. Circulating plasma BCAAs were positively associated with incident CVD in women. Impaired BCAA metabolism may capture the long-term risk of the common cause underlying T2D and CVD. © 2018 American Heart Association, Inc.

Two Distinct Types of CME-flare Relationships Based on SOHO and STEREO Observations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jang, Soojeong; Moon, Yong-Jae; Kim, Rok-Soon

In this paper, we present two distinct types of coronal mass ejection (CME)-flare relationships according to their observing time differences using 107 events from 2010 to 2013. The observing time difference, Δ T , is defined as flare peak time minus CME first appearance time at Solar Terrestrial Relations Observatory ( STEREO ) COR1 field of view. There are 41 events for group A (Δ T < 0) and 66 events for group B (Δ T ≥ 0). We compare CME 3D parameters (speed and kinetic energy) based on multi-spacecraft data ( SOlar and Heliospheric Observatory ( SOHO ) andmore » STEREO A and B ) and their associated flare properties (peak flux, fluence, and duration). Our main results are as follows. First, there are better relationships between CME and flare parameters for group B than that of group A. In particular, CME 3D kinetic energy for group B is well correlated with flare fluence with the correlation coefficient of 0.67, which is much stronger than that (cc = 0.31) of group A. Second, the events belonging to group A have short flare durations of less than 1 hr (mean = 21 minutes), while the events for group B have longer durations up to 4 hr (mean = 81 minutes). Third, the mean value of height at peak speed for group B is 4.05 Rs, which is noticeably higher than that of group A (1.89 Rs). This is well correlated with the CME acceleration duration (cc = 0.75). A higher height at peak speed and a longer acceleration duration of CME for group B could be explained by the fact that magnetic reconnections for group B continuously occur for a longer time than those for group A.« less

The sitting position during neurosurgical procedures does not influence serum biomarkers of pulmonary parenchymal injury.

PubMed

Duda, Izabela; Grzybowska, Konstancja; Jędrzejowska-Szypułka, Halina; Lewin-Kowalik, Joanna

2012-12-05

The sitting position during neurosurgical operations predisposes to air penetration through veins and the movement of the air through the pulmonary circulation. Contact of an air bubble with the endothelium can lead to acute lung injury. The presence of specific pulmonary proteins in the plasma such as surfactant protein D (SP-D) and Clara cell protein (CC16) is a biomarker of damaging processes at the air-blood barrier. The aim of our study was to examine the hypothesis that the level of investigated pulmonary biomarkers in plasma is higher in patients operated on in the sitting position. The study included patients undergoing planned neurosurgical operations, who were divided into two groups: the sitting group (40 patients, operated on in the sitting position) and the supine group (24 patients, operated in the supine position). After the operation blood samples were drawn, centrifuged, frozen and stored until analyses were conducted. The determination of the SP-D and CC16 levels was performed using an ELISA test. Air embolism (VAE) was defined as a sudden drop in etCO2 of more than 2 mmHg and the presence of air bubbles in the aspirated blood from the central cannula. In all patients, the number of hospitalization days in the postoperative period was calculated. There were no differences in the average levels of SP-D between the groups (the mean in the sitting group was 95.56 ng/mL and the mean in the supine group was 101.21 ng/mL). The average levels of CC16 were similar in both groups as well (6.56 ng/mL in the sitting group and 6.79 ng/mL in the supine group). There was a statistically significant positive correlation between SP-D and CC16 values in both groups. VAE was diagnosed clinically in 12.5% of cases in the sitting group without a significant increase in SP-D and CC16 levels. On average, patients in both groups were discharged from the hospital within 9 days of surgery. The sitting position and intraoperative VAE during neurosurgical procedures do not affect the concentration of plasma biomarkers of pulmonary parenchymal injury such as SP-D and CC16.

GPI Spectra of HR 8799 c, d, and e from 1.5 to 2.4 μm with KLIP Forward Modeling

NASA Astrophysics Data System (ADS)

Greenbaum, Alexandra Z.; Pueyo, Laurent; Ruffio, Jean-Baptiste; Wang, Jason J.; De Rosa, Robert J.; Aguilar, Jonathan; Rameau, Julien; Barman, Travis; Marois, Christian; Marley, Mark S.; Konopacky, Quinn; Rajan, Abhijith; Macintosh, Bruce; Ansdell, Megan; Arriaga, Pauline; Bailey, Vanessa P.; Bulger, Joanna; Burrows, Adam S.; Chilcote, Jeffrey; Cotten, Tara; Doyon, Rene; Duchêne, Gaspard; Fitzgerald, Michael P.; Follette, Katherine B.; Gerard, Benjamin; Goodsell, Stephen J.; Graham, James R.; Hibon, Pascale; Hung, Li-Wei; Ingraham, Patrick; Kalas, Paul; Larkin, James E.; Maire, Jérôme; Marchis, Franck; Metchev, Stanimir; Millar-Blanchaer, Maxwell A.; Nielsen, Eric L.; Norton, Andrew; Oppenheimer, Rebecca; Palmer, David; Patience, Jennifer; Perrin, Marshall D.; Poyneer, Lisa; Rantakyrö, Fredrik T.; Savransky, Dmitry; Schneider, Adam C.; Sivaramakrishnan, Anand; Song, Inseok; Soummer, Rémi; Thomas, Sandrine; Wallace, J. Kent; Ward-Duong, Kimberly; Wiktorowicz, Sloane; Wolff, Schuyler

2018-06-01

We explore KLIP forward modeling spectral extraction on Gemini Planet Imager coronagraphic data of HR 8799, using PyKLIP, and show algorithm stability with varying KLIP parameters. We report new and re-reduced spectrophotometry of HR 8799 c, d, and e in the H and K bands. We discuss a strategy for choosing optimal KLIP PSF subtraction parameters by injecting simulated sources and recovering them over a range of parameters. The K1/K2 spectra for HR 8799 c and d are similar to previously published results from the same data set. We also present a K-band spectrum of HR 8799 e for the first time and show that our H-band spectra agree well with previously published spectra from the VLT/SPHERE instrument. We show that HR 8799 c and d show significant differences in their H and K spectra, but do not find any conclusive differences between d and e, nor between c and e, likely due to large error bars in the recovered spectrum of e. Compared to M-, L-, and T-type field brown dwarfs, all three planets are most consistent with mid- and late-L spectral types. All objects are consistent with low gravity, but a lack of standard spectra for low gravity limit the ability to fit the best spectral type. We discuss how dedicated modeling efforts can better fit HR 8799 planets’ near-IR flux, as well as how differences between the properties of these planets can be further explored.

Roof Plans: Section "CC", Roof Plan; Roof Framing Plans: Section ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Roof Plans: Section "C-C", Roof Plan; Roof Framing Plans: Section "C-C", Section "D-D"; Roof Framing Sections: Cross Section "G-G", Cross Section "H-H" - Fort Washington, Fort Washington Light, Northeast side of Potomac River at Fort Washington Park, Fort Washington, Prince George's County, MD

Low Calcium Intake in Midpregnancy Is Associated with Hypertension Development within 10 Years after Pregnancy: The Norwegian Mother and Child Cohort Study.

PubMed

Egeland, Grace M; Skurtveit, Svetlana; Sakshaug, Solveig; Daltveit, Anne Kjersti; Vikse, Bjørn E; Haugen, Margaretha

2017-09-01

Background: Low dietary calcium intake may be a risk factor for hypertension, but studies conflict. Objective: We evaluated the ability to predict hypertension within 10 y after delivery based on calcium intake during midpregnancy. Methods: The Norwegian Mother and Child Cohort Study of women delivering in 2004-2009 was linked to the Norwegian Prescription Database (2004-2013) to ascertain antihypertensive medication usage >90 d after delivery. Women with hypertension before pregnancy were excluded, leaving 60,027 mothers for analyses. Age and energy-adjusted cubic splines evaluated dose-response curves, and Cox proportional hazard analyses evaluated HR and 95% CIs by calcium quartiles adjusting for 7 covariates. Analyses were stratified by gestational hypertension and by sodium-to-potassium intake ratio (<0.76 compared with ≥0.76). Results: Participants had a mean ± SD age of 30.5 ± 4.6 y, a body mass index (in kg/m 2 ) of 24.0 ± 4.3 before pregnancy, and a mean follow-up duration of 7.1 ± 1.6 y. Cubic spline graphs identified a threshold effect of low calcium intake only within the range of dietary inadequacy related to increased risk. The lowest calcium quartile (≤738 mg/d; median: 588 mg/d), relative to the highest quartile (≥1254 mg/d), had an HR for hypertension of 1.34 (95% CI: 1.05, 1.70) among women who were normotensive during pregnancy, and an HR of 1.62 (95% CI: 1.14, 2.35) among women who had gestational hypertension, after adjusting for covariates. Women with gestational hypertension, who were in the lowest quartile of calcium intake, and who had a high sodium-to-potassium intake ratio had a risk of hypertension more than double that of their counterparts with a calcium intake in the highest quartile. Results were attenuated by adjusting for covariates (HR: 1.92; 95% CI: 1.09, 3.39). Conclusions: The results suggest that low dietary calcium intake may be a risk factor or risk marker for the development of hypertension, particularly for women with a history of gestational hypertension. © 2017 American Society for Nutrition.

Common-mask guided image reconstruction (c-MGIR) for enhanced 4D cone-beam computed tomography

NASA Astrophysics Data System (ADS)

Park, Justin C.; Zhang, Hao; Chen, Yunmei; Fan, Qiyong; Li, Jonathan G.; Liu, Chihray; Lu, Bo

2015-12-01

Compared to 3D cone beam computed tomography (3D CBCT), the image quality of commercially available four-dimensional (4D) CBCT is severely impaired due to the insufficient amount of projection data available for each phase. Since the traditional Feldkamp-Davis-Kress (FDK)-based algorithm is infeasible for reconstructing high quality 4D CBCT images with limited projections, investigators had developed several compress-sensing (CS) based algorithms to improve image quality. The aim of this study is to develop a novel algorithm which can provide better image quality than the FDK and other CS based algorithms with limited projections. We named this algorithm ‘the common mask guided image reconstruction’ (c-MGIR). In c-MGIR, the unknown CBCT volume is mathematically modeled as a combination of phase-specific motion vectors and phase-independent static vectors. The common-mask matrix, which is the key concept behind the c-MGIR algorithm, separates the common static part across all phase images from the possible moving part in each phase image. The moving part and the static part of the volumes were then alternatively updated by solving two sub-minimization problems iteratively. As the novel mathematical transformation allows the static volume and moving volumes to be updated (during each iteration) with global projections and ‘well’ solved static volume respectively, the algorithm was able to reduce the noise and under-sampling artifact (an issue faced by other algorithms) to the maximum extent. To evaluate the performance of our proposed c-MGIR, we utilized imaging data from both numerical phantoms and a lung cancer patient. The qualities of the images reconstructed with c-MGIR were compared with (1) standard FDK algorithm, (2) conventional total variation (CTV) based algorithm, (3) prior image constrained compressed sensing (PICCS) algorithm, and (4) motion-map constrained image reconstruction (MCIR) algorithm, respectively. To improve the efficiency of the algorithm, the code was implemented with a graphic processing unit for parallel processing purposes. Root mean square error (RMSE) between the ground truth and reconstructed volumes of the numerical phantom were in the descending order of FDK, CTV, PICCS, MCIR, and c-MGIR for all phases. Specifically, the means and the standard deviations of the RMSE of FDK, CTV, PICCS, MCIR and c-MGIR for all phases were 42.64  ±  6.5%, 3.63  ±  0.83%, 1.31%  ±  0.09%, 0.86%  ±  0.11% and 0.52 %  ±  0.02%, respectively. The image quality of the patient case also indicated the superiority of c-MGIR compared to other algorithms. The results indicated that clinically viable 4D CBCT images can be reconstructed while requiring no more projection data than a typical clinical 3D CBCT scan. This makes c-MGIR a potential online reconstruction algorithm for 4D CBCT, which can provide much better image quality than other available algorithms, while requiring less dose and potentially less scanning time.

Common-mask guided image reconstruction (c-MGIR) for enhanced 4D cone-beam computed tomography.

PubMed

Park, Justin C; Zhang, Hao; Chen, Yunmei; Fan, Qiyong; Li, Jonathan G; Liu, Chihray; Lu, Bo

2015-12-07

Compared to 3D cone beam computed tomography (3D CBCT), the image quality of commercially available four-dimensional (4D) CBCT is severely impaired due to the insufficient amount of projection data available for each phase. Since the traditional Feldkamp-Davis-Kress (FDK)-based algorithm is infeasible for reconstructing high quality 4D CBCT images with limited projections, investigators had developed several compress-sensing (CS) based algorithms to improve image quality. The aim of this study is to develop a novel algorithm which can provide better image quality than the FDK and other CS based algorithms with limited projections. We named this algorithm 'the common mask guided image reconstruction' (c-MGIR).In c-MGIR, the unknown CBCT volume is mathematically modeled as a combination of phase-specific motion vectors and phase-independent static vectors. The common-mask matrix, which is the key concept behind the c-MGIR algorithm, separates the common static part across all phase images from the possible moving part in each phase image. The moving part and the static part of the volumes were then alternatively updated by solving two sub-minimization problems iteratively. As the novel mathematical transformation allows the static volume and moving volumes to be updated (during each iteration) with global projections and 'well' solved static volume respectively, the algorithm was able to reduce the noise and under-sampling artifact (an issue faced by other algorithms) to the maximum extent. To evaluate the performance of our proposed c-MGIR, we utilized imaging data from both numerical phantoms and a lung cancer patient. The qualities of the images reconstructed with c-MGIR were compared with (1) standard FDK algorithm, (2) conventional total variation (CTV) based algorithm, (3) prior image constrained compressed sensing (PICCS) algorithm, and (4) motion-map constrained image reconstruction (MCIR) algorithm, respectively. To improve the efficiency of the algorithm, the code was implemented with a graphic processing unit for parallel processing purposes.Root mean square error (RMSE) between the ground truth and reconstructed volumes of the numerical phantom were in the descending order of FDK, CTV, PICCS, MCIR, and c-MGIR for all phases. Specifically, the means and the standard deviations of the RMSE of FDK, CTV, PICCS, MCIR and c-MGIR for all phases were 42.64  ±  6.5%, 3.63  ±  0.83%, 1.31%  ±  0.09%, 0.86%  ±  0.11% and 0.52 %  ±  0.02%, respectively. The image quality of the patient case also indicated the superiority of c-MGIR compared to other algorithms.The results indicated that clinically viable 4D CBCT images can be reconstructed while requiring no more projection data than a typical clinical 3D CBCT scan. This makes c-MGIR a potential online reconstruction algorithm for 4D CBCT, which can provide much better image quality than other available algorithms, while requiring less dose and potentially less scanning time.

Physicochemical Evaluations of Selected Solvents for Use in Decontaminating Agent: Multipurpose (DAM) Formulation

DTIC Science & Technology

1994-03-01

PARAMETER FOR K-125 POLYMER Molar p, volume, Polymer g/co cc 8d 5p 8• PMMA 1.17 86.5 16.5 5.7 9.0 19.7 PnPrMA 1.08 118.7 16.6 4.1 7.7 18.8 PnBuMA 1.05 135.2...with an usable fluid range. The limited toxicological data (Ref. 2) shows that the compounds have low acute toxicity and are only mildly irritating...expected from the similarity in structure and the similarity in physical properties that its toxicological properties will be quite like those of sulfolane

Microwave measurements of the tropolone–formic acid doubly hydrogen bonded dimer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pejlovas, Aaron M.; Kukolich, Stephen G.; Serrato, Agapito

2016-01-28

The microwave spectrum was measured for the doubly hydrogen bonded dimer formed between tropolone and formic acid. The predicted symmetry of this dimer was C{sub 2v}(M), and it was expected that the concerted proton tunneling motion would be observed. After measuring 25 a- and b-type rotational transitions, no splittings which could be associated with a concerted double proton tunneling motion were observed. The calculated barrier to the proton tunneling motion is near 15 000 cm{sup −1}, which would likely make the tunneling frequencies too small to observe in the microwave spectra. The rotational and centrifugal distortion constants determined from the measuredmore » transitions were A = 2180.7186(98) MHz, B = 470.873 90(25) MHz, C = 387.689 84(22) MHz, D{sub J} = 0.0100(14) kHz, D{sub JK} = 0.102(28) kHz, and D{sub K} = 13.2(81) kHz. The B3LYP/aug-cc-pVTZ calculated rotational constants were within 1% of the experimentally determined values.« less

SU-F-BRA-03: Integrating Novel Electromagnetic Tracking Hollow Needle Assistance in Permanent Implant Brachytherapy Procedures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Racine, E; Hautvast, G; Binnekamp, D

Purpose: To report on the results of a complete permanent implant brachytherapy procedure assisted by an electromagnetic (EM) hollow needle possessing both 3D tracking and seed drop detection abilities. Methods: End-to-end in-phantom EM-assisted LDR procedures were conducted. The novel system consisted of an EM tracking apparatus (NDI Aurora V2, Planar Field Generator), a 3D US scanner (Philips CX50), a hollow needle prototype allowing 3D tracking and seed drop detection and a specially designed treatment planning software (Philips Healthcare). A tungsten-doped 30 cc spherical agarose prostate immersed in gelatin was used for the treatment. A cylindrical shape of 0.8 cc wasmore » carved along its diameter to mimic the urethra. An initial plan of 26 needles and 47 seeds was established with the system. The plan was delivered with the EM-tracked hollow needle, and individual seed drop locations were recorded on the fly. The phantom was subsequently imaged with a CT scanner from which seed positions and contour definitions were obtained. The DVHs were then independently recomputed and compared with those produced by the planning system, both before and after the treatment. Results: Of the 47 seeds, 45 (96%) were detected by the EM technology embedded in the hollow needle design. The executed plan (from CT analysis) differed from the initial plan by 2%, 14% and 8% respectively in terms of V100, D90 and V150 for the prostate, and by 8%, 7% and 10% respectively in terms of D5, V100 and V120 for the urethra. Conclusion: The average DVH deviations between initial and executed plans were within a 5% tolerance imposed for this proof-of-concept assessment. This relatively good concordance demonstrates the feasibility and potential benefits of combining EM tracking and seed drop detection for real-time dosimetry validation and assistance in permanent implant brachytherapy procedures. This project has been entirely funded by Philips Healthcare.« less

On the use of volumetric-modulated arc therapy for single-fraction thoracic vertebral metastases stereotactic body radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pokhrel, Damodar, E-mail: damodar.pokhrel@uky.edu; Sood, Sumit; McClinton, Christopher

To retrospectively evaluate quality, efficiency, and delivery accuracy of volumetric-modulated arc therapy (VMAT) plans for single-fraction treatment of thoracic vertebral metastases using image-guided stereotactic body radiosurgery (SBRS) after RTOG 0631 dosimetric compliance criteria. After obtaining credentialing for MD Anderson spine phantom irradiation validation, 10 previously treated patients with thoracic vertebral metastases with noncoplanar hybrid arcs using 1 to 2 3D-conformal partial arcs plus 7 to 9 intensity-modulated radiation therapy beams were retrospectively re-optimized with VMAT using 3 full coplanar arcs. Tumors were located between T2 and T12. Contrast-enhanced T1/T2-weighted magnetic resonance images were coregistered with planning computed tomography and planningmore » target volumes (PTV) were between 14.4 and 230.1 cc (median = 38.0 cc). Prescription dose was 16 Gy in 1 fraction with 6 MV beams at Novalis-TX linear accelerator consisting of micro multileaf collimators. Each plan was assessed for target coverage using conformality index, the conformation number, the ratio of the volume receiving 50% of the prescription dose over PTV, R50%, homogeneity index (HI), and PTV-1600 coverage per RTOG 0631 requirements. Organs-at-risk doses were evaluated for maximum doses to spinal cord (D{sub 0.03} {sub cc}, D{sub 0.35} {sub cc}), partial spinal cord (D{sub 10%}), esophagus (D{sub 0.03} {sub cc} and D{sub 5} {sub cc}), heart (D{sub 0.03} {sub cc} and D{sub 15} {sub cc}), and lung (V{sub 5}, V{sub 10}, and maximum dose to 1000 cc of lung). Dose delivery efficiency and accuracy of each VMAT-SBRS plan were assessed using quality assurance (QA) plan on MapCHECK device. Total beam-on time was recorded during QA procedure, and a clinical gamma index (2%/2 mm and 3%/3 mm) was used to compare agreement between planned and measured doses. All 10 VMAT-SBRS plans met RTOG 0631 dosimetric requirements for PTV coverage. The plans demonstrated highly conformal and homogenous coverage of the vertebral PTV with mean HI, conformality index, conformation number, and R{sub 50%} values of 0.13 ± 0.03 (range: 0.09 to 0.18), 1.03 ± 0.04 (range: 0.98 to 1.09), 0.81 ± 0.06 (range: 0.72 to 0.89), and 4.2 ± 0.94 (range: 2.7 to 5.4), respectively. All 10 patients met protocol guidelines with maximum dose to spinal cord (average: 8.83 ± 1.9 Gy, range: 5.9 to 10.9 Gy); dose to 0.35 cc of spinal cord (average: 7.62 ± 1.7 Gy, range: 5.4 to 9.6 Gy); and dose to 10% of partial spinal cord (average 6.31 ± 1.5 Gy, range: 3.5 to 8.5 Gy) less than 14, 10, and 10 Gy, respectively. For all 10 patients, the maximum dose to esophagus (average: 9.41 ± 4.3 Gy, range: 1.5 to 14.9 Gy) and dose to 5 cc of esophagus (average: 7.43 ± 3.8 Gy, range: 1.1 to 11.8 Gy) were kept less than protocol requirements 16 Gy and 11.9 Gy, respectively. In a similar manner, all 10 patients met protocol compliance criteria with maximum dose to heart (average: 4.62 ± 3.5 Gy, range: 1.3 to 10.2 Gy) and dose to 15 cc of heart (average: 2.23 ± 1.8 Gy, range: 0.3 to 5.6 Gy) less than 22 and 16 Gy, respectively. The dose to the lung was retained much lower than protocol guidelines for all 10 patients. The total number of monitor units was, on average, 6919 ± 1187. The average beam-on time was 11.5 ± 2.0 minutes. The VMAT plans demonstrated dose delivery accuracy of 95.8 ± 0.7%, on average, for clinical gamma passing rate with 2%/2 mm criteria and 98.3 ± 0.8%, on average, with 3%/3 mm criteria. All VMAT-SBRS plans were considered clinically acceptable per RTOG 0631 dosimetric compliance criteria. VMAT planning provided highly conformal and homogenous dose distributions for the lower-dose vertebral PTV and the spinal cord as well as organs-at-risk such as esophagus, heart, and lung. Higher QA pass rates and shorter beam-on time suggest that VMAT-SBRS is a clinically feasible, fast, and effective treatment option for patients with thoracic vertebral metastases.« less

Effects of stocking rate, forage management, and grazing management on performance and economics of cow-calf production in Southwest Arkansas.

PubMed

Beck, P A; Stewart, C B; Sims, M B; Gadberry, M S; Jennings, J A

2016-09-01

The objective this research was to determine the effect of application of multiple grazing management practices at 2 stocking rates (SR) on the productivity and economics of the cow-calf enterprise in the Southeastern United States over a 4-yr period. Pasture management systems included: continuous grazing management at a moderate SR (0.8 ha/cow; CG) without additional forage management, rotational grazing management at a moderate SR (0.8 ha/cow (MR) with addition of stockpiled bermudagrass [ (L.) Pers.] and complementary cool season annuals, and rotational grazing management similar to MR but with a high SR (0.4 ha/cow; HR). Stockpiling in MR and HR was managed by fertilization of 0.2 ha/cow of bermudagrass in early August with 168 kg ammonium nitrate and deferring grazing until November. Wheat (; 112 kg/ha) and annual ryegrass ( Lam.; 28 kg/ha) were interseeded (0.2 ha/cow) in HR and MR with a no-till drill in the fall. Cow and calf performance and economics data were analyzed by ANOVA using the MIXED procedure of SAS (SAS Inst. Inc., Cary, NC) and pregnancy percentage was analyzed using the GLIMMIX procedure of SAS; pasture was the experimental unit and year was the random block. Hay feeding days decreased ( < 0.01) from 107 ± 10.9 d for CG to 37 ± 10.9 d for HR, which was further reduced ( = 0.01) to 15 ± 10.9 d for MR. Pregnancy percentage did not differ ( = 0.20) among treatments. Weaning BW in CG (237 ± 7.3 kg) tended ( = 0.09) to be greater than in MR (227 ± 7.3 kg) and were greater ( < 0.01) than in HR (219 ± 7.3 kg). However, total weaning BW per hectare was 89% greater ( < 0.01) for HR compared with CG and MR, which did not differ ( = 0.31). With rotational stocking, there was the opportunity to harvest excess forage as hay in both MR and HR with a net value of US$52.90/ha ± 25.73 and $15.50/ha ± 25.73, respectively. Net returns per hectare did not differ ( = 0.30) between CG ($429 ± 63.0/ha) and MR ($479 ± 63.0/ha) but were increased ( < 0.01) by 107% by HR ($1,024 ± 63.0/ha). Using rotational grazing, stockpiled bermudagrass, and complementary cool-season annual grasses can drastically reduce winter feed requirements and simultaneously increase carrying capacity and net return.

Teaching enthesis ultrasound: experience of an ultrasound training workshop.

PubMed

Miguel, Cláudia; De Miguel, Eugenio; Batlle-Gualda, Enrique; Rejón, Eduardo; Lojo, Leticia

2012-12-01

To evaluate a standardised enthesis ultrasound training method, a workshop was conducted to train rheumatologists on enthesis ultrasound. After a theoretical session about ultrasound elementary enthesis lesions (changes in tendon architecture/thickness, bone proliferation/erosion, bursitis or Doppler signal), a reading exercise of 28 entheses' ultrasonographic images (plantar fasciae, Achilles, origin and insertion of patellar tendon) was completed. Participants scored through an electronic multiple-choice device with six possible lesions in each enthesis. To assess the adequacy and efficacy of the workshop, we explored the following: (1) subjective outcomes: a 12-item structured satisfaction questionnaire (graded 1-5 using Likert scale) and (2) objective outcomes of reliability: sensitivity (Se), specificity (Sp) and percentage of correctly classified cases (CC). Forty-nine participants attended the workshop. The satisfaction questionnaire demonstrated a 4.7 mean global value. The inter-reader Kappa reliability coefficient was moderate for the plantar fascia (0.47), Achilles tendon (0.47), and distal patellar tendons (0.50) and good for the proximal patellar tendon (0.63). The whole group means comparing to teachers' consensus were as follows: (a) plantar fascia: Se, 73.2%; Sp, 87.7%; CC, 83.3%; (b) Achilles: Se, 66.9%; Sp, 85.0%; CC, 79.5%; (c) distal patellar tendon: Se, 74.6%; Sp, 85.3%; CC, 82.1%; and (d) proximal patellar tendon: Se, 82.2%; Sp, 90.6%; CC, 88%. The proposed learning method seemed to be simple, easily performed, effective and well accepted by the target audience.

Selection of Human Antibody Fragments Which Bind Novel Breast Tumor Antigens

DTIC Science & Technology

1997-09-01

Human monoclonal antibody production: current status and future prospects. J. Immunol. Methods. 100: 5-. 16. Marks, J.D., Hoogenboom , H.R., Griffiths...16007-16010. 17. Hoogenboom , H.R., Marks, J.D., Griffiths, A.D., and Winter, G. (1992) Building antibodies from their genes. Immunol. Rev. 130: 41-68...Nature. 348: 552-4. page (21) Annual report, Grant No. DAMD17-94-J-4433 James D. Marks M.D., Ph.D. 19. Hoogenboom , H.R., Griffiths, A.D., Johnson, K.S

Single oral dose safety of D-allulose in dogs.

PubMed

Nishii, Naohito; Nomizo, Toru; Takashima, Satoshi; Matsubara, Tatsuya; Tokuda, Masaaki; Kitagawa, Hitoshi

2016-07-01

Healthy dogs were administered acute oral doses of D-allulose (also called D-psicose) to evaluate its toxicity. Six dogs received oral doses of either a placebo or D-allulose solution (1 and 4 g/kg) on three different study days. One dog experienced vomiting, and five dogs showed transient diarrhea when 4 g/kg of D-allulose was administered. All dogs were active and had a good appetite throughout the study period. Blood glucose concentration slightly decreased without a rise in plasma insulin concentration 2 hr after D-allulose administration. Plasma alkaline phosphatase activities showed a mild increase between 12 and 48 hr after D-allulose administration. These data suggested that a single oral dose of D-allulose does not show severe toxicity in dogs.

Structural basis for cargo binding and autoinhibition of Bicaudal-D1 by a parallel coiled-coil with homotypic registry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Terawaki, Shin-ichi, E-mail: terawaki@gunma-u.ac.jp; SPring-8 Center, RIKEN, 1-1-1 Koto, Sayo-cho, Sayo-gun, Hyogo 679-5148; Yoshikane, Asuka

Bicaudal-D1 (BICD1) is an α-helical coiled-coil protein mediating the attachment of specific cargo to cytoplasmic dynein. It plays an essential role in minus end-directed intracellular transport along microtubules. The third C-terminal coiled-coil region of BICD1 (BICD1 CC3) has an important role in cargo sorting, including intracellular vesicles associating with the small GTPase Rab6 and the nuclear pore complex Ran binding protein 2 (RanBP2), and inhibiting the association with cytoplasmic dynein by binding to the first N-terminal coiled-coil region (CC1). The crystal structure of BICD1 CC3 revealed a parallel homodimeric coiled-coil with asymmetry and complementary knobs-into-holes interactions, differing from Drosophila BicDmore » CC3. Furthermore, our binding study indicated that BICD1 CC3 possesses a binding surface for two distinct cargos, Rab6 and RanBP2, and that the CC1-binding site overlaps with the Rab6-binding site. These findings suggest a molecular basis for cargo recognition and autoinhibition of BICD proteins during dynein-dependent intracellular retrograde transport. - Highlights: • BICD1 CC3 is a parallel homodimeric coiled-coil with axial asymmetry. • The coiled-coil packing of BICD1 CC3 is adapted to the equivalent heptad position. • BICD1 CC3 has distinct binding sites for two classes of cargo, Rab6 and RanBP2. • The CC1-binding site of BICD1 CC3 overlaps with the Rab6-binding site.« less

[Clinical-pathological features and survival in young women with cervical cancer: a retrospective analysis from the instituto nacional de enfermedades neoplásicas].

PubMed

Ruiz, Rossana; Serrano, Mariana; Ruiz, Eloy F; Mantilla, Raul; Valdivieso, Natalia; Olivera, Mivael; Álvarez, Manuel; Mas, Luis; Gomez, Henry L

2017-01-01

To determine the clinical and histological characteristics and prognostic factors of cervical cancer (CC) in young Peruvian patients. Retrospective analysis of patients younger than 35 years old diagnosed with CC between 2008 and 2012 in the Instituto Nacional de Enfermedades Neoplásicas. 449 patients had epithelial neoplasms. The main histological types were: squamous cell carcinoma (84.9%), adenocarcinoma (11.0%) and adenosquamous carcinoma (2.4%). The average tumor size was 4.98 cm. Anemia (55.7%), elevated creatinine (21.2%) and hydronephrosis (13.8%) were also identified. 82.3% of the patients presented locally advanced disease. Stages IIB (47.4%) and IIIB (25.8%) were the most common. Overall 5-year survival was 59.5% (I, 90.9%; II, 57.5%; III, 42.7% and IV, 13.3%). Elevated creatinine, anemia, tumor size, parametrial involvement and hydronephrosis were factors that affected survival. No significant relation was found between histological type and survival. The presence of anemia (adjusted hazard ratio [aHR]: 2.5; 95% confidence interval [CI 95%]: 1.6-4.0) and hydronephrosis (aHR: 1.6; CI 95%: 1.0-4.0) were independently associated with survival; likewise, the parametrial commitment with (aHR: 3.3; CI 95%: 1.5-7.2) or without (aRH: 2.6; CI 95%: 1.3-5.3) extension to the pelvic bone. Cervical cancer in young Peruvians is diagnosed in advanced stages. Overall survival in each stage is similar to the reported in older patients. The importance of conventional prognosis- related factors was confirmed. Anemia was an important independent prognostic factor requiring further investigations.

Maize Homologs of CCoAOMT and HCT, Two Key Enzymes in Lignin Biosynthesis, Form Complexes with the NLR Rp1 Protein to Modulate the Defense Response1

PubMed Central

2016-01-01

Disease resistance (R) genes encode nucleotide binding Leu-rich-repeat (NLR) proteins that confer resistance to specific pathogens. Upon pathogen recognition they trigger a defense response that usually includes a so-called hypersensitive response (HR), a rapid localized cell death at the site of pathogen infection. Intragenic recombination between two maize (Zea mays) NLRs, Rp1-D and Rp1-dp2, resulted in the formation of a hybrid NLR, Rp1-D21, which confers an autoactive HR in the absence of pathogen infection. From a previous quantitative trait loci and genome-wide association study, we identified genes encoding two key enzymes in lignin biosynthesis, hydroxycinnamoyltransferase (HCT) and caffeoyl CoA O-methyltransferase (CCoAOMT), adjacent to the nucleotide polymorphisms that were highly associated with variation in the severity of Rp1-D21-induced HR. We have previously shown that the two maize HCT homologs suppress the HR conferred by Rp1-D21 in a heterologous system, very likely through physical interaction. Here, we show, similarly, that CCoAOMT2 suppresses the HR induced by either the full-length or by the N-terminal coiled-coil domain of Rp1-D21 also likely via physical interaction and that the metabolic activity of CCoAOMT2 is unlikely to be necessary for its role in suppressing HR. We also demonstrate that CCoAOMT2, HCTs, and Rp1 proteins can form in the same complexes. A model is derived to explain the roles of CCoAOMT and HCT in Rp1-mediated defense resistance. PMID:27208251

Maize Homologs of CCoAOMT and HCT, Two Key Enzymes in Lignin Biosynthesis, Form Complexes with the NLR Rp1 Protein to Modulate the Defense Response.

PubMed

Wang, Guan-Feng; Balint-Kurti, Peter J

2016-07-01

Disease resistance (R) genes encode nucleotide binding Leu-rich-repeat (NLR) proteins that confer resistance to specific pathogens. Upon pathogen recognition they trigger a defense response that usually includes a so-called hypersensitive response (HR), a rapid localized cell death at the site of pathogen infection. Intragenic recombination between two maize (Zea mays) NLRs, Rp1-D and Rp1-dp2, resulted in the formation of a hybrid NLR, Rp1-D21, which confers an autoactive HR in the absence of pathogen infection. From a previous quantitative trait loci and genome-wide association study, we identified genes encoding two key enzymes in lignin biosynthesis, hydroxycinnamoyltransferase (HCT) and caffeoyl CoA O-methyltransferase (CCoAOMT), adjacent to the nucleotide polymorphisms that were highly associated with variation in the severity of Rp1-D21-induced HR We have previously shown that the two maize HCT homologs suppress the HR conferred by Rp1-D21 in a heterologous system, very likely through physical interaction. Here, we show, similarly, that CCoAOMT2 suppresses the HR induced by either the full-length or by the N-terminal coiled-coil domain of Rp1-D21 also likely via physical interaction and that the metabolic activity of CCoAOMT2 is unlikely to be necessary for its role in suppressing HR. We also demonstrate that CCoAOMT2, HCTs, and Rp1 proteins can form in the same complexes. A model is derived to explain the roles of CCoAOMT and HCT in Rp1-mediated defense resistance. © 2016 American Society of Plant Biologists. All Rights Reserved.

Supernova rates from the Southern inTermediate Redshift ESO Supernova Search (STRESS)

NASA Astrophysics Data System (ADS)

Botticella, M. T.; Riello, M.; Cappellaro, E.; Benetti, S.; Altavilla, G.; Pastorello, A.; Turatto, M.; Greggio, L.; Patat, F.; Valenti, S.; Zampieri, L.; Harutyunyan, A.; Pignata, G.; Taubenberger, S.

2008-02-01

Aims:To measure the supernova (SN) rates at intermediate redshift we performed a search, the Southern inTermediate Redshift ESO Supernova Search (STRESS). Unlike most of the current high redshift SN searches, this survey was specifically designed to estimate the rate for both type Ia and core collapse (CC) SNe. Methods: We counted the SNe discovered in a selected galaxy sample measuring SN rate per unit blue band luminosity. Our analysis is based on a sample of 43 000 galaxies and on 25 spectroscopically confirmed SNe plus 64 selected SN candidates. Our approach is aimed at obtaining a direct comparison of the high redshift and local rates and at investigating the dependence of the rates on specific galaxy properties, most notably their colour. Results: The type Ia SN rate, at mean redshift z=0.3, is 0.22+0.10 +0.16-0.08 -0.14 h702 SNu, while the CC SN rate, at z=0.21, is 0.82+0.31 +0.30-0.24 -0.26 h702 SNu. The quoted errors are the statistical and systematic uncertainties. Conclusions: With respect to the local value, the CC SN rate at z=0.2 is higher by a factor of 2, whereas the type Ia SN rate remains almost constant. This implies that a significant fraction of SN Ia progenitors has a lifetime longer than 2{-}3 Gyr. We also measured the SN rates in the red and blue galaxies and found that the SN Ia rate seems to be constant in galaxies of different colour, whereas the CC SN rate seems to peak in blue galaxies, as in the local Universe. SN rates per unit volume were found to be consistent with other measurements showing a steeper evolution with redshift for CC SNe than SNe Ia. We have exploited the link between SFH and SN rates to predict the evolutionary behaviour of the SN rates and compare it with the path indicated by observations. We conclude that in order to constrain the mass range of CC SN progenitors and SN Ia progenitor models it is necessary to reduce the uncertainties in the cosmic SFH. In addition it is important to apply a consistent dust extinction correction both to SF and to CC SN rate and to measure the SN Ia rate in star forming and in passively evolving galaxies over a wide redshift range. Based on observations collected at the European Southern Observatory, using the 2.2 m MPG/ESO telescope on the La Silla (ESO Programmes 62.H-0833, 63.H-0322, 64.H-0390, 67.D-0422, 68.D-0273, 69.D-0453, 72.D-0670, 72.D-0745, 73.D-0670, 74.A-9008, 75.D-0662) and using Very Large Telescope on the Cerro Paranal (ESO Programme 74.D-0714). Table [see full textsee full textsee full text], Figs. [see full textsee full textsee full text]-[see full textsee full textsee full text] are only available in electronic form at http://www.aanda.org

Triterpene tetraglycosides from the sea cucumber Stichopus horrens.

PubMed

Vien, Le Thi; Hoang, Le; Hanh, Tran Thi Hong; Thanh, Nguyen Van; Cuong, Nguyen Xuan; Nam, Nguyen Hoai; Thung, Do Cong; Kiem, Phan Van; Minh, Chau Van

2018-05-01

Using various chromatographic separations, three triterpene tetraglycosides (1-3), including one new compound, namely stichorrenoside E (1) along with thelenotoside B (2) and deacetyl thelenotoside B (3), were isolated from the MeOH extract of the Vietnamese sea cucumber Stichopus horrens. Their structures were confirmed by spectroscopic experiments, such as 1D and 2D NMR and HR-ESI-MS. Deacetylated thelenotoside B (3) is firstly isolated as a natural product. Among these compounds, thelenotoside B (2) showed strong cytotoxicities against five human cancer cell lines as HepG2, KB, LNCaP, MCF7 and SK-Mel2 with the IC 50 values from 0.95 ± 0.08 to 1.90 ± 0.13 μM, whereas stichorrenoside E (1) and deacetyl thelenotoside B (3) exhibited significant activities with the IC 50 values from 6.87 ± 0.25 to 11.62 ± 1.05 μM.

Baroreflex dysfunction in sick newborns makes heart rate an unreliable surrogate for blood pressure changes.

PubMed

Govindan, Rathinaswamy B; Al-Shargabi, Tareq; Massaro, An N; Metzler, Marina; Andescavage, Nickie N; Joshi, Radhika; Dave, Rhiya; du Plessis, Adre

2016-06-01

Cerebral pressure passivity (CPP) in sick newborns can be detected by evaluating coupling between mean arterial pressure (MAP) and cerebral blood flow measured by near infra-red spectroscopy hemoglobin difference (HbD). However, continuous MAP monitoring requires invasive catheterization with its inherent risks. We tested whether heart rate (HR) could serve as a reliable surrogate for MAP in the detection of CPP in sick newborns. Continuous measurements of MAP, HR, and HbD were made and partitioned into 10-min epochs. Spectral coherence (COH) was computed between MAP and HbD (COHMAP-HbD) to detect CPP, between HR and HbD (COHHR-HbD) for comparison, and between MAP and HR (COHMAP-HR) to quantify baroreflex function (BRF). The agreement between COHMAP-HbD and COHHR-HbD was assessed using ROC analysis. We found poor agreement between COHMAP-HbD and COHHR-HbD in left hemisphere (area under the ROC curve (AUC) 0.68) and right hemisphere (AUC 0.71). Baroreflex failure (COHMAP-HR not significant) was present in 79% of epochs. Confining comparison to epochs with intact BRF showed an AUC of 0.85 for both hemispheres. In these sick newborns, HR was an unreliable surrogate for MAP required for the detection of CPP. This is likely due to the prevalence of BRF failure in these infants.

New syndrome decoder for (n, 1) convolutional codes

NASA Technical Reports Server (NTRS)

Reed, I. S.; Truong, T. K.

1983-01-01

The letter presents a new syndrome decoding algorithm for the (n, 1) convolutional codes (CC) that is different and simpler than the previous syndrome decoding algorithm of Schalkwijk and Vinck. The new technique uses the general solution of the polynomial linear Diophantine equation for the error polynomial vector E(D). A recursive, Viterbi-like, algorithm is developed to find the minimum weight error vector E(D). An example is given for the binary nonsystematic (2, 1) CC.

Alternative initial proton acceptors for the D pathway of Rhodobacter sphaeroides cytochrome c oxidase

PubMed Central

Varanasi, Lakshman; Hosler, Jonathan

2011-01-01

In order to characterize protein structures that control proton uptake, forms of cytochrome c oxidase (CcO) containing a carboxyl or a thiol group in line with the initial, internal waters of the D pathway for proton transfer have been assayed in the presence and absence of subunit III. Subunit III provides approximately half of the protein surrounding the entry region of the D pathway. The mutant N139D-D132N contains a carboxyl group 6Å within the D pathway and lacks the normal, surface-exposed proton acceptor, Asp-132. With subunit III, the steady-state activity of this mutant is slow but once subunit III is removed its activity is the same as wild-type CcO lacking subunit III (∼1800 H+ s-1). Thus, a carboxyl group ∼25% within the pathway enhances proton uptake even though the carboxyl has no direct contact with bulk solvent. Protons from solvent apparently move to internal Asp-139 through a short file of waters, normally blocked by subunit III. Cysteine-139 also supports rapid steady-state proton uptake, demonstrating that an anion other than a carboxyl can attract and transfer protons into the D pathway. When both Asp-132 and Asp/Cys-139 are present, the removal of subunit III increases CcO activity to rates greater than that of normal CcO due to simultaneous proton uptake by two initial acceptors. The results show how the environment of the initial proton acceptor for the D pathway in these CcO forms dictates the pH range of CcO activity, with implications for the function of Asp-132, the normal proton acceptor. PMID:21344856

Validation of calcaneus trabecular microstructure measurements by HR-pQCT.

PubMed

Metcalf, Louis M; Dall'Ara, Enrico; Paggiosi, Margaret A; Rochester, John R; Vilayphiou, Nicolas; Kemp, Graham J; McCloskey, Eugene V

2018-01-01

Assessment of calcaneus microstructure using high-resolution peripheral quantitative computed tomography (HR-pQCT) might be used to improve fracture risk predictions or to assess responses to pharmacological and physical interventions. To develop a standard clinical protocol for the calcaneus, we validated calcaneus trabecular microstructure measured by HR-pQCT against 'gold-standard' micro-CT measurements. Ten human cadaveric feet were scanned in situ using HR-pQCT (isotropic 82μm voxel size) at 100, 150 and 200ms integration times, and at 100ms integration time following removal of the calcaneus from the foot (ex vivo). Dissected portions of these bones were scanned using micro-computed tomography (micro-CT) at an isotropic 17.4μm voxel size. HR-pQCT images were rigidly registered to those obtained with micro-CT and divided into multiple 5mm sided cubes to evaluate and compare morphometric parameters between the modalities. Standard HR-pQCT measurements (derived bone volume fraction (BV/TV d ); trabecular number, Tb.N; derived trabecular thickness, Tb.Th d ; derived trabecular spacing, Tb.Sp d ) and corresponding micro-CT voxel-based measurements (BV/TV, Tb.N, Tb.Th, Tb.Sp) were compared. A total of 108 regions of interest were analysed across the 10 specimens. At all integration times HR-pQCT BV/TV d was strongly correlated with micro-CT BV/TV (r 2 =0.95-0.98, RMSE=1%), but BV/TV d was systematically lower than that measured by micro-CT (mean bias=5%). In contrast, HR-pQCT systematically overestimated Tb.N at all integration times; of the in situ scans, 200ms yielded the lowest mean bias and the strongest correlation with micro-CT (r 2 =0.61, RMSE=0.15mm -1 ). Regional analysis revealed greater accuracy for Tb.N in the superior regions of the calcaneus at all integration times in situ (mean bias=0.44-0.85mm -1 ; r 2 =0.70-0.88, p<0.001 versus mean bias=0.63-1.46mm -1 ; r 2 ≤0.08, p≥0.21 for inferior regions). Tb.Sp d was underestimated by HR-pQCT compared to micro-CT, but showed similar trends with integration time and the region evaluated as Tb.N. HR-pQCT Tb.Th d was also underestimated and moderately correlated (r 2 =0.53-0.59) with micro-CT Tb.Th, independently from the integration time. Stronger correlations, smaller biases and error were found in the scans of the calcaneus ex vivo compared to in situ. Calcaneus trabecular BV/TV d and trabecular microstructure, particularly in the superior region of the calcaneus, can be assessed by HR-pQCT. The highest integration time examined, 200ms, compared best with micro-CT. Weaker correlations for microstructure at inferior regions, and also with lower integration times, might limit the use of the proposed protocol, which warrants further investigation in vivo. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A multi-institutional analysis of the untreated course of cerebral dural arteriovenous fistulas.

PubMed

Gross, Bradley A; Albuquerque, Felipe C; McDougall, Cameron G; Jankowitz, Brian T; Jadhav, Ashutosh P; Jovin, Tudor G; Du, Rose

2017-12-15

OBJECTIVE The rarity of cerebral dural arteriovenous fistulas (dAVFs) has precluded analysis of their natural history across large cohorts. Investigators from a considerable proportion of the few reports that do exist have evaluated heterogeneous groups of untreated and partially treated lesions. In the present study, the authors exclusively evaluated the untreated course of dAVFs across a multi-institutional data set to delineate demographic, angiographic, and natural history data. METHODS A multi-institutional database of dAVFs was queried for demographic and angiographic data as well as untreated disease course. After dAVFs were stratified by Djindjian type, annual nonhemorrhagic neurological deficit (NHND) and hemorrhage rates were derived, as were risk factors for each. A multivariable Cox proportional-hazards regression model was used to calculate hazard ratios. RESULTS Two hundred ninety-five dAVFs had at least 1 month of untreated follow-up. For 126 Type I dAVFs, there were no episodes of NHND or hemorrhage over 177 lesion-years. Respective annualized NHND and hemorrhage rates were 4.5% and 3.4% for Type II, 6.0% and 4.0% for Type III, and 4.5% and 9.1% for Type IV dAVFs. The respective annualized NHND and hemorrhage rates were 2.3% and 2.9% for asymptomatic Type II-IV dAVFs, 23.1% and 3.3% for dAVFs presenting with NHND, and 0% and 46.2% for lesions presenting with hemorrhage. On multivariate analysis, NHND presentation (HR 11.49, 95% CI 3.19-63) and leptomeningeal venous drainage (HR 5.03, 95% CI 0.42-694) were significant risk factors for NHND; hemorrhagic presentation (HR 17.67, 95% CI 2.99-117) and leptomeningeal venous drainage (HR 10.39, 95% CI 1.11-1384) were significant risk factors for hemorrhage. CONCLUSIONS All Type II-IV dAVFs should be considered for treatment. Given the high risk of rebleeding, lesions presenting with NHND and/or hemorrhage should be treated expediently.

The Chloroplastic Protein THF1 Interacts with the Coiled-Coil Domain of the Disease Resistance Protein N′ and Regulates Light-Dependent Cell Death1[OPEN

PubMed Central

Sekine, Ken-Taro; Wallon, Thérèse; Sugiwaka, Yuji; Kobayashi, Kappei

2016-01-01

One branch of plant immunity is mediated through nucleotide-binding/Leu-rich repeat (NB-LRR) family proteins that recognize specific effectors encoded by pathogens. Members of the I2-like family constitute a well-conserved subgroup of NB-LRRs from Solanaceae possessing a coiled-coil (CC) domain at their N termini. We show here that the CC domains of several I2-like proteins are able to induce a hypersensitive response (HR), a form of programmed cell death associated with disease resistance. Using yeast two-hybrid screens, we identified the chloroplastic protein Thylakoid Formation1 (THF1) as an interacting partner for several I2-like CC domains. Co-immunoprecipitations and bimolecular fluorescence complementation assays confirmed that THF1 and I2-like CC domains interact in planta and that these interactions take place in the cytosol. Several HR-inducing I2-like CC domains have a negative effect on the accumulation of THF1, suggesting that the latter is destabilized by active CC domains. To confirm this model, we investigated N′, which recognizes the coat protein of most Tobamoviruses, as a prototypical member of the I2-like family. Transient expression and gene silencing data indicated that THF1 functions as a negative regulator of cell death and that activation of full-length N′ results in the destabilization of THF1. Consistent with the known function of THF1 in maintaining chloroplast homeostasis, we show that the HR induced by N′ is light-dependent. Together, our results define, to our knowledge, novel molecular mechanisms linking light and chloroplasts to the induction of cell death by a subgroup of NB-LRR proteins. PMID:26951433

Vitamin D insufficiency is associated with increased risk of first-trimester miscarriage in the Odense Child Cohort.

PubMed

Andersen, Louise B; Jørgensen, Jan S; Jensen, Tina K; Dalgård, Christine; Barington, Torben; Nielsen, Jan; Beck-Nielsen, Signe S; Husby, Steffen; Abrahamsen, Bo; Lamont, Ronald F; Christesen, Henrik T

2015-09-01

Miscarriage is the most common negative outcome of pregnancy, and identification of modifiable risk factors is potentially of great importance for public health. Low vitamin D concentrations in pregnancy are widespread worldwide, and vitamin D deficiency is implicated in immune cell regulation at the feto-maternal interface and several diseases of pregnancy. We investigated whether 25-hydroxyvitamin D serum concentration was a modifiable risk factor for early miscarriage. In a prospective cohort study of 1683 pregnant women donating serum before gestational week 22, we investigated the association between maternal serum concentrations of serum 25-hydroxyvitamin D [25(OH)D] and the risk of subsequent miscarriage (n = 58). The adjusted hazard of first-trimester miscarriage was lower with higher 25(OH)D concentrations (HR: 0.98; 95% CI: 0.96, 0.99). Concentrations of 25(OH)D <50 nmol/L were associated with a >2-fold increased adjusted HR for miscarriage (HR: 2.50; 95% CI: 1.10, 5.69). Concentrations of 25(OH)D were not associated with an increased risk of second-trimester miscarriage. We found an association between 25(OH)D and first-trimester miscarriages, suggesting vitamin D as a modifiable risk factor for miscarriage. To test this hypothesis, randomized controlled trials should investigate the possible effect of vitamin D supplementation to increase 25(OH)D concentrations in early pregnancy, or before conception, to decrease risk of miscarriage. This trial was registered at clinicaltrials.gov as NCT02434900. © 2015 American Society for Nutrition.

Fabrication and Testing of Low Cost 2D Carbon-Carbon Nozzle Extensions at NASA/MSFC

NASA Technical Reports Server (NTRS)

Greene, Sandra Elam; Shigley, John K.; George, Russ; Roberts, Robert

2015-01-01

Subscale liquid engine tests were conducted at NASA/MSFC using a 1.2 Klbf engine with liquid oxygen (LOX) and gaseous hydrogen. Testing was performed for main-stage durations ranging from 10 to 160 seconds at a chamber pressure of 550 psia and a mixture ratio of 5.7. Operating the engine in this manner demonstrated a new and affordable test capability for evaluating subscale nozzles by exposing them to long duration tests. A series of 2D C-C nozzle extensions were manufactured, oxidation protection applied and then tested on a liquid engine test facility at NASA/MSFC. The C-C nozzle extensions had oxidation protection applied using three very distinct methods with a wide range of costs and process times: SiC via Polymer Impregnation & Pyrolysis (PIP), Air Plasma Spray (APS) and Melt Infiltration. The tested extensions were about 6" long with an exit plane ID of about 6.6". The test results, material properties and performance of the 2D C-C extensions and attachment features will be discussed.

GROUDWATER REMEDIATION AT THE 100-HR-3 OPERABLE UNIT HANFORD SITE WASHINGTON USA - 11507

DOE Office of Scientific and Technical Information (OSTI.GOV)

SMOOT JL; BIEBESHEIMER FH; ELUSKIE JA

2011-01-12

The 100-HR-3 Groundwater Operable Unit (OU) at the Hanford Site underlies three former plutonium production reactors and the associated infrastructure at the 100-D and 100-H Areas. The primary contaminant of concern at the site is hexavalent chromium; the secondary contaminants are strontium-90, technetium-99, tritium, uranium, and nitrate. The hexavalent chromium plume is the largest plume of its type in the state of Washington, covering an area of approximately 7 km{sup 2} (2.7 mi{sup 2}) with concentrations greater than 20 {micro}g/L. Concentrations range from 60,000 {micro}g/L near the former dichromate transfer station in the 100-D Area to large areas of 20more » to 100 {micro}g/L across much of the plume area. Pump-and-treat operations began in 1997 and continued into 2010 at a limited scale of approximately 200 gal/min. Remediation of groundwater has been fairly successful in reaching remedial action objectives (RAOs) of 20 {micro}g/L over a limited region at the 100-H, but less effective at 100-D. In 2000, an in situ, permeable reactive barrier was installed downgradient of the hotspot in 100-D as a second remedy. The RAOs are still being exceeded over a large portion of the area. The CH2M HILL Plateau Remediation Company was awarded the remediation contract for groundwater in 2008 and initiated a remedial process optimization study consisting of modeling and technical studies intended to enhance the remediation. As a result of the study, 1,400 gal/min of expanded treatment capacity are being implemented. These new systems are designed to meet 2012 and 2020 target milestones for protection of the Columbia River and cleanup of the groundwater plumes.« less

Accelerated partial breast irradiation using 3D conformal radiotherapy: toxicity and cosmetic outcome.

PubMed

Gatti, M; Ponzone, R; Bresciani, S; Panaia, R; Kubatzki, F; Maggiorotto, F; Di Virgilio, M R; Salatino, A; Baiotto, B; Montemurro, F; Stasi, M; Gabriele, P

2013-12-01

The aim of this paper is to analyze the incidence of acute and late toxicity and cosmetic outcome in breast cancer patients submitted to breast conserving surgery and three-dimensional conformal radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI). 84 patients were treated with 3D-CRT for APBI. This technique was assessed in patients with low risk stage I breast cancer enrolled from September 2005 to July 2011. The prescribed dose was 34/38.5 Gy delivered in 10 fractions twice daily over 5 consecutive days. Four to five no-coplanar 6 MV beams were used. In all CT scans Gross Tumor Volume (GTV) was defined around the surgical clips. A 1.5 cm margin was added by defining a Clinical Target Volume (CTV). A margin of 1 cm was added to CTV to define the planning target volume (PTV). The dose-volume constraints were followed in accordance with the NSABP/RTOG protocol. Late toxicity was evaluated according to the RTOG grading schema. The cosmetic assessment was performed using the Harvard scale. Median patient age was 66 years (range 51-87). Median follow-up was 36.5 months (range 13-83). The overall incidence of acute skin toxicities was 46.4% for grade 1 and 1% for grade 2. The incidence of late toxicity was 16.7% for grade 1, 2.4% for grade 2 and 3.6% for grade 3. No grade 4 toxicity was observed. The most pronounced grade 2 late toxicity was telangiectasia, developed in three patients. Cosmetics results were excellent for 52%, good for 42%, fair for 5% and poor for 1% of the patients. There was no statistical correlation between toxicity rates and prescribed doses (p = 0.33) or irradiated volume (p = 0.45). APBI using 3D-CRT is technically feasible with very low acute and late toxicity. Long-term results are needed to assess its efficacy in reducing the incidence of breast relapse. Copyright © 2013 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pokhrel, D; Sood, S; Badkul, R

Purpose: To evaluate XVMC computed rib doses for peripherally located non-small-cell-lung tumors treated with SBRT following RTOG-0915 guidelines. Methods: Twenty patients with solitary peripherally located non-small-cell-lung tumors were treated using XVMC-based SBRT to 50–54Gy in 5−3 fractions, respectively, for PTV(V100%)=95%. Based on 4D-CT, ITV was delineated on MaximumIP images and organs-at-risk(OARs) including ribs were contoured on MeanIP images. Mean PTV(ITV+5mm uniform margin) was 46.1±38.7cc (range, 11.1–163.0cc). XVMC SBRT treatment plans were generated with a combination of non-coplanar 3D-conformal arcs/beams, and were delivered by Novalis-TX consisting of HD-MLCs and a 6MV-SRS(1000MU/min) beam, following RTOG-0915 criteria. XVMC rib maximum dose and dosemore » to <1cc, <5cc, <10cc were evaluated as a function of PTV, prescription dose and 3D-distance from tumor isocenter to the most proximal rib contour. Plans were re-computed using heterogeneity-corrected pencil-beam (PB-hete) algorithm utilizing identical beam geometry/MLC positions and MUs and subsequently compared to XVMC. Results: XVMC average maximum rib dose was 50.9±6.4Gy (range, 35.1–59.3Gy). XVMC mean rib dose to <1cc was 41.6±5.6Gy (range, 27.9–47.9Gy), <5cc was 31.2±7.3Gy (range, 10.6–43.1Gy), and <10cc was 21.2±8.7Gy (range, 1.1–36Gy), respectively. For the given prescription, correlation between PTV and rib doses to <5cc (p=0.005) and <10cc (p=0.018) was observed. 3D-distance from the tumor isocenter to the proximal rib contour strongly correlated with maximum rib dose (p=0.0001). PB-hete algorithm overestimated maximum rib dose and dose to <1cc, <5cc, and <10cc of ribs by 5%, 3%, 3%, and 3%, respectively. Conclusion: PB-hete overestimates ribs dose relative to XVMC. Since all the clinical XVMC plans were generated without compromising the target coverage (per RTOG-0915), almost all patient’s ribs doses were higher than the protocol guidelines. As expected, larger tumor size and proximity to ribs received higher absolute dose to ribs. Prospective observation is needed to determine if XVMC delivered rib doses correlates with patient symptoms including chest wall pain and/or rib fractures.« less

Noncore RAG1 regions promote Vβ rearrangements and αβ T cell development by overcoming inherent inefficiency of Vβ recombination signal sequences.

PubMed

Horowitz, Julie E; Bassing, Craig H

2014-02-15

The RAG proteins are comprised of core endonuclease domains and noncore regions that modulate endonuclease activity. Mutation or deletion of noncore RAG regions in humans causes immunodeficiency and altered TCR repertoire, and mice expressing core but not full-length Rag1 (Rag1(C/C)) or Rag2 (Rag2(C/C)) exhibit lymphopenia, reflecting impaired V(D)J recombination and lymphocyte development. Rag1(C/C) mice display reduced D-to-J and V-to-DJ rearrangements of TCRβ and IgH loci, whereas Rag2(C/C) mice show decreased V-to-DJ rearrangements and altered Vβ/VH repertoire. Because Vβs/VHs only recombine to DJ complexes, the Rag1(C/C) phenotype could reflect roles for noncore RAG1 regions in promoting recombination during only the D-to-J step or during both steps. In this study, we demonstrate that a preassembled TCRβ gene, but not a preassembled DβJβ complex or the prosurvival BCL2 protein, completely rescues αβ T cell development in Rag1(C/C) mice. We find that Rag1(C/C) mice exhibit altered Vβ utilization in Vβ-to-DJβ rearrangements, increased usage of 3'Jα gene segments in Vα-to-Jα rearrangements, and abnormal changes in Vβ repertoire during αβ TCR selection. Inefficient Vβ/VH recombination signal sequences (RSSs) have been hypothesized to cause impaired V-to-DJ recombination on the background of a defective recombinase as in core-Rag mice. We show that replacement of the Vβ14 RSS with a more efficient RSS increases Vβ14 recombination and rescues αβ T cell development in Rag1(C/C) mice. Our data indicate that noncore RAG1 regions establish a diverse TCR repertoire by overcoming Vβ RSS inefficiency to promote Vβ recombination and αβ T cell development, and by modulating TCRβ and TCRα gene segment utilization.

SU-E-T-810: Volumetric Modulated Arc Therapy and Conventional Intensity-Modulated Radiotherapy for Non-Small-Cell Lung Cancer with Simultaneously Integrated Boost Radiation Therapy: A Planning Comparison Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, T; Chen, J; Zhang, G

2015-06-15

Purpose: To compare and analyze the characteristics of intensity-modulated arc therapy(IMAT) versus fixed-gantry intensity-modulated radiotherapy(IMRT) in treatment of non-small-cell lung cancer. Methods: Twelve patients treated in our radiotherapy center were selected for this study. The patient subsequently underwent 4D-CT simulation.Margins of 5mm and 10mm were added to the ITV to generate the CTV and PTV respectively. Three treatment plans (IMRT,one single arc (RA1),double arcs (RA2))were generated with Eclipse ver.8.6 planning systems. Using a dose level of 75Gy in 15fractions to the ITV,60Gy in 15fractions to the CTV and 45Gy in 15fractions to the PTV respectively. The target and normol tissuemore » volumes were compared,as were the dosimetry parameters. Results: There were no significant differences in CI of ITV,PTV,HI of ITV,CTV and PTV, V5,V10,V15,V20,V25,V30,V45,V50 of total-lung and mean lung dose (all p>0.05). However, the differences were significant in terms of CI of CTV,V5 of B-P (all p<0.05). On the MU, IMRT=1540MU,RA1=1006 MU and RA2=1096 MU. (F=12.00,P=0.000).On the treatment time, IMRT= 13.5min,RA1= 1.5min,and RA2=2.5 min (F= 30.11,P=0.000 ). Conclusion: IMAT is equal to IMRT in dosimetril evaluation. Due to much less Mu and delivery time,IMAT is an ideal technique in treating patients by reduceing the uncomfortable influnce which could effect the treatment.« less

Heart rate complexity: A novel approach to assessing cardiac stress reactivity.

PubMed

Brindle, Ryan C; Ginty, Annie T; Phillips, Anna C; Fisher, James P; McIntyre, David; Carroll, Douglas

2016-04-01

Correlation dimension (D2), a measure of heart rate (HR) complexity, has been shown to decrease in response to acute mental stress and relate to adverse cardiovascular health. However, the relationship between stress-induced changes in D2 and HR has yet to be established. The present studies aimed to assess this relationship systematically while controlling for changes in respiration and autonomic activity. In Study 1 (N = 25) D2 decreased during stress and predicted HR reactivity even after adjusting for changes in respiration rate, and cardiac vagal tone. This result was replicated in Study 2 (N = 162) and extended by including a measure of cardiac sympathetic activity; correlation dimension remained an independent predictor of HR reactivity in a hierarchical linear model containing measures of cardiac parasympathetic and sympathetic activity and their interaction. These results suggest that correlation dimension may provide additional information regarding cardiac stress reactivity above that provided by traditional measures of cardiac autonomic function. © 2015 Society for Psychophysiological Research.

Dietary vitamin D intake and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition: the EPIC-InterAct study.

PubMed

Abbas, S; Linseisen, J; Rohrmann, S; Beulens, J W J; Buijsse, B; Amiano, P; Ardanaz, E; Balkau, B; Boeing, H; Clavel-Chapelon, F; Fagherazzi, G; Franks, P W; Gavrila, D; Grioni, S; Kaaks, R; Key, T J; Khaw, K T; Kühn, T; Mattiello, A; Molina-Montes, E; Nilsson, P M; Overvad, K; Quirós, J R; Rolandsson, O; Sacerdote, C; Saieva, C; Slimani, N; Sluijs, I; Spijkerman, A M W; Tjonneland, A; Tumino, R; van der A, D L; Zamora-Ros, R; Sharp, S J; Langenberg, C; Forouhi, N G; Riboli, E; Wareham, N J

2014-02-01

Prospective cohort studies have indicated that serum vitamin D levels are inversely related to risk of type 2 diabetes. However, such studies cannot determine the source of vitamin D. Therefore, we examined the association of dietary vitamin D intake with incident type 2 diabetes within the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study in a heterogeneous European population including eight countries with large geographical variation. Using a case-cohort design, 11,245 incident cases of type 2 diabetes and a representative subcohort (N=15,798) were included in the analyses. Hazard ratios (HR) and 95% confidence intervals (CIs) for type 2 diabetes were calculated using a Prentice-weighted Cox regression adjusted for potential confounders. Twenty-four-hour diet-recall data from a subsample (N=2347) were used to calibrate habitual intake data derived from dietary questionnaires. Median follow-up time was 10.8 years. Dietary vitamin D intake was not significantly associated with the risk of type 2 diabetes. HR and 95% CIs for the highest compared to the lowest quintile of uncalibrated vitamin D intake was 1.09 (0.97-1.22) (Ptrend=0.17). No associations were observed in a sex-specific analysis. The overall pooled effect (HR (95% CI)) using the continuous calibrated variable was 1.00 (0.97-1.03) per increase of 1 μg/day dietary vitamin D. This observational study does not support an association between higher dietary vitamin D intake and type 2 diabetes incidence. This result has to be interpreted in light of the limited contribution of dietary vitamin D on the overall vitamin D status of a person.

Cumulus cell expansion and first polar body extrusion during in vitro oocyte maturation in relation to morphological and morphometric characteristics of the dromedary camel ovary.

PubMed

Mesbah, F; Kafi, M; Nili, H

2016-12-01

The morphological and morphometric characteristics of the ovary are fundamental properties for in vitro oocyte maturation. Nuclear maturation, including first polar body (1PB) extrusion, cytoplasmic maturation and cumulus cell (CC) expansion are the criteria for in vitro maturation (IVM) of oocyte. This study was designed to determine the effect of morphological and morphometric features of the ovary on CC expansion and 1PB extrusion during IVM of oocyte in the adult female dromedary camel. The weight, volume and three dimensions of ovaries from slaughtered dromedary camels and oocytes inside zona diameter and zona pellucida thickness were measured. The follicles were classified in regard to the size and oocytes according to their ooplasm appearance and CC compactness. Aspirated cumulus oocyte complexes (COCs) were incubated for 48 hr (with a 6-hr interval) in Hams-F10, and CC expansion and 1PB extrusion were assessed. Significant differences were seen in the shape, weight, volume and three dimensions of the ovaries between ≤4-year-old and >4-year-old dromedary camel (p < .5). Approximately, 95.82% of follicles were 2-4 mm in diameter. The mean (±SD) of inside zona diameter of the oocyte and zona pellucida thickness was 132.22 ± 13.8 and 14.64 ± 2.24 μm, respectively, in >4-year-old dromedary camel. The CC expansion and 1PB extrusion were seen in 86% and 21.88% of COCs, respectively. Age and sexual conditions of dromedary camel influence the morphological and morphometric characteristics of the ovary. Most COCs retrieved from 2-6 mm follicles are cultivable. The most slaughterhouse-derived COCs retrieved from 2-6 mm follicles of non-pregnant dromedary camels are excellent and good and yielding a most favourable diameter to achieve the developmental competence for IVM in an optimal time of 24-30 hr; the optimal time for CC expansion is 24-30 hr in this species. However, the CC expansion is a prerequisite process, but not sufficient for IVM. © 2016 Blackwell Verlag GmbH.

Negative transfer of heart rate control following biofeedback training: a partial replication.

PubMed

Steptoe, A; Macready, D

1985-09-01

Ability to raise and lower heart rate (HR) on instruction was tested before and after unidirectional biofeedback training in two groups of 10 male volunteers. Instructional control was assessed in 2-min trials before training, and after 5 and 10 biofeedback trials of increasing (Group I) and decreasing (Group D) HR. The magnitude of HR elevations produced by Group D diminished following training, while modifications in Group I were unchanged. This negative transfer effect is discussed in relation to whether voluntary speeding and slowing HR reflect distinct capacities.

Fiber Intake and Survival After Colorectal Cancer Diagnosis.

PubMed

Song, Mingyang; Wu, Kana; Meyerhardt, Jeffrey A; Ogino, Shuji; Wang, Molin; Fuchs, Charles S; Giovannucci, Edward L; Chan, Andrew T

2018-01-01

Although high dietary fiber intake has been associated with a lower risk of colorectal cancer (CRC), it remains unknown whether fiber benefits CRC survivors. To assess the association of postdiagnostic fiber intake with mortality. A total of 1575 health care professionals with stage I to III CRC were evaluated in 2 prospective cohorts, Nurses' Health Study and Health Professionals Follow-up Study. Colorectal cancer-specific and overall mortality were determined after adjusting for other potential predictors for cancer survival. The study was conducted from December 23, 2016, to August 23, 2017. Consumption of total fiber and different sources of fiber and whole grains assessed by a validated food frequency questionnaire between 6 months and 4 years after CRC diagnosis. Hazard ratios (HRs) and 95% CIs of CRC-specific and overall mortality after adjusting for other potential predictors for cancer survival. Of the 1575 participants, 963 (61.1%) were women; mean (SD) age was 68.6 (8.9) years. During a median of 8 years of follow-up, 773 deaths were documented, including 174 from CRC. High intake of total fiber after diagnosis was associated with lower mortality. The multivariable HR per each 5-g increment in intake per day was 0.78 (95% CI, 0.65-0.93; P = .006) for CRC-specific mortality and 0.86 (95% CI, 0.79-0.93; P < .001) for all-cause mortality. Patients who increased their fiber intake after diagnosis from levels before diagnosis had a lower mortality, and each 5-g/d increase in intake was associated with 18% lower CRC-specific mortality (95% CI, 7%-28%; P = .002) and 14% lower all-cause mortality (95% CI, 8%-19%; P < .001). According to the source of fiber, cereal fiber was associated with lower CRC-specific mortality (HR per 5-g/d increment, 0.67; 95% CI, 0.50-0.90; P = .007) and all-cause mortality (HR, 0.78; 95% CI, 0.68-0.90; P < .001); vegetable fiber was associated with lower all-cause mortality (HR, 0.83; 95% CI, 0.72-0.96; P = .009) but not CRC-specific mortality (HR, 0.82; 95% CI, 0.60-1.13; P = .22); no association was found for fruit fiber. Whole grain intake was associated with lower CRC-specific mortality (HR per 20-g/d increment, 0.72; 95% CI, 0.59-0.88; P = .002), and this beneficial association was attenuated after adjusting for fiber intake (HR, 0.77; 95% CI, 0.62-0.96; P = .02). Higher fiber intake after the diagnosis of nonmetastatic CRC is associated with lower CRC-specific and overall mortality. Increasing fiber consumption after diagnosis may confer additional benefits to patients with CRC.

Proposed formation mechanism and active species of hydrogen molecules generated from a novel magnesium-citric acid-hydroxypropyl cellulose coating (MgCC) material

NASA Astrophysics Data System (ADS)

Kobayashi, Shigeki; Chikuma, Toshiyuki; Chiba, Kazuyoshi; Tsuchiya, Daisuke; Hirai, Tomomitsu

2016-02-01

The presence of acids is known to accelerate the reaction (Mg + 2H2O = Mg(OH)2 + H2). We developed a novel Mg-citric acid coating (MgCC) material produced by milling Mg powder coated with hydroxypropyl cellulose (HPC); because of its H2 generation, this material could be used in antioxidant therapy and antiaging applications. After milling in the presence of citric acid, this material produced H2-rich water upon addition to cooled water. Although the reaction was considered to involve a two-electron transfer from Mg to 2H2O, the role of the acid in H2 generation remains incompletely understood. To clarify the reaction mechanism, we performed studies on the deuterium kinetic isotope effects (KIE) and electron spin resonance (ESR). We observed differences in the concentration ratios, such as H2/D2 > 1 and H2/(H2 + D2 + HD) > 1, involved in H2, D2, and (H2 + D2 + HD) production, and found that adducts with hydrogen atoms (Hrad) were not obtained from the spin-trapping reaction between 5-(2, 2-Dimethyl-1,3-propoxy cyclophosphoryl)-5-methyl-1-pyrroline N-oxide (CYPMPO) and the MgCC material. The H2, D2, and HD produced from MgCC were identified by using a gas chromatograph connected to a mass spectrometer. The spin-trapping techniques showed that the Hrad adducts formed by the reaction of NaBH4 with CYPMPO could not be observed from reaction of MGCC with CYPMPO in H2O. The data suggest that the rate-controlling step and proposed transition state (TS) exist in the reaction pathway of the O-H bond cleavage and H-H bond formation. A TS of a structure such as [Mg(OH2)2]∗ could be expected in the reaction pathway between Mg and 2H2O by density functional theory calculations. Also, these results show that H2 generation is accelerated in the presence of acids because the activation energy of the TS is significantly smaller than that of H2O.

Neutron scattering studies of K3H(SO4)2 and K3D(SO4)2: the particle-in-a-box model for the quantum phase transition.

PubMed

Fillaux, François; Cousson, Alain

2012-08-21

In the crystal of K(3)H(SO(4))(2) or K(3)D(SO(4))(2), dimers SO(4)···H···SO(4) or SO(4)···D···SO(4) are linked by strong centrosymmetric hydrogen or deuterium bonds whose O···O length is ≈2.50 Å. We address two open questions. (i) Are H or D sites split or not? (ii) Is there any structural counterpart to the phase transition observed for K(3)D(SO(4))(2) at T(c) ≈ 85.5 K, which does not exist for K(3)H(SO(4))(2)? Neutron diffraction by single-crystals at cryogenic or room temperature reveals no structural transition and no resolvable splitting of H or D sites. However, the width of the probability densities suggest unresolved splitting of the wavefunctions suggesting rigid entities H(L1/2)-H(R1/2) or D(L1/2)-D(R1/2) whose separation lengths are l(H) ≈ 0.16 Å or l(D) ≈ 0.25 Å. The vibrational eigenstates for the center of mass of H(L1/2)-H(R1/2) revealed by inelastic neutron scattering are amenable to a square-well and we suppose the same potential holds for D(L1/2)-D(R1/2). In order to explain dielectric and calorimetric measurements of mixed crystals K(3)D((1-ρ))H(ρ)(SO(4))(2) (0 ≤ ρ ≤ 1), we replace the classical notion of order-disorder by the quantum notion of discernible (e.g., D(L1/2)-D(R1/2)) or indiscernible (e.g., H(L1/2)-H(R1/2)) components depending on the separation length of the split wavefunction. The discernible-indiscernible isostructural transition at finite temperatures is induced by a thermal pure quantum state or at 0 K by ρ.

Chronic Consumption of Artificial Sweetener in Packets or Tablets and Type 2 Diabetes Risk: Evidence from the E3N-European Prospective Investigation into Cancer and Nutrition Study.

PubMed

Fagherazzi, Guy; Gusto, Gaëlle; Affret, Aurélie; Mancini, Francesca Romana; Dow, Courtney; Balkau, Beverley; Clavel-Chapelon, Françoise; Bonnet, Fabrice; Boutron-Ruault, Marie-Christine

2017-01-01

The influence of artificial sweeteners on metabolic diseases is controversial. Artificially sweetened beverages have been associated with an increased risk of type 2 diabetes (T2D) but biases and reverse causation have been suspected to have influenced the observed association. In addition, it has been suggested that investigation into the relationship between the frequency and duration of the consumption of packet or tablet artificial sweeteners and T2D risk is necessary. We used data from 61,440 women in the prospective E3N-European Prospective Investigation into Cancer and Nutrition study, conducted between 1993 and 2011. We estimated hazards ratios (HRs) and 95% CIs of T2D risk associated with both the frequency and the duration of use of artificial sweeteners consumed in packets or tablets. Compared to "never or rare" consumers of artificial sweeteners, those using them "always or almost always" had an increased risk of T2D (HR = 1.83 [95% CI 1.66-2.02] in the multivariate model [MM], HR = 1.33 [95% CI 1.20-1.47] when further adjusted for body mass index, BMI). Women consuming artificial sweeteners in packets or tablets for more than 10 years also had an increased risk of T2D compared to never or rare users (HR = 2.10 [95% CI 1.83-2.40] in the MM and HR = 1.15 [95% CI 1.00-1.33] when adjusted for BMI, respectively). Our data suggest that both a higher frequency and a longer consumption of artificial sweeteners in packets or tablets was associated with T2D risk, independently of major T2D risk factors, but partially mediated by adiposity. A precautionary principle should be applied to the promotion of these products that are still largely recommended as healthy sugar substitutes. © 2017 S. Karger AG, Basel.

Implementation of image-guided brachytherapy (IGBT) for patients with uterine cervix cancer: a tumor volume kinetics approach.

PubMed

Carvalho, Heloisa de Andrade; Mendez, Lucas Castro; Stuart, Silvia Radwanski; Guimarães, Roger Guilherme Rodrigues; Ramos, Clarissa Cerchi Angotti; de Paula, Lucas Assad; de Sales, Camila Pessoa; Chen, André Tsin Chih; Blasbalg, Roberto; Baroni, Ronaldo Hueb

2016-08-01

To evaluate tumor shrinking kinetics in order to implement image-guided brachytherapy (IGBT) for the treatment of patients with cervix cancer. This study has prospectively evaluated tumor shrinking kinetics of thirteen patients with uterine cervix cancer treated with combined chemoradiation. Four high dose rate brachytherapy fractions were delivered during the course of pelvic external beam radiation therapy (EBRT). Magnetic resonance imaging (MRI) exams were acquired at diagnosis (D), first (B1), and third (B3) brachytherapy fractions. Target volumes (GTV and HR-CTV) were calculated by both the ellipsoid formula (VE) and MRI contouring (VC), which were defined by a consensus between at least two radiation oncologists and a pelvic expert radiologist. Most enrolled patients had squamous cell carcinoma and FIGO stage IIB disease, and initiated brachytherapy after the third week of pelvic external beam radiation. Gross tumor volume volume reduction from diagnostic MRI to B1 represented 61.9% and 75.2% of the initial volume, when measured by VE and VC, respectively. Only a modest volume reduction (15-20%) was observed from B1 to B3. The most expressive tumor shrinking occurred in the first three weeks of oncological treatment and was in accordance with gynecological examination. These findings may help in IGBT implementation.

Extent of lymph node dissection for adenocarcinoma of the stomach.

PubMed

Mocellin, Simone; McCulloch, Peter; Kazi, Hussain; Gama-Rodrigues, Joaquin J; Yuan, Yuhong; Nitti, Donato

2015-08-12

The impact of lymphadenectomy extent on the survival of patients with primary resectable gastric carcinoma is debated. We aimed to systematically review and meta-analyze the evidence on the impact of the three main types of progressively more extended lymph node dissection (that is, D1, D2 and D3 lymphadenectomy) on the clinical outcome of patients with primary resectable carcinoma of the stomach. The primary objective was to assess the impact of lymphadenectomy extent on survival (overall survival [OS], disease specific survival [DSS] and disease free survival [DFS]). The secondary aim was to assess the impact of lymphadenectomy on post-operative mortality. We searched CENTRAL, MEDLINE and EMBASE until 2001, including references from relevant articles and conference proceedings. We also contacted known researchers in the field. For the updated review, CENTRAL, MEDLINE and EMBASE were searched from 2001 to February 2015. We considered randomized controlled trials (RCTs) comparing the three main types of lymph node dissection (i.e., D1, D2 and D3 lymphadenectomy) in patients with primary non-metastatic resectable carcinoma of the stomach. Two authors independently extracted data from the included studies. Hazard ratios (HR) and relative risks (RR) along with their 95% confidence intervals (CI) were used to measure differences in survival and mortality rates between trial arms, respectively. Potential sources of between-study heterogeneity were investigated by means of subgroup and sensitivity analyses. The same two authors independently assessed the risk of bias of eligible studies according to the standards of the Cochrane Collaboration and the quality of the overall evidence based on the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) criteria. Eight RCTs (enrolling 2515 patients) met the inclusion criteria. Three RCTs (all performed in Asian countries) compared D3 with D2 lymphadenectomy: data suggested no significant difference in OS between these two types of lymph node dissection (HR 0.99, 95% CI 0.81 to 1.21), with no significant difference in postoperative mortality (RR 1.67, 95% CI 0.41 to 6.73). Data for DFS were available only from one trial and for no trial were DSS data available. Five RCTs (n = 3 European; n = 2 Asian) compared D2 to D1 lymphadenectomy: OS (n = 5; HR 0.91, 95% CI 0.71 to 1.17) and DFS (n=3; HR 0.95, 95% CI 0.84 to 1.07) findings suggested no significant difference between these two types of lymph node dissection. In contrast, D2 lymphadenectomy was associated with a significantly better DSS compared to D1 lymphadenectomy (HR 0.81, 95% CI 0.71 to 0.92), the quality of the body of evidence being moderate; however, D2 lymphadenectomy was also associated with a higher postoperative mortality rate (RR 2.02, 95% CI 1.34 to 3.04). D2 lymphadenectomy can improve DSS in patients with resectable carcinoma of the stomach, although the increased incidence of postoperative mortality reduces its therapeutic benefit.

WE-EF-210-06: Ultrasound 2D Strain Measurement of Radiation-Induced Toxicity: Phantom and Ex Vivo Experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, T; Torres, M; Rossi, P

Purpose: Radiation-induced fibrosis is a common long-term complication affecting many patients following cancer radiotherapy. Standard clinical assessment of subcutaneous fibrosis is subjective and often limited to visual inspection and palpation. Ultrasound strain imaging describes the compressibility (elasticity) of biological tissues. This study’s purpose is to develop a quantitative ultrasound strain imaging that can consistently and accurately characterize radiation-induce fibrosis. Methods: In this study, we propose a 2D strain imaging method based on deformable image registration. A combined affine and B-spline transformation model is used to calculate the displacement of tissue between pre-stress and post-stress B-mode image sequences. The 2D displacementmore » is estimated through a hybrid image similarity measure metric, which is a combination of the normalized mutual information (NMI) and normalized sum-of-squared-differences (NSSD). And 2D strain is obtained from the gradient of the local displacement. We conducted phantom experiments under various compressions and compared the performance of our proposed method with the standard cross-correlation (CC)- based method using the signal-to-noise (SNR) and contrast-to-noise (CNS) ratios. In addition, we conducted ex-vivo beef muscle experiment to further validate the proposed method. Results: For phantom study, the SNR and CNS values of the proposed method were significantly higher than those calculated from the CC-based method under different strains. The SNR and CNR increased by a factor of 1.9 and 2.7 comparing to the CC-based method. For the ex-vivo experiment, the CC-based method failed to work due to large deformation (6.7%), while our proposed method could accurately detect the stiffness change. Conclusion: We have developed a 2D strain imaging technique based on the deformable image registration, validated its accuracy and feasibility with phantom and ex-vivo data. This 2D ultrasound strain imaging technology may be valuable as physicians try to eliminate radiation-induce fibrosis and improve the therapeutic ratio of cancer radiotherapy. This research is supported in part by DOD PCRP Award W81XWH-13-1-0269, and National Cancer Institute (NCI) Grant CA114313.« less

Blood Lead Levels and Delayed Onset of Puberty in a Longitudinal Study of Russian Boys

PubMed Central

Williams, Paige L.; Sergeyev, Oleg; Lee, Mary M.; Korrick, Susan A.; Burns, Jane S.; Humblet, Olivier; DelPrato, Julie; Revich, Boris; Hauser, Russ

2011-01-01

Background World-wide trends towards earlier pubertal onset have raised concerns regarding the potential role of environmental exposures, including lead. Previous animal studies and studies in girls have revealed associations of lead with perturbations in pubertal onset. We evaluated the association of blood lead levels (BLLs) with pubertal onset in a longitudinal cohort of Russian boys. Methods 489 Russian boys were enrolled in 2003–2005 at ages 8–9 years and followed annually through May 2008. Cox proportional hazards models were used to evaluate the association of BLLs at enrollment with time to pubertal onset during follow-up based on testicular volume (TV) and pubertal staging, adjusting for birth characteristics, nutritional status, maternal exposures during pregnancy, height and BMI, and socioeconomic status. Results 481 boys had BLLs, with median=3 µg/dL and 28% ≥ 5 µg/dL. The percentage of pubertal boys increased with age, from 12% at age 8 to 83% at age 12 as defined by TV>3ml, from 22% to 90% as defined by genitalia stage 2 or higher, and from 4% to 40% as defined by pubic hair stage 2 or higher. After adjustment for potential confounders including BMI and height, boys with high BLLs (≥ 5 µg/dL) had a 24%–31% reduced risk of pubertal onset based on TV>3ml (Hazard Ratio (HR)= 0.73; 95% CI: 0.55, 0.97, p=0.03), genital staging (HR=0.76, 95% CI: 0.59, 0.98, p=0.04), and pubic hair staging (HR=0.69, 95% CI: 0.44, 1.07, p=0.10) as compared to those with lower lead levels. Pubertal onset occurred 6–8 months later on average for boys with high BLLs compared to those with BLLs < 5 µg/dL. Conclusions Higher blood lead was associated with later pubertal onset in this prospective study of peri-pubertal Russian boys. Given the large numbers of children with BLLs≥5 µg/dL worldwide, this shift has important public health implications and supports review of current lead policies. PMID:20368318

Strategic Aircraft Maintenance Career Ladder AFSC 452X4 (Formerly AFSC 431X1)

DTIC Science & Technology

1989-02-01

career field). While they perform many of the same basic maintenance and administrative tasks, these incumbents are differentiated from the TACTICAL...00L of A~ D.yf I I.. cc cc 1 I do c- 0.aA C . .9 ~ 0 v ’cc 115 -C GD q Z U. . 4 D 44 O U -1. 10. ING.. aL. 0 -0 6 2’ we fA VI0U G.4 A GD..IGD-A - I U. C...00 a 00o cloca-40 o m r-4raCO0O.4ONNO4 -40N0 N1E -: 004040 o4 *-4 * * n N0 t0- W r-1 1 P 4 .140 d 0 omQ na, F-mQ % I M~ 4r .40 ~~~~~~~~ W -4 ’,Q 4 4Oi

Large Eddy Simulations of Surface Winds Above Water Waves: Effects of Wind-Wave Alignment and Wave Age

DTIC Science & Technology

2008-06-30

LLJ Cz tD LL LO Lij LO CO ur LL S, -1 LLA U) LIJ LIJ > CC < \\1 Ln LIJ o4 LL LLJ I 1q LO cr- Lj 0 ca C) w Li U)>) w...0 LL >Cc CCo0g o l Aoebez I- C,0) o 1,1u AplliqeqoJ d A!ilnwno (1)cq P C\\!-0 0 0 0 0 >WIN NUNN Z ,, ....... ,,0 U)) i tD z C) II iii. .i i i...t ~ ~ IL ,u UJ 4- •3:: 0 bb -0 𔃾o 4-4 0 t0 0 CL 4vJ .C E C L ’ 2t 0u bO~I uj U , b. U DO LU > LL 𔄁 0 LLJ w t 1*0 CC -~4-J Iuo a- E "

Decreasing Temporal Lobe Dose With Five-Field Intensity-Modulated Radiotherapy for Treatment of Pituitary Macroadenomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parhar, Preeti K.; Duckworth, Tamara; Shah, Parinda

2010-10-01

Purpose: To compare temporal lobe dose delivered by three pituitary macroadenoma irradiation techniques: three-field three-dimensional conformal radiotherapy (3D-CRT), three-field intensity-modulated radiotherapy (3F IMRT), and a proposed novel alternative of five-field IMRT (5F IMRT). Methods and Materials: Computed tomography-based external beam radiotherapy planning was performed for 15 pituitary macroadenoma patients treated at New York University between 2002 and 2007 using: 3D-CRT (two lateral, one midline superior anterior oblique [SAO] beams), 3F IMRT (same beam angles), and 5F IMRT (same beam angles with additional right SAO and left SAO beams). Prescription dose was 45 Gy. Target volumes were: gross tumor volume (GTV)more » = macroadenoma, clinical target volume (CTV) = GTV, and planning target volume = CTV + 0.5 cm. Structure contouring was performed by two radiation oncologists guided by an expert neuroradiologist. Results: Five-field IMRT yielded significantly decreased temporal lobe dose delivery compared with 3D-CRT and 3F IMRT. Temporal lobe sparing with 5F IMRT was most pronounced at intermediate doses: mean V25Gy (% of total temporal lobe volume receiving {>=}25 Gy) of 13% vs. 28% vs. 29% for right temporal lobe and 14% vs. 29% vs. 30% for left temporal lobe for 5F IMRT, 3D-CRT, and 3F IMRT, respectively (p < 10{sup -7} for 5F IMRT vs. 3D-CRT and 5F IMRT vs. 3F IMRT). Five-field IMRT plans did not compromise target coverage, exceed normal tissue dose constraints, or increase estimated brain integral dose. Conclusions: Five-field IMRT irradiation technique results in a statistically significant decrease in the dose to the temporal lobes and may thus help prevent neurocognitive sequelae in irradiated pituitary macroadenoma patients.« less

Understanding and Modeling Vortical Flows to Improve the Technology Readiness Level for Military Aircraft (Comprehension et Modelisation des Flux de Vortex Pour Ameliorer le Niveau de Maturite Technologique au Profit des Avions Militaires)

DTIC Science & Technology

2009-10-01

636.7 115,418 0 2500 5000 7500 10000 12500 iterations -5 -4 -3 -2 -1 0 lo g( dρ /d t) SA EARSM EARSM + CC Hellsten EARSM Hellsten EARSM + CC DRSM...VORTEX BREAKDOWN RTO-TR-AVT-113 29 - 13 θU URo axial= (1) As a vortex passes through a normal shock, the tangential velocity is

David Miller | NREL

Science.gov Websites

Publications D.C. Miller, E. Annigoni, A. Ballion, J.G. Bokria, L.S. Bruckman, D.M. Burns, X. Chen, L. Elliott , J. Feng, R.H. French, S. Fowler, C.C. Honeker, M.D. Kempe, H. Khonkar, M. Köhl, L.-E. Perret-Aebi , L. Elliott, L. Feng, R.H. French, S. Fowler, X. Gu, P.L. Hacke, C.C. Honeker, M.D. Kempe, H. Khonkar

Intact cell MALDI-TOF mass spectrometry on single bovine oocyte and follicular cells combined with top-down proteomics: A novel approach to characterise markers of oocyte maturation.

PubMed

Labas, Valérie; Teixeira-Gomes, Ana-Paula; Bouguereau, Laura; Gargaros, Audrey; Spina, Lucie; Marestaing, Aurélie; Uzbekova, Svetlana

2018-03-20

Intact cell MALDI-TOF mass spectrometry (ICM-MS) was adapted to bovine follicular cells from individual ovarian follicles to obtain the protein/peptide signatures (<17kDa) of single oocytes, cumulus cells (CC) and granulosa cells (GC), which shared a total of 439 peaks. By comparing the ICM-MS profiles of single oocytes and CC before and after in vitro maturation (IVM), 71 different peaks were characterised, and their relative abundance was found to vary depending on the stage of oocyte meiotic maturation. To identify these endogenous biomolecules, top-down workflow using high resolution MS/MS (TD HR-MS) was performed on the protein extracts from oocytes, CC and GC. The TD HR-MS proteomic approach allowed for: (1) identification of 386 peptide/proteoforms encoded by 194 genes; and (2) characterisation of proteolysis products likely resulting from the action of kallikreins and caspases. In total, 136 peaks observed by ICM-MS were annotated by TD HR-MS (ProteomeXchange PXD004892). Among these, 16 markers of maturation were identified, including IGF2 binding protein 3 and hemoglobin B in the oocyte, thymosins beta-4 and beta-10, histone H2B and ubiquitin in CC. The combination of ICM-MS and TD HR-MS proved to be a suitable strategy to identify non-invasive markers of oocyte quality using limited biological samples. Intact cell MALDI-TOF mass spectrometry on single oocytes and their surrounding cumulus cells, coupled to an optimised top-down HR-MS proteomic approach on ovarian follicular cells, was used to identify specific markers of oocyte meiotic maturation represented by whole low molecular weight proteins or products of degradation by specific proteases. Copyright © 2017 Elsevier B.V. All rights reserved.

D-He-3 spherical torus fusion reactor system study

NASA Astrophysics Data System (ADS)

Macon, William A., Jr.

1992-04-01

This system study extrapolates present physics knowledge and technology to predict the anticipated characteristics of D-He3 spherical torus fusion reactors and their sensitivity to uncertainties in important parameters. Reference cases for steady-state 1000 MWe reactors operating in H-mode in both the 1st stability regime and the 2nd stability regime were developed and assessed quantitatively. These devices would a very small aspect ratio (A=1,2), a major radius of about 2.0 m, an on-axis magnetic field less than 2 T, a large plasma current (80-120 MA) dominated by the bootstrap effect, and high plasma beta (greater than O.6). The estimated cost of electricity is in the range of 60-90 mills/kW-hr, assuming the use of a direct energy conversion system. The inherent safety and environmental advantages of D-He3 fusion indicate that this reactor concept could be competitive with advanced fission breeder reactors and large-scale solar electric plants by the end of the 21st century if research and development can produce the anticipated physics and technology advances.

Genetic variants in fanconi anemia pathway genes BRCA2 and FANCA predict melanoma survival.

PubMed

Yin, Jieyun; Liu, Hongliang; Liu, Zhensheng; Wang, Li-E; Chen, Wei V; Zhu, Dakai; Amos, Christopher I; Fang, Shenying; Lee, Jeffrey E; Wei, Qingyi

2015-02-01

Cutaneous melanoma (CM) is the most lethal skin cancer. The Fanconi anemia (FA) pathway involved in DNA crosslink repair may affect CM susceptibility and prognosis. Using data derived from published genome-wide association study, we comprehensively analyzed the associations of 2,339 common single-nucleotide polymorphisms (SNPs) in 14 autosomal FA genes with overall survival (OS) in 858 CM patients. By performing false-positive report probability corrections and stepwise Cox proportional hazards regression analyses, we identified significant associations between CM OS and four putatively functional SNPs: BRCA2 rs10492396 (AG vs. GG: adjusted hazard ratio (adjHR)=1.85, 95% confidence interval (CI)=1.16-2.95, P=0.010), rs206118 (CC vs. TT+TC: adjHR=2.44, 95% CI=1.27-4.67, P=0.007), rs3752447 (CC vs. TT+TC: adjHR=2.10, 95% CI=1.38-3.18, P=0.0005), and FANCA rs62068372 (TT vs. CC+CT: adjHR=1.85, 95% CI=1.27-2.69, P=0.001). Moreover, patients with an increasing number of unfavorable genotypes (NUG) of these loci had markedly reduced OS and melanoma-specific survival (MSS). The final model incorporating with NUG, tumor stage, and Breslow thickness showed an improved discriminatory ability to classify both 5-year OS and 5-year MSS. Additional investigations, preferably prospective studies, are needed to validate our findings.

Cerebroside C Increases Tolerance to Chilling Injury and Alters Lipid Composition in Wheat Roots

PubMed Central

Li, Hong-Xia; Xiao, Yu; Cao, Ling-Ling; Yan, Xu; Li, Cong; Shi, Hai-Yan; Wang, Jian-Wen; Ye, Yong-Hao

2013-01-01

Chilling tolerance was increased in seed germination and root growth of wheat seedlings grown in media containing 20 µg/mL cerebroside C (CC), isolated from the endophytic Phyllosticta sp. TG78. Seeds treated with 20 µg/mL CC at 4°C expressed the higher germination rate (77.78%), potential (23.46%), index (3.44) and the shorter germination time (6.19 d); root growth was also significantly improved by 13.76% in length, 13.44% in fresh weight and 6.88% in dry mass compared to controls. During the cultivation process at 4°C for three days and the followed 24 h at 25°C, lipid peroxidation, expressed by malondialdehyde (MDA) content and relative membrane permeability (RMP) was significantly reduced in CC-treated roots; activities of lipoxygenase (LOX), phospholipid C (PLC) and phospholipid D (PLD) were inhibited by 13.62–62.26%, 13.54–63.93% and 13.90–61.17%, respectively; unsaturation degree of fatty acids was enhanced through detecting the contents of CC-induced linoleic acid, linolenic acid, palmitic acid and stearic acid using GC-MS; capacities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were individually increased by 7.69–46.06%, 3.37–37.96%, and −7.00–178.07%. These results suggest that increased chilling tolerance may be due, in part, to the reduction of lipid peroxidation and alternation of lipid composition of roots in the presence of CC. PMID:24058471

Interleukin-6 genotype is associated with high-density lipoprotein cholesterol responses to exercise training.

PubMed

Halverstadt, Amy; Phares, Dana A; Roth, Stephen; Ferrell, Robert E; Goldberg, Andrew P; Hagberg, James M

2005-05-15

High-density lipoprotein cholesterol (HDL-C) and its subfractions are modifiable with exercise training and these responses are heritable. The interleukin-6 (IL6)-174G/C polymorphism may be associated with HDL-C levels. We hypothesized that the IL6-174G/C polymorphism would be associated with plasma HDL-C response to exercise training. Sixty-five 50- to 75-year-olds on a standardized diet were studied before and after 24 weeks of aerobic exercise training. Significant differences existed among genotype groups for change with exercise training in HDL-C, HDL3-C, integrated HDL4,5NMR-C, and HDLsize. The CC genotype group increased HDL-C more than the GG (7.0 +/- 1.3 v. 1.0 +/- 1.1 mg/dL, p = 0.001) and GC groups (3.3 +/- 0.9 mg/dL, p = 0.02); for HDL3-C, the CC group increased more than the GG (6.1 +/- 1.0 v. 0.9 +/- 0.9, mg/dL p < 0.001) and GC groups (2.5 +/- 0.7 mg/dL, p = 0.006). Integrated HDL4,5NMR-C increased more in the CC than GG group (6.5 +/- 1.6 mg/dL v. 1.0 +/- 1.3 mg/dL, p = 0.01), as did HDLsize compared to the GG (CC: 0.3 +/- 0.1 v. GG: 0.1 +/- 0.1 nm, p = 0.02) and GC (0.0 +/- 0.0 nm, p = 0.007) groups. IL6 genotype is associated with HDL-C response to exercise training.

Sex differences in the association of social network satisfaction and the risk for type 2 diabetes.

PubMed

Lukaschek, K; Baumert, J; Kruse, J; Meisinger, C; Ladwig, K H

2017-05-02

The role of an individual's social network satisfaction (SNS) in the association of social isolation or living alone and incident type 2 diabetes (T2D) is unclear. We assessed the association of SNS with incident T2D and analysed potential modifications of the SNS-T2D association by social isolation or living alone. The study population (N = 6839 aged 25-74 years without diabetes at baseline) derived from the prospective population-based MONICA/KORA study (1989-2009). Social network satisfaction was assessed by a single item. Cox regression was used to estimate hazard ratios (HR) for SNS separately in men and women. In men with low SNS, risk for incident T2D increased significantly (HR: 2.15, 95% CI: 1.33-3.48, p value 0.002). After additional adjustments for social isolation or living alone, the risk for incident T2D was still significant, albeit less pronounced (HRs 1.85 or 2.05, p values 0.001 or 0.004). The interaction analysis showed an increased T2D risk effect for low SNS compared to high SNS in women living in a partnership (HR: 2.11, 95% CI: 1.00-4.44, p value for interaction: 0.047) and for moderate SNS compared to high SNS in socially connected women (1.56, 1.01-2.39, 0.010). Further research is needed to address the complexities of the perception of social relationships and social interactions, or interdependence, especially when another major public health issue such as T2D is concerned.

Porous NiCo2O4 nanoarray-integrated binder-free 3D open electrode offers a highly efficient sensing platform for enzyme-free glucose detection.

PubMed

Luo, X; Huang, M; He, D; Wang, M; Zhang, Y; Jiang, P

2018-05-29

High electrical conductivity and the exposure to more active sites are crucial to boost the performance of a glucose sensor. A porous binary metal oxide nanoarray integrated on a binder-free 3D electrode is expected to offer a highly sensitive sensing platform. As a model, porous NiCo2O4 nanowire arrays supported on carbon cloth (NiCo2O4 NWA/CC) have been prepared and used for enzyme-free glucose sensing. NiCo2O4 NWA/CC shows larger effective surface area, superior electronic conductivity, and higher catalytic activity towards enzyme-free glucose sensing, with a linear range from 1 μM to 0.63 mM, a sensitivity of 4.12 mA mM-1 cm-2, and low detection limit of 0.5 μM. Moreover, NiCo2O4 NWA/CC also displays good selectivity and stability and thus, it can be reliable for glucose detection in human serum samples. These findings inspire the fabrication of a high-performance electrochemical sensing platform by preparing porous binary metal oxide nanoarrays supported on a 3D conductive substrate.

Coupling Mo2C@C core-shell nanocrystals on 3D graphene hybrid aerogel for high-performance lithium ion battery

NASA Astrophysics Data System (ADS)

Xin, Hailin; Hai, Yang; Li, Dongzhi; Qiu, Zhaozheng; Lin, Yemao; Yang, Bo; Fan, Haosen; Zhu, Caizhen

2018-05-01

Hybrid aerogel by dispersing Mo2C@C core-shell nanocrystals into three-dimensional (3D) graphene (Mo2C@C-GA) has been successfully prepared through two-step methods. Firstly, carbon-coated MoO2 nanocrystals uniformly anchor on 3D graphene aerogel (MoO2@C-GA) via hydrothermal reaction. Then the MoO2@C-GA precursor is transformed into Mo2C@C-GA after the following carbonization process. Furthermore, the freeze-drying step plays an important role in the resulting pore size distribution of the porous networks. Moreover, graphene aerogels exhibit extremely low densities and superior electrical properties. When evaluated as anode material for lithium ion battery, Mo2C@C-GA delivers excellent rate capability and stable cycle performance when compared with C-GA and Mo2C nanoparticles. Mo2C@C-GA exhibits the initial discharge capacity of 1461.4 mA h g-1 at the current density of 0.1 A g-1, and retains a reversible capacity of 1089.8 mA h g-1 after 100 cycles at a current density of 0.1 A g-1. Even at high current density of 5 A g-1, a discharge capacity of 623.5 mA h g-1 can be still achieved. The excellent performance of Mo2C@C-GA could be attributed to the synergistic effect of Mo2C@C nanocrystals and the 3D graphene conductive network.

Chemical and biological characterization of pectin-like polysaccharides from the bark of the Malian medicinal tree Cola cordifolia.

PubMed

Austarheim, Ingvild; Christensen, Bjørn E; Hegna, Ida K; Petersen, Bent O; Duus, Jens O; Bye, Ragnar; Michaelsen, Terje E; Diallo, Drissa; Inngjerdingen, Marit; Paulsen, Berit S

2012-06-05

The bark of Cola cordifolia used in Malian traditional medicine contains unusual types of polysaccharides with immunomodulating activities. We report for the first time on the structure of a polymer designated CC1P1 having the repeating structure [2→)[α-D-Gal(1→3)]α-L-Rha(1→4)α-d-GalA(1→] as determined by NMR and GC/MS. α-Linked Gal is unusual in pectins. The Mw of 135 kDa was determined by SEC-MALLS. CC1P2 (1400 kDa), another polymer, having the same backbone, but this was substituted with α-4-OMe-GlcA, α-2-OMe-Gal and α-Gal as terminal units. CC1P1 shows a high complement-fixing activity, IC₅₀ being 2.2 times lower than the positive pectin control PMII (IC₅₀ appr. 71 μg/mL) while IC₅₀ of CC1P2 is 1.8 times lower. The simple structure of CC1P1 did not activate macrophages, while CC1P2 (100 μg/mL) showed the same potency as the positive controls PMII (100 μg/mL) and LPS (500 ng/mL). No cytotoxicity was detected. Copyright © 2012 Elsevier Ltd. All rights reserved.

A pilot study to assess residential noise exposure near natural gas compressor stations.

PubMed

Boyle, Meleah D; Soneja, Sutyajeet; Quirós-Alcalá, Lesliam; Dalemarre, Laura; Sapkota, Amy R; Sangaramoorthy, Thurka; Wilson, Sacoby; Milton, Donald; Sapkota, Amir

2017-01-01

U.S. natural gas production increased 40% from 2000 to 2015. This growth is largely related to technological advances in horizontal drilling and high-volume hydraulic fracturing. Environmental exposures upon impacted communities are a significant public health concern. Noise associated with natural gas compressor stations has been identified as a major concern for nearby residents, though limited studies exist. We conducted a pilot study to characterize noise levels in 11 homes located in Doddridge County, West Virginia, and determined whether these levels differed based on time of day, indoors vs. outdoors, and proximity of homes to natural gas compressor stations. We also compared noise levels at increasing distances from compressor stations to available noise guidelines, and evaluated low frequency noise presence. We collected indoor and outdoor 24-hour measurements (Leq, 24hr) in eight homes located within 750 meters (m) of the nearest compressor station and three control homes located >1000m. We then evaluated how A-weighted decibel (dBA) exposure levels differed based on factors outlined above. The geometric mean (GM) for 24-hour outdoor noise levels at homes located <300m (Leq,24hr: 60.3 dBA; geometric standard deviation (GSD): 1.0) from the nearest compressor station was nearly 9 dBA higher than control homes (Leq,24hr: 51.6 dBA; GSD: 1.1). GM for 24 hour indoor noise for homes <300m (Leq,24hr: 53.4 dBA; GSD: 1.2) from the nearest compressor station was 11.2 dBA higher than control homes (Leq,24hr: 42.2 dBA; GSD: 1.1). Indoor average daytime noise for homes <300m of the nearest compressor stations were 13.1 dBA higher than control homes, while indoor nighttime readings were 9.4 dBA higher. Findings indicate that living near a natural gas compressor station could potentially result in high environmental noise exposures. Larger studies are needed to confirm these findings and evaluate potential health impacts and protection measures.

A pilot study to assess residential noise exposure near natural gas compressor stations

PubMed Central

Boyle, Meleah D.; Quirós-Alcalá, Lesliam; Dalemarre, Laura; Sapkota, Amy R.; Sangaramoorthy, Thurka; Wilson, Sacoby; Milton, Donald; Sapkota, Amir

2017-01-01

Background U.S. natural gas production increased 40% from 2000 to 2015. This growth is largely related to technological advances in horizontal drilling and high-volume hydraulic fracturing. Environmental exposures upon impacted communities are a significant public health concern. Noise associated with natural gas compressor stations has been identified as a major concern for nearby residents, though limited studies exist. Objectives We conducted a pilot study to characterize noise levels in 11 homes located in Doddridge County, West Virginia, and determined whether these levels differed based on time of day, indoors vs. outdoors, and proximity of homes to natural gas compressor stations. We also compared noise levels at increasing distances from compressor stations to available noise guidelines, and evaluated low frequency noise presence. Methods We collected indoor and outdoor 24-hour measurements (Leq, 24hr) in eight homes located within 750 meters (m) of the nearest compressor station and three control homes located >1000m. We then evaluated how A-weighted decibel (dBA) exposure levels differed based on factors outlined above. Results The geometric mean (GM) for 24-hour outdoor noise levels at homes located <300m (Leq,24hr: 60.3 dBA; geometric standard deviation (GSD): 1.0) from the nearest compressor station was nearly 9 dBA higher than control homes (Leq,24hr: 51.6 dBA; GSD: 1.1). GM for 24 hour indoor noise for homes <300m (Leq,24hr: 53.4 dBA; GSD: 1.2) from the nearest compressor station was 11.2 dBA higher than control homes (Leq,24hr: 42.2 dBA; GSD: 1.1). Indoor average daytime noise for homes <300m of the nearest compressor stations were 13.1 dBA higher than control homes, while indoor nighttime readings were 9.4 dBA higher. Conclusions Findings indicate that living near a natural gas compressor station could potentially result in high environmental noise exposures. Larger studies are needed to confirm these findings and evaluate potential health impacts and protection measures. PMID:28369113

25(OH)D deficiency is associated with fatal stroke among whites but not blacks: The NHANES-III linked mortality files

PubMed Central

Michos, Erin D.; Reis, Jared P.; Post, Wendy S.; Lutsey, Pamela L.; Gottesman, Rebecca F.; Mosley, Thomas H.; Sharrett, A. Richey; Melamed, Michal L.

2011-01-01

Objective Deficient 25-hydroxyvitamin D [25(OH)D] levels are associated with cardiovascular disease (CVD) events and mortality. Both 25(OH)D deficiency and stroke are more prevalent among blacks. We examined whether low 25(OH)D contributes to the excess risk of fatal stroke in blacks compared to whites. Research Methods and Procedures The Third National Health and Nutrition Examination Survey, a probability sample of US civilians, measured 25(OH)D levels and CVD risk factors between 1988–1994. Vital status through December 2006 was obtained via linkage with the National Death Index. Among white and black adults without CVD reported at baseline (n=7981), Cox regression models were fit to estimate hazard ratios (HR) for fatal stroke by 25(OH)D status and race. Results During a median of 14.1 years, there were 116 and 60 fatal strokes among whites and blacks respectively. The risk of fatal stroke was greater in blacks compared to whites in models adjusted for socio-economic status and CVD risk factors, [HR 1.60 (95% CI 1.01–2.53)]. Mean baseline 25(OH)D levels were significantly lower in blacks compared to whites (19.4 vs 30.8 ng/mL, respectively). In multivariable-adjusted models, deficient 25(OH)D levels <15 ng/mL were associated with fatal stroke among whites [HR 2.13 (1.01–4.50)] but not blacks [HR 0.93 (0.49–1.80)]. Conclusions Vitamin D deficiency was associated with increased risk of stroke death in whites but not blacks. Although blacks had a higher rate of fatal stroke compared to whites, the low 25(OH)D levels in blacks were unrelated to stroke incidence and therefore 25(OH)D levels did not explain this excess risk. PMID:22261577

Target localization of 3D versus 4D cone beam computed tomography in lipiodol-guided stereotactic radiotherapy of hepatocellular carcinomas.

PubMed

Chan, Mark; Chiang, Chi Leung; Lee, Venus; Cheung, Steven; Leung, Ronnie; Wong, Matthew; Lee, Frankle; Blanck, Oliver

2017-01-01

Aim of this study was to comparatively evaluate the accuracy of respiration-correlated (4D) and uncorrelated (3D) cone beam computed tomography (CBCT) in localizing lipiodolized hepatocellular carcinomas during stereotactic body radiotherapy (SBRT). 4D-CBCT scans of eighteen HCCs were acquired during free-breathing SBRT following trans-arterial chemo-embolization (TACE) with lipiodol. Approximately 1320 x-ray projections per 4D-CBCT were collected and phase-sorted into ten bins. A 4D registration workflow was followed to register the reconstructed time-weighted average CBCT with the planning mid-ventilation (MidV) CT by an initial bone registration of the vertebrae and then tissue registration of the lipiodol. For comparison, projections of each 4D-CBCT were combined to synthesize 3D-CBCT without phase-sorting. Using the lipiodolized tumor, uncertainties of the treatment setup estimated from the absolute and relative lipiodol position to bone were analyzed separately for 4D- and 3D-CBCT. Qualitatively, 3D-CBCT showed better lipiodol contrast than 4D-CBCT primarily because of a tenfold increase of projections used for reconstruction. Motion artifact was observed to subside in 4D-CBCT compared to 3D-CBCT. Group mean, systematic and random errors estimated from 4D- and 3D-CBCT agreed to within 1 mm in the cranio-caudal (CC) and 0.5 mm in the anterior-posterior (AP) and left-right (LR) directions. Systematic and random errors are largest in the CC direction, amounting to 4.7 mm and 3.7 mm from 3D-CBCT and 5.6 mm and 3.8 mm from 4D-CBCT, respectively. Safety margin calculated from 3D-CBCT and 4D-CBCT differed by 2.1, 0.1 and 0.0 mm in the CC, AP, and LR directions. 3D-CBCT is an adequate alternative to 4D-CBCT when lipoid is used for localizing HCC during free-breathing SBRT. Similar margins are anticipated with 3D- and 4D-CBCT.

Theoretical study of the gas-phase reactions of iodine atoms ((2)P(3/2)) with H(2), H(2)O, HI, and OH.

PubMed

Canneaux, Sébastien; Xerri, Bertrand; Louis, Florent; Cantrel, Laurent

2010-09-02

The rate constants of the reactions of iodine atoms with H(2), H(2)O, HI, and OH have been estimated using 39, 21, 13, and 39 different levels of theory, respectively, and have been compared to the available literature values over the temperature range of 250-2500 K. The aim of this methodological work is to demonstrate that standard theoretical methods are adequate to obtain quantitative rate constants for the reactions involving iodine-containing species. Geometry optimizations and vibrational frequency calculations are performed using three methods (MP2, MPW1K, and BHandHLYP) combined with three basis sets (cc-pVTZ, cc-pVQZ, and 6-311G(d,p)). Single-point energy calculations are performed with the highly correlated ab initio coupled cluster method in the space of single, double, and triple (pertubatively) electron excitations CCSD(T) using the cc-pVnZ (n = T, Q, and 5), aug-cc-pVnZ (n = T, Q, and 5), 6-311G(d,p), 6-311+G(3df,2p), and 6-311++G(3df,3pd) basis sets. Canonical transition state theory with a simple Wigner tunneling correction is used to predict the rate constants as a function of temperature. CCSD(T)/cc-pVnZ//MP2/cc-pVTZ (n = T and Q), CCSD(T)/6-311+G(3df,2p)//MP2/6-311G(d,p), and CCSD(T)/6-311++G(3df,3pd)//MP2/6-311G(d,p) levels of theory provide accurate kinetic rate constants when compared to available literature data. The use of the CCSD(T)/cc-pVQZ//MP2/cc-pVTZ and CCSD(T)/6-311++G(3df,3pd) levels of theory allows one to obtain a better agreement with the literature data for all reactions with the exception of the I + H(2) reaction R(1) . This computational procedure has been also used to predict rate constants for some reactions where no available experimental data exist. The use of quantum chemistry tools could be therefore extended to other elements and next applied to develop kinetic networks involving various fission products, steam, and hydrogen in the absence of literature data. The final objective is to implement the kinetics of gaseous reactions in the ASTEC (Accident Source Term Evaluation Code) code to improve speciation of fission transport, which can be transported along the Reactor Coolant System (RCS) of a Pressurized Water Reactor (PWR) in case of a severe accident.

47 CFR 90.233 - Base/mobile non-voice operations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 5 2013-10-01 2013-10-01 false Base/mobile non-voice operations. 90.233... SERVICES PRIVATE LAND MOBILE RADIO SERVICES Non-Voice and Other Specialized Operations § 90.233 Base/mobile non-voice operations. The use of A1D, A2D, F1D, F2D, G1D, or G2D emission may be authorized to base...

47 CFR 90.233 - Base/mobile non-voice operations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false Base/mobile non-voice operations. 90.233... SERVICES PRIVATE LAND MOBILE RADIO SERVICES Non-Voice and Other Specialized Operations § 90.233 Base/mobile non-voice operations. The use of A1D, A2D, F1D, F2D, G1D, or G2D emission may be authorized to base...

47 CFR 90.233 - Base/mobile non-voice operations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 5 2011-10-01 2011-10-01 false Base/mobile non-voice operations. 90.233... SERVICES PRIVATE LAND MOBILE RADIO SERVICES Non-Voice and Other Specialized Operations § 90.233 Base/mobile non-voice operations. The use of A1D, A2D, F1D, F2D, G1D, or G2D emission may be authorized to base...

47 CFR 90.233 - Base/mobile non-voice operations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Base/mobile non-voice operations. 90.233... SERVICES PRIVATE LAND MOBILE RADIO SERVICES Non-Voice and Other Specialized Operations § 90.233 Base/mobile non-voice operations. The use of A1D, A2D, F1D, F2D, G1D, or G2D emission may be authorized to base...

[Association between variations in protocadherin 15 gene and occupational noise-induced hearing loss].

PubMed

Xu, X R; Yang, Q Y; Jiao, J; Zheng, Y X; He, L H; Yu, S F; Gu, G Z; Chen, G S; Zhou, W H; Wu, H; Li, Y H; Zhang, H L; Zhang, Z R

2017-01-06

Objective: The aim of this study was to investigate whether genetic variability in the protocadherin 15 (PCDH15) gene may correspond with increased susceptibility to noise-induced hearing loss (NIHL) in a Chinese population. Methods: A nested case-control study was performed that followed a cohort of 7 445 noise-exposed workers in a steel factory of Henan province in China from January 1, 2006 to December 31, 2015. In this study, 394 cases who had an average hearing threshold of more than 40 dB (A) in high frequency were defined as the case group, and 721 controls who had an average hearing threshold of less than 35 dB (A) in high frequency and less than 25 dB (A) in speech frequency were defined as the control group. A questionnaire was completed by participants and a physical test was also conducted. SNP genotyping was performed using the SNPscan TM Kit. Multivariate unconditional logistic regression additive models were used to analyze the genotypes in different groups, and the association with NIHL. Unconditional logistic regression models were used to assess the associations between the genotypes and NIHL. Results: The average age of study participants was (40.5±8.3) years and the median number of noise-exposed working years M ( P 25 , P 75 ) was 21.1 (9.1, 27.3). The range of noise exposed levels and the levels of cumulative noise exposure (CNE) were 80.1- 98.8 dB(A) and 86.6- 111.2 dB(A), respectively. Only the distribution of the genotypes (TT/CC/CT) of rs11004085 in the PCDH15 gene showed a significant difference between the case and control groups ( P= 0.049). In the case group, the distribution was 370 (93.9%), 24 (6.1%) and 0; in the control group, the distribution was 694 (96.3%), 23 (3.2%) and 1 (0.1% ). After smoking, drinking, hypertension, height and CNE adjustment, compared with the TT genotype individuals with the CC/CT genotype had a 1.90-fold increased risk of NIHL (95% CI: 1.06- 3.40). After stratified these data by the noise exposure level or CNE when the noise exposure level was>85 dB (A), compared with cases with the AA genotype of rs10825113, individuals with the GA/GG genotype had a 2.63-fold increased risk of NIHL (95% CI: 1.12- 6.14). When the CNE was ≤ 98 dB(A), compared with cases with the TT genotype of rs11004085, individuals with the CC/CT genotype had a 2.96-fold increased risk of NIHL (95% CI: 1.33- 6.56). However, these differences were not significant after Bonferroni correction had been applied. Conclusions: The results confirmed that genetic variation within the PCDH15 gene may affect the susceptibility to NIHL.

Genetic variants in Fanconi Anemia Pathway Genes BRCA2 and FANCA Predict Melanoma Survival

PubMed Central

Liu, Zhensheng; Wang, Li-E; Chen, Wei V.; Zhu, Dakai; Amos, Christopher I.; Fang, Shenying; Lee, Jeffrey E.; Wei, Qingyi

2014-01-01

Cutaneous melanoma (CM) is the most lethal skin cancer. The Fanconi Anemia (FA) pathway involved in DNA crosslinks repair may affect CM susceptibility and prognosis. Using data derived from published genome-wide association study, we comprehensively analyzed the associations of 2339 common single nucleotide polymorphisms (SNPs) in 14 autosomal FA genes with overall survival (OS) in 858 CM patients. By performing false-positive report probability corrections and stepwise Cox proportional hazards regression analyses, we identified significant associations between CM OS and four putatively functional SNPs: BRCA2 rs10492396 [AG vs. GG: adjusted hazard ratio (adjHR)=1.85, 95% confident interval (CI)=1.16-2.95, P=0.010], rs206118 (CC vs. TT+TC: adjHR=2.44, 95% CI=1.27-4.67, P=0.007), rs3752447 (CC vs. TT+TC: adjHR=2.10, 95% CI=1.38-3.18, P=0.0005), and FANCA rs62068372 (TT vs. CC+CT: adjHR=1.85, 95% CI=1.27-2.69, P=0.001). Moreover, patients with an increasing number of unfavorable genotypes (NUG) of these loci had markedly reduced OS and melanoma-specific survival (MSS). The final model incorporating with NUG, tumor stage and Breslow thickness showed an improved discriminatory ability to classify both 5-year OS and 5-year MSS. Additional investigations, preferably prospective studies, are needed to validate our findings. PMID:25243787

A Prototype Regional GSI-based EnKF-Variational Hybrid Data Assimilation System for the Rapid Refresh Forecasting System: Dual-Resolution Implementation and Testing Results

NASA Astrophysics Data System (ADS)

Pan, Yujie; Xue, Ming; Zhu, Kefeng; Wang, Mingjun

2018-05-01

A dual-resolution (DR) version of a regional ensemble Kalman filter (EnKF)-3D ensemble variational (3DEnVar) coupled hybrid data assimilation system is implemented as a prototype for the operational Rapid Refresh forecasting system. The DR 3DEnVar system combines a high-resolution (HR) deterministic background forecast with lower-resolution (LR) EnKF ensemble perturbations used for flow-dependent background error covariance to produce a HR analysis. The computational cost is substantially reduced by running the ensemble forecasts and EnKF analyses at LR. The DR 3DEnVar system is tested with 3-h cycles over a 9-day period using a 40/˜13-km grid spacing combination. The HR forecasts from the DR hybrid analyses are compared with forecasts launched from HR Gridpoint Statistical Interpolation (GSI) 3D variational (3DVar) analyses, and single LR hybrid analyses interpolated to the HR grid. With the DR 3DEnVar system, a 90% weight for the ensemble covariance yields the lowest forecast errors and the DR hybrid system clearly outperforms the HR GSI 3DVar. Humidity and wind forecasts are also better than those launched from interpolated LR hybrid analyses, but the temperature forecasts are slightly worse. The humidity forecasts are improved most. For precipitation forecasts, the DR 3DEnVar always outperforms HR GSI 3DVar. It also outperforms the LR 3DEnVar, except for the initial forecast period and lower thresholds.

Sensitive Determination of Onco-metabolites of D- and L-2-hydroxyglutarate Enantiomers by Chiral Derivatization Combined with Liquid Chromatography/Mass Spectrometry Analysis

PubMed Central

Cheng, Qing-Yun; Xiong, Jun; Huang, Wei; Ma, Qin; Ci, Weimin; Feng, Yu-Qi; Yuan, Bi-Feng

2015-01-01

2-hydroxyglutarate (2HG) is a potent competitor of α-ketoglutarate (α-KG) and can inhibit multiple α-KG dependent dioxygenases that function on the epigenetic modifications. The accumulation of 2HG contributes to elevated risk of malignant tumors. 2HG carries an asymmetric carbon atom in its carbon backbone and differentiation between D-2-hydroxyglutarate (D-2HG) and L-2-hydroxyglutarate (L-2HG) is crucially important for accurate diagnosis of 2HG related diseases. Here we developed a strategy by chiral derivatization combined with liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis for highly sensitive determination of D-2HG and L-2HG enantiomers. N-(p-toluenesulfonyl)-L-phenylalanyl chloride (TSPC) was used to derivatize 2HG. The formed diastereomers by TSPC labeling can efficiently improve the chromatographic separation of D-2HG and L-2HG. And derivatization by TSPC could also markedly increase the detection sensitivities by 291 and 346 folds for D-2HG and L-2HG, respectively. Using the developed method, we measured the contents of D-2HG and L-2HG in clear cell renal cell carcinoma (ccRCC) tissues. We observed 12.9 and 29.8 folds increase of D-2HG and L-2HG, respectively, in human ccRCC tissues compared to adjacent normal tissues. The developed chiral derivatization combined with LC-ESI-MS/MS analysis offers sensitive determination of D-2HG and L-2HG enantiomers, which benefits the precise diagnosis of 2HG related metabolic diseases. PMID:26458332

Effect of vitamin D on all-cause mortality in heart failure (EVITA): a 3-year randomized clinical trial with 4000 IU vitamin D daily.

PubMed

Zittermann, Armin; Ernst, Jana B; Prokop, Sylvana; Fuchs, Uwe; Dreier, Jens; Kuhn, Joachim; Knabbe, Cornelius; Birschmann, Ingvild; Schulz, Uwe; Berthold, Heiner K; Pilz, Stefan; Gouni-Berthold, Ioanna; Gummert, Jan F; Dittrich, Marcus; Börgermann, Jochen

2017-08-01

Circulating 25-hydroxyvitamin D (25OHD) levels <75 nmol/L are associated with a nonlinear increase in mortality risk. Such 25OHD levels are common in heart failure (HF). We therefore examined whether oral vitamin D supplementation reduces mortality in patients with advanced HF. Four hundred HF patients with 25OHD levels <75 nmol/L were randomized to receive 4000 IU vitamin D daily or matching placebo for 3 years. Primary endpoint was all-cause mortality. Key secondary outcome measures included hospitalization, resuscitation, mechanical circulatory support (MCS) implant, high urgent listing for heart transplantation, heart transplantation, and hypercalcaemia. Initial 25OHD levels were on average <40 nmol/L, remained around 40 nmol/L in patients assigned to placebo and plateaued around 100 nmol/L in patients assigned to vitamin D. Mortality was not different in patients receiving vitamin D (19.6%; n = 39) or placebo (17.9%; n = 36) with a hazard ratio (HR) of 1.09 [95% confidence interval (CI): 0.69-1.71; P = 0.726]. The need for MCS implant was however greater in patients assigned to vitamin D (15.4%, n = 28) vs. placebo [9.0%, n = 15; HR: 1.96 (95% CI: 1.04-3.66); P = 0.031]. Other secondary clinical endpoints were similar between groups. The incidence of hypercalcaemia was 6.2% (n = 10) and 3.1% (n = 5) in patients receiving vitamin D or placebo (P = 0.192). A daily vitamin D dose of 4000 IU did not reduce mortality in patients with advanced HF but was associated with a greater need for MCS implants. Data indicate caution regarding long-term supplementation with moderately high vitamin D doses. clinicaltrials.gov Idenitfier: NCT01326650. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Cancer linked to Alzheimer disease but not vascular dementia

PubMed Central

Roe, C M.; Fitzpatrick, A L.; Xiong, C; Sieh, W; Kuller, L; Miller, J P.; Williams, M M.; Kopan, R; Behrens, M I.; Morris, J C.

2010-01-01

Objective: To investigate whether cancer is associated with Alzheimer disease (AD) and vascular dementia (VaD). Methods: Cox proportional hazards models were used to test associations between prevalent dementia and risk of future cancer hospitalization, and associations between prevalent cancer and risk of subsequent dementia. Participants in the Cardiovascular Health Study–Cognition Substudy, a prospective cohort study, aged 65 years or older (n = 3,020) were followed a mean of 5.4 years for dementia and 8.3 years for cancer. Results: The presence of any AD (pure AD + mixed AD/VaD; hazard ratio [HR] = 0.41, 95% confidence interval [CI] = 0.20–0.84) and pure AD (HR = 0.31, 95% CI = 0.12–0.86) was associated with a reduced risk of future cancer hospitalization, adjusted for demographic factors, smoking, obesity, and physical activity. No significant associations were found between dementia at baseline and rate of cancer hospitalizations for participants with diagnoses of VaD. Prevalent cancer was associated with reduced risk of any AD (HR = 0.72; 95% CI = 0.52–0.997) and pure AD (HR = 0.57; 95% CI = 0.36–0.90) among white subjects after adjustment for demographics, number of APOE ε4 alleles, hypertension, diabetes, and coronary heart disease; the opposite association was found among minorities, but the sample size was too small to provide stable estimates. No significant association was found between cancer and subsequent development of VaD. Conclusions: In white older adults, prevalent Alzheimer disease (AD) was longitudinally associated with a reduced risk of cancer, and a history of cancer was associated with a reduced risk of AD. Together with other work showing associations between cancer and Parkinson disease, these findings suggest the possibility that cancer is linked to neurodegeneration. GLOSSARY 3MSE = modified Mini-Mental State Examination; AD = Alzheimer disease; ADDTC = Alzheimer Disease Diagnostic and Treatment Centers; CHD = coronary heart disease; CHS = Cardiovascular Health Study; CI = confidence interval; HR = hazard ratio; ICD-9 = International Classification of Diseases–Ninth Revision; MCI = mild cognitive impairment; NINCDS-ADRDA = National Institute of Neurological and Communicative Diseases and Stroke–Alzheimer's Disease and Related Disorders Association; PD = Parkinson disease; VaD = vascular dementia. PMID:20032288

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uchida, Y; Tachibana, H

Purpose: For head and neck VMAT (HN-VMAT), variations of position and deformation of patient’s shoulders is a concern to affect inaccuracy of dose distribution. It has been reported that the setup error of the shoulders was variable from 5 mm – 1 cm. The beams of the HN-VMAT pass through the shoulders. We assessed the impact of shoulder deformation to dose distribution for HN-VMAT. Methods: One HN-VMAT plan was generated using a patient’s CT. The patient’s CT was deformed using ImSimQA (Oncology Systems Limited, Shrewsbury, Shropshire, UK) to generate several patterns of the shoulders’ deformations when the right and leftmore » humeral heads were shifted with 3, 6, and 15 mm in the superior and inferior directions (SI), 3, 5, and 15 mm in the anterior and posterior directions (AP), and 5 and 15 mm in the right or left direction (LR). DVH comparison was performed in the different deformation patterns. The dosimetric parameters of D95% for CTV70Gy, CTV60Gy and CTV54Gy and dmax for Spinal cord were also measured. Gamma index evaluation (Criteria: 3%/2mm) was performed to exhibit clinically tolerable area in the comparison. Results: DVH comparison shows similar for all structures. As the comparison for the dosimetric parameters, the variations of D95% in the LR and AP were within 1%. There were larger variations in the SI than those in the other directions, however were within 1.5%. In gamma index evaluation, the small spots with higher gamma index values were appeared when the shift was 6 mm, however the pass ratio was 99.13%. Conclusion: HN-VMAT should be robust for shoulder deformation and geometric accuracy within 6 mm from patient’s setup and image-guided radiotherapy may be clinically acceptable for target dose coverage or normal tissue dose sparing.« less

In vivo verification of particle therapy: how Compton camera configurations affect 3D image quality

NASA Astrophysics Data System (ADS)

Mackin, D.; Draeger, E.; Peterson, S.; Polf, J.; Beddar, S.

2017-05-01

The steep dose gradients enabled by the Bragg peaks of particle therapy beams are a double edged sword. They enable highly conformal dose distributions, but even small deviations from the planned beam range can cause overdosing of healthy tissue or under-dosing of the tumour. To reduce this risk, particle therapy treatment plans include margins large enough to account for all the sources of range uncertainty, which include patient setup errors, patient anatomy changes, and CT number to stopping power ratios. Any system that could verify the beam range in vivo, would allow reduced margins and more conformal dose distributions. Toward our goal developing such a system based on Compton camera (CC) imaging, we studied how three configurations (single camera, parallel opposed, and orthogonal) affect the quality of the 3D images. We found that single CC and parallel opposed configurations produced superior images in 2D. The increase in parallax produced by an orthogonal CC configuration was shown to be beneficial in producing artefact free 3D images.

Adherence to recommendations of the German food pyramid and risk of chronic diseases: results from the EPIC-Potsdam study.

PubMed

von Ruesten, A; Illner, A-K; Buijsse, B; Heidemann, C; Boeing, H

2010-11-01

The German food pyramid was set up to foster and communicate healthy food choices. The adherence to recommendations of the food pyramid was translated into an index (German Food Pyramid Index (GFPI)) by scoring the ratio of consumed and recommended daily servings of eight food groups, wherein higher scores indicated greater adherence. The GFPI was calculated for 23 531 subjects who participated in the European Prospective Investigation into Cancer and Nutrition-Potsdam study and were recruited between 1994 and 1998. Associations between quintiles of GFPI scores and risk of incident cardiovascular diseases (CVD), type-2 diabetes (T2D) and cancer were evaluated using Cox proportional hazard regression models. During 183 740 person-years of follow-up, 363 incident cases of CVD (myocardial infarction or stroke), 837 incident cases of T2D and 844 incident cases of cancer occurred. The GFPI was inversely related to CVD risk in men (multivariable-adjusted hazard ratio (HR) for highest versus lowest quintiles=0.56; 95% confidence interval (CI): 0.34-0.94) but not in women (HR=1.39; 95% CI: 0.76-2.55). No association between GFPI and cancer was observed. An inverse relation between GFPI and T2D (men: HR= 0.71 (0.52-0.97); women: HR= 0.69 (0.50-0.96)) in age-adjusted models was substantially attenuated after multivariable adjustments, particularly by body mass index (BMI) (men: HR=0.94 (0.69-1.30); women: HR=1.09 (0.77-1.54)). The same was observed for overall major chronic disease risk (CVD, T2D and total cancer). Adherence to the German food pyramid recommendations is not associated with a decreased risk of chronic diseases when considering BMI as confounder, except of CVD in men.

Systematically convergent basis sets for transition metals. I. All-electron correlation consistent basis sets for the 3d elements Sc-Zn

NASA Astrophysics Data System (ADS)

Balabanov, Nikolai B.; Peterson, Kirk A.

2005-08-01

Sequences of basis sets that systematically converge towards the complete basis set (CBS) limit have been developed for the first-row transition metal elements Sc-Zn. Two families of basis sets, nonrelativistic and Douglas-Kroll-Hess (-DK) relativistic, are presented that range in quality from triple-ζ to quintuple-ζ. Separate sets are developed for the description of valence (3d4s) electron correlation (cc-pVnZ and cc-pVnZ-DK; n =T,Q, 5) and valence plus outer-core (3s3p3d4s) correlation (cc-pwCVnZ and cc-pwCVnZ-DK; n =T,Q, 5), as well as these sets augmented by additional diffuse functions for the description of negative ions and weak interactions (aug-cc-pVnZ and aug-cc-pVnZ-DK). Extensive benchmark calculations at the coupled cluster level of theory are presented for atomic excitation energies, ionization potentials, and electron affinities, as well as molecular calculations on selected hydrides (TiH, MnH, CuH) and other diatomics (TiF, Cu2). In addition to observing systematic convergence towards the CBS limits, both 3s3p electron correlation and scalar relativity are calculated to strongly impact many of the atomic and molecular properties investigated for these first-row transition metal species.

Cancer Risk in Women Treated with Fertility Drugs According to Parity status - A Registry-based Cohort Study

PubMed Central

Reigstad, Marte Myhre; Storeng, Ritsa; Myklebust, Tor Åge; Oldereid, Nan Birgitte; Omland, Anne Katerine; Robsahm, Trude Eid; Brinton, Louise Anette; Vangen, Siri; Furu, Kari; Larsen, Inger Kristin

2017-01-01

Background Long-term safety of assisted reproductive techniques (ART) is of interest as use is increasing. Cancer risk is known to be affected by parity. This study examined risk of cancer after fertility treatment, stratified by women’s parity. Methods Data was obtained on all women (n=1 353 724) born in Norway between 1960–1996. Drug exposure data (2004–2014) was obtained from the Norwegian Prescription Database [drugs used in ART and clomiphene citrate (CC)]. The Medical Birth Registry of Norway provided parity status. Hazard ratios were calculated for all site cancer, breast, cervical, endometrial, ovarian, colorectal, central nervous system, thyroid cancer and malignant melanoma. Results In 12 354 392 person-years of follow-up, 20 128 women were diagnosed with cancer. All-site cancer risk was (1.14, 1.03–1.26) and (1.10, 0.98–1.23) following CC and ART exposure respectively. For ovarian cancer, a stronger association was observed for both exposures in nulliparous (HR 2.49, 1.30–4.78, and HR 1.62, 0.78–3.35) versus parous women (HR 1.37, 0.64–2.96, and HR 0.87, 0.33–2.27). Elevated risk of endometrial cancers was observed for CC exposure in nulliparous women (4.59, 2.68–7.84 vs. 1.44, 0.63–3.31). Risk was elevated for breast cancer in parous women exposed to CC (1.26, 1.03–1.54) and among nulliparous women after ART treatment (2.19, 1.08–4.44). Conclusion CC appears associated with increased risk of ovarian and endometrial cancer. Elevations in risks of breast and thyroid cancer were less consistent across type of drug exposure and parity. Impact Continued monitoring of fertility treatments is warranted. PMID:28108444

REFORMATION OF NUCLEOLI AFTER ETHIONE-INDUCED FRAGMENTATION IN THE ABSENCE OF SIGNIFICANT PROTEIN SYNTHESIS

PubMed Central

Shinozuka, Hisashi; Farber, Emmanuel

1969-01-01

The rat liver nucleolus, after fragmentation induced by ethionine treatment, has been found to undergo complete reformation by adenine in the presence of a dose of cycloheximide sufficient to cause inhibition of protein synthesis by 90–95%. In contrast, actinomycin D given along with adenine was followed by the appearance of a small compact mass containing only the fibrillar component with no evident granules. This structure resembled pseudonucleoli seen in the anucleolate mutant of Xenopus laevis or in certain early stages of amphibian oocytes. Actinomycin D administered 2 hr after adenine induced a segregation of the fibrillar and granular components of nucleoli similar to that induced in the normal nucleolus. The implications of these findings in relation to nucleolar organization are briefly discussed. PMID:5775789

Maize Homologs of Hydroxycinnamoyltransferase, a Key Enzyme in Lignin Biosynthesis, Bind the Nucleotide Binding Leucine-Rich Repeat Rp1 Proteins to Modulate the Defense Response.

PubMed

Wang, Guan-Feng; He, Yijian; Strauch, Renee; Olukolu, Bode A; Nielsen, Dahlia; Li, Xu; Balint-Kurti, Peter J

2015-11-01

In plants, most disease resistance genes encode nucleotide binding Leu-rich repeat (NLR) proteins that trigger a rapid localized cell death called a hypersensitive response (HR) upon pathogen recognition. The maize (Zea mays) NLR protein Rp1-D21 derives from an intragenic recombination between two NLRs, Rp1-D and Rp1-dp2, and confers an autoactive HR in the absence of pathogen infection. From a previous quantitative trait loci and genome-wide association study, we identified a single-nucleotide polymorphism locus highly associated with variation in the severity of Rp1-D21-induced HR. Two maize genes encoding hydroxycinnamoyltransferase (HCT; a key enzyme involved in lignin biosynthesis) homologs, termed HCT1806 and HCT4918, were adjacent to this single-nucleotide polymorphism. Here, we show that both HCT1806 and HCT4918 physically interact with and suppress the HR conferred by Rp1-D21 but not other autoactive NLRs when transiently coexpressed in Nicotiana benthamiana. Other maize HCT homologs are unable to confer the same level of suppression on Rp1-D21-induced HR. The metabolic activity of HCT1806 and HCT4918 is unlikely to be necessary for their role in suppressing HR. We show that the lignin pathway is activated by Rp1-D21 at both the transcriptional and metabolic levels. We derive a model to explain the roles of HCT1806 and HCT4918 in Rp1-mediated disease resistance. © 2015 American Society of Plant Biologists. All Rights Reserved.

Maize Homologs of Hydroxycinnamoyltransferase, a Key Enzyme in Lignin Biosynthesis, Bind the Nucleotide Binding Leucine-Rich Repeat Rp1 Proteins to Modulate the Defense Response1

PubMed Central

Wang, Guan-Feng; He, Yijian; Strauch, Renee; Olukolu, Bode A.; Nielsen, Dahlia; Li, Xu; Balint-Kurti, Peter J.

2015-01-01

In plants, most disease resistance genes encode nucleotide binding Leu-rich repeat (NLR) proteins that trigger a rapid localized cell death called a hypersensitive response (HR) upon pathogen recognition. The maize (Zea mays) NLR protein Rp1-D21 derives from an intragenic recombination between two NLRs, Rp1-D and Rp1-dp2, and confers an autoactive HR in the absence of pathogen infection. From a previous quantitative trait loci and genome-wide association study, we identified a single-nucleotide polymorphism locus highly associated with variation in the severity of Rp1-D21-induced HR. Two maize genes encoding hydroxycinnamoyltransferase (HCT; a key enzyme involved in lignin biosynthesis) homologs, termed HCT1806 and HCT4918, were adjacent to this single-nucleotide polymorphism. Here, we show that both HCT1806 and HCT4918 physically interact with and suppress the HR conferred by Rp1-D21 but not other autoactive NLRs when transiently coexpressed in Nicotiana benthamiana. Other maize HCT homologs are unable to confer the same level of suppression on Rp1-D21-induced HR. The metabolic activity of HCT1806 and HCT4918 is unlikely to be necessary for their role in suppressing HR. We show that the lignin pathway is activated by Rp1-D21 at both the transcriptional and metabolic levels. We derive a model to explain the roles of HCT1806 and HCT4918 in Rp1-mediated disease resistance. PMID:26373661

Green leafy and cruciferous vegetable consumption and risk of type 2 diabetes: results from the Singapore Chinese Health Study and meta-analysis.

PubMed

Chen, Guo-Chong; Koh, Woon-Puay; Yuan, Jian-Min; Qin, Li-Qiang; van Dam, Rob M

2018-05-01

Several previous prospective studies suggest that consumption of green leafy and cruciferous vegetables may lower the risk of type 2 diabetes (T2D). We investigated the association between consumption of different types of vegetables in relation to T2D risk in an Asian Population. We included 45 411 participants (age range: 45-74 years) of the Singapore Chinese Health Study (SCHS) free of diabetes, cancer or CVD at baseline (1993-1998). Dietary information was collected using a validated FFQ. Physician-diagnosed incident diabetes was reported at follow-up I (1999-2004) and II (2006-2010) interviews. Cox proportional hazards regression was used to estimate hazard ratio (HR) and 95 % CI of T2D risk. An updated meta-analysis was also conducted to summarise results for green leafy and cruciferous vegetables. During 494 741 person-years of follow-up, 5207 incident T2D occurred. After adjustment for potential confounders, neither total vegetables (top v. bottom quintile HR=1·08; 95 % CI 0·98, 1·18, P trend=0·66) nor specific vegetables including dark green leafy vegetables (HR=1·05; 95 % CI 0·96, 1·15, P trend=0·21) and cruciferous vegetables (HR=0·97; 95 % CI 0·88, 1·06, P trend=0·29) were substantially associated with risk of T2D. A meta-analysis (eleven studies with 754 729 participants and 58 297 cases) including the SCHS and all previous prospective studies suggested borderline significant inverse associations between green leafy (summary relative risk (RR)=0·91; 95 % CI 0·84, 1·00) and cruciferous vegetable consumption (RR=0·87; 95 % CI 0·76, 1·00) and T2D risk, with moderate-to-high heterogeneity. In conclusion, green leafy or cruciferous vegetable consumption was not substantially associated with risk of T2D in an Asian population. Meta-analysis of available cohort data indicated that evidence for a beneficial effect of green leafy or cruciferous vegetable consumption on T2D risk is not convincing.

The regulation of delta-opiate receptor density on 108CC15 neuroblastoma X glioma hybrid cells.

PubMed Central

Moses, M. A.; Snell, C. R.

1984-01-01

The effect of exogenous substances on the expression of opiate receptors on 108CC15 neuroblastoma X glioma hybrid cells has been studied. Cell differentiation by culture in the presence of N6-O2-dibutyryl adenosine 3',5'-cyclic monophosphate induced a three fold increase in opiate receptor density. When the cells were grown in the presence of 10(-5) M morphine hydrochloride for up to 23 days, opiate receptor densities were reduced by only 30% when compared with matched controls. Culture in the presence of 10(-7) M D-Ala2-D-Leu5-enkephalin produced opiate receptor down regulation of 73% compared to controls after only 4 h of treatment. The down regulation process could be inhibited by continued exposure to D-Ala2 D-Leu5-enkephalin at concentrations greater than 4 nM; below this concentration down regulation was rapid and irreversible. A model to explain these observations is described. PMID:6322893

Four-Dimensional Dose Reconstruction for Scanned Proton Therapy Using Liver 4DCT-MRI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bernatowicz, Kinga, E-mail: kinga.bernatowicz@psi.ch; Proton Therapy Center, Paul Scherrer Institute, PSI Villigen; Peroni, Marta

Purpose: Four-dimensional computed tomography-magnetic resonance imaging (4DCT-MRI) is an image-processing technique for simulating many 4DCT data sets from a static reference CT and motions extracted from 4DMRI studies performed using either volunteers or patients. In this work, different motion extraction approaches were tested using 6 liver cases, and a detailed comparison between 4DCT-MRI and 4DCT was performed. Methods and Materials: 4DCT-MRI has been generated using 2 approaches. The first approach used motion extracted from 4DMRI as being “most similar” to that of 4DCT from the same patient (subject-specific), and the second approach used the most similar motion obtained from amore » motion library derived from 4DMRI liver studies of 13 healthy volunteers (population-based). The resulting 4DCT-MRI and 4DCTs were compared using scanned proton 4D dose calculations (4DDC). Results: Dosimetric analysis showed that 93% ± 8% of points inside the clinical target volume (CTV) agreed between 4DCT and subject-specific 4DCT-MRI (gamma analysis: 3%/3 mm). The population-based approach however showed lower dosimetric agreement with only 79% ± 14% points in the CTV reaching the 3%/3 mm criteria. Conclusions: 4D CT-MRI extends the capabilities of motion modeling for dose calculations by accounting for realistic and variable motion patterns, which can be directly employed in clinical research studies. We have found that the subject-specific liver modeling appears more accurate than the population-based approach. The former is particularly interesting for clinical applications, such as improved target delineation and 4D dose reconstruction for patient-specific QA to allow for inter- and/or intra-fractional plan corrections.« less

Dietary Diversity, Diet Cost, and Incidence of Type 2 Diabetes in the United Kingdom: A Prospective Cohort Study

PubMed Central

Conklin, Annalijn I.; Monsivais, Pablo; Khaw, Kay-Tee; Forouhi, Nita G.

2016-01-01

Background Diet is a key modifiable risk factor for multiple chronic conditions, including type 2 diabetes (T2D). Consuming a range of foods from the five major food groups is advocated as critical to healthy eating, but the association of diversity across major food groups with T2D is not clear and the relationship of within-food-group diversity is unknown. In addition, there is a growing price gap between more and less healthy foods, which may limit the uptake of varied diets. The current study had two aims: first, to examine the association of reported diversity of intake of food groups as well as their subtypes with risk of developing T2D, and second, to estimate the monetary cost associated with dietary diversity. Methods and Findings A prospective study of 23,238 participants in the population-based EPIC-Norfolk cohort completed a baseline Food Frequency Questionnaire in 1993–1997 and were followed up for a median of 10 y. We derived a total diet diversity score and additional scores for diversity within each food group (dairy products, fruits, vegetables, meat and alternatives, and grains). We used multivariable Cox regression analyses for incident diabetes (892 new cases), and multivariable linear regression for diet cost. Greater total diet diversity was associated with 30% lower risk of developing T2D (Hazard ratio [HR] 0.70 [95% CI 0.51 to 0.95]) comparing diets comprising all five food groups to those with three or fewer, adjusting for confounders including obesity and socioeconomic status. In analyses of diversity within each food group, greater diversity in dairy products (HR 0.61 [0.45 to 0.81]), fruits (HR 0.69 [0.52 to 0.90]), and vegetables (HR 0.67 [0.52 to 0.87]) were each associated with lower incident diabetes. The cost of consuming a diet covering all 5 food groups was 18% higher (£4.15/day [4.14 to 4.16]) than one comprising three or fewer groups. Key limitations are the self-reported dietary data and the binary scoring approach whereby some food groups contained both healthy and less healthy food items. Conclusions A diet characterized by regular consumption of all five food groups and by greater variety of dairy, fruit, and vegetable subtypes, appears important for a reduced risk of diabetes. However, such a diet is more expensive. Public health efforts to prevent diabetes should include food price policies to promote healthier, more varied diets. PMID:27433799

Dietary Diversity, Diet Cost, and Incidence of Type 2 Diabetes in the United Kingdom: A Prospective Cohort Study.

PubMed

Conklin, Annalijn I; Monsivais, Pablo; Khaw, Kay-Tee; Wareham, Nicholas J; Forouhi, Nita G

2016-07-01

Diet is a key modifiable risk factor for multiple chronic conditions, including type 2 diabetes (T2D). Consuming a range of foods from the five major food groups is advocated as critical to healthy eating, but the association of diversity across major food groups with T2D is not clear and the relationship of within-food-group diversity is unknown. In addition, there is a growing price gap between more and less healthy foods, which may limit the uptake of varied diets. The current study had two aims: first, to examine the association of reported diversity of intake of food groups as well as their subtypes with risk of developing T2D, and second, to estimate the monetary cost associated with dietary diversity. A prospective study of 23,238 participants in the population-based EPIC-Norfolk cohort completed a baseline Food Frequency Questionnaire in 1993-1997 and were followed up for a median of 10 y. We derived a total diet diversity score and additional scores for diversity within each food group (dairy products, fruits, vegetables, meat and alternatives, and grains). We used multivariable Cox regression analyses for incident diabetes (892 new cases), and multivariable linear regression for diet cost. Greater total diet diversity was associated with 30% lower risk of developing T2D (Hazard ratio [HR] 0.70 [95% CI 0.51 to 0.95]) comparing diets comprising all five food groups to those with three or fewer, adjusting for confounders including obesity and socioeconomic status. In analyses of diversity within each food group, greater diversity in dairy products (HR 0.61 [0.45 to 0.81]), fruits (HR 0.69 [0.52 to 0.90]), and vegetables (HR 0.67 [0.52 to 0.87]) were each associated with lower incident diabetes. The cost of consuming a diet covering all 5 food groups was 18% higher (£4.15/day [4.14 to 4.16]) than one comprising three or fewer groups. Key limitations are the self-reported dietary data and the binary scoring approach whereby some food groups contained both healthy and less healthy food items. A diet characterized by regular consumption of all five food groups and by greater variety of dairy, fruit, and vegetable subtypes, appears important for a reduced risk of diabetes. However, such a diet is more expensive. Public health efforts to prevent diabetes should include food price policies to promote healthier, more varied diets.

Medicare D Subsidies and Racial Disparities in Persistence and Adherence With Hormonal Therapy

PubMed Central

Shi, Yushu; Charlson, John; Smith, Elizabeth C.; Smallwood, Alicia J.; Nattinger, Ann B.; Laud, Purushottam W.; Neuner, Joan M.

2016-01-01

Purpose To investigate the role of out-of-pocket cost supports through the Medicare Part D Low-Income Subsidy on disparities in breast cancer hormonal therapy persistence and adherence by race or ethnicity. Methods A nationwide cohort of women age ≥ 65 years with a breast cancer operation between 2006 and 2007 and at least one prescription filled for oral breast cancer hormonal therapy was identified from all Medicare D enrollees. The association of race or ethnicity with nonpersistence (90 consecutive days with no claims for a hormonal therapy prescription) and nonadherence (medication possession rate < 80%) was examined. Survival analyses were used to account for potential differences in age, comorbidity, or intensity of other treatments. Results Among the 25,111 women in the study sample, 77% of the Hispanic and 70% of the black women received a subsidy compared with 21% of the white women. By 2 years, 69% of black and 70% of Hispanic patients were persistent compared with 61% of white patients. In adjusted analyses, patients in all three unsubsidized race or ethnicity groups had greater discontinuation than subsidized groups (white patients: hazard ratio [HR], 1.83; 95% CI, 1.70 to 1.95; black patients: HR, 2.09; 95% CI, 1.73 to 2.51; Hispanic patients: HR, 3.00; 95% CI, 2.37 to 3.89). Racial or ethnic persistence disparities that were present for unsubsidized patients were not present or reversed among subsidized patients. All three subsidized race or ethnicity groups also had higher adherence than all three unsubsidized groups, although with the smallest difference occurring in black women. Conclusion Receipt of a prescription subsidy was associated with substantially improved persistence to breast cancer hormonal therapy among white, black, and Hispanic women and lack of racial or ethnic disparities in persistence. Given high subsidy enrollment among black and Hispanic women, policies targeted at low-income patients have the potential to also substantially reduce racial and ethnic disparities. PMID:27998232

Medicare D Subsidies and Racial Disparities in Persistence and Adherence With Hormonal Therapy.

PubMed

Biggers, Alana; Shi, Yushu; Charlson, John; Smith, Elizabeth C; Smallwood, Alicia J; Nattinger, Ann B; Laud, Purushottam W; Neuner, Joan M

2016-12-20

Purpose To investigate the role of out-of-pocket cost supports through the Medicare Part D Low-Income Subsidy on disparities in breast cancer hormonal therapy persistence and adherence by race or ethnicity. Methods A nationwide cohort of women age ≥ 65 years with a breast cancer operation between 2006 and 2007 and at least one prescription filled for oral breast cancer hormonal therapy was identified from all Medicare D enrollees. The association of race or ethnicity with nonpersistence (90 consecutive days with no claims for a hormonal therapy prescription) and nonadherence (medication possession rate < 80%) was examined. Survival analyses were used to account for potential differences in age, comorbidity, or intensity of other treatments. Results Among the 25,111 women in the study sample, 77% of the Hispanic and 70% of the black women received a subsidy compared with 21% of the white women. By 2 years, 69% of black and 70% of Hispanic patients were persistent compared with 61% of white patients. In adjusted analyses, patients in all three unsubsidized race or ethnicity groups had greater discontinuation than subsidized groups (white patients: hazard ratio [HR], 1.83; 95% CI, 1.70 to 1.95; black patients: HR, 2.09; 95% CI, 1.73 to 2.51; Hispanic patients: HR, 3.00; 95% CI, 2.37 to 3.89). Racial or ethnic persistence disparities that were present for unsubsidized patients were not present or reversed among subsidized patients. All three subsidized race or ethnicity groups also had higher adherence than all three unsubsidized groups, although with the smallest difference occurring in black women. Conclusion Receipt of a prescription subsidy was associated with substantially improved persistence to breast cancer hormonal therapy among white, black, and Hispanic women and lack of racial or ethnic disparities in persistence. Given high subsidy enrollment among black and Hispanic women, policies targeted at low-income patients have the potential to also substantially reduce racial and ethnic disparities.

Ghosts in the self-accelerating brane universe

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koyama, Kazuya; Institute of Cosmology and Gravitation, Portsmouth University, Portsmouth, PO1 2EG

2005-12-15

We study the spectrum of gravitational perturbations about a vacuum de Sitter brane with the induced 4D Einstein-Hilbert term, in a 5D Minkowski spacetime (DGP model). We consider solutions that include a self-accelerating universe, where the accelerating expansion of the universe is realized without introducing a cosmological constant on the brane. The mass of the discrete mode for the spin-2 graviton is calculated for various Hr{sub c}, where H is the Hubble parameter and r{sub c} is the crossover scale determined by the ratio between the 5D Newton constant and the 4D Newton constant. We show that, if we introducemore » a positive cosmological constant on the brane (Hr{sub c}>1), the spin-2 graviton has mass in the range 01/2. In a self-accelerating universe Hr{sub c}=1, the spin-2 graviton has mass m{sup 2}=2H{sup 2}, which coincides with the mass of the brane fluctuation mode. Then there arises a mixing between the brane fluctuation mode and the spin-2 graviton. We argue that this mixing presumably gives a ghost in the self-accelerating universe by continuity across Hr{sub c}=1, although a careful calculation of the effective action is required to verify this rigorously.« less

Postoperative Morbidity and Mortality of Perforated Peptic Ulcer: Retrospective Cohort Study of Risk Factors among Black Africans in Côte d'Ivoire.

PubMed

Gona, Soro Kountele; Alassan, Mahassadi Kouamé; Marcellin, Koffi Gnangoran; Henriette, Kissi Ya; Adama, Coulibaly; Toussaint, Assohoun; Manuela, Ehua Adjoba; Sylvain, Seu Gagon; Anthony, Afum-Adjei Awuah; Francis, Ehua Somian

2016-01-01

Introduction. Surgical treatment of perforated peptic ulcer (PPU) is a challenge for surgeons in Africa. Aim. To determine risk factors of postoperative complications or mortality among black Ivoirian patients with PPU. Methods. All 161 patients (median age = 34 years, 90.7 male) operated on for PPU in the visceral and general surgery unit were enrolled in a retrospective cohort study. Variables were studied with Kaplan Meier and Cox proportional hazard models. Results. Among 161 patients operated on for PPU, 36 (27.5%) experienced complications and 31 (19.3%) died. Follow-up results were the incidence of complications and mortality of 6.4 (95% CI: 4.9-8.0) per 100 person-days and 3.0 (95% CI: 1.9-4.0) per 100 person-days for incidence of mortality. In multivariate analysis, risk factors of postoperative complications or mortality were comorbidities (HR = 2.1, P = 0.03), tachycardia (pulse rate > 100/minutes) (HR = 2.4, P = 0.02), purulent intra-abdominal fluid collection (HR = 2.1, P = 0.04), hyponatremia (median value ≤ 134 mEq/L) (HR = 2.3, P = 0.01), delayed time of hospital admission > 72 hours (HR = 2.6, P < 0.0001), and delayed time of surgical intervention between 24 and 48 hours (HR = 3.8, P < 0.0001). Conclusion. The delayed hospital admission or surgical intervention and hyponatremia may be considered as additional risk of postoperative complications or mortality in Black African patients with PPU.

Automated circumferential construction of first-order aqueous humor outflow pathways using spectral-domain optical coherence tomography

NASA Astrophysics Data System (ADS)

Huang, Alex S.; Belghith, Akram; Dastiridou, Anna; Chopra, Vikas; Zangwill, Linda M.; Weinreb, Robert N.

2017-06-01

The purpose was to create a three-dimensional (3-D) model of circumferential aqueous humor outflow (AHO) in a living human eye with an automated detection algorithm for Schlemm's canal (SC) and first-order collector channels (CC) applied to spectral-domain optical coherence tomography (SD-OCT). Anterior segment SD-OCT scans from a subject were acquired circumferentially around the limbus. A Bayesian Ridge method was used to approximate the location of the SC on infrared confocal laser scanning ophthalmoscopic images with a cross multiplication tool developed to initiate SC/CC detection automated through a fuzzy hidden Markov Chain approach. Automatic segmentation of SC and initial CC's was manually confirmed by two masked graders. Outflow pathways detected by the segmentation algorithm were reconstructed into a 3-D representation of AHO. Overall, only <1% of images (5114 total B-scans) were ungradable. Automatic segmentation algorithm performed well with SC detection 98.3% of the time and <0.1% false positive detection compared to expert grader consensus. CC was detected 84.2% of the time with 1.4% false positive detection. 3-D representation of AHO pathways demonstrated variably thicker and thinner SC with some clear CC roots. Circumferential (360 deg), automated, and validated AHO detection of angle structures in the living human eye with reconstruction was possible.

Analysis of Hairless Corepressor Mutants to Characterize Molecular Cooperation with the Vitamin D Receptor in Promoting the Mammalian Hair Cycle

PubMed Central

Hsieh, Jui-Cheng; Slater, Stephanie A.; Whitfield, G. Kerr; Dawson, Jamie L.; Hsieh, Grace; Sheedy, Craig; Haussler, Carol A.; Haussler, Mark R.

2010-01-01

The mammalian hair cycle requires both the vitamin D receptor (VDR) and the hairless (Hr) corepressor, each of which is expressed in the hair follicle. Hr interacts directly with VDR to repress VDR-targeted transcription. Herein, we further map the VDR-interaction domain to regions in the C-terminal half of Hr that contain two LXXLL-like pairs of motifs known to mediate contact of Hr with the RAR-related orphan receptor alpha and with the thyroid hormone receptor, respectively. Site-directed mutagenesis indicates that all four hydrophobic motifs are required for VDR transrepression by Hr. Point mutation of rat Hr at conserved residues corresponding to natural mutants causing alopecia in mice (G985W and a C-terminal deletion ΔAK) and in humans (P95S, C422Y, E611G, R640Q, C642G, N988S, D1030N, A1040T, V1074M and V1154D), as well as alteration of residues in the C-terminal Jumonji C domain implicated in histone demethylation activity (C1025G/E1027G and H1143G) revealed that all Hr mutants retained VDR association, and that transrepressor activity was selectively abrogated in C642G, G985W, N988S, D1030N, V1074M, H1143G and V1154D. Four of these latter Hr mutants (C642G, N988S, D1030N and V1154D) were found to associate normally with histone deacetylase-3. Finally, we identified three regions of human VDR necessary for association with Hr, namely residues 109–111, 134–201, and 202–303. It is concluded that Hr and VDR interact via multiple protein-protein interfaces, with Hr recruiting histone deacetylases and possibly itself catalyzing histone demethylation to effect chromatin remodeling and repress the transcription of VDR target genes that control the hair cycle. PMID:20512927

Clinical applications of 3-dimensional printing in radiation therapy.

PubMed

Zhao, Yizhou; Moran, Kathryn; Yewondwossen, Mammo; Allan, James; Clarke, Scott; Rajaraman, Murali; Wilke, Derek; Joseph, Paul; Robar, James L

2017-01-01

Three-dimensional (3D) printing is suitable for the fabrication of complex radiotherapy bolus. Although investigated from dosimetric and feasibility standpoints, there are few reports to date of its use for actual patient treatment. This study illustrates the versatile applications of 3D printing in clinical radiation oncology through a selection of patient cases, namely, to create bolus for photon and modulated electron radiotherapy (MERT), as well as applicators for surface high-dose rate (HDR) brachytherapy. Photon boluses were 3D-printed to treat a recurrent squamous cell carcinoma (SCC) of the nasal septum and a basal cell carcinoma (BCC) of the posterior pinna. For a patient with a mycosis fungoides involving the upper face, a 3D-printed MERT bolus was used. To treat an SCC of the nose, a 3D-printed applicator for surface brachytherapy was made. The structures' fit to the anatomy and the radiotherapy treatment plans were assessed. Based on the treatment planning computed tomography (CT), the size of the largest air gap at the interface of the 3D-printed structure was 3 mm for the SCC of the nasal septum, 3 mm for the BCC of the pinna, 2 mm for the mycosis fungoides of the face, and 2 mm for the SCC of the nose. Acceptable treatment plans were obtained for the SCC of the nasal septum (95% isodose to 99.8% of planning target volume [PTV]), the BCC of the pinna (95% isodose to 97.7% of PTV), and the mycosis fungoides of the face (90% isodose to 92.5% of PTV). For the latter, compared with a plan with a uniform thickness bolus, the one featuring the MERT bolus achieved relative sparing of all the organs at risk (OARs) distal to the target volume, while maintaining similar target volume coverage. The surface brachytherapy plan for the SCC of the nose had adequate coverage (95% isodose to 95.6% of clinical target volume [CTV]), but a relatively high dose to the left eye, owing to its proximity to the tumor. 3D printing can be implemented effectively in the clinical setting to create highly conformal bolus for photon and MERT, as well as applicators for surface brachytherapy. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Antagonism of bromocriptine-induced cage climbing behaviour in mice by the selective D-2 dopamine receptor antagonists, metoclopramide and molindone.

PubMed

Balsara, J J; Nandal, N V; Gada, V P; Bapat, T R; Chandorkar, A G

1986-01-01

Bromocriptine (5-30 mg/kg, ip), 2 hr after administration, induced cage climbing behaviour in mice. Pretreatment with haloperidol, an antagonist of both D-1 and D-2 dopamine receptors, metoclopramide and molindone, the selective D-2 dopamine receptor antagonists, effectively antagonised bromocriptine-induced climbing behaviour. The results indicate that bromocriptine most probably induces climbing behaviour in mice by stimulating the postsynaptic striatal D-2 dopamine receptors.

No association between dietary sodium intake and the risk of multiple sclerosis.

PubMed

Cortese, Marianna; Yuan, Changzheng; Chitnis, Tanuja; Ascherio, Alberto; Munger, Kassandra L

2017-09-26

To prospectively investigate the association between dietary sodium intake and multiple sclerosis (MS) risk. In this cohort study, we assessed dietary sodium intake by a validated food frequency questionnaire administered every 4 years to 80,920 nurses in the Nurses' Health Study (NHS) (1984-2002) and to 94,511 in the Nurses' Health Study II (NHSII) (1991-2007), and calibrated it using data from a validation study. There were 479 new MS cases during follow-up. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the effect of energy-adjusted dietary sodium on MS risk, adjusting also for age, latitude of residence at age 15, ancestry, body mass index at age 18, supplemental vitamin D intake, cigarette smoking, and total energy intake in each cohort. The results in both cohorts were pooled using fixed effects models. Total dietary intake of sodium at baseline was not associated with MS risk (highest [medians: 3.2 g/d NHS; 3.5 g/d NHSII] vs lowest [medians: 2.5 g/d NHS; 2.8 g/d NHSII] quintile: HR pooled 0.98, 95% CI 0.74-1.30, p for trend = 0.75). Cumulative average sodium intake during follow-up was also not associated with MS risk (highest [medians: 3.3 g/d NHS; 3.4 g/d NHSII] vs lowest [medians: 2.7 g/d NHS; 2.8 g/d NHSII] quintile: HR pooled 1.02, 95% CI 0.76-1.37, p for trend = 0.76). Comparing more extreme sodium intake in deciles yielded similar results ( p for trend = 0.95). Our findings suggest that higher dietary sodium intake does not increase the risk of developing MS. © 2017 American Academy of Neurology.

Dietary sugarcane bagasse and coarse particle size of corn are beneficial to performance and gizzard development in broilers fed normal and high sodium diets.

PubMed

Kheravii, S K; Swick, R A; Choct, M; Wu, Shu-Biao

2017-09-01

An experiment was conducted to evaluate the effects of sugarcane bagasse (SB) and particle size on broiler performance, gizzard development, ileal microflora, litter quality, and bird welfare under a wet litter challenge model. A total of 672 one-day-old Ross 308 male broilers was allocated to 48 pens using a 2 × 2 × 2 factorial arrangement of treatments with corn particle size-coarse 3,576 μm (CC) or fine 1,113 μm (FC) geometric mean diameter, SB - 0 or 2% and sodium (Na) - 0.16 or 0.40% with increased Na level to induce wet litter. A 3-way particle size × Na × SB interaction (P < 0.05) was observed for weight gain at d 10. Birds fed FC showed a higher weight gain compared to birds fed CC when 0.40% Na without SB diet or 0.16% Na with 2% SB diet was offered. A significant particle size × SB interaction was observed at d 24 on feed conversion ratio (FCR; P < 0.001) and weight gain (P < 0.05). FCR was reduced by 2% SB supplementation in birds fed CC but increased in birds fed FC. Further, weight gain of birds fed 2% SB was higher in birds fed CC but not in those fed FC. On d 35, birds fed 2% SB had a higher weight gain (P < 0.001) compared to those without SB, and a SB × particle size interaction on relative gizzard weight (P < 0.05) and pH (P < 0.05) was present. SB reduced gizzard pH and increased the relative gizzard weight in birds fed the FC diet but not the CC diet (P < 0.05). Counts of ileal Bacillus spp. were increased in birds fed SB (P < 0.05) on d 24. No effects of SB and particle size on litter quality and bird welfare were observed, but higher Na increased litter moisture and footpad dermatitis (FPD) scores (P < 0.001). These findings suggest that SB independently or in combination with CC improves performance in older birds regardless of Na level in diets, possibly through improved gizzard development and gut microflora of birds. © 2017 Poultry Science Association Inc.

Transcriptome analysis of sweet orange trees infected with 'Candidatus Liberibacter asiaticus' and two strains of Citrus Tristeza Virus.

PubMed

Fu, Shimin; Shao, Jonathan; Zhou, Changyong; Hartung, John S

2016-05-11

Huanglongbing (HLB) and tristeza, are diseases of citrus caused by a member of the α-proteobacteria, 'Candidatus Liberibacter asiaticus' (CaLas), and Citrus tristeza virus (CTV) respectively. HLB is a devastating disease, but CTV strains vary from very severe to very mild. Both CaLas and CTV are phloem-restricted. The CaLas-B232 strain and CTV-B6 cause a wide range of severe and similar symptoms. The mild strain CTV-B2 doesn't induce significant symptoms or damage to plants. Transcriptome profiles obtained through RNA-seq revealed 611, 404 and 285 differentially expressed transcripts (DETs) after infection with CaLas-B232, CTV-B6 and CTV-B2. These DETs were components of a wide range of pathways involved in circadian rhythm, cell wall modification and cell organization, as well as transcription factors, transport, hormone response and secondary metabolism, signaling and stress response. The number of transcripts that responded to both CTV-B6 and CaLas-B232 was much larger than the number of transcripts that responded to both strains of CTV or to both CTV-B2 and CaLas-B232. A total of 38 genes were assayed by RT-qPCR and the correlation coefficients between Gfold and RT-qPCR were 0.82, 0.69, 0.81 for sweet orange plants infected with CTV-B2, CTV-B6 and CaLas-B232, respectively. The number and composition of DETs reflected the complexity of symptoms caused by the pathogens in established infections, although the leaf tissues sampled were asymptomatic. There were greater similarities between the sweet orange in response to CTV-B6 and CaLas-B232 than between the two CTV strains, reflecting the similar physiological changes caused by both CTV-B6 and CaLas-B232. The circadian rhythm system of plants was perturbed by all three pathogens, especially by CTV-B6, and the ion balance was also disrupted by all three pathogens, especially by CaLas-B232. Defense responses related to cell wall modification, transcriptional regulation, hormones, secondary metabolites, kinases and stress were activated by all three pathogens but with different patterns. The transcriptome profiles of Citrus sinensis identified host genes whose expression is affected by the presence of a pathogen in the phloem without producing symptoms (CTV-B2), and host genes whose expression leads to induction of symptoms in the plant (CTV-B6, CaLas-B232).

Protein Biomarkers for Insulin Resistance and Type 2 Diabetes Risk in Two Large Community Cohorts

PubMed Central

Nowak, Christoph; Sundström, Johan; Gustafsson, Stefan; Giedraitis, Vilmantas; Lind, Lars; Ingelsson, Erik; Fall, Tove

2016-01-01

Insulin resistance (IR) is a precursor of type 2 diabetes (T2D), and improved risk prediction and understanding of the pathogenesis are needed. We used a novel high-throughput 92-protein assay to identify circulating biomarkers for HOMA of IR in two cohorts of community residents without diabetes (n = 1,367) (mean age 73 ± 3.6 years). Adjusted linear regression identified cathepsin D and confirmed six proteins (leptin, renin, interleukin-1 receptor antagonist [IL-1ra], hepatocyte growth factor, fatty acid–binding protein 4, and tissue plasminogen activator [t-PA]) as IR biomarkers. Mendelian randomization analysis indicated a positive causal effect of IR on t-PA concentrations. Two biomarkers, IL-1ra (hazard ratio [HR] 1.28, 95% CI 1.03–1.59) and t-PA (HR 1.30, 1.02–1.65) were associated with incident T2D, and t-PA predicted 5-year transition to hyperglycemia (odds ratio 1.30, 95% CI 1.02–1.65). Additional adjustment for fasting glucose rendered both coefficients insignificant and revealed an association between renin and T2D (HR 0.79, 0.62–0.99). LASSO regression suggested a risk model including IL-1ra, t-PA, and the Framingham Offspring Study T2D score, but prediction improvement was nonsignificant (difference in C-index 0.02, 95% CI −0.08 to 0.12) over the T2D score only. In conclusion, proteomic blood profiling indicated cathepsin D as a new IR biomarker and suggested a causal effect of IR on t-PA. PMID:26420861

Cycloheximide and actinomycin D delay death and affect bcl-2, bax, and Ice gene expression in astrocytes under in vitro ischemia.

PubMed

Yu, Albert Cheung Hoi; Yung, Hon Wa; Hui, Michael Hung Kit; Lau, Lok Ting; Chen, Xiao Qian; Collins, Richard A

2003-10-15

An in vitro ischemia model was established and the effect of the metabolic inhibitors cycloheximide (CHX) and actinomycin D (ActD) on apoptosis in astrocytes under ischemia studied. CHX decreased by 75% the number of cells dying after 6 hr of ischemia compared with control cultures. TdT-mediated dUTP nick end labelling (TUNEL) staining of comparable cultures was reduced by 40%. ActD decreased cell death by 60% compared with controls. The number of TUNEL-positive cells was reduced by 38%. The nuclear shrinkage in TUNEL-positive astrocytes in control cultures did not occur in ActD-treated astrocytes, indicating that nuclear shrinkage and DNA fragmentation during apoptosis are two unrelated processes. Expression of bcl-2 (alpha and beta), bax, and Ice in astrocytes under similar ischemic conditions, as measured by quantitative reverse transcription-polymerase chain reaction, indicated that ischemia down-regulated bcl-2 (alpha and beta) and bax. Ice was initially down-regulated from 0 to 4 hr, before returning to control levels after 8 hr of ischemia. ActD decreased the expression of these genes. CHX reduced the expression of bcl-2 (alpha and beta) but increased bax and Ice expression. It is hypothesized that the balance of proapoptotic (Bad, Bax) and antiapoptotic (Bcl-2, Bcl-Xl) proteins determines apoptosis. The data suggest that the ratio of Bcl-2/Bad in astrocytes following ActD and CHX treatment does not decrease as much in untreated cells during ischemia. Our data indicate that it is the ratio of Bcl-2 family members that plays a critical role in determining ischemia-induced apoptosis. It is also important to note that ischemia-induced apoptosis involves the regulation of RNA and protein synthesis. Copyright 2003 Wiley-Liss, Inc.

EQ-5D-5L and SF-6D Utility Measures in Symptomatic benign Thyroid Nodules: Acceptability and Psychometric Evaluation.

PubMed

Wong, Carlos K H; Lang, Brian H H; Yu, Hill M S; Lam, Cindy L K

2017-08-01

The aim of this study was to examine the acceptability, validity, and reliability of the EuroQoL Five-Dimension Five-Level (EQ-5D-5L) and Short-Form Six-Dimension (SF-6D) health utility measures in patients with symptomatic benign thyroid nodules. Data from a randomized controlled trial (ClinicalTrials.gov identifier: NCT02398721) of 294 patients with symptomatic benign thyroid nodules were utilized for this psychometric evaluation of health-related quality of life (HR-QOL) measurement. Three HR-QOL questionnaires-the generic 12-item Short Form Health Survey (SF-12v2), EQ-5D-5L, and SF-6D-were interviewer-administered at baseline and 2 weeks afterwards. Responses to SF-6D were transformed to SF-6D utility scores using a Hong Kong population scoring algorithm derived by standard gamble, whereas responses to EQ-5D-5L were mapped onto EQ-5D-3L response via interim mapping algorithms and then converted to EQ-5D-5L utility scores using a Chinese-specific value set. Construct validity was determined by evaluating Spearman correlation between SF-12v2 scores and utility scores. Two-week test-retest reliability was assessed using intra-class correlation coefficient. No significant (>15%) floor and ceiling effects were observed for SF-6D utility scores. The SF-6D utility scores had a moderate Spearman rank correlation with the SF-12v2 domain score providing evidence for adequate construct validity. The SF-6D utility scores showed good test-retest reliability (0.794; range 0.696-0.860). Better reliability was observed in SF-6D utility scores than in EQ-5D-5L utility scores. While the EQ-5D-5L instrument was less reproducible, the SF-6D instrument appeared to be an applicable, valid, and reliable measure in assessing the HR-QOL of Chinese patients with symptomatic benign thyroid nodules. The impact of utility score selection on the effectiveness and cost effectiveness of clinical interventions targeted to these patients needs further exploration. NCT02398721, ClinicalTrials.gov.

Towards clinical application of RayStretch for heterogeneity corrections in LDR permanent 125I prostate brachytherapy.

PubMed

Hueso-González, Fernando; Ballester, Facundo; Perez-Calatayud, Jose; Siebert, Frank-André; Vijande, Javier

RayStretch is a simple algorithm proposed for heterogeneity corrections in low-dose-rate brachytherapy. It is built on top of TG-43 consensus data, and it has been validated with Monte Carlo (MC) simulations. In this study, we take a real clinical prostate implant with 71 125 I seeds as reference and we apply RayStretch to analyze its performance in worst-case scenarios. To do so, we design two cases where large calcifications are located in the prostate lobules. RayStretch resilience under various calcification density values is also explored. Comparisons against MC calculations are performed. Dose-volume histogram-related parameters like prostate D 90 , rectum D 2cc , or urethra D 10 obtained with RayStretch agree within a few percent with the detailed MC results for all cases considered. The robustness and compatibility of RayStretch with commercial treatment planning systems indicate its applicability in clinical practice for dosimetric corrections in prostate calcifications. Its use during intraoperative ultrasound planning is foreseen. Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

The Cost Growth Problem: A Realistic Diagnosis and Solution.

DTIC Science & Technology

1983-06-01

access 30 0~ LJ 0 CD 0 ( 4c CD - V2 0 C.2 ~~CD.------ 0.0 4-J V) 0 0.0 C.,I Cdc = CC, 0 0D C2 =I . 31 haua La OC I- c C _g .- C2 n C2 __. 6.34 LIA ca D...Department Navy Military Personnel Command Washington, D.C. 20370 6. Director for HRM Plans and Policy (OP-IS0) 1 Human Resource Management Division...Washington, D.C. 20301 25. Dana French, CAPT, USN HD HRM Plans & Policy Branch Washington, D.C. 20301 26. Robert Aaron 820 Lamberton Drive Silver

Quantifying the Performances of DFT for Predicting Vibrationally Resolved Optical Spectra: Asymmetric Fluoroborate Dyes as Working Examples.

PubMed

Bednarska, Joanna; Zaleśny, Robert; Bartkowiak, Wojciech; Ośmiałowski, Borys; Medved', Miroslav; Jacquemin, Denis

2017-09-12

This article aims at a quantitative assessment of the performances of a panel of exchange-correlation functionals, including semilocal (BLYP and PBE), global hybrids (B3LYP, PBE0, M06, BHandHLYP, M06-2X, and M06-HF), and range-separated hybrids (CAM-B3LYP, LC-ωPBE, LC-BLYP, ωB97X, and ωB97X-D), in predicting the vibrationally resolved absorption spectra of BF 2 -carrying compounds. To this end, for 19 difluoroborates as examples, we use, as a metric, the vibrational reorganization energy (λ vib ) that can be determined based on the computationally efficient linear coupling model (a.k.a. vertical gradient method). The reference values of λ vib were determined by employing the CC2 method combined with the cc-pVTZ basis set for a representative subset of molecules. To validate the performances of CC2, comparisons with experimental data have been carried out as well. This study shows that the vibrational reorganization energy, involving Huang-Rhys factors and normal-mode frequencies, can indeed be used to quantify the reliability of functionals in the calculations of the vibrational fine structure of absorption bands, i.e., an accurate prediction of the vibrational reorganization energy leads to absorption band shapes better fitting the selected reference. The CAM-B3LYP, M06-2X, ωB97X-D, ωB97X, and BHandHLYP functionals all deliver vibrational reorganization energies with absolute relative errors smaller than 20% compared to CC2, whereas 10% accuracy can be achieved with the first three functionals. Indeed, the set of examined exchange-correlation functionals can be divided into three groups: (i) BLYP, B3LYP, PBE, PBE0, and M06 yield inaccurate band shapes (λ vib,TDDFT < λ vib,CC2 ), (ii) BHandHLYP, CAM-B3LYP, M06-2X, ωB97X, and ωB97X-D provide accurate band shapes (λ vib,TDDFT ≈ λ vib,CC2 ), and (iii) LC-ωPBE, LC-BLYP, and M06-HF deliver rather poor band topologies (λ vib,TDDFT > λ vib,CC2 ). This study also demonstrates that λ vib can be reliably estimated using the CC2 model and the relatively small cc-pVDZ basis set. Therefore, the linear coupling model combined with the CC2/cc-pVDZ level of theory can be used as a very efficient approach to determine λ vib values that can be used to select the most adequate functional for more accurate vibronic calculations, e.g., including more refined models and environmental effects.

Extrapolating MP2 and CCSD explicitly correlated correlation energies to the complete basis set limit with first and second row correlation consistent basis sets

NASA Astrophysics Data System (ADS)

Hill, J. Grant; Peterson, Kirk A.; Knizia, Gerald; Werner, Hans-Joachim

2009-11-01

Accurate extrapolation to the complete basis set (CBS) limit of valence correlation energies calculated with explicitly correlated MP2-F12 and CCSD(T)-F12b methods have been investigated using a Schwenke-style approach for molecules containing both first and second row atoms. Extrapolation coefficients that are optimal for molecular systems containing first row elements differ from those optimized for second row analogs, hence values optimized for a combined set of first and second row systems are also presented. The new coefficients are shown to produce excellent results in both Schwenke-style and equivalent power-law-based two-point CBS extrapolations, with the MP2-F12/cc-pV(D,T)Z-F12 extrapolations producing an average error of just 0.17 mEh with a maximum error of 0.49 for a collection of 23 small molecules. The use of larger basis sets, i.e., cc-pV(T,Q)Z-F12 and aug-cc-pV(Q,5)Z, in extrapolations of the MP2-F12 correlation energy leads to average errors that are smaller than the degree of confidence in the reference data (˜0.1 mEh). The latter were obtained through use of very large basis sets in MP2-F12 calculations on small molecules containing both first and second row elements. CBS limits obtained from optimized coefficients for conventional MP2 are only comparable to the accuracy of the MP2-F12/cc-pV(D,T)Z-F12 extrapolation when the aug-cc-pV(5+d)Z and aug-cc-pV(6+d)Z basis sets are used. The CCSD(T)-F12b correlation energy is extrapolated as two distinct parts: CCSD-F12b and (T). While the CCSD-F12b extrapolations with smaller basis sets are statistically less accurate than those of the MP2-F12 correlation energies, this is presumably due to the slower basis set convergence of the CCSD-F12b method compared to MP2-F12. The use of larger basis sets in the CCSD-F12b extrapolations produces correlation energies with accuracies exceeding the confidence in the reference data (also obtained in large basis set F12 calculations). It is demonstrated that the use of the 3C(D) Ansatz is preferred for MP2-F12 CBS extrapolations. Optimal values of the geminal Slater exponent are presented for the diagonal, fixed amplitude Ansatz in MP2-F12 calculations, and these are also recommended for CCSD-F12b calculations.

Upregulation of genes encoding digestive enzymes and nutrient transporters in the digestive system of broiler chickens by dietary supplementation of fiber and inclusion of coarse particle size corn.

PubMed

Kheravii, Sarbast K; Swick, Robert A; Choct, Mingan; Wu, Shu-Biao

2018-03-20

Measures to improve bird performance have been sought due to the imminent phase out of in-feed antibiotics in poultry and continued demand for higher poultry feeding efficiency. Increasing grain particle size and dietary fibre may improve gizzard function, digestive efficiency and nutrient absorption. This study was conducted to evaluate the effect increased particle size of corn and inclusion of sugarcane bagasse (SB) on mRNA expression of genes encoding digestive enzymes and nutrient transporters in broilers. A total of 336 day-old Ross 308 males were assigned in a 2 × 2 factorial arrangement of treatments with corn particle size - coarse 3576 μm or fine 1113 μm geometric mean diameter, and SB - 0 or 2% inclusion. Feed conversion ratio (FCR), weight gain and feed intake were measured from d 0-10 and d 10-24. The relative gizzard weight and mRNA expression of genes encoding digestive enzymes and intestinal nutrient transporters were measured on d 24. During d 10-24, a particle size × SB interaction was observed for FCR (P < 0.01), where birds fed coarsely ground corn (CC) with 2% SB had lower FCR than those fed CC without SB. A particle size × SB interaction was observed for both expression of pepsinogen A and C (P < 0.01) which were negatively correlated with FCR on d 24. Addition of 2% SB upregulated pepsinogen A and C only in CC fed birds. Further, 2% SB also upregulated pancreatic amylase (AMY2A) and intestinal cationic amino acid transporter-1 (CAT1). Inclusion of dietary CC upregulated duodenal amino peptidase N (APN), jejunal alanine, serine, cysteine and threonine transporter-1 (ASCT1), and ileal peptide transporter-2 (PepT2). These results suggest that both SB and coarse particle size modulate expression of genes encoding important digestive enzymes and nutrient transporters and thus are directly related to bird performance. These findings provide insights into the combination effects of dietary fiber and particle size in the future management of broiler feeding.

Using the DFT-D method to describe dispersion interactions in systems of weakly-bonded Xe-aromatic molecules

NASA Astrophysics Data System (ADS)

Andriichenko, N. N.; Ermilov, A. Yu.

2013-08-01

The optimum version of the DFT-D class of methods (BHHLYP-D2, 6-31G*) is chosen to describe binding in a Xe-phenol system with the aim of subsequent KM/MM calculations for complex Xe-containing protein systems. It is shown that the stability of the Xe-phenol system is due to weak dispersion interactions not described in conventional approaches using the density functional. The MP2 approach using the (aug)-cc-pVTZ basis and Stuttgart pseudopotential, which yield the best reproduction of the characteristics of a Xe2 xenon dimer, is chosen as the reference standard. It is noted that the 2010 DFT-D3 methods underestimate the binding energy by a factor of nearly three, while DFT methods without dispersion corrections do not reproduce the stability of Xe2 and Xe-phenol systems. It is found that in the best version of calculations, BHHLYP-D2, the binding energy in Xe-phenol complex is estimated to be 2.7 kcal/mol versus the 3.1 kcal/mol found using the comparative approach. It is concluded that BHHLYP-D2 adequately reproduces the difference between the two conformers of the Xe-phenol complex and trend toward an increase in binding energy in the series of aromatic amino acids (phenylalanine, tyrosine, and tryptophan). DFT-D can also indicate the existence of excess conformers that are missing in systems according to more precise descriptions (MP2/(aug)-cc-pVTZ).

Prevention of secondary hyperparathyroidism in hemodialysis patients: the key role of native vitamin D supplementation.

PubMed

Jean, G; Vanel, T; Terrat, J-C; Chazot, C

2010-10-01

Secondary hyperparathyroidism (SHPT) is a frequent complication in chronic kidney disease, especially in hemodialysis (HD) patients. Treatments for SHPT include calcitriol analogues (CA), phosphate binders, cinacalcet (CC), and surgical parathyroidectomy (PTX). This study aimed to assess the incidence and prevalence of SHPT in a single center during the period when native vitamin D (N-VitD) supplementation and CC treatment became available. All incident and prevalent HD patients were prospectively recorded and compared using 3 periods from 2004 to 2005 (period 1), 2006 to 2007 (period 2), and 2008 to 2009 (period 3). SHPT was diagnosed with serum parathyroid hormone (PTH) levels >300 pg/mL or the need for CA, CC, or PTX. Between periods 1 and 3, in incident patients (n=120 and 101), N-VitD prescription increased from 11% to 68% (P<0.0001), CA prescription remained stable (40%), and patients with PTH>300 pg/mL decreased from 40% to 12% (P<0.0001). In prevalent HD patients (n=235), N-VitD treatment increased from 55% to 91% (P<0.0001), whereas treatment with CA decreased from 67% to 17% (P<0.0001). Patients with serum PTH>300 pg/mL decreased from 38% to 13% (P<0.001), whereas patients with PTH<150 pg/mL remained stable (<30%). New CC prescriptions decreased from 45 to 3 (P<0.0001). Since 2004, SHPT has decreased drastically in incident and prevalent HD patients. The preventive role of N-VitD supplementation appears to be obvious and represents one more argument for its general recommendation in CKD patients. © 2010 The Authors. Hemodialysis International © 2010 International Society for Hemodialysis.

Evaluation of dietary calcium level and source and phytase on growth performance, serum metabolites, and ileum mineral contents in broiler chicks fed adequate phosphorus diets from one to 28 days of age.

PubMed

Momeneh, T; Karimi, A; Sadeghi, G; Vaziry, A; Bedford, M R

2018-04-01

A total of 936 one-day-old broiler chicks (Ross 308) was used to evaluate the effects of dietary calcium (Ca) source (1.0 and 0.6% from Ca carbonate [CC], or 0.6% from Celtic sea minerals [CSM]) on broiler chick response to phytase supplementation (0, 500, or 2,500 FTU per kg of diet) in phosphorus (P) adequate diets. Birds were randomly assigned to 9 treatments, each replicated 8 times (4 repeats of male and 4 repeats of female birds; 13 birds per replicate) in a completely randomized design. Results showed that birds fed low Ca CC diets had significantly (P ≤ 0.05) lower body weight at 14 and 21 d; weight gain during 1 to 14 d; feed intake during 1 to 14 d and 1 to 28 d; and toe and tibia ash content, ileum ash, and Ca, and P contents at 28 days. Feed conversion ratio and feed intake between 21 and 28 d, and serum Ca, Fe, and alkaline phosphatase levels at 28 d of age were not affected by dietary Ca level. The negative influence of reducing the dietary Ca level on body weight and weight gain was less severe when CC was replaced with CSM, and birds fed the CSM diet had a significantly lower feed conversion ratio and higher tibia P content compared to CC. Phytase did not have a significant influence (P > 0.05) on most measured parameters, but significantly reduced ileum P and ash contents, especially at the higher level of 2,500 vs. 500 units of phytase per kg of diet. These results confirm that CSM has a valuable potential to improve feed conversion ratio, and that phytase was less effective in compensating for a significantly reduced dietary Ca level as it is for P.

The Association of Multiple Biomarkers of Iron Metabolism and Type 2 Diabetes - the EPIC-InterAct Study

PubMed Central

Podmore, Clara; Meidtner, Karina; Schulze, Matthias B; Scott, Robert A; Ramond, Anna; Butterworth, Adam S; Di Angelantonio, Emanuele; Danesh, John; Arriola, Larraitz; Barricarte, Aurelio; Boeing, Heiner; Clavel-Chapelon, Françoise; Cross, Amanda J; Dahm, Christina C; Fagherazzi, Guy; Franks, Paul W; Gavrila, Diana; Grioni, Sara; Gunter, Marc J; Gusto, Gaelle; Jakszyn, Paula; Katzke, Verena; Key, Timothy J; Kühn, Tilman; Mattiello, Amalia; Nilsson, Peter M; Olsen, Anja; Overvad, Kim; Palli, Domenico; Quirós, J. Ramón; Rolandsson, Olov; Sacerdote, Carlotta; Sánchez-Cantalejo, Emilio; Slimani, Nadia; Sluijs, Ivonne; Spijkerman, Annemieke MW; Tjonneland, Anne; Tumino, Rosario; van der A, Daphne L; van der Schouw, Yvonne T; Feskens, Edith JM; Forouhi, Nita G; Sharp, Stephen J; Riboli, Elio; Langenberg, Claudia; Wareham, Nicholas J

2016-01-01

Objective Observational studies show an association between ferritin and type 2 diabetes (T2D), suggesting a role of high iron stores for T2D development. However, ferritin is influenced by factors other than iron stores, which is less the case for other biomarkers of iron metabolism. We investigate associations of ferritin, transferrin saturation (TSAT), serum iron and transferrin with T2D incidence, to clarify the role of iron in the pathogenesis of T2D. Research and Design Methods The EPIC-InterAct study includes 12,403 incident T2D cases and a representative sub-cohort of 16,154 individuals from a European cohort with 3.99 million person-years of follow-up. We studied the prospective association of ferritin, TSAT, serum iron and transferrin with incident T2D in 11,052 cases and a random sub-cohort of 15,182 individuals and assessed whether these associations differed by subgroups of the population. Results Higher levels of ferritin and transferrin were associated with a higher risk of T2D [HR in men and women, respectively: 1.07 (95% CI: 1.01; 1.12) and 1.12 (1.05; 1.19) per 100 μg/L higher ferritin level; 1.11 (1.00; 1.24) and 1.22 (1.12; 1.33) per 0.5 g/L higher transferrin level] after adjustment for age, centre, BMI, physical activity, smoking status, education, hsCRP, ALT and GGT. Elevated TSAT (≥45% versus <45%) was associated with a lower risk of T2D in women [0.68 (0.54; 0.86)] but was not statistically significantly associated in men [0.90 (0.75; 1.08)]. Serum iron was not associated with T2D. The association of ferritin with T2D was stronger among leaner individuals (pinteraction<0.01). Conclusions The pattern of association of TSAT and transferrin with T2D suggests that the underlying relationship between iron stores and T2D is more complex than the simple link suggested by the association of ferritin with T2D. PMID:26861925

1,2-Dichlorohexafluoro-Cyclobutane (1,2-c-C4F6Cl2, R-316c) a Potent Ozone Depleting Substance and Greenhouse Gas: Atmospheric Loss Processes, Lifetimes, and Ozone Depletion and Global Warming Potentials for the (E) and (Z) stereoisomers

NASA Technical Reports Server (NTRS)

Papadimitriou, Vassileios C.; McGillen, Max R.; Smith, Shona C.; Jubb, Aaron M.; Portmann, Robert W.; Hall, Bradley D.; Fleming, Eric L.; Jackman, Charles H.; Burkholder, James B.

2013-01-01

The atmospheric processing of (E)- and (Z)-1,2-dichlorohexafluorocyclobutane (1,2-c-C4F6Cl2, R-316c) was examined in this work as the ozone depleting (ODP) and global warming (GWP) potentials of this proposed replacement compound are presently unknown. The predominant atmospheric loss processes and infrared absorption spectra of the R-316c isomers were measured to provide a basis to evaluate their atmospheric lifetimes and, thus, ODPs and GWPs. UV absorption spectra were measured between 184.95 to 230 nm at temperatures between 214 and 296 K and a parametrization for use in atmospheric modeling is presented. The Cl atom quantum yield in the 193 nm photolysis of R- 316c was measured to be 1.90 +/- 0.27. Hexafluorocyclobutene (c-C4F6) was determined to be a photolysis co-product with molar yields of 0.7 and 1.0 (+/-10%) for (E)- and (Z)-R-316c, respectively. The 296 K total rate coefficient for the O(1D) + R-316c reaction, i.e., O(1D) loss, was measured to be (1.56 +/- 0.11) × 10(exp -10)cu cm/ molecule/s and the reactive rate coefficient, i.e., R-316c loss, was measured to be (1.36 +/- 0.20) × 10(exp -10)cu cm/molecule/s corresponding to a approx. 88% reactive yield. Rate coefficient upper-limits for the OH and O3 reaction with R-316c were determined to be <2.3 × 10(exp -17) and <2.0 × 10(exp -22)cu cm/molecule/s, respectively, at 296 K. The quoted uncertainty limits are 2(sigma) and include estimated systematic errors. Local and global annually averaged lifetimes for the (E)- and (Z)-R-316c isomers were calculated using a 2-D atmospheric model to be 74.6 +/- 3 and 114.1 +/-10 years, respectively, where the estimated uncertainties are due solely to the uncertainty in the UV absorption spectra. Stratospheric photolysis is the predominant atmospheric loss process for both isomers with the O(1D) reaction making a minor, approx. 2% for the (E) isomer and 7% for the (Z) isomer, contribution to the total atmospheric loss. Ozone depletion potentials for (E)- and (Z)-R-316c were calculated using the 2-D model to be 0.46 and 0.54, respectively. Infrared absorption spectra for (E)- and (Z)-R-316c were measured at 296 K and used to estimate their radiative efficiencies (REs) and GWPs; 100-year time-horizon GWPs of 4160 and 5400 were obtained for (E)- and (Z)-R-316c, respectively. Both isomers of R-316c are shown in this work to be long-lived ozone depleting substances and potent greenhouse gases.

TU-F-CAMPUS-J-02: Evaluation of Textural Feature Extraction for Radiotherapy Response Assessment of Early Stage Breast Cancer Patients Using Diffusion Weighted MRI and Dynamic Contrast Enhanced MRI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xie, Y; Wang, C; Horton, J

Purpose: To investigate the feasibility of using classic textural feature extraction in radiotherapy response assessment, we studied a unique cohort of early stage breast cancer patients with paired pre - and post-radiation Diffusion Weighted MRI (DWI-MRI) and Dynamic Contrast Enhanced MRI (DCE-MRI). Methods: 15 female patients from our prospective phase I trial evaluating preoperative radiotherapy were included in this retrospective study. Each patient received a single-fraction radiation treatment, and DWI and DCE scans were conducted before and after the radiotherapy. DWI scans were acquired using a spin-echo EPI sequence with diffusion weighting factors of b = 0 and b =more » 500 mm{sup 2} /s, and the apparent diffusion coefficient (ADC) maps were calculated. DCE-MRI scans were acquired using a T{sub 1}-weighted 3D SPGR sequence with a temporal resolution of about 1 minute. The contrast agent (CA) was intravenously injected with a 0.1 mmol/kg bodyweight dose at 2 ml/s. Two parameters, volume transfer constant (K{sup trans} ) and k{sub ep} were analyzed using the two-compartment Tofts kinetic model. For DCE parametric maps and ADC maps, 33 textural features were generated from the clinical target volume (CTV) in a 3D fashion using the classic gray level co-occurrence matrix (GLCOM) and gray level run length matrix (GLRLM). Wilcoxon signed-rank test was used to determine the significance of each texture feature’s change after the radiotherapy. The significance was set to 0.05 with Bonferroni correction. Results: For ADC maps calculated from DWI-MRI, 24 out of 33 CTV features changed significantly after the radiotherapy. For DCE-MRI pharmacokinetic parameters, all 33 CTV features of K{sup trans} and 33 features of k{sub ep} changed significantly. Conclusion: Initial results indicate that those significantly changed classic texture features are sensitive to radiation-induced changes and can be used for assessment of radiotherapy response in breast cancer.« less

Structural elucidation of rhamnogalacturonans from flaxseed hulls.

PubMed

Qian, Ke-Ying; Cui, Steve W; Nikiforuk, John; Goff, H Douglas

2012-11-15

The structure of acidic fraction gum (AFG) from flaxseed hulls was elucidated by methylation analysis and 1D/2D NMR spectroscopy. This acidic fraction was separated from water-soluble flaxseed gum using anion-exchange chromatography. AFG consisted of a rhamnogalacturonan-I (RG-I) backbone that features diglycosyl repeating units, →2)-α-l-Rhap-(1→4)-α-d-GalpA-(1→. Rhamnosyl residues (38.2%) were the most abundant neutral sugar component. It was present mainly as unbranched (16.5%) and branched (19.5%) →2)-α-l-Rhap-(1→ at O-3. Most of its branches were terminated by monosaccharides, α/β-d-Galp-(1→ (19.6%), α-l-Fucp-(1→ (4.5%) or β-d-Xylp-(1→ (3.1%). However, when this branching site was occasionally appended with →4)-α-d-GalpA-(1→ or →2)-α-l-Rhap-(1→, side chains may consist of rhamnogalacturonan-I (RG-I), homorhamnan (HR) or a mixture of both. AFG was highly branched as indicated by its high degree of branching (0.55). A possible structure of AFG was proposed: (HR, RG-I, and HG refer to homorhamnan, rhamnogalacturonan-I, and homogalacturonan, respectively. The locations of HR, RG-I, and HG are interchangeable; (m+n)/(n+i)≈1.5. The substitution rate of R(1) is ∼54%. R(1) is mostly monosaccharide (α/β-d-Galp-(1→, α-l-Fucp-(1→ or β-d-Xylp-(1→). R(1) may also occasionally be a longer side chain with more than two residues beginning with →4)-α-GalpA-(1→ or →2)-α-l-Rhap-(1→, wherein the side-chain structure may be similar to part of the main chain.). Copyright © 2012. Published by Elsevier Ltd.

Correcting oral contraceptive pharmacokinetic alterations due to obesity. A randomized controlled trial

PubMed Central

Edelman, Alison B; Cherala, Ganesh; Munar, Myrna Y.; McInnis, Martha; Stanczyk, Frank Z.; Jensen, Jeffrey T

2014-01-01

Objective To determine if increasing the hormone dose or eliminating the hormone-free interval improves key pharmacokinetic (PK) alterations caused by obesity during oral contraceptive (OC) use. Study design Obese (BMI ≥ 30 kg/m2), ovulatory, otherwise healthy, women received an OC containing 20 mcg ethinyl estradiol (EE)/100 mcg levonorgestrel (LNG) dosed cyclically (21 days active pills with 7-day placebo week) for two cycles and then were randomized for two additional cycles to: Continuous Cycling [CC, a dose neutral arm using the same OC with no hormone-free interval] or Increased Dose [ID, a dose escalation arm using an OC containing 30 mcg EE/150 mcg LNG cyclically]. During Cycle 2, 3, and 4, outpatient visits were performed to assess maximum serum concentration (Cmax), area under the curve (AUC0-∞), and time to steady state as well as pharmacodynamics. These key PK parameters were calculated and compared within groups between baseline and treatment cycles. Results A total of 31 women enrolled and completed the study (CC group n = 16; ID group n = 15). Demographics were similar between groups [mean BMI: CC 38kg/m2 (SD 5.1), ID 41kg/m2 (SD 7.6)]. At baseline, the key LNG PK parameters were no different between groups; average time to reach steady-state was 12 days in both groups; Cmax were CC: 3.82 ± 1.28 ng/mL and ID: 3.13 ± 0.87 ng/mL; and AUC0-∞ were CC: 267 ± 115 hr*ng/mL and ID: 199±75 hr*ng/mL. Following randomization, the CC group maintained steady-state serum levels whereas the ID group had a significantly higher Cmax (p< 0.001) but again required 12 days to achieve steady-state. However, AUC was not significantly different between CC (412 ± 255 hr*ng/mL) and ID (283 ± 130 hr*ng/mL). Forty-five percent (14/31) of the study population had evidence of an active follicle-like structure prior to randomization and afterwards this decreased to 9% (3/31). Conclusion Both increasing the OC dose and continuous dosing appear to counteract the impact of obesity on key OC PK parameters. PMID:25070547

Observation of a Neutral Structure near the DD[over ¯]^{*} Mass Threshold in e^{+}e^{-}→(DD[over ¯]^{*})^{0}π^{0} at sqrt[s]=4.226 and 4.257 GeV.

PubMed

Ablikim, M; Achasov, M N; Ai, X C; Albayrak, O; Albrecht, M; Ambrose, D J; Amoroso, A; An, F F; An, Q; Bai, J Z; Ferroli, R Baldini; Ban, Y; Bennett, D W; Bennett, J V; Bertani, M; Bettoni, D; Bian, J M; Bianchi, F; Boger, E; Boyko, I; Briere, R A; Cai, H; Cai, X; Cakir, O; Calcaterra, A; Cao, G F; Cetin, S A; Chang, J F; Chelkov, G; Chen, G; Chen, H S; Chen, H Y; Chen, J C; Chen, M L; Chen, S Chen; Chen, S J; Chen, X; Chen, X R; Chen, Y B; Cheng, H P; Chu, X K; Cibinetto, G; Dai, H L; Dai, J P; Dbeyssi, A; Dedovich, D; Deng, Z Y; Denig, A; Denysenko, I; Destefanis, M; De Mori, F; Ding, Y; Dong, C; Dong, J; Dong, L Y; Dong, M Y; Du, S X; Duan, P F; Fan, J Z; Fang, J; Fang, S S; Fang, X; Fang, Y; Fava, L; Feldbauer, F; Felici, G; Feng, C Q; Fioravanti, E; Fritsch, M; Fu, C D; Gao, Q; Gao, X L; Gao, X Y; Gao, Y; Gao, Z; Garzia, I; Goetzen, K; Gong, W X; Gradl, W; Greco, M; Gu, M H; Gu, Y T; Guan, Y H; Guo, A Q; Guo, L B; Guo, R P; Guo, Y; Guo, Y P; Haddadi, Z; Hafner, A; Han, S; Hao, X Q; Harris, F A; He, K L; He, X Q; Held, T; Heng, Y K; Hou, Z L; Hu, C; Hu, H M; Hu, J F; Hu, T; Hu, Y; Huang, G M; Huang, G S; Huang, J S; Huang, X T; Huang, Y; Hussain, T; Ji, Q; Ji, Q P; Ji, X B; Ji, X L; Jiang, L W; Jiang, X S; Jiang, X Y; Jiao, J B; Jiao, Z; Jin, D P; Jin, S; Johansson, T; Julin, A; Kalantar-Nayestanaki, N; Kang, X L; Kang, X S; Kavatsyuk, M; Ke, B C; Kiese, P; Kliemt, R; Kloss, B; Kolcu, O B; Kopf, B; Kornicer, M; Kühn, W; Kupsc, A; Lange, J S; Lara, M; Larin, P; Leng, C; Li, C; Li, Cheng; Li, D M; Li, F; Li, F Y; Li, G; Li, H B; Li, H J; Li, J C; Li, Jin; Li, K; Li, K; Li, Lei; Li, P R; Li, T; Li, W D; Li, W G; Li, X L; Li, X M; Li, X N; Li, X Q; Li, Z B; Liang, H; Liang, J J; Liang, Y F; Liang, Y T; Liao, G R; Lin, D X; Liu, B J; Liu, C X; Liu, D; Liu, F H; Liu, Fang; Liu, Feng; Liu, H B; Liu, H H; Liu, H H; Liu, H M; Liu, J; Liu, J B; Liu, J P; Liu, J Y; Liu, K; Liu, K Y; Liu, L D; Liu, P L; Liu, Q; Liu, S B; Liu, X; Liu, Y B; Liu, Z A; Liu, Zhiqing; Loehner, H; Lou, X C; Lu, H J; Lu, J G; Lu, Y; Lu, Y P; Luo, C L; Luo, M X; Luo, T; Luo, X L; Lyu, X R; Ma, F C; Ma, H L; Ma, L L; Ma, M M; Ma, Q M; Ma, T; Ma, X N; Ma, X Y; Maas, F E; Maggiora, M; Mao, Y J; Mao, Z P; Marcello, S; Messchendorp, J G; Min, J; Mitchell, R E; Mo, X H; Mo, Y J; Morales, C Morales; Moriya, K; Muchnoi, N Yu; Muramatsu, H; Nefedov, Y; Nerling, F; Nikolaev, I B; Ning, Z; Nisar, S; Niu, S L; Niu, X Y; Olsen, S L; Ouyang, Q; Pacetti, S; Pan, Y; Patteri, P; Pelizaeus, M; Peng, H P; Peters, K; Pettersson, J; Ping, J L; Ping, R G; Poling, R; Prasad, V; Qi, M; Qian, S; Qiao, C F; Qin, L Q; Qin, N; Qin, X S; Qin, Z H; Qiu, J F; Rashid, K H; Redmer, C F; Ripka, M; Rong, G; Rosner, Ch; Ruan, X D; Sarantsev, A; Savrié, M; Schoenning, K; Schumann, S; Shan, W; Shao, M; Shen, C P; Shen, P X; Shen, X Y; Sheng, H Y; Shi, M; Song, W M; Song, X Y; Sosio, S; Spataro, S; Sun, G X; Sun, J F; Sun, S S; Sun, X H; Sun, Y J; Sun, Y Z; Sun, Z J; Sun, Z T; Tang, C J; Tang, X; Tapan, I; Thorndike, E H; Tiemens, M; Ullrich, M; Uman, I; Varner, G S; Wang, B; Wang, D; Wang, D Y; Wang, K; Wang, L L; Wang, L S; Wang, M; Wang, P; Wang, P L; Wang, S G; Wang, W; Wang, W P; Wang, X F; Wang, Y D; Wang, Y F; Wang, Y Q; Wang, Z; Wang, Z G; Wang, Z H; Wang, Z Y; Wang, Z Y; Weber, T; Wei, D H; Wei, J B; Weidenkaff, P; Wen, S P; Wiedner, U; Wolke, M; Wu, L H; Wu, L J; Wu, Z; Xia, L; Xia, L G; Xia, Y; Xiao, D; Xiao, H; Xiao, Z J; Xie, Y G; Xiu, Q L; Xu, G F; Xu, J J; Xu, L; Xu, Q J; Xu, X P; Yan, L; Yan, W B; Yan, W C; Yan, Y H; Yang, H J; Yang, H X; Yang, L; Yang, Y; Yang, Y X; Ye, M; Ye, M H; Yin, J H; Yu, B X; Yu, C X; Yu, J S; Yuan, C Z; Yuan, W L; Yuan, Y; Yuncu, A; Zafar, A A; Zallo, A; Zeng, Y; Zeng, Z; Zhang, B X; Zhang, B Y; Zhang, C; Zhang, C C; Zhang, D H; Zhang, H H; Zhang, H Y; Zhang, J; Zhang, J J; Zhang, J L; Zhang, J Q; Zhang, J W; Zhang, J Y; Zhang, J Z; Zhang, K; Zhang, L; Zhang, X Y; Zhang, Y; Zhang, Y N; Zhang, Y H; Zhang, Y T; Zhang, Yu; Zhang, Z H; Zhang, Z P; Zhang, Z Y; Zhao, G; Zhao, J W; Zhao, J Y; Zhao, J Z; Zhao, Lei; Zhao, Ling; Zhao, M G; Zhao, Q; Zhao, Q W; Zhao, S J; Zhao, T C; Zhao, Y B; Zhao, Z G; Zhemchugov, A; Zheng, B; Zheng, J P; Zheng, W J; Zheng, Y H; Zhong, B; Zhou, L; Zhou, X; Zhou, X K; Zhou, X R; Zhou, X Y; Zhu, K; Zhu, K J; Zhu, S; Zhu, S H; Zhu, X L; Zhu, Y C; Zhu, Y S; Zhu, Z A; Zhuang, J; Zotti, L; Zou, B S; Zou, J H

2015-11-27

A neutral structure in the DD[over ¯]^{*} system around the DD[over ¯]^{*} mass threshold is observed with a statistical significance greater than 10σ in the processes e^{+}e^{-}→D^{+}D^{*-}π^{0}+c.c. and e^{+}e^{-}→D^{0}D[over ¯]^{*0}π^{0}+c.c. at sqrt[s]=4.226 and 4.257 GeV in the BESIII experiment. The structure is denoted as Z_{c}(3885)^{0}. Assuming the presence of a resonance, its pole mass and width are determined to be [3885.7_{-5.7}^{+4.3}(stat)±8.4(syst)]  MeV/c^{2} and [35_{-12}^{+11}(stat)±15(syst)]  MeV, respectively. The Born cross sections are measured to be σ[e^{+}e^{-}→Z_{c}(3885)^{0}π^{0},Z_{c}(3885)^{0}→DD[over ¯]^{*}]=[77±13(stat)±17(syst)]  pb at 4.226 GeV and [47±9(stat)±10(syst)]  pb at 4.257 GeV. The ratio of decay rates B[Z_{c}(3885)^{0}→D^{+}D^{*-}+c.c.]/B[Z_{c}(3885)^{0}→D^{0}D[over ¯]^{*0}+c.c.] is determined to be 0.96±0.18(stat)±0.12(syst), consistent with no isospin violation in the process, Z_{c}(3885)^{0}→DD[over ¯]^{*}.