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Sample records for lyman normal-tissue complication

  1. Prediction of radiation-induced liver disease by Lyman normal-tissue complication probability model in three-dimensional conformal radiation therapy for primary liver carcinoma

    International Nuclear Information System (INIS)

    Xu ZhiYong; Liang Shixiong; Zhu Ji; Zhu Xiaodong; Zhao Jiandong; Lu Haijie; Yang Yunli; Chen Long; Wang Anyu; Fu Xiaolong; Jiang Guoliang

    2006-01-01

    Purpose: To describe the probability of RILD by application of the Lyman-Kutcher-Burman normal-tissue complication (NTCP) model for primary liver carcinoma (PLC) treated with hypofractionated three-dimensional conformal radiotherapy (3D-CRT). Methods and Materials: A total of 109 PLC patients treated by 3D-CRT were followed for RILD. Of these patients, 93 were in liver cirrhosis of Child-Pugh Grade A, and 16 were in Child-Pugh Grade B. The Michigan NTCP model was used to predict the probability of RILD, and then the modified Lyman NTCP model was generated for Child-Pugh A and Child-Pugh B patients by maximum-likelihood analysis. Results: Of all patients, 17 developed RILD in which 8 were of Child-Pugh Grade A, and 9 were of Child-Pugh Grade B. The prediction of RILD by the Michigan model was underestimated for PLC patients. The modified n, m, TD 5 (1) were 1.1, 0.28, and 40.5 Gy and 0.7, 0.43, and 23 Gy for patients with Child-Pugh A and B, respectively, which yielded better estimations of RILD probability. The hepatic tolerable doses (TD 5 ) would be MDTNL of 21 Gy and 6 Gy, respectively, for Child-Pugh A and B patients. Conclusions: The Michigan model was probably not fit to predict RILD in PLC patients. A modified Lyman NTCP model for RILD was recommended

  2. Normal Tissue Complication Probability Estimation by the Lyman-Kutcher-Burman Method Does Not Accurately Predict Spinal Cord Tolerance to Stereotactic Radiosurgery

    International Nuclear Information System (INIS)

    Daly, Megan E.; Luxton, Gary; Choi, Clara Y.H.; Gibbs, Iris C.; Chang, Steven D.; Adler, John R.; Soltys, Scott G.

    2012-01-01

    Purpose: To determine whether normal tissue complication probability (NTCP) analyses of the human spinal cord by use of the Lyman-Kutcher-Burman (LKB) model, supplemented by linear–quadratic modeling to account for the effect of fractionation, predict the risk of myelopathy from stereotactic radiosurgery (SRS). Methods and Materials: From November 2001 to July 2008, 24 spinal hemangioblastomas in 17 patients were treated with SRS. Of the tumors, 17 received 1 fraction with a median dose of 20 Gy (range, 18–30 Gy) and 7 received 20 to 25 Gy in 2 or 3 sessions, with cord maximum doses of 22.7 Gy (range, 17.8–30.9 Gy) and 22.0 Gy (range, 20.2–26.6 Gy), respectively. By use of conventional values for α/β, volume parameter n, 50% complication probability dose TD 50 , and inverse slope parameter m, a computationally simplified implementation of the LKB model was used to calculate the biologically equivalent uniform dose and NTCP for each treatment. Exploratory calculations were performed with alternate values of α/β and n. Results: In this study 1 case (4%) of myelopathy occurred. The LKB model using radiobiological parameters from Emami and the logistic model with parameters from Schultheiss overestimated complication rates, predicting 13 complications (54%) and 18 complications (75%), respectively. An increase in the volume parameter (n), to assume greater parallel organization, improved the predictive value of the models. Maximum-likelihood LKB fitting of α/β and n yielded better predictions (0.7 complications), with n = 0.023 and α/β = 17.8 Gy. Conclusions: The spinal cord tolerance to the dosimetry of SRS is higher than predicted by the LKB model using any set of accepted parameters. Only a high α/β value in the LKB model and only a large volume effect in the logistic model with Schultheiss data could explain the low number of complications observed. This finding emphasizes that radiobiological models traditionally used to estimate spinal cord NTCP

  3. Normal tissue complication probability for salivary glands

    International Nuclear Information System (INIS)

    Rana, B.S.

    2008-01-01

    The purpose of radiotherapy is to make a profitable balance between the morbidity (due to side effects of radiation) and cure of malignancy. To achieve this, one needs to know the relation between NTCP (normal tissue complication probability) and various treatment variables of a schedule viz. daily dose, duration of treatment, total dose and fractionation along with tissue conditions. Prospective studies require that a large number of patients be treated with varied schedule parameters and a statistically acceptable number of patients develop complications so that a true relation between NTCP and a particular variable is established. In this study Salivary Glands Complications have been considered. The cases treated in 60 Co teletherapy machine during the period 1994 to 2002 were analyzed and the clinicians judgement in ascertaining the end points was the only means of observations. The only end points were early and late xerestomia which were considered for NTCP evaluations for a period of 5 years

  4. Statistical validation of normal tissue complication probability models

    NARCIS (Netherlands)

    Xu, Cheng-Jian; van der Schaaf, Arjen; van t Veld, Aart; Langendijk, Johannes A.; Schilstra, Cornelis

    2012-01-01

    PURPOSE: To investigate the applicability and value of double cross-validation and permutation tests as established statistical approaches in the validation of normal tissue complication probability (NTCP) models. METHODS AND MATERIALS: A penalized regression method, LASSO (least absolute shrinkage

  5. A new formula for normal tissue complication probability (NTCP) as a function of equivalent uniform dose (EUD).

    Science.gov (United States)

    Luxton, Gary; Keall, Paul J; King, Christopher R

    2008-01-07

    To facilitate the use of biological outcome modeling for treatment planning, an exponential function is introduced as a simpler equivalent to the Lyman formula for calculating normal tissue complication probability (NTCP). The single parameter of the exponential function is chosen to reproduce the Lyman calculation to within approximately 0.3%, and thus enable easy conversion of data contained in empirical fits of Lyman parameters for organs at risk (OARs). Organ parameters for the new formula are given in terms of Lyman model m and TD(50), and conversely m and TD(50) are expressed in terms of the parameters of the new equation. The role of the Lyman volume-effect parameter n is unchanged from its role in the Lyman model. For a non-homogeneously irradiated OAR, an equation relates d(ref), n, v(eff) and the Niemierko equivalent uniform dose (EUD), where d(ref) and v(eff) are the reference dose and effective fractional volume of the Kutcher-Burman reduction algorithm (i.e. the LKB model). It follows in the LKB model that uniform EUD irradiation of an OAR results in the same NTCP as the original non-homogeneous distribution. The NTCP equation is therefore represented as a function of EUD. The inverse equation expresses EUD as a function of NTCP and is used to generate a table of EUD versus normal tissue complication probability for the Emami-Burman parameter fits as well as for OAR parameter sets from more recent data.

  6. A new formula for normal tissue complication probability (NTCP) as a function of equivalent uniform dose (EUD)

    International Nuclear Information System (INIS)

    Luxton, Gary; Keall, Paul J; King, Christopher R

    2008-01-01

    To facilitate the use of biological outcome modeling for treatment planning, an exponential function is introduced as a simpler equivalent to the Lyman formula for calculating normal tissue complication probability (NTCP). The single parameter of the exponential function is chosen to reproduce the Lyman calculation to within ∼0.3%, and thus enable easy conversion of data contained in empirical fits of Lyman parameters for organs at risk (OARs). Organ parameters for the new formula are given in terms of Lyman model m and TD 50 , and conversely m and TD 50 are expressed in terms of the parameters of the new equation. The role of the Lyman volume-effect parameter n is unchanged from its role in the Lyman model. For a non-homogeneously irradiated OAR, an equation relates d ref , n, v eff and the Niemierko equivalent uniform dose (EUD), where d ref and v eff are the reference dose and effective fractional volume of the Kutcher-Burman reduction algorithm (i.e. the LKB model). It follows in the LKB model that uniform EUD irradiation of an OAR results in the same NTCP as the original non-homogeneous distribution. The NTCP equation is therefore represented as a function of EUD. The inverse equation expresses EUD as a function of NTCP and is used to generate a table of EUD versus normal tissue complication probability for the Emami-Burman parameter fits as well as for OAR parameter sets from more recent data

  7. Statistical Validation of Normal Tissue Complication Probability Models

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    Xu Chengjian, E-mail: c.j.xu@umcg.nl [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schaaf, Arjen van der; Veld, Aart A. van' t; Langendijk, Johannes A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schilstra, Cornelis [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Radiotherapy Institute Friesland, Leeuwarden (Netherlands)

    2012-09-01

    Purpose: To investigate the applicability and value of double cross-validation and permutation tests as established statistical approaches in the validation of normal tissue complication probability (NTCP) models. Methods and Materials: A penalized regression method, LASSO (least absolute shrinkage and selection operator), was used to build NTCP models for xerostomia after radiation therapy treatment of head-and-neck cancer. Model assessment was based on the likelihood function and the area under the receiver operating characteristic curve. Results: Repeated double cross-validation showed the uncertainty and instability of the NTCP models and indicated that the statistical significance of model performance can be obtained by permutation testing. Conclusion: Repeated double cross-validation and permutation tests are recommended to validate NTCP models before clinical use.

  8. Statistical validation of normal tissue complication probability models.

    Science.gov (United States)

    Xu, Cheng-Jian; van der Schaaf, Arjen; Van't Veld, Aart A; Langendijk, Johannes A; Schilstra, Cornelis

    2012-09-01

    To investigate the applicability and value of double cross-validation and permutation tests as established statistical approaches in the validation of normal tissue complication probability (NTCP) models. A penalized regression method, LASSO (least absolute shrinkage and selection operator), was used to build NTCP models for xerostomia after radiation therapy treatment of head-and-neck cancer. Model assessment was based on the likelihood function and the area under the receiver operating characteristic curve. Repeated double cross-validation showed the uncertainty and instability of the NTCP models and indicated that the statistical significance of model performance can be obtained by permutation testing. Repeated double cross-validation and permutation tests are recommended to validate NTCP models before clinical use. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Options and pitfalls of normal tissues complication probability models

    International Nuclear Information System (INIS)

    Dorr, Wolfgang

    2011-01-01

    Full text: Technological improvements in the physical administration of radiotherapy have led to increasing conformation of the treatment volume (TV) with the planning target volume (PTV) and of the irradiated volume (IV) with the TV. In this process of improvement of the physical quality of radiotherapy, the total volumes of organs at risk exposed to significant doses have significantly decreased, resulting in increased inhomogeneities in the dose distributions within these organs. This has resulted in a need to identify and quantify volume effects in different normal tissues. Today, irradiated volume today must be considered a 6t h 'R' of radiotherapy, in addition to the 5 'Rs' defined by Withers and Steel in the mid/end 1980 s. The current status of knowledge of these volume effects has recently been summarized for many organs and tissues by the QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) initiative [Int. J. Radiat. Oncol. BioI. Phys. 76 (3) Suppl., 2010]. However, the concept of using dose-volume histogram parameters as a basis for dose constraints, even without applying any models for normal tissue complication probabilities (NTCP), is based on (some) assumptions that are not met in clinical routine treatment planning. First, and most important, dose-volume histogram (DVH) parameters are usually derived from a single, 'snap-shot' CT-scan, without considering physiological (urinary bladder, intestine) or radiation induced (edema, patient weight loss) changes during radiotherapy. Also, individual variations, or different institutional strategies of delineating organs at risk are rarely considered. Moreover, the reduction of the 3-dimentional dose distribution into a '2dimensl' DVH parameter implies that the localization of the dose within an organ is irrelevant-there are ample examples that this assumption is not justified. Routinely used dose constraints also do not take into account that the residual function of an organ may be

  10. A simple method to calculate the influence of dose inhomogeneity and fractionation in normal tissue complication probability evaluation

    International Nuclear Information System (INIS)

    Begnozzi, L.; Gentile, F.P.; Di Nallo, A.M.; Chiatti, L.; Zicari, C.; Consorti, R.; Benassi, M.

    1994-01-01

    Since volumetric dose distributions are available with 3-dimensional radiotherapy treatment planning they can be used in statistical evaluation of response to radiation. This report presents a method to calculate the influence of dose inhomogeneity and fractionation in normal tissue complication probability evaluation. The mathematical expression for the calculation of normal tissue complication probability has been derived combining the Lyman model with the histogram reduction method of Kutcher et al. and using the normalized total dose (NTD) instead of the total dose. The fitting of published tolerance data, in case of homogeneous or partial brain irradiation, has been considered. For the same total or partial volume homogeneous irradiation of the brain, curves of normal tissue complication probability have been calculated with fraction size of 1.5 Gy and of 3 Gy instead of 2 Gy, to show the influence of fraction size. The influence of dose distribution inhomogeneity and α/β value has also been simulated: Considering α/β=1.6 Gy or α/β=4.1 Gy for kidney clinical nephritis, the calculated curves of normal tissue complication probability are shown. Combining NTD calculations and histogram reduction techniques, normal tissue complication probability can be estimated taking into account the most relevant contributing factors, including the volume effect. (orig.) [de

  11. Normal tissue complication probabilities correlated with late effects in the rectum after prostate conformal radiotherapy

    International Nuclear Information System (INIS)

    Dale, Einar; Olsen, Dag R.; Fossa, Sophie D.

    1999-01-01

    Purpose: Radiation therapy of deep-sited tumours will always result in normal tissue doses to some extent. The aim of this study was to calculate different risk estimates of late effects in the rectum for a group of cancer prostate patients treated with conformal radiation therapy (CRT) and correlate these estimates with the occurrences of late effects. Since the rectum is a hollow organ, several ways of generating dose-volume distributions over the organ are possible, and we wanted to investigate two of them. Methods and Materials: A mathematical model, known as the Lyman-Kutcher model, conventionally used to estimate normal tissue complication probabilities (NTCP) associated with radiation therapy, was applied to a material of 52 cancer prostate patients. The patients were treated with a four field box technique, with the rectum as organ at risk. Dose-volume histograms (DVH) were generated for the whole rectum (including the cavity) and of the rectum wall. One to two years after the treatment, the patients completed a questionnaire concerning bowel (rectum) related morbidity quantifying the extent of late effects. Results: A correlation analysis using Spearman's rank correlation coefficient, for NTCP values calculated from the DVHs and the patients' scores, gave correlation coefficients which were not statistically significant at the p max , of the whole rectum, correlated better to observed late toxicity than D max derived from histograms of the rectum wall. Correlation coefficients from 'high-dose' measures were larger than those calculated from the NTCP values. Accordingly, as the volume parameter of the Lyman-Kutcher model was reduced, raising the impact of small high-dose volumes on the NTCP values, the correlation between observed effects and NTCP values became significant at p < 0.01 level. Conclusions: 1) High-dose levels corresponding to small volume fractions of the cumulative dose-volume histograms were best correlated with the occurrences of late

  12. The use of normal tissue complication probability to predict radiation hepatitis

    International Nuclear Information System (INIS)

    Keum, Ki Chang; Seong, Jin Sil; Suh, Chang Ok; Lee, Sang Wook; Chung, Eun Ji; Shin, Hyun Soo; Kim, Gwi Eon

    2000-01-01

    Although it has been known that the tolerance of the liver to external beam irradiation depends on the irradiated volume and dose, few data exist which quantify this dependence. However, recently, with the development of three dimensional (3-D) treatment planning, have the tools to quantify the relationships between dose, volume, and normal tissue complications become available. The objective of this study is to investigate the relationships between normal tissue complication probability (NTCP) and the risk of radiation hepatitis for patients who received variant dose partial liver irradiation. From March 1992 to December 1994, 10 patients with hepatoma and 10 patients with bile duct cancer were included in this study. Eighteen patients had normal hepatic function, but 2 patients (prothrombin time 73%, 68%) had mild liver cirrhosis before irradiation. Radiation therapy was delivered with 10MV linear accelerator, 180-200 cGy fraction per day. The total dose ranged from 3,960 cGy to 6,000 cGy (median dose 5,040 cGy). The normal tissue complication probability was calculated by using Lyman's model. Radiation hepatitis was defined as the development of anicteric elevation of alkaline phosphatase of at least two fold and non-malignant ascites in the absence of documented progressive. The calculated NTCP ranged from 0.001 to 0.840 (median 0.05). Three of the 20 patients developed radiation hepatitis. The NTCP of the patients with radiation hepatitis were 0.390, 0.528, 0.844 (median: O.58±0.23), but that of the patients without radiation hepatitis ranged from 0.001 to 0.308 (median: 0.09±0.09). When the NTCP was calculated by using the volume factor of 0.32, a radiation hepatitis was observed only in patients with the NTCP value more than 0.39. By contrast, clinical results of evolving radiation hepatitis were not well correlated with NTCP value calculated when the volume factor of 0.69 was applied. On the basis of these observations, volume factor of 0.32 was more

  13. Normal tissue complication probability (NTCP), the clinician,s perspective

    International Nuclear Information System (INIS)

    Yeoh, E.K.

    2011-01-01

    Full text: 3D radiation treatment planning has enabled dose distributions to be related to the volume of normal tissues irradiated. The dose volume histograms thus derived have been utilized to set NTCP dose constraints to facilitate optimization of treatment planning. However, it is not widely appreciated that a number of important variables other than DYH's which determine NTCP in the individual patient. These variables will be discussed under the headings of patient and treatment related as well as tumour related factors. Patient related factors include age, co-morbidities such as connective tissue disease and diabetes mellitus, previous tissue/organ damage, tissue architectural organization (parallel or serial), regional tissue/organ and individual tissue/organ radiosensitivities as well as the development of severe acute toxicity. Treatment related variables which need to be considered include dose per fraction (if not the conventional 1.8012.00 Gy/fraction, particularly for IMRT), number of fractions and total dose, dose rate (particularly if combined with brachytherapy) and concurrent chemotherapy or other biological dose modifiers. Tumour related factors which impact on NTCP include infiltration of normal tissue/organ usually at presentation leading to compromised function but also with recurrent disease after radiation therapy as well as variable tumour radiosensitivities between and within tumour types. Whilst evaluation of DYH data is a useful guide in the choice of treatment plan, the current state of knowledge requires the clinician to make an educated judgement based on a consideration of the other factors.

  14. Impact of statistical learning methods on the predictive power of multivariate normal tissue complication probability models

    NARCIS (Netherlands)

    Xu, Cheng-Jian; van der Schaaf, Arjen; Schilstra, Cornelis; Langendijk, Johannes A.; van t Veld, Aart A.

    2012-01-01

    PURPOSE: To study the impact of different statistical learning methods on the prediction performance of multivariate normal tissue complication probability (NTCP) models. METHODS AND MATERIALS: In this study, three learning methods, stepwise selection, least absolute shrinkage and selection operator

  15. Normal tissue complication probabilities: dependence on choice of biological model and dose-volume histogram reduction scheme

    International Nuclear Information System (INIS)

    Moiseenko, Vitali; Battista, Jerry; Van Dyk, Jake

    2000-01-01

    Purpose: To evaluate the impact of dose-volume histogram (DVH) reduction schemes and models of normal tissue complication probability (NTCP) on ranking of radiation treatment plans. Methods and Materials: Data for liver complications in humans and for spinal cord in rats were used to derive input parameters of four different NTCP models. DVH reduction was performed using two schemes: 'effective volume' and 'preferred Lyman'. DVHs for competing treatment plans were derived from a sample DVH by varying dose uniformity in a high dose region so that the obtained cumulative DVHs intersected. Treatment plans were ranked according to the calculated NTCP values. Results: Whenever the preferred Lyman scheme was used to reduce the DVH, competing plans were indistinguishable as long as the mean dose was constant. The effective volume DVH reduction scheme did allow us to distinguish between these competing treatment plans. However, plan ranking depended on the radiobiological model used and its input parameters. Conclusions: Dose escalation will be a significant part of radiation treatment planning using new technologies, such as 3-D conformal radiotherapy and tomotherapy. Such dose escalation will depend on how the dose distributions in organs at risk are interpreted in terms of expected complication probabilities. The present study indicates considerable variability in predicted NTCP values because of the methods used for DVH reduction and radiobiological models and their input parameters. Animal studies and collection of standardized clinical data are needed to ascertain the effects of non-uniform dose distributions and to test the validity of the models currently in use

  16. Quantifying Unnecessary Normal Tissue Complication Risks due to Suboptimal Planning: A Secondary Study of RTOG 0126

    International Nuclear Information System (INIS)

    Moore, Kevin L.; Schmidt, Rachel; Moiseenko, Vitali; Olsen, Lindsey A.; Tan, Jun; Xiao, Ying; Galvin, James; Pugh, Stephanie; Seider, Michael J.; Dicker, Adam P.; Bosch, Walter; Michalski, Jeff; Mutic, Sasa

    2015-01-01

    Purpose: The purpose of this study was to quantify the frequency and clinical severity of quality deficiencies in intensity modulated radiation therapy (IMRT) planning in the Radiation Therapy Oncology Group 0126 protocol. Methods and Materials: A total of 219 IMRT patients from the high-dose arm (79.2 Gy) of RTOG 0126 were analyzed. To quantify plan quality, we used established knowledge-based methods for patient-specific dose-volume histogram (DVH) prediction of organs at risk and a Lyman-Kutcher-Burman (LKB) model for grade ≥2 rectal complications to convert DVHs into normal tissue complication probabilities (NTCPs). The LKB model was validated by fitting dose-response parameters relative to observed toxicities. The 90th percentile (22 of 219) of plans with the lowest excess risk (difference between clinical and model-predicted NTCP) were used to create a model for the presumed best practices in the protocol (pDVH 0126,top10% ). Applying the resultant model to the entire sample enabled comparisons between DVHs that patients could have received to DVHs they actually received. Excess risk quantified the clinical impact of suboptimal planning. Accuracy of pDVH predictions was validated by replanning 30 of 219 patients (13.7%), including equal numbers of presumed “high-quality,” “low-quality,” and randomly sampled plans. NTCP-predicted toxicities were compared to adverse events on protocol. Results: Existing models showed that bladder-sparing variations were less prevalent than rectum quality variations and that increased rectal sparing was not correlated with target metrics (dose received by 98% and 2% of the PTV, respectively). Observed toxicities were consistent with current LKB parameters. Converting DVH and pDVH 0126,top10% to rectal NTCPs, we observed 94 of 219 patients (42.9%) with ≥5% excess risk, 20 of 219 patients (9.1%) with ≥10% excess risk, and 2 of 219 patients (0.9%) with ≥15% excess risk. Replanning demonstrated the predicted NTCP

  17. Quantifying Unnecessary Normal Tissue Complication Risks due to Suboptimal Planning: A Secondary Study of RTOG 0126.

    Science.gov (United States)

    Moore, Kevin L; Schmidt, Rachel; Moiseenko, Vitali; Olsen, Lindsey A; Tan, Jun; Xiao, Ying; Galvin, James; Pugh, Stephanie; Seider, Michael J; Dicker, Adam P; Bosch, Walter; Michalski, Jeff; Mutic, Sasa

    2015-06-01

    The purpose of this study was to quantify the frequency and clinical severity of quality deficiencies in intensity modulated radiation therapy (IMRT) planning in the Radiation Therapy Oncology Group 0126 protocol. A total of 219 IMRT patients from the high-dose arm (79.2 Gy) of RTOG 0126 were analyzed. To quantify plan quality, we used established knowledge-based methods for patient-specific dose-volume histogram (DVH) prediction of organs at risk and a Lyman-Kutcher-Burman (LKB) model for grade ≥2 rectal complications to convert DVHs into normal tissue complication probabilities (NTCPs). The LKB model was validated by fitting dose-response parameters relative to observed toxicities. The 90th percentile (22 of 219) of plans with the lowest excess risk (difference between clinical and model-predicted NTCP) were used to create a model for the presumed best practices in the protocol (pDVH0126,top10%). Applying the resultant model to the entire sample enabled comparisons between DVHs that patients could have received to DVHs they actually received. Excess risk quantified the clinical impact of suboptimal planning. Accuracy of pDVH predictions was validated by replanning 30 of 219 patients (13.7%), including equal numbers of presumed "high-quality," "low-quality," and randomly sampled plans. NTCP-predicted toxicities were compared to adverse events on protocol. Existing models showed that bladder-sparing variations were less prevalent than rectum quality variations and that increased rectal sparing was not correlated with target metrics (dose received by 98% and 2% of the PTV, respectively). Observed toxicities were consistent with current LKB parameters. Converting DVH and pDVH0126,top10% to rectal NTCPs, we observed 94 of 219 patients (42.9%) with ≥5% excess risk, 20 of 219 patients (9.1%) with ≥10% excess risk, and 2 of 219 patients (0.9%) with ≥15% excess risk. Replanning demonstrated the predicted NTCP reductions while maintaining the volume of the PTV

  18. Investigation of normal tissue complication probabilities in prostate and partial breast irradiation radiotherapy techniques

    International Nuclear Information System (INIS)

    Bezak, E.; Takam, R.; Bensaleh, S.; Yeoh, E.; Marcu, L.

    2011-01-01

    Full text: Normal- Tissue-Complication Probabilities of rectum, bladder and urethra following various radiation techniques for prostate cancer were evaluated using the relative-seriality and Lyman models. NTCPs of lungs, heart and skin, their dependence on sourceposition, balloon-deformation were also investigated for HDR mammosite brachytherapy. The prostate treatment techniques included external three dimentional conformal-radiotherapy, Low-Dose-Rate brachytherapy (1-125), High-Dose-Rate brachytherapy (Ir-I92). Dose- Volume-Histograms of critical structures for prostate and breast radiotherapy, retrieved from corresponding treatment planning systems, were converted to Biological Effective Dose (BEffD)-based and Equivalent Dose(Deq)-based DVHs to account for differences in radiation delivery and fractionation schedule. Literature-based model parameters were used to calculate NTCPs. Hypofractionated 3D-CRT (2.75 Gy/fraction, total dose 55 Gy) NTCPs of rectum, bladder and urethra were less than those for standard fractionated 4-field 3D-CRT (2-Gy/fraction, 64 Gy) and dose-escalated 4- and 5-field 3D-CRT (74 Gy). Rectal and bladder NTCPs (5.2% and 6.6%) following the dose-escalated 4-field 3D-CRT (74 Gy) were the highest among analyzed techniques. The average NTCP for rectum and urethra were 0.6% and 24.7% for LDRBT and 0.5% and 11.2% for HDR-BT. For Mammosite, NTCP was estimated to be 0.1 %, 0.1 %, 1.2% and 3.5% for skin desquamation, erythema, telangiectasia and fibrosis respectively (the source positioned at the balloon centre). A 4 mm Mammosite-balloon deformation leads to overdosing of PTV regions by ∼40%, resulting in excessive skin dose and increased NTCP. Conclusions Prostate brachytherapy resulted in NTCPs lower compared to external beam techniques. Mammosite-brachytherapy resulted in no heart/lung complications regardless of balloon deformation. However, 4 mm deformation caused 0.6% increase in tissue fibrosis NTCP.

  19. Improving normal tissue complication probability models: the need to adopt a "data-pooling" culture.

    Science.gov (United States)

    Deasy, Joseph O; Bentzen, Søren M; Jackson, Andrew; Ten Haken, Randall K; Yorke, Ellen D; Constine, Louis S; Sharma, Ashish; Marks, Lawrence B

    2010-03-01

    Clinical studies of the dependence of normal tissue response on dose-volume factors are often confusingly inconsistent, as the QUANTEC reviews demonstrate. A key opportunity to accelerate progress is to begin storing high-quality datasets in repositories. Using available technology, multiple repositories could be conveniently queried, without divulging protected health information, to identify relevant sources of data for further analysis. After obtaining institutional approvals, data could then be pooled, greatly enhancing the capability to construct predictive models that are more widely applicable and better powered to accurately identify key predictive factors (whether dosimetric, image-based, clinical, socioeconomic, or biological). Data pooling has already been carried out effectively in a few normal tissue complication probability studies and should become a common strategy. Copyright 2010 Elsevier Inc. All rights reserved.

  20. Normal tissue complication probability modeling of radiation-induced hypothyroidism after head-and-neck radiation therapy.

    Science.gov (United States)

    Bakhshandeh, Mohsen; Hashemi, Bijan; Mahdavi, Seied Rabi Mehdi; Nikoofar, Alireza; Vasheghani, Maryam; Kazemnejad, Anoshirvan

    2013-02-01

    To determine the dose-response relationship of the thyroid for radiation-induced hypothyroidism in head-and-neck radiation therapy, according to 6 normal tissue complication probability models, and to find the best-fit parameters of the models. Sixty-five patients treated with primary or postoperative radiation therapy for various cancers in the head-and-neck region were prospectively evaluated. Patient serum samples (tri-iodothyronine, thyroxine, thyroid-stimulating hormone [TSH], free tri-iodothyronine, and free thyroxine) were measured before and at regular time intervals until 1 year after the completion of radiation therapy. Dose-volume histograms (DVHs) of the patients' thyroid gland were derived from their computed tomography (CT)-based treatment planning data. Hypothyroidism was defined as increased TSH (subclinical hypothyroidism) or increased TSH in combination with decreased free thyroxine and thyroxine (clinical hypothyroidism). Thyroid DVHs were converted to 2 Gy/fraction equivalent doses using the linear-quadratic formula with α/β = 3 Gy. The evaluated models included the following: Lyman with the DVH reduced to the equivalent uniform dose (EUD), known as LEUD; Logit-EUD; mean dose; relative seriality; individual critical volume; and population critical volume models. The parameters of the models were obtained by fitting the patients' data using a maximum likelihood analysis method. The goodness of fit of the models was determined by the 2-sample Kolmogorov-Smirnov test. Ranking of the models was made according to Akaike's information criterion. Twenty-nine patients (44.6%) experienced hypothyroidism. None of the models was rejected according to the evaluation of the goodness of fit. The mean dose model was ranked as the best model on the basis of its Akaike's information criterion value. The D(50) estimated from the models was approximately 44 Gy. The implemented normal tissue complication probability models showed a parallel architecture for the

  1. Normal Tissue Complication Probability Modeling of Radiation-Induced Hypothyroidism After Head-and-Neck Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Bakhshandeh, Mohsen [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Hashemi, Bijan, E-mail: bhashemi@modares.ac.ir [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Mahdavi, Seied Rabi Mehdi [Department of Medical Physics, Faculty of Medical Sciences, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Nikoofar, Alireza; Vasheghani, Maryam [Department of Radiation Oncology, Hafte-Tir Hospital, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Kazemnejad, Anoshirvan [Department of Biostatistics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of)

    2013-02-01

    Purpose: To determine the dose-response relationship of the thyroid for radiation-induced hypothyroidism in head-and-neck radiation therapy, according to 6 normal tissue complication probability models, and to find the best-fit parameters of the models. Methods and Materials: Sixty-five patients treated with primary or postoperative radiation therapy for various cancers in the head-and-neck region were prospectively evaluated. Patient serum samples (tri-iodothyronine, thyroxine, thyroid-stimulating hormone [TSH], free tri-iodothyronine, and free thyroxine) were measured before and at regular time intervals until 1 year after the completion of radiation therapy. Dose-volume histograms (DVHs) of the patients' thyroid gland were derived from their computed tomography (CT)-based treatment planning data. Hypothyroidism was defined as increased TSH (subclinical hypothyroidism) or increased TSH in combination with decreased free thyroxine and thyroxine (clinical hypothyroidism). Thyroid DVHs were converted to 2 Gy/fraction equivalent doses using the linear-quadratic formula with {alpha}/{beta} = 3 Gy. The evaluated models included the following: Lyman with the DVH reduced to the equivalent uniform dose (EUD), known as LEUD; Logit-EUD; mean dose; relative seriality; individual critical volume; and population critical volume models. The parameters of the models were obtained by fitting the patients' data using a maximum likelihood analysis method. The goodness of fit of the models was determined by the 2-sample Kolmogorov-Smirnov test. Ranking of the models was made according to Akaike's information criterion. Results: Twenty-nine patients (44.6%) experienced hypothyroidism. None of the models was rejected according to the evaluation of the goodness of fit. The mean dose model was ranked as the best model on the basis of its Akaike's information criterion value. The D{sub 50} estimated from the models was approximately 44 Gy. Conclusions: The implemented

  2. Hypothyroidism after primary radiotherapy for head and neck squamous cell carcinoma: Normal tissue complication probability modeling with latent time correction

    DEFF Research Database (Denmark)

    Rønjom, Marianne Feen; Brink, Carsten; Bentzen, Søren

    2013-01-01

    To develop a normal tissue complication probability (NTCP) model of radiation-induced biochemical hypothyroidism (HT) after primary radiotherapy for head and neck squamous cell carcinoma (HNSCC) with adjustment for latency and clinical risk factors.......To develop a normal tissue complication probability (NTCP) model of radiation-induced biochemical hypothyroidism (HT) after primary radiotherapy for head and neck squamous cell carcinoma (HNSCC) with adjustment for latency and clinical risk factors....

  3. Impact of Statistical Learning Methods on the Predictive Power of Multivariate Normal Tissue Complication Probability Models

    Energy Technology Data Exchange (ETDEWEB)

    Xu Chengjian, E-mail: c.j.xu@umcg.nl [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schaaf, Arjen van der; Schilstra, Cornelis; Langendijk, Johannes A.; Veld, Aart A. van' t [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands)

    2012-03-15

    Purpose: To study the impact of different statistical learning methods on the prediction performance of multivariate normal tissue complication probability (NTCP) models. Methods and Materials: In this study, three learning methods, stepwise selection, least absolute shrinkage and selection operator (LASSO), and Bayesian model averaging (BMA), were used to build NTCP models of xerostomia following radiotherapy treatment for head and neck cancer. Performance of each learning method was evaluated by a repeated cross-validation scheme in order to obtain a fair comparison among methods. Results: It was found that the LASSO and BMA methods produced models with significantly better predictive power than that of the stepwise selection method. Furthermore, the LASSO method yields an easily interpretable model as the stepwise method does, in contrast to the less intuitive BMA method. Conclusions: The commonly used stepwise selection method, which is simple to execute, may be insufficient for NTCP modeling. The LASSO method is recommended.

  4. Impact of statistical learning methods on the predictive power of multivariate normal tissue complication probability models.

    Science.gov (United States)

    Xu, Cheng-Jian; van der Schaaf, Arjen; Schilstra, Cornelis; Langendijk, Johannes A; van't Veld, Aart A

    2012-03-15

    To study the impact of different statistical learning methods on the prediction performance of multivariate normal tissue complication probability (NTCP) models. In this study, three learning methods, stepwise selection, least absolute shrinkage and selection operator (LASSO), and Bayesian model averaging (BMA), were used to build NTCP models of xerostomia following radiotherapy treatment for head and neck cancer. Performance of each learning method was evaluated by a repeated cross-validation scheme in order to obtain a fair comparison among methods. It was found that the LASSO and BMA methods produced models with significantly better predictive power than that of the stepwise selection method. Furthermore, the LASSO method yields an easily interpretable model as the stepwise method does, in contrast to the less intuitive BMA method. The commonly used stepwise selection method, which is simple to execute, may be insufficient for NTCP modeling. The LASSO method is recommended. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Impact of Statistical Learning Methods on the Predictive Power of Multivariate Normal Tissue Complication Probability Models

    International Nuclear Information System (INIS)

    Xu Chengjian; Schaaf, Arjen van der; Schilstra, Cornelis; Langendijk, Johannes A.; Veld, Aart A. van’t

    2012-01-01

    Purpose: To study the impact of different statistical learning methods on the prediction performance of multivariate normal tissue complication probability (NTCP) models. Methods and Materials: In this study, three learning methods, stepwise selection, least absolute shrinkage and selection operator (LASSO), and Bayesian model averaging (BMA), were used to build NTCP models of xerostomia following radiotherapy treatment for head and neck cancer. Performance of each learning method was evaluated by a repeated cross-validation scheme in order to obtain a fair comparison among methods. Results: It was found that the LASSO and BMA methods produced models with significantly better predictive power than that of the stepwise selection method. Furthermore, the LASSO method yields an easily interpretable model as the stepwise method does, in contrast to the less intuitive BMA method. Conclusions: The commonly used stepwise selection method, which is simple to execute, may be insufficient for NTCP modeling. The LASSO method is recommended.

  6. MO-D-BRF-01: Pediatric Treatment Planning II: The PENTEC Report On Normal Tissue Complications

    International Nuclear Information System (INIS)

    Constine, L; Hodgson, D; Bentzen, S

    2014-01-01

    With advances in multimodality therapy, childhood cancer cure rates approach 80%. However, both radiotherapy and chemotherapy may cause debilitating or even fatal ‘late effects’ that are critical to understand, mitigate, or prevent. QUANTEC identified the uncertainties relating to side-effects of adult treatments, but this is more complicated for children in whom a mosaic of tissues develops at different rates and temporal sequences. Childhood cancer survivors have long life expectancy and may develop treatmentinduced secondary cancers and severe organ/tissue injury decades after treatment. Collaborative long-term observational studies and clinical research programs for survivors of pediatric and adolescent cancer provide some dose-response data for follow-up periods exceeding 40 years. Data analysis is challenging due to the influence of both therapeutic and developmental variables. PENTEC is a group of radiation oncologists, pediatric oncologists, subsepcialty physicians, medical physicists, biomathematic modelers/statisticians, and epidemiologists charged with conducting a critical synthesis of existing literature aiming to: critically analyze radiation dose-volume effects on normal tissue tolerances as a function of age/development in pediatric cancer patients in order to inform treatment planning and improve outcomes for survivors; describe relevant physics issues specific to pediatric radiotherapy; propose dose-volumeoutcome reporting standards to improve the knowledge base to inform future treatment guidelines. PENTEC has developed guidelines for systematic literature reviews, data extraction tolls and data analysis. This education session will discuss:1. Special considerations for normal tissue radiation response of children/adolescents, e.g. the interplay between development and radiotherapy effects.2. Epidemiology of organ/tissue injuries and secondary cancers.3. Exploration of dose-response differences between children and adults4. Methodology for

  7. MO-D-BRF-01: Pediatric Treatment Planning II: The PENTEC Report On Normal Tissue Complications

    Energy Technology Data Exchange (ETDEWEB)

    Constine, L; Hodgson, D; Bentzen, S [University of Maryland, Baltimore, MD (United States)

    2014-06-15

    With advances in multimodality therapy, childhood cancer cure rates approach 80%. However, both radiotherapy and chemotherapy may cause debilitating or even fatal ‘late effects’ that are critical to understand, mitigate, or prevent. QUANTEC identified the uncertainties relating to side-effects of adult treatments, but this is more complicated for children in whom a mosaic of tissues develops at different rates and temporal sequences. Childhood cancer survivors have long life expectancy and may develop treatmentinduced secondary cancers and severe organ/tissue injury decades after treatment. Collaborative long-term observational studies and clinical research programs for survivors of pediatric and adolescent cancer provide some dose-response data for follow-up periods exceeding 40 years. Data analysis is challenging due to the influence of both therapeutic and developmental variables. PENTEC is a group of radiation oncologists, pediatric oncologists, subsepcialty physicians, medical physicists, biomathematic modelers/statisticians, and epidemiologists charged with conducting a critical synthesis of existing literature aiming to: critically analyze radiation dose-volume effects on normal tissue tolerances as a function of age/development in pediatric cancer patients in order to inform treatment planning and improve outcomes for survivors; describe relevant physics issues specific to pediatric radiotherapy; propose dose-volumeoutcome reporting standards to improve the knowledge base to inform future treatment guidelines. PENTEC has developed guidelines for systematic literature reviews, data extraction tolls and data analysis. This education session will discuss:1. Special considerations for normal tissue radiation response of children/adolescents, e.g. the interplay between development and radiotherapy effects.2. Epidemiology of organ/tissue injuries and secondary cancers.3. Exploration of dose-response differences between children and adults4. Methodology for

  8. Normal Tissue Complication Probability Modeling of Acute Hematologic Toxicity in Cervical Cancer Patients Treated With Chemoradiotherapy

    International Nuclear Information System (INIS)

    Rose, Brent S.; Aydogan, Bulent; Liang, Yun; Yeginer, Mete; Hasselle, Michael D.; Dandekar, Virag; Bafana, Rounak; Yashar, Catheryn M.; Mundt, Arno J.; Roeske, John C.; Mell, Loren K.

    2011-01-01

    Purpose: To test the hypothesis that increased pelvic bone marrow (BM) irradiation is associated with increased hematologic toxicity (HT) in cervical cancer patients undergoing chemoradiotherapy and to develop a normal tissue complication probability (NTCP) model for HT. Methods and Materials: We tested associations between hematologic nadirs during chemoradiotherapy and the volume of BM receiving ≥10 and 20 Gy (V 10 and V 20 ) using a previously developed linear regression model. The validation cohort consisted of 44 cervical cancer patients treated with concurrent cisplatin and pelvic radiotherapy. Subsequently, these data were pooled with data from 37 identically treated patients from a previous study, forming a cohort of 81 patients for normal tissue complication probability analysis. Generalized linear modeling was used to test associations between hematologic nadirs and dosimetric parameters, adjusting for body mass index. Receiver operating characteristic curves were used to derive optimal dosimetric planning constraints. Results: In the validation cohort, significant negative correlations were observed between white blood cell count nadir and V 10 (regression coefficient (β) = -0.060, p = 0.009) and V 20 (β = -0.044, p = 0.010). In the combined cohort, the (adjusted) β estimates for log (white blood cell) vs. V 10 and V 20 were as follows: -0.022 (p = 0.025) and -0.021 (p = 0.002), respectively. Patients with V 10 ≥ 95% were more likely to experience Grade ≥3 leukopenia (68.8% vs. 24.6%, p 20 > 76% (57.7% vs. 21.8%, p = 0.001). Conclusions: These findings support the hypothesis that HT increases with increasing pelvic BM volume irradiated. Efforts to maintain V 10 20 < 76% may reduce HT.

  9. The Benefits of Including Clinical Factors in Rectal Normal Tissue Complication Probability Modeling After Radiotherapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Defraene, Gilles; Van den Bergh, Laura; Al-Mamgani, Abrahim; Haustermans, Karin; Heemsbergen, Wilma; Van den Heuvel, Frank; Lebesque, Joos V.

    2012-01-01

    Purpose: To study the impact of clinical predisposing factors on rectal normal tissue complication probability modeling using the updated results of the Dutch prostate dose-escalation trial. Methods and Materials: Toxicity data of 512 patients (conformally treated to 68 Gy [n = 284] and 78 Gy [n = 228]) with complete follow-up at 3 years after radiotherapy were studied. Scored end points were rectal bleeding, high stool frequency, and fecal incontinence. Two traditional dose-based models (Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) and a logistic model were fitted using a maximum likelihood approach. Furthermore, these model fits were improved by including the most significant clinical factors. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminating ability of all fits. Results: Including clinical factors significantly increased the predictive power of the models for all end points. In the optimal LKB, RS, and logistic models for rectal bleeding and fecal incontinence, the first significant (p = 0.011–0.013) clinical factor was “previous abdominal surgery.” As second significant (p = 0.012–0.016) factor, “cardiac history” was included in all three rectal bleeding fits, whereas including “diabetes” was significant (p = 0.039–0.048) in fecal incontinence modeling but only in the LKB and logistic models. High stool frequency fits only benefitted significantly (p = 0.003–0.006) from the inclusion of the baseline toxicity score. For all models rectal bleeding fits had the highest AUC (0.77) where it was 0.63 and 0.68 for high stool frequency and fecal incontinence, respectively. LKB and logistic model fits resulted in similar values for the volume parameter. The steepness parameter was somewhat higher in the logistic model, also resulting in a slightly lower D 50 . Anal wall DVHs were used for fecal incontinence, whereas anorectal wall dose best described the other two endpoints. Conclusions

  10. The Benefits of Including Clinical Factors in Rectal Normal Tissue Complication Probability Modeling After Radiotherapy for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Defraene, Gilles, E-mail: gilles.defraene@uzleuven.be [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Van den Bergh, Laura [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Al-Mamgani, Abrahim [Department of Radiation Oncology, Erasmus Medical Center - Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Haustermans, Karin [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Heemsbergen, Wilma [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Van den Heuvel, Frank [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Lebesque, Joos V. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)

    2012-03-01

    Purpose: To study the impact of clinical predisposing factors on rectal normal tissue complication probability modeling using the updated results of the Dutch prostate dose-escalation trial. Methods and Materials: Toxicity data of 512 patients (conformally treated to 68 Gy [n = 284] and 78 Gy [n = 228]) with complete follow-up at 3 years after radiotherapy were studied. Scored end points were rectal bleeding, high stool frequency, and fecal incontinence. Two traditional dose-based models (Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) and a logistic model were fitted using a maximum likelihood approach. Furthermore, these model fits were improved by including the most significant clinical factors. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminating ability of all fits. Results: Including clinical factors significantly increased the predictive power of the models for all end points. In the optimal LKB, RS, and logistic models for rectal bleeding and fecal incontinence, the first significant (p = 0.011-0.013) clinical factor was 'previous abdominal surgery.' As second significant (p = 0.012-0.016) factor, 'cardiac history' was included in all three rectal bleeding fits, whereas including 'diabetes' was significant (p = 0.039-0.048) in fecal incontinence modeling but only in the LKB and logistic models. High stool frequency fits only benefitted significantly (p = 0.003-0.006) from the inclusion of the baseline toxicity score. For all models rectal bleeding fits had the highest AUC (0.77) where it was 0.63 and 0.68 for high stool frequency and fecal incontinence, respectively. LKB and logistic model fits resulted in similar values for the volume parameter. The steepness parameter was somewhat higher in the logistic model, also resulting in a slightly lower D{sub 50}. Anal wall DVHs were used for fecal incontinence, whereas anorectal wall dose best described the other two endpoints

  11. Method for Automatic Selection of Parameters in Normal Tissue Complication Probability Modeling.

    Science.gov (United States)

    Christophides, Damianos; Appelt, Ane L; Gusnanto, Arief; Lilley, John; Sebag-Montefiore, David

    2018-07-01

    To present a fully automatic method to generate multiparameter normal tissue complication probability (NTCP) models and compare its results with those of a published model, using the same patient cohort. Data were analyzed from 345 rectal cancer patients treated with external radiation therapy to predict the risk of patients developing grade 1 or ≥2 cystitis. In total, 23 clinical factors were included in the analysis as candidate predictors of cystitis. Principal component analysis was used to decompose the bladder dose-volume histogram into 8 principal components, explaining more than 95% of the variance. The data set of clinical factors and principal components was divided into training (70%) and test (30%) data sets, with the training data set used by the algorithm to compute an NTCP model. The first step of the algorithm was to obtain a bootstrap sample, followed by multicollinearity reduction using the variance inflation factor and genetic algorithm optimization to determine an ordinal logistic regression model that minimizes the Bayesian information criterion. The process was repeated 100 times, and the model with the minimum Bayesian information criterion was recorded on each iteration. The most frequent model was selected as the final "automatically generated model" (AGM). The published model and AGM were fitted on the training data sets, and the risk of cystitis was calculated. The 2 models had no significant differences in predictive performance, both for the training and test data sets (P value > .05) and found similar clinical and dosimetric factors as predictors. Both models exhibited good explanatory performance on the training data set (P values > .44), which was reduced on the test data sets (P values < .05). The predictive value of the AGM is equivalent to that of the expert-derived published model. It demonstrates potential in saving time, tackling problems with a large number of parameters, and standardizing variable selection in NTCP

  12. Multivariate Normal Tissue Complication Probability Modeling of Heart Valve Dysfunction in Hodgkin Lymphoma Survivors

    International Nuclear Information System (INIS)

    Cella, Laura; Liuzzi, Raffaele; Conson, Manuel; D’Avino, Vittoria; Salvatore, Marco; Pacelli, Roberto

    2013-01-01

    Purpose: To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced asymptomatic heart valvular defects (RVD). Methods and Materials: Fifty-six patients treated with sequential chemoradiation therapy for Hodgkin lymphoma (HL) were retrospectively reviewed for RVD events. Clinical information along with whole heart, cardiac chambers, and lung dose distribution parameters was collected, and the correlations to RVD were analyzed by means of Spearman's rank correlation coefficient (Rs). For the selection of the model order and parameters for NTCP modeling, a multivariate logistic regression method using resampling techniques (bootstrapping) was applied. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Results: When we analyzed the whole heart, a 3-variable NTCP model including the maximum dose, whole heart volume, and lung volume was shown to be the optimal predictive model for RVD (Rs = 0.573, P<.001, AUC = 0.83). When we analyzed the cardiac chambers individually, for the left atrium and for the left ventricle, an NTCP model based on 3 variables including the percentage volume exceeding 30 Gy (V30), cardiac chamber volume, and lung volume was selected as the most predictive model (Rs = 0.539, P<.001, AUC = 0.83; and Rs = 0.557, P<.001, AUC = 0.82, respectively). The NTCP values increase as heart maximum dose or cardiac chambers V30 increase. They also increase with larger volumes of the heart or cardiac chambers and decrease when lung volume is larger. Conclusions: We propose logistic NTCP models for RVD considering not only heart irradiation dose but also the combined effects of lung and heart volumes. Our study establishes the statistical evidence of the indirect effect of lung size on radio-induced heart toxicity

  13. Impact of Chemotherapy on Normal Tissue Complication Probability Models of Acute Hematologic Toxicity in Patients Receiving Pelvic Intensity Modulated Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Bazan, Jose G.; Luxton, Gary; Kozak, Margaret M.; Anderson, Eric M.; Hancock, Steven L.; Kapp, Daniel S.; Kidd, Elizabeth A.; Koong, Albert C.; Chang, Daniel T., E-mail: dtchang@stanford.edu

    2013-12-01

    Purpose: To determine how chemotherapy agents affect radiation dose parameters that correlate with acute hematologic toxicity (HT) in patients treated with pelvic intensity modulated radiation therapy (P-IMRT) and concurrent chemotherapy. Methods and Materials: We assessed HT in 141 patients who received P-IMRT for anal, gynecologic, rectal, or prostate cancers, 95 of whom received concurrent chemotherapy. Patients were separated into 4 groups: mitomycin (MMC) + 5-fluorouracil (5FU, 37 of 141), platinum ± 5FU (Cis, 32 of 141), 5FU (26 of 141), and P-IMRT alone (46 of 141). The pelvic bone was contoured as a surrogate for pelvic bone marrow (PBM) and divided into subsites: ilium, lower pelvis, and lumbosacral spine (LSS). The volumes of each region receiving 5-40 Gy were calculated. The endpoint for HT was grade ≥3 (HT3+) leukopenia, neutropenia or thrombocytopenia. Normal tissue complication probability was calculated using the Lyman-Kutcher-Burman model. Logistic regression was used to analyze association between HT3+ and dosimetric parameters. Results: Twenty-six patients experienced HT3+: 10 of 37 (27%) MMC, 14 of 32 (44%) Cis, 2 of 26 (8%) 5FU, and 0 of 46 P-IMRT. PBM dosimetric parameters were correlated with HT3+ in the MMC group but not in the Cis group. LSS dosimetric parameters were well correlated with HT3+ in both the MMC and Cis groups. Constrained optimization (0Lyman-Kutcher-Burman model resulted in n=1, m = 0.11, TD{sub 50} = 31 Gy for LSS in the MMC group and n=1, m = 0.27, TD{sub 50} = 35 Gy for LSS in the Cis group. Conclusions: The incidence of HT3+ depends on type of chemotherapy received. Patients receiving P-IMRT ± 5FU have better bone marrow tolerance than those receiving irradiation concurrent with either Cis or MMC. Treatment with MMC has a lower TD{sub 50} and more steeply rising normal tissue complication probability curve compared with treatment with Cis. Dose tolerance of PBM and the LSS subsite may be lower for

  14. The effect of customized beam shaping on normal tissue complications in radiation therapy of parotid gland tumors

    International Nuclear Information System (INIS)

    Keus, R.; Boer, R. de; Lebesque, J.; Noach, P.

    1991-01-01

    The impact of customized beam shaping was studied for 5 patients with parotid tumors treated with a paired wedged field technique. For each patient 2 plans were generated. The standard plan had unblocked portals with field sizes defined by the largest target contour found in any CT slice. In the 2nd plan customized beam's view (BEV) designed blocks were added to both beams. The differences in those distributions between the 2 types of plans were evaluated using dose-volume histograms (DVH). As expected, the dose distribution within the target volume showed no difference. However, a considerable sparing of normal tissue was observed for the plans with customized blocks. The volume of un-necessary exposed normal tissue that received more than 90 percent of the prescribed dose, was reduced by a factor of about 4: from 165 to 44 percent on an average, if the volume is expressed as a percentage of the target volume in each patient. In particular, the homolateral mandible showed a mean decrease of 21 percent of integral dose when blocks were used. Normal tissue complication probabilities (NTCP) were calculated. For a tumor dose of 70 Gy, the average bone necrosis probability was reduced from 8.4 percent (no blocks) to 4.1. percent (blocks). For other normal tissues such as nervous tissue, other soft tissues and bones a substantial reduction of integral dose was found for al patients when individual blocks were used. (author). 10 refs.; 4 figs.; 2 tabs

  15. Normal tissue complications after radiation therapy Las complicaciones de la radioterapia en los tejidos sanos

    Directory of Open Access Journals (Sweden)

    Jolyon H. Hendry

    2006-09-01

    Full Text Available This paper describes the biological mechanisms of normal tissue reactions after radiation therapy, with reference to conventional treatments, new treatments, and treatments in developing countries. It also describes biological reasons for the latency period before tissue complications arise, the relationship of dose to incidence, the effect of increasing the size of the irradiated volume, early and late tissue reactions, effects of changes in dose fractionation and dose rate, and combined chemotherapy and radiotherapy responses. Examples are given of increases in knowledge of clinical radiobiology from trials of new protocols. Potential modification to treatments include the use of biological response modifiers. The introduction of "response prediction" modifications to treatments might also be available in the near future. Finally, the paper points out that in some radiotherapy centers, the biologically-effective doses prescribed for combined brachytherapy and teletherapy treatment of cervix cancer are lower than those prescribed in other centers. This issue needs to be addressed further. The wealth of preclinical and clinical data has led to a much greater understanding of the biological basis to radiotherapy. This understanding has underpinned a variety of new approaches in radiotherapy, including both physical and biological strategies. There is also the important issue of treatment of a large number of cancers in developing countries, for which efficacious resource-sparing protocols are being continuously developed. A unified scoring system should be widely accepted as the new standard in reporting the adverse effects of radiation therapy. Likewise, late toxicity should be reported on an actuarial basis as a mandatory endpoint.En este artículo se describen los mecanismos biológicos que intervienen en las reacciones provocadas por la radioterapia, tanto con tratamientos convencionales como con los más nuevos, y los aplicados en países en

  16. A new plan-scoring method using normal tissue complication probability for personalized treatment plan decisions in prostate cancer

    Science.gov (United States)

    Kim, Kwang Hyeon; Lee, Suk; Shim, Jang Bo; Yang, Dae Sik; Yoon, Won Sup; Park, Young Je; Kim, Chul Yong; Cao, Yuan Jie; Chang, Kyung Hwan

    2018-01-01

    The aim of this study was to derive a new plan-scoring index using normal tissue complication probabilities to verify different plans in the selection of personalized treatment. Plans for 12 patients treated with tomotherapy were used to compare scoring for ranking. Dosimetric and biological indexes were analyzed for the plans for a clearly distinguishable group ( n = 7) and a similar group ( n = 12), using treatment plan verification software that we developed. The quality factor ( QF) of our support software for treatment decisions was consistent with the final treatment plan for the clearly distinguishable group (average QF = 1.202, 100% match rate, n = 7) and the similar group (average QF = 1.058, 33% match rate, n = 12). Therefore, we propose a normal tissue complication probability (NTCP) based on the plan scoring index for verification of different plans for personalized treatment-plan selection. Scoring using the new QF showed a 100% match rate (average NTCP QF = 1.0420). The NTCP-based new QF scoring method was adequate for obtaining biological verification quality and organ risk saving using the treatment-planning decision-support software we developed for prostate cancer.

  17. Normal tissue complication probability modeling for cochlea constraints to avoid causing tinnitus after head-and-neck intensity-modulated radiation therapy

    International Nuclear Information System (INIS)

    Lee, Tsair-Fwu; Yeh, Shyh-An; Chao, Pei-Ju; Chang, Liyun; Chiu, Chien-Liang; Ting, Hui-Min; Wang, Hung-Yu; Huang, Yu-Jie

    2015-01-01

    Radiation-induced tinnitus is a side effect of radiotherapy in the inner ear for cancers of the head and neck. Effective dose constraints for protecting the cochlea are under-reported. The aim of this study is to determine the cochlea dose limitation to avoid causing tinnitus after head-and-neck cancer (HNC) intensity-modulated radiation therapy (IMRT). In total 211 patients with HNC were included; the side effects of radiotherapy were investigated for 422 inner ears in the cohort. Forty-nine of the four hundred and twenty-two samples (11.6 %) developed grade 2+ tinnitus symptoms after IMRT, as diagnosed by a clinician. The Late Effects of Normal Tissues–Subjective, Objective, Management, Analytic (LENT-SOMA) criteria were used for tinnitus evaluation. The logistic and Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) models were used for the analyses. The NTCP-fitted parameters were TD 50 = 46.31 Gy (95 % CI, 41.46–52.50), γ 50 = 1.27 (95 % CI, 1.02–1.55), and TD 50 = 46.52 Gy (95 % CI, 41.91–53.43), m = 0.35 (95 % CI, 0.30–0.42) for the logistic and LKB models, respectively. The suggested guideline TD 20 for the tolerance dose to produce a 20 % complication rate within a specific period of time was TD 20 = 33.62 Gy (95 % CI, 30.15–38.27) (logistic) and TD 20 = 32.82 Gy (95 % CI, 29.58–37.69) (LKB). To maintain the incidence of grade 2+ tinnitus toxicity <20 % in IMRT, we suggest that the mean dose to the cochlea should be <32 Gy. However, models should not be extrapolated to other patient populations without further verification and should first be confirmed before clinical implementation

  18. Normal tissue complication models for clinically relevant acute esophagitis (≥ grade 2) in patients treated with dose differentiated accelerated radiotherapy (DART-bid)

    International Nuclear Information System (INIS)

    Zehentmayr, Franz; Söhn, Matthias; Exeli, Ann-Katrin; Wurstbauer, Karl; Tröller, Almut; Deutschmann, Heinz; Fastner, Gerd; Fussl, Christoph; Steininger, Philipp; Kranzinger, Manfred; Belka, Claus; Studnicka, Michael; Sedlmayer, Felix

    2015-01-01

    One of the primary dose-limiting toxicities during thoracic irradiation is acute esophagitis (AE). The aim of this study is to investigate dosimetric and clinical predictors for AE grade ≥ 2 in patients treated with accelerated radiotherapy for locally advanced non-small cell lung cancer (NSCLC). 66 NSCLC patients were included in the present analysis: 4 stage II, 44 stage IIIA and 18 stage IIIB. All patients received induction chemotherapy followed by dose differentiated accelerated radiotherapy (DART-bid). Depending on size (mean of three perpendicular diameters) tumors were binned in four dose groups: <2.5 cm 73.8 Gy, 2.5–4.5 cm 79.2 Gy, 4.5–6 cm 84.6 Gy, >6 cm 90 Gy. Patients were treated in 3D target splitting technique. In order to estimate the normal tissue complication probability (NTCP), two Lyman models and the cutoff-logistic regression model were fitted to the data with AE ≥ grade 2 as statistical endpoint. Inter-model comparison was performed with the corrected Akaike information criterion (AIC c ), which calculates the model’s quality of fit (likelihood value) in relation to its complexity (i.e. number of variables in the model) corrected by the number of patients in the dataset. Toxicity was documented prospectively according to RTOG. The median follow up was 686 days (range 84–2921 days), 23/66 patients (35 %) experienced AE ≥ grade 2. The actuarial local control rates were 72.6 % and 59.4 % at 2 and 3 years, regional control was 91 % at both time points. The Lyman-MED model (D50 = 32.8 Gy, m = 0.48) and the cutoff dose model (D c = 38 Gy) provide the most efficient fit to the current dataset. On multivariate analysis V38 (volume of the esophagus that receives 38 Gy or above, 95 %-CI 28.2–57.3) was the most significant predictor of AE ≥ grade 2 (HR = 1.05, CI 1.01–1.09, p = 0.007). Following high-dose accelerated radiotherapy the rate of AE ≥ grade 2 is slightly lower than reported for concomitant radio-chemotherapy with the

  19. Calculation of normal tissue complication probability and dose-volume histogram reduction schemes for tissues with a critical element architecture

    International Nuclear Information System (INIS)

    Niemierko, Andrzej; Goitein, Michael

    1991-01-01

    The authors investigate a model of normal tissue complication probability for tissues that may be represented by a critical element architecture. They derive formulas for complication probability that apply to both a partial volume irradiation and to an arbitrary inhomogeneous dose distribution. The dose-volume isoeffect relationship which is a consequence of a critical element architecture is discussed and compared to the empirical power law relationship. A dose-volume histogram reduction scheme for a 'pure' critical element model is derived. In addition, a point-based algorithm which does not require precomputation of a dose-volume histogram is derived. The existing published dose-volume histogram reduction algorithms are analyzed. The authors show that the existing algorithms, developed empirically without an explicit biophysical model, have a close relationship to the critical element model at low levels of complication probability. However, it is also showed that they have aspects which are not compatible with a critical element model and the authors propose a modification to one of them to circumvent its restriction to low complication probabilities. (author). 26 refs.; 7 figs

  20. Hypothyroidism after primary radiotherapy for head and neck squamous cell carcinoma: Normal tissue complication probability modeling with latent time correction

    International Nuclear Information System (INIS)

    Rønjom, Marianne Feen; Brink, Carsten; Bentzen, Søren M.; Hegedüs, Laszlo; Overgaard, Jens; Johansen, Jørgen

    2013-01-01

    Background and purpose: To develop a normal tissue complication probability (NTCP) model of radiation-induced biochemical hypothyroidism (HT) after primary radiotherapy for head and neck squamous cell carcinoma (HNSCC) with adjustment for latency and clinical risk factors. Patients and methods: Patients with HNSCC receiving definitive radiotherapy with 66–68 Gy without surgery were followed up with serial post-treatment thyrotropin (TSH) assessment. HT was defined as TSH >4.0 mU/l. Data were analyzed with both a logistic and a mixture model (correcting for latency) to determine risk factors for HT and develop an NTCP model based on mean thyroid dose (MTD) and thyroid volume. Results: 203 patients were included. Median follow-up: 25.1 months. Five-year estimated risk of HT was 25.6%. In the mixture model, the only independent risk factors for HT were thyroid volume (cm 3 ) (OR = 0.75 [95% CI: 0.64–0.85], p 3 , respectively. Conclusions: Comparing the logistic and mixture models demonstrates the importance of latent-time correction in NTCP-modeling. Thyroid dose constraints in treatment planning should be individualized based on thyroid volume

  1. Normal tissue complication probability: Does simultaneous integrated boost intensity-modulated radiotherapy score over other techniques in treatment of prostate adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Jothy Basu K

    2009-01-01

    Full Text Available Aim: The main objective of this study was to analyze the radiobiological effect of different treatment strategies on high-risk prostate adenocarcinoma. Materials and Methods: Ten cases of high-risk prostate adenocarcinoma were selected for this dosimetric study. Four different treatment strategies used for treating prostate cancer were compared. Conventional four-field box technique covering prostate and nodal volumes followed by three-field conformal boost (3D + 3DCRT, four-field box technique followed by intensity-modulated radiotherapy (IMRT boost (3D + IMRT, IMRT followed by IMRT boost (IMRT + IMRT, and simultaneous integrated boost IMRT (SIBIMRT were compared in terms of tumor control probability (TCP and normal tissue complication probability (NTCP. The dose prescription except for SIBIMRT was 45 Gy in 25 fractions for the prostate and nodal volumes in the initial phase and 27 Gy in 15 fractions for the prostate in the boost phase. For SIBIMRT, equivalent doses were calculated using biologically equivalent dose assuming the α/β ratio of 1.5 Gy with a dose prescription of 60.75 Gy for the gross tumor volume (GTV and 45 Gy for the clinical target volume in 25 fractions. IMRT plans were made with 15-MV equispaced seven coplanar fields. NTCP was calculated using the Lyman-Kutcher-Burman (LKB model. Results: An NTCP of 10.7 ± 0.99%, 8.36 ± 0.66%, 6.72 ± 0.85%, and 1.45 ± 0.11% for the bladder and 14.9 ± 0.99%, 14.04 ± 0.66%, 11.38 ± 0.85%, 5.12 ± 0.11% for the rectum was seen with 3D + 3DCRT, 3D + IMRT, IMRT + IMRT, and SIBIMRT respectively. Conclusions: SIBIMRT had the least NTCP over all other strategies with a reduced treatment time (3 weeks less. It should be the technique of choice for dose escalation in prostate carcinoma.

  2. Multivariate normal tissue complication probability modeling of gastrointestinal toxicity after external beam radiotherapy for localized prostate cancer

    International Nuclear Information System (INIS)

    Cella, Laura; D’Avino, Vittoria; Liuzzi, Raffaele; Conson, Manuel; Doria, Francesca; Faiella, Adriana; Loffredo, Filomena; Salvatore, Marco; Pacelli, Roberto

    2013-01-01

    The risk of radio-induced gastrointestinal (GI) complications is affected by several factors other than the dose to the rectum such as patient characteristics, hormonal or antihypertensive therapy, and acute rectal toxicity. Purpose of this work is to study clinical and dosimetric parameters impacting on late GI toxicity after prostate external beam radiotherapy (RT) and to establish multivariate normal tissue complication probability (NTCP) model for radiation-induced GI complications. A total of 57 men who had undergone definitive RT for prostate cancer were evaluated for GI events classified using the RTOG/EORTC scoring system. Their median age was 73 years (range 53–85). The patients were assessed for GI toxicity before, during, and periodically after RT completion. Several clinical variables along with rectum dose-volume parameters (Vx) were collected and their correlation to GI toxicity was analyzed by Spearman’s rank correlation coefficient (Rs). Multivariate logistic regression method using resampling techniques was applied to select model order and parameters for NTCP modeling. Model performance was evaluated through the area under the receiver operating characteristic curve (AUC). At a median follow-up of 30 months, 37% (21/57) patients developed G1-2 acute GI events while 33% (19/57) were diagnosed with G1-2 late GI events. An NTCP model for late mild/moderate GI toxicity based on three variables including V65 (OR = 1.03), antihypertensive and/or anticoagulant (AH/AC) drugs (OR = 0.24), and acute GI toxicity (OR = 4.3) was selected as the most predictive model (Rs = 0.47, p < 0.001; AUC = 0.79). This three-variable model outperforms the logistic model based on V65 only (Rs = 0.28, p < 0.001; AUC = 0.69). We propose a logistic NTCP model for late GI toxicity considering not only rectal irradiation dose but also clinical patient-specific factors. Accordingly, the risk of G1-2 late GI increases as V65 increases, it is higher for patients experiencing

  3. Design and Selection of Machine Learning Methods Using Radiomics and Dosiomics for Normal Tissue Complication Probability Modeling of Xerostomia.

    Science.gov (United States)

    Gabryś, Hubert S; Buettner, Florian; Sterzing, Florian; Hauswald, Henrik; Bangert, Mark

    2018-01-01

    The purpose of this study is to investigate whether machine learning with dosiomic, radiomic, and demographic features allows for xerostomia risk assessment more precise than normal tissue complication probability (NTCP) models based on the mean radiation dose to parotid glands. A cohort of 153 head-and-neck cancer patients was used to model xerostomia at 0-6 months (early), 6-15 months (late), 15-24 months (long-term), and at any time (a longitudinal model) after radiotherapy. Predictive power of the features was evaluated by the area under the receiver operating characteristic curve (AUC) of univariate logistic regression models. The multivariate NTCP models were tuned and tested with single and nested cross-validation, respectively. We compared predictive performance of seven classification algorithms, six feature selection methods, and ten data cleaning/class balancing techniques using the Friedman test and the Nemenyi post hoc analysis. NTCP models based on the parotid mean dose failed to predict xerostomia (AUCs  0.85), dose gradients in the right-left (AUCs > 0.78), and the anterior-posterior (AUCs > 0.72) direction. Multivariate models of long-term xerostomia were typically based on the parotid volume, the parotid eccentricity, and the dose-volume histogram (DVH) spread with the generalization AUCs ranging from 0.74 to 0.88. On average, support vector machines and extra-trees were the top performing classifiers, whereas the algorithms based on logistic regression were the best choice for feature selection. We found no advantage in using data cleaning or class balancing methods. We demonstrated that incorporation of organ- and dose-shape descriptors is beneficial for xerostomia prediction in highly conformal radiotherapy treatments. Due to strong reliance on patient-specific, dose-independent factors, our results underscore the need for development of personalized data-driven risk profiles for NTCP models of xerostomia. The facilitated

  4. Methods for Reducing Normal Tissue Complication Probabilities in Oropharyngeal Cancer: Dose Reduction or Planning Target Volume Elimination

    Energy Technology Data Exchange (ETDEWEB)

    Samuels, Stuart E.; Eisbruch, Avraham; Vineberg, Karen; Lee, Jae; Lee, Choonik; Matuszak, Martha M.; Ten Haken, Randall K.; Brock, Kristy K., E-mail: kbrock@med.umich.edu

    2016-11-01

    Purpose: Strategies to reduce the toxicities of head and neck radiation (ie, dysphagia [difficulty swallowing] and xerostomia [dry mouth]) are currently underway. However, the predicted benefit of dose and planning target volume (PTV) reduction strategies is unknown. The purpose of the present study was to compare the normal tissue complication probabilities (NTCP) for swallowing and salivary structures in standard plans (70 Gy [P70]), dose-reduced plans (60 Gy [P60]), and plans eliminating the PTV margin. Methods and Materials: A total of 38 oropharyngeal cancer (OPC) plans were analyzed. Standard organ-sparing volumetric modulated arc therapy plans (P70) were created and then modified by eliminating the PTVs and treating the clinical tumor volumes (CTVs) only (C70) or maintaining the PTV but reducing the dose to 60 Gy (P60). NTCP dose models for the pharyngeal constrictors, glottis/supraglottic larynx, parotid glands (PGs), and submandibular glands (SMGs) were analyzed. The minimal clinically important benefit was defined as a mean change in NTCP of >5%. The P70 NTCP thresholds and overlap percentages of the organs at risk with the PTVs (56-59 Gy, vPTV{sub 56}) were evaluated to identify the predictors for NTCP improvement. Results: With the P60 plans, only the ipsilateral PG (iPG) benefited (23.9% vs 16.2%; P<.01). With the C70 plans, only the iPG (23.9% vs 17.5%; P<.01) and contralateral SMG (cSMG) (NTCP 32.1% vs 22.9%; P<.01) benefited. An iPG NTCP threshold of 20% and 30% predicted NTCP benefits for the P60 and C70 plans, respectively (P<.001). A cSMG NTCP threshold of 30% predicted for an NTCP benefit with the C70 plans (P<.001). Furthermore, for the iPG, a vPTV{sub 56} >13% predicted benefit with P60 (P<.001) and C70 (P=.002). For the cSMG, a vPTV{sub 56} >22% predicted benefit with C70 (P<.01). Conclusions: PTV elimination and dose-reduction lowered the NTCP of the iPG, and PTV elimination lowered the NTCP of the cSMG. NTCP thresholds and the

  5. Design and Selection of Machine Learning Methods Using Radiomics and Dosiomics for Normal Tissue Complication Probability Modeling of Xerostomia

    Directory of Open Access Journals (Sweden)

    Hubert S. Gabryś

    2018-03-01

    Full Text Available PurposeThe purpose of this study is to investigate whether machine learning with dosiomic, radiomic, and demographic features allows for xerostomia risk assessment more precise than normal tissue complication probability (NTCP models based on the mean radiation dose to parotid glands.Material and methodsA cohort of 153 head-and-neck cancer patients was used to model xerostomia at 0–6 months (early, 6–15 months (late, 15–24 months (long-term, and at any time (a longitudinal model after radiotherapy. Predictive power of the features was evaluated by the area under the receiver operating characteristic curve (AUC of univariate logistic regression models. The multivariate NTCP models were tuned and tested with single and nested cross-validation, respectively. We compared predictive performance of seven classification algorithms, six feature selection methods, and ten data cleaning/class balancing techniques using the Friedman test and the Nemenyi post hoc analysis.ResultsNTCP models based on the parotid mean dose failed to predict xerostomia (AUCs < 0.60. The most informative predictors were found for late and long-term xerostomia. Late xerostomia correlated with the contralateral dose gradient in the anterior–posterior (AUC = 0.72 and the right–left (AUC = 0.68 direction, whereas long-term xerostomia was associated with parotid volumes (AUCs > 0.85, dose gradients in the right–left (AUCs > 0.78, and the anterior–posterior (AUCs > 0.72 direction. Multivariate models of long-term xerostomia were typically based on the parotid volume, the parotid eccentricity, and the dose–volume histogram (DVH spread with the generalization AUCs ranging from 0.74 to 0.88. On average, support vector machines and extra-trees were the top performing classifiers, whereas the algorithms based on logistic regression were the best choice for feature selection. We found no advantage in using data cleaning or class balancing

  6. Incidence of late rectal bleeding in high-dose conformal radiotherapy of prostate cancer using equivalent uniform dose-based and dose-volume-based normal tissue complication probability models

    International Nuclear Information System (INIS)

    Soehn, Matthias; Yan Di; Liang Jian; Meldolesi, Elisa; Vargas, Carlos; Alber, Markus

    2007-01-01

    Purpose: Accurate modeling of rectal complications based on dose-volume histogram (DVH) data are necessary to allow safe dose escalation in radiotherapy of prostate cancer. We applied different equivalent uniform dose (EUD)-based and dose-volume-based normal tissue complication probability (NTCP) models to rectal wall DVHs and follow-up data for 319 prostate cancer patients to identify the dosimetric factors most predictive for Grade ≥ 2 rectal bleeding. Methods and Materials: Data for 319 patients treated at the William Beaumont Hospital with three-dimensional conformal radiotherapy (3D-CRT) under an adaptive radiotherapy protocol were used for this study. The following models were considered: (1) Lyman model and (2) logit-formula with DVH reduced to generalized EUD (3) serial reconstruction unit (RU) model (4) Poisson-EUD model, and (5) mean dose- and (6) cutoff dose-logistic regression model. The parameters and their confidence intervals were determined using maximum likelihood estimation. Results: Of the patients, 51 (16.0%) showed Grade 2 or higher bleeding. As assessed qualitatively and quantitatively, the Lyman- and Logit-EUD, serial RU, and Poisson-EUD model fitted the data very well. Rectal wall mean dose did not correlate to Grade 2 or higher bleeding. For the cutoff dose model, the volume receiving > 73.7 Gy showed most significant correlation to bleeding. However, this model fitted the data more poorly than the EUD-based models. Conclusions: Our study clearly confirms a volume effect for late rectal bleeding. This can be described very well by the EUD-like models, of which the serial RU- and Poisson-EUD model can describe the data with only two parameters. Dose-volume-based cutoff-dose models performed worse

  7. Comparison of Dose Response Models for Predicting Normal Tissue Complications from Cancer Radiotherapy: Application in Rat Spinal Cord

    Energy Technology Data Exchange (ETDEWEB)

    Adamus-Górka, Magdalena; Mavroidis, Panayiotis, E-mail: panayiotis.mavroidis@ki.se; Lind, Bengt K.; Brahme, Anders [Department of Medical Radiation Physics, Karolinska Institutet and Stockholm University, Stockholm S-17176 (Sweden)

    2011-05-18

    Seven different radiobiological dose-response models have been compared with regard to their ability to describe experimental data. The first four models, namely the critical volume, the relative seriality, the inverse tumor and the critical element models are mainly based on cell survival biology. The other three models: the Lyman (Gaussian distribution), the parallel architecture and the Weibull distribution models are semi-empirical and rather based on statistical distributions. The maximum likelihood estimation was used to fit the models to experimental data and the χ{sup 2}-distribution, AIC criterion and F-test were applied to compare the goodness-of-fit of the models. The comparison was performed using experimental data for rat spinal cord injury. Both the shape of the dose-response curve and the ability of handling the volume dependence were separately compared for each model. All the models were found to be acceptable in describing the present experimental dataset (p > 0.05). For the white matter necrosis dataset, the Weibull and Lyman models were clearly superior to the other models, whereas for the vascular damage case, the Relative Seriality model seems to have the best performance although the Critical volume, Inverse tumor, Critical element and Parallel architecture models gave similar results. Although the differences between many of the investigated models are rather small, they still may be of importance in indicating the advantages and limitations of each particular model. It appears that most of the models have favorable properties for describing dose-response data, which indicates that they may be suitable to be used in biologically optimized intensity modulated radiation therapy planning, provided a proper estimation of their radiobiological parameters had been performed for every tissue and clinical endpoint.

  8. Comparison of Dose Response Models for Predicting Normal Tissue Complications from Cancer Radiotherapy: Application in Rat Spinal Cord

    International Nuclear Information System (INIS)

    Adamus-Górka, Magdalena; Mavroidis, Panayiotis; Lind, Bengt K.; Brahme, Anders

    2011-01-01

    Seven different radiobiological dose-response models have been compared with regard to their ability to describe experimental data. The first four models, namely the critical volume, the relative seriality, the inverse tumor and the critical element models are mainly based on cell survival biology. The other three models: the Lyman (Gaussian distribution), the parallel architecture and the Weibull distribution models are semi-empirical and rather based on statistical distributions. The maximum likelihood estimation was used to fit the models to experimental data and the χ 2 -distribution, AIC criterion and F-test were applied to compare the goodness-of-fit of the models. The comparison was performed using experimental data for rat spinal cord injury. Both the shape of the dose-response curve and the ability of handling the volume dependence were separately compared for each model. All the models were found to be acceptable in describing the present experimental dataset (p > 0.05). For the white matter necrosis dataset, the Weibull and Lyman models were clearly superior to the other models, whereas for the vascular damage case, the Relative Seriality model seems to have the best performance although the Critical volume, Inverse tumor, Critical element and Parallel architecture models gave similar results. Although the differences between many of the investigated models are rather small, they still may be of importance in indicating the advantages and limitations of each particular model. It appears that most of the models have favorable properties for describing dose-response data, which indicates that they may be suitable to be used in biologically optimized intensity modulated radiation therapy planning, provided a proper estimation of their radiobiological parameters had been performed for every tissue and clinical endpoint

  9. SU-E-T-630: Predictive Modeling of Mortality, Tumor Control, and Normal Tissue Complications After Stereotactic Body Radiotherapy for Stage I Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Lindsay, WD; Berlind, CG; Gee, JC; Simone, CB

    2015-01-01

    Purpose: While rates of local control have been well characterized after stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC), less data are available characterizing survival and normal tissue toxicities, and no validated models exist assessing these parameters after SBRT. We evaluate the reliability of various machine learning techniques when applied to radiation oncology datasets to create predictive models of mortality, tumor control, and normal tissue complications. Methods: A dataset of 204 consecutive patients with stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) at the University of Pennsylvania between 2009 and 2013 was used to create predictive models of tumor control, normal tissue complications, and mortality in this IRB-approved study. Nearly 200 data fields of detailed patient- and tumor-specific information, radiotherapy dosimetric measurements, and clinical outcomes data were collected. Predictive models were created for local tumor control, 1- and 3-year overall survival, and nodal failure using 60% of the data (leaving the remainder as a test set). After applying feature selection and dimensionality reduction, nonlinear support vector classification was applied to the resulting features. Models were evaluated for accuracy and area under ROC curve on the 81-patient test set. Results: Models for common events in the dataset (such as mortality at one year) had the highest predictive power (AUC = .67, p < 0.05). For rare occurrences such as radiation pneumonitis and local failure (each occurring in less than 10% of patients), too few events were present to create reliable models. Conclusion: Although this study demonstrates the validity of predictive analytics using information extracted from patient medical records and can most reliably predict for survival after SBRT, larger sample sizes are needed to develop predictive models for normal tissue toxicities and more advanced

  10. SU-E-T-630: Predictive Modeling of Mortality, Tumor Control, and Normal Tissue Complications After Stereotactic Body Radiotherapy for Stage I Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lindsay, WD [University of Pennsylvania, Philadelphia, PA (United States); Oncora Medical, LLC, Philadelphia, PA (United States); Berlind, CG [Georgia Institute of Technology, Atlanta, GA (Georgia); Oncora Medical, LLC, Philadelphia, PA (United States); Gee, JC; Simone, CB [University of Pennsylvania, Philadelphia, PA (United States)

    2015-06-15

    Purpose: While rates of local control have been well characterized after stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC), less data are available characterizing survival and normal tissue toxicities, and no validated models exist assessing these parameters after SBRT. We evaluate the reliability of various machine learning techniques when applied to radiation oncology datasets to create predictive models of mortality, tumor control, and normal tissue complications. Methods: A dataset of 204 consecutive patients with stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) at the University of Pennsylvania between 2009 and 2013 was used to create predictive models of tumor control, normal tissue complications, and mortality in this IRB-approved study. Nearly 200 data fields of detailed patient- and tumor-specific information, radiotherapy dosimetric measurements, and clinical outcomes data were collected. Predictive models were created for local tumor control, 1- and 3-year overall survival, and nodal failure using 60% of the data (leaving the remainder as a test set). After applying feature selection and dimensionality reduction, nonlinear support vector classification was applied to the resulting features. Models were evaluated for accuracy and area under ROC curve on the 81-patient test set. Results: Models for common events in the dataset (such as mortality at one year) had the highest predictive power (AUC = .67, p < 0.05). For rare occurrences such as radiation pneumonitis and local failure (each occurring in less than 10% of patients), too few events were present to create reliable models. Conclusion: Although this study demonstrates the validity of predictive analytics using information extracted from patient medical records and can most reliably predict for survival after SBRT, larger sample sizes are needed to develop predictive models for normal tissue toxicities and more advanced

  11. Normal tissue complication probability model parameter estimation for xerostomia in head and neck cancer patients based on scintigraphy and quality of life assessments

    International Nuclear Information System (INIS)

    Lee, Tsair-Fwu; Chao, Pei-Ju; Wang, Hung-Yu; Hsu, Hsuan-Chih; Chang, PaoShu; Chen, Wen-Cheng

    2012-01-01

    With advances in modern radiotherapy (RT), many patients with head and neck (HN) cancer can be effectively cured. However, xerostomia is a common complication in patients after RT for HN cancer. The purpose of this study was to use the Lyman–Kutcher–Burman (LKB) model to derive parameters for the normal tissue complication probability (NTCP) for xerostomia based on scintigraphy assessments and quality of life (QoL) questionnaires. We performed validation tests of the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) guidelines against prospectively collected QoL and salivary scintigraphic data. Thirty-one patients with HN cancer were enrolled. Salivary excretion factors (SEFs) measured by scintigraphy and QoL data from self-reported questionnaires were used for NTCP modeling to describe the incidence of grade 3 + xerostomia. The NTCP parameters estimated from the QoL and SEF datasets were compared. Model performance was assessed using Pearson’s chi-squared test, Nagelkerke’s R 2 , the area under the receiver operating characteristic curve, and the Hosmer–Lemeshow test. The negative predictive value (NPV) was checked for the rate of correctly predicting the lack of incidence. Pearson’s chi-squared test was used to test the goodness of fit and association. Using the LKB NTCP model and assuming n=1, the dose for uniform irradiation of the whole or partial volume of the parotid gland that results in 50% probability of a complication (TD 50 ) and the slope of the dose–response curve (m) were determined from the QoL and SEF datasets, respectively. The NTCP-fitted parameters for local disease were TD 50 =43.6 Gy and m=0.18 with the SEF data, and TD 50 =44.1 Gy and m=0.11 with the QoL data. The rate of grade 3 + xerostomia for treatment plans meeting the QUANTEC guidelines was specifically predicted, with a NPV of 100%, using either the QoL or SEF dataset. Our study shows the agreement between the NTCP parameter modeling based on SEF and

  12. Normal tissue complication probability model parameter estimation for xerostomia in head and neck cancer patients based on scintigraphy and quality of life assessments

    Science.gov (United States)

    2012-01-01

    Background With advances in modern radiotherapy (RT), many patients with head and neck (HN) cancer can be effectively cured. However, xerostomia is a common complication in patients after RT for HN cancer. The purpose of this study was to use the Lyman–Kutcher–Burman (LKB) model to derive parameters for the normal tissue complication probability (NTCP) for xerostomia based on scintigraphy assessments and quality of life (QoL) questionnaires. We performed validation tests of the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) guidelines against prospectively collected QoL and salivary scintigraphic data. Methods Thirty-one patients with HN cancer were enrolled. Salivary excretion factors (SEFs) measured by scintigraphy and QoL data from self-reported questionnaires were used for NTCP modeling to describe the incidence of grade 3+ xerostomia. The NTCP parameters estimated from the QoL and SEF datasets were compared. Model performance was assessed using Pearson’s chi-squared test, Nagelkerke’s R2, the area under the receiver operating characteristic curve, and the Hosmer–Lemeshow test. The negative predictive value (NPV) was checked for the rate of correctly predicting the lack of incidence. Pearson’s chi-squared test was used to test the goodness of fit and association. Results Using the LKB NTCP model and assuming n=1, the dose for uniform irradiation of the whole or partial volume of the parotid gland that results in 50% probability of a complication (TD50) and the slope of the dose–response curve (m) were determined from the QoL and SEF datasets, respectively. The NTCP-fitted parameters for local disease were TD50=43.6 Gy and m=0.18 with the SEF data, and TD50=44.1 Gy and m=0.11 with the QoL data. The rate of grade 3+ xerostomia for treatment plans meeting the QUANTEC guidelines was specifically predicted, with a NPV of 100%, using either the QoL or SEF dataset. Conclusions Our study shows the agreement between the NTCP

  13. Normal tissue complication probability model parameter estimation for xerostomia in head and neck cancer patients based on scintigraphy and quality of life assessments

    Directory of Open Access Journals (Sweden)

    Lee Tsair-Fwu

    2012-12-01

    Full Text Available Abstract Background With advances in modern radiotherapy (RT, many patients with head and neck (HN cancer can be effectively cured. However, xerostomia is a common complication in patients after RT for HN cancer. The purpose of this study was to use the Lyman–Kutcher–Burman (LKB model to derive parameters for the normal tissue complication probability (NTCP for xerostomia based on scintigraphy assessments and quality of life (QoL questionnaires. We performed validation tests of the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC guidelines against prospectively collected QoL and salivary scintigraphic data. Methods Thirty-one patients with HN cancer were enrolled. Salivary excretion factors (SEFs measured by scintigraphy and QoL data from self-reported questionnaires were used for NTCP modeling to describe the incidence of grade 3+ xerostomia. The NTCP parameters estimated from the QoL and SEF datasets were compared. Model performance was assessed using Pearson’s chi-squared test, Nagelkerke’s R2, the area under the receiver operating characteristic curve, and the Hosmer–Lemeshow test. The negative predictive value (NPV was checked for the rate of correctly predicting the lack of incidence. Pearson’s chi-squared test was used to test the goodness of fit and association. Results Using the LKB NTCP model and assuming n=1, the dose for uniform irradiation of the whole or partial volume of the parotid gland that results in 50% probability of a complication (TD50 and the slope of the dose–response curve (m were determined from the QoL and SEF datasets, respectively. The NTCP-fitted parameters for local disease were TD50=43.6 Gy and m=0.18 with the SEF data, and TD50=44.1 Gy and m=0.11 with the QoL data. The rate of grade 3+ xerostomia for treatment plans meeting the QUANTEC guidelines was specifically predicted, with a NPV of 100%, using either the QoL or SEF dataset. Conclusions Our study shows the agreement

  14. Identification of Patient Benefit From Proton Therapy for Advanced Head and Neck Cancer Patients Based on Individual and Subgroup Normal Tissue Complication Probability Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Jakobi, Annika, E-mail: Annika.Jakobi@OncoRay.de [OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Bandurska-Luque, Anna [OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Stützer, Kristin; Haase, Robert; Löck, Steffen [OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Wack, Linda-Jacqueline [Section for Biomedical Physics, University Hospital for Radiation Oncology, Eberhard Karls Universät Tübingen (Germany); Mönnich, David [Section for Biomedical Physics, University Hospital for Radiation Oncology, Eberhard Karls Universät Tübingen (Germany); German Cancer Research Center, Heidelberg (Germany); German Cancer Consortium, Tübingen (Germany); Thorwarth, Daniela [Section for Biomedical Physics, University Hospital for Radiation Oncology, Eberhard Karls Universät Tübingen (Germany); and others

    2015-08-01

    Purpose: The purpose of this study was to determine, by treatment plan comparison along with normal tissue complication probability (NTCP) modeling, whether a subpopulation of patients with head and neck squamous cell carcinoma (HNSCC) could be identified that would gain substantial benefit from proton therapy in terms of NTCP. Methods and Materials: For 45 HNSCC patients, intensity modulated radiation therapy (IMRT) was compared to intensity modulated proton therapy (IMPT). Physical dose distributions were evaluated as well as the resulting NTCP values, using modern models for acute mucositis, xerostomia, aspiration, dysphagia, laryngeal edema, and trismus. Patient subgroups were defined based on primary tumor location. Results: Generally, IMPT reduced the NTCP values while keeping similar target coverage for all patients. Subgroup analyses revealed a higher individual reduction of swallowing-related side effects by IMPT for patients with tumors in the upper head and neck area, whereas the risk reduction of acute mucositis was more pronounced in patients with tumors in the larynx region. More patients with tumors in the upper head and neck area had a reduction in NTCP of more than 10%. Conclusions: Subgrouping can help to identify patients who may benefit more than others from the use of IMPT and, thus, can be a useful tool for a preselection of patients in the clinic where there are limited PT resources. Because the individual benefit differs within a subgroup, the relative merits should additionally be evaluated by individual treatment plan comparisons.

  15. Identification of Patient Benefit From Proton Therapy for Advanced Head and Neck Cancer Patients Based on Individual and Subgroup Normal Tissue Complication Probability Analysis

    International Nuclear Information System (INIS)

    Jakobi, Annika; Bandurska-Luque, Anna; Stützer, Kristin; Haase, Robert; Löck, Steffen; Wack, Linda-Jacqueline; Mönnich, David; Thorwarth, Daniela

    2015-01-01

    Purpose: The purpose of this study was to determine, by treatment plan comparison along with normal tissue complication probability (NTCP) modeling, whether a subpopulation of patients with head and neck squamous cell carcinoma (HNSCC) could be identified that would gain substantial benefit from proton therapy in terms of NTCP. Methods and Materials: For 45 HNSCC patients, intensity modulated radiation therapy (IMRT) was compared to intensity modulated proton therapy (IMPT). Physical dose distributions were evaluated as well as the resulting NTCP values, using modern models for acute mucositis, xerostomia, aspiration, dysphagia, laryngeal edema, and trismus. Patient subgroups were defined based on primary tumor location. Results: Generally, IMPT reduced the NTCP values while keeping similar target coverage for all patients. Subgroup analyses revealed a higher individual reduction of swallowing-related side effects by IMPT for patients with tumors in the upper head and neck area, whereas the risk reduction of acute mucositis was more pronounced in patients with tumors in the larynx region. More patients with tumors in the upper head and neck area had a reduction in NTCP of more than 10%. Conclusions: Subgrouping can help to identify patients who may benefit more than others from the use of IMPT and, thus, can be a useful tool for a preselection of patients in the clinic where there are limited PT resources. Because the individual benefit differs within a subgroup, the relative merits should additionally be evaluated by individual treatment plan comparisons

  16. Development of a multivariable normal tissue complication probability (NTCP) model for tube feeding dependence after curative radiotherapy/chemo-radiotherapy in head and neck cancer

    International Nuclear Information System (INIS)

    Wopken, Kim; Bijl, Hendrik P.; Schaaf, Arjen van der; Laan, Hans Paul van der; Chouvalova, Olga; Steenbakkers, Roel J.H.M.; Doornaert, Patricia; Slotman, Ben J.; Oosting, Sjoukje F.; Christianen, Miranda E.M.C.; Laan, Bernard F.A.M. van der; Roodenburg, Jan L.N.; René Leemans, C.; Verdonck-de Leeuw, Irma M.; Langendijk, Johannes A.

    2014-01-01

    Background and purpose: Curative radiotherapy/chemo-radiotherapy for head and neck cancer (HNC) may result in severe acute and late side effects, including tube feeding dependence. The purpose of this prospective cohort study was to develop a multivariable normal tissue complication probability (NTCP) model for tube feeding dependence 6 months (TUBE M6 ) after definitive radiotherapy, radiotherapy plus cetuximab or concurrent chemoradiation based on pre-treatment and treatment characteristics. Materials and methods: The study included 355 patients with HNC. TUBE M6 was scored prospectively in a standard follow-up program. To design the prediction model, the penalized learning method LASSO was used, with TUBE M6 as the endpoint. Results: The prevalence of TUBE M6 was 10.7%. The multivariable model with the best performance consisted of the variables: advanced T-stage, moderate to severe weight loss at baseline, accelerated radiotherapy, chemoradiation, radiotherapy plus cetuximab, the mean dose to the superior and inferior pharyngeal constrictor muscle, to the contralateral parotid gland and to the cricopharyngeal muscle. Conclusions: We developed a multivariable NTCP model for TUBE M6 to identify patients at risk for tube feeding dependence. The dosimetric variables can be used to optimize radiotherapy treatment planning aiming at prevention of tube feeding dependence and to estimate the benefit of new radiation technologies

  17. Normal Tissue Complication Probability Analysis of Acute Gastrointestinal Toxicity in Cervical Cancer Patients Undergoing Intensity Modulated Radiation Therapy and Concurrent Cisplatin

    International Nuclear Information System (INIS)

    Simpson, Daniel R.; Song, William Y.; Moiseenko, Vitali; Rose, Brent S.; Yashar, Catheryn M.; Mundt, Arno J.; Mell, Loren K.

    2012-01-01

    Purpose: To test the hypothesis that increased bowel radiation dose is associated with acute gastrointestinal (GI) toxicity in cervical cancer patients undergoing concurrent chemotherapy and intensity-modulated radiation therapy (IMRT), using a previously derived normal tissue complication probability (NTCP) model. Methods: Fifty patients with Stage I–III cervical cancer undergoing IMRT and concurrent weekly cisplatin were analyzed. Acute GI toxicity was graded using the Radiation Therapy Oncology Group scale, excluding upper GI events. A logistic model was used to test correlations between acute GI toxicity and bowel dosimetric parameters. The primary objective was to test the association between Grade ≥2 GI toxicity and the volume of bowel receiving ≥45 Gy (V 45 ) using the logistic model. Results: Twenty-three patients (46%) had Grade ≥2 GI toxicity. The mean (SD) V 45 was 143 mL (99). The mean V 45 values for patients with and without Grade ≥2 GI toxicity were 176 vs. 115 mL, respectively. Twenty patients (40%) had V 45 >150 mL. The proportion of patients with Grade ≥2 GI toxicity with and without V 45 >150 mL was 65% vs. 33% (p = 0.03). Logistic model parameter estimates V50 and γ were 161 mL (95% confidence interval [CI] 60–399) and 0.31 (95% CI 0.04–0.63), respectively. On multivariable logistic regression, increased V 45 was associated with an increased odds of Grade ≥2 GI toxicity (odds ratio 2.19 per 100 mL, 95% CI 1.04–4.63, p = 0.04). Conclusions: Our results support the hypothesis that increasing bowel V 45 is correlated with increased GI toxicity in cervical cancer patients undergoing IMRT and concurrent cisplatin. Reducing bowel V 45 could reduce the risk of Grade ≥2 GI toxicity by approximately 50% per 100 mL of bowel spared.

  18. Increase in tumor control and normal tissue complication probabilities in advanced head-and-neck cancer for dose-escalated intensity-modulated photon and proton therapy

    Directory of Open Access Journals (Sweden)

    Annika eJakobi

    2015-11-01

    Full Text Available Introduction:Presently used radio-chemotherapy regimens result in moderate local control rates for patients with advanced head and neck squamous cell carcinoma (HNSCC. Dose escalation (DE may be an option to improve patient outcome, but may also increase the risk of toxicities in healthy tissue. The presented treatment planning study evaluated the feasibility of two DE levels for advanced HNSCC patients, planned with either intensity-modulated photon therapy (IMXT or proton therapy (IMPT.Materials and Methods:For 45 HNSCC patients, IMXT and IMPT treatment plans were created including DE via a simultaneous integrated boost (SIB in the high-risk volume, while maintaining standard fractionation with 2 Gy per fraction in the remaining target volume. Two DE levels for the SIB were compared: 2.3 Gy and 2.6 Gy. Treatment plan evaluation included assessment of tumor control probabilities (TCP and normal tissue complication probabilities (NTCP.Results:An increase of approximately 10% in TCP was estimated between the DE levels. A pronounced high-dose rim surrounding the SIB volume was identified in IMXT treatment. Compared to IMPT, this extra dose slightly increased the TCP values and to a larger extent the NTCP values. For both modalities, the higher DE level led only to a small increase in NTCP values (mean differences < 2% in all models, except for the risk of aspiration, which increased on average by 8% and 6% with IMXT and IMPT, respectively, but showed a considerable patient dependence. Conclusions:Both DE levels appear applicable to patients with IMXT and IMPT since all calculated NTCP values, except for one, increased only little for the higher DE level. The estimated TCP increase is of relevant magnitude. The higher DE schedule needs to be investigated carefully in the setting of a prospective clinical trial, especially regarding toxicities caused by high local doses that lack a sound dose response description, e.g., ulcers.

  19. Comparison of incidences of normal tissue complications with tumor response in a phase III trial comparing heat plus radiation to radiation alone

    International Nuclear Information System (INIS)

    Dewhirst, M.W.; Sim, D.A.; Grochowski, K.J.

    1984-01-01

    The success of hyperthermia (/sup Δ/) as an adjuvant to radiation (XRT) will depend on whether the increase in tumor control is greater than that for normal tissue reactions. One hundred and thirty dogs and cats were stratified by histology and randomized to receive XRT (460 rads per fraction, two fractions per week, for eight fractions) or /sup Δ/ + XRT (30 min. at 44 +-2 0 C; one fraction per week, four fractions; immediately prior to XRT). Heat induced changes in tumor and normal tissue responses were made by comparing ratios of incidence for /sup Δ/ + XRT and XRT alone (TRR; Thermal Relative Risk). Change in tumor response duration was calculated from statistical analysis of response duration curves (RRR; Relative Relapse Rate). Heat increased early normal tissue reactions (moist desquamation and mucositis by a factor of 1.08. Tumor complete response, by comparison, was significantly improved (TRR = 2.12, p < .001). Late skin fibrosis was also increased (TRR = 1.51), but the prolongation in tumor response was greater (RRR 1.85). The degree of thermal enhancement for all tissues was dependent on the minimum temperature achieved on the first treatment, but the values for tumor were consistently greater than those achieved for normal tissues

  20. SU-E-T-214: Comparison of Treatment Techniques for Dupuytren’s Contracture and Risk Assessment of Normal Tissue Complications

    International Nuclear Information System (INIS)

    Arentsen, L; Lopater, Z; Dusenbery, K; Gerbi, B

    2015-01-01

    Purpose: Duputren’s contracture (DC) is a benign disease characterized by abnormal thickening of the fascial surfaces of the hands or feet causing curling of the surface, functional impairment, weakness, and pain. The purpose of the investigation is to describe the radiation treatment approaches, compare these techniques, and discuss the potential side effects and complications of these techniques. Methods: Early stage DC has been treated with 120 kVp X rays but also with high-energy electrons or photons. High-energy electrons have been the radiation of choice but severe contracture of the hand makes it difficult to produce a plan with acceptable dose uniformity. High-energy photons can overcome this difficulty either by directing a beam onto the palmer or back of the surface of the hand, including bolus to maximize the surface dose. We calculated the dose to the bone for the 120 kVp treatment using published %DD data and mass energy absorption coefficients for bone and muscle. Results: The dose to underlying bone from megavoltage photons and electrons is essentially the same, but dose to the bone for using 120 kVp can be 4–5 times greater due to the photoelectric effect. For the 30 Gy dose deliver using this technique, the dose to the bone could be 84–105 Gy after taking the penetration of the beam into account. After radiotherapy, there is often decreased osteoblastic activity and vascular fibrosis that leads to osteitis, atrophy, and decreased metabolic bone activity. Incidence of fractures occurs routinely above 60 Gy with higher doses potentially leading to higher incidences of bone complications. Conclusion: Radiation therapy for DC using low-energy X rays can deliver a prohibitively high dose to the underlying bone potentially leading to severe bone complications

  1. Neutron RBE for normal tissues

    International Nuclear Information System (INIS)

    Field, S.B.; Hornsey, S.

    1979-01-01

    RBE for various normal tissues is considered as a function of neutron dose per fraction. Results from a variety of centres are reviewed. It is shown that RBE is dependent on neutron energy and is tissue dependent, but is not specially high for the more critical tissues or for damage occurring late after irradiation. (author)

  2. The effect of 6 and 15 MV on intensity-modulated radiation therapy prostate cancer treatment: plan evaluation, tumour control probability and normal tissue complication probability analysis, and the theoretical risk of secondary induced malignancies

    Science.gov (United States)

    Hussein, M; Aldridge, S; Guerrero Urbano, T; Nisbet, A

    2012-01-01

    Objective The aim of this study was to investigate the effect of 6 and 15-MV photon energies on intensity-modulated radiation therapy (IMRT) prostate cancer treatment plan outcome and to compare the theoretical risks of secondary induced malignancies. Methods Separate prostate cancer IMRT plans were prepared for 6 and 15-MV beams. Organ-equivalent doses were obtained through thermoluminescent dosemeter measurements in an anthropomorphic Aldersen radiation therapy human phantom. The neutron dose contribution at 15 MV was measured using polyallyl-diglycol-carbonate neutron track etch detectors. Risk coefficients from the International Commission on Radiological Protection Report 103 were used to compare the risk of fatal secondary induced malignancies in out-of-field organs and tissues for 6 and 15 MV. For the bladder and the rectum, a comparative evaluation of the risk using three separate models was carried out. Dose–volume parameters for the rectum, bladder and prostate planning target volume were evaluated, as well as normal tissue complication probability (NTCP) and tumour control probability calculations. Results There is a small increased theoretical risk of developing a fatal cancer from 6 MV compared with 15 MV, taking into account all the organs. Dose–volume parameters for the rectum and bladder show that 15 MV results in better volume sparing in the regions below 70 Gy, but the volume exposed increases slightly beyond this in comparison with 6 MV, resulting in a higher NTCP for the rectum of 3.6% vs 3.0% (p=0.166). Conclusion The choice to treat using IMRT at 15 MV should not be excluded, but should be based on risk vs benefit while considering the age and life expectancy of the patient together with the relative risk of radiation-induced cancer and NTCPs. PMID:22010028

  3. Measurement of human normal tissue and tumour responses

    International Nuclear Information System (INIS)

    Ross, G.; Yarnold, J.R.

    1988-01-01

    The scarcity of quantitative measures of normal tissue damage and tumour response in patients undergoing radiotherapy is an obstacle to the clinical evaluation of new treatment strategies. Retrospective studies of complications in critical normal tissues taught important lessons in the past concerning the potential dangers of hypofractionation. However, it is unethical to use serious complications as planned end-points in prospective studies. This paper reviews the desirable characteristics of clinical end-points required to compare alternative treatments employing radiotherapy, with emphasis on simple scales applied by clinicians or even the patients themselves

  4. Late Rectal Toxicity on RTOG 94-06: Analysis Using a Mixture Lyman Model

    International Nuclear Information System (INIS)

    Tucker, Susan L.; Dong Lei; Bosch, Walter R.; Michalski, Jeff; Winter, Kathryn; Mohan, Radhe; Purdy, James A.; Kuban, Deborah; Lee, Andrew K.; Cheung, M. Rex; Thames, Howard D.; Cox, James D.

    2010-01-01

    Purpose: To estimate the parameters of the Lyman normal-tissue complication probability model using censored time-to-event data for Grade ≥2 late rectal toxicity among patients treated on Radiation Therapy Oncology Group 94-06, a dose-escalation trial designed to determine the maximum tolerated dose for three-dimensional conformal radiotherapy of prostate cancer. Methods and Materials: The Lyman normal-tissue complication probability model was fitted to data from 1,010 of the 1,084 patients accrued on Radiation Therapy Oncology Group 94-06 using an approach that accounts for censored observations. Separate fits were obtained using dose-volume histograms for whole rectum and dose-wall histograms for rectal wall. Results: With a median follow-up of 7.2 years, the crude incidence of Grade ≥2 late rectal toxicity was 15% (n = 148). The parameters of the Lyman model fitted to dose-volume histograms data, with 95% profile-likelihood confidence intervals, were TD 50 = 79.1 Gy (75.3 Gy, 84.3 Gy), m = 0.146 (0.107, 0.225), and n = 0.077 (0.041, 0.156). The fit based on dose-wall histogram data was not significantly different. Patients with cardiovascular disease had a significantly higher incidence of late rectal toxicity (p = 0.015), corresponding to a dose-modifying factor of 5.3%. No significant association with late rectal toxicity was found for diabetes, hypertension, rectal volume, rectal length, neoadjuvant hormone therapy, or prescribed dose per fraction (1.8 Gy vs. 2 Gy). Conclusions: These results, based on a large cohort of patients from a multi-institutional trial, are expected to be widely representative of the ability of the Lyman model to describe the long-term risk of Grade ≥2 late rectal toxicity after three-dimensional conformal radiotherapy of prostate cancer.

  5. Normal tissue dose-effect models in biological dose optimisation

    International Nuclear Information System (INIS)

    Alber, M.

    2008-01-01

    Sophisticated radiotherapy techniques like intensity modulated radiotherapy with photons and protons rely on numerical dose optimisation. The evaluation of normal tissue dose distributions that deviate significantly from the common clinical routine and also the mathematical expression of desirable properties of a dose distribution is difficult. In essence, a dose evaluation model for normal tissues has to express the tissue specific volume effect. A formalism of local dose effect measures is presented, which can be applied to serial and parallel responding tissues as well as target volumes and physical dose penalties. These models allow a transparent description of the volume effect and an efficient control over the optimum dose distribution. They can be linked to normal tissue complication probability models and the equivalent uniform dose concept. In clinical applications, they provide a means to standardize normal tissue doses in the face of inevitable anatomical differences between patients and a vastly increased freedom to shape the dose, without being overly limiting like sets of dose-volume constraints. (orig.)

  6. Radiogenomics: predicting clinical normal tissue radiosensitivity

    DEFF Research Database (Denmark)

    Alsner, Jan

    2006-01-01

    Studies on the genetic basis of normal tissue radiosensitivity, or  'radiogenomics', aims at predicting clinical radiosensitivity and optimize treatment from individual genetic profiles. Several studies have now reported links between variations in certain genes related to the biological response...... to radiation injury and risk of normal tissue morbidity in cancer patients treated with radiotherapy. However, after these initial association studies including few genes, we are still far from being able to predict clinical radiosensitivity on an individual level. Recent data from our own studies on risk...

  7. Radiobiology in clinical radiation therapy - Part III: Normal tissue damage

    International Nuclear Information System (INIS)

    Travis, Elizabeth L.

    1996-01-01

    relationship of tissue architecture to radiation-induced damage and the available clinical and experimental data which demonstrate volume effects as well as those factors which complicate efforts to estimate normal tissue complication probabilities

  8. Effects of pions on normal tissues

    International Nuclear Information System (INIS)

    Tokita, N.

    1981-01-01

    Verification of the uniform biological effectiveness of pion beams of various dimensions produced at LAMPF has been made using cultured mammalian cells and mouse jejunum. Normal tissue radiobiology studies at LAMPF are reviewed with regard to biological beam characterization for the therapy program and the current status of acute and late effect studies on rodents

  9. Potential clinical impact of normal-tissue intrinsic radiosensitivity testing

    International Nuclear Information System (INIS)

    Bentzen, Soeren M.

    1997-01-01

    assays may be as a guide for the prescription of treatment schedules that are costly or involves a high risk of complications. Examples of this are certain strategies attempting to widen the therapeutic window, the use of very high doses or re-irradiation of a previously irradiated region, or the selection of patients for experimental strategies like the use of biological response modifiers to reduce normal-tissue toxicity. Finally, published data are summarized on the possible correlation between the radiosensitivities of tumor and normal tissues or between the sensitivities of various normal tissues

  10. Oxygen delivery in irradiated normal tissue

    Energy Technology Data Exchange (ETDEWEB)

    Kiani, M.F.; Ansari, R. [Univ. of Tennessee Health Science Center, Memphis, TN (United States). School of Biomedical Engineering; Gaber, M.W. [St. Jude Children' s Research Hospital, Memphis, TN (United States)

    2003-03-01

    Ionizing radiation exposure significantly alters the structure and function of microvascular networks, which regulate delivery of oxygen to tissue. In this study we use a hamster cremaster muscle model to study changes in microvascular network parameters and use a mathematical model to study the effects of these observed structural and microhemodynamic changes in microvascular networks on oxygen delivery to the tissue. Our experimental observations indicate that in microvascular networks while some parameters are significantly affected by irradiation (e.g. red blood cell (RBC) transit time), others remain at the control level (e.g. RBC path length) up to 180 days post-irradiation. The results from our mathematical model indicate that tissue oxygenation patterns are significantly different in irradiated normal tissue as compared to age-matched controls and the differences are apparent as early as 3 days post irradiation. However, oxygen delivery to irradiated tissue was not found to be significantly different from age matched controls at any time between 7 days to 6 months post-irradiation. These findings indicate that microvascular late effects in irradiated normal tissue may be due to factors other than compromised tissue oxygenation. (author)

  11. Human normal tissue reactions in radiotherapy

    International Nuclear Information System (INIS)

    Taniike, Keiko

    1990-01-01

    Acute and late normal tissue reactions in radiotherapy have not been considered to be major problems with conventional fractionation. But they may cause certain problems when newer schedules such as hyperfractionation or accelerated fractionation are used. In opposing parallel radiotherapy, the dose fractionation of skin or subcutaneous connective tissue are different between in one portal and two portals daily. So we examined acute skin erythema and late connective tissue fibrosis in the two groups (one and two portals) of the patients with uterus cancer. Acute skin erythema and late connective tissue fibrosis were slightly stronger in case of one portal daily. In relation to the anatomical site of skin, acute skin erythema was stronger at the buttocks than the lower abdomen, but late fibrosis was reverse to that. So the degree of acute skin erythema did not predict the degree of late connective tissue fibrosis. The number of Time Dose Fractionation Factor could roughly estimate the degree of erythema and fibrosis. Late fibrosis in 36 fractions increased with an increase of abdominal thickness, but acute erythema did not. (author)

  12. Dosimetric precision requirements and quantities for characterizing the response of tumors and normal tissues

    Energy Technology Data Exchange (ETDEWEB)

    Brahme, A [Karolinska Inst., Stockholm (Sweden). Dept. of Radiation Physics

    1996-08-01

    Based on simple radiobiological models the effect of the distribution of absorbed dose in therapy beams on the radiation response of tumor and normal tissue volumes are investigated. Under the assumption that the dose variation in the treated volume is small it is shown that the response of the tissue to radiation is determined mainly by the mean dose to the tumor or normal tissue volume in question. Quantitative expressions are also given for the increased probability of normal tissue complications and the decreased probability of tumor control as a function of increasing dose variations around the mean dose level to these tissues. When the dose variations are large the minimum tumor dose (to cm{sup 3} size volumes) will generally be better related to tumor control and the highest dose to significant portions of normal tissue correlates best to complications. In order not to lose more than one out of 20 curable patients (95% of highest possible treatment outcome) the required accuracy in the dose distribution delivered to the target volume should be 2.5% (1{sigma}) for a mean dose response gradient {gamma} in the range 2 - 3. For more steeply responding tumors and normal tissues even stricter requirements may be desirable. (author). 15 refs, 6 figs.

  13. Lyman Alpha Control

    CERN Document Server

    Nielsen, Daniel Stefaniak

    2015-01-01

    This document gives an overview of how to operate the Lyman Alpha Control application written in LabVIEW along with things to watch out for. Overview of the LabVIEW code itself as well as the physical wiring of and connections from/to the NI PCI-6229 DAQ box is also included. The Lyman Alpha Control application is the interface between the ALPHA sequencer and the HighFinesse Wavelength Meter as well as the Lyman Alpha laser setup. The application measures the wavelength of the output light from the Lyman Alpha cavity through the Wavelength Meter. The application can use the Wavelength Meter’s PID capabilities to stabilize the Lyman Alpha laser output as well as switch between up to three frequencies.

  14. Local stem cell depletion model for normal tissue damage

    International Nuclear Information System (INIS)

    Yaes, R.J.; Keland, A.

    1987-01-01

    The hypothesis that radiation causes normal tissue damage by completely depleting local regions of tissue of viable stem cells leads to a simple mathematical model for such damage. In organs like skin and spinal cord where destruction of a small volume of tissue leads to a clinically apparent complication, the complication probability is expressed as a function of dose, volume and stem cell number by a simple triple negative exponential function analogous to the double exponential function of Munro and Gilbert for tumor control. The steep dose response curves for radiation myelitis that are obtained with our model are compared with the experimental data for radiation myelitis in laboratory rats. The model can be generalized to include other types or organs, high LET radiation, fractionated courses of radiation, and cases where an organ with a heterogeneous stem cell population receives an inhomogeneous dose of radiation. In principle it would thus be possible to determine the probability of tumor control and of damage to any organ within the radiation field if the dose distribution in three dimensional space within a patient is known

  15. Radiation therapy and late reactions in normal tissues

    International Nuclear Information System (INIS)

    Aoyama, Takashi; Kuroda, Yasumasa

    1998-01-01

    Recent developments in cancer therapy have made us increasingly aware that the quality of life of a patient is as valuable as other benefits received from therapy. This awareness leads to an emphasis on organ and/or function preservation in the course of therapy. In line with this new thinking, greater consideration is placed on radiation therapy as an appropriate modality of cancer therapy. Possible complications in normal tissues, especially those of late reaction type after the therapy must be overcome. This review, therefore, focuses on recent progress of studies on mechanisms of the complications of the late reaction type. An observation of a clinical case concerning a late reaction of spinal cord (radiation myelopathy) and surveys of experimental studies on the mechanisms of late reactions (including radiation pneumonitis and lung fibrosis, and radiation response of vascular endothelial cells) provide a hypothesis that apoptosis through the pathway starting with radiation-induced sphingomyelin hydrolysis may play an important role in causing a variety of late reactions. This insight is based on the fact that radiation also activates protein kinase C which appears to block apoptosis. The mechanisms of late reactions, therefore, may involve a balance between radiation-induced apoptotic death and its down regulation by suppressor mechanisms through protein kinase C. (author)

  16. Acute and late effects of multimodal therapy on normal tissues

    International Nuclear Information System (INIS)

    Phillips, T.L.; Fu, K.K.

    1977-01-01

    The increasing use of combined radiation, chemotherapy, and surgery has led to an increased incidence of acute and late complications. The complications are, in general, similar to those seen with each modality alone, but occur with increased incidence. Enhanced effects of combined radiation and surgery are modest in number and consist primarily of problems with wound healing and fibrosis, as well as late gastrointestinal damage. Combinations of radiotherapy and chemotherapy have shown a greater degree of enhanced acute and late reactions. Drugs, such as actinomycin-D and Adriamycin, are particularly dangerous if the marked enhancement of radiation effects caused by the drugs in almost all organs is not appreciated and the radiation dose not adjusted accordingly. Proper selection of drugs can lead to enhanced local control by radiotherapy and/or surgery, as well as eradication of microscopic distant metastases, without increased normal tissue injury. Late induction of malignancy can occur with either radiation or chemotherapy alone and, in some cases, this appears to be enhanced when they are combined

  17. Radiobiology of normal tissue. Scientific advances and perspectives; Strahlenbiologie der Normalgewebe. Wissenschaftliche Fortschritte und Perspektiven

    Energy Technology Data Exchange (ETDEWEB)

    Doerr, W. [Medizinische Univ. Wien (Austria). Universitaetsklinik fuer Strahlentherapie; Medizinische Univ. Wien (Austria). Universitaetsklinik fuer Radioonkologie; Medizinische Univ. Wien (Austria). Christian Doppler Labor fuer Medizinische Strahlenforschung fuer die Radioonkologie; Herskind, C. [Universitaetsmedizin Mannheim, Heidelberg Univ., Mannheim (Germany). Labor fuer Zellulaere und Molekulare Radioonkologie

    2012-11-15

    Radiotherapy involves always the exposure of normal tissue, resulting in an excepted risk of complications. The side effect rate is therefore the compromise between optimized tumor doses and the side effect minimization. The report covers the issues target cell hypothesis and the consequences, new aspect of the pathogenesis of normal issue reactions and strategies of targeted reduction of normal tissue effects. The complexity of the radiobiological processes, the specificity and action mechanisms, the mutual interactions of chemical and radiological processes require further coordinated radiobiological research in the future.

  18. DNA-repair, cell killing and normal tissue damage

    International Nuclear Information System (INIS)

    Dahm-Daphi, J.; Dikomey, E.; Brammer, I.

    1998-01-01

    Background: Side effects of radiotherapy in normal tissue is determined by a variety of factors of which cellular and genetic contributions are described here. Material and methods: Review. Results: Normal tissue damage after irradiation is largely due to loss of cellular proliferative capacity. This can be due to mitotic cell death, apoptosis, or terminal differentiation. Dead or differentiated cells release cytokines which additionally modulate the tissue response. DNA damage, in particular non-reparable or misrepaired double-strand breaks are considered the basic lesion leading to G1-arrest and ultimately to cell inactivation. Conclusion: Evidence for genetic bases of normal tissue response, cell killing and DNA-repair capacity is presented. However, a direct link of all 3 endpoints has not yet been proved directly. (orig.) [de

  19. Pelvic Normal Tissue Contouring Guidelines for Radiation Therapy: A Radiation Therapy Oncology Group Consensus Panel Atlas

    Energy Technology Data Exchange (ETDEWEB)

    Gay, Hiram A., E-mail: hgay@radonc.wustl.edu [Washington University School of Medicine, St Louis, MO (United States); Barthold, H. Joseph [Commonwealth Hematology and Oncology, Weymouth, MA (United States); Beth Israel Deaconess Medical Center, Boston, MA (Israel); O' Meara, Elizabeth [Radiation Therapy Oncology Group, Philadelphia, PA (United States); Bosch, Walter R. [Washington University School of Medicine, St Louis, MO (United States); El Naqa, Issam [Department of Radiation Oncology, McGill University Health Center, Montreal, Quebec (Canada); Al-Lozi, Rawan [Washington University School of Medicine, St Louis, MO (United States); Rosenthal, Seth A. [Radiation Oncology Centers, Radiological Associates of Sacramento, Sacramento, CA (United States); Lawton, Colleen [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Lee, W. Robert [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Sandler, Howard [Cedars-Sinai Medical Center, Los Angeles, CA (United States); Zietman, Anthony [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Myerson, Robert [Washington University School of Medicine, St Louis, MO (United States); Dawson, Laura A. [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Willett, Christopher [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Kachnic, Lisa A. [Department of Radiation Oncology, Boston Medical Center, Boston University School of Medicine, Boston, MA (United States); Jhingran, Anuja [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Portelance, Lorraine [University of Miami, Miami, FL (United States); Ryu, Janice [Radiation Oncology Centers, Radiological Associates of Sacramento, Sacramento, CA (United States); and others

    2012-07-01

    Purpose: To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials. Methods and Materials: One male pelvis computed tomography (CT) data set and one female pelvis CT data set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The following were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified. Results: The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa{sub R}, Adnexa{sub L}, Prostate, SeminalVesc, PenileBulb, Femur{sub R}, and Femur{sub L}. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed. Conclusions: Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research.

  20. Role of endothelium in radiation-induced normal tissue damages

    International Nuclear Information System (INIS)

    Milliat, F.

    2007-05-01

    More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

  1. Genetic markers for prediction of normal tissue toxicity after radiotherapy

    DEFF Research Database (Denmark)

    Alsner, Jan; Andreassen, Christian Nicolaj; Overgaard, Jens

    2008-01-01

    During the last decade, a number of studies have supported the hypothesis that there is an important genetic component to the observed interpatient variability in normal tissue toxicity after radiotherapy. This review summarizes the candidate gene association studies published so far on the risk...

  2. Evaluation of normal tissue responses to high-LET radiations

    International Nuclear Information System (INIS)

    Halnan, K.E.

    1979-01-01

    Clinical results presented have been analysed to evaluate normal tissue responses to high-LET radiations. Damage to brain, spinal cord, gut, skin, connective tissue and bone has occurred. A high RBE is probable for brain and possible for spinal cord and gut but other reasons for damage are also discussed. A net gain seems likely. Random controlled trials are advocated. (author)

  3. Radiation-induced normal tissue damage: implications for radiotherapy

    International Nuclear Information System (INIS)

    Prasanna, Pataje G.

    2014-01-01

    Radiotherapy is an important treatment modality for many malignancies, either alone or as a part of combined modality treatment. However, despite technological advances in physical treatment delivery, patients suffer adverse effects from radiation therapy due to normal tissue damage. These side effects may be acute, occurring during or within weeks after therapy, or intermediate to late, occurring months to years after therapy. Minimizing normal tissue damage from radiotherapy will allow enhancement of tumor killing and improve tumor control and patients quality of life. Understanding mechanisms through which radiation toxicity develops in normal tissue will facilitate the development of next generation radiation effect modulators. Translation of these agents to the clinic will also require an understanding of the impact of these protectors and mitigators on tumor radiation response. In addition, normal tissues vary in radiobiologically important ways, including organ sensitivity to radiation, cellular turnover rate, and differences in mechanisms of injury manifestation and damage response. Therefore, successful development of radiation modulators may require multiple approaches to address organ/site-specific needs. These may include treatments that modify cellular damage and death processes, inflammation, alteration of normal flora, wound healing, tissue regeneration and others, specifically to counter cancer site-specific adverse effects. Further, an understanding of mechanisms of normal tissue damage will allow development of predictive biomarkers; however harmonization of such assays is critical. This is a necessary step towards patient-specific treatment customization. Examples of important adverse effects of radiotherapy either alone or in conjunction with chemotherapy, and important limitations in the current approaches of using radioprotectors for improving therapeutic outcome will be highlighted. (author)

  4. Incorporating Single-nucleotide Polymorphisms Into the Lyman Model to Improve Prediction of Radiation Pneumonitis

    Energy Technology Data Exchange (ETDEWEB)

    Tucker, Susan L., E-mail: sltucker@mdanderson.org [Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Li Minghuan [Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong (China); Xu Ting; Gomez, Daniel [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Yuan Xianglin [Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Yu Jinming [Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong (China); Liu Zhensheng; Yin Ming; Guan Xiaoxiang; Wang Lie; Wei Qingyi [Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mohan, Radhe [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Vinogradskiy, Yevgeniy [University of Colorado School of Medicine, Aurora, Colorado (United States); Martel, Mary [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao Zhongxing [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-01-01

    Purpose: To determine whether single-nucleotide polymorphisms (SNPs) in genes associated with DNA repair, cell cycle, transforming growth factor-{beta}, tumor necrosis factor and receptor, folic acid metabolism, and angiogenesis can significantly improve the fit of the Lyman-Kutcher-Burman (LKB) normal-tissue complication probability (NTCP) model of radiation pneumonitis (RP) risk among patients with non-small cell lung cancer (NSCLC). Methods and Materials: Sixteen SNPs from 10 different genes (XRCC1, XRCC3, APEX1, MDM2, TGF{beta}, TNF{alpha}, TNFR, MTHFR, MTRR, and VEGF) were genotyped in 141 NSCLC patients treated with definitive radiation therapy, with or without chemotherapy. The LKB model was used to estimate the risk of severe (grade {>=}3) RP as a function of mean lung dose (MLD), with SNPs and patient smoking status incorporated into the model as dose-modifying factors. Multivariate analyses were performed by adding significant factors to the MLD model in a forward stepwise procedure, with significance assessed using the likelihood-ratio test. Bootstrap analyses were used to assess the reproducibility of results under variations in the data. Results: Five SNPs were selected for inclusion in the multivariate NTCP model based on MLD alone. SNPs associated with an increased risk of severe RP were in genes for TGF{beta}, VEGF, TNF{alpha}, XRCC1 and APEX1. With smoking status included in the multivariate model, the SNPs significantly associated with increased risk of RP were in genes for TGF{beta}, VEGF, and XRCC3. Bootstrap analyses selected a median of 4 SNPs per model fit, with the 6 genes listed above selected most often. Conclusions: This study provides evidence that SNPs can significantly improve the predictive ability of the Lyman MLD model. With a small number of SNPs, it was possible to distinguish cohorts with >50% risk vs <10% risk of RP when they were exposed to high MLDs.

  5. The Lyman alpha reference sample

    DEFF Research Database (Denmark)

    Hayes, M.; Östlin, G.; Schaerer, D.

    2013-01-01

    We report on new imaging observations of the Lyman alpha emission line (Lyα), performed with the Hubble Space Telescope, that comprise the backbone of the Lyman alpha Reference Sample. We present images of 14 starburst galaxies at redshifts 0.028

  6. DNA Double-Strand Break Rejoining in Complex Normal Tissues

    International Nuclear Information System (INIS)

    Ruebe, Claudia E.; Dong, Xiaorong; Kuehne, Martin; Fricke, Andreas; Kaestner, Lars; Lipp, Peter; Ruebe, Christian

    2008-01-01

    Purpose: The clinical radiation responses of different organs vary widely and likely depend on the intrinsic radiosensitivities of their different cell populations. Double-strand breaks (DSBs) are the most deleterious form of DNA damage induced by ionizing radiation, and the cells' capacity to rejoin radiation-induced DSBs is known to affect their intrinsic radiosensitivity. To date, only little is known about the induction and processing of radiation-induced DSBs in complex normal tissues. Using an in vivo model with repair-proficient mice, the highly sensitive γH2AX immunofluorescence was established to investigate whether differences in DSB rejoining could account for the substantial differences in clinical radiosensitivity observed among normal tissues. Methods and Materials: After whole body irradiation of C57BL/6 mice (0.1, 0.5, 1.0, and 2.0 Gy), the formation and rejoining of DSBs was analyzed by enumerating γH2AX foci in various organs representative of both early-responding (small intestine) and late-responding (lung, brain, heart, kidney) tissues. Results: The linear dose correlation observed in all analyzed tissues indicated that γH2AX immunofluorescence allows for the accurate quantification of DSBs in complex organs. Strikingly, the various normal tissues exhibited identical kinetics for γH2AX foci loss, despite their clearly different clinical radiation responses. Conclusion: The identical kinetics of DSB rejoining measured in different organs suggest that tissue-specific differences in radiation responses are independent of DSB rejoining. This finding emphasizes the fundamental role of DSB repair in maintaining genomic integrity, thereby contributing to cellular viability and functionality and, thus, tissue homeostasis

  7. A compendium of canine normal tissue gene expression.

    Directory of Open Access Journals (Sweden)

    Joseph Briggs

    Full Text Available BACKGROUND: Our understanding of disease is increasingly informed by changes in gene expression between normal and abnormal tissues. The release of the canine genome sequence in 2005 provided an opportunity to better understand human health and disease using the dog as clinically relevant model. Accordingly, we now present the first genome-wide, canine normal tissue gene expression compendium with corresponding human cross-species analysis. METHODOLOGY/PRINCIPAL FINDINGS: The Affymetrix platform was utilized to catalogue gene expression signatures of 10 normal canine tissues including: liver, kidney, heart, lung, cerebrum, lymph node, spleen, jejunum, pancreas and skeletal muscle. The quality of the database was assessed in several ways. Organ defining gene sets were identified for each tissue and functional enrichment analysis revealed themes consistent with known physio-anatomic functions for each organ. In addition, a comparison of orthologous gene expression between matched canine and human normal tissues uncovered remarkable similarity. To demonstrate the utility of this dataset, novel canine gene annotations were established based on comparative analysis of dog and human tissue selective gene expression and manual curation of canine probeset mapping. Public access, using infrastructure identical to that currently in use for human normal tissues, has been established and allows for additional comparisons across species. CONCLUSIONS/SIGNIFICANCE: These data advance our understanding of the canine genome through a comprehensive analysis of gene expression in a diverse set of tissues, contributing to improved functional annotation that has been lacking. Importantly, it will be used to inform future studies of disease in the dog as a model for human translational research and provides a novel resource to the community at large.

  8. T lymphocytes and normal tissue responses to radiation

    International Nuclear Information System (INIS)

    Schaue, Dörthe; McBride, William H.

    2012-01-01

    There is compelling evidence that lymphocytes are a recurring feature in radiation damaged normal tissues, but assessing their functional significance has proven difficult. Contradictory roles have been postulated in both tissue pathogenesis and protection, although these are not necessarily mutually exclusive as the immune system can display what may seem to be opposing faces at any one time. While the exact role of T lymphocytes in irradiated normal tissue responses may still be obscure, their accumulation after tissue damage suggests they may be critical targets for radiotherapeutic intervention and worthy of further study. This is accentuated by recent findings that pathologically damaged “self,” such as occurs after exposure to ionizing radiation, can generate danger signals with the ability to activate pathways similar to those that activate adoptive immunity to pathogens. In addition, the demonstration of T cell subsets with their recognition radars tuned to “self” moieties has revolutionized our ideas on how all immune responses are controlled and regulated. New concepts of autoimmunity have resulted based on the dissociation of immune functions between different subsets of immune cells. It is becoming axiomatic that the immune system has the power to regulate radiation-induced tissue damage, from failure of regeneration to fibrosis, to acute and chronic late effects, and even to carcinogenesis. Our understanding of the interplay between T lymphocytes and radiation-damaged tissue may still be rudimentary but this is a good time to re-examine their potential roles, their radiobiological and microenvironmental influences, and the possibilities for therapeutic manipulation. This review will discuss the yin and yang of T cell responses within the context of radiation exposures, how they might drive or protect against normal tissue side effects and what we may be able do about it.

  9. Analytical formulae in fractionated irradiation of normal tissue

    International Nuclear Information System (INIS)

    Kozubek, S.

    1982-01-01

    The new conception of the modeling of the cell tissue kinetics after fractionated irradiation is proposed. The formulae given earlier are compared with experimental data on various normal tissues and further adjustments are considered. The tissues are shown to exhibit several general patterns of behaviour. The repopulation, if it takes place, seems to start after some time, independently of fractionation in first approximation and can be treated as simple autogenesis. The results are compared with the commonly used NSD conception and the well-known Cohen cell tissue kinetic model

  10. Mathematical models of tumour and normal tissue response

    International Nuclear Information System (INIS)

    Jones, B.; Dale, R.G.; Charing Cross Group of Hospitals, London

    1999-01-01

    The historical application of mathematics in the natural sciences and in radiotherapy is compared. The various forms of mathematical models and their limitations are discussed. The Linear Quadratic (LQ) model can be modified to include (i) radiobiological parameter changes that occur during fractionated radiotherapy, (ii) situations such as focal forms of radiotherapy, (iii) normal tissue responses, and (iv) to allow for the process of optimization. The inclusion of a variable cell loss factor in the LQ model repopulation term produces a more flexible clonogenic doubling time, which can simulate the phenomenon of 'accelerated repopulation'. Differential calculus can be applied to the LQ model after elimination of the fraction number integers. The optimum dose per fraction (maximum cell kill relative to a given normal tissue fractionation sensitivity) is then estimated from the clonogen doubling times and the radiosensitivity parameters (or α/β ratios). Economic treatment optimization is described. Tumour volume studies during or following teletherapy are used to optimize brachytherapy. The radiation responses of both individual tumours and tumour populations (by random sampling 'Monte-Carlo' techniques from statistical ranges of radiobiological and physical parameters) can be estimated. Computerized preclinical trials can be used to guide choice of dose fractionation scheduling in clinical trials. The potential impact of gene and other biological therapies on the results of radical radiotherapy are testable. New and experimentally testable hypotheses are generated from limited clinical data by exploratory modelling exercises. (orig.)

  11. Radioprotection of normal tissues of the mouse by hypoxic breathing

    International Nuclear Information System (INIS)

    Stevens, G.N.; Joiner, B.; Denekamp, J.

    1989-01-01

    Hypoxic breathing during irradiation has been advocated as a therapeutic modality, to increase the efficacy of radiotherapy. In this form of treatment, the total and daily X-ray dose is increased by a factor of 1.25, on the assumption that all normal tissues in the beam will be protected to a similar extent by breathing gas containing a reduced oxygen concentration (usually 10%). To test this concept, we have determined the effect of varying the inspired oxygen tension on the radiosensitivity of 3 normal tissues in the mouse (kidney, jejunum and skin), and have compared these results with data from the literature for mouse lung. Reduction of the inspired oxygen tension from 21% (air) to 7-8% led to much greater radioprotection of skin (protection factor 1.37) than of lung (1.09). Protection factors for jejunum and kidney were 1.16 and 1.36 respectively. The results show that the extent of radioprotection afforded by hypoxic breathing is tissue dependent, and that great care must be taken clinically in choosing the increased radiation dose to be used in conjunction with hypoxic breathing

  12. Mathematical model of normal tissue injury in telegammatherapy

    International Nuclear Information System (INIS)

    Belov, S.A.; Lyass, F.M.; Mamin, R.G.; Minakova, E.I.; Raevskaya, S.A.

    1983-01-01

    A model of normal tissue injury as a result of exposure to ionizing radiation is based on an assumption that the degree of tissue injury is determined by the degree of destruction by certain critical cells. The dependence of the number of lethal injuriies on a single dose is expressed by a trinomial - linear and quadratic parts and a constant, obtained as a result of the processing of experimental data. Quantitative correlations have been obtained for the skin and brain. They have been tested using clinical and experimental material. The results of the testing point out to the absence of time dependence on a single up to 6-week irradiation cources. Correlation with an irradiation field has been obtained for the skin. A conclusion has been made that the concept of isoefficacy of irradiation cources is conditional. Spatial-time fractionation is a promising direction in the development of radiation therapy

  13. Role of plasminogen activator inhibitor type-1 in radiation-induced normal tissues injury

    International Nuclear Information System (INIS)

    Abderrahmani, R.

    2010-01-01

    Radiotherapy is an essential tool for cancer treatment, but there is a balance between benefits and risks related to the use of ionizing radiation: the objective is to deliver a maximum dose to the tumour to destroy or to sterilize it while protecting surrounding normal tissues. Radio-induced damages to normal tissues are therefore a limiting factor when increasing the dose delivered to the tumour. One of the objectives of this research thesis is to bring to the fore a relationship between the initiation of lesions and the development of late damages, more particularly in the intestine, and to identify the involved molecular actors and their inter-connectivity. After a first part presenting ionizing radiation, describing biological effects of ionizing radiation and their use in radiotherapy, presenting the intestine and the endothelium and discussing the intestine radio-sensitivity, discussing the radio-induced intestine damages and radiotherapy-induced complications, and presenting the plasminogen activator inhibitor (PAI-1) and its behaviour in presence of ionizing radiation, two articles are reproduced. The first one addresses the effect of a pharmacological inhibition and of genetic deficiency in PAI-1 on the evolution of radio-induced intestine lesions. The second one discusses the fact that radio-induced PAI-1-related death of endothelial cells determines the severity of early radio-induced intestine lesions

  14. Lyman NTCP model analysis of radiation-induced liver disease in hypofractionated conformal radiotherapy for primary liver carcinoma

    International Nuclear Information System (INIS)

    Xu Zhiyong; Zhu Yi; Zhao Jiaodong; Fu Xiaolong; Jiang Guoliang; Liang Shixiong; Zhu Xiaodong

    2006-01-01

    Objective: To identify the factors associated with radiation-induced liver disease (RILD) and to describe the probability of RILD using the Lyman normal tissue complication(NTCP) model for primary liver carcinoma(PLC) treated with hypofractionated conformal therapy (CRT). Methods: A total of 109 PLC patients treated with hypofractionated CRT were prospectively followed according to the Child-Pugh classification for liver cirrhosis, 93 patients in class A and 16 in class B. The mean dose of radiation to the isocenter was (53.5±5.5) Gy, fractions of (4.8±0.5) Gy, with interfraction interval of 48 hours and irradiation 3 times per week. Maximal likelihood analysis yielded the best estimates of parameters of the Lyman NTCP model for all patients; Child-Pugh A and Child-Pugh B patients, respectively. Results: Of all the patients, 17 developed RILD (17/109), 8 in Child-Pugh A (8/93) and 9 in Child-Pugh B (9/16). By multivariate analysis, only the Child-Pugh Grade of liver cirrhosis was the independent factor (P=0.000) associated with the developing of BILD. The best estimates of the NTCP parameters for all 109 patients were n=1.1, m=0.35 and TD 50 (1)=38.5 Gy. The n, m, TD 50 (1) estimated from patients with Child-Pugh A was 1.1, 0.28, 40.5 Gy, respectively, compared with 0.7, 0.43, 23 Gy respectively, for patients with Child-Pugh B. Conclusions: Primary liver cancer patients who possess Child-Pugh B cirrhosis would present a significantly greater susceptibility to RILD after hypofractionated CRT than patients with Child-Pugh A cirrhosis. The predominant risk factor for developing RILD is the severity of hepatic cirrhosis in the liver of PLC patients. (authors)

  15. Canine tumor and normal tissue response to heat and radiation

    International Nuclear Information System (INIS)

    Gillette, E.L.; McChesney, S.L.

    1985-01-01

    Oral squamous cell carcinomas of dogs were treated with either irradiation alone or combined with hyperthermia. Tumor control was assessed as no evidence of disease one year following treatment. Dogs were randomized to variable radiation doses which were given in ten fractions three times a week for three weeks. Heat was given three hours after the first and third radiation dose each week for seven treatments. The attempt was made to achieve a minimum tumor temperature of 42 0 C for thirty minutes with a maximum normal tissue temperature of 40 0 C. It was usually possible to selectively heat tumors. The TCD 50 for irradiation alone was about 400 rads greater than for heat plus irradiation. The dose response curve for heat plus radiation was much steeper than for radiation alone indicating less heterogeneity of tumor response. That also implies a much greater effectiveness of radiation combined with heat at higher tumor control probabilities. Early necrosis caused by heating healed with conservative management. No increase in late radiation necrosis was observed

  16. SU-D-18A-04: Quantifying the Ability of Tumor Tracking to Spare Normal Tissue

    Energy Technology Data Exchange (ETDEWEB)

    Burger, A; Buzurovic, I; Hurwitz, M; Williams, C; Lewis, J [Brigham and Women' s Hospital, Dana-Farber Cancer Center, Harvard Medical Sc, Boston, MA (United States); Mishra, P [Varian Medical Systems, Palo Alto, CA (United States); Seco, J [Mass General Hospital, Harvard Medical, Boston, MA (United States)

    2014-06-01

    Purpose: Tumor tracking allows for smaller tissue volumes to be treated, potentially reducing normal tissue damage. However, tumor tracking is a more complex treatment and has little benefit in some scenarios. Here we quantify the benefit of tumor tracking for a range of patients by estimating the dose of radiation to organs at risk and the normal tissue complication probability (NTCP) for both standard and tracking treatment plans. This comparison is performed using both patient 4DCT data and extended Cardiac-Torso (XCAT) digital phantoms. Methods: We use 4DCT data for 10 patients. Additionally, we generate digital phantoms with motion derived from measured patient long tumor trajectories to compare standard and tracking treatment plans. The standard treatment is based on the average intensity projection (AIP) of 4DCT images taken over a breath cycle. The tracking treatment is based on doses calculated on images representing the anatomy at each time point. It is assumed that there are no errors in tracking the target. The NTCP values are calculated based on RTOG guidelines. Results: The mean reduction in the mean dose delivered was 5.5% to the lungs (from 7.3 Gy to 6.9 Gy) and 4.0% to the heart (from 12.5 Gy to 12.0 Gy). The mean reduction in the max dose delivered was 13% to the spinal cord (from 27.6 Gy to 24.0 Gy), 2.5% to the carina (from 31.7 Gy to 30.9 Gy), and 15% to the esophagus (from 69.6 Gy to 58.9 Gy). The mean reduction in the probability of 2nd degree radiation pneumonitis (RP) was 8.7% (3.1% to 2.8%) and the mean reduction in the effective volume was 6.8% (10.8% to 10.2%). Conclusions: Tumor tracking has the potential to reduce irradiation of organs at risk, and consequentially reduce the normal tissue complication probability. The benefits vary based on the clinical scenario. This study is supported by Varian Medical Systems, Inc.

  17. Large animal normal tissue tolerance with boron neutron capture.

    Science.gov (United States)

    Gavin, P R; Kraft, S L; DeHaan, C E; Swartz, C D; Griebenow, M L

    1994-03-30

    Normal tissue tolerance of boron neutron capture irradiation using borocaptate sodium (NA2B12H11SH) in an epithermal neutron beam was studied. Large retriever-type dogs were used and the irradiations were performed by single dose, 5 x 10 dorsal portal. Fourteen dogs were irradiated with the epithermal neutron beam alone and 35 dogs were irradiated following intravenous administration of borocaptate sodium. Total body irradiation effect could be seen from the decreased leukocytes and platelets following irradiation. Most values returned to normal within 40 days postirradiation. Severe dermal necrosis occurred in animals given 15 Gy epithermal neutrons alone and in animals irradiated to a total peak physical dose greater than 64 Gy in animals following borocaptate sodium infusion. Lethal brain necrosis was seen in animals receiving between 27 and 39 Gy. Lethal brain necrosis occurred at 22-36 weeks postirradiation. A total peak physical dose of approximately 27 Gy and blood-boron concentrations of 25-50 ppm resulted in abnormal magnetic resonance imaging results in 6 months postexamination. Seven of eight of these animals remained normal and the lesions were not detected at the 12-month postirradiation examination. The bimodal therapy presents a complex challenge in attempting to achieve dose response assays. The resultant total radiation dose is a composite of low and high LET components. The short track length of the boron fission fragments and the geometric effect of the vessels causes much of the intravascular dose to miss the presumed critical target of the endothelial cells. The results indicate a large dose-sparing effect from the boron capture reactions within the blood.

  18. Large animal normal tissue tolerance with boron neutron capture

    International Nuclear Information System (INIS)

    Gavin, P.R.; Swartz, C.D.; Kraft, S.L.; Briebenow, M.L.; DeHaan, C.E.

    1994-01-01

    Normal tissue tolerance of boron neutron capture irradiation using borocaptate sodium (NA 2 B 12 H 11 SH) in an epithermal neutron beam was studied. Large retriever-type dogs were used and the irradiations were performed by single dose, 5 x 10 dorsal portal. Fourteen dogs were irradiated with the epithermal neutron beam alone and 35 dogs were irradiated following intravenous administration of borocaptate sodium. Total body irradiation effect could be seen from the decreased leukocytes and platelets following irradiation. Most values returned to normal within 40 days postirradiation. Severe dermal necrosis occurred in animals given 15 Gy epithermal neutrons alone and in animals irradiated to a total peak physical dose greater than 64 Gy in animals following borocaptate sodium infusion. Lethal brain necrosis was seen in animals receiving between 27 and 39 Gy. Lethal brain necrosis occurred at 22-36 weeks postirradiation. A total peak physical dose of approximately 27 Gy and blood-boron concentrations of 25-50 ppm resulted in abnormal magnetic resonance imaging results in 6 months postexamination. Seven of eight of these animals remained normal and the lesions were not detected at the 12-month postirradiation examination. The bimodal therapy presents a complex challenge in attempting to achieve dose response assays. The resultant total radiation dose is a composite of low and high LET components. The short track length of the boron fission fragments and the geometric effect of the vessels causes much of the intravascular dose to miss the presumed critical target of the endothelial cells. The results indicate a large dose-sparing effect from the boron capture reactions within the blood. 23 refs., 6 figs., 2 tabs

  19. Radiobiological Determination of Dose Escalation and Normal Tissue Toxicity in Definitive Chemoradiation Therapy for Esophageal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Warren, Samantha, E-mail: Samantha.warren@oncology.ox.ac.uk [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Partridge, Mike [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Carrington, Rhys [Velindre Cancer Centre, Velindre Hospital, Cardiff (United Kingdom); Hurt, Chris [Wales Cancer Trials Unit, School of Medicine, Heath Park, Cardiff (United Kingdom); Crosby, Thomas [Velindre Cancer Centre, Velindre Hospital, Cardiff (United Kingdom); Hawkins, Maria A. [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom)

    2014-10-01

    Purpose: This study investigated the trade-off in tumor coverage and organ-at-risk sparing when applying dose escalation for concurrent chemoradiation therapy (CRT) of mid-esophageal cancer, using radiobiological modeling to estimate local control and normal tissue toxicity. Methods and Materials: Twenty-one patients with mid-esophageal cancer were selected from the SCOPE1 database (International Standard Randomised Controlled Trials number 47718479), with a mean planning target volume (PTV) of 327 cm{sup 3}. A boost volume, PTV2 (GTV + 0.5 cm margin), was created. Radiobiological modeling of tumor control probability (TCP) estimated the dose required for a clinically significant (+20%) increase in local control as 62.5 Gy/25 fractions. A RapidArc (RA) plan with a simultaneously integrated boost (SIB) to PTV2 (RA{sub 62.5}) was compared to a standard dose plan of 50 Gy/25 fractions (RA{sub 50}). Dose-volume metrics and estimates of normal tissue complication probability (NTCP) for heart and lungs were compared. Results: Clinically acceptable dose escalation was feasible for 16 of 21 patients, with significant gains (>18%) in tumor control from 38.2% (RA{sub 50}) to 56.3% (RA{sub 62.5}), and only a small increase in predicted toxicity: median heart NTCP 4.4% (RA{sub 50}) versus 5.6% (RA{sub 62.5}) P<.001 and median lung NTCP 6.5% (RA{sub 50}) versus 7.5% (RA{sub 62.5}) P<.001. Conclusions: Dose escalation to the GTV to improve local control is possible when overlap between PTV and organ-at-risk (<8% heart volume and <2.5% lung volume overlap for this study) generates only negligible increase in lung or heart toxicity. These predictions from radiobiological modeling should be tested in future clinical trials.

  20. Method for Automatic Selection of Parameters in Normal Tissue Complication Probability Modeling

    DEFF Research Database (Denmark)

    Christophides, Damianos; Appelt, Ane L; Gusnanto, Arief

    2018-01-01

    by multicollinearity reduction using the variance inflation factor and genetic algorithm optimization to determine an ordinal logistic regression model that minimizes the Bayesian information criterion. The process was repeated 100 times, and the model with the minimum Bayesian information criterion was recorded...

  1. Normal tissue tolerance to external beam radiation therapy: The stomach

    International Nuclear Information System (INIS)

    Oberdiac, P.; Mineur, L.

    2010-01-01

    In the following article, we will discuss general issues relating to acute and late gastric's radiation toxicities. The tolerance of the stomach to complete or partial organ irradiation is more un-appreciated than for most other organs. We consulted the Medline database via PubMed and used the key words gastric - radiotherapy - toxicity. Currently, 60 Gy or less is prescribed in gastric radiation therapy. Acute clinical toxicity symptoms are predominantly nausea and vomiting. Although there is a general agreement that the whole stomach tolerance is for doses of 40 to 45 Gy without unacceptable complication, it is well established that a stomach dose of 35 Gy increases the risk of ulcer complications. (authors)

  2. Mechanistic simulation of normal-tissue damage in radiotherapy-implications for dose-volume analyses

    International Nuclear Information System (INIS)

    Rutkowska, Eva; Baker, Colin; Nahum, Alan

    2010-01-01

    A radiobiologically based 3D model of normal tissue has been developed in which complications are generated when 'irradiated'. The aim is to provide insight into the connection between dose-distribution characteristics, different organ architectures and complication rates beyond that obtainable with simple DVH-based analytical NTCP models. In this model the organ consists of a large number of functional subunits (FSUs), populated by stem cells which are killed according to the LQ model. A complication is triggered if the density of FSUs in any 'critical functioning volume' (CFV) falls below some threshold. The (fractional) CFV determines the organ architecture and can be varied continuously from small (series-like behaviour) to large (parallel-like). A key feature of the model is its ability to account for the spatial dependence of dose distributions. Simulations were carried out to investigate correlations between dose-volume parameters and the incidence of 'complications' using different pseudo-clinical dose distributions. Correlations between dose-volume parameters and outcome depended on characteristics of the dose distributions and on organ architecture. As anticipated, the mean dose and V 20 correlated most strongly with outcome for a parallel organ, and the maximum dose for a serial organ. Interestingly better correlation was obtained between the 3D computer model and the LKB model with dose distributions typical for serial organs than with those typical for parallel organs. This work links the results of dose-volume analyses to dataset characteristics typical for serial and parallel organs and it may help investigators interpret the results from clinical studies.

  3. The normal tissue sparing obtained with simultaneous treatment of pelvic lymph nodes and bladder using intensity-modulated radiotherapy

    International Nuclear Information System (INIS)

    Soendergaard, Jimmi; Hoeyer, Morten; Wright, Pauliina; Grau, Cai; Muren, Ludvig Paul; Petersen, Joergen B.

    2009-01-01

    We have implemented an intensity-modulated radiotherapy (IMRT) protocol for simultaneous irradiation of bladder and lymph nodes. In this report, doses to normal tissue from IMRT and our previous conformal sequential boost technique are compared. Material and methods. Sixteen patients with urinary bladder cancer were treated using a six-field dynamic IMRT beam arrangement delivering 60 Gy to the bladder and 48 Gy to the pelvic lymph nodes. Dose-volume histogram (DVH) parameters for relevant normal tissues (bowel, bowel cavity, rectum and femoral heads) for the IMRT plans were compared with corresponding DVHs from our previous conformal sequential boost technique. Calculations of the generalized Equivalent Uniform Dose (gEUD) were performed for the bowel, with a reference volume of 200 cm 3 and a volume effect parameter k = 4, as well as for the rectum, using k = 12. Acute gastrointestinal (GI) and genitourinary (GU) RTOG toxicity was recorded. Results. Statistical significant normal tissue sparing was obtained by IMRT. For the bowel, a significant reduction was obtained at all dose levels between 20 and 50 Gy (p 3 at 50 Gy, while the gEUD was reduced from 58 to 53 Gy (p 3 at 50 Gy. The rectum gEUD was reduced from 55 to 53 Gy (p < 0.05). For the femoral heads, IMRT reduced the maximum dose as well as the volumes above all dose levels. The rate of acute peak Grade 2 GI RTOG complications was 38% after IMRT. Conclusion. IMRT to the urinary bladder and elective lymph nodes result in considerable normal tissue sparing compared to conformal sequential boost technique. This has paved the way for further studies combining IMRT with image-guided radiotherapy (IGRT) in bladder cancer

  4. Relationship between acute and late normal tissue injury after postoperative radiotherapy in endometrial cancer

    International Nuclear Information System (INIS)

    Jereczek-Fossa, Barbara A.; Jassem, Jacek; Badzio, Andrzej

    2002-01-01

    Purpose: To evaluate the relationship between acute and late normal tissue reactions in 317 consecutive endometrial cancer patients treated with surgery and adjuvant radiotherapy (RT). Methods: The data of 317 patients (staging according to the International Federation of Gynecology and Obstetrics) treated with postoperative RT were analyzed. Both low-dose-rate brachytherapy and external beam RT were applied in 247 patients (78%); brachytherapy only in 49 (15%) and external beam irradiation only in 21 (7%). The median follow-up was 7.3 years (range 4-21). The European Organization for Research and Treatment of Cancer, Radiation Therapy Oncology Group system with elements of the late effects of normal tissue, subjective, objective, management, analytic (LENT/SOMA) scale was used to score the RT reactions. The correlation between the occurrence and severity of acute and late bowel and bladder toxicity, as well as the relationship between the severity of acute effects and time to occurrence of late reactions, were assessed using linear and logistic regression analyses. Results: Of the 317 patients, 268 (85%) experienced acute RT reactions of any grade. Severe acute bowel reactions were observed in 15 patients (5%), urinary bladder complications in 1 patient (0.5%), cutaneous in 1 patient (0.5%), and vaginal in 1 patient (0.5%). Severe acute hematologic toxicity was seen in 3 patients (1%). A total of 158 patients (51%) experienced late RT reactions of any grade. Severe late bowel reactions were observed in 19 patients (6%), urinary bladder in 5 (2%), vaginal in 3 (1%), and bone in 10 (4%). When all toxic events were considered, there was a highly significant correlation between the acute and late bowel reactions (p <0.001), but the acute and late urinary bladder reactions did not correlate (p=0.64). The grade of acute toxicity was found to predict the grade of late toxicity for the bowel but not for the bladder (p<0.001 and p=0.47, respectively). The severity of acute

  5. DNA double strand break repair pathway plays a significant role in determining the radiotherapy induced normal tissue toxicity among head-and-neck and breast cancer

    International Nuclear Information System (INIS)

    Sadashiva, Satish Rao Bola; Mumbrekar, Kamalesh Dattaram; Venkatesh, Goutham Hassan; Fernandes, Donald Jerard; Bejadi, Vadhiraja Manjunath; Kapaettu, Satyamoorthy

    2014-01-01

    The ability to predict individual risk of radiotherapy induced normal tissue complications prior to the therapy may give an opportunity to personalize the treatment aiming improved therapeutic effect and quality of life. Therefore, predicting the risk of developing acute reactions before the initiation of radiation therapy may serve as a potential biomarker. DNA double-strand break (DSB) induction and its repair kinetics in lymphocytes of Head-and-Neck (n = 183) and Breast cancer (n = 132) patients undergoing chemoradiation or radiation therapy alone were analyzed by performing γ-H2AX foci, neutral comet and a modified neutral filter elution assay. Candidate radioresponsive genes like DNA repair, antioxidant pathway, profibrotic cytokine genes were screened for the common variants for their association with normal tissue toxicity outcome. Patients were stratified as non-over responders (NOR) and over responders (OR) based on their Radiation Therapy Oncology Group grading for normal tissue adverse reactions. Our results suggest that DSB repair plays a major role in the development of normal tissue adverse reactions in H and N and Breast cancer patients. The cellular (γ-H2AX analysis) and SNP analysis may have the potential to be developed into a clinically useful predictive assay for identifying the normal tissue over reactors

  6. Normal tissue tolerance to external beam radiation therapy: Ovaries

    International Nuclear Information System (INIS)

    Gross, E.; Champetier, C.; Zaccariotto, A.; Duberge, T.; Guerder, C.; Pointreau, Y.; Ortholan, C.; Chauvet, B.

    2010-01-01

    Clinical situations requiring protections of ovaries are mainly paediatric irradiations and pre-menopausal pelvic irradiations. The main complication of ovarian irradiation is the induced castration. Ovaries are extremely radiosensitive organs with strong interpersonal variations. The castrative effect of irradiation depends mainly on two factors: patient's age and the dose delivered to ovaries. The surgical technique of ovarian transposition allows to minimize the dose received by ovaries by taking them away, out of irradiation fields; the aim is to exclude them from the volume receiving 5 Gy or more, and if possible from those receiving 2 Gy. This technique becomes integrated into a multidisciplinary approach of conservation of fertility for patients exposed to other cytotoxic treatments. (authors)

  7. Normal tissue tolerance to external beam radiation therapy: Peripheral nerves

    International Nuclear Information System (INIS)

    Henriques de Figueiredo, B.; Dejean, C.; Sargos, P.; Kantor, G.; Huchet, A.; Mamou, N.; Loiseau, H.

    2010-01-01

    Plexopathies and peripheral neuropathies appear progressively and with several years delay after radiotherapy. These lesions are observed principally after three clinical situations: supraclavicular and axillar irradiations for breast cancer, pelvic irradiations for various pathologies and limb irradiations for soft tissue sarcomas. Peripheral nerves and plexus (brachial and lumbosacral) are described as serial structures and are supposed to receive less than a given maximum dose linked to the occurrence of late injury. Literature data, mostly ancient, define the maximum tolerable dose to a threshold of 60 Gy and highlight also a great influence of fractionation and high fraction doses. For peripheral nerves, most frequent late effects are pain with significant differences of occurrence between 50 and 60 Gy. At last, associated pathologies (diabetes, vascular pathology, neuropathy) and associated treatments have probably to be taken into account as additional factors, which may increase the risk of these late radiation complications. (authors)

  8. Tolerance of normal tissues to radiation therapy: Ear

    International Nuclear Information System (INIS)

    Fleury, B.; Lapeyre, M.

    2010-01-01

    The main objective of this work was to describe, based on a literature survey, the radiation-induced toxicity of the ear and to try to establish the limiting dose. The limiting toxicity was the sensorineural hearing loss. A dose-effect relationship has been described by several authors. Thirty to 40% of patients who are irradiated for head and neck cancer are concerned, but the intensity of the hearing loss tends to depend on the exact localisation of the primary tumour: nasopharyngeal irradiations, paranasal sinusal and parotid irradiation are at greater risk of complication. High frequencies are more vulnerable than the lower ones. Age of patients, as well as baseline hearing abilities, deeply influence the issue. As far as possible, the dose to the inner ear (the cochlea more precisely) should be kept under 40 Gy. In case of association with other causes of toxicity (such as age, low baseline value, association to cisplatin), this dose should be as low as possible. Should carcinologic constraints lead to toxic doses, then patients should be properly informed. (authors)

  9. Therapy-induced effects in normal tissue; Therapieinduzierte Effekte am Normalgewebe

    Energy Technology Data Exchange (ETDEWEB)

    Kaick, G. van; Delorme, S. [Deutsches Krebsforschungszentrum (DKFZ), Abteilung E010 - Radiologie, Heidelberg (Germany)

    2008-09-15

    More than 50% of cancer patients survive for more than 5 years, owing to modern and effective treatment. Therefore, long-term sequelae of treatment are more frequently seen than in the past. Such effects on normal tissue may both mimic and obscure tumor recurrences. Besides the direct consequences of surgery, tissue damage due to radiation or chemotherapy frequently cause problems in differential diagnosis. Among the numerous sequelae of radiotherapy, the most prominent are disturbance of the blood-brain barrier, radiation pneumonitis, osteodystrophy and osteoradionecrosis, fatty changes of bone marrow, or increased radiodensity of breast parenchyma. Chemotherapy may cause, e.g., diffuse abnormalities of white matter, pneumonitis and lung fibrosis, cardiomyopathy, or diffuse and patchy changes in bone marrow signals in MRI. The most devastating long-term complications are secondary cancers and leukemia induced by both radiotherapy and chemotherapy. (orig.) [German] Mehr als 50% der Tumorpatienten ueberleben dank moderner Therapie laenger als 5 Jahre, sodass die Spaetfolgen am gesunden Gewebe haeufiger und genauer erfasst werden. Diese koennen Tumorrezidive sowohl verschleiern als auch vortaeuschen. Neben den unmittelbaren Folgen operativer Eingriffe sind Auswirkungen der Chemo- und Strahlentherapie ein haeufiges differenzialdiagnostisches Problem. Wichtige Folgen einer Strahlentherapie sind z. B. Blut-Hirn-Schranken-Stoerungen, Strahlenpneumonitis, Osteodystrophie und -radionekrose, Verfettung des blutbildenden Knochenmarks oder Parenchymverdichtungen der Brust. Chemotherapie kann u. a. zur Leukenzephalopathie, Pneumonitis und Lungenfibrose, Kardiomyopathie sowie zu diffusen und fleckfoermigen Signalaenderungen des Knochenmarks in der MRT fuehren. Die schwerstwiegende Spaetkomplikation ist die Induktion solider Zweittumoren und Leukaemien sowohl nach Strahlen- als auch Chemotherapie. (orig.)

  10. A method of analyzing rectal surface area irradiated and rectal complications in prostate conformal radiotherapy

    International Nuclear Information System (INIS)

    Lu Yong; Song, Paul Y.; Li Shidong; Spelbring, Danny R.; Vijayakumar, Srinivasan; Haraf, Daniel J.; Chen, George T.Y.

    1995-01-01

    Purpose: To develop a method of analyzing rectal surface area irradiated and rectal complications in prostate conformal radiotherapy. Methods and Materials: Dose-surface histograms of the rectum, which state the rectal surface area irradiated to any given dose, were calculated for a group of 27 patients treated with a four-field box technique to a total (tumor minimum) dose ranging from 68 to 70 Gy. Occurrences of rectal toxicities as defined by the Radiation Therapy Oncology Group (RTOG) were recorded and examined in terms of dose and rectal surface area irradiated. For a specified end point of rectal complication, the complication probability was analyzed as a function of dose irradiated to a fixed rectal area, and as a function of area receiving a fixed dose. Lyman's model of normal tissue complication probability (NTCP) was used to fit the data. Results: The observed occurrences of rectal complications appear to depend on the rectal surface area irradiated to a given dose level. The patient distribution of each toxicity grade exhibits a maximum as a function of percentage surface area irradiated, and the maximum moves to higher values of percentage surface area as the toxicity grade increases. The dependence of the NTCP for the specified end point on dose and percentage surface area irradiated was fitted to Lyman's NTCP model with a set of parameters. The curvature of the NTCP as a function of the surface area suggests that the rectum is a parallel structured organ. Conclusions: The described method of analyzing rectal surface area irradiated yields interesting insight into understanding rectal complications in prostate conformal radiotherapy. Application of the method to a larger patient data set has the potential to facilitate the construction of a full dose-surface-complication relationship, which would be most useful in guiding clinical practice

  11. Predicting Lung Radiotherapy-Induced Pneumonitis Using a Model Combining Parametric Lyman Probit With Nonparametric Decision Trees

    International Nuclear Information System (INIS)

    Das, Shiva K.; Zhou Sumin; Zhang, Junan; Yin, F.-F.; Dewhirst, Mark W.; Marks, Lawrence B.

    2007-01-01

    Purpose: To develop and test a model to predict for lung radiation-induced Grade 2+ pneumonitis. Methods and Materials: The model was built from a database of 234 lung cancer patients treated with radiotherapy (RT), of whom 43 were diagnosed with pneumonitis. The model augmented the predictive capability of the parametric dose-based Lyman normal tissue complication probability (LNTCP) metric by combining it with weighted nonparametric decision trees that use dose and nondose inputs. The decision trees were sequentially added to the model using a 'boosting' process that enhances the accuracy of prediction. The model's predictive capability was estimated by 10-fold cross-validation. To facilitate dissemination, the cross-validation result was used to extract a simplified approximation to the complicated model architecture created by boosting. Application of the simplified model is demonstrated in two example cases. Results: The area under the model receiver operating characteristics curve for cross-validation was 0.72, a significant improvement over the LNTCP area of 0.63 (p = 0.005). The simplified model used the following variables to output a measure of injury: LNTCP, gender, histologic type, chemotherapy schedule, and treatment schedule. For a given patient RT plan, injury prediction was highest for the combination of pre-RT chemotherapy, once-daily treatment, female gender and lowest for the combination of no pre-RT chemotherapy and nonsquamous cell histologic type. Application of the simplified model to the example cases revealed that injury prediction for a given treatment plan can range from very low to very high, depending on the settings of the nondose variables. Conclusions: Radiation pneumonitis prediction was significantly enhanced by decision trees that added the influence of nondose factors to the LNTCP formulation

  12. Normal tissue damage in radiotherapy development of a clinical audit tool

    International Nuclear Information System (INIS)

    Barrett, A.

    2001-01-01

    Radiotherapy treatments are evaluated by two main outcomes, rates of cure or local tumour control and normal tissue complication rates. Many excellent schemes have been devised for recording the late effects of radiotherapy treatments including the RTOG and LENT SOMA Scales. These have proved invaluable in documenting the outcome of clinical trials, but have proved too complex and time consuming for routine daily use in busy departments. A group in Eindhoven led by Professor Lybeert undertook a pilot study of a potential way of auditing late radiation complications. Using a simplified form derived from the LENT SOMA scales, they collected data on grade 3 and 4 complications in a total of 675 patients and were able to correlate a number of particular complications with specific protocols, ICD codes and physician practice. Further review of the case records made it possible to identify specific factors which may have led to toxicity and could be taken into account to modify treatment protocols. From September 1999 clinicians in participating centres undertaking normal follow-up procedures were asked to identify patients who showed evidence of grade 3 or 4 toxicity as defined in the pro-forma. Date of radiotherapy was recorded so that a temporal correlation of complication with treatment could be made, but this study did not attempt to assess the incidence of complications, but to provide a cross-sectional study of prevalence. Centres participating in the study have been Eindhoven, Koeln, Gent, Brussels, Glasgow, Mount Vernon, Madrid, Geneva and Lyon. In Eindhoven 651 reports were collected between January 1995 and December 1999. 89 reports had to be discarded because complications were not validated by the reviewing radiotherapists. Dr Lybeert noticed that individual radiotherapists appeared to have different thresholds for reporting specific complications. 13 patients deaths appeared to be related to radiation problems. An overall level of detection of morbidity was

  13. Identification of molecular mechanisms of radiation-induced vascular damage in normal tissues using microarray analyses

    International Nuclear Information System (INIS)

    Kruse, J.J.C.M.; Te Poele, J.A.M.; Russell, N.S.; Boersma, L.J.; Stewart, F.A.

    2003-01-01

    Radiation-induced telangiectasia, characterized by thin-walled dilated blood vessels, can be a serious late complication in patients that have been previously treated for cancer. It might cause cosmetic problems when occurring in the skin, and excessive bleeding requiring surgery when occurring in rectal mucosa. The mechanisms underlying the development of radiation-induced telangiectasia are unclear. The aim of the present study is to determine whether microarrays are useful for studying mechanisms of radiation-induced telangiectasia. The second aim is to test the hypotheses that telangiectasia is characterized by a final common pathway in different tissues. Microarray experiments were performed using amplified RNA from (sham)irradiated mouse tissues (kidney, rectum) at different intervals (1-30 weeks) after irradiation. After normalization procedures, the differentially expressed genes were identified. Control/repeat experiments were done to confirm that the observations were not artifacts of the array procedure. The mouse kidney experiments showed significant upregulation of 31 and 42 genes and downregulation of 9 and 4 genes at 10 and 20 weeks after irradiation, respectively. Irradiated mouse rectum has 278 upregulated and 537 downregulated genes at 10 weeks and 86 upregulated and 29 downregulated genes at 20 weeks. During the development of telangiectasia, 19 upregulated genes and 5 downregulated genes were common to both tissues. Upregulation of Jagged-1, known to play a role in angiogenesis, is particularly interesting in the context of radiation-induced telangiectasia. Microarrays are affective discovery tools to identify novel genes of interest, which may be involved in radiation-induced normal tissue injury. Using information from control arrays (particularly straight color, color reverse and self-self experiments) allowed for a more accurate and reproducible identification of differentially expressed genes than the selection of an arbitrary 2-fold change

  14. SU-E-T-168: Evaluation of Normal Tissue Damage in Head and Neck Cancer Treatments

    International Nuclear Information System (INIS)

    Ai, H; Zhang, H

    2014-01-01

    Purpose: To evaluate normal tissue toxicity in patients with head and neck cancer by calculating average survival fraction (SF) and equivalent uniform dose (EUD) for normal tissue cells. Methods: 20 patients with head and neck cancer were included in this study. IMRT plans were generated using EclipseTM treatment planning system by dosimetrist following clinical radiotherapy treatment guidelines. The average SF for three different normal tissue cells of each concerned structure can be calculated from dose spectrum acquired from differential dose volume histogram (DVH) using linear quadratic model. The three types of normal tissues include radiosensitive, moderately radiosensitive and radio-resistant that represents 70%, 50% and 30% survival fractions, respectively, for a 2-Gy open field. Finally, EUDs for three types of normal tissue of each structure were calculated from average SF. Results: The EUDs of the brainstem, spinal cord, parotid glands, brachial plexus and etc were calculated. Our analysis indicated that the brainstem can absorb as much as 14.3% of prescription dose to the tumor if the cell line is radiosensitive. In addition, as much as 16.1% and 18.3% of prescription dose were absorbed by the brainstem for moderately radiosensitive and radio-resistant cells, respectively. For the spinal cord, the EUDs reached up to 27.6%, 35.0% and 42.9% of prescribed dose for the three types of radiosensitivities respectively. Three types of normal cells for parotid glands can get up to 65.6%, 71.2% and 78.4% of prescription dose, respectively. The maximum EUDs of brachial plexsus were calculated as 75.4%, 76.4% and 76.7% of prescription for three types of normal cell lines. Conclusion: The results indicated that EUD can be used to quantify and evaluate the radiation damage to surrounding normal tissues. Large variation of normal tissue EUDs may come from variation of target volumes and radiation beam orientations among the patients

  15. The effect of setup uncertainty on normal tissue sparing with IMRT for head-and-neck cancer

    International Nuclear Information System (INIS)

    Manning, Matthew A.; Wu Quiwen; Cardinale, Robert M.; Mohan, Radhe; Lauve, Andrew D.; Kavanagh, Brian D.; Morris, Monica M.; Schmidt-Ullrich, Rupert K.

    2001-01-01

    coverage of the nodal region adjacent to the parotid gland. As expected, when the plans were shifted, the greatest increase in contralateral parotid irradiation was noted with shifts toward the contralateral parotid gland. With these shifts, the average volume of contralateral parotid receiving greater than 30 Gy was reduced from 22% to 4% when a PRV was used. This correlated with a reduction in the average normal-tissue complication probability (NTCP) from 22% to 7%. Conclusions: The use of PRV may limit the volume of normal tissue structures, such as the parotid gland, exceeding tolerance dose as a result of setup errors. Consequently, it will be important to incorporate the nomenclature of ICRU-62 into the design of future IMRT studies, if the clinical gains of increased normal-tissue sparing are to be realized

  16. Late effects of normal tissues (lent) scoring system: the soma scale

    International Nuclear Information System (INIS)

    Mornex, F.; Pavy, J.J.; Denekamp, J.

    1997-01-01

    Radiation tolerance of normal tissues remains the limiting factor for delivering tumoricidal dose. The late toxicity of normal tissues is the most critical element of an irradiation: somatic, functional and structural alterations occur during the actual treatment itself, but late effects manifest months to years after acute effects heal, and may progress with time. The optimal therapeutic ratio ultimately requires not only complete tumor clearance, but also minimal residual injury to surrounding vital normal tissues. The disparity between the intensity of acute and late effects and the inability to predict the eventual manifestation of late normal tissue injury has made radiation oncologists recognize the importance of careful patient follow-up. There is so far no uniform toxicity scoring system to compare several clinical studies in the absence of a 'common toxicity language'. This justifies the need to establish a precise evaluation system for the analysis of late effects of radiation on normal tissues. The SOMA/LENT scoring system results from an international collaboration. European Organization Treatment of Cancer (EORTC) and Radiation Therapy Oncology Group (RTOG) have created subcommittees with the aim of addressing the question of standardized toxic effects criteria. This effort appeared as a necessity to standardize and improve the data recording, to then describe and evaluate uniform toxicity at regular time intervals. The current proposed scale is not yet validated, and should be used cautiously. (authors)

  17. Radiotherapy- and chemotherapy-induced normal tissue damage. The role of cytokines and adhesion molecules

    International Nuclear Information System (INIS)

    Plevova, P.

    2002-01-01

    Background. Ionising radiation and cytostatic agents used in cancer therapy exert damaging effects on normal tissues and induce a complex response at the cellular and molecular levels. Cytokines and adhesion molecules are involved in this response. Methods. Published data on the given topic have been reviewed. Results and conclusions. Various cytokines and adhesion molecules, including tumor necrosis factor α, interleukins- 1,-2,-4, and -6, interferon γ, granulocyte macrophage- and macrophage- colony stimulating factors, transforming growth factor β, platelet-derived growth factor, insulin-like growth factor I, fibroblast and epidermal growth factors, platelet-activating factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E- and P-selectins are involved in the response of normal tissues to ionizing radiation- and chemotherapy- induced normal tissues damage and are co-responsible for some side effects of these treatment modalities, including fever, anorexia and fatigue, suppression of hematopoiesis, both acute and late local tissue response. (author)

  18. Iso-effect tables and therapeutic ratios for epidermoid cancer and normal tissue stroma

    International Nuclear Information System (INIS)

    Cohen, L.; Creditor, M.

    1983-01-01

    Available literature on radiation injury to normal tissue stroma and ablation of epidermoid carcinoma was surveyed. Computer programs (RAD3 and RAD1) were then used to derive cell kinetic parameters and generate iso-effect tables for the relevant tissues. The two tables provide a set of limiting doses for tolerance of normal connective tissue (16% risk of injury) and for ablation of epidermoid cancer (16% risk of recurrence) covering a wide range of treatment schedules. Calculating the ratios of normal tissue tolerance to tumor control doses for each treatment scheme provides an array of therapeutic ratios, from which appropriate treatment schemes can be selected

  19. Modification of the biologic dose to normal tissue by daily fraction

    Energy Technology Data Exchange (ETDEWEB)

    Wollin, M; Kagan, A R [Southern California Permanente Medical Group, Los Angeles Calif. (USA). Dep. of Radiation Therapy

    1976-12-01

    A method to predict normal tissue injury is proposed that includes high daily doses and unusual times successfully by calculating a new value called BIR (Biologic Index of Reaction). BIR and NSD were calculated for various normal tissue reactions. With the aid of statistical correlation techniques it is found that the BIR model is better than the NSD model in predicting radiation myelopathy and vocal edema and as good as NSD IN PREDICTING RIB FRACTURE/ Neither model predicts pericardial effusion. In no case were the results of BIR inferior to those of NSD.

  20. Stem Cell Therapy to Reduce Radiation-Induced Normal Tissue Damage

    NARCIS (Netherlands)

    Coppes, Rob P.; van der Goot, Annemieke; Lombaert, Isabelle M. A.

    Normal tissue damage after radiotherapy is still a major problem in cancer treatment. Stem cell therapy may provide a means to reduce radiation-induced side effects and improve the quality of life of patients. This review discusses the current status in stem cell research with respect to their

  1. Review of RBE values of 15 MeV neutrons for effects on normal tissues

    NARCIS (Netherlands)

    Broerse, J.J.

    1974-01-01

    Values of the relative biological effectiveness (RBE) of fast neutrons for effect on normal tissue depend not only on the neutron energy and the dose, but also on the type of tissue irradiated. Values of the RBE of 15 MeV neutrons are reviewed for rapidly proliferating rodent tissue, such as mouse

  2. Tumor control and normal tissue toxicity: The two faces of radiotherapy

    NARCIS (Netherlands)

    van Oorschot, B.

    2016-01-01

    This thesis discusses the two contrasting sides of radiotherapy: tumor control and normal tissue toxicity. On one hand, radiation treatment aims to target the tumor with the highest possible radiation dose, inducing as much lethal DNA damage as possible. On the other hand however, escalation of the

  3. High and Low LET Radiation Differentially Induce Normal Tissue Damage Signals

    International Nuclear Information System (INIS)

    Niemantsverdriet, Maarten; Goethem, Marc-Jan van; Bron, Reinier; Hogewerf, Wytse; Brandenburg, Sytze; Langendijk, Johannes A.; Luijk, Peter van; Coppes, Robert P.

    2012-01-01

    Purpose: Radiotherapy using high linear energy transfer (LET) radiation is aimed at efficiently killing tumor cells while minimizing dose (biological effective) to normal tissues to prevent toxicity. It is well established that high LET radiation results in lower cell survival per absorbed dose than low LET radiation. However, whether various mechanisms involved in the development of normal tissue damage may be regulated differentially is not known. Therefore the aim of this study was to investigate whether two actions related to normal tissue toxicity, p53-induced apoptosis and expression of the profibrotic gene PAI-1 (plasminogen activator inhibitor 1), are differentially induced by high and low LET radiation. Methods and Materials: Cells were irradiated with high LET carbon ions or low LET photons. Cell survival assays were performed, profibrotic PAI-1 expression was monitored by quantitative polymerase chain reaction, and apoptosis was assayed by annexin V staining. Activation of p53 by phosphorylation at serine 315 and serine 37 was monitored by Western blotting. Transfections of plasmids expressing p53 mutated at serines 315 and 37 were used to test the requirement of these residues for apoptosis and expression of PAI-1. Results: As expected, cell survival was lower and induction of apoptosis was higher in high -LET irradiated cells. Interestingly, induction of the profibrotic PAI-1 gene was similar with high and low LET radiation. In agreement with this finding, phosphorylation of p53 at serine 315 involved in PAI-1 expression was similar with high and low LET radiation, whereas phosphorylation of p53 at serine 37, involved in apoptosis induction, was much higher after high LET irradiation. Conclusions: Our results indicate that diverse mechanisms involved in the development of normal tissue damage may be differentially affected by high and low LET radiation. This may have consequences for the development and manifestation of normal tissue damage.

  4. Radiosensitization In Vivo by Histone Deacetylase Inhibition with No Increase in Early Normal Tissue Radiation Toxicity.

    Science.gov (United States)

    Groselj, Blaz; Ruan, Jia-Ling; Scott, Helen; Gorrill, Jessica; Nicholson, Judith; Kelly, Jacqueline; Anbalagan, Selvakumar; Thompson, James; Stratford, Michael R L; Jevons, Sarah J; Hammond, Ester M; Scudamore, Cheryl L; Kerr, Martin; Kiltie, Anne E

    2018-02-01

    As the population ages, more elderly patients require radiotherapy-based treatment for their pelvic malignancies, including muscle-invasive bladder cancer, as they are unfit for major surgery. Therefore, there is an urgent need to find radiosensitizing agents minimally toxic to normal tissues, including bowel and bladder, for such patients. We developed methods to determine normal tissue toxicity severity in intestine and bladder in vivo , using novel radiotherapy techniques on a small animal radiation research platform (SARRP). The effects of panobinostat on in vivo tumor growth delay were evaluated using subcutaneous xenografts in athymic nude mice. Panobinostat concentration levels in xenografts, plasma, and normal tissues were measured in CD1-nude mice. CD1-nude mice were treated with drug/irradiation combinations to assess acute normal tissue effects in small intestine using the intestinal crypt assay, and later effects in small and large intestine at 11 weeks by stool assessment and at 12 weeks by histologic examination. In vitro effects of panobinostat were assessed by qPCR and of panobinostat, TMP195, and mocetinostat by clonogenic assay, and Western blot analysis. Panobinostat resulted in growth delay in RT112 bladder cancer xenografts but did not significantly increase acute (3.75 days) or 12 weeks' normal tissue radiation toxicity. Radiosensitization by panobinostat was effective in hypoxic bladder cancer cells and associated with class I HDAC inhibition, and protein downregulation of HDAC2 and MRE11. Pan-HDAC inhibition is a promising strategy for radiosensitization, but more selective agents may be more useful radiosensitizers clinically, resulting in fewer systemic side effects. Mol Cancer Ther; 17(2); 381-92. ©2017 AACR See all articles in this MCT Focus section, "Developmental Therapeutics in Radiation Oncology." ©2017 American Association for Cancer Research.

  5. LYMAN : a new window on the universe

    International Nuclear Information System (INIS)

    Dopita, M.A.; Tuohy, I.R.; Mathewson, D.S.; Hunstead, R.W.; Waterworth, M.D.

    1988-01-01

    This document is the final Phase A Science Report of the Australian LYMAN Science Working Group, and describes in detail the scientific objectives, technical feasibility, and engineering implementation of the LYMAN mission as developed in the Australian studies. LYMAN represents the next generation, high-orbit, UV space observatory, and is designed to operate over the wavelength range λ 100 - 1900 Angstrom. The prime spectral range is λ 900 - 1250 Angstrom, which will be covered at a resolution of λ/Δ λ = 30000, and the sensitivity of the instrumentation will be orders of magnitude better than previous missions. In this region we find the Lyman series of molecular and atomic hydrogen, as well as a whole host of atomic and ionic lines of great diagnostic power. LYMAN will be able to accomplish uniquely valuable astrophysics as a result, and will be applied to the study of all types of astronomical targets in the fields of cosmology, galactic research, the interstellar medium, stars in all stages of their evolution, and to particular solar system objects. The LYMAN Mission was the subject of a $1M study contract awarded by the Australian Space Office, a section of DITAC, to Auspace Pty. Ltd. The Phase A study was conduced in parallel with the ESA Phase A Study, and with a strong scientific and technical liaison between the two groups. LYMAN is now likely to be launched as a joint ESA/NASA project, but the future Australian role in the mission, as determined by current policy, would be minimal. Australia would therefore be effectively locked out of the very exciting front-line science described in this document, and the valuable university - industry liaison that has been developed over the last eight years will be lost

  6. SU-E-J-264: Using Magnetic Resonance Imaging-Derived Features to Quantify Radiotherapy-Induced Normal Tissue Morbidity

    Energy Technology Data Exchange (ETDEWEB)

    Thor, M; Tyagi, N; Deasy, J [Memorial Sloan Kettering Cancer Center, New York, NY (United States)

    2015-06-15

    Purpose: The aim of this study was to explore the use of Magnetic Resonance Imaging (MRI)-derived features as indicators of Radiotherapy (RT)-induced normal tissue morbidity. We also investigate the relationship between these features and RT dose in four critical structures. Methods: We demonstrate our approach for four patients treated with RT for base of tongue cancer in 2005–2007. For each patient, two MRI scans (T1-weighted pre (T1pre) and post (T1post) gadolinium contrast-enhancement) were acquired within the first six months after RT. The assessed morbidity endpoint observed in 2/4 patients was Grade 2+ CTCAEv.3 trismus. Four ipsilateral masticatory-related structures (masseter, lateral and medial pterygoid, and the temporal muscles) were delineated on both T1pre and T1post and these scans were co-registered to the treatment planning CT using a deformable demons algorithm. For each structure, the maximum and mean RT dose, and six MRI-derived features (the second order texture features entropy and homogeneity, and the first order mean, median, kurtosis, and skewness) were extracted and compared structure-wise between patients with and without trismus. All MRI-derived features were calculated as the difference between T1pre and T1post, ΔS. Results: For 5/6 features and all structures, ΔS diverged between trismus and non-trismus patients particularly for the masseter, lateral pterygoid, and temporal muscles using the kurtosis feature (−0.2 vs. 6.4 for lateral pterygoid). Both the maximum and mean RT dose in all four muscles were higher amongst the trismus patients (with the maximum dose being up to 25 Gy higher). Conclusion: Using MRI-derived features to quantify RT-induced normal tissue complications is feasible. We showed that several features are different between patients with and without morbidity and that the RT dose in all investigated structures are higher amongst patients with morbidity. MRI-derived features, therefore, has the potential to

  7. Chemical modification of conventional cancer radiotherapy. Tumor sensitization combined with normal tissue protection

    International Nuclear Information System (INIS)

    Kagiya, Tsutomu

    2006-01-01

    Nitrotriazole radiosensitizer, Sanazole (AK-2123, N-(2'-methoxyethyl)-2-(3''-nitro-1''-triazolyl) acetamide) developed by Kyoto University group was studied by 18 groups of 7 countries on fundamental aspects and clinical studies by 30 groups of 12 countries, and reported its effects on tumor sensitization of conventional cancer radiotherapy. On the other hand, the glucosides of vitamin C (Ascorbic acid glucoside, (AsAG) and water soluble derivative of vitamin-E (α-tocopherol glucoside, TMG) developed by Kyoto University group were studied fundamentally by 4 groups of 4 countries and clinically by 2 groups of 2 countries, and reported their effects on normal tissue protection in cancer treatments. These two studies of tumor sensitization and normal tissue protection were proposed as an advanced strategy of conventional cancer radiotherapy. (author)

  8. CURED I - LENT. Late effects of cancer treatment on normal tissues

    International Nuclear Information System (INIS)

    Rubin, P.; Okunieff, P.; Constine, L.S.; Rochester Univ. School of Medicine and Dentistry, Rochester, NY; Marks, L.B.

    2008-01-01

    The search for the most favorable therapeutic ratio - at which ablation of cancer is achieved while normal tissues are conserved - has been modern radiation oncology's equivalent of the quest for the Holy Grail. Our awareness of the late effects of radiation grew during the past century as new modalities were introduced. Heightened normal tissue reactions accompanied the higher rates of cancer ablation achieved by escalation of radiation doses, accelerated fractionated radiotherapy, and aggressive concurrent chemotherapy and radiation regimens. This volume is based on the LENT V NCI-sponsored meeting held in May 2004 and the CURED I conference held in 2006. Written by experts in the field, it addresses a number of critical topics relating to late effects, such as mechanisms of injury, the role of screening, options for interventions, second malignancies, and prevention. It is hoped that it will assist the reader in understanding how to prevent and treat the long-term side-effects of irradiation. (orig.)

  9. SU-F-T-103: Analysis of Hepatitis B Virus Reactivation After Conformal Radiotherapy in Patients with Hepatocellular Carcinoma Using the Lyman NTCP Model

    International Nuclear Information System (INIS)

    Li, Z; Li, B; Huang, W; Li, H

    2016-01-01

    Purpose: The aim of this research was to investigate the feasibility of Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model in analyzing hepatitis B virus (HBV) reactivation in patients receiving conformal radiotherapy for patients with hepatocellular carcinoma (HCC). Methods: Between June 2009 and June 2012, 108 HBV-related HCC patients (90 were specifically selected and 18 patients were excluded) treated with conformal RT at three centers were enrolled in this retrospective study. They were all diagnosed as HCC by pathology or cytology. All 90 patients were followed up to September 2013 with a median follow-up time of 25.2 months. The parameters (TD50 (1), n, and m) of the modified LKB NTCP model were derived using maximum likelihood estimation. Bootstrap and leave-one-out were employed to test the generalizability of the results for use in a general population. Results: The incidences of complications in the study population were as follows: radiation-induced liver diseases (RILD) were 17.6%, HBV reactivation was 24.8%, and HBV reactivation-induced hepatitis was 22.7%, respectively. In multivariate analysis, the NTCP (p<0.001), and V20 were associated with HBV reactivation. TD50 (1), m and n were 42.9Gy (95% CI) (38.2–46.8), 0.14 (0.12–0.15) and 0.30 (0.2–0.33), respectively, for HBV reactivation. Bootstrap and leave-one-out results showed that the HBV parameter fits were extremely robust. Conclusion: A modified LKB NTCP model has been established to predict HBV reactivation for patients with HCC receiving conformal RT. The finding derives parameters set to predict potential endpoints of HBV reactivation.

  10. SU-F-T-103: Analysis of Hepatitis B Virus Reactivation After Conformal Radiotherapy in Patients with Hepatocellular Carcinoma Using the Lyman NTCP Model

    Energy Technology Data Exchange (ETDEWEB)

    Li, Z; Li, B [Laboratory of Image Science and Technology, Southeast University (China); Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences (China); Huang, W; Li, H [Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences (China)

    2016-06-15

    Purpose: The aim of this research was to investigate the feasibility of Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model in analyzing hepatitis B virus (HBV) reactivation in patients receiving conformal radiotherapy for patients with hepatocellular carcinoma (HCC). Methods: Between June 2009 and June 2012, 108 HBV-related HCC patients (90 were specifically selected and 18 patients were excluded) treated with conformal RT at three centers were enrolled in this retrospective study. They were all diagnosed as HCC by pathology or cytology. All 90 patients were followed up to September 2013 with a median follow-up time of 25.2 months. The parameters (TD50 (1), n, and m) of the modified LKB NTCP model were derived using maximum likelihood estimation. Bootstrap and leave-one-out were employed to test the generalizability of the results for use in a general population. Results: The incidences of complications in the study population were as follows: radiation-induced liver diseases (RILD) were 17.6%, HBV reactivation was 24.8%, and HBV reactivation-induced hepatitis was 22.7%, respectively. In multivariate analysis, the NTCP (p<0.001), and V20 were associated with HBV reactivation. TD50 (1), m and n were 42.9Gy (95% CI) (38.2–46.8), 0.14 (0.12–0.15) and 0.30 (0.2–0.33), respectively, for HBV reactivation. Bootstrap and leave-one-out results showed that the HBV parameter fits were extremely robust. Conclusion: A modified LKB NTCP model has been established to predict HBV reactivation for patients with HCC receiving conformal RT. The finding derives parameters set to predict potential endpoints of HBV reactivation.

  11. The influence of dose fractionation and dose rate on normal tissue responses

    International Nuclear Information System (INIS)

    Barendsen, G.W.

    1982-01-01

    An analysis of responses of a variety of normal tissues in animals to fractionated irradiations has been made with the aim of developing a formalism for the prediction of tolerance doses as a function of the dose per fraction and the overall treatment time. An important feature of the formalism is that it is directly based on radiological insights and therefore provides a logical concept to account for the diversity of tissue responses. (Auth.)

  12. Tumor and normal tissue responses to fractioned non-uniform dose delivery

    Energy Technology Data Exchange (ETDEWEB)

    Kaellman, P; Aegren, A; Brahme, A [Karolinska Inst., Stockholm (Sweden). Dept. of Radiation Physics

    1996-08-01

    The volume dependence of the radiation response of a tumor is straight forward to quantify because it depends primarily on the eradication of all its clonogenic cells. A tumor therefore has a parallel organization as any surviving clonogen in principle can repopulate the tumor. The difficulty with the response of the tumor is instead to know the density and sensitivity distribution of the most resistant clonogenic cells. The increase in the 50% tumor control dose and the decrease in the maximum normalized slope of the dose response relation, {gamma}, in presence of small compartments of resistant tumor cells have therefore been quantified to describe their influence on the dose response relation. Injury to normal tissue is a much more complex and gradual process. It depends on earlier effects induced long before depletion of the differentiated and clonogenic cells that in addition may have a complex structural and functional organization. The volume dependence of the dose response relation of normal tissues is therefore described here by the relative seriality, s, of the infrastructure of the organ. The model can also be generalized to describe the response of heterogeneous tissues to non uniform dose distributions. The new model is compared with clinical and experimental data on normal tissue response, and shows good agreement both with regard to the shape of dose response relation and the volume dependence of the isoeffect dose. The response of tumors and normal tissues are quantified for arbitrary dose fractionations using the linear quadratic cell survival parameters {alpha} and {beta}. The parameters of the dose response relation are derived both for a constant dose per fraction and a constant number of dose fractions, thus in the latter case accounting also for non uniform dose delivery. (author). 26 refs, 4 figs.

  13. Reirradiation of normal tissues: Preclinical radiobiological data; Reirradiation des tissus sains: donnees radiobiologiques precliniques

    Energy Technology Data Exchange (ETDEWEB)

    Bourgier, C.; Vozenin, M.C.; Deutsch, E. [Departement de radiotherapie et laboratoire Upres EA2710, institut Gustave-Roussy, 94 - Villejuif (France)

    2010-10-15

    Reirradiation represent an unfrequent particular clinical situation. The risk/benefit ratio assessment must be taken into account, considering both clinical and dosimetric aspects. There is a relatively limited amount of preclinical data available to date and clinicians should cautiously perform re-irradiations in selected indications. This review summarizes the experimental data available on reirradiation of normal tissues, the consequences on early and late toxicities as well as the intrinsic limitations of these models. (authors)

  14. Responses of some normal tissues to low doses of γ-radiation

    International Nuclear Information System (INIS)

    Withers, H.R.

    1975-01-01

    The response of four normal tissues to low doses of γ-radiation was measured in mice using three indirect methods. The survival curves for cells of the tissues studied (colon, jejunum, testis and haemoleucopoietic system) may be exponential over an uncertain dose range (from zero to between 100 to 230 rad), the slope being about one third of that in the high-dose region. Some of the uncertainties in the data probably reflect variations in age-density distribution. (author)

  15. Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Ho; Jenrow, Kenneth A.; Brown, Stephen L. [Dept.of Radiation Oncology, Henry Ford Health System, Detroit (United States)

    2014-09-15

    To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.

  16. ALERT. Adverse late effects of cancer treatment. Vol. 2. Normal tissue specific sites and systems

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, Philip; Constine, Louis S. [Univ. Rochester Medical Center, NY (United States). Dept. of Radiation Oncology; Marks, Lawrence B. (ed.) [Univ. North Carolina and Lineberger, Comprehensive Cancer Center, Chapel Hill, NC (United States). Dept. of Radiation Oncology

    2014-09-01

    Comprehensively documents potential late effects in all the normal tissue sites in the human body. Considers in detail the detection, diagnosis, management and prevention of effects and discusses prognostic outcomes. Clearly presents radiation risk factors and interactions with chemotherapy effects. Provides the most current evidence-based medicine for cancer care survivorship guidelines. The literature on the late effects of cancer treatment is widely scattered in different journals since all major organ systems are affected and management is based on a variety of medical and surgical treatments. The aim of ALERT - Adverse Late Effects of Cancer Treatment is to offer a coherent multidisciplinary approach to the care of cancer survivors. The central paradigm is that cytotoxic multimodal therapy results in a perpetual cascade of events that affects each major organ system differently and is expressed continually over time. Essentially, radiation and chemotherapy are intense biologic modifiers that allow for cancer cure and cancer survivorship but accelerate senescence of normal tissues and increase the incidence of age-related diseases and second malignant tumors. Volume 2 of this two-volume work comprehensively documents potential late effects in all the normal tissue anatomic sites in the human body. The detection, diagnosis, management and prevention of effects are all considered in detail, and prognostic outcomes are discussed. Radiation risk factors and interactions with chemotherapy effects are clearly presented. The text is accompanied by numerous supportive illustrations and tables.

  17. Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

    International Nuclear Information System (INIS)

    Kim, Jae Ho; Jenrow, Kenneth A.; Brown, Stephen L.

    2014-01-01

    To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.

  18. A System for Continual Quality Improvement of Normal Tissue Delineation for Radiation Therapy Treatment Planning

    Energy Technology Data Exchange (ETDEWEB)

    Breunig, Jennifer; Hernandez, Sophy; Lin, Jeffrey; Alsager, Stacy; Dumstorf, Christine; Price, Jennifer; Steber, Jennifer; Garza, Richard; Nagda, Suneel; Melian, Edward; Emami, Bahman [Department of Radiation Oncology, Loyola University Medical Center, Maywood, Illinois (United States); Roeske, John C., E-mail: jroeske@lumc.edu [Department of Radiation Oncology, Loyola University Medical Center, Maywood, Illinois (United States)

    2012-08-01

    Purpose: To implement the 'plan-do-check-act' (PDCA) cycle for the continual quality improvement of normal tissue contours used for radiation therapy treatment planning. Methods and Materials: The CT scans of patients treated for tumors of the brain, head and neck, thorax, pancreas and prostate were selected for this study. For each scan, a radiation oncologist and a diagnostic radiologist, outlined the normal tissues ('gold' contours) using Radiation Therapy Oncology Group (RTOG) guidelines. A total of 30 organs were delineated. Independently, 5 board-certified dosimetrists and 1 trainee then outlined the same organs. Metrics used to compare the agreement between the dosimetrists' contours and the gold contours included the Dice Similarity Coefficient (DSC), and a penalty function using distance to agreement. Based on these scores, dosimetrists were re-trained on those organs in which they did not receive a passing score, and they were subsequently re-tested. Results: Passing scores were achieved on 19 of 30 organs evaluated. These scores were correlated to organ volume. For organ volumes <8 cc, the average DSC was 0.61 vs organ volumes {>=}8 cc, for which the average DSC was 0.91 (P=.005). Normal tissues that had the lowest scores included the lenses, optic nerves, chiasm, cochlea, and esophagus. Of the 11 organs that were considered for re-testing, 10 showed improvement in the average score, and statistically significant improvement was noted in more than half of these organs after education and re-assessment. Conclusions: The results of this study indicate the feasibility of applying the PDCA cycle to assess competence in the delineation of individual organs, and to identify areas for improvement. With testing, guidance, and re-evaluation, contouring consistency can be obtained across multiple dosimetrists. Our expectation is that continual quality improvement using the PDCA approach will ensure more accurate treatments and dose

  19. Accumulation of DNA Double-Strand Breaks in Normal Tissues After Fractionated Irradiation

    International Nuclear Information System (INIS)

    Ruebe, Claudia E.; Fricke, Andreas; Wendorf, Juliane; Stuetzel, Annika; Kuehne, Martin; Ong, Mei Fang; Lipp, Peter; Ruebe, Christian

    2010-01-01

    Purpose: There is increasing evidence that genetic factors regulating the recognition and/or repair of DNA double-strand breaks (DSBs) are responsible for differences in radiosensitivity among patients. Genetically defined DSB repair capacities are supposed to determine patients' individual susceptibility to develop adverse normal tissue reactions after radiotherapy. In a preclinical murine model, we analyzed the impact of different DSB repair capacities on the cumulative DNA damage in normal tissues during the course of fractionated irradiation. Material and Methods: Different strains of mice with defined genetic backgrounds (SCID -/- homozygous, ATM -/- homozygous, ATM +/- heterozygous, and ATM +/+ wild-type mice) were subjected to single (2 Gy) or fractionated irradiation (5 x 2 Gy). By enumerating γH2AX foci, the formation and rejoining of DSBs were analyzed in organs representative of both early-responding (small intestine) and late-responding tissues (lung, kidney, and heart). Results: In repair-deficient SCID -/- and ATM -/- homozygous mice, large proportions of radiation-induced DSBs remained unrepaired after each fraction, leading to the pronounced accumulation of residual DNA damage after fractionated irradiation, similarly visible in early- and late-responding tissues. The slight DSB repair impairment of ATM +/- heterozygous mice was not detectable after single-dose irradiation but resulted in a significant increase in unrepaired DSBs during the fractionated irradiation scheme. Conclusions: Radiation-induced DSBs accumulate similarly in acute- and late-responding tissues during fractionated irradiation, whereas the whole extent of residual DNA damage depends decisively on the underlying genetically defined DSB repair capacity. Moreover, our data indicate that even minor impairments in DSB repair lead to exceeding DNA damage accumulation during fractionated irradiation and thus may have a significant impact on normal tissue responses in clinical

  20. Lovastatin attenuates ionizing radiation-induced normal tissue damage in vivo

    International Nuclear Information System (INIS)

    Ostrau, Christian; Huelsenbeck, Johannes; Herzog, Melanie; Schad, Arno; Torzewski, Michael; Lackner, Karl J.; Fritz, Gerhard

    2009-01-01

    Background and purpose: HMG-CoA-reductase inhibitors (statins) are widely used lipid-lowering drugs. Moreover, they have pleiotropic effects on cellular stress responses, proliferation and apoptosis in vitro. Here, we investigated whether lovastatin attenuates acute and subchronic ionizing radiation-induced normal tissue toxicity in vivo. Materials and methods: Four hours to 24 h after total body irradiation (6 Gy) of Balb/c mice, acute pro-inflammatory and pro-fibrotic responses were analyzed. To comprise subchronic radiation toxicity, mice were irradiated twice with 2.5 Gy and analyses were performed 3 weeks after the first radiation treatment. Molecular markers of inflammation and fibrosis as well as organ toxicities were measured. Results: Lovastatin attenuated IR-induced activation of NF-κB, mRNA expression of cell adhesion molecules and mRNA expression of pro-inflammatory and pro-fibrotic marker genes (i.e. TNFα, IL-6, TGFβ, CTGF, and type I and type III collagen) in a tissue- and time-dependent manner. γH2AX phosphorylation stimulated by IR was not affected by lovastatin, indicating that the statin has no major impact on the induction of DNA damage in vivo. Radiation-induced thrombopenia was significantly alleviated by lovastatin. Conclusions: Lovastatin inhibits both acute and subchronic IR-induced pro-inflammatory and pro-fibrotic responses and cell death in normal tissue in vivo. Therefore, lovastatin might be useful for selectively attenuating acute and subchronic normal tissue damage caused by radiotherapy.

  1. A System for Continual Quality Improvement of Normal Tissue Delineation for Radiation Therapy Treatment Planning

    International Nuclear Information System (INIS)

    Breunig, Jennifer; Hernandez, Sophy; Lin, Jeffrey; Alsager, Stacy; Dumstorf, Christine; Price, Jennifer; Steber, Jennifer; Garza, Richard; Nagda, Suneel; Melian, Edward; Emami, Bahman; Roeske, John C.

    2012-01-01

    Purpose: To implement the “plan-do-check-act” (PDCA) cycle for the continual quality improvement of normal tissue contours used for radiation therapy treatment planning. Methods and Materials: The CT scans of patients treated for tumors of the brain, head and neck, thorax, pancreas and prostate were selected for this study. For each scan, a radiation oncologist and a diagnostic radiologist, outlined the normal tissues (“gold” contours) using Radiation Therapy Oncology Group (RTOG) guidelines. A total of 30 organs were delineated. Independently, 5 board-certified dosimetrists and 1 trainee then outlined the same organs. Metrics used to compare the agreement between the dosimetrists' contours and the gold contours included the Dice Similarity Coefficient (DSC), and a penalty function using distance to agreement. Based on these scores, dosimetrists were re-trained on those organs in which they did not receive a passing score, and they were subsequently re-tested. Results: Passing scores were achieved on 19 of 30 organs evaluated. These scores were correlated to organ volume. For organ volumes <8 cc, the average DSC was 0.61 vs organ volumes ≥8 cc, for which the average DSC was 0.91 (P=.005). Normal tissues that had the lowest scores included the lenses, optic nerves, chiasm, cochlea, and esophagus. Of the 11 organs that were considered for re-testing, 10 showed improvement in the average score, and statistically significant improvement was noted in more than half of these organs after education and re-assessment. Conclusions: The results of this study indicate the feasibility of applying the PDCA cycle to assess competence in the delineation of individual organs, and to identify areas for improvement. With testing, guidance, and re-evaluation, contouring consistency can be obtained across multiple dosimetrists. Our expectation is that continual quality improvement using the PDCA approach will ensure more accurate treatments and dose assessment in

  2. Prodrugs designed to discriminate pathological (tumour) and physiological (normal tissue) hypoxia

    International Nuclear Information System (INIS)

    Wilson, W.R.; Patterson, A.V.

    2003-01-01

    There is now abundant evidence that hypoxic contributes to treatment failure in radiation therapy. As a target for therapeutic intervention, hypoxia is especially attractive because it is a common feature of most human tumours and therefore a potential 'pan target' across many tumour types. However, attempts to exploit hypoxia face the problem that oxygen concentrations in some normal tissues are also heterogeneous and that O 2 distributions in tumours and normal tissues overlap. Simply adjusting the K value (O 2 concentration for 50% inhibition of activation) does not provide a satisfactory solution. Bioreductive drugs like tirapazamine with high K values are activated significantly in several normal tissues, while nitro compounds and quinones with low K values spare the hypoxic tumour cells at 'intermediate' O 2 tensions (1-10 mM O 2 ) which are considered to be major contributors to tumour radioresistance. A potential strategy for overcoming this dilemma is to design prodrugs that are activated only at very low K values, but give relatively stable cytotoxic metabolites capable of diffusing to cells at higher O 2 concentrations. This approach redefines the therapeutic target as cells adjacent to zones of pathological hypoxia ( 2 ), providing discrimination from physiological hypoxia in normal tissues. Detecting bioreductive prodrugs capable of providing bystander killing of this kind is not straightforward. We have adapted a multicellular layer (MCL) co-culture model for quantifying bystander effects in GDEPT (Wilson et al., Cancer Res., 62: 1425-1432, 2002), and have used this to measure bystander effects of hypoxia-activated prodrugs. This model uses differences in metabolic activation of bioreductive drugs between A459 cell lines with low and high cytochrome P450 reductase activity, rather than O 2 gradients, to effect localised prodrug activation. It shows that TPZ and the nitroimidazole RSU-1069 have little or no bystander effect, but that dinitrobenzamide

  3. Clinical evaluation of normal tissue toxicity induced by ionizing radiation in cases of laryngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ramos, Adriano de Paula; Marques, Gustavo Inacio de Gomes; Soares, Renata da Bastos Ascenco; Dourado, Juliana Castro Dourado [Pontificia Universidade Catolica de Goias (PUCGO), Goiania, GO (Brazil). Dept. of Medicine; Mendonca, Yuri de Abreu, E-mail: renata.soares@pucgoias.edu.br [Goias Association Against Cancer, Goiania, GO (Brazil). Lab. of Radiobiology and Oncogenetics

    2012-07-01

    Laryngeal cancer is the second most frequent head and neck cancer in the Brazilian male population. For treatment, radiotherapy combined with chemotherapy is now used in substitution for total laryngectomy, becoming the standard treatment for advanced larynx cancer cases, with the aim of organ preservation. However, this method needs assessment of the side effects caused to normal tissue and organ functionality after treatment and the relation of these clinical factors to the individual characteristics of patients. Thus, the clinical characteristics of 229 patients with laryngeal cancer treated with radiotherapy were evaluated by medical records analysis in relation to normal tissue radiosensibility. Significant relations between smoking (p = 0.018) and combined chemoradiotherapy assistance (p = 0.03) were identified with high frequency of treatment suspension cases. The application of combined chemoradiotherapy also resulted in a higher incidence of oral mucositis (p = 0.04), xerostomia (p = 0.001) and treatment side effects to GIT (p = 0.04). Advanced clinical staging was associated with worse prognosis (p = 0.002) and a higher occurrence of treatment failure (p < 0.001). Radiotherapy was also less effective depending on the primary tumor location (p = 0.001). (author)

  4. An automatic method to discriminate malignant masses from normal tissue in digital mammograms

    International Nuclear Information System (INIS)

    Brake, Guido M. te; Karssemeijer, Nico; Hendriks, Jan H.C.L.

    2000-01-01

    Specificity levels of automatic mass detection methods in mammography are generally rather low, because suspicious looking normal tissue is often hard to discriminate from real malignant masses. In this work a number of features were defined that are related to image characteristics that radiologists use to discriminate real lesions from normal tissue. An artificial neural network was used to map the computed features to a measure of suspiciousness for each region that was found suspicious by a mass detection method. Two data sets were used to test the method. The first set of 72 malignant cases (132 films) was a consecutive series taken from the Nijmegen screening programme, 208 normal films were added to improve the estimation of the specificity of the method. The second set was part of the new DDSM data set from the University of South Florida. A total of 193 cases (772 films) with 372 annotated malignancies was used. The measure of suspiciousness that was computed using the image characteristics was successful in discriminating tumours from false positive detections. Approximately 75% of all cancers were detected in at least one view at a specificity level of 0.1 false positive per image. (author)

  5. Radioprotection of normal tissues in tumor-bearing mice by troxerutin

    International Nuclear Information System (INIS)

    Maurya, D.K.; Salvi, V.P.; Krishnan Nair, C.K.

    2004-01-01

    The flavanoid derivative troxerutin, used clinically for treating venous disorders, protected biomembranes and cellular DNA against the deleterious effects of γ-radiation. The peroxidation of lipids (measured as thiobarbituric acid-reacting substances, or TBARS) in rat liver microsomal and mitochondrial membranes resulting from γ-irradiation up to doses of 500 Gy in vitro was prevented by 0.2 mM troxerutin. The administration of troxerutin (175 mg/kg body weight) to tumor-bearing mice by intraperitoneal (ip) one hour prior to 4 Gy whole-body γ-irradiation significantly decreased the radiation-induced peroxidation of lipids in tissues such as liver and spleen, but there was no reduction of lipid peroxidation in tumor. The effect of troxerutin in γ-radiation-induced DNA strand breaks in different tissues of tumor-bearing mice was studied by comet assay. The administration of troxerutin to tumor-bearing animals protected cellular DNA against radiation-induced strand breaks. This was evidenced from decreases in comet tail length, tail moment, and percent of DNA in the tails in cells of normal tissues such as blood leukocytes and bone marrow, and these parameters were not altered in cells of fibrosarcoma tumor. The results revealed that troxerutin could preferentially protect normal tissues against radiation-induced damages in tumor-bearing animals. (author)

  6. Distribution of the anticancer drugs doxorubicin, mitoxantrone and topotecan in tumors and normal tissues.

    Science.gov (United States)

    Patel, Krupa J; Trédan, Olivier; Tannock, Ian F

    2013-07-01

    Pharmacokinetic analyses estimate the mean concentration of drug within a given tissue as a function of time, but do not give information about the spatial distribution of drugs within that tissue. Here, we compare the time-dependent spatial distribution of three anticancer drugs within tumors, heart, kidney, liver and brain. Mice bearing various xenografts were treated with doxorubicin, mitoxantrone or topotecan. At various times after injection, tumors and samples of heart, kidney, liver and brain were excised. Within solid tumors, the distribution of doxorubicin, mitoxantrone and topotecan was limited to perivascular regions at 10 min after administration and the distance from blood vessels at which drug intensity fell to half was ~25-75 μm. Although drug distribution improved after 3 and 24 h, there remained a significant decrease in drug fluorescence with increasing distance from tumor blood vessels. Drug distribution was relatively uniform in the heart, kidney and liver with substantially greater perivascular drug uptake than in tumors. There was significantly higher total drug fluorescence in the liver than in tumors after 10 min, 3 and 24 h. Little to no drug fluorescence was observed in the brain. There are marked differences in the spatial distributions of three anticancer drugs within tumor tissue and normal tissues over time, with greater exposure to most normal tissues and limited drug distribution to many cells in tumors. Studies of the spatial distribution of drugs are required to complement pharmacokinetic data in order to better understand and predict drug effects and toxicities.

  7. The effect of irradiation on function in self-renewing normal tissues with differing proliferative organisation

    International Nuclear Information System (INIS)

    Wheldon, T.E.; Michalowski, A.S.

    1982-01-01

    The primary effect of irradiation on self-renewing normal tissues is sterilisation of their proliferative cells, but how this translates into failure of tissue function depends on the mode of organisation of the tissue concerned. It has recently been suggested (Michalowski, 1981) that proliferative normal tissues may be classed as ''hierarchical'' (like haemopoietic tissues) or as ''flexible'' (like liver parenchyma) and that radiation injury to tissue function develops by different pathways in these tissues. Mathematical model studies confirm the different radiation responses of differently organized tissues. Tissues of the ''flexible'' or ''F-type'' category display a variety of novel radiobiological properties, different from those of the more familiar ''hierarchical'' or ''H-type'' tissues. The ''F-type'' responses are strongly influenced by radiation-sterilised (''doomed'') cells, and is is suggested that the role of ''doomed'' cells has been undervalued relative to that of clonogenic survivors. Since ''F-type'' tissues have characteristically low rates of cell renewal, it is possible that these tissues are preferentially responsible for late effects of irradiation in clinical radiotherapy. (author)

  8. External validation of a normal tissue complication probability model for radiation-induced hypothyroidism in an independent cohort

    DEFF Research Database (Denmark)

    Rønjom, Marianne F; Brink, Carsten; Bentzen, Søren M

    2015-01-01

    blood tests in the validation cohort relative to the original cohort. However, Pearson's correlation coefficients between model and clinical outcome were high: r = 0.97 estimated by the original model versus the original cohort, and r = 0.97 estimated by the original model versus the new cohort....... CONCLUSION: Dmean and Vthyroid were significant predictors of RIHT in both cohorts. The original NTCP model demonstrated external validity owing to high Pearson's correlation coefficients between estimated and observed incidence rates of RIHT in the original as well as in the validation cohort. This model...

  9. Probabilities of Pulmonary and Cardiac Complications and Radiographic Parameters in Breast Cancer Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Noh, O Kyu; Paek, Sung Ho; Ahn, Seung Do; Choi, Eun Kyung; Lee, Sang Wook; Song, Si Yeol; Yoon, Sang Min; Kim, Jong Hoon [Dept. of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2010-11-15

    To evaluate the relationship between the normal tissue complication probability (NTCP) of 3- dimensional (3-D) radiotherapy and the radiographic parameters of 2-dimensional (2-D) radiotherapy such as central lung distance (CLD) and maximal heart distance (MHD). We analyzed 110 patients who were treated with postoperative radiotherapy for breast cancer. A two-field tangential technique, a three-field technique, and the reverse hockey stick method were used. The radiation dose administered to whole breast or the chest wall was 50.4 Gy, whereas a 45 Gy was administered to the supraclavicular field. The NTCPs of the heart and lung were calculated by the modified Lyman model and the relative seriality model. For all patients, the NTCPs of radiation-induced pneumonitis and cardiac mortality were 0.5% and 0.7%, respectively. The NTCP of radiation-induced pneumonitis was higher in patients treated with the reverse hockey stick method than in those treated by other two techniques (0.0%, 0.0%, 3.1%, p<0.001). The NTCP of radiation-induced pneumonitis increased with CLD. The NTCP of cardiac mortality increased with MHD (R2=0.808). We found a close correlation between the NTCP of 3-D radiotherapy and 2-D radiographic parameters. Our results are useful to reanalyze the previous 2-D based clinical reports about breast radiation therapy complications as a viewpoint of NTCP.

  10. Probabilities of Pulmonary and Cardiac Complications and Radiographic Parameters in Breast Cancer Radiotherapy

    International Nuclear Information System (INIS)

    Noh, O Kyu; Paek, Sung Ho; Ahn, Seung Do; Choi, Eun Kyung; Lee, Sang Wook; Song, Si Yeol; Yoon, Sang Min; Kim, Jong Hoon

    2010-01-01

    To evaluate the relationship between the normal tissue complication probability (NTCP) of 3- dimensional (3-D) radiotherapy and the radiographic parameters of 2-dimensional (2-D) radiotherapy such as central lung distance (CLD) and maximal heart distance (MHD). We analyzed 110 patients who were treated with postoperative radiotherapy for breast cancer. A two-field tangential technique, a three-field technique, and the reverse hockey stick method were used. The radiation dose administered to whole breast or the chest wall was 50.4 Gy, whereas a 45 Gy was administered to the supraclavicular field. The NTCPs of the heart and lung were calculated by the modified Lyman model and the relative seriality model. For all patients, the NTCPs of radiation-induced pneumonitis and cardiac mortality were 0.5% and 0.7%, respectively. The NTCP of radiation-induced pneumonitis was higher in patients treated with the reverse hockey stick method than in those treated by other two techniques (0.0%, 0.0%, 3.1%, p<0.001). The NTCP of radiation-induced pneumonitis increased with CLD. The NTCP of cardiac mortality increased with MHD (R2=0.808). We found a close correlation between the NTCP of 3-D radiotherapy and 2-D radiographic parameters. Our results are useful to reanalyze the previous 2-D based clinical reports about breast radiation therapy complications as a viewpoint of NTCP.

  11. Genomic instability: potential contributions to tumour and normal tissue response, and second tumours, after radiotherapy

    International Nuclear Information System (INIS)

    Hendry, Jolyon H.

    2001-01-01

    Purpose: Induced genomic instability generally refers to a type of damage which is transmissible down cell generations, and which results in a persistently enhanced frequency of de novo mutations, chromosomal abnormalities or lethality in a significant fraction of the descendant cell population. The potential contribution of induced genomic instability to tumour and normal tissue response, and second tumours, after radiotherapy, is explored. Results: The phenomenon of spontaneous genomic instability is well known in some rare genetic diseases (e.g. Gorlin's syndrome), and there is evidence in such cases that it can lead to a greater propensity for carcinogenesis (with shortened latency) which is enhanced after irradiation. It is unclear what role induced genomic instability plays in the response of normal individuals, but persistent chromosomal instability has been detected in vivo in lymphocytes and keratinocytes from irradiated normal individuals. Such induced genomic instability might play some role in tumour response in a subset of tumours with specific defects in damage response genes, but again its contribution to radiocurability in the majority of cancer patients is unclear. In normal tissues, genomic instability induced in wild-type cells leading to delayed cell death might contribute to more severe or prolonged early reactions as a consequence of increased cell loss, a longer time required for recovery, and greater residual injury. In tumours, induced genomic instability reflected in delayed reductions in clonogenic capacity might contribute to the radiosensitivity of primary tumours, and also to a lower incidence, longer latency and slower growth rate of recurrences and metastases. Conclusions: The evidence which is reviewed shows that there is little information at present to support these propositions, but what exists is consistent with their expectations. Also, it is not yet clear to what extent mutations associated with genomic instability

  12. Utility of Normal Tissue-to-Tumor {alpha}/{beta} Ratio When Evaluating Isodoses of Isoeffective Radiation Therapy Treatment Plans

    Energy Technology Data Exchange (ETDEWEB)

    Gay, Hiram A., E-mail: hgay@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Jin Jianyue [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Chang, Albert J. [Department of Radiation Oncology, University of California, San Francisco, California (United States); Ten Haken, Randall K. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

    2013-01-01

    Purpose: To achieve a better understanding of the effect of the number of fractions on normal tissue sparing for equivalent tumor control in radiation therapy plans by using equivalent biologically effective dose (BED) isoeffect calculations. Methods and Materials: The simple linear quadratic (LQ) model was assumed to be valid up to 10 Gy per fraction. Using the model, we formulated a well-known mathematical equality for the tumor prescription dose and probed and solved a second mathematical problem for normal tissue isoeffect. That is, for a given arbitrary relative isodose distribution (treatment plan in percentages), 2 isoeffective tumor treatment regimens (N fractions of the dose D and n fractions of the dose d) were denoted, which resulted in the same BED (corresponding to 100% prescription isodose). Given these situations, the LQ model was further exploited to mathematically establish a unique relative isodose level, z (%), for the same arbitrary treatment plan, where the BED to normal tissues was also isoeffective for both fractionation regimens. Results: For the previously stated problem, the relative isodose level z (%), where the BEDs to the normal tissue were also equal, was defined by the normal tissue {alpha}/{beta} ratio divided by the tumor {alpha}/{beta} times 100%. Fewer fractions offers a therapeutic advantage for those portions of the normal tissue located outside the isodose surface, z, whereas more fractions offer a therapeutic advantage for those portions of the normal tissue within the isodose surface, z. Conclusions: Relative isodose-based treatment plan evaluations may be useful for comparing isoeffective tumor regimens in terms of normal tissue effects. Regions of tissues that would benefit from hypofractionation or standard fractionation can be identified.

  13. Fractionation in normal tissues: the (α/β)eff concept can account for dose heterogeneity and volume effects.

    Science.gov (United States)

    Hoffmann, Aswin L; Nahum, Alan E

    2013-10-07

    The simple Linear-Quadratic (LQ)-based Withers iso-effect formula (WIF) is widely used in external-beam radiotherapy to derive a new tumour dose prescription such that there is normal-tissue (NT) iso-effect when changing the fraction size and/or number. However, as conventionally applied, the WIF is invalid unless the normal-tissue response is solely determined by the tumour dose. We propose a generalized WIF (gWIF) which retains the tumour prescription dose, but replaces the intrinsic fractionation sensitivity measure (α/β) by a new concept, the normal-tissue effective fractionation sensitivity, [Formula: see text], which takes into account both the dose heterogeneity in, and the volume effect of, the late-responding normal-tissue in question. Closed-form analytical expressions for [Formula: see text] ensuring exact normal-tissue iso-effect are derived for: (i) uniform dose, and (ii) arbitrary dose distributions with volume-effect parameter n = 1 from the normal-tissue dose-volume histogram. For arbitrary dose distributions and arbitrary n, a numerical solution for [Formula: see text] exhibits a weak dependence on the number of fractions. As n is increased, [Formula: see text] increases from its intrinsic value at n = 0 (100% serial normal-tissue) to values close to or even exceeding the tumour (α/β) at n = 1 (100% parallel normal-tissue), with the highest values of [Formula: see text] corresponding to the most conformal dose distributions. Applications of this new concept to inverse planning and to highly conformal modalities are discussed, as is the effect of possible deviations from LQ behaviour at large fraction sizes.

  14. Lyman continuum observations of solar flares

    Science.gov (United States)

    Machado, M. E.; Noyes, R. W.

    1978-01-01

    A study is made of Lyman continuum observations of solar flares, using data obtained by the EUV spectroheliometer on the Apollo Telescope Mount. It is found that there are two main types of flare regions: an overall 'mean' flare coincident with the H-alpha flare region, and transient Lyman continuum kernels which can be identified with the H-alpha and X-ray kernels observed by other authors. It is found that the ground level hydrogen population in flares is closer to LTE than in the quiet sun and active regions, and that the level of Lyman continuum formation is lowered in the atmosphere from a mass column density .000005 g/sq cm in the quiet sun to .0003 g/sq cm in the mean flare, and to .001 g/sq cm in kernels. From these results the amount of chromospheric material 'evaporated' into the high temperature region is derived, which is found to be approximately 10 to the 15th g, in agreement with observations of X-ray emission measures.

  15. The measurement of intrinsic cellular radiosensitivity in human tumours and normal tissues

    International Nuclear Information System (INIS)

    Lawton, P.A.

    1995-01-01

    Human tumour and normal cell radiosensitivity are thought to be important factors determining the response of tumour and normal tissues to radiotherapy, respectively. Clonogenic assays are the standard method for measuring radiosensitivity but they are of limited applicability for clinical use with fresh human tumours. The main aim of this work was to evaluate the Adhesive Tumour Cell Culture System (ATCCS), as a method for measuring the radiosensitivity of human tumours. A soft agar clonogenic assay, the modified Courtenay-Mills assay, was used as a standard to compare with the ATCCS. The demonstration that fibroblast contamination could occur with both assay methods led to the investigation of a new technique for removing unwanted fibroblasts from tumour cell suspensions and to the use of a multiwell assay for measuring fibroblast radiosensitivity. (author)

  16. The measurement of intrinsic cellular radiosensitivity in human tumours and normal tissues

    Energy Technology Data Exchange (ETDEWEB)

    Lawton, P.A.

    1995-12-31

    Human tumour and normal cell radiosensitivity are thought to be important factors determining the response of tumour and normal tissues to radiotherapy, respectively. Clonogenic assays are the standard method for measuring radiosensitivity but they are of limited applicability for clinical use with fresh human tumours. The main aim of this work was to evaluate the Adhesive Tumour Cell Culture System (ATCCS), as a method for measuring the radiosensitivity of human tumours. A soft agar clonogenic assay, the modified Courtenay-Mills assay, was used as a standard to compare with the ATCCS. The demonstration that fibroblast contamination could occur with both assay methods led to the investigation of a new technique for removing unwanted fibroblasts from tumour cell suspensions and to the use of a multiwell assay for measuring fibroblast radiosensitivity. (author).

  17. Normal-tissue radioprotection by overexpression of the copper-zinc and manganese superoxide dismutase genes

    Energy Technology Data Exchange (ETDEWEB)

    Veldwijk, Marlon R. [Dept. of Radiation Oncology, Univ. Medical Center Mannheim, Univ. of Heidelberg, Mannheim (Germany); Pharmacology of Cancer Treatment (G402), German Cancer Research Center, Heidelberg (Germany); Herskind, Carsten; Wenz, Frederik [Dept. of Radiation Oncology, Univ. Medical Center Mannheim, Univ. of Heidelberg, Mannheim (Germany); Sellner, Leopold; Zeller, W. Jens [Pharmacology of Cancer Treatment (G402), German Cancer Research Center, Heidelberg (Germany); Radujkovic, Aleksandar [Dept. of Internal Medicine V, Univ. of Heidelberg (Germany); Laufs, Stephanie [Dept. of Experimental Surgery, Univ. Medical Center Mannheim, Univ. of Heidelberg, Mannheim (Germany); Molecular Oncology of Solid Tumors (G360), German Cancer Research Center, Heidelberg (Germany); Fruehauf, Stefan [Center for Tumor Diagnostic and Therapy, Paracelsus-Klinik, Osnabrueck (Germany)

    2009-08-15

    Background and Purpose: Protection of normal tissue against radiation-induced damage may increase the therapeutic ratio of radiotherapy. A promising strategy for testing this approach is gene therapy-mediated overexpression of the copper-zinc (CuZnSOD) or manganese superoxide dismutase (MnSOD) using recombinant adeno-associated viral (rAAV2) vectors. The purpose of this study was to test the modulating effects of the SOD genes on human primary lung fibroblasts (HPLF) after irradiation. Material and Methods: HPLF were transduced with rAAV2 vectors containing cDNA for the CuZnSOD, MnSOD or a control gene. The cells were irradiated (1-6 Gy), and gene transfer efficiency, apoptosis, protein expression/activity, and radiosensitivity measured by the colony-forming assay determined. Results: After transduction, 90.0% {+-} 6.4% of the cells expressed the transgene. A significant fivefold overexpression of both SOD was confirmed by an SOD activity assay (control: 21.1 {+-} 12.6, CuZnSOD: 95.1 {+-} 17.1, MnSOD: 108.5 {+-} 36.0 U SOD/mg protein) and immunohistochemistry. CuZnSOD and MnSOD overexpression resulted in a significant radioprotection of HPLF compared to controls (surviving fraction [SF] ratio SOD/control > 1): CuZnSOD: 1.18-fold (95% confidence interval [CI]: 1.06-1.32; p = 0.005), MnSOD: 1.23-fold (95% CI: 1.07-1.43; p = 0.01). Conclusion: Overexpression of CuZnSOD and MnSOD in HPLF mediated an increase in clonogenic survival after irradiation compared to controls. In previous works, a lack of radioprotection in SOD-overexpressing tumor cells was observed. Therefore, the present results suggest that rAAV2 vectors are promising tools for the delivery of radioprotective genes in normal tissue. (orig.)

  18. Impact of margin on tumour and normal tissue dosimetry in patients treated with IMRT using an endorectal balloon for prostate immobilization

    International Nuclear Information System (INIS)

    Ahmad, S.

    2004-01-01

    Full text: In treatment of prostate cancer with IMRT (Intensity Modulated Radiation Therapy), clinical target volume margin is determined by organ motion and set-up error. However, the margin width that achieves the desired dose escalation while minimizing normal tissue exposure is dependent upon the patient immobilization and/or organ localization techniques. In this study, we compare the impact of margin width on the dosimetry of tumour and normal tissues using the endorectal balloon for prostate immobilization. IMRT plans were generated for ten patients using margin widths of 0, 3, 5, 8 and 10 mm. Patients had a planning CT scan in the prone position with an endorectal balloon filled with 100 cc of air for prostate immobilization. The Corvus version 3.0.11 was used for treatment planning. The dose for the prostate and seminal vesicles was 70 Gy in 2 Gy per fractions, prescribed at the 83% isodose line. Dose restrictions to normal tissues were as follows: 33% of bladder was allowed to receive above 65 Gy, 15% of rectum above 68 Gy and 10% of femurs above 45 Gy. Analysis of Variance was used to compare the target and normal tissue doses. Tumour control probability and normal tissue complication probability calculations are currently being performed and will be presented. The mean doses ranged from 73.93 to 75.31 Gy for the prostate and from 73.71 to 75.31 Gy for the seminal vesicles. A 10 mm margin produced significantly lower mean doses compared to 0 or 5 mm for both targets (prostate p 0.062). For bladder and rectum the mean doses ranged from 18.49 to 22.30 Gy (p=0.605) and from 29.34 to 31.33 Gy (p=0.135), respectively, while the percent rectal volumes above 68 Gy were significantly higher for margins of 5, 8 and 10 mm (p<0.006) ranging from 10.72% to 15.81%. Mean doses to the femurs and pelvis were significantly higher for 8 and 10 mm margins, ranging from 20.9 to 29.39 Gy for femurs (p<0.015) and from 15.05 to 19.98 Gy for pelvis (p<0.0005). Also the percent

  19. Lyman alpha SMM/UVSP absolute calibration and geocoronal correction

    Science.gov (United States)

    Fontenla, Juan M.; Reichmann, Edwin J.

    1987-01-01

    Lyman alpha observations from the Ultraviolet Spectrometer Polarimeter (UVSP) instrument of the Solar Maximum Mission (SMM) spacecraft were analyzed and provide instrumental calibration details. Specific values of the instrument quantum efficiency, Lyman alpha absolute intensity, and correction for geocoronal absorption are presented.

  20. Continuous coherent Lyman-alpha excitation of atomic hydrogen.

    NARCIS (Netherlands)

    Eikema, K.S.E.; Waltz, J.; Hänsch, T.

    2001-01-01

    The first near natural linewidth of the 1S-2P transition in atomic hydrogen was reported with a high degree of accuracy. A high yield of continuous Lyman-α radiation based on four wave mixing in mercury was employed. It was shown that laser cooloing and detection with Lyman-α radiation has excellent

  1. Mammary stem cell and macrophage markers are enriched in normal tissue adjacent to inflammatory breast cancer.

    Science.gov (United States)

    Reddy, Jay P; Atkinson, Rachel L; Larson, Richard; Burks, Jared K; Smith, Daniel; Debeb, Bisrat G; Ruffell, Brian; Creighton, Chad J; Bambhroliya, Arvind; Reuben, James M; Van Laere, Steven J; Krishnamurthy, Savitri; Symmans, William F; Brewster, Abenaa M; Woodward, Wendy A

    2018-06-01

    We hypothesized that breast tissue not involved by tumor in inflammatory breast cancer (IBC) patients contains intrinsic differences, including increased mammary stem cells and macrophage infiltration, which may promote the IBC phenotype. Normal breast parenchyma ≥ 5 cm away from primary tumors was obtained from mastectomy specimens. This included an initial cohort of 8 IBC patients and 60 non-IBC patients followed by a validation cohort of 19 IBC patients and 25 non-IBC patients. Samples were immunostained for either CD44 + CD49f + CD133/2 + mammary stem cell markers or the CD68 macrophage marker and correlated with IBC status. Quantitation of positive cells was determined using inForm software from PerkinElmer. We also examined the association between IBC status and previously published tumorigenic stem cell and IBC tumor signatures in the validation cohort samples. 8 of 8 IBC samples expressed isolated CD44 + CD49f + CD133/2 + stem cell marked cells in the initial cohort as opposed to 0/60 non-IBC samples (p = 0.001). Similarly, the median number of CD44 + CD49f + CD133/2 + cells was significantly higher in the IBC validation cohort as opposed to the non-IBC validation cohort (25.7 vs. 14.2, p = 0.007). 7 of 8 IBC samples expressed CD68 + histologically confirmed macrophages in initial cohort as opposed to 12/48 non-IBC samples (p = 0.001). In the validation cohort, the median number of CD68 + cells in IBC was 3.7 versus 1.0 in the non-IBC cohort (p = 0.06). IBC normal tissue was positively associated with a tumorigenic stem cell signature (p = 0.02) and with a 79-gene IBC signature (p stem cell signature and IBC-specific tumor signature. Collectively, these data suggest that IBC normal tissue differs from non-IBC tissue. Whether these changes occur before the tumor develops or is induced by tumor warrants further investigation.

  2. Variability of individual normal tissue radiation sensitivity. An international empirical evaluation of endogenous and exogenous

    International Nuclear Information System (INIS)

    Zimmermann, J.S.; Kumpf, L.; Kimmig, B.

    1998-01-01

    Background: The variability of normal-tissue response is of major concern for radiation therapy. Multiple endogenous and exogenous factors are qualitatively known to alter the acute and late tissue response. Which of them are regarded most important by the European radiation oncologists and what is, empirically, their quantitative influence on the acute or late tissue tolerance? Methods: In August 1997, we sent a questionnaire to 255 European radiation oncology departments. Among others, the questionnaire asked for endogenous and exogenous factors modifying the tissue response to radiation therapy and their quantitative influence on the acute and late radiation morbidity (TD5/5). Fifty-five questionnaires (21.5%) were answered. Results: Empirically, the most important endogenous factors to modify the acute tissue tolerance are (a) metabolic/other diseases with macro- or microangiopathia (17 answers [a]/32% mean decrease of tissue tolerance), (b) collagen diseases (9 a/37%) and (c) immune diseases (5 a/53%). As endogenous response modifiers for the TD5/5 are recognized (a) metabolic or other diseases leading to marcro- or microangiopathia (15 a/31%), (b) collagen diseases (11 a/38%) and (c) immune diseases (2 a/50%). Inflammations from any reason are assumed to alter the acute tissue tolerance by (6 a/26%) and the TD5/5 by (10 a/24%). Exogenous modifiers of the acute tissue response mentioned are (a) smoking (34 a/44%), (b) alcohol (23 a/45%), (c) nutrition/diets (16 a/45%), (d) hygiene (9 a/26%) and (e) medical therapies (10 a/37%). Exogenous factors assumed to influence the TD5/5 are (a) smoking (22 a/40%), (b) alcohol (15 a/38%), (c) nutrition/diets (9 a/48%), (d) hygiene (5 a/34%) and (e) medical therapies (10 a/30%). Conclusions: Exogenous factors are regarded more important by number and extent on the acute and late tissue response than endogenous modifiers. Both may have an important influence on the individual expression of normal tissue response. (orig

  3. Simulation study of pO2 distribution in induced tumour masses and normal tissues within a microcirculation environment.

    Science.gov (United States)

    Li, Mao; Li, Yan; Wen, Peng Paul

    2014-01-01

    The biological microenvironment is interrupted when tumour masses are introduced because of the strong competition for oxygen. During the period of avascular growth of tumours, capillaries that existed play a crucial role in supplying oxygen to both tumourous and healthy cells. Due to limitations of oxygen supply from capillaries, healthy cells have to compete for oxygen with tumourous cells. In this study, an improved Krogh's cylinder model which is more realistic than the previously reported assumption that oxygen is homogeneously distributed in a microenvironment, is proposed to describe the process of the oxygen diffusion from a capillary to its surrounding environment. The capillary wall permeability is also taken into account. The simulation study is conducted and the results show that when tumour masses are implanted at the upstream part of a capillary and followed by normal tissues, the whole normal tissues suffer from hypoxia. In contrast, when normal tissues are ahead of tumour masses, their pO2 is sufficient. In both situations, the pO2 in the whole normal tissues drops significantly due to the axial diffusion at the interface of normal tissues and tumourous cells. As the existence of the axial oxygen diffusion cannot supply the whole tumour masses, only these tumourous cells that are near the interface can be partially supplied, and have a small chance to survive.

  4. Radiobiological predictors of tumor and acute normal tissue response in radiotherapy for head and neck cancers

    International Nuclear Information System (INIS)

    Maciejewski, B.; Skladowski, K.; Zajusz, A.

    1991-01-01

    The importance of measurements of the potential doubling time (T pot. ) and of the survival fraction at 2.0 Gy (SF 2 ), and a method modifying acute radiation response of normal oral mucosa are discussed. Tumor clonogen repopulation accelerates around day 28 of the treatment, and the rate of repopulation is not constant but continuously increases from about 0.3 Gy/day to 1.0-1.3 Gy/day between day 28 and 65 of the treatment. This may suggest that T pot. values decrease correspondingly. The relevance of prior-to-treatment T pot. measurements to clinical situations is discussed. The SF 2 value reflects the intrinsic radiosensitivity of human tumors. The SF 2 values are expected to be valuable as predictors for tumor response to irradiation. Variations in the SF 2 values depending on tumor characteristics and assay methods are discussed in relation to the dose response and tumor cure probability. The effect of modifying the repopulation rate in the oral mucosa by stimulation with a 2% silver nitrate solution is discussed. Although these prognosticators are different in their nature, they might provide a rational basis for selecting patients into optimal irradiation treatment and might allow to modify the radiation response of dose-limiting normal tissues. (author). 5 figs., 1 tab., 28 refs

  5. ALK1 heterozygosity delays development of late normal tissue damage in the irradiated mouse kidney

    International Nuclear Information System (INIS)

    Scharpfenecker, Marion; Floot, Ben; Korlaar, Regina; Russell, Nicola S.; Stewart, Fiona A.

    2011-01-01

    Background and Purpose: Activin receptor-like kinase 1 (ALK1) is a transforming growth factor β (TGF-β) receptor, which is mainly expressed in endothelial cells regulating proliferation and migration in vitro and angiogenesis in vivo. Endothelial cells also express the co-receptor endoglin, which modulates ALK1 effects on endothelial cells. Our previous studies showed that mice with reduced endoglin levels develop less irradiation-induced vascular damage and fibrosis, caused by an impaired inflammatory response. This study was aimed at investigating the role of ALK1 in late radiation toxicity. Material and Methods: Kidneys of ALK +/+ and ALK1 +/- mice were irradiated with 14 Gy. Mice were sacrificed at 10, 20, and 30 weeks after irradiation and gene expression and protein levels were analyzed. Results: Compared to wild type littermates, ALK1 +/- mice developed less inflammation and fibrosis at 20 weeks after irradiation, but displayed an increase in pro-inflammatory and pro-fibrotic gene expression at 30 weeks. In addition, ALK1 +/- mice showed superior vascular integrity at 10 and 20 weeks after irradiation which deteriorated at 30 weeks coinciding with changes in the VEGF pathway. Conclusions: ALK1 +/- mice develop a delayed normal tissue response by modulating the inflammatory response and growth factor expression after irradiation.

  6. Immunohistochemical Expression of FXR1 in Canine Normal Tissues and Melanomas.

    Science.gov (United States)

    Nordio, Laura; Marques, Andreia T; Lecchi, Cristina; Luciano, Alberto M; Stefanello, Damiano; Giudice, Chiara

    2018-04-01

    Fragile X mental retardation-related protein 1 (FXR1) is a cytoplasmic RNA-binding protein highly conserved among vertebrates. It has been studied for its role in muscle development, inflammation, and tumorigenesis, being related, for example, to metastasizing behavior in human and canine uveal melanoma. Anti-FXR1 antibodies have never been validated in the canine species. To investigate FXR1 expression in canine melanocytic tumors, the present study tested two commercially available polyclonal anti-human FXR1 antibodies, raised in goat and rabbit, respectively. The cross-reactivity of the anti-FXR1 antibodies was assessed by Western blot analysis, and the protein was localized by IHC in a set of normal canine tissues and in canine melanocytic tumors (10 uveal and 10 oral). Western blot results demonstrated that the antibody raised in rabbit specifically recognized the canine FXR1, while the antibody raised in goat did not cross-react with this canine protein. FXR1 protein was immunodetected using rabbit anti-FXR1 antibody, in canine normal tissues with different levels of intensity and distribution. It was also detected in 10/10 uveal and 9/10 oral melanocytic tumors. The present study validated for the first time the use of anti-FXR1 antibody in dogs and highlighted different FXR1 protein expression in canine melanocytic tumors, the significance of which is undergoing further investigations.

  7. The expression of Egfl7 in human normal tissues and epithelial tumors.

    Science.gov (United States)

    Fan, Chun; Yang, Lian-Yue; Wu, Fan; Tao, Yi-Ming; Liu, Lin-Sen; Zhang, Jin-Fan; He, Ya-Ning; Tang, Li-Li; Chen, Guo-Dong; Guo, Lei

    2013-04-23

    To investigate the expression of Egfl7 in normal adult human tissues and human epithelial tumors.
 RT-PCR and Western blot were employed to detect Egfl7 expression in normal adult human tissues and 10 human epithelial tumors including hepatocellular carcinoma (HCC), lung cancer, breast cancer, prostate cancer, colorectal cancer, gastric cancer, esophageal cancer, malignant glioma, ovarian cancer and renal cancer. Immunohistochemistry and cytoimmunofluorescence were subsequently used to determine the localization of Egfl7 in human epithelial tumor tissues and cell lines. ELISA was also carried out to examine the serum Egfl7 levels in cancer patients. In addition, correlations between Egfl7 expression and clinicopathological features as well as prognosis of HCC and breast cancer were also analyzed on the basis of immunohistochemistry results.
 Egfl7 was differentially expressed in 19 adult human normal tissues and was overexpressed in all 10 human epithelial tumor tissues. The serum Egfl7 level was also significantly elevated in cancer patients. The increased Egfl7 expression in HCC correlated with vein invasion, absence of capsule formation, multiple tumor nodes and poor prognosis. Similarly, upregulation of Egfl7 in breast cancer correlated strongly with TNM stage, lymphatic metastasis, estrogen receptor positivity, Her2 positivity and poor prognosis. 
 Egfl7 is significantly upregulated in human epithelial tumor tissues, suggesting Egfl7 to be a potential biomarker for human epithelial tumors, especially HCC and breast cancer.

  8. Optical redox imaging indices discriminate human breast cancer from normal tissues

    Science.gov (United States)

    Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

    2016-01-01

    Abstract. Our long-term goal was to investigate the potential of incorporating redox imaging technique as a breast cancer (BC) diagnosis component to increase the positive predictive value of suspicious imaging finding and to reduce unnecessary biopsies and overdiagnosis. We previously found that precancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. We also revealed abnormal mitochondrial redox state in cancerous specimens from three BC patients. Here, we extend our study to include biopsies of 16 patients. Tissue aliquots were collected from both apparently normal and cancerous tissues from the affected cancer-bearing breasts shortly after surgical resection. All specimens were snap-frozen and scanned with the Chance redox scanner, i.e., the three-dimensional cryogenic NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins) fluorescence imager. We found both Fp and NADH in the cancerous tissues roughly tripled that in the normal tissues (predox ratio Fp/(NADH + Fp) was ∼27% higher in the cancerous tissues (predox ratio alone could predict cancer with reasonable sensitivity and specificity. Our findings suggest that the optical redox imaging technique can provide parameters independent of clinical factors for discriminating cancer from noncancer breast tissues in human patients. PMID:27896360

  9. Variability of the Lyman alpha flux with solar activity

    International Nuclear Information System (INIS)

    Lean, J.L.; Skumanich, A.

    1983-01-01

    A three-component model of the solar chromosphere, developed from ground based observations of the Ca II K chromospheric emission, is used to calculate the variability of the Lyman alpha flux between 1969 and 1980. The Lyman alpha flux at solar minimum is required in the model and is taken as 2.32 x 10 11 photons/cm 2 /s. This value occurred during 1975 as well as in 1976 near the commencement of solar cycle 21. The model predicts that the Lyman alpha flux increases to as much as 5 x 10 11 photons/cm 2 /s at the maximum of the solar cycle. The ratio of the average fluxes for December 1979 (cycle maximum) and July 1976 (cycle minimum) is 1.9. During solar maximum the 27-day solar rotation is shown to cause the Lyman alpha flux to vary by as much as 40% or as little as 5%. The model also shows that the Lyman alpha flux varies over intermediate time periods of 2 to 3 years, as well as over the 11-year sunspot cycle. We conclude that, unlike the sunspot number and the 10.7-cm radio flux, the Lyman alpha flux had a variability that was approximately the same during each of the past three cycles. Lyman alpha fluxes calculated by the model are consistent with measurements of the Lyman alpha flux made by 11 of a total of 14 rocket experiments conducted during the period 1969--1980. The model explains satisfactorily the absolute magnitude, long-term trends, and the cycle variability seen in the Lyman alpha irradiances by the OSO 5 satellite experiment. The 27-day variability observed by the AE-E satellite experiment is well reproduced. However, the magntidue of the AE-E 1 Lyman alpha irradiances are higher than the model calculations by between 40% and 80%. We suggest that the assumed calibration of the AE-E irradiances is in error

  10. The use of biological isodoses ''IsobioGy 2'' for evaluation of tumour and normal tissues response for fractionated irradiation

    International Nuclear Information System (INIS)

    Maciejewski, B.; Skolyszewski, J.; Majewski, S.; Lobodziec, W.; Jedynak, T.; Slosarek, K.

    1988-01-01

    Divergences between physical and biological dose distributions were analysed using linear quadratic model. It was found that small variations in physical dose distribution and differences in normal tissue sensitivity for change in dose per fraction, expressed by a α/β value, can cause a high difference between physical and biological doses. This difference significantly increases when one field instead of two fields is daily treated. If there is no enough separation between treated fields, the biological dose may dramatically increase. The use of biological ''isobioGy 2'' isodoses, instead of physical isodoses, can provide an important information on biological effect in tumour or normal tissue and may diminish the risk of giving too high dose to normal tissue and too low dose to the tumour. 6 figs., 13 refs. (author)

  11. SU-E-T-573: Normal Tissue Dose Effect of Prescription Isodose Level Selection in Lung Stereotactic Body Radiation Therapy

    International Nuclear Information System (INIS)

    Zhang, Q; Lei, Y; Zheng, D; Zhu, X; Wahl, A; Lin, C; Zhou, S; Zhen, W

    2015-01-01

    Purpose: To evaluate dose fall-off in normal tissue for lung stereotactic body radiation therapy (SBRT) cases planned with different prescription isodose levels (IDLs), by calculating the dose dropping speed (DDS) in normal tissue on plans computed with both Pencil Beam (PB) and Monte-Carlo (MC) algorithms. Methods: The DDS was calculated on 32 plans for 8 lung SBRT patients. For each patient, 4 dynamic conformal arc plans were individually optimized for prescription isodose levels (IDL) ranging from 60% to 90% of the maximum dose with 10% increments to conformally cover the PTV. Eighty non-overlapping rind structures each of 1mm thickness were created layer by layer from each PTV surface. The average dose in each rind was calculated and fitted with a double exponential function (DEF) of the distance from the PTV surface, which models the steep- and moderate-slope portions of the average dose curve in normal tissue. The parameter characterizing the steep portion of the average dose curve in the DEF quantifies the DDS in the immediate normal tissue receiving high dose. Provided that the prescription dose covers the whole PTV, a greater DDS indicates better normal tissue sparing. The DDS were compared among plans with different prescription IDLs, for plans computed with both PB and MC algorithms. Results: For all patients, the DDS was found to be the lowest for 90% prescription IDL and reached a highest plateau region for 60% or 70% prescription. The trend was the same for both PB and MC plans. Conclusion: Among the range of prescription IDLs accepted by lung SBRT RTOG protocols, prescriptions to 60% and 70% IDLs were found to provide best normal tissue sparing

  12. On radiation damage to normal tissues and its treatment. Pt. 2

    International Nuclear Information System (INIS)

    Michalowski, A.S.

    1994-01-01

    In addition to transiently inhibiting cell cycle progression and sterilizing those cells capable of proliferation, irradiation disturbs the homeostasis effected by endogenous mediators of intercellular communication (humoral component of tissue response to radiation). Changes in the mediator levels may modulate radiation effects either by a assisting a return to normality (e.g., through a rise in H-type cell lineage-specific growth factors) or by aggravating the damage. The latter mode is illustrated with reports on changes in eicosanoid levels after irradiation and on results of empirical treatment of radiation injuries with anti-inflammatory drugs. Prodromal, acute and chronic effects of radiation are accompanied by excessive production of eicosanoids (prostaglandins, prostacyclin, thromboxanes and leukotrienes). These endogenous mediators of inflammatory reactions may be responsible for the vasodilatation, vasoconstriction, increased microvascular permeability, thrombosis and chemotaxis observed after radiation exposure. Glucocorticoids inhibit eicosanoid synthesis primarily by interfering with phospholipase A 2 whilst non-steroidal anti-inflammatory drugs prevent prostaglandin/thromboxane synthesis by inhibiting cycloxygenase. When administered after irradiation on empirical grounds, drugs belonging to both groups tend to attenuate a range of prodomal, acute and chronic effects of radiation in man and animals. Taken together, these two sets of observations are highly suggestive of a contribution of humoral factors to the adverse responses of normal tissues and organs to radiation. A full account of radiation damage should therefore consist of complementary descriptions of cellular and humoral events. Further studies on anti-inflammatory drug treatment of radiation damage to normal organs are justified and desirable. (orig.)

  13. Lewis x is highly expressed in normal tissues: a comparative immunohistochemical study and literature revision.

    Science.gov (United States)

    Croce, María V; Isla-Larrain, Marina; Rabassa, Martín E; Demichelis, Sandra; Colussi, Andrea G; Crespo, Marina; Lacunza, Ezequiel; Segal-Eiras, Amada

    2007-01-01

    An immunohistochemical analysis was employed to determine the expression of carbohydrate antigens associated to mucins in normal epithelia. Tissue samples were obtained as biopsies from normal breast (18), colon (35) and oral cavity mucosa (8). The following carbohydrate epitopes were studied: sialyl-Lewis x, Lewis x, Lewis y, Tn hapten, sialyl-Tn and Thomsen-Friedenreich antigen. Mucins were also studied employing antibodies against MUC1, MUC2, MUC4, MUC5AC, MUC6 and also normal colonic glycolipid. Statistical analysis was performed and Kendall correlations were obtained. Lewis x showed an apical pattern mainly at plasma membrane, although cytoplasmic staining was also found in most samples. TF, Tn and sTn haptens were detected in few specimens, while sLewis x was found in oral mucosa and breast tissue. Also, normal breast expressed MUC1 at a high percentage, whereas MUC4 was observed in a small number of samples. Colon specimens mainly expressed MUC2 and MUC1, while most oral mucosa samples expressed MUC4 and MUC1. A positive correlation between MUC1VNTR and TF epitope (r=0.396) was found in breast samples, while in colon specimens MUC2 and colonic glycolipid versus Lewis x were statistically significantly correlated (r=0.28 and r=0.29, respectively). As a conclusion, a defined carbohydrate epitope expression is not exclusive of normal tissue or a determined localization, and it is possible to assume that different glycoproteins and glycolipids may be carriers of carbohydrate antigens depending on the tissue localization considered.

  14. Experimental studies on interactions of radiation and cancer chemotherapeutic drugs in normal tissues and a solid tumour

    International Nuclear Information System (INIS)

    Maase, H. van der

    1986-01-01

    The interactions of radiation and seven cancer chemotherapeutic drugs have been investigated in four normal tissues and in a solid C 3 H mouse mammary carcinoma in vivo. The investigated drugs were adriamycin (ADM), bleomycin (BLM), cyclophosphamide (CTX), 5-fluorouracil (5-FU), methotrexate (MTX), mitomycin C (MM-C) and cis-diamminedichloroplatinum(II) (cis-DDP). The drugs enhanced the radiation response in most cases. However, signs of radioprotection was observed for CTX in skin and for MTX in haemopoietic tissue. The interval and the sequence of the two treatment modalities were of utmost importance for the normal tissue reactions. In general, the most serious interactions occurred when drugs were administered simultaneously with or a few hours before radiation. The radiation-modifying effect of the drugs deviated from this pattern in the haemopoietic tissue as the radiation response was most enhanced on drug administration 1-3 days after radiation. Enhancement of the radiation response was generally less pronounced in the tumour model than in the normal tissues. The combined drug-radiation effect was apparently less time-dependent in the tumour than in the normal tissues. (Auth.)

  15. Adverse event reporting and developments in radiation biology after normal tissue injury: International Atomic Energy Agency consultation

    International Nuclear Information System (INIS)

    Chen Yuhchyau; Trotti, Andy; Coleman, C. Norman; Machtay, Mitchell; Mirimanoff, Rene O.; Hay, John; O'Brien, Peter C.; El-Gueddari, Brahim; Salvajoli, Joao V.; Jeremic, Branislav

    2006-01-01

    Purpose: Recent research has enhanced our understanding of radiation injury at the molecular-cellular and tissue levels; significant strides have occurred in standardization of adverse event reporting in clinical trials. In response, the International Atomic Energy Agency, through its Division of Human Health and its section for Applied Radiation Biology and Radiotherapy, organized a consultation meeting in Atlanta (October 2, 2004) to discuss developments in radiobiology, normal tissue reactions, and adverse event reporting. Methods and Materials: Representatives from cooperative groups of African Radiation Oncology Group, Curriculo Radioterapeutica Ibero Latino Americana, European Organization for Research and Treatment of Cancer, National Cancer Institute of Canada Clinical Trials Group, Radiation Therapy Oncology Group, and Trans-Tasman Radiation Oncology Group held the meeting discussion. Results: Representatives of major radiotherapy groups/organizations and prominent leaders in radiotherapy discussed current understanding of normal tissue radiobiologic effects, the design and implementation of future clinical and translational projects for normal tissue injury, and the standardization of adverse-event reporting worldwide. Conclusions: The consensus was to adopt NCI comprehensive adverse event reporting terminology and grading system (CTCAE v3.0) as the new standard for all cooperative group trials. Future plans included the implementation of coordinated research projects focusing on normal tissue biomarkers and data collection methods

  16. Effect of different BNCT protocols on DNA synthesis in precancerous and normal tissues in an experimental model of oral cancer

    International Nuclear Information System (INIS)

    Heber, Elisa M.; Aromando, Romina; Trivillin, Veronica A.; Itoiz, Maria E.; Kreimann, Erica L.; Schwint, Amanda E.; Nigg, David W.

    2006-01-01

    We previously reported the therapeutic success of different BNCT protocols in the treatment of oral cancer, employing the hamster cheek pouch model. The aim of the present study was to evaluate the effect of these BNCT protocols on DNA synthesis in precancerous and normal tissue in this model and assess the potential lag in the development of second primary tumors in precancerous tissue. The data are relevant to potential control of field cancerized tissue and tolerance of normal tissue. We evaluated DNA synthesis in precancerous and normal pouch tissue 1-30 days post-BNCT mediated by BPA, GB-10 or BPA + GB-10 employing incorporation of bromo-deoxyuridine as an end-point. The BNCT-induced potential lag in the development of second primary tumors in precancerous tissue was monitored. A drastic, statistically significant reduction in DNA synthesis occurred in pacancerous tissue as early as 1 day post-BNCT and was sustained at virtually all time points until 30 days post-BNCT for all protocols. The histological categories evaluated individually within precancerous tissue (dysplasia, hyperplasia and NUMF [no unusual microscopic features]) responded similarly. DNA synthesis in normal tissue treated with BNCT oscillated around the very low pre-treatment values. A BNCT-induced lag in the development of second primary tumors was observed. BNCT induced a drastic fall in DNA synthesis in precancerous tissue that would be associated to the observed lag in the development of second primary tumors. The minimum variations in DNA synthesis in BNCT-treated normal tissue would correlate with the absence of normal tissue radiotoxicity. The present data would contribute to optimize therapeutic efficacy in the treatment of field-cancerized areas. (author)

  17. Constraining Lyman continuum escape using Machine Learning

    Science.gov (United States)

    Giri, Sambit K.; Zackrisson, Erik; Binggeli, Christian; Pelckmans, Kristiaan; Cubo, Rubén; Mellema, Garrelt

    2018-05-01

    The James Webb Space Telescope (JWST) will observe the rest-frame ultraviolet/optical spectra of galaxies from the epoch of reionization (EoR) in unprecedented detail. While escaping into the intergalactic medium, hydrogen-ionizing (Lyman continuum; LyC) photons from the galaxies will contribute to the bluer end of the UV slope and make nebular emission lines less prominent. We present a method to constrain leakage of the LyC photons using the spectra of high redshift (z >~ 6) galaxies. We simulate JWST/NIRSpec observations of galaxies at z =6-9 by matching the fluxes of galaxies observed in the Frontier Fields observations of galaxy cluster MACS-J0416. Our method predicts the escape fraction fesc with a mean absolute error Δfesc ~ 0.14. The method also predicts the redshifts of the galaxies with an error .

  18. Modulation of antioxidant enzymes as radioprotector mechanism of oligo elements and lachesis muta in normal tissues

    International Nuclear Information System (INIS)

    Crescenti, E.; Croci, M.; Mohamad, N.; Medina, V.; Sambuco, L.; Gutierrez, A.; Nunez, M.; Martin, G.; Cricco, G.; Bergoc, R.; Rivera, E.

    2006-01-01

    The therapeutic use of the ionizing radiations (IR) it has acquired great relevance in the last decades although their effects are not selective and they are also manifested on the normal tissues. In previous works we demonstrate the radioprotector effect that the combination of oligo elements Zinc, Selenium and Manganese associated to the snake poison Lachesis muta (O-LM) it exercises on the small intestine and the bone marrow of irradiated mouse. The objective of this work was to study the molecular mechanisms, and particularly the paper of the anti-oxidant superoxide dismutases enzymes (MnSOD and Cu/ZnSOD), Catalase (CAT), and Glutathione Peroxidase (GPx), in the radioprotector action that exercises the combination O-LM. Four groups of mice were used: A) control; B) treated with O-LM; C) irradiated; D) irradiated and treated with O-LM. The two treated groups were injected daily via s.c. with 0,1 ml of O-LM from 30 days before the irradiation and until to 4 days later. The two irradiated groups received 10 Gy in whole body the day 30. The day 35 all the animals were sacrificed. The histological intestinal cuts of the mucous one were evaluated by tint with hematoxyline-eosin; the presence of apoptotic cells it was determined by the Tunel method (Apoptag kit); the expression of PCNA (nuclear antigen of proliferating cells), MnSOD, CuZnSOD, CAT and GPx, by immunohistochemistry. The results demonstrated that in the lot D it was preserved totally the histology of the intestinal mucous. In the control A it was observed PCNA expression in the crypts, of MnSOD in the hairiness and CuZnSOD, CAT and Gpx in both. The change produced by O-LM (group B) it was the increase of PCNA, of CAT and the appearance of MnSOD in the crypts. On the other hand, the irradiation (C) it produced a marked descent in the GPx, the complete disappearance of PCNA and an increase of the apoptotic cells. The group D showed that O-LM it reverted totally the effect of the RI on the expression of PCNA

  19. Correlation of in vitro lymphocyte radiosensitivity and gene expression with late normal tissue reactions following curative radiotherapy for breast cancer

    International Nuclear Information System (INIS)

    Finnon, Paul; Kabacik, Sylwia; MacKay, Alan; Raffy, Claudine; A’Hern, Roger; Owen, Roger; Badie, Christophe; Yarnold, John; Bouffler, Simon

    2012-01-01

    Background and purpose: Identification of mechanisms of late normal tissue responses to curative radiotherapy that discriminate individuals with marked or mild responses would aid response prediction. This study aimed to identify differences in gene expression, apoptosis, residual DNA double strand breaks and chromosomal damage after in vitro irradiation of lymphocytes in a series of patients with marked (31 cases) or mild (28 controls) late adverse reaction to adjuvant breast radiotherapy. Materials and methods: Gene expression arrays, residual γH2AX, apoptosis, G2 chromosomal radiosensitivity and G0 micronucleus assay were used to compare case and control lymphocyte radiation responses. Results: Five hundred and thirty genes were up-regulated and 819 down-regulated by ionising radiation. Irradiated samples were identified with an overall cross-validated error rate of 3.4%. Prediction analyses to classify cases and controls using unirradiated (0 Gy), irradiated (4 Gy) or radiation response (4–0 Gy) expression profiles correctly identified samples with, respectively, 25%, 22% or 18.5% error rates. Significant inter-sample variation was observed for all cellular endpoints but cases and controls could not be distinguished. Conclusions: Variation in lymphocyte radiosensitivity does not necessarily correlate with normal tissue response to radiotherapy. Gene expression analysis can predict of radiation exposure and may in the future help prediction of normal tissue radiosensitivity.

  20. Comparison of normal tissue pharmacokinetics with 111In/9Y monoclonal antibody m170 for breast and prostate cancer

    International Nuclear Information System (INIS)

    Lehmann, Joerg; DeNardo, Gerald L.; Yuan, Aina; Shen Sui; O'Donnell, Robert T.; Richman, Carol M.; De Nardo, Sally J.

    2006-01-01

    Purpose: Radioactivity deposition in normal tissues limits the dose deliverable by radiopharmaceuticals (RP) in radioimmunotherapy (RIT). This study investigated the absorbed radiation dose in normal tissues for prostate cancer patients in comparison to breast cancer patients for 2 RPs using the monoclonal antibody (MAb) m170. Methods and Materials: 111 In-DOTA-glycylglycylglycyl-L-p-isothiocyanatophenylalanine amide (GGGF)-m170 and 111 In-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) 2-iminothiolane (2IT)-m170, representing the same MAb and chelate with and without a cleavable linkage, were studied in 13 breast cancer and 26 prostate cancer patients. Dosimetry for 9 Y was calculated using 111 In MAb pharmacokinetics from the initial imaging study for each patient, using reference man- and patient-specific masses. Results: The reference man-specific radiation doses (cGy/MBq) were not significantly different for the breast and the prostate cancer patients for both RPs in all but one tissue-RP combination (liver, DOTA-2IT). The patient-specific doses had differences between the groups most of which can be related to weight differences. Conclusions: Similar normal tissue doses were calculated for two groups of patients having different cancers and genders. This similarity combined with continued careful analysis of the imaging data might allow the use of higher starting doses in early phase RIT studies

  1. Complications of cancer therapy

    International Nuclear Information System (INIS)

    Moskowitz, P.S.; Parker, B.R.

    1985-01-01

    The purpose of this chapter is to review systematically the toxicity of contemporary chemotherapy and irradiation on normal tissues of growing children. Whenever possible, the separate toxicity of chemotherapy, irradiation, and combination therapy is addressed. However, it is not always possible to quantitate specifically such reactions in the face of multiple drug therapy, which may enhance radiation injury or reactivate prior radiation injury. Prior detailed reviews have provided important sources of information concerning radiation injury for this more general discussion. The information provided will assist both the clinician and the radiologist in the recognition of early and late complications of therapy in pediatric oncology

  2. Long-term effects of an intracavitary treatment with californium-252 on normal tissue

    International Nuclear Information System (INIS)

    Sullivan, M.F.; Beamer, J.L.; Mahony, T.D.; Cross, F.T.; Lund, J.E.; Endres, G.W.R.

    1976-01-01

    About one hundred fifty swine were exposed to either radium-226 or californium-252 sources in the uterine cervix to determine an RBE for both acute and long-term effects. That value for early changes in the tissues at risk in the treatment of cervical cancer was between 6.2 and 6.8. The incidence of complications increased with time after exposure, especially among animals treated with 252 Cf. Analysis of rectal injury showed that ulceration occurred frequently within a year postexposure at doses between 1600 and 2400 rad calculated at 2 cm lateral to the source midline. Fat necrosis and smooth muscle atrophy, resulting in a local rectal stricture, were delayed changes observed in some animals. The lower ureter was the site for a greater frequency of complications than the GI tract. Ureteral stricture often occurred at doses of 1200 rad from 252 Cf and 7000 rad from 226 Ra. Observation of delayed effects in the uterine-cervix in animals held up to 4 years postexposure indicate that the RBE for 252 Cf may be increased to a value as high as 18, while repair may have even decreased it to about 5.6 in the rectum. Fifty swine are still being observed for long-term effects after doses above 800 rad from 252 Cf and 5000 rad from 226 Ra

  3. Weak lensing of the Lyman α forest

    Science.gov (United States)

    Croft, Rupert A. C.; Romeo, Alessandro; Metcalf, R. Benton

    2018-06-01

    The angular positions of quasars are deflected by the gravitational lensing effect of foreground matter. The Lyman α (Lyα) forest seen in the spectra of these quasars is therefore also lensed. We propose that the signature of weak gravitational lensing of the Lyα forest could be measured using similar techniques that have been applied to the lensed cosmic microwave background (CMB), and which have also been proposed for application to spectral data from 21-cm radio telescopes. As with 21-cm data, the forest has the advantage of spectral information, potentially yielding many lensed `slices' at different redshifts. We perform an illustrative idealized test, generating a high-resolution angular grid of quasars (of order arcminute separation), and lensing the Lyα forest spectra at redshifts z = 2-3 using a foreground density field. We find that standard quadratic estimators can be used to reconstruct images of the foreground mass distribution at z ˜ 1. There currently exists a wealth of Lyα forest data from quasar and galaxy spectral surveys, with smaller sightline separations expected in the future. Lyα forest lensing is sensitive to the foreground mass distribution at redshifts intermediate between CMB lensing and galaxy shear, and avoids the difficulties of shape measurement associated with the latter. With further refinement and application of mass reconstruction techniques, weak gravitational lensing of the high-redshift Lyα forest may become a useful new cosmological probe.

  4. THE LYMAN ALPHA REFERENCE SAMPLE: EXTENDED LYMAN ALPHA HALOS PRODUCED AT LOW DUST CONTENT

    International Nuclear Information System (INIS)

    Hayes, Matthew; Östlin, Göran; Duval, Florent; Guaita, Lucia; Melinder, Jens; Sandberg, Andreas; Schaerer, Daniel; Verhamme, Anne; Orlitová, Ivana; Mas-Hesse, J. Miguel; Otí-Floranes, Héctor; Adamo, Angela; Atek, Hakim; Cannon, John M.; Herenz, E. Christian; Kunth, Daniel; Laursen, Peter

    2013-01-01

    We report on new imaging observations of the Lyman alpha emission line (Lyα), performed with the Hubble Space Telescope, that comprise the backbone of the Lyman alpha Reference Sample. We present images of 14 starburst galaxies at redshifts 0.028 P20 , Lyα radii are larger than those of Hα by factors ranging from 1 to 3.6, with an average of 2.4. The average ratio of Lyα-to-FUV radii is 2.9. This suggests that much of the Lyα light is pushed to large radii by resonance scattering. Defining the Relative Petrosian Extension of Lyα compared to Hα, ξ Lyα = R Lyα P20 /R Hα P20 , we find ξ Lyα to be uncorrelated with total Lyα luminosity. However, ξ Lyα is strongly correlated with quantities that scale with dust content, in the sense that a low dust abundance is a necessary requirement (although not the only one) in order to spread Lyα photons throughout the interstellar medium and drive a large extended Lyα halo.

  5. Markers of fibrosis and epithelial to mesenchymal transition demonstrate field cancerization in histologically normal tissue adjacent to breast tumors

    Science.gov (United States)

    Trujillo, Kristina A.; Heaphy, Christopher M.; Mai, Minh; Vargas, Keith M.; Jones, Anna C.; Vo, Phung; Butler, Kimberly S.; Joste, Nancy E.; Bisoffi, Marco; Griffith, Jeffrey K

    2011-01-01

    Previous studies have shown that a field of genetically altered but histologically normal tissue extends 1 cm or more from the margins of human breast tumors. The extent, composition and biological significance of this field are only partially understood, but the molecular alterations in affected cells could provide mechanisms for limitless replicative capacity, genomic instability and a microenvironment that supports tumor initiation and progression. We demonstrate by microarray, qRT-PCR and immunohistochemistry a signature of differential gene expression that discriminates between patient-matched, tumor-adjacent histologically normal breast tissues located 1 cm and 5 cm from the margins of breast adenocarcinomas (TAHN-1 and TAHN-5, respectively). The signature includes genes involved in extracellular matrix remodeling, wound healing, fibrosis and epithelial to mesenchymal transition (EMT). Myofibroblasts, which are mediators of wound healing and fibrosis, and intra-lobular fibroblasts expressing MMP2, SPARC, TGF-β3, which are inducers of EMT, were both prevalent in TAHN-1 tissues, sparse in TAHN-5 tissues, and absent in normal tissues from reduction mammoplasty. Accordingly, EMT markers S100A4 and vimentin were elevated in both luminal and myoepithelial cells, and EMT markers α-smooth muscle actin and SNAIL were elevated in luminal epithelial cells of TAHN-1 tissues. These results identify cellular processes that are differentially activated between TAHN-1 and TAHN-5 breast tissues, implicate myofibroblasts as likely mediators of these processes, provide evidence that EMT is occurring in histologically normal tissues within the affected field and identify candidate biomarkers to investigate whether or how field cancerization contributes to the development of primary or recurrent breast tumors. PMID:21105047

  6. SU-F-T-150: Comparing Normal Tissue Irradiated Volumes for Proton Vs. Photon Treatment Plans On Lung Patients

    Energy Technology Data Exchange (ETDEWEB)

    Liu, A; Mohan, R; Liao, Z [UT MD Anderson Cancer Center, Houston, TX (United States)

    2016-06-15

    Purpose: The aim of this work is to compare the “irradiated volume” (IRV) of normal tissues receiving 5, 20, 50, 80 and 90% or higher of the prescription dose with passively scattered proton therapy (PSPT) vs. IMRT of lung cancer patients. The overall goal of this research is to understand the factors affecting outcomes of a randomized PSPT vs. IMRT lung trial. Methods: Thirteen lung cancer patients, selected randomly, were analyzed. Each patient had PSPT and IMRT 74 Gy (RBE) plans meeting the same normal tissue constraints generated. IRVs were created for pairs of IMRT and PSPT plans on each patient. The volume of iGTV, (respiratory motion-incorporated GTV) was subtracted from each IRV to create normal tissue irradiated volume IRVNT. The average of IRVNT DVHs over all patients was also calculated for both modalities and inter-compared as were the selected dose-volume indices. Probability (p value) curves were calculated based on the Wilcoxon matched-paired signed-rank test to determine the dose regions where the statistically significant differences existed. Results: As expected, the average 5, 20 and 50% IRVNT’s for PSPT was found to be significantly smaller than for IMRT (p < 0.001, 0.01, and 0.001 respectively). However, the average 90% IRVNT for PSPT was greater than for IMRT (p = 0.003) presumably due to larger penumbra of protons and the long range of protons in lower density media. The 80% IRVNT for PSPT was also larger but not statistically distinguishable (p = .224). Conclusion: PSPT modality has smaller irradiated volume at lower doses, but larger volume at high doses. A larger cohort of lung patients will be analyzed in the future and IRVNT of patients treated with PSPT and IMRT will be compared to determine if the irradiated volumes (the magnitude of “dose bath”) correlate with outcomes.

  7. Normal tissue tolerance to external beam radiation therapy: Larynx and pharynx

    International Nuclear Information System (INIS)

    Debelleix, C.; Pointreau, Y.; Calais, G.; Pointreau, Y.; Lafond, C.; Denis, F.; Bourhis, J.H.

    2010-01-01

    For head and neck cancers, the radiation dose usually needed to sterilize a macroscopic tumour is at least 70 Gy in conventional fractionation. In the larynx, this dose level enables optimal tumour control while exposing the patient to a limited risk of severe complications. For oropharynx and nasopharynx tumors, it is sometimes possible to limit the dose received by the larynx according to the extent of the primary lesion. Thus, if the tumour constraints permit, the maximum dose to the larynx must be less than 63 to 66 Gy. To reduce the risk of laryngeal edema, it is recommended if possible to limit the mean non-involved larynx dose to 40 to 45 Gy. In the pharynx, literature's data suggested to minimize the volume of the pharyngeal constrictor muscles receiving a dose greater than or equal to 60 Gy. Limiting the volume receiving a dose greater than or equal to 50 Gy reduces the risk of dysphagia. These dose constraints should be tailored to each patient taking into account the extent of the initial primary lesion, the possible addition of chemotherapy or a modified fractionation radiotherapy. (authors)

  8. Proteinase-activated receptors - mediators of early and delayed normal tissue radiation responses

    International Nuclear Information System (INIS)

    Hauer-Jensen, M.

    2003-01-01

    Proteinase-activated receptors (PARs) are G-protein coupled receptors that are activated by proteolytic exposure of a receptor-tethered ligand. The discovery of this receptor family represents one of the most intriguing recent developments in signal transduction. PARs are involved in the regulation of many normal and pathophysiological processes, notably inflammatory and fibroproliferative responses to injury. Preclinical studies performed in our laboratory suggest that proteinase-activated receptor-1 (PAR-1) plays a critical role in the mechanism of chronicity of radiation fibrosis, while proteinase-activated receptor-2 (PAR-2) may mediate important fibroproliferative responses in irradiated intestine. Specifically, activation of PAR-1 by thrombin, and PAR-2 by pancreatic trypsin and mast cell proteinases, appears to be involved in acute radiation-induced inflammation, as well as in subsequent extracellular matrix deposition, leading to the development of intestinal wall fibrosis and clinical complications. Pharmacological modulators of PAR-1 or PAR-2 expression or activation would be potentially useful as preventive or therapeutic agents in patients who receive radiation therapy, especially if blockade could be targeted to specific tissues or cellular compartments

  9. Isolating the Lyman alpha forest BAO anomaly

    Energy Technology Data Exchange (ETDEWEB)

    Evslin, Jarah, E-mail: jarah@impcas.ac.cn [Institute of Modern Physics, Chinese Academy of Sciences, NanChangLu 509, Lanzhou 730000 (China)

    2017-04-01

    A 2.5-3σ discrepancy has been reported between the baryonic acoustic oscillation peak (BAO) in the Lyman α forest at z ∼ 2.34 and the best fit Planck ΛCDM cosmology. To isolate the origin of the tension, we consider unanchored BAO, in which the standard BAO ruler is not calibrated, eliminating any dependence on cosmology before redshift z ∼ 2.34. We consider BOSS BAO measurements at z ∼ 0.32, 0.57 and 2.34, using the full 2-dimensional constraints on the angular and line of sight BAO scale, as well as isotropic BAO measurements by 6dF and SDSS at z ∼ 0.106 and z ∼ 0.15. We find that the z >0.43 data alone is in 2.9σ of tension with ΛCDM with or without the Planck best fit values of the mass fraction Ω {sub m} and the BAO scale r {sub d} H {sub 0}, indicating that the tension arises not from the ΛCDM parameters but from the dark energy evolution itself at 0.57< z <2.34. This conclusion is supported when the acoustic scale measured by the CMB is included, which further increases the tension and excludes a solution with a constant dark energy equation of state. Including the low z BAO data, which is itself consistent with ΛCDM, reduces the tension to just over 2σ, however in this case a CPL parametrization of the dark energy evolution yields only a modest improvement.

  10. Lyman Limit Absorbers in GALEX Spectra

    Science.gov (United States)

    Williger, Gerard M.; Haberzettl, Lutz G.; Ribaudo, Joseph; Kuchner, Marc J.; Burchett, Joseph; Clowes, Roger G.; Lauroesch, James T.; Mills, Brianna; Borden, Jeremy

    2018-01-01

    We describe the method and early results for crowdsourcing a search for low-redshift partial and complete Lyman Limit Systems (pLLSs and LLSs) in the GALEX spectral archive. LLSs have been found in large numbers at z>3 and traced to lower redshift through a relatively small number of QSO spectra from spaced-based telescopes. From a sample of 44 pLLSs and 11 LLSs at 0.1 = -0.32 +/- 0.07 and the low-metallicity portion centered at = -1.87 +/- 0.11.The GALEX spectral archive offers a vast dataset potentially containing hundreds of LLSs, which may be leveraged to search for such a bimodality and track its evolution within the unconstrained near-UV gap at 1data coverage and signal-to-noise ratio are highly variable, which hampers an automated search. We have therefore begun crowdsourcing a subset of the GALEX archive for LLSs and pLLSs via a Zooniverse project. Initially, undergraduate physics majors are performing a pilot project before releasing to citizen scientists in the public at large. We will then vet candidate systems and estimate column densities in a follow-up analysis. Upon assessing the accuracy of the physics majors’ identifications, the results will be used to devise a larger program with the help of the general public. The resulting data set would then provide the best available link between the HST-selected far-UV and ground-based pLLS+LLS samples and provide an ideal sample for consequent metallicity determinations.

  11. Effect of implanted radioactive 125I seeds on normal tissue structures of bronchus, esophagus, pulmonary artery, pulmonary vein and alveolus in dogs

    International Nuclear Information System (INIS)

    Qi Liangchen; Han Zhenguo; Yang Bin; Heersitai

    2008-01-01

    Objective: To investigate the effect of implanted radioactive 125 I seeds on normal tissue structures of bronchus, esophagus, pulmonary artery, pulmonary vein and alveolus in dogs. Methods: Nine healthy male dogs weighing 17-21 kg were randomly divided into three groups: 30 d, 60 d experimental groups and control group. Radioactive 125 I seeds (3.7 x 10 7 Bg, 1.0 mCi) were implanted into the sides of bronchus, esophagus, pulmonary artery, pulmonary vein respectively, the samples of bronchus, esophagus, pulmonary artery, pulmonary vein were taken 30 and 60 d after transplantation, HE staining was used to observe the pathologic changes of the tissues under light microscope. Results: The damages of normal bronchus, esophagus, pulmonary artery, pulmonary vein and alveolus after radioactive 125 I seeds implantation in 30 d group were weaker than those in control group and 60 d group, there were no complications such as perforation, hemorrhage, necrosis, etc. Histopathological score indicated that the scores of bronchus, esophagus and alveolar in 30 d group and 60 d group were higher than those in control group (P 0.05); there was no significant difference in histopathological score of pulmonary vein among all groups (P>0.05). Conclusion: The implanted radioactive 125 I seeds can damage all kinds of tissues at different degrees, but this kind of damage is reversible, the dog may repair the damage through its own repair ability, its clinical application is safe. (authors)

  12. Estimating functional liver reserve following hepatic irradiation: Adaptive normal tissue response models

    International Nuclear Information System (INIS)

    Stenmark, Matthew H.; Cao, Yue; Wang, Hesheng; Jackson, Andrew; Ben-Josef, Edgar; Ten Haken, Randall K.; Lawrence, Theodore S.; Feng, Mary

    2014-01-01

    Purpose: To estimate the limit of functional liver reserve for safe application of hepatic irradiation using changes in indocyanine green, an established assay of liver function. Materials and methods: From 2005 to 2011, 60 patients undergoing hepatic irradiation were enrolled in a prospective study assessing the plasma retention fraction of indocyanine green at 15-min (ICG-R15) prior to, during (at 60% of planned dose), and after radiotherapy (RT). The limit of functional liver reserve was estimated from the damage fraction of functional liver (DFL) post-RT [1 − (ICG-R15 pre-RT /ICG-R15 post-RT )] where no toxicity was observed using a beta distribution function. Results: Of 48 evaluable patients, 3 (6%) developed RILD, all within 2.5 months of completing RT. The mean ICG-R15 for non-RILD patients pre-RT, during-RT and 1-month post-RT was 20.3%(SE 2.6), 22.0%(3.0), and 27.5%(2.8), and for RILD patients was 6.3%(4.3), 10.8%(2.7), and 47.6%(8.8). RILD was observed at post-RT damage fractions of ⩾78%. Both DFL assessed by during-RT ICG and MLD predicted for DFL post-RT (p < 0.0001). Limiting the post-RT DFL to 50%, predicted a 99% probability of a true complication rate <15%. Conclusion: The DFL as assessed by changes in ICG during treatment serves as an early indicator of a patient’s tolerance to hepatic irradiation

  13. SU-F-T-681: Does the Biophysical Modeling for Immunological Aspects in Radiotherapy Precisely Predict Tumor and Normal Tissue Responses?

    Energy Technology Data Exchange (ETDEWEB)

    Oita, M [Graduate School of Health Sciences, Okayama University, Okayama, Okayama (Japan); Nakata, K [Tokyo University of Science, Noda, Chiba (Japan); Sasaki, M [Tokushima University Hospital, Tokushima, Tokushima (Japan); Tominaga, M [Tokushima University Graduate School, Tokushima, Tokushima (Japan); Aoyama, H [Okayama University Hospital, Okayama, Okayama (Japan); Honda, H [Ehime University Hospital, Tohon, Ehime (Japan); Uto, Y [Tokushima University, Tokushima, Tokushima (Japan)

    2016-06-15

    Purpose: Recent advances in immunotherapy make possible to combine with radiotherapy. The aim of this study was to assess the TCP/NTCP model with immunological aspects including stochastic distribution as intercellular uncertainties. Methods: In the clinical treatment planning system (Eclipse ver.11.0, Varian medical systems, US), biological parameters such as α/β, D50, γ, n, m, TD50 including repair parameters (bi-exponential repair) can be set as any given values to calculate the TCP/NTCP. Using a prostate cancer patient data with VMAT commissioned as a 6-MV photon beam of Novalis-Tx (BrainLab, US) in clinical use, the fraction schedule were hypothesized as 70–78Gy/35–39fr, 72–81Gy/40–45fr, 52.5–66Gy/16–22fr, 35–40Gy/5fr of 5–7 fractions in a week. By use of stochastic biological model applying for Gaussian distribution, the effects of the TCP/NTCP variation of repair parameters of the immune system as well as the intercellular uncertainty of tumor and normal tissues have been evaluated. Results: As respect to the difference of the α/β, the changes of the TCP/NTCP were increased in hypo-fraction regimens. The difference between the values of n and m affect the variation of the NTCP with the fraction schedules, independently. The elongation of repair half-time (long) increased the TCP/NTCP twice or much higher in the case of hypo-fraction scheme. For tumor, the repopulation parameters such as Tpot and Tstart, which is immunologically working to the tumor, improved TCP. Conclusion: Compared to default fixed value, which has affected by the probability of cell death and cure, hypo-fractionation schemes seemed to have advantages for the variations of the values of m. The possibility of an increase of the α/β or TD50 and repair parameters in tumor and normal tissue by immunological aspects were highly expected. For more precise prediction, treatment planning systems should be incorporated the complicated biological optimization in clinical

  14. Expression of Apoptosis Inducing-Ligands, TRAIL and Fas-L in Hydatid Cyst Germinal Layer and Normal Tissue

    Directory of Open Access Journals (Sweden)

    Adel Spotin

    2012-04-01

    Full Text Available Background & objectives: Hydaticosis is a zoonotic helminthic disease of human and other intermediated hosts in which larval stages of the tapeworm Echinococcus granulosu transfect human. The liver and lung are the host tissues for the hydatid cyst . It is unknown which mechanisms are involved in infertility of the cyst and suppression of the fertile cyst. This study was aimed to evaluate the expression of the apoptosis inducing-ligands such as TRAIL and Fas-L in germinal layer of the cyst and human normal tissue surrounding the cyst that is one of the unknown host innate immunity mechanisms against the hydatid cyst.   Methods: In this study, four isolated hydatid cysts were used which had been diagnosed in patients by radiography and parasitological examination in Mashhad Ghaem hospital. Furthermore, the germinal layer of the cyst and accompanied normal peripheral tissues were separated by scalpel in sterile conditions. After homogenization, expression of TRAIL and Fas-L genes were studied by semi-quantitive RT-PCR method.   Results: The TRAIL and Fas-L showed significant higher level expression in germinal layer of infertile cyst than the fertile cyst and host normal tissues.   Conclusion: The host tissue-induced apoptosis of germinal layer of the fertile cysts is probably one of the infertility mechanism in patients with hydaticosis

  15. THE LYMAN ALPHA REFERENCE SAMPLE: EXTENDED LYMAN ALPHA HALOS PRODUCED AT LOW DUST CONTENT

    Energy Technology Data Exchange (ETDEWEB)

    Hayes, Matthew [Universite de Toulouse, UPS-OMP, IRAP, Toulouse (France); Oestlin, Goeran; Duval, Florent; Guaita, Lucia; Melinder, Jens; Sandberg, Andreas [Department of Astronomy, Oskar Klein Centre, Stockholm University, AlbaNova University Centre, SE-106 91 Stockholm (Sweden); Schaerer, Daniel [CNRS, IRAP, 14, avenue Edouard Belin, F-31400 Toulouse (France); Verhamme, Anne; Orlitova, Ivana [Geneva Observatory, University of Geneva, 51 Chemin des Maillettes, CH-1290 Versoix (Switzerland); Mas-Hesse, J. Miguel; Oti-Floranes, Hector [Centro de Astrobiologia (CSIC-INTA), Departamento de Astrofisica, POB 78, 28691 Villanueva de la Canada (Spain); Adamo, Angela [Max Planck Institute for Astronomy, Koenigstuhl 17, D-69117 Heidelberg (Germany); Atek, Hakim [Laboratoire d' Astrophysique, Ecole Polytechnique Federale de Lausanne (EPFL), Observatoire, CH-1290 Sauverny (Switzerland); Cannon, John M. [Department of Physics and Astronomy, Macalester College, 1600 Grand Avenue, Saint Paul, MN 55105 (United States); Herenz, E. Christian [Leibniz-Institut fuer Astrophysik (AIP), An der Sternwarte 16, D-14482 Potsdam (Germany); Kunth, Daniel [Institut d' Astrophysique de Paris, UMR 7095 CNRS and UPMC, 98 bis Bd Arago, F-75014 Paris (France); Laursen, Peter, E-mail: matthew@astro.su.se [Dark Cosmology Centre, Niels Bohr Institute, University of Copenhagen, Juliane Maries Vej 30, DK-2100 Copenhagen (Denmark)

    2013-03-10

    We report on new imaging observations of the Lyman alpha emission line (Ly{alpha}), performed with the Hubble Space Telescope, that comprise the backbone of the Lyman alpha Reference Sample. We present images of 14 starburst galaxies at redshifts 0.028 < z < 0.18 in continuum-subtracted Ly{alpha}, H{alpha}, and the far ultraviolet continuum. We show that Ly{alpha} is emitted on scales that systematically exceed those of the massive stellar population and recombination nebulae: as measured by the Petrosian 20% radius, R{sub P20}, Ly{alpha} radii are larger than those of H{alpha} by factors ranging from 1 to 3.6, with an average of 2.4. The average ratio of Ly{alpha}-to-FUV radii is 2.9. This suggests that much of the Ly{alpha} light is pushed to large radii by resonance scattering. Defining the Relative Petrosian Extension of Ly{alpha} compared to H{alpha}, {xi}{sub Ly{alpha}} = R {sup Ly{alpha}}{sub P20}/R {sup H{alpha}}{sub P20}, we find {xi}{sub Ly{alpha}} to be uncorrelated with total Ly{alpha} luminosity. However, {xi}{sub Ly{alpha}} is strongly correlated with quantities that scale with dust content, in the sense that a low dust abundance is a necessary requirement (although not the only one) in order to spread Ly{alpha} photons throughout the interstellar medium and drive a large extended Ly{alpha} halo.

  16. Oxygen sensitivity of krypton and Lyman-alpha hygrometers

    NARCIS (Netherlands)

    Dijk, van A.; Kohsiek, W.; Bruin, de H.A.R.

    2003-01-01

    The oxygen sensitivity of krypton and Lyman-¿ hygrometers is studied. Using a dewpoint generator and a controlled nitrogen/oxygen flow the extinction coefficients of five hygrometers associated with the third-order Taylor expansion of the Lambert¿Beer law around reference conditions for oxygen and

  17. Protons Offer Reduced Normal-Tissue Exposure for Patients Receiving Postoperative Radiotherapy for Resected Pancreatic Head Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nichols, Romaine C., E-mail: rnichols@floridaproton.org [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Huh, Soon N. [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Prado, Karl L.; Yi, Byong Y.; Sharma, Navesh K. [Department of Radiation Oncology, University of Maryland, Baltimore, MD (United States); Ho, Meng W.; Hoppe, Bradford S.; Mendenhall, Nancy P.; Li, Zuofeng [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Regine, William F. [Department of Radiation Oncology, University of Maryland, Baltimore, MD (United States)

    2012-05-01

    Purpose: To determine the potential role for adjuvant proton-based radiotherapy (PT) for resected pancreatic head cancer. Methods and Materials: Between June 2008 and November 2008, 8 consecutive patients with resected pancreatic head cancers underwent optimized intensity-modulated radiotherapy (IMRT) treatment planning. IMRT plans used between 10 and 18 fields and delivered 45 Gy to the initial planning target volume (PTV) and a 5.4 Gy boost to a reduced PTV. PTVs were defined according to the Radiation Therapy Oncology Group 9704 radiotherapy guidelines. Ninety-five percent of PTVs received 100% of the target dose and 100% of the PTVs received 95% of the target dose. Normal tissue constraints were as follows: right kidney V18 Gy to <70%; left kidney V18 Gy to <30%; small bowel/stomach V20 Gy to <50%, V45 Gy to <15%, V50 Gy to <10%, and V54 Gy to <5%; liver V30 Gy to <60%; and spinal cord maximum to 46 Gy. Optimized two- to three-field three-dimensional conformal proton plans were retrospectively generated on the same patients. The team generating the proton plans was blinded to the dose distributions achieved by the IMRT plans. The IMRT and proton plans were then compared. A Wilcoxon paired t-test was performed to compare various dosimetric points between the two plans for each patient. Results: All proton plans met all normal tissue constraints and were isoeffective with the corresponding IMRT plans in terms of PTV coverage. The proton plans offered significantly reduced normal-tissue exposure over the IMRT plans with respect to the following: median small bowel V20 Gy, 15.4% with protons versus 47.0% with IMRT (p = 0.0156); median gastric V20 Gy, 2.3% with protons versus 20.0% with IMRT (p = 0.0313); and median right kidney V18 Gy, 27.3% with protons versus 50.5% with IMRT (p = 0.0156). Conclusions: By reducing small bowel and stomach exposure, protons have the potential to reduce the acute and late toxicities of postoperative chemoradiation in this setting.

  18. A hybrid electron and photon IMRT planning technique that lowers normal tissue integral patient dose using standard hardware.

    Science.gov (United States)

    Rosca, Florin

    2012-06-01

    To present a mixed electron and photon IMRT planning technique using electron beams with an energy range of 6-22 MeV and standard hardware that minimizes integral dose to patients for targets as deep as 7.5 cm. Ten brain cases, two lung, a thyroid, an abdominal, and a parotid case were planned using two planning techniques: a photon-only IMRT (IMRT) versus a mixed modality treatment (E+IMRT) that includes an enface electron beam and a photon IMRT portion that ensures a uniform target coverage. The electron beam is delivered using a regular cutout placed in an electron cone. The electron energy was chosen to provide a good trade-off between minimizing integral dose and generating a uniform, deliverable plan. The authors choose electron energies that cover the deepest part of PTV with the 65%-70% isodose line. The normal tissue integral dose, the dose for ring structures around the PTV, and the volumes of the 75%, 50%, and 25% isosurfaces were used to compare the dose distributions generated by the two planning techniques. The normal tissue integral dose was lowered by about 20% by the E+IMRT plans compared to the photon-only IMRT ones for most studied cases. With the exception of lungs, the dose reduction associated to the E+IMRT plans was more pronounced further away from the target. The average dose ratio delivered to the 0-2 cm and the 2-4 cm ring structures for brain patients for the two planning techniques were 89.6% and 70.8%, respectively. The enhanced dose sparing away from the target for the brain patients can also be observed in the ratio of the 75%, 50%, and 25% isodose line volumes for the two techniques, which decreases from 85.5% to 72.6% and further to 65.1%, respectively. For lungs, the lateral electron beams used in the E+IMRT plans were perpendicular to the mostly anterior/posterior photon beams, generating much more conformal plans. The authors proved that even using the existing electron delivery hardware, a mixed electron/photon planning

  19. Generation of benchmark DVH's for normal tissues in IMRT for base of tongue and tonsil cancer patients

    International Nuclear Information System (INIS)

    Rana, B.S.; Arun Singh, O.; Goswami, P.; Bhardwaj, A.; Santam; Susmita, Goshal; Sharma, S.C.

    2007-01-01

    IMRT is the treatment of choice for treatment of prostate and H and N cancer treatment but it take quality of time to generate an optimal treatment plan and Dose Volume Histogram (DVH) varies significantly from one plan to other patient plan which is difficult to compare. Here the authors propose to generate bench mark DVH's for normal tissues for Base of tongue (BOT) and Tonsil cancer treatment to bring consistency in selection of plans and reduce the overall time of planning and comparison b/n different plan will be simpler and easier. Here the authors propose to generate benchmark DVH for spinal cord, larynx, pharynx, parotid and brain stem for BOT and tonsil patients treated with Intensity modulated radiotherapy in Postgraduate Institute of Medical Education and Research. And to see whether Benchmark DVH can be effectively used in IMRT for BOT and Ca Tonsil

  20. Enhancing the radiation response of tumors but not early or late responding normal tissues using a vascular disrupting agent

    DEFF Research Database (Denmark)

    Horsman, Michael R

    2017-01-01

    INTRODUCTION: Vascular disrupting agents (VDAs) damage tumor vasculature and enhance tumor radiation response. In this pre-clinical study, we combined radiation with the leading VDA in clinical development, combretastatin A-4 phosphate (CA4P), and compared the effects seen in tumors and relevant...... normal tissues. MATERIAL AND METHODS: Radiation was applied locally to tissues in CDF1 mice to produce full radiation dose-response curves. CA4P (250 mg/kg) was intraperitoneally (i.p.) injected within 30 minutes after irradiating. Response of 200 mm3 foot implanted C3H mammary carcinomas was assessed......% increase in ventilation rate measured by plethysmography within 9 months). A Chi-squared test was used for statistical comparisons (significance level of p 4P. The radiation...

  1. Tumor and normal tissue motion in the thorax during respiration: Analysis of volumetric and positional variations using 4D CT

    International Nuclear Information System (INIS)

    Weiss, Elisabeth; Wijesooriya, Krishni; Dill, S. Vaughn; Keall, Paul J.

    2007-01-01

    Purpose: To investigate temporospatial variations of tumor and normal tissue during respiration in lung cancer patients. Methods and Materials: In 14 patients, gross tumor volume (GTV) and normal tissue structures were manually contoured on four-dimensional computed tomography (4D-CT) scans. Structures were evaluated for volume changes, centroid (center of mass) motion, and phase dependence of variations relative to inspiration. Only volumetrically complete structures were used for analysis (lung in 2, heart in 8, all other structures in >10 patients). Results: During respiration, the magnitude of contoured volumes varied up to 62.5% for GTVs, 25.5% for lungs, and 12.6% for hearts. The range of maximum three-dimensional centroid movement for individual patients was 1.3-24.0 mm for GTV, 2.4-7.9 mm for heart, 5.2-12.0 mm for lungs, 0.3-5.5 mm for skin markers, 2.9-10.0 mm for trachea, and 6.6-21.7 mm for diaphragm. During respiration, the centroid positions of normal structures varied relative to the centroid position of the respective GTV by 1.5-8.1 mm for heart, 2.9-9.3 mm for lungs, 1.2-9.2 mm for skin markers, 0.9-7.1 mm for trachea, and 2.7-16.4 mm for diaphragm. Conclusion: Using 4D-CT, volumetric changes, positional alterations as well as changes in the position of contoured structures relative to the GTV were observed with large variations between individual patients. Although the interpretation of 4D-CT data has considerable uncertainty because of 4D-CT artifacts, observer variations, and the limited acquisition time, the findings might have a significant impact on treatment planning

  2. Radioprotection by WR-151327 against the late normal tissue damage in mouse hind legs from gamma ray radiation

    International Nuclear Information System (INIS)

    Matsushita, Satoru; Ando, Koichi; Koike, Sachiko

    1994-01-01

    To evaluate the protective effect of WR-151327 on late radiation-induced damaged to normal tissues in mice, the right hind legs of mice with or without WR-151327 administration (400 mg/kg) were irradiated with 137 Cs gamma rays. Leg contracture and skin shrinkage assays were performed at 380 days after irradiation. The mice were killed on day 400 postirradiation and histological sections of the legs were made. The thickness of the dermis, epidermis, and skin (dermis plus epidermis) was measured. The muscular area of the legs and the posterior knee angle between the femur and tibia were also measured. The left hind legs were similarly assessed as nonirradiated controls. Group means and standard deviations were calculated and dose-response curves were drawn for every endpoint. Then, the dose modifying factor (DMF) for each endpoint and the correlations among endpoints were determined. Latae damage assayed by leg contracture and skin shrinkage progressed with increasing radiation dose. However, it was reduced by drug treatment. The significant effect was indicated for skin shrinkage by a DMF of 1.8 at 35%. The DMF for leg contracture was 1.3 at 6 mm. In the irradiated legs, epidermal hyperplasia and dermal fibrosis in the skin, muscular atrophy, and extension disturbance of the knee joint were observed. These changes progressed with increasing radiation dose. Skin damage assayed by the present endpoints was also reduced by drug treatment by DMFs of 1.4 to 1.7. However, DMFs for damage to the muscle and knee were not determined because no isoeffect was observed. There were good correlations between leg contracture or skin shrinkage and the other endpoints in both untreated and drug-treated mice. WR-151327 has the potential to protect against radiation-induced late normal tissue damage. 17 refs., 6 figs., 2 tabs

  3. Normal tissue consequences

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    This chapter discusses radiotherapy planning and irradiation effects on the following: pelvis (bone, bone marrow, muscles, genital organs, urinary bladder, urethra, ureter, small intestine, rectum, anus); abdomen (stomach, liver, small intestine, kidneys, adrenal glands, pancreas, spleen); thorax (respiratory system, esophagus, heart, ribs, breasts, brachial plexus, spinal cord); head and neck (salivary glands, teeth, mandible, mucosa, ears, eyes, facial muscles, larynx, thyroid gland, pituitary gland, brain, spinal cord); central nervous system (brain, optic nerves, pituitary gland, scalp, skull, spinal cord); and the extremities

  4. SU-F-T-187: Quantifying Normal Tissue Sparing with 4D Robust Optimization of Intensity Modulated Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Newpower, M; Ge, S; Mohan, R [UT MD Anderson Cancer Center, Houston, TX (United States)

    2016-06-15

    Purpose: To report an approach to quantify the normal tissue sparing for 4D robustly-optimized versus PTV-optimized IMPT plans. Methods: We generated two sets of 90 DVHs from a patient’s 10-phase 4D CT set; one by conventional PTV-based optimization done in the Eclipse treatment planning system, and the other by an in-house robust optimization algorithm. The 90 DVHs were created for the following scenarios in each of the ten phases of the 4DCT: ± 5mm shift along x, y, z; ± 3.5% range uncertainty and a nominal scenario. A Matlab function written by Gay and Niemierko was modified to calculate EUD for each DVH for the following structures: esophagus, heart, ipsilateral lung and spinal cord. An F-test determined whether or not the variances of each structure’s DVHs were statistically different. Then a t-test determined if the average EUDs for each optimization algorithm were statistically significantly different. Results: T-test results showed each structure had a statistically significant difference in average EUD when comparing robust optimization versus PTV-based optimization. Under robust optimization all structures except the spinal cord received lower EUDs than PTV-based optimization. Using robust optimization the average EUDs decreased 1.45% for the esophagus, 1.54% for the heart and 5.45% for the ipsilateral lung. The average EUD to the spinal cord increased 24.86% but was still well below tolerance. Conclusion: This work has helped quantify a qualitative relationship noted earlier in our work: that robust optimization leads to plans with greater normal tissue sparing compared to PTV-based optimization. Except in the case of the spinal cord all structures received a lower EUD under robust optimization and these results are statistically significant. While the average EUD to the spinal cord increased to 25.06 Gy under robust optimization it is still well under the TD50 value of 66.5 Gy from Emami et al. Supported in part by the NCI U19 CA021239.

  5. The theoretical benefit of beam fringe compensation and field size reduction for iso-normal tissue complication probability dose escalation in radiotherapy of lung cancer

    NARCIS (Netherlands)

    Engelsman, Martijn; Remeijer, Peter; van Herk, Marcel; Mijnheer, Ben; Damen, Eugène

    2003-01-01

    To assess the benefit of beam fringe (50%-90% dose level) sharpening for lung tumors, we performed a numerical simulation in which all geometrical errors (breathing motion, random and systematic errors) are included. A 50 mm diameter lung tumor, located centrally in a lung-equivalent phantom was

  6. Variation of normal tissue complication probability (NTCP) estimates of radiation-induced hypothyroidism in relation to changes in delineation of the thyroid gland

    DEFF Research Database (Denmark)

    Rønjom, Marianne Feen; Brink, Carsten; Laugaard Lorenzen, Ebbe

    2015-01-01

    volume, Dmean and estimated risk of HT. Bland-Altman plots were used for assessment of the systematic (mean) and random [standard deviation (SD)] variability of the three parameters, and a method for displaying the spatial variation in delineation differences was developed. Results. Intra......-observer variability resulted in a mean difference in thyroid volume and Dmean of 0.4 cm(3) (SD ± 1.6) and -0.5 Gy (SD ± 1.0), respectively, and 0.3 cm(3) (SD ± 1.8) and 0.0 Gy (SD ± 1.3) for inter-observer variability. The corresponding mean differences of NTCP values for radiation-induced HT due to intra- and inter...

  7. Radiobiological influence of megavoltage electron pulses of ultra-high pulse dose rate on normal tissue cells.

    Science.gov (United States)

    Laschinsky, Lydia; Karsch, Leonhard; Leßmann, Elisabeth; Oppelt, Melanie; Pawelke, Jörg; Richter, Christian; Schürer, Michael; Beyreuther, Elke

    2016-08-01

    Regarding the long-term goal to develop and establish laser-based particle accelerators for a future radiotherapeutic treatment of cancer, the radiobiological consequences of the characteristic short intense particle pulses with ultra-high peak dose rate, but low repetition rate of laser-driven beams have to be investigated. This work presents in vitro experiments performed at the radiation source ELBE (Electron Linac for beams with high Brilliance and low Emittance). This accelerator delivered 20-MeV electron pulses with ultra-high pulse dose rate of 10(10) Gy/min either at the low pulse frequency analogue to previous cell experiments with laser-driven electrons or at high frequency for minimizing the prolonged dose delivery and to perform comparison irradiation with a quasi-continuous electron beam analogue to a clinically used linear accelerator. The influence of the different electron beam pulse structures on the radiobiological response of the normal tissue cell line 184A1 and two primary fibroblasts was investigated regarding clonogenic survival and the number of DNA double-strand breaks that remain 24 h after irradiation. Thereby, no considerable differences in radiation response were revealed both for biological endpoints and for all probed cell cultures. These results provide evidence that the radiobiological effectiveness of the pulsed electron beams is not affected by the ultra-high pulse dose rates alone.

  8. Cell kinetical aspect of normal tissue damages in relation to radiosensitivity of cells, especially from the points of LQ model

    International Nuclear Information System (INIS)

    Tsubouchi, Susumu; Oohara, Hiroshi.

    1989-01-01

    Several points on the early and late radiation induced-normal tissue damages in terms of LQ model in multifractionation experiments of isoeffect were discussed from two fractors, (1) dose-responses of cell survivals or of tissue damages and (2) principles of the model. Application of the model to the both early and late tissue damages was fairly difficult in several tissues and several experimental conditions. In early damages, cell survival curve of single irradiation did not always fit to LQ model and further more incomlete repair as well as repopulation in multifractionation experiment contradicted the model especially in low dose fractionation. In late damages, the damages themselves did not express directly cell survival but probably indicate the degree of functional cell damage at the level of 10 -1 . As most isoeffects in early damages were taken at the level of 10 -3 , the comparison of two results from early and late tissue damages indicated the lack of coordinations both conceptionally and experimentally. (author)

  9. Radiobiological influence of megavoltage electron pulses of ultra-high pulse dose rate on normal tissue cells

    International Nuclear Information System (INIS)

    Laschinsky, Lydia; Karsch, Leonhard; Schuerer, Michael; Lessmann, Elisabeth; Beyreuther, Elke; Oppelt, Melanie; Pawelke, Joerg; Richter, Christian

    2016-01-01

    Regarding the long-term goal to develop and establish laser-based particle accelerators for a future radiotherapeutic treatment of cancer, the radiobiological consequences of the characteristic short intense particle pulses with ultra-high peak dose rate, but low repetition rate of laser-driven beams have to be investigated. This work presents in vitro experiments performed at the radiation source ELBE (Electron Linac for beams with high Brilliance and low Emittance). This accelerator delivered 20-MeV electron pulses with ultra-high pulse dose rate of 10"1"0 Gy/min either at the low pulse frequency analogue to previous cell experiments with laser-driven electrons or at high frequency for minimizing the prolonged dose delivery and to perform comparison irradiation with a quasi-continuous electron beam analogue to a clinically used linear accelerator. The influence of the different electron beam pulse structures on the radiobiological response of the normal tissue cell line 184A1 and two primary fibroblasts was investigated regarding clonogenic survival and the number of DNA double-strand breaks that remain 24 h after irradiation. Thereby, no considerable differences in radiation response were revealed both for biological endpoints and for all probed cell cultures. These results provide evidence that the radiobiological effectiveness of the pulsed electron beams is not affected by the ultra-high pulse dose rates alone. (orig.)

  10. Feasibility of a novel deformable image registration technique to facilitate classification, targeting, and monitoring of tumor and normal tissue

    International Nuclear Information System (INIS)

    Brock, Kristy K.; Dawson, Laura A.; Sharpe, Michael B.; Moseley, Douglas J.; Jaffray, David A.

    2006-01-01

    Purpose: To investigate the feasibility of a biomechanical-based deformable image registration technique for the integration of multimodality imaging, image guided treatment, and response monitoring. Methods and Materials: A multiorgan deformable image registration technique based on finite element modeling (FEM) and surface projection alignment of selected regions of interest with biomechanical material and interface models has been developed. FEM also provides an inherent method for direct tracking specified regions through treatment and follow-up. Results: The technique was demonstrated on 5 liver cancer patients. Differences of up to 1 cm of motion were seen between the diaphragm and the tumor center of mass after deformable image registration of exhale and inhale CT scans. Spatial differences of 5 mm or more were observed for up to 86% of the surface of the defined tumor after deformable image registration of the computed tomography (CT) and magnetic resonance images. Up to 6.8 mm of motion was observed for the tumor after deformable image registration of the CT and cone-beam CT scan after rigid registration of the liver. Deformable registration of the CT to the follow-up CT allowed a more accurate assessment of tumor response. Conclusions: This biomechanical-based deformable image registration technique incorporates classification, targeting, and monitoring of tumor and normal tissue using one methodology

  11. CT-based patient modeling for head and neck hyperthermia treatment planning: manual versus automatic normal-tissue-segmentation.

    Science.gov (United States)

    Verhaart, René F; Fortunati, Valerio; Verduijn, Gerda M; van Walsum, Theo; Veenland, Jifke F; Paulides, Margarethus M

    2014-04-01

    Clinical trials have shown that hyperthermia, as adjuvant to radiotherapy and/or chemotherapy, improves treatment of patients with locally advanced or recurrent head and neck (H&N) carcinoma. Hyperthermia treatment planning (HTP) guided H&N hyperthermia is being investigated, which requires patient specific 3D patient models derived from Computed Tomography (CT)-images. To decide whether a recently developed automatic-segmentation algorithm can be introduced in the clinic, we compared the impact of manual- and automatic normal-tissue-segmentation variations on HTP quality. CT images of seven patients were segmented automatically and manually by four observers, to study inter-observer and intra-observer geometrical variation. To determine the impact of this variation on HTP quality, HTP was performed using the automatic and manual segmentation of each observer, for each patient. This impact was compared to other sources of patient model uncertainties, i.e. varying gridsizes and dielectric tissue properties. Despite geometrical variations, manual and automatic generated 3D patient models resulted in an equal, i.e. 1%, variation in HTP quality. This variation was minor with respect to the total of other sources of patient model uncertainties, i.e. 11.7%. Automatically generated 3D patient models can be introduced in the clinic for H&N HTP. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. CT-based patient modeling for head and neck hyperthermia treatment planning: Manual versus automatic normal-tissue-segmentation

    International Nuclear Information System (INIS)

    Verhaart, René F.; Fortunati, Valerio; Verduijn, Gerda M.; Walsum, Theo van; Veenland, Jifke F.; Paulides, Margarethus M.

    2014-01-01

    Background and purpose: Clinical trials have shown that hyperthermia, as adjuvant to radiotherapy and/or chemotherapy, improves treatment of patients with locally advanced or recurrent head and neck (H and N) carcinoma. Hyperthermia treatment planning (HTP) guided H and N hyperthermia is being investigated, which requires patient specific 3D patient models derived from Computed Tomography (CT)-images. To decide whether a recently developed automatic-segmentation algorithm can be introduced in the clinic, we compared the impact of manual- and automatic normal-tissue-segmentation variations on HTP quality. Material and methods: CT images of seven patients were segmented automatically and manually by four observers, to study inter-observer and intra-observer geometrical variation. To determine the impact of this variation on HTP quality, HTP was performed using the automatic and manual segmentation of each observer, for each patient. This impact was compared to other sources of patient model uncertainties, i.e. varying gridsizes and dielectric tissue properties. Results: Despite geometrical variations, manual and automatic generated 3D patient models resulted in an equal, i.e. 1%, variation in HTP quality. This variation was minor with respect to the total of other sources of patient model uncertainties, i.e. 11.7%. Conclusions: Automatically generated 3D patient models can be introduced in the clinic for H and N HTP

  13. A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts

    Directory of Open Access Journals (Sweden)

    Max Nobis

    2017-10-01

    Full Text Available The small GTPase RhoA is involved in a variety of fundamental processes in normal tissue. Spatiotemporal control of RhoA is thought to govern mechanosensing, growth, and motility of cells, while its deregulation is associated with disease development. Here, we describe the generation of a RhoA-fluorescence resonance energy transfer (FRET biosensor mouse and its utility for monitoring real-time activity of RhoA in a variety of native tissues in vivo. We assess changes in RhoA activity during mechanosensing of osteocytes within the bone and during neutrophil migration. We also demonstrate spatiotemporal order of RhoA activity within crypt cells of the small intestine and during different stages of mammary gestation. Subsequently, we reveal co-option of RhoA activity in both invasive breast and pancreatic cancers, and we assess drug targeting in these disease settings, illustrating the potential for utilizing this mouse to study RhoA activity in vivo in real time.

  14. Obtaining Normal Tissue Constraints Using Intensity Modulated Radiotherapy (IMRT) in Patients with Oral Cavity, Oropharnygeal, and Laryngeal Carcinoma

    International Nuclear Information System (INIS)

    Skinner, William K.J.; Muse, Evan D.; Yaparpalvi, Ravindra; Guha, Chandan; Garg, Madhur K.; Kalnicki, Shalom

    2009-01-01

    The purpose of this study was to evaluate normal tissue dose constraints while maintaining planning target volume (PTV) prescription without reducing PTV margins. Sixteen patients with oral cavity carcinoma (group I), 27 patients with oropharyngeal carcinoma (group II), and 28 patients with laryngeal carcinoma (group III) were reviewed. Parotid constraints were a mean dose to either parotid < 26 Gy (PP1), 50% of either parotid < 30 Gy (PP2), or 20 cc of total parotid < 20 Gy (PP3). Treatment was intensity modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB). All patients met constraints for cord and brain stem. The mandibular constraints were met in 66%, 29%, and 57% of patients with oral, oropharyngeal, and laryngeal cancers, respectively. Mean dose of 26 Gy (PP1) was achieved in 44%, 41%, and 38% of oral, oropharyngeal, and laryngeal patients. PP2 (parotid constraint of 30 Gy to less than 50% of one parotid) was the easiest to achieve (group I, II, and III: 82%, 76%, and 78%, respectively). PP3 (20 cc of total parotid < 20 Gy) was difficult, and was achieved in 25%, 17%, and 35% of oral, oropharyngeal, and laryngeal patients, respectively. Mean parotid dose of 26 Gy was met 40% of the time. However, a combination of constraints allowed for sparing of the parotid based on different criteria and was met in high numbers. This was accomplished without reducing PTV-parotid overlap. What dose constraint best correlates with subjective and objective functional outcomes remains a focus for future study.

  15. Dose reduction to normal tissues as compared to the gross tumor by using intensity modulated radiotherapy in thoracic malignancies

    Directory of Open Access Journals (Sweden)

    Bhalla NK

    2006-08-01

    Full Text Available Abstract Background and purpose Intensity modulated radiotherapy (IMRT is a powerful tool, which might go a long way in reducing radiation doses to critical structures and thereby reduce long term morbidities. The purpose of this paper is to evaluate the impact of IMRT in reducing the dose to the critical normal tissues while maintaining the desired dose to the volume of interest for thoracic malignancies. Materials and methods During the period January 2002 to March 2004, 12 patients of various sites of malignancies in the thoracic region were treated using physical intensity modulator based IMRT. Plans of these patients treated with IMRT were analyzed using dose volume histograms. Results An average dose reduction of the mean values by 73% to the heart, 69% to the right lung and 74% to the left lung, with respect to the GTV could be achieved with IMRT. The 2 year disease free survival was 59% and 2 year overall survival was 59%. The average number of IMRT fields used was 6. Conclusion IMRT with inverse planning enabled us to achieve desired dose distribution, due to its ability to provide sharp dose gradients at the junction of tumor and the adjacent critical organs.

  16. Comparison of single, fractionated and hyperfractionated irradiation on the development of normal tissue damage in rat lung

    International Nuclear Information System (INIS)

    Giri, P.G.S.; Kimler, B.F.; Giri, U.P.; Cox, G.G.; Reddy, E.K.

    1985-01-01

    The effect of fractionated thoracic irradiation on the development of normal tissue damage in rats was compared to that produced by single doses. Animals received a single dose of 15 Gy, 30 Gy in 10 daily fractions of 3 Gy each (fractionation), or 30 Gy in 30 fractions of 1 Gy each 3 times a day (hyperfractionation). The treatments produced minimal lethality since a total of only 6 animals died between days 273 and 475 after the initiation of treatment, with no difference in survival observed between the control and any of the 3 treated groups. Despite the lack of lethality, evidence of lung damage was obtained by histological examination. Animals that had received either single doses or fractionated doses had more of the pulmonary parenchyma involved than did animals that had received hyperfractionated doses. The authors conclude that, in the rat lung model, a total radiation dose of 30 Gy fractionated over 14 days produces no more lethality nor damage to lung tissue than does 15 Gy delivered as a single dose. However, long-term effects as evidenced by deposits of collagen and development of fibrosis are significantly reduced by hyperfractionation when compared to single doses and daily fractionation

  17. Differential action on cancer and normal tissue by adrenochrome monoaminoguanidine methanesulfonate and cytochrome C combined with radiotherapy

    International Nuclear Information System (INIS)

    Nakatsugawa, S.; Sugahara, T.

    1994-01-01

    The possibility that radioprotective effects on potent natural killer (NK) cells by adrenochrome monoaminoguanidine methanesulfonate (AMM) + cytochrome C during radiotherapy (RT) for lung cancer might result in the radiosensitization of human lung cancer cells in vivo is examined. Human lung cancer xenografts in the right hind legs of KSN mice (10 weeks old) were locally irradiated with 20 Gy of X ray. AMM (10 mg/kg/day) and/or cytochrome C (CCC) (5 mg/kg/day) were given intraperitoneally immediately before or after RT, followed by daily administration for 4 days. Natural killer activities of host splenocytes were also tested with the standard 51 Cr releasing assay with YAC-1 cells as target cells. In a clinical study, 65 patients with lung cancer were treated with more than 50 Gy of RT with or without combination with AMM + CCC, OK-432 or AMM + CCC + OK-432. Before and after RT, lymphocyte subsets in the peripheral blood were examined with dichromatic analysis using an Ortho Spectrum IIIFCM system and fluorescent MABs. In this study, the change in the absolute number of each subset was investigated. AMM + cytochrome C augumented NK activity in KSN nude mice, protected potent NK cells in patients with lung cancer against RT and sensitized the human lung cancer xenografts to RT. AMM + cytochrome C may have potential as a differential modulator of radiosensitivity of normal tissues and of tumors. 8 refs., 2 figs., 1 tab

  18. Quantitative radiation dose-response relationships for normal tissues in man - I. Gustatory tissues response during photon and neutron radiotherapy

    International Nuclear Information System (INIS)

    Mossman, K.L.

    1982-01-01

    Quantitative radiation dose-response curves for normal gustatory tissue in man were studied. Taste function, expressed as taste loss, was evaluated in 84 patients who were given either photon or neutron radiotherapy for tumors in the head and neck region. Patients were treated to average tumor doses of 6600 cGy (photon) or 2200 cGy intervals for photon patients and 320-cGy intervals for neutron patients during radiotherapy. The dose-response curves for photons and neutrons were analyzed by fitting a four-parameter logistic equation to the data. Photon and neutron curves differed principally in their relative position along the dose axis. Comparison of the dose-response curves were made by determination of RBE. At 320 cGy, the lowest neutron dose at which taste measurements were made, RBE = 5.7. If this RBE is correct, then the therapeutic gain factor may be equal to or less than 1, indicating no biological advantage in using neutrons over photons for this normal tissue. These studies suggest measurements of taste function and evaluation of dose-response relationships may also be useful in quantitatively evaluating the efficacy of chemical modifiers of radiation response such as hypoxic cell radiosensitizers and radioprotectors

  19. Weighing the Low-Redshift Lyman-alpha Forest

    Science.gov (United States)

    Shull, Mike

    2005-01-01

    In 2003-2004, our FUSE research group prepared several major surveys of the amount of baryonic matter in the intergalactic medium (IGM), using the Far Ultraviolet Spectroscopic Explorer (FUSE) satellite. These surveys include measurements of the Lyman-alpha absorption line of neutral hydrogen (H I), the far-ultraviolet (1032,1038 Angstrom) doublet of highly ionized oxygen ( O VI), the higher Lyman-series lines (Ly-beta, Ly-gamma, etc) of H I, and the 977 Angstrom line of c III. As an overview, our FUSE spectroscopic studies, taken together with data from the Hubble Space Telescope, show that approximately 30% of the normal matter is contained in intergalactic hydrogen gas clouds (the Lyman-alpha forest). Another 5-10% resides in hotter gas at temperatures of 10(exp 5) to 10(exp 6) K, visible in 0 VI and C III absorption. Along with the matter attributed to galaxies, we have now accounted for approximately HALF of all the baryonic matter in the universe. Where is the other half? That matter my exist in even hotter gas, invisible through the ultraviolet absorption lines, but perhaps detectable through X-ray absorption lines of more highly ionized oxygen and neon.

  20. Chromospheric Lyman-alpha spectro-polarimeter (CLASP)

    Science.gov (United States)

    Kano, Ryouhei; Bando, Takamasa; Narukage, Noriyuki; Ishikawa, Ryoko; Tsuneta, Saku; Katsukawa, Yukio; Kubo, Masahito; Ishikawa, Shin-nosuke; Hara, Hirohisa; Shimizu, Toshifumi; Suematsu, Yoshinori; Ichimoto, Kiyoshi; Sakao, Taro; Goto, Motoshi; Kato, Yoshiaki; Imada, Shinsuke; Kobayashi, Ken; Holloway, Todd; Winebarger, Amy; Cirtain, Jonathan; De Pontieu, Bart; Casini, Roberto; Trujillo Bueno, Javier; Štepán, Jiří; Manso Sainz, Rafael; Belluzzi, Luca; Asensio Ramos, Andres; Auchère, Frédéric; Carlsson, Mats

    2012-09-01

    One of the biggest challenges in heliophysics is to decipher the magnetic structure of the solar chromosphere. The importance of measuring the chromospheric magnetic field is due to both the key role the chromosphere plays in energizing and structuring the outer solar atmosphere and the inability of extrapolation of photospheric fields to adequately describe this key boundary region. Over the last few years, significant progress has been made in the spectral line formation of UV lines as well as the MHD modeling of the solar atmosphere. It is found that the Hanle effect in the Lyman-alpha line (121.567 nm) is a most promising diagnostic tool for weaker magnetic fields in the chromosphere and transition region. Based on this groundbreaking research, we propose the Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP) to NASA as a sounding rocket experiment, for making the first measurement of the linear polarization produced by scattering processes and the Hanle effect in the Lyman-alpha line (121.567 nm), and making the first exploration of the magnetic field in the upper chromosphere and transition region of the Sun. The CLASP instrument consists of a Cassegrain telescope, a rotating 1/2-wave plate, a dual-beam spectrograph assembly with a grating working as a beam splitter, and an identical pair of reflective polarization analyzers each equipped with a CCD camera. We propose to launch CLASP in December 2014.

  1. SU-F-J-45: Sparing Normal Tissue with Ultra-High Dose Rate in Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Y [DCH Reg. Medical Center, Tuscaloosa, AL (United States)

    2016-06-15

    Purpose: To spare normal tissue by reducing the location uncertainty of a moving target, we proposed an ultra-high dose rate system and evaluated. Methods: High energy electrons generated with a linear accelerator were injected into a storage ring to be accumulated. The number of the electrons in the ring was determined based on the prescribed radiation dose. The dose was delivered within a millisecond, when an online imaging system found that the target was in the position that was consistent with that in a treatment plan. In such a short time period, the displacement of the target was negligible. The margin added to the clinical target volume (CTV) could be reduced that was evaluated by comparing of volumes between CTV and ITV in 14 cases of lung stereotactic body radiation therapy (SBRT) treatments. A design of the ultra-high dose rate system was evaluated based clinical needs and the recent developments of low energy (a few MeV) electron storage ring. Results: This design of ultra-high dose rate system was feasible based on the techniques currently available. The reduction of a target volume was significant by reducing the margin that accounted the motion of the target. ∼50% volume reduction of the internal target volume (ITV) could be achieved in lung SBRT treatments. Conclusion: With this innovation of ultra-high dose rate system, the margin of target is able to be significantly reduced. It will reduce treatment time of gating and allow precisely specified gating window to improve the accuracy of dose delivering.

  2. Normal tissue sparing in a phase II trial on daily adaptive plan selection in radiotherapy for urinary bladder cancer.

    Science.gov (United States)

    Vestergaard, Anne; Muren, Ludvig P; Lindberg, Henriette; Jakobsen, Kirsten L; Petersen, Jørgen B B; Elstrøm, Ulrik V; Agerbæk, Mads; Høyer, Morten

    2014-08-01

    Background: Patients with urinary bladder cancer often display large changes in the shape and size of their bladder target during a course of radiotherapy (RT), making adaptive RT (ART) appealing for this tumour site. We are conducting a clinical phase II trial of daily plan selection-based ART for bladder cancer and here report dose-volume data from the first 20 patients treated in the trial. All patients received 60 Gy in 30 fractions to the bladder; in 13 of the patients the pelvic lymph nodes were simultaneously treated to 48 Gy. Daily patient set-up was by use of cone beam computed tomography (CBCT) guidance. The first 5 fractions were delivered with large, population-based (non-adaptive) margins. The bladder contours from the CBCTs acquired in the first 4 fractions were used to create a patient-specific library of three plans, corresponding to a small, medium and large size bladder. From fraction 6, daily online plan selection was performed, where the smallest plan covering the bladder was selected prior to each treatment delivery. A total of 600 treatment fractions in the 20 patients were evaluated. Small, medium and large size plans were used almost equally often, with an average of 10, 9 and 11 fractions, respectively. The median volume ratio of the course-averaged PTV (PTV-ART) relative to the non-adaptive PTV was 0.70 (range: 0.46-0.89). A linear regression analysis showed a 183 cm(3) (CI 143-223 cm(3)) reduction in PTV-ART compared to the non-adaptive PTV (R(2) = 0.94). Daily adaptive plan selection in RT of bladder cancer results in a considerable normal tissue sparing, of a magnitude that we expect will translate into a clinically significant reduction of the treatment-related morbidity.

  3. The effects of simultaneous application of ultrasound and ionizing radiation on cultured mammalian cells and normal tissues

    International Nuclear Information System (INIS)

    Fujita, Shozo

    1976-01-01

    The influence of therapeutic ultrasound on ionizing radiation effects was studied. Cultured mammalian cells, FM3A, and normal tissues, auricle and kidney of rabbits, were irradiated with ionizing radiation alone, ultrasound alone and both simultaneously. The biological experiments were conducted on the basis of the investigations about the physical and the chemical aspects of ultrasound. The results obtained from such a systematic study were as follows. It was considered that so called ''cavitation'' with bubble formation played an important role on the chemical effects of ultrasound. The chemical effect showed an intensity threshold in the range from 0.5 to 1 W/cm 2 . In the biological studies of ultrasound, the following must be considered; (1) the inhomogeneity of ultrasound intensity on the same plane (2) the distance between ultrasound transducer and sample. At a distance of 3 cm, the radiosensitizing effect due to simultaneous irradiation of x-rays and ultrasound on cells in suspension was detected at intensities above 2 W/cm 2 . The KI starch system in solution also showed a similar tendency. The irreversible tissue destruction was observed in the auricle irradiated with 690 R of 60 Co gamma-rays with simultaneous ultrasound at an intensity of 3 W/cm 2 for 15 minutes. However, no irreversible damage was recognized in the separate treatments with a dose four times of the combined irradiation. The interstitial nephritis was found in the kidney irradiated with 200 R of gamma-rays with simultaneous ultrasound for 5 minutes. No histological change was detectable in the separate treatments with a dose three times of the combined irradiation. The results seem to indicate that the ionizing radiation effects are enhanced by therapeutic ultrasound. (auth.)

  4. Role of endothelium in radiation-induced normal tissue damages; Role de l'endothelium dans les dommages radio-induits aux tissus sains

    Energy Technology Data Exchange (ETDEWEB)

    Milliat, F

    2007-05-15

    More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

  5. A preclinical study on the rescue of normal tissue by nicotinic acid in high-dose treatment with APO866, a specific nicotinamide phosphoribosyltransferase inhibitor

    DEFF Research Database (Denmark)

    Olesen, Uffe Høgh; Thougaard, Annemette V; Jensen, Peter Buhl

    2010-01-01

    Inhibitor of nicotinamide phosphoribosyltransferase APO866 is a promising cancer drug currently in phase II clinical trials in oncology. Here, we present a strategy for increasing the therapeutic potential of APO866 through the rescue of normal tissues by coadministration of nicotinic acid (Vitam...

  6. Role of endothelium in radiation-induced normal tissue damages; Role de l'endothelium dans les dommages radio-induits aux tissus sains

    Energy Technology Data Exchange (ETDEWEB)

    Milliat, F

    2007-05-15

    More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

  7. Normal tissue tolerance to external beam radiation therapy: Cardiac structures; Dose de tolerance des tissus sains: le coeur

    Energy Technology Data Exchange (ETDEWEB)

    Doyen, J. [Service d' oncologie-radiotherapie, centre Antoine-Lacassagne, 06 - Nice (France); Giraud, P. [Universite Rene-Descartes Paris 5, 75 - Paris (France); Service d' oncologie-radiotherapie, hopital europeen Georges-Pompidou, 75 - Paris (France); Belkacemi, Y. [Faculte de medecine de Creteil, universite Paris 12, 94 - Creteil (France); Service d' oncologie-radiotherapie, CHU Henri-Mondor, 94 - Creteil (France)

    2010-07-15

    Radiation thoracic tumors may be associated with cardiac toxicity because of the central position of the heart in the thorax. The present review aims to describe the cardiotoxicity during radiotherapy of different tumor sites most associated with this complication and the risk factors of cardiotoxicity during radiation therapy. Medline literature searches were performed using the following cardiac - heart - radiotherapy - toxicity - cardiotoxicity - breast cancer - lymphoma. Cardiac toxicity after breast cancer and mediastinal lymphoma is the most reported radiation-induced complication. The most frequent clinical complications are pericarditis, congestive heart failure, and heart infarction. These events are mostly asymptomatic. Thus clinicians have to give particular attention to these complications. Anthracycline treatment is a major risk factor for additional cardiotoxicity during radiotherapy with a synergistic effect. Correction of cardiovascular risk is an important point of the prevention of heart complications. Total dose delivered to the planned target volume (PTV), the dose per fraction and the irradiated volume were correlated to the risk of cardiotoxicity. Volume of heart receiving 35 Gy must be inferior to 30% and dose per fraction should not exceed 2 Gy when dose of prescription exceeds 30 Gy. Maximum heart distance (maximal thickness of heart irradiated) must be less than 1 cm during irradiation of breast cancer. Modern irradiation techniques seem to be associated with a limited risk of heart complication. The use of anthracycline, other cardio-toxic chemotherapies and targeted therapies should incite for great caution by performing a careful treatment planning and optimisation. (authors)

  8. Calculation of the uncertainty in complication probability for various dose-response models, applied to the parotid gland

    International Nuclear Information System (INIS)

    Schilstra, C.; Meertens, H.

    2001-01-01

    Purpose: Usually, models that predict normal tissue complication probability (NTCP) are fitted to clinical data with the maximum likelihood (ML) method. This method inevitably causes a loss of information contained in the data. In this study, an alternative method is investigated that calculates the parameter probability distribution (PD), and, thus, conserves all information. The PD method also allows the calculation of the uncertainty in the NTCP, which is an (often-neglected) prerequisite for the intercomparison of both treatment plans and NTCP models. The PD and ML methods are applied to parotid gland data, and the results are compared. Methods and Materials: The drop in salivary flow due to radiotherapy was measured in 25 parotid glands of 15 patients. Together with the parotid gland dose-volume histograms (DVH), this enabled the calculation of the parameter PDs for three different NTCP models (Lyman, relative seriality, and critical volume). From these PDs, the NTCP and its uncertainty could be calculated for arbitrary parotid gland DVHs. ML parameters and resulting NTCP values were calculated also. Results: All models fitted equally well. The parameter PDs turned out to have nonnormal shapes and long tails. The NTCP predictions of the ML and PD method usually differed considerably, depending on the NTCP model and the nature of irradiation. NTCP curves and ML parameters suggested a highly parallel organization of the parotid gland. Conclusions: Considering the substantial differences between the NTCP predictions of the ML and PD method, the use of the PD method is preferred, because this is the only method that takes all information contained in the clinical data into account. Furthermore, PD method gives a true measure of the uncertainty in the NTCP

  9. On Predicting lung cancer subtypes using ‘omic’ data from tumor and tumor-adjacent histologically-normal tissue

    International Nuclear Information System (INIS)

    Pineda, Arturo López; Ogoe, Henry Ato; Balasubramanian, Jeya Balaji; Rangel Escareño, Claudia; Visweswaran, Shyam; Herman, James Gordon; Gopalakrishnan, Vanathi

    2016-01-01

    Adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are the most prevalent histological types among lung cancers. Distinguishing between these subtypes is critically important because they have different implications for prognosis and treatment. Normally, histopathological analyses are used to distinguish between the two, where the tissue samples are collected based on small endoscopic samples or needle aspirations. However, the lack of cell architecture in these small tissue samples hampers the process of distinguishing between the two subtypes. Molecular profiling can also be used to discriminate between the two lung cancer subtypes, on condition that the biopsy is composed of at least 50 % of tumor cells. However, for some cases, the tissue composition of a biopsy might be a mix of tumor and tumor-adjacent histologically normal tissue (TAHN). When this happens, a new biopsy is required, with associated cost, risks and discomfort to the patient. To avoid this problem, we hypothesize that a computational method can distinguish between lung cancer subtypes given tumor and TAHN tissue. Using publicly available datasets for gene expression and DNA methylation, we applied four classification tasks, depending on the possible combinations of tumor and TAHN tissue. First, we used a feature selector (ReliefF/Limma) to select relevant variables, which were then used to build a simple naïve Bayes classification model. Then, we evaluated the classification performance of our models by measuring the area under the receiver operating characteristic curve (AUC). Finally, we analyzed the relevance of the selected genes using hierarchical clustering and IPA® software for gene functional analysis. All Bayesian models achieved high classification performance (AUC > 0.94), which were confirmed by hierarchical cluster analysis. From the genes selected, 25 (93 %) were found to be related to cancer (19 were associated with ADC or SCC), confirming the biological relevance of our

  10. Radiation-induced damage to normal tissues after radiotherapy in patients treated for gynecologic tumors: Association with single nucleotide polymorphisms in XRCC1, XRCC3, and OGG1 genes and in vitro chromosomal radiosensitivity in lymphocytes

    International Nuclear Information System (INIS)

    Ruyck, Kim de; Eijkeren, Marc van; Claes, Kathleen; Morthier, Rudy; Paepe, Anne de; Vral, Anne; Ridder, Leo de; Thierens, Hubert

    2005-01-01

    Purpose: To examine the association of polymorphisms in XRCC1 (194Arg/Trp, 280Arg/His, 399Arg/Gln, 632Gln/Gln), XRCC3 (5' UTR 4.541A>G, IVS5-14 17.893A>G, 241Thr/Met), and OGG1 (326Ser/Cys) with the development of late radiotherapy (RT) reactions and to assess the correlation between in vitro chromosomal radiosensitivity and clinical radiosensitivity. Methods and Materials: Sixty-two women with cervical or endometrial cancer treated with RT were included in the study. According to the Common Terminology Criteria for Adverse Events, version 3.0, scale, 22 patients showed late adverse RT reactions. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays were performed to examine polymorphic sites, the G2 assay was used to measure chromosomal radiosensitivity, and patient groups were compared using actuarial methods. Results: The XRCC3 IVS5-14 polymorphic allele was significantly associated with the risk of developing late RT reactions (odds ratio 3.98, p = 0.025), and the XRCC1 codon 194 variant showed a significant protective effect (p = 0.028). Patients with three or more risk alleles in XRCC1 and XRCC3 had a significantly increased risk of developing normal tissue reactions (odds ratio 10.10, p = 0.001). The mean number of chromatid breaks per cell was significantly greater in patients with normal tissue reactions than in patients with no reactions (1.16 and 1.34, respectively; p = 0.002). Patients with high chromosomal radiosensitivity showed a 9.2-fold greater annual risk of complications than patients with intermediate chromosomal radiosensitivity. Combining the G2 analysis with the risk allele model allowed us to identify 23% of the patients with late normal tissue reactions, without false-positive results. Conclusion: The results of the present study showed that clinical radiosensitivity is associated with an enhanced G2 chromosomal radiosensitivity and is significantly associated with a combination of different polymorphisms in

  11. Hyperbaric oxygen therapy in the treatment of radio-induced lesions in normal tissues: a literature review

    International Nuclear Information System (INIS)

    Pasquier, David; Hoelscher, Tobias; Schmutz, Jorg; Dische, Stanley; Mathieu, Daniel; Baumann, Michael; Lartigau, Eric

    2004-01-01

    Late complications are one of the major factors limiting radiotherapy treatment, and their treatment is not codified. Hyperbaric oxygen (HBO) has been used in combination with radiotherapy for over half a century, either to maximise its effectiveness or in an attempt to treat late complications. In this latter case, retrospective trials and case reports are prevailing in literature. This prompted European Society for Therapeutic Radiotherapy and Oncology and European Committee for Hyperbaric Medicine to organise a consensus conference in October 2001, dealing with the HBO indications on radiotherapy for the treatment and prevention of late complications. This updated literature review is part of the documents the jury based its opinion on. A systematic search was done on literature from 1960 to 2004, by only taking into account the articles that appeared in peer review journals. Hyperbaric oxygen treatment involving complications to the head and neck, pelvis and nervous system, and the prevention of complications after surgery in irradiated tissues have been studied. Despite the small number of controlled trials, it may be indicated for the treatment of mandibular osteoradionecrosis in combination with surgery, haemorrhagic cystitis resistant to conventional treatments and the prevention of osteoradionecrosis after dental extraction, whose level of evidence seems to be the most significant though randomised trials are still necessary. The other treatment methods are also outlined for each location

  12. Nuclear medicine in the detection of radiation associated normal tissue damage of kidney, brain and salivary glands

    International Nuclear Information System (INIS)

    Liu Xiaomei; Li Dongxue; Pan Liping

    2005-01-01

    The radiation induced damage of kidney, brain and salivary glands is an important complicating disease after limit radiotherapy. The routine technology of nuclear medicine, such as tracing and imaging technique conduce to dose-effect calculations used in the planning of modern radiotherapy to three major organ systems and early detection of irradiation induced organ dysfunctions, as well as increased availability of radiotherapy. (authors)

  13. The z~4 Lyman Break Galaxies: Colors and Theoretical Predictions

    Science.gov (United States)

    Idzi, Rafal; Somerville, Rachel; Papovich, Casey; Ferguson, Henry C.; Giavalisco, Mauro; Kretchmer, Claudia; Lotz, Jennifer

    2004-01-01

    We investigate several fundamental properties of z~4 Lyman break galaxies by comparing observations with the predictions of a semianalytic model based on the cold dark matter theory of hierarchical structure formation. We use a sample of B435-dropouts from the Great Observatories Origins Deep Survey and complement the Advanced Camera for Surveys optical B435, V606, i775, and z850 data with the Very Large Telescope Infrared Spectrometer and Array Camera J, H, and Ks observations. We extract B435-dropouts from our semianalytic mock catalog using the same color criteria and magnitude limits that were applied to the observed sample. We find that the i775-Ks colors of the model-derived and observed B435-dropouts are in good agreement. However, we find that the i775-z850 colors differ significantly, indicating perhaps that either too little dust or an incorrect extinction curve has been used. Motivated by the reasonably good agreement between the model and observed data, we present predictions for the stellar masses, star formation rates, and ages for the z~4 Lyman break sample. We find that according to our model, the color selection criteria used to select our z~4 sample surveys 67% of all galaxies at this epoch down to z850Universities for Research in Astronomy (AURA), Inc., under NASA contract NAS5-26555. Based on observations collected at the European Southern Observatory, Chile (ESO programmes 168.A-0485, 64.0-0643, 66.A-0572, and 68.A-0544).

  14. Normal tissue adverse side effects in radiotherapy cancer patients and applicability of predictive radiosensitivity tests for new radiation treatment decision

    International Nuclear Information System (INIS)

    Di Giorgio, Marina; Vallerga, Maria B.; Radl, Analia; Sardi, Mabel

    2008-01-01

    Full text: Around 5 % -7 % of cancer patients develop adverse side effects, which include acute effects, late effects and cancer induction to radiation therapy in normal tissues in the treatment field. Such effects are of particular interest as the cancer patient population that reaches prolonged survival has increased with the improvements in cancer therapy and health care. These adverse reactions are mainly influenced by deficiencies in DNA repair pathways. However, tissue response to IR could be modified by several treatment- and patient- related factors. Numerous studies have been carried out to evaluate the correlation between clinical and cellular radiosensitivity, by in vitro tests. Previous own studies, characterizing DNA repair capacity in peripheral lymphocytes of cancer patients through cytokinesis blocked micronucleus test and alkaline single-cell microgel electrophoresis (comet), indicated that such assays correlated with the clinical radiation signs of radiosensitivity and showed the predictive potential of both techniques in the identification of radiosensitivity subgroups. In this paper, retrospective studies are conducted in 10 representative cases, which had developed acute or late toxicity in previous treatments and at present require new radiation treatments due to secondary malignancies or recurrence. Samples were in vitro irradiated with 2 Gy. MN data were analyzed comparing expected MN frequencies with values observed after in vitro irradiation. DNA repair capacity was evaluated through comet assay for initial damage and after specific times of repair (0-120 minutes). Captured images were analyzed by CASP image analysis software. Repair capacity was quantified by the Olive tail moment. Weibull alpha parameter was applied to describe DNA damage at the different evaluated repair times after in vitro irradiation and fitted by a mono-exponential model to describe the kinetic profile. In every evaluated patient a correlation between mean half

  15. Normal tissue adverse side effects in radiotherapy cancer patients and applicability of predictive radiosensitivity tests for new radiation treatment decision

    International Nuclear Information System (INIS)

    Di Giorgio, M.; Vallerga, M.B.; Radl, A.; Sardi, M.

    2011-01-01

    Around 5%-7% of cancer patients develop adverse side effects, which include acute effects, late effects and cancer induction to radiation therapy in normal tissues in the treatment field. Such effects are of particular interest as the cancer patient population that reaches prolonged survival has increased with the improvements in cancer therapy and health care. These adverse reactions are mainly influenced by deficiencies in DNA repair pathways. However, tissue response to IR could be modified by several treatment- and patient- related factors. Numerous studies have been carried out to evaluate the correlation between clinical and cellular radiosensitivity, by in vitro tests. Previous own studies, characterizing DNA repair capacity in peripheral lymphocytes of cancer patients through cytokinesis blocked micronucleus test and alkaline single-cell microgel electrophoresis (comet), indicated that such assays correlated with the clinical radiation signs of radiosensitivity and showed the predictive potential of both techniques in the identification of radiosensitivity subgroups. In this paper, retrospective studies are conducted in 10 representative cases, which had developed acute or late toxicity in previous treatments and at present require new radiation treatments due to secondary malignancies or recurrence. Samples were in vitro irradiated with 2 Gy. MN data were analyzed comparing expected MN frequencies with values observed after in vitro irradiation. DNA repair capacity was evaluated through comet assay for initial damage and after specific times of repair (0-120 minutes). Captured images were analyzed by CASP image analysis software. Repair capacity was quantified by the Olive tail moment. Weibull alpha parameter was applied to describe DNA damage at the different evaluated repair times after in vitro irradiation and fitted by a mono-exponential model to describe the kinetic profile. In every evaluated patient a correlation between mean half-time (T1/2) and

  16. Comparison of the predictions of the LQ and CRE models for normal tissue damage due to biologically targeted radiotherapy with exponentially decaying dose rates

    International Nuclear Information System (INIS)

    O'Donoghue, J.A.; West of Schotland Health Boards, Glasgow

    1989-01-01

    For biologically targeted radiotherapy organ dose rates may be complex functions of time, related to the biodistribution kinetics of the delivery vehicle and radiolabel. The simples situation is where dose rates are exponentially decaying functions of time. Two normal tissue isoeffect models enable the effects of exponentially decaying dose rates to be addressed. These are the extension of the linear-quadratic model and the cumulative radiation effect model. This communication will compare the predictions of these models. (author). 14 refs.; 1 fig

  17. Suberoylanilide hydroxamic acid affects γH2AX expression in osteosarcoma, atypical teratoid rhabdoid tumor and normal tissue cell lines after irradiation

    International Nuclear Information System (INIS)

    Blattmann, C.; Oertel, S.; Thiemann, M.; Weber, K.J.; Schmezer, P.; Zelezny, O.; Lopez Perez, R.; Kulozik, A.E.; Debus, J.; Ehemann, V.

    2012-01-01

    Osteosarcoma and atypical teratoid rhabdoid tumors are tumor entities with varying response to common standard therapy protocols. Histone acetylation affects chromatin structure and gene expression which are considered to influence radiation sensitivity. The aim of this study was to investigate the effect of the combination therapy with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and irradiation on atypical teratoid rhabdoid tumors and osteosarcoma compared to normal tissue cell lines. Clonogenic assay was used to determine cell survival. DNA double-strand breaks (DSB) were examined by pulsed-field electrophoresis (PFGE) as well as by γH2AX immunostaining involving flow cytometry, fluorescence microscopy, and immunoblot analysis. SAHA lead to an increased radiosensitivity in tumor but not in normal tissue cell lines. γH2AX expression as an indicator for DSB was significantly increased when SAHA was applied 24 h before irradiation to the sarcoma cell cultures. In contrast, γH2AX expression in the normal tissue cell lines was significantly reduced when irradiation was combined with SAHA. Analysis of initial DNA fragmentation and fragment rejoining by PFGE, however, did not reveal differences in response to the SAHA pretreatment for either cell type. SAHA increases radiosensitivity in tumor but not normal tissue cell lines. The increased H2AX phosphorylation status of the SAHA-treated tumor cells post irradiation likely reflects its delayed dephosphorylation within the DNA damage signal decay rather than chromatin acetylation-dependent differences in the overall efficacy of DSB induction and rejoining. The results support the hypothesis that combining SAHA with irradiation may provide a promising strategy in the treatment of solid tumors. (orig.)

  18. DNA double-strand break repair of blood lymphocytes and normal tissues analysed in a preclinical mouse model: implications for radiosensitivity testing.

    Science.gov (United States)

    Rübe, Claudia E; Grudzenski, Saskia; Kühne, Martin; Dong, Xiaorong; Rief, Nicole; Löbrich, Markus; Rübe, Christian

    2008-10-15

    Radiotherapy is an effective cancer treatment, but a few patients suffer severe radiation toxicities in neighboring normal tissues. There is increasing evidence that the variable susceptibility to radiation toxicities is caused by the individual genetic predisposition, by subtle mutations, or polymorphisms in genes involved in cellular responses to ionizing radiation. Double-strand breaks (DSB) are the most deleterious form of radiation-induced DNA damage, and DSB repair deficiencies lead to pronounced radiosensitivity. Using a preclinical mouse model, the highly sensitive gammaH2AX-foci approach was tested to verify even subtle, genetically determined DSB repair deficiencies known to be associated with increased normal tissue radiosensitivity. By enumerating gammaH2AX-foci in blood lymphocytes and normal tissues (brain, lung, heart, and intestine), the induction and repair of DSBs after irradiation with therapeutic doses (0.1-2 Gy) was investigated in repair-proficient and repair-deficient mouse strains in vivo and blood samples irradiated ex vivo. gammaH2AX-foci analysis allowed to verify the different DSB repair deficiencies; even slight impairments caused by single polymorphisms were detected similarly in both blood lymphocytes and solid tissues, indicating that DSB repair measured in lymphocytes is valid for different and complex organs. Moreover, gammaH2AX-foci analysis of blood samples irradiated ex vivo was found to reflect repair kinetics measured in vivo and, thus, give reliable information about the individual DSB repair capacity. gammaH2AX analysis of blood and tissue samples allows to detect even minor genetically defined DSB repair deficiencies, affecting normal tissue radiosensitivity. Future studies will have to evaluate the clinical potential to identify patients more susceptible to radiation toxicities before radiotherapy.

  19. A Comparative Evaluation of Normal Tissue Doses for Patients Receiving Radiation Therapy for Hodgkin Lymphoma on the Childhood Cancer Survivor Study and Recent Children's Oncology Group Trials

    International Nuclear Information System (INIS)

    Zhou, Rachel; Ng, Angela; Constine, Louis S.; Stovall, Marilyn; Armstrong, Gregory T.; Neglia, Joseph P.; Friedman, Debra L.; Kelly, Kara; FitzGerald, Thomas J.; Hodgson, David C.

    2016-01-01

    Purpose: Survivors of pediatric Hodgkin lymphoma (HL) are recognized to have an increased risk of delayed adverse health outcomes related to radiation therapy (RT). However, the necessary latency required to observe these late effects means that the estimated risks apply to outdated treatments. We sought to compare the normal tissue dose received by children treated for HL and enrolled in the Childhood Cancer Survivor Study (CCSS) (diagnosed 1970-1986) with that of patients treated in recent Children's Oncology Group (COG) trials (enrolled 2002-2012). Methods and Materials: RT planning data were obtained for 50 HL survivors randomly sampled from the CCSS cohort and applied to computed tomography planning data sets to reconstruct the normal tissue dosimetry. For comparison, the normal tissue dosimetry data were obtained for all 191 patients with full computed tomography–based volumetric RT planning on COG protocols AHOD0031 and AHOD0831. Results: For early-stage patients, the mean female breast dose in the COG patients was on average 83.5% lower than that for CCSS patients, with an absolute reduction of 15.5 Gy. For advanced-stage patients, the mean breast dose was decreased on average by 70% (11.6 Gy average absolute dose reduction). The mean heart dose decreased on average by 22.9 Gy (68.6%) and 17.6 Gy (56.8%) for early- and advanced-stage patients, respectively. All dose comparisons for breast, heart, lung, and thyroid were significantly lower for patients in the COG trials than for the CCSS participants. Reductions in the prescribed dose were a major contributor to these dose reductions. Conclusions: These are the first data quantifying the significant reduction in the normal tissue dose using actual, rather than hypothetical, treatment plans for children with HL. These findings provide useful information when counseling families regarding the risks of contemporary RT.

  20. Lyman series profiles: From laser-plasmas to white dwarf stars

    Energy Technology Data Exchange (ETDEWEB)

    Kielkopf, J.F. [University of Louisville, Louisville, Kentucky 40292 (United States); Allard, N.F. [Observatoire de Paris-Meudon, France and Institut d Astrophysique, Paris (France)

    1999-04-01

    The low energy interactions of neutral and ionized hydrogen atoms are fundamental processes which also have important applications to the diagnostics of laboratory and astrophysical plasmas. Satellites in the far wings of Lyman {alpha} and Lyman {beta} have been identified as ultraviolet absorption features in the spectra of white dwarf and {lambda} Bootis stars, and they are seen in the emission spectra of plasmas produced when a pulsed laser excites a target H{sub 2} gas. The observed Lyman series profiles agree with unified line shape theory which includes variation of the dipole transition moment during the radiative collision. {copyright} {ital 1999 American Institute of Physics.}

  1. Quantitative analysis of normal tissue effects in the clinic (QUANTEC) guideline validation using quality of life questionnaire datasets for parotid gland constraints to avoid causing xerostomia during head-and-neck radiotherapy

    International Nuclear Information System (INIS)

    Lee, Tsair-Fwu; Fang, Fu-Min

    2013-01-01

    Purpose: To perform a validation test of the quantitative analysis of normal tissue effects in the clinic (QUANTEC) guidelines against quality of life (QoL) questionnaire datasets collected prospectively from patients with head and neck (HN) cancers, including HN squamous cell carcinoma (HNSCC) and nasopharyngeal carcinoma (NPC). Methods and materials: QoL questionnaire datasets from 95 patients with NPC and 142 with HNSCC were analyzed separately. The European Organization for Research and Treatment of Cancer H and N35 QoL questionnaire was used as the endpoint evaluation. The primary endpoint (grade 3 + xerostomia) was defined as moderate to severe xerostomia 3 and 12 months after the completion of RT, and excluded patients with grade 3 + xerostomia at the baseline. The Lyman–Kutcher–Burman normal tissue complication probability (NTCP) model was used to describe the incidence of xerostomia. Negative predictive values (NPVs) were used to determine the rate of correctly predicting the lack of complications. Results: NTCP fitted parameters were TD 50 = 37.8 Gy (CI: 29.1–46.9 Gy), m = 0.59 (CI: 0.48–0.80) and TD 50 = 43.9 Gy (CI: 33.2–52.8 Gy), m = 0.48 (CI: 0.37–0.76) at the 3-month and 12-month time points, respectively. For QUANTEC validation, HN and HNSCC data validation gave similar results at 3 months; at mean doses to the spared parotid of ⩽20 and ⩽25 Gy, the QoL dataset showed approximately 22% and 28% rates of xerostomia, respectively. At 12 months, the rates of xerostomia were approximately 13% and 19%, respectively. For NPC cases, the dataset showed approximately 0% and 33% (∼67% NPV) rates of xerostomia at 3 months. At 12 months, both rates of xerostomia were approximately 0% (∼100% NPV), which differed significantly from the results for the HNSCC cohort. Conclusion: The QoL datasets validated the QUANTEC guidelines and suggested that the modified QUANTEC 20/20-Gy spared-gland guideline is suitable for clinical use in HNSCC cohorts to

  2. Long-term effects of an intracavitary treatment with californium-252 on normal tissue. [Swine, /sup 226/Ra

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan, M.F.; Beamer, J.L.; Mahony, T.D.; Cross, F.T.; Lund, J.E.; Endres, G.W.R.

    1976-01-01

    About one hundred fifty swine were exposed to either radium-226 or californium-252 sources in the uterine cervix to determine an RBE for both acute and long-term effects. That value for early changes in the tissues at risk in the treatment of cervical cancer was between 6.2 and 6.8. The incidence of complications increased with time after exposure, especially among animals treated with /sup 252/Cf. Analysis of rectal injury showed that ulceration occurred frequently within a year postexposure at doses between 1600 and 2400 rad calculated at 2 cm lateral to the source midline. Fat necrosis and smooth muscle atrophy, resulting in a local rectal stricture, were delayed changes observed in some animals. The lower ureter was the site for a greater frequency of complications than the GI tract. Ureteral stricture often occurred at doses of 1200 rad from /sup 252/Cf and 7000 rad from /sup 226/Ra. Observation of delayed effects in the uterine-cervix in animals held up to 4 years postexposure indicate that the RBE for /sup 252/Cf may be increased to a value as high as 18, while repair may have even decreased it to about 5.6 in the rectum. Fifty swine are still being observed for long-term effects after doses above 800 rad from /sup 252/Cf and 5000 rad from /sup 226/Ra.

  3. Diagnostics of the Solar Wind and Global Heliosphere with Lyman-α Emission Measurements

    Science.gov (United States)

    Provornikova, E. P.; Izmodenov, V. V.; Laming, J. M.; Strachan, L.; Wood, B. E.; Katushkina, O. A.; Ko, Y.-K.; Tun Beltran, S.; Chakrabarti, S.

    2018-02-01

    We propose to develop an instrument measuring full sky intensity maps and spectra of interplanetary Lyman-α emission to reveal the global solar wind variability and the nature of the heliosphere and the local interstellar medium.

  4. Normal tissue tolerance to external beam radiation therapy: Ovaries; Tolerance a l'irradiation des tissus sains: les ovaires

    Energy Technology Data Exchange (ETDEWEB)

    Gross, E.; Champetier, C.; Zaccariotto, A.; Duberge, T.; Guerder, C. [Departement de radiotherapie, hopital de la Timone, 13 - Marseille (France); Pointreau, Y. [Service Corad, pole Henry-S.-Kaplan, CHU Bretonneau, 37 - Tours (France); Ortholan, C. [Service de radiotherapie, centre Antoine-Lacassagne, 06 - Nice (France); Chauvet, B. [Institut Sainte-Catherine, 84 - Avignon (France)

    2010-07-15

    Clinical situations requiring protections of ovaries are mainly paediatric irradiations and pre-menopausal pelvic irradiations. The main complication of ovarian irradiation is the induced castration. Ovaries are extremely radiosensitive organs with strong interpersonal variations. The castrative effect of irradiation depends mainly on two factors: patient's age and the dose delivered to ovaries. The surgical technique of ovarian transposition allows to minimize the dose received by ovaries by taking them away, out of irradiation fields; the aim is to exclude them from the volume receiving 5 Gy or more, and if possible from those receiving 2 Gy. This technique becomes integrated into a multidisciplinary approach of conservation of fertility for patients exposed to other cytotoxic treatments. (authors)

  5. A reliable cw Lyman-α laser source for future cooling of antihydrogen

    International Nuclear Information System (INIS)

    Kolbe, Daniel; Beczkowiak, Anna; Diehl, Thomas; Koglbauer, Andreas; Sattler, Matthias; Stappel, Matthias; Steinborn, Ruth; Walz, Jochen

    2012-01-01

    We demonstrate a reliable continuous-wave (cw) laser source at the 1 S–2 P transition in (anti)hydrogen at 121.56 nm (Lyman-α) based on four-wave sum-frequency mixing in mercury. A two-photon resonance in the four-wave mixing scheme is essential for a powerful cw Lyman-α source and is well investigated.

  6. A reliable cw Lyman-{alpha} laser source for future cooling of antihydrogen

    Energy Technology Data Exchange (ETDEWEB)

    Kolbe, Daniel, E-mail: kolbed@uni-mainz.de; Beczkowiak, Anna; Diehl, Thomas; Koglbauer, Andreas; Sattler, Matthias; Stappel, Matthias; Steinborn, Ruth; Walz, Jochen [Johannes Gutenberg-Universitaet, Institut fuer Physik (Germany)

    2012-12-15

    We demonstrate a reliable continuous-wave (cw) laser source at the 1 S-2 P transition in (anti)hydrogen at 121.56 nm (Lyman-{alpha}) based on four-wave sum-frequency mixing in mercury. A two-photon resonance in the four-wave mixing scheme is essential for a powerful cw Lyman-{alpha} source and is well investigated.

  7. Discovery of a very Lyman-α-luminous quasar at z = 6.62.

    Science.gov (United States)

    Koptelova, Ekaterina; Hwang, Chorng-Yuan; Yu, Po-Chieh; Chen, Wen-Ping; Guo, Jhen-Kuei

    2017-02-02

    Distant luminous quasars provide important information on the growth of the first supermassive black holes, their host galaxies and the epoch of reionization. The identification of quasars is usually performed through detection of their Lyman-α line redshifted to 0.9 microns at z > 6.5. Here, we report the discovery of a very Lyman-α luminous quasar, PSO J006.1240 + 39.2219 at redshift z = 6.618, selected based on its red colour and multi-epoch detection of the Lyman-α emission in a single near-infrared band. The Lyman-α line luminosity of PSO J006.1240 + 39.2219 is unusually high and estimated to be 0.8 × 10 12 Solar luminosities (about 3% of the total quasar luminosity). The Lyman-α emission of PSO J006.1240 + 39.2219 shows fast variability on timescales of days in the quasar rest frame, which has never been detected in any of the known high-redshift quasars. The high luminosity of the Lyman-α line, its narrow width and fast variability resemble properties of local Narrow-Line Seyfert 1 galaxies which suggests that the quasar is likely at the active phase of the black hole growth accreting close or even beyond the Eddington limit.

  8. A Preliminary Study on Racial Differences in HMOX1, NFE2L2, and TGFβ1 Gene Polymorphisms and Radiation-Induced Late Normal Tissue Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Alam, Asim [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia (United States); Mukhopadhyay, Nitai D. [Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia (United States); Ning, Yi [Department of Family Medicine and Population Health, Virginia Commonwealth University, Richmond, Virginia (United States); Reshko, Leonid B.; Cardnell, Robert J.G.; Alam, Omair; Rabender, Christopher S.; Yakovlev, Vasily A.; Walker, Linda; Anscher, Mitchell S. [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia (United States); Mikkelsen, Ross B., E-mail: rmikkels@vcu.edu [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia (United States)

    2015-10-01

    Purpose: This study tested whether racial differences in genetic polymorphisms of 4 genes involved in wound repair and response to radiation can be used to predict the occurrence of normal tissue late effects of radiation therapy and indicate potential therapeutic targets. Methods and Materials: This prospective study examined genetic polymorphisms that modulate the expression of 4 genes involved in inflammation and fibrosis and response to radiation (HMOX1, NFE2L2, NOS3, and TGFβ1). DNA from blood samples of 179 patients (∼80% breast and head and neck) collected at the time of diagnosis by their radiation oncologist as exhibiting late normal tissue toxicity was used for the analysis. Patient demographics were as follows: 56% white, 43% African American, 1% other. Allelic frequencies of the different polymorphisms of the participants were compared with those of the general American population stratified by race. Twenty-six additional patients treated with radiation, but without toxicity at 3 months or later after therapy, were also analyzed. Results: Increased frequency of a long GT repeat in the HMOX1 promoter was associated with late effects in both African American and white populations. The single nucleotide polymorphisms (SNP) rs1800469 in the TGFβ1 promoter and the rs6721961 SNP in the NFE2L2 promoter were also found to significantly associate with late effects in African Americans but not whites. A combined analysis of these polymorphisms revealed that >90% of African American patients with late effects had at least 1 of these minor alleles, and 58% had 2 or more. No statistical significance was found relating the studied NOS3 polymorphisms and normal tissue toxicity. Conclusions: These results support a strong association between wound repair and late toxicities of radiation. The presence of these genetic risk factors can vary significantly among different ethnic groups, as demonstrated for some of the SNPs. Future studies should account for the

  9. A Preliminary Study on Racial Differences in HMOX1, NFE2L2, and TGFβ1 Gene Polymorphisms and Radiation-Induced Late Normal Tissue Toxicity

    International Nuclear Information System (INIS)

    Alam, Asim; Mukhopadhyay, Nitai D.; Ning, Yi; Reshko, Leonid B.; Cardnell, Robert J.G.; Alam, Omair; Rabender, Christopher S.; Yakovlev, Vasily A.; Walker, Linda; Anscher, Mitchell S.; Mikkelsen, Ross B.

    2015-01-01

    Purpose: This study tested whether racial differences in genetic polymorphisms of 4 genes involved in wound repair and response to radiation can be used to predict the occurrence of normal tissue late effects of radiation therapy and indicate potential therapeutic targets. Methods and Materials: This prospective study examined genetic polymorphisms that modulate the expression of 4 genes involved in inflammation and fibrosis and response to radiation (HMOX1, NFE2L2, NOS3, and TGFβ1). DNA from blood samples of 179 patients (∼80% breast and head and neck) collected at the time of diagnosis by their radiation oncologist as exhibiting late normal tissue toxicity was used for the analysis. Patient demographics were as follows: 56% white, 43% African American, 1% other. Allelic frequencies of the different polymorphisms of the participants were compared with those of the general American population stratified by race. Twenty-six additional patients treated with radiation, but without toxicity at 3 months or later after therapy, were also analyzed. Results: Increased frequency of a long GT repeat in the HMOX1 promoter was associated with late effects in both African American and white populations. The single nucleotide polymorphisms (SNP) rs1800469 in the TGFβ1 promoter and the rs6721961 SNP in the NFE2L2 promoter were also found to significantly associate with late effects in African Americans but not whites. A combined analysis of these polymorphisms revealed that >90% of African American patients with late effects had at least 1 of these minor alleles, and 58% had 2 or more. No statistical significance was found relating the studied NOS3 polymorphisms and normal tissue toxicity. Conclusions: These results support a strong association between wound repair and late toxicities of radiation. The presence of these genetic risk factors can vary significantly among different ethnic groups, as demonstrated for some of the SNPs. Future studies should account for the

  10. Association between Single Nucleotide Polymorphisms in XRCC3 and Radiation-Induced Adverse Effects on Normal Tissue: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Yu-Zhe Song

    Full Text Available The X-ray repair cross-complementing group 3 (XRCC3 protein plays an important role in the repair of DNA double-strand breaks. The relationship between XRCC3 polymorphisms and the risk of radiation-induced adverse effects on normal tissue remains inconclusive. Thus, we performed a meta-analysis to elucidate the association between XRCC3 polymorphisms and radiation-induced adverse effects on normal tissue. All eligible studies up to December 2014 were identified through a search of the PubMed, Embase and Web of Science databases. Seventeen studies involving 656 cases and 2193 controls were ultimately included in this meta-analysis. The pooled odds ratios (ORs with corresponding 95% confidence intervals (CIs were calculated to evaluate the association between XRCC3 polymorphisms and the risk of radiation-induced normal tissue adverse effects. We found that the XRCC3 p.Thr241Met (rs861539 polymorphism was significantly associated with early adverse effects induced by radiotherapy (OR = 1.99, 95%CI: 1.31-3.01, P = 0.001. A positive association lacking statistical significance with late adverse effects was also identified (OR = 1.28, 95%CI: 0.97-1.68, P = 0.08. In addition, the rs861539 polymorphism was significantly correlated with a higher risk of adverse effects induced by head and neck area irradiation (OR = 2.41, 95%CI: 1.49-3.89, p = 0.0003 and breast irradiation (OR = 1.41, 95%CI: 1.02-1.95, p = 0.04, whereas the correlation was not significant for lung irradiation or pelvic irradiation. Furthermore, XRCC3 rs1799794 polymorphism may have a protective effect against late adverse effects induced by radiotherapy (OR = 0.47, 95%CI: 0.26-0.86, P = 0.01. Well-designed large-scale clinical studies are required to further validate our results.

  11. Effects on normal tissues during radiosensitization of Dalton's Lymphoma by the DNA ligand Hoechst 33342 in Balb/c mice

    International Nuclear Information System (INIS)

    Kalra, Namita; Sampath, Swapna; Adhikari, J.S.; Dwarakanath, B.S.

    2014-01-01

    Hoechst 33342 is a bisbenzimidazole derivative with AT specific minor groove DNA binding ability. Scavenging of free radicals and stabilization of macromolecular structure resulting in reduced induction of DNA damage contributes to radioprotection afforded by the ligand. Their ability to inhibit topoisomerases I and II, which play important roles in damage response pathways including DNA repair has been shown to sensitize tumor cells in vitro and in vivo. Due to its mutagenic and clastogenic potentials, damage to vital normal tissues are a matter of concern in deploying the ligand as adjuvant in radiotherapy. Therefore, we investigated the effects of the ligand in Dalton's Lymphoma (DL) bearing Balb/c mice by studying the local tumor control and animal survival, besides damage to normal tissues like bone marrow, kidney and testis. Hoechst 33342 (10 mg/kg b wt) was administered (i.v.) 1 h before focal irradiation (10 Gy) of the tumor (∼ 500 mm 3 ) grown on the hind leg of the mice. Partial response with a growth delay of 16 days (3 x initial volume) was seen following irradiation, while a complete response (cure; tumor-free survival) was observed in 88% mice following the combined treatment (Hoechst 33342+radiation); ligand alone had no significant effect. Although the ligand induced marginal degree of chromosomal aberrations in the bone marrow, it did not enhance aberrations induced by radiation further. In testes, the proportions of diploid, haploid and hypo-haploid cells as well as resting primary spermatocytes (RPS) were not significantly altered by either. In kidney, Hoechst 33342 alone or in combination with radiation did not cause significant damage to the proximal tubules and glomeruli. These observations suggest that radiosensitization of tumor by the DNA ligand Hoechst 33342 may not be associated with enhanced toxicity to bone marrow as well as proximal normal tissues. (author)

  12. HDR monotherapy for prostate cancer: A simulation study to determine the effect of catheter displacement on target coverage and normal tissue irradiation

    International Nuclear Information System (INIS)

    Kolkman-Deurloo, Inger-Karine K.; Roos, Martin A.; Aluwini, Shafak

    2011-01-01

    Purpose: The aim of this study was to systematically analyse the effect of catheter displacements both on target coverage and normal tissue irradiation in fractionated high dose rate (HDR) prostate brachytherapy, using a simulation study, and to define tolerances for catheter displacement ensuring that both target coverage and normal tissue doses remain clinically acceptable. Besides the effect of total implant displacement, also displacements of catheters belonging to selected template rows only were evaluated in terms of target coverage and normal tissue dose, in order to analyse the change in dose distribution as a function of catheter dwell weight and catheter location. Material and methods: Five representative implant geometries, with 17 catheters each, were selected. The clinical treatment plan was compared to treatment plans in which an entire implant displacement in caudal direction over 3, 5, 7 and 10 mm was simulated. Besides, treatment plans were simulated considering a displacement of either the central, most ventral or most dorsal catheter rows only, over 5 mm caudally. Results: Due to displacement of the entire implant the target coverage drops below the tolerance of 93% for all displacements studied. The effect of displacement of the entire implant on organs at risk strongly depended on the patient anatomy; e.g., for 80% of the implant geometries the V 80 of the rectum exceeded its tolerance for all displacements. The effect of displacement of catheters belonging to selected template rows depended strongly on the relative weight of each catheter row when considering the target coverage and on its location when considering the dose in the organs at risk. Conclusion: This study supports the need for a check of the catheter locations before each fraction and correction of deviations of the catheter position exceeding 3 mm.

  13. Development of Flight Slit-Jaw Optics for Chromospheric Lyman-Alpha SpectroPolarimeter

    Science.gov (United States)

    Kubo, Masahito; Suematsu, Yoshinori; Kano, Ryohei; Bando, Takamasa; Hara, Hirohisa; Narukage, Noriyuki; Katsukawa, Yukio; Ishikawa, Ryoko; Ishikawa, Shin-nosuke; Kobiki, Toshihiko; hide

    2015-01-01

    In sounding rocket experiment CLASP, I have placed a slit a mirror-finished around the focal point of the telescope. The light reflected by the mirror surface surrounding the slit is then imaged in Slit-jaw optical system, to obtain the alpha-ray Lyman secondary image. This image, not only to use the real-time image in rocket flight rocket oriented direction selection, and also used as a scientific data showing the spatial structure of the Lyman alpha emission line intensity distribution and solar chromosphere around the observation area of the polarimetric spectroscope. Slit-jaw optical system is a two off-axis mirror unit part including a parabolic mirror and folding mirror, Lyman alpha transmission filter, the optical system magnification 1x consisting camera. The camera is supplied from the United States, and the other was carried out fabrication and testing in all the Japanese side. Slit-jaw optical system, it is difficult to access the structure, it is necessary to install the low place clearance. Therefore, influence the optical performance, the fine adjustment is necessary optical elements are collectively in the form of the mirror unit. On the other hand, due to the alignment of the solar sensor in the US launch site, must be removed once the Lyman alpha transmission filter holder including a filter has a different part from the mirror unit. In order to make the structure simple, stray light measures Aru to concentrate around Lyman alpha transmission filter. To overcome the difficulties of performing optical alignment in Lyman alpha wavelength absorbed by the atmosphere, it was planned following four steps in order to reduce standing time alignment me. 1: is measured in advance refractive index at Lyman alpha wavelength of Lyman alpha transmission filter (121.567nm), to prepare a visible light Firuwo having the same optical path length in the visible light (630nm). 2: The mirror structure CLASP before mounting unit standing, dummy slit and camera standing

  14. Transcriptome profiling of the cancer, adjacent non-tumor and distant normal tissues from a colorectal cancer patient by deep sequencing.

    Directory of Open Access Journals (Sweden)

    Yan'an Wu

    Full Text Available Colorectal cancer (CRC is one of the most commonly diagnosed cancers in the world. A genome-wide screening of transcriptome dysregulation between cancer and normal tissue would provide insight into the molecular basis of CRC initiation and progression. Compared with microarray technology, which is commonly used to identify transcriptional changes, the recently developed RNA-seq technique has the ability to detect other abnormal regulations in the cancer transcriptome, such as alternative splicing, novel transcripts or gene fusion. In this study, we performed high-throughput transcriptome sequencing at ~50× coverage on CRC, adjacent non-tumor and distant normal tissue. The results revealed cancer-specific, differentially expressed genes and differential alternative splicing, suggesting that the extracellular matrix and metabolic pathways are activated and the genes related to cell homeostasis are suppressed in CRC. In addition, one tumor-restricted gene fusion, PRTEN-NOTCH2, was also detected and experimentally confirmed. This study reveals some common features in tumor invasion and provides a comprehensive survey of the CRC transcriptome, which provides better insight into the complexity of regulatory changes during tumorigenesis.

  15. Continuous emission from the gaseous nebula beyond the Lyman limit

    International Nuclear Information System (INIS)

    Bolgova, G.T.; Khromov, G.S.

    1975-01-01

    Models of spherically-symmetric isothermic hydrogen nebula with an exciting star in the centre are considered. Spectra and energies of diffuse radiation of nebula and of direct radiation of its kernel are calculated in the Lyman continuum for the external boundary of the object. The spectrum of the diffuse radiation is shown to be to a great extent invariant in relation to all parameters of models except for Tsub(e). The total loss in energy of Lsub(c)-radiation of kernel through the external border of the ionized nebula, amounts to 20-30% in the average even at a considerable optical thickness of the object tausub(0). The greater part of this energy is transferred via direct ionizing radiation, though the relative contribution of the diffuse Lsub(c)-radiation of nebula reaches 30% at low temperatures of the exciting star and at large tausub(0). The results of this work may be applied to calculating the energy balance of the star-nebula system, the heating of dust particles and ionization of the neighbouring interstellar medium, and also for determining the conditions of observation of the far ultra-violet radiation of similar objects

  16. The Lyman-alpha signature of the first galaxies

    Science.gov (United States)

    Smith, Aaron

    2018-01-01

    Radiation from the first stars and galaxies initiated the dramatic phase transition marking an end to the cosmic dark ages. The emission and absorption signatures from the Lyman-alpha (Lyα) transition of neutral hydrogen have been indispensable in extending the observational frontier for high-redshift galaxies into the epoch of reionization. Lyα radiative transfer provides clues about the processes leading to Lyα escape from individual galaxies and the subsequent transmission through the intergalactic medium. Cosmological simulations incorporating Lyα radiative transfer enhance our understanding of fundamental physics by supplying the inferred spectra and feedback on the gas. In this talk, I will discuss the dynamical impact of Lyα radiation pressure on galaxy formation throughout cosmic reionization with the first fully coupled Lyα radiation-hydrodynamics simulations. Based on a suite of spherically symmetric models and high-resolution ab initio cosmological simulations we find that Lyα radiation pressure is dynamically important during the assembly of direct collapse black holes (DCBHs), which may be the seeds of the first supermassive black holes in the universe. Finally, I will discuss recent advances in Lyα modeling based on current state-of-the-art simulations and observational insights.

  17. Incase of Same Region Treatment by using a Tomotherapy and a Linear Accelerator Absorbed Dose Evaluation of Normal Tissues and a Tumor

    International Nuclear Information System (INIS)

    Cheon, Geum Seong; Kim, Chang Uk; Kim, Hoi Nam; Heo, Gyeong Hun; Song, Jin Ho; Hong, Joo Yeong; Jeong, Jae Yong

    2010-01-01

    Treating same region with different modalities there is a limit to evaluate the total absorbed dose of normal tissues. The reason is that it does not support to communication each modalities yet. In this article, it evaluates absorbed dose of the patients who had been treated same region by a tomotherapy and a linear accelerator. After reconstructing anatomic structure with a anthropomorphic phantom, administrate 45 Gy to a tumor in linac plan system as well as prescribe 15 Gy in tomotherapy plan system for make an ideal treatment plan. After the plan which made by tomoplan system transfers to the oncentra plan system for reproduce plan under the same condition and realize total treatment plan with summation 45 Gy linac treatment plan. To evaluate the absorbed dose of two different modalities, do a comparative study both a simple summation dose values and integration dose values. Then compare and analyze absorbed dose of normal tissues and a tumor with the patients who had been exposured radiation by above two different modalities. The result of compared data, in case of minimum dose, there are big different dose values in spleen (12.4%). On the other hand, in case of the maximum dose, it reports big different in a small bowel (10.2%) and a cord (5.8%) in head and neck cancer patients, there presents that oral (20.3%), right lens (7.7%) in minimum dose value. About maximum dose, it represents that spinal (22.5), brain stem (12%), optic chiasm (8.9%), Rt lens (11.5%), mandible (8.1%), pituitary gland (6.2%). In case of Rt abdominal cancer patients, there represents big different minimum dose as Lt kidney (20.3%), stomach (8.1%) about pelvic cancer patients, it reports there are big different in minimum dose as a bladder (15.2%) as well as big different value in maximum dose as a small bowel (5.6%), a bladder (5.5%) in addition, making treatment plan it is able us to get. In case of comparing both simple summation absorbed dose and integration absorbed dose, the

  18. A preclinical study on the rescue of normal tissue by nicotinic acid in high-dose treatment with APO866, a specific nicotinamide phosphoribosyltransferase inhibitor

    DEFF Research Database (Denmark)

    Olesen, Uffe Høgh; Thougaard, Annemette V; Jensen, Peter Buhl

    2010-01-01

    Inhibitor of nicotinamide phosphoribosyltransferase APO866 is a promising cancer drug currently in phase II clinical trials in oncology. Here, we present a strategy for increasing the therapeutic potential of APO866 through the rescue of normal tissues by coadministration of nicotinic acid (Vitamin...... B(3)). We examined the toxicity profile of APO866 in B6D2F1 mice and the effect of oral administration of nicotinic acid on tissue toxicity. Nicotinic acid (50 mg/kg) protects mice from death and severe toxicity from an APO866 dose (60 mg/kg) four times the monotherapy maximum tolerated dose (15 mg....../kg). In a panel of six cancer cell lines, we find that three (including ML-2 cells) are protected by nicotinic acid in vitro, whereas the cytotoxicity of APO866 remains unaffected in the remaining three (including A2780 cells). A selective biomarker for the protection by nicotinic acid was subsequently identified...

  19. Relationship between in vitro chromosomal radiosensitivity of peripheral blood lymphocytes and the expression of normal tissue damage following radiotherapy for breast cancer

    International Nuclear Information System (INIS)

    Barber, J.B.P.; Burrill, W.; Spreadborough, A.R.; Levine, E.; Warren, C.; Scott, D.; Kiltie, A.E.; Roberts, S.A.

    2000-01-01

    There is a need for rapid and reliable tests for the prediction of normal tissue responses to radiotherapy, as this could lead to individualization of patient radiotherapy schedules and thus improvements in the therapeutic ratio. Because the use of cultured fibroblasts is too slow to be practicable in a clinical setting, we evaluated the predictive role of assays of lymphocyte chromosomal radiosensitivity in patients having radiotherapy for breast cancer. Radiosensitivity was assessed using a macronucleus (MN) assay at high dose rate (HDR) and low dose rate (LDR) on lymphocytes irradiated in the G 0 phase of the cell cycle (Scott D, Barber JB, Levine EL, Burril W, Roberts SA. Radiation-induced micronucleus induction in lymphocytes identifies a frequency of radiosensitive cases among breast cancer patients: a test for predisposition? Br. J. Cancer 1998;77;614-620) and an assay of G 2 phase chromatid radiosensitivity ('G 2 assay') (Scott D, Spreadborough A, Levine E, Roberts SA. Genetic predisposition in breast cancer. Lancet 1994; 344: 1444). In a study of acute reactions, blood samples were taken from breast cancer patients before the start of radiotherapy, and the skin reaction documented. 116 patients were tested with the HDR MN assay, 73 with the LDR MN assay and 123 with the G 2 assay. In a study of late reactions, samples were taken from a series of breast cancer patients 8-14 years after radiotherapy and the patients assessed for the severity of late effects according to the 'LENT SOMA' scales. 47 were tested with the HDR assay, 26 with the LDR assay and 19 with the G 2 assay. For each clinical endpoint, patients were classified as being normal reactors or 'highly radiosensitive patients' (HR patients (Burnet NG. Johansen J, Turesson I, Nyman J. Describing patients' normal tissue reactions: Concerning the possibility of individualising radiotherapy dose prescriptions based on potential predictive assays of normal tissue radiosensitivity. Int. J. Cancer 1998

  20. SU-F-J-174: A Series of Computational Human Phantoms in DICOM-RT Format for Normal Tissue Dose Reconstruction in Epidemiological Studies

    International Nuclear Information System (INIS)

    Pyakuryal, A; Moroz, B; Lee, C; Pelletier, C; Jung, J; Lee, C

    2016-01-01

    Purpose: Epidemiological studies of second cancer risk in radiotherapy patients often require individualized dose estimates of normal tissues. Prior to 3D conformal radiation therapy planning, patient anatomy information was mostly limited to 2D radiological images or not even available. Generic patient CT images are often used in commercial radiotherapy treatment planning system (TPS) to reconstruct normal tissue doses. The objective of the current work was to develop a series of reference size computational human phantoms in DICOM-RT format for direct use in dose reconstruction in TPS. Methods: Contours of 93 organs and tissues were extracted from a series of pediatric and adult hybrid computational human phantoms (newborn, 1-, 5-, 10-, 15-year-old, and adult males and females) using Rhinoceros software. A MATLAB script was created to convert the contours into the DICOM-RT structure format. The simulated CT images with the resolution of 1×1×3 mm3 were also generated from the binary phantom format and coupled with the DICOM-structure files. Accurate volumes of the organs were drawn in the format using precise delineation of the contours in converted format. Due to complex geometry of organs, higher resolution (1×1×1 mm3) was found to be more efficient in the conversion of newborn and 1-year-old phantoms. Results: Contour sets were efficiently converted into DICOM-RT structures in relatively short time (about 30 minutes for each phantom). A good agreement was observed in the volumes between the original phantoms and the converted contours for large organs (NRMSD<1.0%) and small organs (NRMSD<7.7%). Conclusion: A comprehensive series of computational human phantoms in DICOM-RT format was created to support epidemiological studies of second cancer risks in radiotherapy patients. We confirmed the DICOM-RT phantoms were successfully imported into the TPS programs of major vendors.

  1. Comparison of telomere length and insulin-like growth factor-binding protein 7 promoter methylation between breast cancer tissues and adjacent normal tissues in Turkish women.

    Science.gov (United States)

    Kaya, Zehra; Akkiprik, Mustafa; Karabulut, Sevgi; Peker, Irem; Gullu Amuran, Gokce; Ozmen, Tolga; Gulluoglu, Bahadır M; Kaya, Handan; Ozer, Ayse

    2017-09-01

    Both insulin-like growth factor-binding protein 7 (IGFBP7) and telomere length (TL) are associated with proliferation and senescence of human breast cancer. This study assessed the clinical significance of both TL and IGFBP7 methylation status in breast cancer tissues compared with adjacent normal tissues. We also investigated whether IGFBP7 methylation status could be affecting TL. Telomere length was measured by quantitative PCR to compare tumors with their adjacent normal tissues. The IGFBP7 promoter methylation status was evaluated by methylation-specific PCR and its expression levels were determined by western blotting. Telomeres were shorter in tumor tissues compared to controls (Pbreast cancer with invasive ductal carcinoma (IDC; n=72; P=.014) compared with other histological type (n=29), and TL in IDC with HER2 negative (n=53; P=.017) was higher than TL in IDC with HER2 positive (n=19). However, telomeres were shortened in advanced stages and growing tumors. IGFBP7 methylation was observed in 90% of tumor tissues and 59% of controls (P=.0002). Its frequency was significantly higher in IDC compared with invasive mixed carcinoma (IMC; P=.002) and it was not correlated either with protein expression or the other clinicopathological parameters. These results suggest that IGFBP7 promoter methylation and shorter TL in tumor compared with adjacent tissues may be predictive biomarkers for breast cancer. Telomere maintenance may be indicative of IDC and IDC with HER2 (-) of breast cancer. Further studies with larger number of cases are necessary to verify this association. © 2016 Wiley Periodicals, Inc.

  2. Intraoperative radiotherapy in combination with misonidazole. In special reference to the drug concentration in tumors and normal tissues and to the initial effect of the treatment

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Masaji; Ono, Kouji; Hamanaka, Daizaburo; Dodo, Yoshihiro; Hiraoka, Masahiro [Kyoto Univ. (Japan). Faculty of Medicine

    1983-03-01

    A hypoxic cell radiosensitizer, misonidazole, was applied to 28 patients with carcinoma who received intraoperative radiotherapy. A single dose of 2-3g/m/sup 2/ of the drug was given orally to each patient three hours prior to the start of general anesthesia. The levels of misonidazole and its metabolite, desmethylmisonidazole, in blood, tumors and normal tissues taken from excised materials were measured by a high performance liquid chromatography. The results showed that the concentration levels of misonidazole and desmethylmisonidazole in blood correlated neither to oral doses of 2-3g/m/sup 2/ nor to the function of time after drug ingestion until eight hours. The mean value of blood levels was 77.1 +- 10.9..mu..g/ml. A wide range of 10-96% of the blood level was found in tumors. High levels were observed in gastric cancer and brain tumor (glioblastoma) but not in colorectal cancer and osteosarcoma. It was, however, likely that the concentrations in tumors depended on tumor sizes and/or necrotic areas rather than histologic types and/or sites of tumors. It was also noted that the concentration in normal tissues ranged widely from 11 to 87% of the blood level. Higher concentrations showing more than 75% were found in the ulnar nerve, the stomach and the skin. However, 3 of 4 materials for the stomach and 2 of 3 materials for the skin showed low levels of less than 30% and less than 22% respectively. In 27 of 28 cases different doses of 28-50 Gy with different energies of electrons were delivered intraoperatively. It is impossible so far to derive conclusive results of this study, really because of the short period of observation following the treatment.

  3. Dosimetric Coverage of the Prostate, Normal Tissue Sparing, and Acute Toxicity with High-Dose-Rate Brachytherapy for Large Prostate Volumes

    Directory of Open Access Journals (Sweden)

    George Yang

    2015-06-01

    Full Text Available ABSTRACTPurposeTo evaluate dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with HDR brachytherapy for large prostate volumes.Materials and MethodsOne hundred and two prostate cancer patients with prostate volumes >50 mL (range: 5-29 mL were treated with high-dose-rate (HDR brachytherapy ± intensity modulated radiation therapy (IMRT to 4,500 cGy in 25 daily fractions between 2009 and 2013. HDR brachytherapy monotherapy doses consisted of two 1,350-1,400 cGy fractions separated by 2-3 weeks, and HDR brachytherapy boost doses consisted of two 950-1,150 cGy fractions separated by 4 weeks. Twelve of 32 (38% unfavorable intermediate risk, high risk, and very high risk patients received androgen deprivation therapy. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.ResultsMedian follow-up was 14 months. Dosimetric goals were achieved in over 90% of cases. Three of 102 (3% patients developed Grade 2 acute proctitis. No variables were significantly associated with Grade 2 acute proctitis. Seventeen of 102 (17% patients developed Grade 2 acute urinary retention. American Urological Association (AUA symptom score was the only variable significantly associated with Grade 2 acute urinary retention (p=0.04. There was no ≥ Grade 3 acute toxicity.ConclusionsDosimetric coverage of the prostate and normal tissue sparing were adequate in patients with prostate volumes >50 mL. Higher pre-treatment AUA symptom scores increased the relative risk of Grade 2 acute urinary retention. However, the overall incidence of acute toxicity was acceptable in patients with large prostate volumes.

  4. Dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with high-dose-rate brachytherapy for large prostate volumes

    Energy Technology Data Exchange (ETDEWEB)

    Yang, George; Strom, Tobin J.; Shrinath, Kushagra; Mellon, Eric A.; Fernandez, Daniel C.; Biagioli, Matthew C. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States); Wilder, Richard B., E-mail: mcbiagioli@yahoo.com [Cancer Treatment Centers of America, Newnan, GA (United States)

    2015-05-15

    Purpose: to evaluate dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with HDR brachytherapy for large prostate volumes. Materials and methods: one hundred and two prostate cancer patients with prostate volumes >50 mL (range: 5-29 mL) were treated with high-dose-rate (HDR) brachytherapy ± intensity modulated radiation therapy (IMRT) to 4,500 cGy in 25 daily fractions between 2009 and 2013. HDR brachytherapy monotherapy doses consisted of two 1,350-1,400 cGy fractions separated by 2-3 weeks, and HDR brachytherapy boost doses consisted of two 950-1,150 cGy fractions separated by 4 weeks. Twelve of 32 (38%) unfavorable intermediate risk, high risk, and very high risk patients received androgen deprivation therapy. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4. Results: median follow-up was 14 months. Dosimetric goals were achieved in over 90% of cases. Three of 102 (3%) patients developed Grade 2 acute proctitis. No variables were significantly associated with Grade 2 acute proctitis. Seventeen of 102 (17%) patients developed Grade 2 acute urinary retention. American Urological Association (AUA) symptom score was the only variable significantly associated with Grade 2 acute urinary retention (p-0.04). There was no ≥ Grade 3 acute toxicity. Conclusions: dosimetric coverage of the prostate and normal tissue sparing were adequate in patients with prostate volumes >50 mL. Higher pre-treatment AUA symptom scores increased the relative risk of Grade 2 acute urinary retention. However, the overall incidence of acute toxicity was acceptable in patients with large prostate volumes. (author)

  5. SU-F-J-174: A Series of Computational Human Phantoms in DICOM-RT Format for Normal Tissue Dose Reconstruction in Epidemiological Studies

    Energy Technology Data Exchange (ETDEWEB)

    Pyakuryal, A; Moroz, B [National Cancer Institute, National Institutes of Health, Rockville, MD (United States); Lee, C [University of Michigan, Ann Arbor, MI (United States); Pelletier, C; Jung, J [East Carolina University Greenville, NC (United States); Lee, C [National Cancer Institute, Rockville, MD (United States)

    2016-06-15

    Purpose: Epidemiological studies of second cancer risk in radiotherapy patients often require individualized dose estimates of normal tissues. Prior to 3D conformal radiation therapy planning, patient anatomy information was mostly limited to 2D radiological images or not even available. Generic patient CT images are often used in commercial radiotherapy treatment planning system (TPS) to reconstruct normal tissue doses. The objective of the current work was to develop a series of reference size computational human phantoms in DICOM-RT format for direct use in dose reconstruction in TPS. Methods: Contours of 93 organs and tissues were extracted from a series of pediatric and adult hybrid computational human phantoms (newborn, 1-, 5-, 10-, 15-year-old, and adult males and females) using Rhinoceros software. A MATLAB script was created to convert the contours into the DICOM-RT structure format. The simulated CT images with the resolution of 1×1×3 mm3 were also generated from the binary phantom format and coupled with the DICOM-structure files. Accurate volumes of the organs were drawn in the format using precise delineation of the contours in converted format. Due to complex geometry of organs, higher resolution (1×1×1 mm3) was found to be more efficient in the conversion of newborn and 1-year-old phantoms. Results: Contour sets were efficiently converted into DICOM-RT structures in relatively short time (about 30 minutes for each phantom). A good agreement was observed in the volumes between the original phantoms and the converted contours for large organs (NRMSD<1.0%) and small organs (NRMSD<7.7%). Conclusion: A comprehensive series of computational human phantoms in DICOM-RT format was created to support epidemiological studies of second cancer risks in radiotherapy patients. We confirmed the DICOM-RT phantoms were successfully imported into the TPS programs of major vendors.

  6. Haro 11: Where is the Lyman Continuum Source?

    Energy Technology Data Exchange (ETDEWEB)

    Keenan, Ryan P.; Oey, M. S. [Department of Astronomy, University of Michigan, 1085 South University Avenue, Ann Arbor, MI 48109 (United States); Jaskot, Anne E. [Department of Astronomy, Smith College, Northampton, MA 01063 (United States); James, Bethan L. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States)

    2017-10-10

    Identifying the mechanism by which high-energy Lyman continuum (LyC) photons escaped from early galaxies is one of the most pressing questions in cosmic evolution. Haro 11 is the best known local LyC-leaking galaxy, providing an important opportunity to test our understanding of LyC escape. The observed LyC emission in this galaxy presumably originates from one of the three bright, photoionizing knots known as A, B, and C. It is known that Knot C has strong Ly α emission, and Knot B hosts an unusually bright ultraluminous X-ray source, which may be a low-luminosity active galactic nucleus. To clarify the LyC source, we carry out ionization-parameter mapping (IPM) by obtaining narrow-band imaging from the Hubble Space Telescope WFC3 and ACS cameras to construct spatially resolved ratio maps of [O iii]/[O ii] emission from the galaxy. IPM traces the ionization structure of the interstellar medium and allows us to identify optically thin regions. To optimize the continuum subtraction, we introduce a new method for determining the best continuum scale factor derived from the mode of the continuum-subtracted, image flux distribution. We find no conclusive evidence of LyC escape from Knots B or C, but instead we identify a high-ionization region extending over at least 1 kpc from Knot A. This knot shows evidence of an extremely young age (≲1 Myr), perhaps containing very massive stars (>100 M {sub ⊙}). It is weak in Ly α , so if it is confirmed as the LyC source, our results imply that LyC emission may be independent of Ly α emission.

  7. A Lyman Break Galaxy Candidate at z ~ 9

    Science.gov (United States)

    Henry, Alaina L.; Malkan, Matthew A.; Colbert, James W.; Siana, Brian; Teplitz, Harry I.; McCarthy, Patrick

    2008-06-01

    We report the discovery of a z ~ 9 Lyman break galaxy candidate, selected from the NICMOS Parallel Imaging Survey as a J-dropout with J110 - H160 = 1.7. Spitzer/IRAC photometry reveals that the galaxy has a blue H160 - 3.6 μm color and a spectral break between 3.6 and 4.5 μm. We interpret this break as the Balmer break and derive a best-fit photometric redshift of z ~ 9. We use Monte Carlo simulations to test the significance of this photometric redshift, and we show that there is a 96% probability of z >= 7. We estimate that the lower limit to the comoving number density of such galaxies at z ~ 9 is phi > 3.8 × 10-6 Mpc-3. If the high redshift of this galaxy is confirmed, this will indicate that the luminous end of the rest-frame UV luminosity function has not evolved substantially from z ~ 9 to z ~ 3. Still, some small degeneracy remains between this z ~ 9 model and models at z ~ 2-3 deep optical imaging (reaching IAB ~ 29) can rule out the lower z models. This work is based in part on observations made with the Spitzer Space Telescope, which is operated by the Jet Propulsion Laboratory (JPL), California Institute of Technology, under a contract with NASA. Support for this work was provided by NASA through an award issued by JPL/Caltech. This work is also based in part on observations made with the NASA/ESA Hubble Space Telescope, obtained from the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555. These observations are associated with proposals 9484, 9865, 10226, and 10899.

  8. Lyman Break Galaxies At z 2 In The GOODS Fields

    Science.gov (United States)

    Haberzettl, Lutz; Williger, G.; Lehnert, M.; Nesvadba, N.

    2009-12-01

    Lyman Break Galaxies (LBGs) have been the benchmarks against which other samples of high redshift galaxies have been compared for the last 2 decades. They are unique in that no other selection mechanism allows us to study galaxies selected in a consistent manner over the span of redshifts from z=0 to 7. An important remaining gap is the redshift range z ˜ 1.5-2.5, which includes near UV (NUV)-band drop-outs. We present first results of a search for LBGs at these redshifts using very sensitive multi-frequency data from the far UV to mid-IR of the GOODS CDF-S and HDF-N. We modelled colors of star-forming galaxies, and found only a small overlap with the BM/BX selection method (Adelberger et al. 2004, ApJ, 607, 226). We developed new color selection criteria using GALEX NUV and optical photometry to identify high star formation galaxies, including NUV-dropouts for 2.0methods, we identified a sample of ? z˜ 2 LBG candidates in both the GOODS CDF-S and the HDF-N. A first analysis of the mean SED of our LBG candidate sample shows results consistent with red LBGs at z ˜ 1, indicating massive galaxies with high star formation rates. Nearly 10% of our selected LBG candidates have mid-IR (IRAC+MIPS) colors comparable both to z ˜ 3 IR-luminous LBGs, which are believed to be dusty, vigorously star-forming massive progenitors of modern ellipticals.

  9. Postpartum complications

    International Nuclear Information System (INIS)

    Kronthal, A.J.; Kuhlman, J.E.; Fishman, E.K.

    1990-01-01

    This paper reports the CT findings of major postpartum complications and determine what role CT plays in their evaluation. The CT scans of nine patients with major postpartum complications were retrospectively reviewed. Patients had been referred to CT for evaluation of postpartum fever, abdominal pain, and elevated results of liver function tests. Complications identified at CT included hepatic infarctions (n = 2), endometritis (n = 2), postoperative wound abscess (n = 1), massive abdominal hemorrhage (n = 1), septic thrombophlebitis (n = 1), and renal vein thrombosis (n = 1). CT findings of hepatic infarction included wedge-shaped areas of decreased enhancement conforming to a vascular distribution

  10. Are the brightest Lyman Alpha Emitters at z=5.7 primeval galaxies?

    Science.gov (United States)

    Lidman, Christopher; Jones, Heath; Meisenheimer, Klaus; Pompei, Emanuela; Tapken, Christian; Vanzi, Leonardo; Westra, Eduard

    2008-03-01

    Wide-field, narrow-band surveys have proven to be effective at finding very high redshift galaxies that emit brightly in the Lyman alpha line, the so-called Lyman alpha emitters (LAEs). It was through this technique that the most distant spectroscopically confirmed galaxy, a galaxy at z=6.96, was discovered. Considerable effort is currently being spent on discovering these galaxies at ever higher redshifts by extending this technique into the near-IR. In contrast to this effort, there has been relatively little work on understanding these galaxies. In particular, how do LAEs relate to other high redshift galaxies, such as the galaxies discovered through broad band drop out techniques, and, perhaps, more importantly, what role do LAEs play in re-ionising the universe. We recently discovered two extremely luminous LAEs at z=5.7. These LAEs are among the brightest LAEs ever discovered at this redshift. In a recent paper by Mao et al. the brightest LAEs are associated to the most massive halos. We propose to use the IRAC 3.6 micron imager on Spitzer to measure the rest-frame optical flux of the these LAEs. With additional data from the near-IR (rest-frame UV) and very deep optical spectra around the Lyman alpha line, we propose to make a detailed study of the spectral energy distribution from the Lyman alpha line to the rest frame optical of these exceptional LAEs. These data will enable us to estimate the age and mass of the stellar burst that produces the Lyman alpha line, to estimate the contribution from an older stellar population, if any, and to estimate the fraction of Lyman continuum photons that can escape the galaxy and are thus available to reionise the universe.

  11. Skin Complications

    Science.gov (United States)

    ... Text Size: A A A Listen En Español Skin Complications Diabetes can affect every part of the ... lipoidica diabeticorum, diabetic blisters, and eruptive xanthomatosis. General Skin Conditions Bacterial Infections Several kinds of bacterial infections ...

  12. Diphtheria Complications

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search The CDC Diphtheria Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Diphtheria Home About Diphtheria Causes and Transmission Symptoms Complications ...

  13. Lyman-alpha detector designed for rocket measurements of the direct solar radiation at 121.5 nm

    International Nuclear Information System (INIS)

    Guineva, V.; Tashev, V.; Witt, G.; Gumbel, J.; Khaplanov, M.

    2007-01-01

    Rocket measurements of the direct Lyman-alpha radiation penetrating in the atmosphere were planned during the HotPay I rocket experiment, June 2006, Project ASLAF (Attenuation of the Solar Lyman-Alpha Flux), Andoya Rocket Range (ARR), Norway. The basic goal of ASLAF project was the study of the processes in the summer mesosphere and thermosphere (up to 110 km), at high latitudes using the Lyman-alpha measurements. The resonance transition 2 P- 2 S of the atomic hydrogen (Lyman-alpha emission) is the strongest and most conspicuous feature in the solar EUV spectrum. Due to the favourable circumstance, that the Lyman-alpha wavelength (121.5 nm) coincides with a minimum of the O 2 absorption spectrum, the direct Lyman-alpha radiation penetrates well in the mesosphere. The Lyman-alpha radiation is the basic agent of the NO molecules ionization, thus generating the ionospheric D-layer, and of the water vapour photolysis, being one of the main H 2 O loss processes. The Lyman-alpha radiation transfer depends on the resonance scattering from the hydrogen atoms in the atmosphere and on the O 2 absorption. Since the Lyman-alpha extinction in the atmosphere is a measure for the column density of the oxygen molecules, the atmospheric temperature profile can be calculated thereof. The detector of solar Lyman-alpha radiation was manufactured in the Stara Zagora Department of the Solar-Terrestrial Influences Laboratory (STIL). Its basic part is an ionization chamber, filled in with NO. A 60 V power supply is applied to the chamber. The produced photoelectric current from the sensor is fed to a 2-channels amplifier, providing an analogue signal. The characteristics of the Lyman-alpha detector were studied. It passed successfully all tests and the results showed that the instrument could be used in rocket experiments to measure the Lyman-alpha flux. From the measurements of the detector, the Lyman-alpha vertical profile can be obtained. The forthcoming scientific data analysis will

  14. TU-F-12A-09: GLCM Texture Analysis for Normal-Tissue Toxicity: A Prospective Ultrasound Study of Acute Toxicity in Breast-Cancer Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Liu, T; Yang, X; Curran, W; Torres, M [Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA (United States)

    2014-06-15

    Purpose: To evaluate the morphologic and structural integrity of the breast glands using sonographic textural analysis, and identify potential early imaging signatures for radiation toxicity following breast-cancer radiotherapy (RT). Methods: Thirty-eight patients receiving breast RT participated in a prospective ultrasound imaging study. Each participant received 3 ultrasound scans: 1 week before RT (baseline), and at 6-week and 3-month follow-ups. Patients were imaged with a 10-MHz ultrasound on the four quadrant of the breast. A second order statistical method of texture analysis, called gray level co-occurrence matrix (GLCM), was employed to assess RT-induced breast-tissue toxicity. The region of interest (ROI) was 28 mm × 10 mm in size at a 10 mm depth under the skin. Twenty GLCM sonographic features, ratios of the irradiated breast and the contralateral breast, were used to quantify breast-tissue toxicity. Clinical assessment of acute toxicity was conducted using the RTOG toxicity scheme. Results: Ninety-seven ultrasound studies (776 images) were analyzed; and 5 out of 20 sonographic features showed significant differences (p < 0.05) among the baseline scans, the acute toxicity grade 1 and 2 groups. These sonographic features quantified the degree of tissue damage through homogeneity, heterogeneity, randomness, and symmetry. Energy ratio value decreased from 108±0.05 (normal) to 0.99±0.05 (Grade 1) and 0.84±0.04 (Grade 2); Entropy ratio value increased from 1.01±0.01 to 1.02±0.01 and 1.04±0.01; Contrast ratio value increased from 1.03±0.03 to 1.07±0.06 and 1.21±0.09; Variance ratio value increased from 1.06±0.03 to 1.20±0.04 and 1.42±0.10; Cluster Prominence ratio value increased from 0.98±0.02 to 1.01±0.04 and 1.25±0.07. Conclusion: This work has demonstrated that the sonographic features may serve as imaging signatures to assess radiation-induced normal tissue damage. While these findings need to be validated in a larger cohort, they suggest

  15. Intensity-Modulated Proton Therapy Further Reduces Normal Tissue Exposure During Definitive Therapy for Locally Advanced Distal Esophageal Tumors: A Dosimetric Study

    Energy Technology Data Exchange (ETDEWEB)

    Welsh, James, E-mail: jwelsh@mdanderson.org [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Gomez, Daniel; Palmer, Matthew B.; Riley, Beverly A.; Mayankkumar, Amin V.; Komaki, Ritsuko [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Dong, Lei; Zhu, X. Ronald [Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Likhacheva, Anna; Liao, Zhongxing [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Hofstetter, Wayne L. [Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Cox, James D. [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)

    2011-12-01

    Purpose: We have previously found that {<=} 75% of treatment failures after chemoradiotherapy for unresectable esophageal cancer appear within the gross tumor volume and that intensity-modulated (photon) radiotherapy (IMRT) might allow dose escalation to the tumor without increasing normal tissue toxicity. Proton therapy might allow additional dose escalation, with even lower normal tissue toxicity. In the present study, we compared the dosimetric parameters for photon IMRT with that for intensity-modulated proton therapy (IMPT) for unresectable, locally advanced, distal esophageal cancer. Patients and Methods: Four plans were created for each of 10 patients. IMPT was delivered using anteroposterior (AP)/posteroanterior beams, left posterior oblique/right posterior oblique (LPO/RPO) beams, or AP/LPO/RPO beams. IMRT was delivered with a concomitant boost to the gross tumor volume. The dose was 65.8 Gy to the gross tumor volume and 50.4 Gy to the planning target volume in 28 fractions. Results: Relative to IMRT, the IMPT (AP/posteroanterior) plan led to considerable reductions in the mean lung dose (3.18 vs. 8.27 Gy, p < .0001) and the percentage of lung volume receiving 5, 10, and 20 Gy (p {<=} .0006) but did not reduce the cardiac dose. The IMPT LPO/RPO plan also reduced the mean lung dose (4.9 Gy vs. 8.2 Gy, p < .001), the heart dose (mean cardiac dose and percentage of the cardiac volume receiving 10, 20, and 30 Gy, p {<=} .02), and the liver dose (mean hepatic dose 5 Gy vs. 14.9 Gy, p < .0001). The IMPT AP/LPO/RPO plan led to considerable reductions in the dose to the lung (p {<=} .005), heart (p {<=} .003), and liver (p {<=} .04). Conclusions: Compared with IMRT, IMPT for distal esophageal cancer lowered the dose to the heart, lung, and liver. The AP/LPO/RPO beam arrangement was optimal for sparing all three organs. The dosimetric benefits of protons will need to be tailored to each patient according to their specific cardiac and pulmonary risks. IMPT for

  16. Oral complications of radiation therapy

    International Nuclear Information System (INIS)

    Lockhart, P.B.

    1986-01-01

    Approximately 24,000 patients are diagnosed each year with malignant tumors of the head and neck. Many of these patients will be treated with radiotherapy, surgery, or chemotherapy, either singly or in combination. Certain predictable sequelae of radiotherapy exist that may be considered consequences of treatment rather than complications; these may be unavoidable consequences of curative radiotherapy to the head and neck. There are, however, additional problems that occur as a result of radiotherapy that are preventable in both incidence and severity, and are therefore avoidable complications. Cell kinetic factors, radiosensitivity of normal tissues, radiotherapeutic doses necessary for tumor control, and the complex anatomy of the maxillofacial region often predispose patients serious treatment morbidity. The potential for pain, infection, and long-term functional disability with decreased quality of life dictate conscientious management before, during, and after radiotherapy. This chapter discusses common problems that can arise, as well as current methods utilized both to improve patient tolerance to treatment and to decrease the risk of preventable and potentially dose-limiting morbidity

  17. Galex Lyman-alpha Emitters: Physical Properties, Luminosity Bimodality, And Morphologies.

    Science.gov (United States)

    Mallery, Ryan P.

    2010-01-01

    The Galaxy Evolution Explorer spectroscopic survey has uncovered a large statistically significant sample of Lyman-alpha emitters at z sim0.3. ACS imaging of these sources in the COSMOS and AEGIS deep fields reveals that these Lyman-alpha emitters consist of two distinct galaxy morphologies, face on spiral galaxies and compact starburst/merging systems. The morphology bimodality also results in a bimodal distribution of optical luminosity. A comparison between the UV photometry and MIPS 24 micron detections of these sources indicates that they are bluer, and have less dust extinction than similar star forming galaxies that lack Lyman-alpha detection. Our findings show how the global gas and dust distribution of star forming galaxies inhibits Lyman-alpha emission in star forming galaxies. GALEX is a NASA Small Explorer, launched in April 2003. We gratefully acknowledge NASA's support for construction, operation, and science analysis for the GALEX mission, developed in cooperation with the CNES of France and the Korean Ministry of Science and Technology.

  18. Effect of time intervals between irradiation and chemotherapeutic agents on the normal tissue damage. Comparison between in vivo and in vitro experiments

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Hisao; Nakayama, Toshitake; Hashimoto, Shozo (Keio Univ., Tokyo (Japan). School of Medicine)

    1989-05-01

    Experiments have been carried out to determine the effect on the cell survivals at different time intervals between irradiation and chemotherapeutic agents (BLM, cisDDP, ADM and ACNU) in either the in vivo or the in vitro system. The intestinal epithelial assay was applied on the in vivo system. The clonogenic cell survivals of V/sub 79/ cells, both in the proliferative and the plateau phases, were determined in the in vitro system. The V/sub 79/ cells in the plateau phase were more sensitive to BLM, cisDDP and ACNU than those in the proliferative phase, however, the result was reverse with ADM. When BLM, cisDDP or ACNU was combined with irradiation at different time intervals, the response of the plateau phase V/sub 79/ cells to combination therapies were very similar to those of the intestinal epithelial cells. On the other hand, V/sub 79/ cells in the proliferative phase, which were treated with ADM and irradiation, showed the similar response as the intestinal cells. These results suggest that studies of chemo-radiotherapy with cultured cells which are sensitive to chemotherapeutic agents might be suitable to expect the in vivo damage of the normal tissue. (author).

  19. Effect of sodium nitroprusside-induced hypotension on the blood flow in subcutaneous and intramuscular BT4An tumors and normal tissues in rats

    International Nuclear Information System (INIS)

    Krossnes, Baard Kronen; Mella, Olav; Tyssebotn, Ingvald

    1996-01-01

    Purpose: To examine the effect of infusion of the vasodilator sodium nitroprusside (SNP) on the blood flow in normal tissues and BT 4 An tumors growing subcutaneously or intramusculary in BD IX rats. Methods and Materials: Sodium nitroprusside was given as a continuous intravenous infusion to keep the mean arterial pressure stable at 60 mmHg. The cardiac output, organ blood flow, and perfusion of the BT 4 An tumors were measured by injection of radiolabelled microspheres at control conditions and after 20 min SNP infusion in each animal. Two series of experiments were performed with two anesthetics with different mechanisms of action, Inactin and the midazolam-fentanyl-fluanisone combination (MFF), to secure reliable conclusions. Results: Cardiac output, heart rate, and blood flow to the skeletal muscles, heart, and liver increased during SNP infusion in either anesthetic group. In the kidneys and particularly in the skin, decreased blood flow by SNP was observed. When located subcutaneously on the foot, the blood flow in the tumor fell to 23.4% and 21.4% of the control values in the MFF- and Inactin-anesthetized animals, respectively. This was accompanied by a similar fall in the blood flow in the foot (tumor bed) itself. In the intramuscular tumor the blood flow fell to 24.8% of the control value in the MFF group, whereas the corresponding figure was 36.2% in the Inactin group. In the surrounding muscle (tumor bed) the blood flow increased significantly, most pronounced in the MFF experiment, where it was tripled. Conclusion: The fall in the tumor perfusion by SNP may be exploited therapeutically to increase the tumor temperature during hyperthermia. Predominant heating of the tumor compared to the tumor bed can be expected if the tumor is growing in or near skeletal muscles

  20. A comparison of mantle versus involved-field radiotherapy for Hodgkin's lymphoma: reduction in normal tissue dose and second cancer risk

    International Nuclear Information System (INIS)

    Koh, Eng-Siew; Paul, Narinder; Hodgson, David C; Tran, Tu Huan; Heydarian, Mostafa; Sachs, Rainer K; Tsang, Richard W; Brenner, David J; Pintilie, Melania; Xu, Tony; Chung, June

    2007-01-01

    Hodgkin's lymphoma (HL) survivors who undergo radiotherapy experience increased risks of second cancers (SC) and cardiac sequelae. To reduce such risks, extended-field radiotherapy (RT) for HL has largely been replaced by involved field radiotherapy (IFRT). While it has generally been assumed that IFRT will reduce SC risks, there are few data that quantify the reduction in dose to normal tissues associated with modern RT practice for patients with mediastinal HL, and no estimates of the expected reduction in SC risk. Organ-specific dose-volume histograms (DVH) were generated for 41 patients receiving 35 Gy mantle RT, 35 Gy IFRT, or 20 Gy IFRT, and integrated organ mean doses were compared for the three protocols. Organ-specific SC risk estimates were estimated using a dosimetric risk-modeling approach, analyzing DVH data with quantitative, mechanistic models of radiation-induced cancer. Dose reductions resulted in corresponding reductions in predicted excess relative risks (ERR) for SC induction. Moving from 35 Gy mantle RT to 35 Gy IFRT reduces predicted ERR for female breast and lung cancer by approximately 65%, and for male lung cancer by approximately 35%; moving from 35 Gy IFRT to 20 Gy IFRT reduces predicted ERRs approximately 40% more. The median reduction in integral dose to the whole heart with the transition to 35 Gy IFRT was 35%, with a smaller (2%) reduction in dose to proximal coronary arteries. There was no significant reduction in thyroid dose. The significant decreases estimated for radiation-induced SC risks associated with modern IFRT provide strong support for the use of IFRT to reduce the late effects of treatment. The approach employed here can provide new insight into the risks associated with contemporary IFRT for HL, and may facilitate the counseling of patients regarding the risks associated with this treatment

  1. Rapid Discrimination of Malignant Breast Lesions from Normal Tissues Utilizing Raman Spectroscopy System: A Systematic Review and Meta-Analysis of In Vitro Studies.

    Directory of Open Access Journals (Sweden)

    Ke Deng

    Full Text Available The aim of this study is to evaluate the diagnostic accuracy of Raman spectroscopy system in the detection of malignant breast lesions through a systemic review and meta-analysis of published studies.We conducted a comprehensive literature search of PubMed and Embase from 2000 to June 2015. Published studies that evaluated the diagnostic performance of Raman spectroscopy in distinguishing malignant breast lesions from benign lesions and normal tissues were included in our study. The pooled sensitivity, specificity, diagnostic odds ratio, and the area under the curve of summary receiver-operating characteristic curves was derived. A Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies guidelines was used to assess the quality of included studies.The initial search produced a total of 157 articles after removing duplicates. Nine studies (8 in vitro and 1 in vivo were eligible in this meta-analysis. We analyzed the eight in vitro studies with 1756 lesions, the pooled sensitivity and specificity of Raman spectroscopy system for the diagnosis of malignant breast lesions were 0.92 (95% CI 0.86-0.96 and 0.97 (97% CI 0.93-0.98, respectively. Diagnostic odds ratio was 266.70 (95% CI 89.38-795.79, and the area under the curve of summary receiver-operating characteristic curves was 0.98 (95% CI 0.97-0.99. Significant heterogeneity was found between studies. There was no evidence of considerable publication bias.Raman spectroscopy system is an optical diagnostic technology with great value for detecting malignant breast lesions. At the same time, it has advantages of being non-invasive, real-time, and easy to use. Thus it deserves to be further explored for intra-operatory breast tumor margin detection.

  2. Differences in Normal Tissue Response in the Esophagus Between Proton and Photon Radiation Therapy for Non-Small Cell Lung Cancer Using In Vivo Imaging Biomarkers.

    Science.gov (United States)

    Niedzielski, Joshua S; Yang, Jinzhong; Mohan, Radhe; Titt, Uwe; Mirkovic, Dragan; Stingo, Francesco; Liao, Zhongxing; Gomez, Daniel R; Martel, Mary K; Briere, Tina M; Court, Laurence E

    2017-11-15

    To determine whether there exists any significant difference in normal tissue toxicity between intensity modulated radiation therapy (IMRT) or proton therapy for the treatment of non-small cell lung cancer. A total of 134 study patients (n=49 treated with proton therapy, n=85 with IMRT) treated in a randomized trial had a previously validated esophageal toxicity imaging biomarker, esophageal expansion, quantified during radiation therapy, as well as esophagitis grade (Common Terminology Criteria for Adverse Events version 3.0), on a weekly basis during treatment. Differences between the 2 modalities were statically analyzed using the imaging biomarker metric value (Kruskal-Wallis analysis of variance), as well as the incidence and severity of esophagitis grade (χ 2 and Fisher exact tests, respectively). The dose-response of the imaging biomarker was also compared between modalities using esophageal equivalent uniform dose, as well as delivered dose to an isotropic esophageal subvolume. No statistically significant difference in the distribution of esophagitis grade, the incidence of grade ≥3 esophagitis (15 and 11 patients treated with IMRT and proton therapy, respectively), or the esophageal expansion imaging biomarker between cohorts (P>.05) was found. The distribution of imaging biomarker metric values had similar distributions between treatment arms, despite a slightly higher dose volume in the proton arm (P>.05). Imaging biomarker dose-response was similar between modalities for dose quantified as esophageal equivalent uniform dose and delivered esophageal subvolume dose. Regardless of treatment modality, there was high variability in imaging biomarker response, as well as esophagitis grade, for similar esophageal doses between patients. There was no significant difference in esophageal toxicity from either proton- or photon-based radiation therapy as quantified by esophagitis grade or the esophageal expansion imaging biomarker. Copyright © 2017 Elsevier

  3. Radiation-induced DNA damage in tumors and normal tissues. II. Influence of dose, residual DNA damage and physiological factors in oxygenated cells

    International Nuclear Information System (INIS)

    Zhang, H.; Wheeler, K.T.

    1994-01-01

    Detection and quantification of hypoxic cells in solid tumors is important for many experimental and clinical situations. Several laboratories, including ours, have suggested that assays which measure radiation-induced DNA strand breaks and DNA-protein crosslinks (DPCs) might be used to detect or quantify hypoxic cells in tumors and normal tissues. Recently, we demonstrated the feasibility of using an alkaline elution assay that measures strand breaks and DPCs to detect and/or quantify hypoxic cells in tissues. For this approach to be valid, DPCs must not be formed to any great extent in irradiated oxygenated cells, and the formation and repair of strand breaks and DPCs in oxygenated cells must not be modified appreciably by physiological factors (e.g., temperature, pH and nutrient depletion) that are often found in solid tumors. To address these issues, two sets of experiments were performed. In one set of experiments, oxygenated 9L cells in tissue culture, subcutaneous 9L tumors and rat cerebella were irradiated with doses of 15 or 50 Gy and allowed to repair until the residual strand break damage was low enough to detect DPCs. In another set of experiments, oxygenated exponentially growing or plateau-phase 9L cells in tissue culture were irradiated with a dose of 15 Gy at 37 or 20 degrees C, while the cells were maintained at a pH of either 6.6 or 7.3. DNA-protein crosslinks were formed in oxygenated cells about 100 times less efficiently than in hypoxic cells. In addition, temperature, pH, nutrient depletion and growth phase did not appreciably alter the formation and repair of strand breaks or the formation of DPCs in oxygenated 9L cells. These results support the use of this DNA damage assay for the detection and quantification of hypoxic cells in solid tumors. 27 refs., 5 tabs

  4. Monoclonal antibodies to murine thrombospondin-1 and thrombospondin-2 reveal differential expression patterns in cancer and low antigen expression in normal tissues

    International Nuclear Information System (INIS)

    Bujak, Emil; Pretto, Francesca; Ritz, Danilo; Gualandi, Laura; Wulhfard, Sarah; Neri, Dario

    2014-01-01

    There is a considerable interest for the discovery and characterization of tumor-associated antigens, which may facilitate antibody-based pharmacodelivery strategies. Thrombospondin-1 and thrombospondin-2 are homologous secreted proteins, which have previously been reported to be overexpressed during remodeling typical for wound healing and tumor progression and to possibly play a functional role in cell proliferation, migration and apoptosis. To our knowledge, a complete immunohistochemical characterization of thrombospondins levels in normal rodent tissues has not been reported so far. Using antibody phage technology, we have generated and characterized monoclonal antibodies specific to murine thrombospondin-1 and thrombospondin-2, two antigens which share 62% aminoacid identity. An immunofluorescence analysis revealed that both antigens are virtually undetectable in normal mouse tissues, except for a weak staining of heart tissue by antibodies specific to thrombospondin-1. The analysis also showed that thrombospondin-1 was strongly expressed in 5/7 human tumors xenografted in nude mice, while it was only barely detectable in 3/8 murine tumors grafted in immunocompetent mice. By contrast, a high-affinity antibody to thrombospondin-2 revealed a much lower level of expression of this antigen in cancer specimens. Our analysis resolves ambiguities related to conflicting reports on thrombosponding expression in health and disease. Based on our findings, thrombospondin-1 (and not thrombospondin-2) may be considered as a target for antibody-based pharmacodelivery strategies, in consideration of its low expression in normal tissues and its upregulation in cancer. - Highlights: • High affinity monoclonal antibodies to murine and human TSP1 and 2 were raised. • Both antigens are virtually undetectable in normal mouse tissues. • Strong positivity of human tumor xenografts for TSP1 was detected. • Study revealed much lower level of TSP2 expression in cancer specimens

  5. Modulation of the Rho/ROCK pathway in heart and lung after thorax irradiation reveals targets to improve normal tissue toxicity.

    Science.gov (United States)

    Monceau, Virginie; Pasinetti, Nadia; Schupp, Charlotte; Pouzoulet, Fred; Opolon, Paule; Vozenin, Marie-Catherine

    2010-11-01

    The medical options available to prevent or treat radiation-induced injury are scarce and developing effective countermeasures is still an open research field. In addition, more than half of cancer patients are treated with radiation therapy, which displays a high antitumor efficacy but can cause, albeit rarely, disabling long-term toxicities including radiation fibrosis. Progress has been made in the definition of molecular pathways associated with normal tissue toxicity that suggest potentially effective therapeutic targets. Targeting the Rho/ROCK pathway seems a promising anti-fibrotic approach, at least in the gut; the current study was performed to assess whether this target was relevant to the prevention and/or treatment of injury to the main thoracic organs, namely heart and lungs. First, we showed activation of two important fibrogenic pathways (Smad and Rho/ROCK) in response to radiation-exposure to adult cardiomyocytes; we extended these observations in vivo to the heart and lungs of mice, 15 and 30 weeks post-irradiation. We correlated this fibrogenic molecular imprint with alteration of heart physiology and long-term remodelling of pulmonary and cardiac histological structures. Lastly, cardiac and pulmonary radiation injury and bleomycin-induced pulmonary fibrosis were successfully modulated using Rho/ROCK inhibitors (statins and Y-27632) and this was associated with a normalization of fibrogenic markers. In conclusion, the present paper shows for the first time, activation of Rho/ROCK and Smad pathways in pulmonary and cardiac radiation-induced delayed injury. Our findings thereby reveal a safe and efficient therapeutic opportunity for the abrogation of late thoracic radiation injury, potentially usable either before or after radiation exposure; this approach is especially attractive in (1) the radiation oncology setting, as it does not interfere with prior anti-cancer treatment and in (2) radioprotection, as applicable to the treatment of established

  6. Dynamic contrast-enhanced magnetic resonance imaging: a non-invasive method to evaluate significant differences between malignant and normal tissue

    International Nuclear Information System (INIS)

    Rudisch, Ansgar; Kremser, Christian; Judmaier, Werner; Zunterer, Hildegard; DeVries, Alexander F.

    2005-01-01

    Purpose: An ever recurring challenge in diagnostic radiology is the differentiation between non-malignant and malignant tissue. Based on evidence that microcirculation of normal, non-malignant tissue differs from that of malignant tissue, the goal of this study was to assess the reliability of dynamic contrast-enhanced Magnetic Resonance Imaging (dcMRI) for differentiating these two entities. Materials and methods: DcMRI data of rectum carcinoma and gluteus maximus muscles were acquired in 41 patients. Using an fast T1-mapping sequence on a 1.5-T whole body scanner, T1-maps were dynamically retrieved before, during and after constant rate i.v. infusion of a contrast medium (CM). On the basis of the acquired data sets, PI-values were calculated on a pixel-by-pixel basis. The relevance of spatial heterogeneities of microcirculation was investigated by relative frequency histograms of the PI-values. Results: A statistically significant difference between malignant and normal tissue was found for the mean PI-value (P < 0.001; 8.95 ml/min/100 g ± 2.45 versus 3.56 ml/min/100 g ± 1.20). Additionally relative frequency distributions of PI-values with equal class intervals of 2.5 ml/min/100 g revealed significant differences between the histograms of muscles and rectum carcinoma. Conclusion: We could show that microcirculation differences between malignant and normal, non-malignant tissue can be reliably assessed by non-invasive dcMRI. Therefore, dcMRI holds great promise in the aid of cancer assessment, especially in patients where biopsy is contraindicated

  7. ADAM28 is expressed by epithelial cells in human normal tissues and protects from C1q-induced cell death.

    Science.gov (United States)

    Miyamae, Yuka; Mochizuki, Satsuki; Shimoda, Masayuki; Ohara, Kentaro; Abe, Hitoshi; Yamashita, Shuji; Kazuno, Saiko; Ohtsuka, Takashi; Ochiai, Hiroki; Kitagawa, Yuko; Okada, Yasunori

    2016-05-01

    ADAM28 (disintegrin and metalloproteinase 28), which was originally reported to be lymphocyte-specific, is over-expressed by carcinoma cells and plays a key role in cell proliferation and progression in human lung and breast carcinomas. We studied ADAM28 expression in human normal tissues and examined its biological function. By using antibodies specific to ADAM28, ADAM28 was immunolocalized mainly to epithelial cells in several tissues, including epididymis, bronchus and stomach, whereas lymphocytes in lymph nodes and spleen were negligibly immunostained. RT-PCR, immunoblotting and ELISA analyses confirmed the expression in these tissues, and low or negligible expression by lymphocytes was found in the lymph node and spleen. C1q was identified as a candidate ADAM28-binding protein from a human lung cDNA library by yeast two-hybrid system, and specific binding was demonstrated by binding assays, immunoprecipitation and surface plasmon resonance. C1q treatment of normal bronchial epithelial BEAS-2B and NHBE cells, both of which showed low-level expression of ADAM28, caused apoptosis through activation of p38 and caspase-3, and cell death with autophagy through accumulation of LC3-II and autophagosomes, respectively. C1q-induced cell death was attenuated by treatment of the cells with antibodies against the C1q receptor gC1qR/p33 or cC1qR/calreticulin. Treatment of C1q with recombinant ADAM28 prior to addition to culture media reduced C1q-induced cell death, and knockdown of ADAM28 using siRNAs increased cell death. These data demonstrate that ADAM28 is expressed by epithelial cells of several normal organs, and suggest that ADAM28 plays a role in cell survival by suppression of C1q-induced cytotoxicity in bronchial epithelial cells. © 2016 Federation of European Biochemical Societies.

  8. TU-H-CAMPUS-TeP2-05: Selective Protection of Normal Tissue by Cerium Oxide Nanoparticles During Radiation Therapy

    International Nuclear Information System (INIS)

    Ouyang, Z; Ngwa, W; Yasmin-Karim, S; Strack, G; Sajo, E

    2016-01-01

    Purpose: Cerium oxide nanoparticles (CONPs) have unique pH dependent properties such that they act as a radical modulator. These properties may be used in radiation therapy (RT) to protect normal tissue. This work investigates the selective radioprotection of CONPs in-vitro and potential for in-situ delivery of CONPs in prostate cancer RT. Methods: i) Normal human umbilical vein endothelial cells (HUVEC) and human prostate cancer cells (PC-3) were treated with 0 or 2 ng/mL CONPs (NP size: 5 nm). 2 Gy of 100 kVp radiation was delivered to the cells 4 hours after the CONP treatment. Cell viability was checked 48 hours later using MTS assays. ii) A prostate tumor was modeled as a 2-cm diameter sphere. CONPs were proposed to be loaded in a hollow radiotherapy fiducial marker. The concentration profile for the CONPs within the tumor was modeled with a previously validated diffusion equation employed in other studies for nanoparticles 10 nm or less. Results: i) Without radiation, cell viability was above 90% when treated with 2 ng/mL CONPs for both HUVEC and PC-3. After irradiation, a slightly higher viability was observed in HUVEC with CONPs than the ones without CONPs, and this effect was not observed in PC-3. ii) Based on the calculations, 2 ng/mL of CONPs could be delivered to normal cells by diffusion with a 1 µg/mL initial concentration within two weeks. Conclusion: We conclude that CONPs can provide selective radioprotection. The delivery of needed concentrations of CONPs is feasible via in-situ release from radiotherapy biomaterials (e.g. fiducials) loaded with the CONPs.

  9. Radiation-induced DNA damage in tumors and normal tissues. III. Oxygen dependence of the formation of strand breaks and DNA-protein crosslinks

    International Nuclear Information System (INIS)

    Zhang, H.; Wallen, C.A.; Wheeler, K.T.; Joch, C.J.

    1995-01-01

    Results from several laboratories, including ours, have suggested that measurements of radiation-induced DNA strand breaks and DNA-protein crosslinks (DPCs) may be used to estimate the hypoxic fraction or fractional hypoxic volume of tumors and normal tissues. This suggestion has been predicated on both published and nonpublished information that (1) the oxygen dependence of the formation of strand breaks in irradiated mammalian cells is similar to the oxygen dependence of radiation-produced cell killing, and (2) the oxygen dependence of the formation of DPCs in irradiated mammalian cells is the mirror image of the oxygen dependence of radiation-induced cell killing. However, the published studies that attempted to determine the relationship between the oxygen dependence of the formation of strand breaks and the radiation sensitivity of mammalian cells were not performed at 37 degrees C, the exact oxygen concentrations were not always known, and the results were conflicting. In addition, most of the data on the oxygen dependence of the formation of DPCs are unpublished. Consequently, we have undertaken a comprehensive investigation of one cell line, 9L/Ro rat brain tumor cells, to determine if the shape of the oxygen dependence curve and the K m value for radiation-induced strand breaks and DPCs were similar when 9L cells were irradiated under both ideal gas-liquid equilibrium conditions at 4 degrees C and nonideal gas-liquid equilibrium conditions at 37 degrees C. At 4 degrees C under ideal gas-liquid equilibrium conditions, the K m for the formation of strand breaks was approximately 0.0045 mM, and Km for radiation sensitivity was approximately 0.005mM. A similar comparison for the formation of DPCs at 4 degrees C could not be made, because the efficiency of the formation of DPC was much lower at 4 degrees C than at 37 degrees C. 30 refs., 3 figs

  10. Modulation of the ρ/rock pathway in heart and lung after thorax irradiation reveals targets to improve normal tissue toxicity

    International Nuclear Information System (INIS)

    Monceau, V.; Pasinetti, N.; Schupp, C.; Pouzoulet, F.; Opolon, P.; Vozenin, M.C.

    2010-01-01

    The medical options available to prevent or treat radiation-induced injury are scarce and developing effective countermeasures is still an open research field. In addition, more than half of cancer patients are treated with radiation therapy, which displays a high antitumor efficacy but can cause, albeit rarely, disabling long-term toxicities including radiation fibrosis. Progress has been made in the definition of molecular pathways associated with normal tissue toxicity that suggest potentially effective therapeutic targets. Targeting the Rho/ROCK pathway seems a promising anti-fibrotic approach, at least in the gut; the current study was performed to assess whether this target was relevant to the prevention and/or treatment of injury to the main thoracic organs, namely heart and lungs. First, we showed activation of two important fibro-genic pathways (Smad and Rho/ROCK) in response to radiation-exposure to adult cardio-myocytes; we extended these observations in vivo to the heart and lungs of mice, 15 and 30 weeks post-irradiation. We correlated this fibro-genic molecular imprint with alteration of heart physiology and long-term remodelling of pulmonary and cardiac histological structures. Lastly, cardiac and pulmonary radiation injury and bleomycin-induced pulmonary fibrosis were successfully modulated using Rho/ROCK inhibitors (statins and Y-27632) and this was associated with a normalization of fibro-genic markers. In conclusion, the present paper shows for the first time, activation of Rho/ROCK and Smad pathways in pulmonary and cardiac radiation-induced delayed injury. Our findings thereby reveal a safe and efficient therapeutic opportunity for the abrogation of late thoracic radiation injury, potentially usable either before or after radiation exposure; this approach is especially attractive in (1) the radiation oncology setting, as it does not interfere with prior anti-cancer treatment and in (2) radioprotection, as applicable to the treatment of

  11. SU-D-16A-01: A Novel Method to Estimate Normal Tissue Dose for Radiotherapy Patients to Support Epidemiologic Studies of Second Cancer Risk

    Energy Technology Data Exchange (ETDEWEB)

    Lee, C [University of Michigan, Ann Arbor, MI (United States); Jung, J; Pelletier, C [East Carolina University, Greenville, NC (United States); Kim, J [University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Lee, C [National Cancer Institute, Bethesda, MD (United States)

    2014-06-01

    Purpose: Patient cohort of second cancer study often involves radiotherapy patients with no radiological images available: We developed methods to construct a realistic surrogate anatomy by using computational human phantoms. We tested this phantom images both in a commercial treatment planning system (Eclipse) and a custom Monte Carlo (MC) transport code. Methods: We used a reference adult male phantom defined by International Commission on Radiological Protection (ICRP). The hybrid phantom which was originally developed in Non-Uniform Rational B-Spline (NURBS) and polygon mesh format was converted into more common medical imaging format. Electron density was calculated from the material composition of the organs and tissues and then converted into DICOM format. The DICOM images were imported into the Eclipse system for treatment planning, and then the resulting DICOM-RT files were imported into the MC code for MC-based dose calculation. Normal tissue doses were calculation in Eclipse and MC code for an illustrative prostate treatment case and compared to each other. Results: DICOM images were generated from the adult male reference phantom. Densities and volumes of selected organs between the original phantom and ones represented within Eclipse showed good agreements, less than 0.6%. Mean dose from Eclipse and MC code match less than 7%, whereas maximum and minimum doses were different up to 45%. Conclusion: The methods established in this study will be useful for the reconstruction of organ dose to support epidemiological studies of second cancer in cancer survivors treated by radiotherapy. We also work on implementing body size-dependent computational phantoms to better represent patient's anatomy when the height and weight of patients are available.

  12. Monoclonal antibodies to murine thrombospondin-1 and thrombospondin-2 reveal differential expression patterns in cancer and low antigen expression in normal tissues

    Energy Technology Data Exchange (ETDEWEB)

    Bujak, Emil [Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 2, CH-8093 Zurich (Switzerland); Pretto, Francesca; Ritz, Danilo; Gualandi, Laura; Wulhfard, Sarah [Philochem AG, Libernstrasse 3, CH-8112 Otelfingen (Switzerland); Neri, Dario, E-mail: neri@pharma.ethz.ch [Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 2, CH-8093 Zurich (Switzerland)

    2014-09-10

    There is a considerable interest for the discovery and characterization of tumor-associated antigens, which may facilitate antibody-based pharmacodelivery strategies. Thrombospondin-1 and thrombospondin-2 are homologous secreted proteins, which have previously been reported to be overexpressed during remodeling typical for wound healing and tumor progression and to possibly play a functional role in cell proliferation, migration and apoptosis. To our knowledge, a complete immunohistochemical characterization of thrombospondins levels in normal rodent tissues has not been reported so far. Using antibody phage technology, we have generated and characterized monoclonal antibodies specific to murine thrombospondin-1 and thrombospondin-2, two antigens which share 62% aminoacid identity. An immunofluorescence analysis revealed that both antigens are virtually undetectable in normal mouse tissues, except for a weak staining of heart tissue by antibodies specific to thrombospondin-1. The analysis also showed that thrombospondin-1 was strongly expressed in 5/7 human tumors xenografted in nude mice, while it was only barely detectable in 3/8 murine tumors grafted in immunocompetent mice. By contrast, a high-affinity antibody to thrombospondin-2 revealed a much lower level of expression of this antigen in cancer specimens. Our analysis resolves ambiguities related to conflicting reports on thrombosponding expression in health and disease. Based on our findings, thrombospondin-1 (and not thrombospondin-2) may be considered as a target for antibody-based pharmacodelivery strategies, in consideration of its low expression in normal tissues and its upregulation in cancer. - Highlights: • High affinity monoclonal antibodies to murine and human TSP1 and 2 were raised. • Both antigens are virtually undetectable in normal mouse tissues. • Strong positivity of human tumor xenografts for TSP1 was detected. • Study revealed much lower level of TSP2 expression in cancer specimens

  13. SU-F-T-51: Investigating the Effect of Eye Size and Eccentricity On Normal Tissue Doses From Eye Plaque Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Polsdofer, E; Crilly, R [Oregon Health & Science University Portland, OR (United States)

    2016-06-15

    Purpose: This study investigates the effect of eye size and eccentricity on doses to critical tissues by simulating doses in the Plaque Simulator (v. 6.3.1) software. Present OHSU plaque brachytherapy treatment focuses on delivering radiation to the tumor measured with ocular ultrasound plus a small margin and assumes the orbit has the dimensions of a “standard eye.” Accurately modeling the dimensions of the orbit requires a high resolution ocular CT. This study quantifies how standard differences in equatorial diameters and eccentricity affect calculated doses to critical structures in order to query the justification of the additional CT scan to the treatment planning process. Methods: Tumors of 10 mm × 10 mm × 5 mm were modeled at the 12:00:00 hour with a latitude of 45 degrees. Right eyes were modeled at a number of equatorial diameters from 17.5 to 28 mm for each of the standard non-notched COMS plaques with silastic inserts. The COMS plaques were fully loaded with uniform activity, centered on the tumor, and prescribed to a common tumor dose (85 Gy/100 hours). Variations in the calculated doses to normal structures were examined to see if the changes were significant. Results: The calculated dose to normal structures show a marked dependence on eye geometry. This is exemplified by fovea dose which more than doubled in the smaller eyes and nearly halved in the larger model. Additional significant dependence was found in plaque size on the calculated dose in spite of all plaques giving the same dose to the prescription point. Conclusion: The variation in dose with eye dimension fully justifies the addition of a high resolution ocular CT to the planning technique. Additional attention must be made to plaque size beyond simply covering the tumor when considering normal tissue dose.

  14. TU-H-CAMPUS-TeP2-05: Selective Protection of Normal Tissue by Cerium Oxide Nanoparticles During Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ouyang, Z; Ngwa, W [University of Massachusetts Lowell, Lowell, MA (United States); Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (United States); Yasmin-Karim, S [Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (United States); Strack, G; Sajo, E [University of Massachusetts Lowell, Lowell, MA (United States)

    2016-06-15

    Purpose: Cerium oxide nanoparticles (CONPs) have unique pH dependent properties such that they act as a radical modulator. These properties may be used in radiation therapy (RT) to protect normal tissue. This work investigates the selective radioprotection of CONPs in-vitro and potential for in-situ delivery of CONPs in prostate cancer RT. Methods: i) Normal human umbilical vein endothelial cells (HUVEC) and human prostate cancer cells (PC-3) were treated with 0 or 2 ng/mL CONPs (NP size: 5 nm). 2 Gy of 100 kVp radiation was delivered to the cells 4 hours after the CONP treatment. Cell viability was checked 48 hours later using MTS assays. ii) A prostate tumor was modeled as a 2-cm diameter sphere. CONPs were proposed to be loaded in a hollow radiotherapy fiducial marker. The concentration profile for the CONPs within the tumor was modeled with a previously validated diffusion equation employed in other studies for nanoparticles 10 nm or less. Results: i) Without radiation, cell viability was above 90% when treated with 2 ng/mL CONPs for both HUVEC and PC-3. After irradiation, a slightly higher viability was observed in HUVEC with CONPs than the ones without CONPs, and this effect was not observed in PC-3. ii) Based on the calculations, 2 ng/mL of CONPs could be delivered to normal cells by diffusion with a 1 µg/mL initial concentration within two weeks. Conclusion: We conclude that CONPs can provide selective radioprotection. The delivery of needed concentrations of CONPs is feasible via in-situ release from radiotherapy biomaterials (e.g. fiducials) loaded with the CONPs.

  15. Development of a Lyman-α Imaging Solar Telescope for the Satellite

    Directory of Open Access Journals (Sweden)

    M. Jang

    2005-09-01

    Full Text Available Long term observations of full-disk Lyman-α irradiance have been made by the instruments on various satellites. In addition, several sounding rockets dating back to the 1950s and up through the present have measured the Lyman-α irradiance. Previous full disk Lyman-α images of the sun have been very interesting and useful scientifically, but have been only five-minute ``snapshots" obtained on sounding rocket flights. All of these observations to date have been snapshots, with no time resolution to observe changes in the chromospheric structure as a result of the evolving magnetic field, and its effect on the Lyman-α intensity. The Lyman-α Imaging Solar Telescope(LIST can provide a unique opportunity for the study of the sun in the Lyman-α region with the high time and spatial resolution for the first time. Up to the 2nd year development, the preliminary design of the optics, mechanical structure and electronics system has been completed. Also the mechanical structure analysis, thermal analysis were performed and the material for the structure was chosen as a result of these analyses. And the test plan and the verification matrix were decided. The operation systems, technical and scientific operation, were studied and finally decided. Those are the technical operation, mechanical working modes for the observation and safety, the scientific operation and the process of the acquired data. The basic techniques acquired through the development of satellite based solar telescope are essential for the construction of space environment forecast system in the future. The techniques which we developed through this study, like mechanical, optical and data processing techniques, could be applied extensively not only to the process of the future production of flight models of this kind, but also to the related industries. Also, we can utilize the scientific achievements which are obtained throughout the project. And these can be utilized to build a high

  16. Lyman alpha emission in nearby star-forming galaxies with the lowest metallicities and the highest [OIII]/[OII] ratios

    Science.gov (United States)

    Izotov, Yuri

    2017-08-01

    The Lyman alpha line of hydrogen is the strongest emission line in galaxies and the tool of predilection for identifying and studying star-forming galaxies over a wide range of redshifts, especially in the early universe. However, it has become clear over the years that not all of the Lyman alpha radiation escapes, due to its resonant scattering on the interstellar and intergalactic medium, and absorption by dust. Although our knowledge of the high-z universe depends crucially on that line, we still do not have a complete understanding of the mechanisms behind the production, radiative transfer and escape of Lyman alpha in galaxies. We wish here to investigate these mechanisms by studying the properties of the ISM in a unique sample of 8 extreme star-forming galaxies (SFGs) that have the highest excitation in the SDSS spectral data base. These dwarf SFGs have considerably lower stellar masses and metallicities, and higher equivalent widths and [OIII]5007/[OII]3727 ratios compared to all nearby SFGs with Lyman alpha emission studied so far with COS. They are, however, very similar to the dwarf Lyman alpha emitters at redshifts 3-6, which are thought to be the main sources of reionization in the early Universe. By combining the HST/COS UV data with data in the optical range, and using photoionization and radiative transfer codes, we will be able to study the properties of the Lyman alpha in these unique objects, derive column densities of the neutral hydrogen N(HI) and compare them with N(HI) obtained from the HeI emission-line ratios in the optical spectra. We will derive Lyman alpha escape fractions and indirectly Lyman continuum escape fractions.

  17. ORO dental complications of radiotherapy

    International Nuclear Information System (INIS)

    Kaumuri, Sunil

    2014-01-01

    Radiation and radioactivity were discovered more than 100 years ago. Since then, radiation has become important in cancer treatment. Approximately one million people will develop invasive cancer each year. Of these, 40% will receive curative benefit from surgery, radiation, chemotherapy, or a combination modality. Normal body tissues vary in their response to radiation. As with tumors, normal tissues in which cells are quickly dividing may be affected. This causes some of the side effects of radiation treatment. Since radiation is a local treatment, side effects depend on the area of the body being treated. The early effects of radiation may be seen a few days or weeks after treatments have started and may go on for several weeks after treatments have ended. Other effects may not show up until months, or even years, later. As radiotherapy is a viable treatment modality for head and neck cancer, however a wide range of potentially debilitating dental complications may accompany this treatment. The orofacial tissues of dental significance that may be affected by head and neck radiotherapy are the salivary glands, mucous membranes, taste buds, bone and teeth. (author)

  18. New constraints on Lyman-α opacity using 92 quasar lines of sight

    Science.gov (United States)

    Bosman, Sarah E. I.; Fan, Xiaohui; Jiang, Linhua; Reed, Sophie; Matsuoka, Yoshiki; Becker, George; Rorai, Albert

    2018-05-01

    The large scatter in Lyman-α opacity at z > 5.3 has been an ongoing mystery, prompting a flurry of numerical models. A uniform ultra-violet background has been ruled out at those redshifts, but it is unclear whether any proposed models produce sufficient inhomogeneities. In this paper we provide an update on the measurement which first highlighted the issue: Lyman-α effective optical depth along high-z quasar lines of sight. We nearly triple on the previous sample size in such a study thanks to the cooperation of the DES-VHS, SHELLQs, and SDSS collaborations as well as new reductions and spectra. We find that a uniform UVB model is ruled out at 5.1 < z < 5.3, as well as higher redshifts, which is perplexing. We provide the first such measurements at z ~ 6. None of the numerical models we confronted to this data could reproduce the observed scatter.

  19. A Sounding Rocket Experiment for the Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP)

    Science.gov (United States)

    Kubo, M.; Kano, R.; Kobayashi, K.; Bando, T.; Narukage, N.; Ishikawa, R.; Tsuneta, S.; Katsukawa, Y.; Ishikawa, S.; Suematsu, Y.; Hara, H.; Shimizu, T.; Sakao, T.; Ichimoto, K.; Goto, M.; Holloway, T.; Winebarger, A.; Cirtain, J.; De Pontieu, B.; Casini, R.; Auchère, F.; Trujillo Bueno, J.; Manso Sainz, R.; Belluzzi, L.; Asensio Ramos, A.; Štěpán, J.; Carlsson, M.

    2014-10-01

    A sounding-rocket experiment called the Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP) is presently under development to measure the linear polarization profiles in the hydrogen Lyman-alpha (Lyα) line at 121.567 nm. CLASP is a vacuum-UV (VUV) spectropolarimeter to aim for first detection of the linear polarizations caused by scattering processes and the Hanle effect in the Lyα line with high accuracy (0.1%). This is a fist step for exploration of magnetic fields in the upper chromosphere and transition region of the Sun. Accurate measurements of the linear polarization signals caused by scattering processes and the Hanle effect in strong UV lines like Lyα are essential to explore with future solar telescopes the strength and structures of the magnetic field in the upper chromosphere and transition region of the Sun. The CLASP proposal has been accepted by NASA in 2012, and the flight is planned in 2015.

  20. Determination of magnetic field direction in tokamaks from laser-induced Lyman-α fluorescence

    International Nuclear Information System (INIS)

    Voslamber, D.

    1988-04-01

    Resonant laser scattering in the Lyman-α line of hydrogen is investigated as a possible tool for measuring the magnetic field direction in tokamak plasmas. The method is based on the depolarisation-dependence of the scattering process. Limitations arising from depolarising collisions are studied in detail by employing a previously developed theory for the collisional redistribution of light. An error analysis is performed to derive the expected experimental precision under various plasma conditions and for laser energies ranging between 1 micronJ and 10 mJ. This analysis also includes the measurement of neutral hydrogen densities. It is shown that with presently available laser powers application of the method would be restricted to the border regions of the plasma. Application to the central regions would require further developments in laser technology, especially with regard to higher powers at the wavelength of Lyman-α and (or) to fast repetition rates

  1. Clinical Validation of Atlas-Based Auto-Segmentation of Multiple Target Volumes and Normal Tissue (Swallowing/Mastication) Structures in the Head and Neck

    International Nuclear Information System (INIS)

    Teguh, David N.; Levendag, Peter C.; Voet, Peter W.J.; Al-Mamgani, Abrahim; Han Xiao; Wolf, Theresa K.; Hibbard, Lyndon S.; Nowak, Peter; Akhiat, Hafid; Dirkx, Maarten L.P.; Heijmen, Ben J.M.; Hoogeman, Mischa S.

    2011-01-01

    . Conclusion: Multiple-subject ABAS of computed tomography images proved to be a useful novel tool in the rapid delineation of target and normal tissues. Although editing of the autocontours is inevitable, a substantial time reduction was achieved using editing, instead of manual contouring (180 vs. 66 min).

  2. Clinical Validation of Atlas-Based Auto-Segmentation of Multiple Target Volumes and Normal Tissue (Swallowing/Mastication) Structures in the Head and Neck

    Energy Technology Data Exchange (ETDEWEB)

    Teguh, David N. [Department of Radiation Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Levendag, Peter C., E-mail: p.levendag@erasmusmc.nl [Department of Radiation Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Voet, Peter W.J.; Al-Mamgani, Abrahim [Department of Radiation Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Han Xiao; Wolf, Theresa K.; Hibbard, Lyndon S. [Elekta-CMS Software, Maryland Heights, MO 63043 (United States); Nowak, Peter; Akhiat, Hafid; Dirkx, Maarten L.P.; Heijmen, Ben J.M.; Hoogeman, Mischa S. [Department of Radiation Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands)

    2011-11-15

    . Conclusion: Multiple-subject ABAS of computed tomography images proved to be a useful novel tool in the rapid delineation of target and normal tissues. Although editing of the autocontours is inevitable, a substantial time reduction was achieved using editing, instead of manual contouring (180 vs. 66 min).

  3. Late change of normal tissue treated either by high dose rate or low dose rate interstitial brachytherapy. A retrospective comparative study on oral and oropharyngeal mucosa

    International Nuclear Information System (INIS)

    Nose, Takayuki; Koizumi, Masahiko; Nishiyama, Kinji; Inoue, Toshihiko

    2002-01-01

    The purpose of this study was to compare late changes of normal tissue treated either by high dose rate (HDR) or low dose rate (LDR) interstitial brachytherapy. For HDR group, 22 oropharynx cancer patients who were treated by HDR Ir-192 interstitial brachytherapy with/without external beam radiotherapy in Osaka (Osaka Medical Center for Cancer and Cardiovascular Diseases and Osaka University Hospital) during June 1994 through April 2000 and came to the follow-up clinics during July 2000 through December 2000 were studied. For LDR group, 26 oropharynx cancer patients who were treated by LDR Ir-192 interstitial brachytherapy with/without external beam radiotherapy in Nancy (Centre Alexis Vautrin) during February 1989 through July 1998 and came to the follow-up clinics during April 1999 through July 1999 were studied. The standard HDR schedules were 54 Gy/9 fr/5-6 days for monotherapy and 18-24 Gy/3-4 fr/2-3 days following 45 Gy external beam radiotherapy. The standard LDR schedules were 65 Gy/5-6 days for monotherapy and 15-25 Gy/2-3 days following 50 Gy external beam radiotherapy. For evaluation of the late changes, we scored the mucosal and muscular changes inside the treated volume using the modified Dische score system and the RTOG/EORTC late radiation morbidity scoring scheme. For 6 items of the modified Dische score system, no significant difference was found between HDR and LDR groups. For the remaining 2 items (pallor, mobility impairment of faucial pillars), LDR group showed higher scores (p=0.010, 0.002). LDR group showed a trend toward higher scores for the RTOG/EORTC scheme (p=0.059). Some predict late effects by HDR interstitial brachytherapy to be severer than by LDR because no dose-rate effects can be expected. Our study, however, showed at least equivalent or even milder late changes by HDR. Appropriate fractionation schedule and extra geometrical sparing effects by optimized dose distribution of HDR group might result in milder late changes. With our

  4. SU-E-T-417: The Impact of Normal Tissue Constraints On PTV Dose Homogeneity for Intensity Modulated Radiotherapy (IMRT), Volume Modulated Arc Therapy (VMAT) and Tomotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Peng, J; McDonald, D; Ashenafi, M; Ellis, A; Vanek, K [Medical University of South Carolina, Charleston, SC (United States)

    2014-06-01

    Purpose: Complex intensity modulated arc therapy tends to spread low dose to normal tissue(NT)regions to obtain improved target conformity and homogeneity and OAR sparing.This work evaluates the trade-offs between PTV homogeneity and reduction of the maximum dose(Dmax)spread to NT while planning of IMRT,VMAT and Tomotherapy. Methods: Ten prostate patients,previously planned with step-and-shoot IMRT,were selected.To fairly evaluate how PTV homogeneity was affected by NT Dmax constraints,original IMRT DVH objectives for PTV and OARs(femoral heads,and rectal and bladder wall)applied to 2 VMAT plans in Pinnacle(V9.0), and Tomotherapy(V4.2).The only constraint difference was the NT which was defined as body contours excluding targets,OARs and dose rings.NT Dmax constraint for 1st VMAT was set to the prescription dose(Dp).For 2nd VMAT(VMAT-NT)and Tomotherapy,it was set to the Dmax achieved in IMRT(~70-80% of Dp).All NT constraints were set to the lowest priority.Three common homogeneity indices(HI),RTOG-HI=Dmax/Dp,moderated-HI=D95%/D5% and complex-HI=(D2%-D98%)/Dp*100 were calculated. Results: All modalities with similar dosimetric endpoints for PTV and OARs.The complex-HI shows the most variability of indices,with average values of 5.9,4.9,9.3 and 6.1 for IMRT,VMAT,VMAT-NT and Tomotherapy,respectively.VMAT provided the best PTV homogeneity without compromising any OAR/NT sparing.Both VMAT-NT and Tomotherapy,planned with more restrictive NT constraints,showed reduced homogeneity,with VMAT-NT showing the worst homogeneity(P<0.0001)for all HI.Tomotherapy gave the lowest NT Dmax,with slightly decreased homogeneity compared to VMAT. Finally, there was no significant difference in NT Dmax or Dmean between VMAT and VMAT-NT. Conclusion: PTV HI is highly dependent on permitted NT constraints. Results demonstrated that VMAT-NT with more restrictive NT constraints does not reduce Dmax NT,but significantly receives higher Dmax and worse target homogeneity.Therefore, it is critical

  5. Are the brightest Lyman Alpha Emitters at zD5.7 primeval galaxies?

    Science.gov (United States)

    Lidman, Christopher; Hayes, Matthew; Jones, Heath; Meisenheimer, Klaus; Tapken, Christian; Westra, Eduard

    2009-04-01

    Wide-field, narrow-band surveys have proven to be effective at finding very high redshift galaxies that emit brightly in the Lyman alpha line - the so-called Lyman alpha emitters (LAEs). It was through this technique that the most distant spectroscopically confirmed galaxy, a galaxy at zD6.96 (Iye et al. 2006), was discovered. Considerable effort is currently being spent on discovering these galaxies at ever higher redshifts by extending this technique into the near-IR. In contrast to this effort, there has been relatively little work on understanding these galaxies. In particular, how do LAEs relate to other high redshift galaxies, such as those discovered through drop out techniques, and, more importantly, what role LAEs play in re-ionising the universe, if any. We recently discovered two extremely luminous LAEs at zD5.7. These LAEs are among the brightest LAEs ever discovered at this redshift. In a recent paper by Mao et al. (2007), the brightest LAEs are associated to the most massive halos. One of these targets was successfully observed with the IRAC 3.6 micron imager on Spitzer during cycle 5. These data, when combined with constraints that we derive from our deep ground-based spectroscopic data, indicate that the bulk of the flux at 3.6 microns comes from a stellar population that is considserably older than the stars that dominate the flux in the UV. We propose to complete the project and image the second target. These data will enable us to estimate the age and mass of the stellar burst that produces the Lyman alpha line, to estimate the contribution from an older stellar population and to estimate the fraction of Lyman continuum photons that escape the galaxy and are thus available to re-ionise the universe.

  6. Performance Characterization of UV Science Cameras Developed for the Chromospheric Lyman-Alpha Spectro-Polarimeter

    Science.gov (United States)

    Champey, P.; Kobayashi, K.; Winebarger, A.; Cirtain, J.; Hyde, D.; Robertson, B.; Beabout, D.; Beabout, B.; Stewart, M.

    2014-01-01

    The NASA Marshall Space Flight Center (MSFC) has developed a science camera suitable for sub-orbital missions for observations in the UV, EUV and soft X-ray. Six cameras will be built and tested for flight with the Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP), a joint National Astronomical Observatory of Japan (NAOJ) and MSFC sounding rocket mission. The goal of the CLASP mission is to observe the scattering polarization in Lyman-alpha and to detect the Hanle effect in the line core. Due to the nature of Lyman-alpha polarization in the chromosphere, strict measurement sensitivity requirements are imposed on the CLASP polarimeter and spectrograph systems; science requirements for polarization measurements of Q/I and U/I are 0.1 percent in the line core. CLASP is a dual-beam spectro-polarimeter, which uses a continuously rotating waveplate as a polarization modulator, while the waveplate motor driver outputs trigger pulses to synchronize the exposures. The CCDs are operated in frame-transfer mode; the trigger pulse initiates the frame transfer, effectively ending the ongoing exposure and starting the next. The strict requirement of 0.1 percent polarization accuracy is met by using frame-transfer cameras to maximize the duty cycle in order to minimize photon noise. Coating the e2v CCD57-10 512x512 detectors with Lumogen-E coating allows for a relatively high (30 percent) quantum efficiency at the Lyman-alpha line. The CLASP cameras were designed to operate with 10 e-/pixel/second dark current, 25 e- read noise, a gain of 2.0 +/- 0.5 and 1.0 percent residual non-linearity. We present the results of the performance characterization study performed on the CLASP prototype camera; dark current, read noise, camera gain and residual non-linearity.

  7. Small-scale structure and the Lyman-α forest baryon acoustic oscillation feature

    Science.gov (United States)

    Hirata, Christopher M.

    2018-02-01

    The baryon-acoustic oscillation (BAO) feature in the Lyman-α forest is a key probe of the cosmic expansion rate at redshifts z ˜ 2.5, well before dark energy is believed to have become significant. A key advantage of the BAO as a standard ruler is that it is a sharp feature and hence is more robust against broad-band systematic effects than other cosmological probes. However, if the Lyman-α forest transmission is sensitive to the initial streaming velocity of the baryons relative to the dark matter, then the BAO peak position can be shifted. Here we investigate this sensitivity using a suite of hydrodynamic simulations of small regions of the intergalactic medium with a range of box sizes and physics assumptions; each simulation starts from initial conditions at the kinematic decoupling era (z ˜ 1059), undergoes a discrete change from neutral gas to ionized gas thermal evolution at reionization (z ˜ 8), and is finally processed into a Lyman-α forest transmitted flux cube. Streaming velocities suppress small-scale structure, leading to less violent relaxation after reionization. The changes in the gas distribution and temperature-density relation at low redshift are more subtle, due to the convergent temperature evolution in the ionized phase. The change in the BAO scale is estimated to be of the order of 0.12 per cent at z = 2.5; some of the major uncertainties and avenues for future improvement are discussed. The predicted streaming velocity shift would be a subdominant but not negligible effect (of order 0.26σ) for the upcoming DESI Lyman-α forest survey, and exceeds the cosmic variance floor.

  8. Lyman-alpha transit observations of the warm rocky exoplanet GJ1132b

    Science.gov (United States)

    Waalkes, William; Berta-Thompson, Zachory K.; Charbonneau, David; Irwin, Jonathan; Newton, Elisabeth; Dittmann, Jason; Bourrier, Vincent; Ehrenreich, David; Kempton, Eliza; Will

    2018-06-01

    GJ1132b is one of the few known Earth-sized planets, and at 12pc away it is also one of the closest known transiting planets. With an equilibrium temperature of 500 K, this planet is too hot to be habitable but we can use it to learn about the presence and volatile content of rocky planet atmospheres around M dwarf stars. Using Hubble STIS spectra obtained during primary transit, we search for a Lyman-α transit. If we were to observe a deep Lyman-α transit, that would indicate the presence of a neutral hydrogen envelope flowing from GJ1132b. On the other hand, ruling out deep absorption from neutral hydrogen may indicate that this planet has either retained its volatiles or lost them very early in the star’s life. We carry out this analysis by extracting 1D spectra from the STIS pipeline, splitting the time-tagged spectra into higher resolution samples, and producing light curves of the red and blue wings of the Lyman-α line. We fit for the baseline stellar flux and transit depths in order to constrain the characteristics of the cloud of neutral hydrogen gas that may surround the planet. We do not conclusively detect a transit but the results provide an upper limit for the transit depth. We also analyze the stellar variability and Lyman-α spectrum of GJ1132, a slowly-rotating 0.18 solar mass M dwarf with previously uncharacterized UV activity. Understanding the role that UV variability plays in planetary atmospheres and volatile retention is crucial to assess atmospheric evolution and the habitability of cooler rocky planets.

  9. The Lyman Alpha Imaging-Monitor Experiment (LAIME) for TESIS/CORONAS-PHOTON

    Science.gov (United States)

    Damé, L.; Koutchmy, S.; Kuzin, S.; Lamy, P.; Malherbe, J.-M.; Noëns, J.-C.

    LAIME the Lyman Alpha Imaging-Monitor Experiment is a remarkably simple no mechanisms and compact 100x100x400 mm full Sun imager to be flown with TESIS on the CORONAS-PHOTON mission launch expected before mid-2008 As such it will be the only true chromospheric imager to be flown in the next years supporting TESIS EUV-XUV imaging SDO and the Belgian LYRA Lyman Alpha flux monitor on the ESA PROBA-2 microsatellite launch expected in September 2007 We will give a short description of this unique O60 mm aperture imaging telescope dedicated to the investigating of the magnetic sources of solar variability in the UV and chromospheric and coronal disruptive events rapid waves Moreton waves disparitions brusques of prominences filaments eruptions and CMEs onset The resolution pixel is 2 7 arcsec the field of view 1 4 solar radius and the acquisition cadence could be as high as 1 image minute The back thinned E2V CCD in the focal plane is using frame transfer to avoid shutter and mechanisms Further more the double Lyman Alpha filtering allows a 40 AA FWHM bandwidth and excellent rejection yet providing a vacuum seal design of the telescope MgF2 entrance window Structural stability of the telescope focal length 1 m is preserved by a 4-INVAR bars design with Aluminium compensation in a large pm 10 o around 20 o

  10. Fragmentation inside atomic cooling haloes exposed to Lyman-Werner radiation

    Science.gov (United States)

    Regan, John A.; Downes, Turlough P.

    2018-04-01

    Supermassive stars born in pristine environments in the early Universe hold the promise of being the seeds for the supermassive black holes observed as high redshift quasars shortly after the epoch of reionisation. H2 suppression is thought to be crucial in order to negate normal Population III star formation and allow high accretion rates to drive the formation of supermassive stars. Only in the cases where vigorous fragmentation is avoided will a monolithic collapse be successful, giving rise to a single massive central object. We investigate the number of fragmentation sites formed in collapsing atomic cooling haloes subject to various levels of background Lyman-Werner flux. The background Lyman-Werner flux manipulates the chemical properties of the gas in the collapsing halo by destroying H2. We find that only when the collapsing gas cloud shifts from the molecular to the atomic cooling regime is the degree of fragmentation suppressed. In our particular case, we find that this occurs above a critical Lyman-Werner background of J ˜ 10 J21. The important criterion being the transition to the atomic cooling regime rather than the actual value of J, which will vary locally. Once the temperature of the gas exceeds T ≳ 104 K and the gas transitions to atomic line cooling, then vigorous fragmentation is strongly suppressed.

  11. Investigating the Lyman photon escape in local starburst galaxies with the Cosmic Origins Spectrograph ★

    Science.gov (United States)

    Hernandez, Svea; Leitherer, Claus; Boquien, Médéric; Buat, Véronique; Burgarella, Denis; Calzetti, Daniela; Noll, Stefan

    2018-04-01

    We present a study of 7 star-forming galaxies from the Cosmic Evolution Survey (COSMOS) observed with the Cosmic Origins Spectrograph (COS) on board the Hubble Space Telescope (HST). The galaxies are located at relatively low redshifts, z ˜0.3, with morphologies ranging from extended and disturbed to compact and smooth. To complement the HST observations we also analyze observations taken with the VIMOS spectrograph on the Very Large Telescope (VLT). In our galaxy sample we identify three objects with double peak Lyman-α profiles similar to those seen in Green Pea compact galaxies and measure peak separations of 655, 374, and 275 km s-1. We measure Lyman-α escape fractions with values ranging between 5-13%. Given the low flux levels in the individual COS exposures we apply a weighted stacking approach to obtain a single spectrum. From this COS combined spectrum we infer upper limits for the absolute and relative Lyman continuum escape fractions of f_abs(LyC) = 0.4^{+10.1}_{-0.4}% and f_res(LyC) = 1.7^{+15.2}_{-1.7}%, respectively. Finally, we find that most of these galaxies have moderate UV and optical SFRs (SFRs ≲ 10 M⊙ yr-1).

  12. Importance of protocol target definition on the ability to spare normal tissue: An IMRT and 3D-CRT planning comparison for intraorbital tumors

    International Nuclear Information System (INIS)

    Hein, Patrick A.; Gladstone, David J.; Bellerive, Marc R.; Hug, Eugen B.

    2005-01-01

    Purpose: We selected five intraorbital tumor sites that are frequently found in clinical practice in children diagnosed with orbital rhabdomyosarcoma and performed three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated photon radiotherapy (IMRT) planning. Results of target coverage and doses to critical structures were compared. The goal of this study was to evaluate and to document realistic expectations as to organ-sparing capabilities of modern radiation therapy planning technologies with a focus on lens-sparing irradiation. Furthermore, we investigated potential added benefits of IMRT compared with 3D-CRT and the influence of protocol volume criteria definitions on the ability to obtain normal tissue dose sparing using the orbit as an example of a complex anatomic site. Methods and Materials: The five intraorbital tumor sites were placed retrobulbar, temporal, nasal, in the upper inner and upper outer quadrant, the latter two more complex in shape. Gross tumor volume (GTV), clinical target volume (CTV), and planning target volume (PTV) were defined in image-fused computed tomography and magnetic resonance data sets. 3D-CRT and IMRT photon plans, using equal beam angles and collimation for direct comparison, were designed to 45 Gy prescription dose according to Intergroup Rhabdomyosarcoma Study Group-D9602 (IRSG-D9602) protocol (Intergroup Rhabdomyosarcoma Study V [IRS-V] protocol) for Stage I, Clinical Group 3 orbital rhabdomyosarcoma. To compare the impact of changed target definitions in IMRT planning, additional IMRT plans were generated using modified volume and dose coverage criteria. The minimum dose constraint (95%) of the PTV was substituted by a required minimum volume coverage (95%) with the prescribed dose. Dose-volume histograms (DVHs) were obtained, including target volumes, lens, optic nerves, optic chiasm, lacrimal gland, bony orbit, pituitary gland, frontal and temporal lobes. Results: Protocol target volume coverage criteria

  13. Normal tissue tolerance to external beam radiation therapy: The stomach; Dose de tolerance a l'irradiation des tissus sains: l'estomac

    Energy Technology Data Exchange (ETDEWEB)

    Oberdiac, P. [Service de radiotherapie, hopital de Bellevue, CHU de Saint-Etienne, 42 - Saint-Etienne (France); Mineur, L. [Unite d' oncologie digestive et radiotherapie, institut Sainte-Catherine, 84 - Avignon (France)

    2010-07-15

    In the following article, we will discuss general issues relating to acute and late gastric's radiation toxicities. The tolerance of the stomach to complete or partial organ irradiation is more un-appreciated than for most other organs. We consulted the Medline database via PubMed and used the key words gastric - radiotherapy - toxicity. Currently, 60 Gy or less is prescribed in gastric radiation therapy. Acute clinical toxicity symptoms are predominantly nausea and vomiting. Although there is a general agreement that the whole stomach tolerance is for doses of 40 to 45 Gy without unacceptable complication, it is well established that a stomach dose of 35 Gy increases the risk of ulcer complications. (authors)

  14. A Comparative Evaluation of Normal Tissue Doses for Patients Receiving Radiation Therapy for Hodgkin Lymphoma on the Childhood Cancer Survivor Study and Recent Children's Oncology Group Trials

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Rachel; Ng, Angela [Department of Radiation Therapy, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Constine, Louis S. [Department of Radiation Oncology, University of Rochester, Rochester, New York (United States); Stovall, Marilyn [Division of Radiation Oncology, Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Armstrong, Gregory T. [Epidemiology/Cancer Control Department, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Neglia, Joseph P. [Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota (United States); Friedman, Debra L. [Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Kelly, Kara [Division of Pediatric Hematology/Oncology/Stem Cell Transplant, Department of Pediatrics, Columbia University Medical Center, New York, New York (United States); FitzGerald, Thomas J. [Department of Radiation Oncology, University of Massachusetts Medical School, Worcester, Massachusetts (United States); Imaging and Radiation Oncology Core Group, Lincoln, Rhode Island (United States); Hodgson, David C., E-mail: David.hodgson@rmp.uhn.on.ca [Department of Radiation Oncology, University of Toronto, and Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario (Canada)

    2016-06-01

    Purpose: Survivors of pediatric Hodgkin lymphoma (HL) are recognized to have an increased risk of delayed adverse health outcomes related to radiation therapy (RT). However, the necessary latency required to observe these late effects means that the estimated risks apply to outdated treatments. We sought to compare the normal tissue dose received by children treated for HL and enrolled in the Childhood Cancer Survivor Study (CCSS) (diagnosed 1970-1986) with that of patients treated in recent Children's Oncology Group (COG) trials (enrolled 2002-2012). Methods and Materials: RT planning data were obtained for 50 HL survivors randomly sampled from the CCSS cohort and applied to computed tomography planning data sets to reconstruct the normal tissue dosimetry. For comparison, the normal tissue dosimetry data were obtained for all 191 patients with full computed tomography–based volumetric RT planning on COG protocols AHOD0031 and AHOD0831. Results: For early-stage patients, the mean female breast dose in the COG patients was on average 83.5% lower than that for CCSS patients, with an absolute reduction of 15.5 Gy. For advanced-stage patients, the mean breast dose was decreased on average by 70% (11.6 Gy average absolute dose reduction). The mean heart dose decreased on average by 22.9 Gy (68.6%) and 17.6 Gy (56.8%) for early- and advanced-stage patients, respectively. All dose comparisons for breast, heart, lung, and thyroid were significantly lower for patients in the COG trials than for the CCSS participants. Reductions in the prescribed dose were a major contributor to these dose reductions. Conclusions: These are the first data quantifying the significant reduction in the normal tissue dose using actual, rather than hypothetical, treatment plans for children with HL. These findings provide useful information when counseling families regarding the risks of contemporary RT.

  15. Intensity modulated radiotherapy and 3D conformal radiotherapy for whole breast irradiation: a comparative dosimetric study and introduction of a novel qualitative index for plan evaluation, the normal tissue index

    Energy Technology Data Exchange (ETDEWEB)

    Yim, Jackie; Suttie, Clare; Bromley, Regina; Morgia, Marita; Lamoury, Gillian [Department of Radiation Oncology, Royal North Shore Hospital, St Leonards, New South Wales (Australia)

    2015-09-15

    We report on a retrospective dosimetric study, comparing 3D conformal radiotherapy (3DCRT) and hybrid intensity modulated radiotherapy (hIMRT). We evaluated plans based on their planning target volume coverage, dose homogeneity, dose to organs at risk (OARs) and exposure of normal tissue to radiation. The Homogeneity Index (HI) was used to assess the dose homogeneity in the target region, and we describe a new index, the normal tissue index (NTI), to assess the dose in the normal tissue inside the tangent treatment portal. Plans were generated for 25 early-stage breast cancer patients, using a hIMRT technique. These were compared with the 3DCRT plans of the treatment previously received by the patients. Plan quality was evaluated using the HI, NTI and dose to OARs. The hIMRT technique was significantly more homogenous than the 3DCRT technique, while maintaining target coverage. The hIMRT technique was also superior at minimising the amount of tissue receiving D{sub 105%} and above (P < 0.0001). The ipsilateral lung and contralateral breast maximum were significantly lower in the hIMRT plans (P < 0.05 and P < 0.005), but the 3DCRT technique achieved a lower mean heart dose in left-sided breast cancer patients (P < 0.05). Hybrid intensity modulated radiotherapy plans achieved improved dose homogeneity compared to the 3DCRT plans and superior outcome with regard to dose to normal tissues. We propose that the addition of both HI and NTI in evaluating the quality of intensity modulated radiotherapy (IMRT) breast plans provides clinically relevant comparators which more accurately reflect the new paradigm of treatment goals and outcomes in the era of breast IMRT.

  16. Intensity modulated radiotherapy and 3D conformal radiotherapy for whole breast irradiation: a comparative dosimetric study and introduction of a novel qualitative index for plan evaluation, the normal tissue index

    International Nuclear Information System (INIS)

    Yim, Jackie; Suttie, Clare; Bromley, Regina; Morgia, Marita; Lamoury, Gillian

    2015-01-01

    We report on a retrospective dosimetric study, comparing 3D conformal radiotherapy (3DCRT) and hybrid intensity modulated radiotherapy (hIMRT). We evaluated plans based on their planning target volume coverage, dose homogeneity, dose to organs at risk (OARs) and exposure of normal tissue to radiation. The Homogeneity Index (HI) was used to assess the dose homogeneity in the target region, and we describe a new index, the normal tissue index (NTI), to assess the dose in the normal tissue inside the tangent treatment portal. Plans were generated for 25 early-stage breast cancer patients, using a hIMRT technique. These were compared with the 3DCRT plans of the treatment previously received by the patients. Plan quality was evaluated using the HI, NTI and dose to OARs. The hIMRT technique was significantly more homogenous than the 3DCRT technique, while maintaining target coverage. The hIMRT technique was also superior at minimising the amount of tissue receiving D 105% and above (P < 0.0001). The ipsilateral lung and contralateral breast maximum were significantly lower in the hIMRT plans (P < 0.05 and P < 0.005), but the 3DCRT technique achieved a lower mean heart dose in left-sided breast cancer patients (P < 0.05). Hybrid intensity modulated radiotherapy plans achieved improved dose homogeneity compared to the 3DCRT plans and superior outcome with regard to dose to normal tissues. We propose that the addition of both HI and NTI in evaluating the quality of intensity modulated radiotherapy (IMRT) breast plans provides clinically relevant comparators which more accurately reflect the new paradigm of treatment goals and outcomes in the era of breast IMRT

  17. Correlations in the three-dimensional Lyman-alpha forest contaminated by high column density absorbers

    Science.gov (United States)

    Rogers, Keir K.; Bird, Simeon; Peiris, Hiranya V.; Pontzen, Andrew; Font-Ribera, Andreu; Leistedt, Boris

    2018-05-01

    Correlations measured in three dimensions in the Lyman-alpha forest are contaminated by the presence of the damping wings of high column density (HCD) absorbing systems of neutral hydrogen (H I; having column densities N(H I) > 1.6 × 10^{17} atoms cm^{-2}), which extend significantly beyond the redshift-space location of the absorber. We measure this effect as a function of the column density of the HCD absorbers and redshift by measuring three-dimensional (3D) flux power spectra in cosmological hydrodynamical simulations from the Illustris project. Survey pipelines exclude regions containing the largest damping wings. We find that, even after this procedure, there is a scale-dependent correction to the 3D Lyman-alpha forest flux power spectrum from residual contamination. We model this residual using a simple physical model of the HCD absorbers as linearly biased tracers of the matter density distribution, convolved with their Voigt profiles and integrated over the column density distribution function. We recommend the use of this model over existing models used in data analysis, which approximate the damping wings as top-hats and so miss shape information in the extended wings. The simple `linear Voigt model' is statistically consistent with our simulation results for a mock residual contamination up to small scales (|k| account for the effect of the highest column density absorbers on the smallest scales (e.g. |k| > 0.4 h Mpc^{-1} for small damped Lyman-alpha absorbers; HCD absorbers with N(H I) ˜ 10^{21} atoms cm^{-2}). However, these systems are in any case preferentially removed from survey data. Our model is appropriate for an accurate analysis of the baryon acoustic oscillations feature. It is additionally essential for reconstructing the full shape of the 3D flux power spectrum.

  18. Lyman-continuum leakage as dominant source of diffuse ionized gas in the Antennae galaxy

    Science.gov (United States)

    Weilbacher, Peter M.; Monreal-Ibero, Ana; Verhamme, Anne; Sandin, Christer; Steinmetz, Matthias; Kollatschny, Wolfram; Krajnović, Davor; Kamann, Sebastian; Roth, Martin M.; Erroz-Ferrer, Santiago; Marino, Raffaella Anna; Maseda, Michael V.; Wendt, Martin; Bacon, Roland; Dreizler, Stefan; Richard, Johan; Wisotzki, Lutz

    2018-04-01

    The Antennae galaxy (NGC 4038/39) is the closest major interacting galaxy system and is therefore often studied as a merger prototype. We present the first comprehensive integral field spectroscopic dataset of this system, observed with the MUSE instrument at the ESO VLT. We cover the two regions in this system which exhibit recent star formation: the central galaxy interaction and a region near the tip of the southern tidal tail. In these fields, we detect HII regions and diffuse ionized gas to unprecedented depth. About 15% of the ionized gas was undetected by previous observing campaigns. This newly detected faint ionized gas is visible everywhere around the central merger, and shows filamentary structure. We estimate diffuse gas fractions of about 60% in the central field and 10% in the southern region. We are able to show that the southern region contains a significantly different population of HII regions, showing fainter luminosities. By comparing HII region luminosities with the HST catalog of young star clusters in the central field, we estimate that there is enough Lyman-continuum leakage in the merger to explain the amount of diffuse ionized gas that we detect. We compare the Lyman-continuum escape fraction of each HII region against emission line ratios that are sensitive to the ionization parameter. While we find no systematic trend between these properties, the most extreme line ratios seem to be strong indicators of density bounded ionization. Extrapolating the Lyman-continuum escape fractions to the southern region, we conclude that simply from the comparison of the young stellar populations to the ionized gas there is no need to invoke other ionization mechanisms than Lyman-continuum leaking HII regions for the diffuse ionized gas in the Antennae. FITS images and Table of HII regions are available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/611/A95 and at http://muse-vlt.eu/science/antennae/

  19. EFFECT OF HALO BIAS AND LYMAN LIMIT SYSTEMS ON THE HISTORY OF COSMIC REIONIZATION

    International Nuclear Information System (INIS)

    Kaurov, Alexander A.; Gnedin, Nickolay Y.

    2013-01-01

    We extend the existing analytical model of reionization by Furlanetto et al. to include the biasing of reionization sources and additional absorption by Lyman limit systems. Both effects enhance the original model in non-trivial ways, but do not change its qualitative features. Our model is, by construction, consistent with the observed evolution of the galaxy luminosity function at z ∼ 6 galaxies, the inadequacy of simulations and/or some of the observational constraints, or indicates an additional source of ionizing radiation at z > 8 remains to be seen.

  20. Normal tissue tolerance to external beam radiation therapy: Peripheral nerves; Dose de tolerance a l'irradiation des tissus sains: les nerfs peripheriques

    Energy Technology Data Exchange (ETDEWEB)

    Henriques de Figueiredo, B.; Dejean, C.; Sargos, P.; Kantor, G. [Departement de radiotherapie, institut Bergonie, centre regional de lutte contre le cancer, 33 - Bordeaux (France); Huchet, A.; Mamou, N. [Service d' oncologie medicale et de radiotherapie, CHU Saint-Andre, 33 - Bordeaux (France); Loiseau, H. [Service de neurochirurgie, CHU Pellegrin, 33 - Bordeaux (France)

    2010-07-15

    Plexopathies and peripheral neuropathies appear progressively and with several years delay after radiotherapy. These lesions are observed principally after three clinical situations: supraclavicular and axillar irradiations for breast cancer, pelvic irradiations for various pathologies and limb irradiations for soft tissue sarcomas. Peripheral nerves and plexus (brachial and lumbosacral) are described as serial structures and are supposed to receive less than a given maximum dose linked to the occurrence of late injury. Literature data, mostly ancient, define the maximum tolerable dose to a threshold of 60 Gy and highlight also a great influence of fractionation and high fraction doses. For peripheral nerves, most frequent late effects are pain with significant differences of occurrence between 50 and 60 Gy. At last, associated pathologies (diabetes, vascular pathology, neuropathy) and associated treatments have probably to be taken into account as additional factors, which may increase the risk of these late radiation complications. (authors)

  1. Analysis of coronal H I Lyman alpha measurements from a rocket flight on 1979 April 13

    Science.gov (United States)

    Withbroe, G. L.; Kohl, J. L.; Weiser, H.; Noci, G.; Munro, R. H.

    1982-01-01

    It is noted that measurements of the profiles of resonantly scattered hydrogen Lyman-alpha coronal radiation have been used in determining hydrogen kinetic temperatures from 1.5 to 4 solar radii from sun center in a quiet region of the corona. Proton temperatures derived using the line widths decrease with height from 2.6 x 10 to the 6th K at 1.5 solar radii to 1.2 x 10 to the 6th K at 4 solar radii. These measurements, together with temperatures for lower heights determined from earlier Skylab and eclipse data, suggest that there is a maximum in the quiet coronal proton temperature at about 1.5 solar radii. Comparison of measured Lyman-alpha intensities with those calculated using a representative model for the radial variation of the coronal electron density yields information on the magnitude of the electron temperature gradient and suggests that the solar wind flow was subsonic for distances less than 4 solar radii.

  2. The Sunburst Arc: Direct Lyman α escape observed in the brightest known lensed galaxy

    Science.gov (United States)

    Rivera-Thorsen, T. E.; Dahle, H.; Gronke, M.; Bayliss, M.; Rigby, J. R.; Simcoe, R.; Bordoloi, R.; Turner, M.; Furesz, G.

    2017-11-01

    We present rest-frame ultraviolet and optical spectroscopy of the brightest lensed galaxy yet discovered, at redshift z = 2.4. The source reveals a characteristic triple-peaked Lyman α profile that has been predicted in various theoretical works, but to our knowledge has not been unambiguously observed previously. The feature is well fit by a superposition of two components: a double-peak profile emerging from substantial radiative transfer, and a narrow, central component resulting from directly escaping Lyman α photons, but it is poorly fit by either component alone. We demonstrate that the feature is unlikely to contain contamination from nearby sources, and that the central peak is unaffected by radiative transfer effects except for very slight absorption. The feature is detected at signal-to-noise ratios exceeding 80 per pixel at line center, and bears strong resemblance to synthetic profiles predicted by numerical models. Based on observations obtained at the Magellan-I (Baade) Telescope at Las Campanas Observatory, Chile.

  3. GALEX-SELECTED LYMAN BREAK GALAXIES AT z ∼ 2: COMPARISON WITH OTHER POPULATIONS

    International Nuclear Information System (INIS)

    Haberzettl, L.; Williger, G.; Lehnert, M. D.; Nesvadba, N.; Davies, L.

    2012-01-01

    We present results of a search for bright Lyman break galaxies (LBGs) at 1.5 ≤ z ≤ 2.5 in the GOODS-S field using an NUV-dropout technique in combination with color selection. We derived a sample of 73 LBG candidates. We compare our selection efficiencies to BM/BX and BzK methods (techniques solely based on ground-based data sets), and find the NUV data to provide greater efficiency for selecting star-forming galaxies. We estimate LBG candidate ages, masses, star formation rates, and extinction from fitting PEGASE synthesis evolution models. We find that about 20% of our LBG candidates are comparable to infrared-luminous LBGs or submillimeter galaxies which are thought to be precursors of massive elliptical galaxies today. Overall, we can show that although BM/BX and BzK methods do identify star-forming galaxies at z ∼ 2, the sample they provide biases against those star-forming galaxies which are more massive and contain sizeable red stellar populations. A true Lyman break criterion at z ∼ 2 is therefore more directly comparable to the populations found at z ∼ 3, which does contain a red fraction.

  4. Bias of damped Lyman-α systems from their cross-correlation with CMB lensing

    Science.gov (United States)

    Alonso, D.; Colosimo, J.; Font-Ribera, A.; Slosar, A.

    2018-04-01

    We cross-correlate the positions of damped Lyman-α systems (DLAs) and their parent quasar catalog with a convergence map derived from the Planck cosmic microwave background (CMB) temperature data. We make consistent measurements of the lensing signal of both samples in both Fourier and configuration space. By interpreting the excess signal present in the DLA catalog with respect to the parent quasar catalog as caused by the large scale structure traced by DLAs, we are able to infer the bias of these objects: bDLA=2.6±0.9. These results are consistent with previous measurements made in cross-correlation with the Lyman-α forest, although the current noise in the lensing data and the low number density of DLAs limits the constraining power of this measurement. We discuss the robustness of the analysis with respect to a number different systematic effects and forecast prospects of carrying out this measurement with data from future experiments.

  5. Lyman Break Analogs: Constraints on the Formation of Extreme Starbursts at Low and High Redshift

    Science.gov (United States)

    Goncalves, Thiago S.; Overzier, Roderik; Basu-Zych, Antara; Martin, D. Christopher

    2011-01-01

    Lyman Break Analogs (LBAs), characterized by high far-UV luminosities and surface brightnesses as detected by GALEX, are intensely star-forming galaxies in the low-redshift universe (z approximately equal to 0.2), with star formation rates reaching up to 50 times that of the Milky Way. These objects present metallicities, morphologies and other physical properties similar to higher redshift Lyman Break Galaxies (LBGs), motivating the detailed study of LBAs as local laboratories of this high-redshift galaxy population. We present results from our recent integral-field spectroscopy survey of LBAs with Keck/OSIRIS, which shows that these galaxies have the same nebular gas kinematic properties as high-redshift LBGs. We argue that such kinematic studies alone are not an appropriate diagnostic to rule out merger events as the trigger for the observed starburst. Comparison between the kinematic analysis and morphological indices from HST imaging illustrates the difficulties of properly identifying (minor or major) merger events, with no clear correlation between the results using either of the two methods. Artificial redshifting of our data indicates that this problem becomes even worse at high redshift due to surface brightness dimming and resolution loss. Whether mergers could generate the observed kinematic properties is strongly dependent on gas fractions in these galaxies. We present preliminary results of a CARMA survey for LBAs and discuss the implications of the inferred molecular gas masses for formation models.

  6. Performance Characterization of the Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP) CCD Cameras

    Science.gov (United States)

    Joiner, R. K.; Kobayashi, K.; Winebarger, A. R.; Champey, P. R.

    2014-12-01

    The Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP) is a sounding rocket instrument which is currently being developed by NASA's Marshall Space Flight Center (MSFC) and the National Astronomical Observatory of Japan (NAOJ). The goal of this instrument is to observe and detect the Hanle effect in the scattered Lyman-Alpha UV (121.6nm) light emitted by the Sun's Chromosphere to make measurements of the magnetic field in this region. In order to make accurate measurements of this effect, the performance characteristics of the three on-board charge-coupled devices (CCDs) must meet certain requirements. These characteristics include: quantum efficiency, gain, dark current, noise, and linearity. Each of these must meet predetermined requirements in order to achieve satisfactory performance for the mission. The cameras must be able to operate with a gain of no greater than 2 e-/DN, a noise level less than 25e-, a dark current level which is less than 10e-/pixel/s, and a residual non-linearity of less than 1%. Determining these characteristics involves performing a series of tests with each of the cameras in a high vacuum environment. Here we present the methods and results of each of these performance tests for the CLASP flight cameras.

  7. Lyman-alpha clouds as a relic of primordial density fluctuations

    International Nuclear Information System (INIS)

    Bond, J.R.; Szalay, A.S.; Silk, J.

    1988-01-01

    Primordial density fluctuations are studied using a CDM model and primordial clouds some of which are expanding, driven by pressure gradients created when the medium is photionized, and some of which are massive enough to continue collapsing in spite of the pressure. Normalization of CDM models to the clustering properties on large scales are used to predict the parameters of collapsing clouds of subgalactic mass at early epochs. It is shown that the abundance and dimensions of these clouds are comparable to those of the Lyman-alpha systems. The evolutionary history of the clouds is computed, utilizing a spherically symmetric hydrodynamics code with the dark matter treated as a collisionless fluid, and the H I column density distribution is evaluated as a function of N(H I) and redshift. The observed cloud parameters come out naturally in the CDM model and suggest that Lyman-alpha clouds are the missing link between primordial density fluctuations and the formation of galaxies. 31 references

  8. GALEX-SELECTED LYMAN BREAK GALAXIES AT z {approx} 2: COMPARISON WITH OTHER POPULATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Haberzettl, L.; Williger, G. [Department of Physics and Astronomy, University of Louisville, Louisville KY 20492 (United States); Lehnert, M. D. [GEPI, Observatoire de Paris, UMR 8111 du CNRS, 5 Place Jules Janssen, 92195 Meudon (France); Nesvadba, N. [Institut d' Astrophysique Spatiale, CNRS, Universite Paris-Sud, Bat. 120-121, 91405 Orsay (France); Davies, L. [Department of Physics, H H Wills Physics Laboratory, University of Bristol, Tyndall Avenue, Bristol BS8 1TL (United Kingdom)

    2012-01-20

    We present results of a search for bright Lyman break galaxies (LBGs) at 1.5 {<=} z {<=} 2.5 in the GOODS-S field using an NUV-dropout technique in combination with color selection. We derived a sample of 73 LBG candidates. We compare our selection efficiencies to BM/BX and BzK methods (techniques solely based on ground-based data sets), and find the NUV data to provide greater efficiency for selecting star-forming galaxies. We estimate LBG candidate ages, masses, star formation rates, and extinction from fitting PEGASE synthesis evolution models. We find that about 20% of our LBG candidates are comparable to infrared-luminous LBGs or submillimeter galaxies which are thought to be precursors of massive elliptical galaxies today. Overall, we can show that although BM/BX and BzK methods do identify star-forming galaxies at z {approx} 2, the sample they provide biases against those star-forming galaxies which are more massive and contain sizeable red stellar populations. A true Lyman break criterion at z {approx} 2 is therefore more directly comparable to the populations found at z {approx} 3, which does contain a red fraction.

  9. Recovering the systemic redshift of galaxies from their Lyman-alpha line profile

    Science.gov (United States)

    Verhamme, A.; Garel, T.; Ventou, E.; Contini, T.; Bouché, N.; Herenz, E. C.; Richard, J.; Bacon, R.; Schmidt, K. B.; Maseda, M.; Marino, R. A.; Brinchmann, J.; Cantalupo, S.; Caruana, J.; Clément, B.; Diener, C.; Drake, A. B.; Hashimoto, T.; Inami, H.; Kerutt, J.; Kollatschny, W.; Leclercq, F.; Patrício, V.; Schaye, J.; Wisotzki, L.; Zabl, J.

    2018-04-01

    The Lyman alpha (Lyα) line of Hydrogen is a prominent feature in the spectra of star-forming galaxies, usually redshifted by a few hundreds of km s-1 compared to the systemic redshift. This large offset hampers follow-up surveys, galaxy pair statistics and correlations with quasar absorption lines when only Lyα is available. We propose diagnostics that can be used to recover the systemic redshift directly from the properties of the Lyα line profile. We use spectroscopic observations of Lyman-Alpha Emitters (LAEs) for which a precise measurement of the systemic redshift is available. Our sample contains 13 sources detected between z ≈ 3 and z ≈ 6 as part of various Multi Unit Spectroscopic Explorer (MUSE) Guaranteed Time Observations (GTO). We also include a compilation of spectroscopic Lyα data from the literature spanning a wide redshift range (z ≈ 0 - 8). First, restricting our analysis to double-peaked Lyα spectra, we find a tight correlation between the velocity offset of the red peak with respect to the systemic redshift, V_peak^red, and the separation of the peaks. Secondly, we find a correlation between V_peak^red and the full width at half maximum of the Lyα line. Fitting formulas, to estimate systemic redshifts of galaxies with an accuracy of ≤100 km s-1 when only the Lyα emission line is available, are given for the two methods.

  10. Analysis of coronal H I Lyman alpha measurements from a rocket flight on 1979 April 13

    International Nuclear Information System (INIS)

    Withbroe, G.L.; Kohl, J.L.; Weiser, H.; Noci, G.; Munro, R.H.

    1982-01-01

    Measurements of the profiles of resonantly scattered hydrogen Lyman-α coronal radiation have been used to determine hydrogen kinetic temperatures from 1.5 to 4 R/sub sun/ from Sun center in a quiet region of the corona. Proton temperatures derived from the line widths decrease with height from 2.6 x 10 6 K at r = 1.5 R/sub sun/ to 1.2 x 10 6 K at r = 4 R/sub sun/. These measurements combined with temperatures for lower heights determined from earlier Skylab and eclipse data suggest that there is a maximum in the quiet coronal proton temperature at about 1.5 R/sub sun/. Comparison of measured Lyman-α intensities with those calculated using a representative model for the radial variation of the coronal electron density provides information on the magnitude of the electron temperature gradient and suggests that the solar wind flow was subsonic for r<4 R/sub sun/ in the observed region. Comparison of the measured kinetic temperatures to the predictions of a simple two fluid model suggests that there is a small amount of proton heating and/or a nonthermal contribution to the motions of coronal protons between 1.5 and 4 R/sub sun/

  11. The Faint End of the Lyman Alpha Luminosity Function at 2 < z < 3.8

    Science.gov (United States)

    Devarakonda, Yaswant; Livermore, Rachael; Indahl, Briana; Wold, Isak; Davis, Dustin; Finkelstein, Steven

    2018-01-01

    Most current models predict that our universe is mostly composed of small, dim galaxies. Due to these galaxies being so faint, it is very difficult to study these types of galaxies outside of our local universe. This is particularly an issue for studying how these small galaxies evolved over their lifetimes. With the benefit of gravitational lensing, however, we are able to observe galaxies that are farther and fainter than ever before possible. In this particular study, we focus on Lyman-Alpha emitting galaxies between the redshifts of 2-3.8, so that we may study these galaxies during the epoch of peak star formation in the universe. We use the McDonald Observatory 2.7, Harlan Smith telescope with the VIRUS-P IFU spectrograph to observe several Hubble Frontier Field lensing clusters to spectroscopically discover faint galaxies over this redshift range. In addition to providing insight into the faint-end slope of the Lyman alpha luminosity function, the spectroscopic redshifts will allow us to better constrain the mass models of the foreground clusters, such as Abell 370, so that we may better understand lensing effects for this and future studies.

  12. Quantification of late complications after radiation therapy

    International Nuclear Information System (INIS)

    Jung, Horst; Beck-Bornholdt, Hans-Peter; Svoboda, Vladimir; Alberti, Winfried; Herrmann, Thomas

    2001-01-01

    Background: An increasing number of patients survive cancer after having received radiation therapy. Therefore, the occurrence of late normal tissue complications among long-term survivors is of particular concern. Methods: Sixty-three patients treated by radical surgery and irradiation for rectal carcinoma were subjected to an unconventional sandwich therapy. Preoperative irradiation was given in four fractions of 5 Gy each applied within 2 or 3 days; postoperative irradiation consisted mostly of 15x2 Gy (range, 20-40 Gy). A considerable proportion of these patients developed severe late complications (Radiother Oncol 53 (1999) 177). The data allowed a detailed analysis of complication kinetics, leading to a new model which was tested using data from the literature. Results: Data on late complications were obtained for eight different organs with a follow-up of up to 10 years. For the various organs, the percentage of patients being free from late complications, plotted as a function of time after start of radiation therapy, was adequately described by exponential regression. From the fit, the parameter p a was obtained, which is the percentage of patients at risk in a given year of developing a complication in a given organ during that year. The rate p a remained about constant with time. Following sandwich therapy, the annual incidence of complications in the bladder, ileum, lymphatic and soft tissue, and ureters was about the same (p a =10-14%/year), whereas complications in bone or dermis occurred at lower rates (4.7 or 7.5%/year, respectively). Discussion: Numerous data sets collected from published reports were analyzed in the same way. Many of the data sets studied were from patients in a series where there was a high incidence of late effects. Three types of kinetics for the occurrence of late effects after radiotherapy were identified: Type 1, purely exponential kinetics; Type 2, exponential kinetics, the slope of which decreased exponentially with time

  13. Normal tissue tolerance to external beam radiation therapy: Larynx and pharynx; Dose de tolerance a l'irradiation des tissus sains: larynx et pharynx

    Energy Technology Data Exchange (ETDEWEB)

    Debelleix, C. [Service de radiotherapie, centre hospitalier Dax-Cote d' Argent, 40 - Dax (France); Service de radiotherapie, hopital Saint-Andre, CHU de Bordeaux, 33 - Bordeaux (France); Pointreau, Y.; Calais, G. [Service de radiotherapie, centre regional universitaire de cancerologie Henry-S.-Kaplan, hopital Bretonneau, CHU de Tours, 37 - Tours (France); Universite Francois-Rabelais, 37 - Tours (France); Pointreau, Y. [CNRS, UMR 6239 Genetique, immunotherapie, chimie et cancer, 37 - Tours (France); Laboratoire de pharmacologie-toxicologie, CHRU de Tours, 37 - Tours (France); Lafond, C.; Denis, F. [Centre Jean-Bernard, clinique Victor-Hugo, 72 - Le Mans (France); Bourhis, J.H. [Institut Gustave-Roussy, 94 - Villejuif (France)

    2010-07-15

    For head and neck cancers, the radiation dose usually needed to sterilize a macroscopic tumour is at least 70 Gy in conventional fractionation. In the larynx, this dose level enables optimal tumour control while exposing the patient to a limited risk of severe complications. For oropharynx and nasopharynx tumors, it is sometimes possible to limit the dose received by the larynx according to the extent of the primary lesion. Thus, if the tumour constraints permit, the maximum dose to the larynx must be less than 63 to 66 Gy. To reduce the risk of laryngeal edema, it is recommended if possible to limit the mean non-involved larynx dose to 40 to 45 Gy. In the pharynx, literature's data suggested to minimize the volume of the pharyngeal constrictor muscles receiving a dose greater than or equal to 60 Gy. Limiting the volume receiving a dose greater than or equal to 50 Gy reduces the risk of dysphagia. These dose constraints should be tailored to each patient taking into account the extent of the initial primary lesion, the possible addition of chemotherapy or a modified fractionation radiotherapy. (authors)

  14. Normal tissue tolerance to external beam radiation therapy: Spinal cord; Tolerance a l'irradiation des tissus sains: moelle epiniere

    Energy Technology Data Exchange (ETDEWEB)

    Habrand, J.L. [Departement de radiotherapie, institut Gustave-Roussy, 94 - Villejuif (France); Centre de protontherapie, institut Curie, 91 - Orsay (France); Drouet, F. [Departement de radiotherapie, centre Rene-Gauducheau, 44 - Nantes (France)

    2010-07-15

    Radiation myelopathy is one of the most dreadful complications of radiation therapy. Despite multiple animal experiments and human autopsic series, its pathogenesis remains largely unknown. In most instances, the classical aspect of myelomalacia combines glial and vascular injuries in various sequences. Recent studies point out the role of oligo-dendrocytes and their precursors, as well as of intercellular mediators (cytokines and stress molecules). The clinical presentation comprises a spectrum of non specific neurological symptoms whose evolution is sometimes regressive but more commonly progressive and life-threatening. Usually, it occurs following a latent period of six months to two years after irradiation of the cervical, thoracic or upper lumbar spine to a dose in excess of 50 Gy, conventionally fractionated. Nonetheless, these typical features can be altered by extrinsic factors, such as hypo fractionation/acceleration of the dose, multiple surgical procedures, chemotherapy especially mega therapy, or neurotoxic drugs. Conversely, hyperfractionated regimens that take into account protracted half-time repair of sublethal damages to the CNS, as well as sophisticated estimates of the dose to the cord and QA programs during the treatment course minimize such risks. (authors)

  15. The Lyman Continuum Escape Fraction of Emission Line-selected z ∼ 2.5 Galaxies Is Less Than 15%

    Energy Technology Data Exchange (ETDEWEB)

    Rutkowski, Michael J.; Hayes, Matthew [Department of Astronomy, AlbaNova University Centre, Stockholm University, SE-10691 Stockholm (Sweden); Scarlata, Claudia; Mehta, Vihang [Minnesota Institute for Astrophysics, University of Minnesota, 116 Church Street SE, Minneapolis, MN 55455 (United States); Henry, Alaina; Hathi, Nimish; Koekemoer, Anton M. [Space Telescope Science Institute, Baltimore, MD 21218 (United States); Cohen, Seth; Windhorst, Rogier [School of Earth and Space Exploration, Arizona State University, Tempe, AZ 85281 (United States); Teplitz, Harry I. [Infrared Processing and Analysis Center, California Institute of Technology, Pasadena, CA 91125 (United States); Haardt, Francesco [DiSAT, Università dellInsubria, via Valleggio 11, I-22100 Como (Italy); Siana, Brian [Department of Physics, University of California, Riverside, CA 92521 (United States)

    2017-06-01

    Recent work suggests that strong emission line, star-forming galaxies (SFGs) may be significant Lyman continuum leakers. We combine archival Hubble Space Telescope broadband ultraviolet and optical imaging (F275W and F606W, respectively) with emission line catalogs derived from WFC3 IR G141 grism spectroscopy to search for escaping Lyman continuum (LyC) emission from homogeneously selected z ∼ 2.5 SFGs. We detect no escaping Lyman continuum from SFGs selected on [O ii] nebular emission ( N = 208) and, within a narrow redshift range, on [O iii]/[O ii]. We measure 1 σ upper limits to the LyC escape fraction relative to the non-ionizing UV continuum from [O ii] emitters, f {sub esc} ≲ 5.6%, and strong [O iii]/[O ii] > 5 ELGs, f {sub esc} ≲ 14.0%. Our observations are not deep enough to detect f {sub esc} ∼ 10% typical of low-redshift Lyman continuum emitters. However, we find that this population represents a small fraction of the star-forming galaxy population at z ∼ 2. Thus, unless the number of extreme emission line galaxies grows substantially to z ≳ 6, such galaxies may be insufficient for reionization. Deeper survey data in the rest-frame ionizing UV will be necessary to determine whether strong line ratios could be useful for pre-selecting LyC leakers at high redshift.

  16. Twenty years of research on fungal-plant interactions on Lyman Glacier forefront—lessons learned and questions yet unanswered

    Science.gov (United States)

    Ari Jumpponen; Shawn P. Brown; James M. Trappe; Efrén Cázares; Rauni. Strömmer

    2012-01-01

    Retreating glaciers and the periglacial areas that they vacate produce a harsh environment of extreme radiation, nutrient limitations and temperature oscillations. They provide a model system for studying mechanisms that drive the establishment and early assembly of communities. Here, we synthesize more than 20 years of research at the Lyman Glacier forefront in the...

  17. Generation of continuous coherent radiation at Lyman-alpha and 1S-2P Spectroscopy of atomic hydrogen

    NARCIS (Netherlands)

    Pahl, A.; Fendel, P.; Henrich, B.R.; Walz, J.; Hansch, T.W.; Eikema, K.S.E.

    2005-01-01

    Continuous coherent radiation from wavelengths from 121 to 123 nm in the vacuum ultraviolet (VUV) was generated by four-wave sum-frequency mixing in mercury vapor. A yield of 20 nW at Lyman-alpha (121.57 nm) was achieved. We describe the experimental setup in detail and present a calculation of the

  18. The Lyman Continuum Escape Fraction of Emission Line-selected z ∼ 2.5 Galaxies Is Less Than 15%

    International Nuclear Information System (INIS)

    Rutkowski, Michael J.; Hayes, Matthew; Scarlata, Claudia; Mehta, Vihang; Henry, Alaina; Hathi, Nimish; Koekemoer, Anton M.; Cohen, Seth; Windhorst, Rogier; Teplitz, Harry I.; Haardt, Francesco; Siana, Brian

    2017-01-01

    Recent work suggests that strong emission line, star-forming galaxies (SFGs) may be significant Lyman continuum leakers. We combine archival Hubble Space Telescope broadband ultraviolet and optical imaging (F275W and F606W, respectively) with emission line catalogs derived from WFC3 IR G141 grism spectroscopy to search for escaping Lyman continuum (LyC) emission from homogeneously selected z ∼ 2.5 SFGs. We detect no escaping Lyman continuum from SFGs selected on [O ii] nebular emission ( N = 208) and, within a narrow redshift range, on [O iii]/[O ii]. We measure 1 σ upper limits to the LyC escape fraction relative to the non-ionizing UV continuum from [O ii] emitters, f _e_s_c ≲ 5.6%, and strong [O iii]/[O ii] > 5 ELGs, f _e_s_c ≲ 14.0%. Our observations are not deep enough to detect f _e_s_c ∼ 10% typical of low-redshift Lyman continuum emitters. However, we find that this population represents a small fraction of the star-forming galaxy population at z ∼ 2. Thus, unless the number of extreme emission line galaxies grows substantially to z ≳ 6, such galaxies may be insufficient for reionization. Deeper survey data in the rest-frame ionizing UV will be necessary to determine whether strong line ratios could be useful for pre-selecting LyC leakers at high redshift.

  19. Comparison of Lyman-alpha and LI-COR infrared hygrometers for airborne measurement of turbulent fluctuations of water vapour

    Science.gov (United States)

    Lampert, Astrid; Hartmann, Jörg; Pätzold, Falk; Lobitz, Lennart; Hecker, Peter; Kohnert, Katrin; Larmanou, Eric; Serafimovich, Andrei; Sachs, Torsten

    2018-05-01

    To investigate if the LI-COR humidity sensor can be used as a replacement of the Lyman-alpha sensor for airborne applications, the measurement data of the Lyman-alpha and several LI-COR sensors are analysed in direct intercomparison flights on different airborne platforms. One vibration isolated closed-path and two non-isolated open-path LI-COR sensors were installed on a Dornier 128 twin engine turbo-prop aircraft. The closed-path sensor provided absolute values and fluctuations of the water vapour mixing ratio in good agreement with the Lyman-alpha. The signals of the two open-path sensors showed considerable high-frequency noise, and the absolute value of the mixing ratio was observed to drift with time in this vibrational environment. On the helicopter-towed sensor system Helipod, with very low vibration levels, the open-path LI-COR sensor agreed very well with the Lyman-alpha sensor over the entire frequency range up to 3 Hz. The results show that the LI-COR sensors are well suited for airborne measurements of humidity fluctuations, provided that a vibrationless environment is given, and this turns out to be more important than close sensor spacing.

  20. Fluorescence Lyman-Alpha Stratospheric Hygrometer (FLASH): application on meteorological balloons, long duration balloons and unmanned aerial vehicles.

    Science.gov (United States)

    Lykov, Alexey; Khaykin, Sergey; Yushkov, Vladimir; Efremov, Denis; Formanyuk, Ivan; Astakhov, Valeriy

    The FLASH instrument is based on the fluorescent method, which uses H2O molecules photodissociation at a wavelength lambda=121.6 nm (Lalpha - hydrogen emission) followed by the measurement of the fluorescence of excited OH radicals. The source of Lyman-alpha radiation is a hydrogen discharge lamp while the detector of OH fluorescence at 308 -316 nm is a photomultiplier run in photon counting mode. The intensity of the fluorescent light as well as the instrument readings is directly proportional to the water vapor mixing ratio under stratospheric conditions with negligible oxygen absorption. Initially designed for rocket-borne application, FLASH has evolved into a light-weight balloon sonde (FLASH-B) for measurements in the upper troposphere and stratosphere on board meteorological and small plastic balloons. This configuration has been used in over 100 soundings at numerous tropical mid-latitude and polar locations within various international field campaigns. An airborne version of FLASH instrument is successfully utilized onboard stratospheric M55-Geophysica aircraft and tropospheric airborne laboratory YAK42-Roshydromet. The hygrometer was modified for application onboard stratospheric long-duration balloons (FLASH-LDB version). This version was successfully used onboard CNES super-pressure balloon launched from SSC Esrange in March 2007 and flown during 10 days. Special design for polar long duration balloon PoGOLite was created for testing work during polar day in June 2013. Installation and measurement peculiarities as well as observational results are presented. Observations of water vapour using FLASH-B instrument, being of high quality are rather costly as the payload recovery is often complicated and most of the time impossible. Following the goal to find a cost-efficient solution, FLASH was adapted for use onboard Unmanned Aerial Vehicles (UAV). This solution was only possible thanks to compactness and light-weight (0.5 kg) of FLASH instrument. The

  1. Direct method gas-phase oxygen abundances of four Lyman break analogs

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Jonathan S.; Croxall, Kevin V.; Pogge, Richard W. [Department of Astronomy, The Ohio State University, Columbus, OH 43201 (United States)

    2014-09-10

    We measure the gas-phase oxygen abundances in four Lyman break analogs using auroral emission lines to derive direct abundances. The direct method oxygen abundances of these objects are generally consistent with the empirically derived strong-line method values, confirming that these objects are low oxygen abundance outliers from the mass-metallicity (MZ) relation defined by star forming Sloan Digital Sky Survey galaxies. We find slightly anomalous excitation conditions (Wolf-Rayet features) that could potentially bias the empirical estimates toward high values if caution is not exercised in the selection of the strong-line calibration. The high rate of star formation and low oxygen abundance of these objects is consistent with the predictions of the fundamental metallicity relation, in which the infall of relatively unenriched gas simultaneously triggers an episode of star formation and dilutes the interstellar medium of the host galaxy.

  2. Resonance-enhanced two-photon ionization of ions by Lyman alpha radiation in gaseous nebulae.

    Science.gov (United States)

    Johansson, S; Letokhov, V

    2001-01-26

    One of the mysteries of nebulae in the vicinity of bright stars is the appearance of bright emission spectral lines of ions, which imply fairly high excitation temperatures. We suggest that an ion formation mechanism, based on resonance-enhanced two-photon ionization (RETPI) by intense H Lyman alpha radiation (wavelength of 1215 angstroms) trapped inside optically thick nebulae, can produce these spectral lines. The rate of such an ionization process is high enough for rarefied gaseous media where the recombination rate of the ions formed can be 10(-6) to 10(-8) per second for an electron density of 10(3) to 10(5) per cubic centimeter in the nebula. Under such conditions, the photo-ions formed may subsequently undergo further RETPI, catalyzed by intense He i and He ii radiation, which also gets enhanced in optically thick nebulae that contain enough helium.

  3. Stationary inverted Lyman population formed from incandescently heated hydrogen gas with certain catalysts

    International Nuclear Information System (INIS)

    Mills, Randell L; Ray, Paresh C; Mayo, Robert M

    2003-01-01

    A new chemically generated plasma source is reported. The presence of gaseous Rb + or K + ions with thermally dissociated hydrogen formed a low applied temperature, extremely low voltage plasma called a resonant transfer or rt-plasma having strong vacuum ultraviolet emission. We propose an energetic catalytic reaction involving a resonant energy transfer between hydrogen atoms and Rb + or 2K + since Rb + to Rb 2+ , 2K + to K + K 2+ , and K to K 3+ each provide a reaction with a net enthalpy equal to the potential energy of atomic hydrogen. Remarkably, a stationary inverted Lyman population was observed; thus, these catalytic reactions may pump a cw HI laser as predicted by a collisional radiative model used to determine that the observed overpopulation was above threshold

  4. Pollen Dispersal by Catapult: Experiments of Lyman J. Briggs on the Flower of Mountain Laurel

    Science.gov (United States)

    Nimmo, John R.; Hermann, Paula M.; Kirkham, M. B.; Landa, Edward R.

    2014-09-01

    The flower of Kalmia latifolia L. employs a catapult mechanism that flings its pollen to considerable distances. Physicist Lyman J. Briggs investigated this phenomenon in the 1950s after retiring as longtime director of the National Bureau of Standards, attempting to explain how hydromechanical effects inside the flower's stamen could make it possible. Briggs's unfinished manuscript implies that liquid under negative pressure generates stress, which, superimposed on the stress generated from the flower's growth habit, results in force adequate to propel the pollen as observed. With new data and biophysical understanding to supplement Briggs's experimental results and research notes, we show that his postulated negative-pressure mechanism did not play the exclusive and crucial role that he credited to it, though his revisited investigation sheds light on various related processes. Important issues concerning the development and reproductive function of Kalmia flowers remain unresolved, highlighting the need for further biophysical advances.

  5. Stationary inverted Lyman population formed from incandescently heated hydrogen gas with certain catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Mills, Randell L; Ray, Paresh C; Mayo, Robert M [BlackLight Power, Inc., 493 Old Trenton Road, Cranbury, NJ 08512 (United States)

    2003-07-07

    A new chemically generated plasma source is reported. The presence of gaseous Rb{sup +} or K{sup +} ions with thermally dissociated hydrogen formed a low applied temperature, extremely low voltage plasma called a resonant transfer or rt-plasma having strong vacuum ultraviolet emission. We propose an energetic catalytic reaction involving a resonant energy transfer between hydrogen atoms and Rb{sup +} or 2K{sup +} since Rb{sup +} to Rb{sup 2+}, 2K{sup +} to K + K{sup 2+}, and K to K{sup 3+} each provide a reaction with a net enthalpy equal to the potential energy of atomic hydrogen. Remarkably, a stationary inverted Lyman population was observed; thus, these catalytic reactions may pump a cw HI laser as predicted by a collisional radiative model used to determine that the observed overpopulation was above threshold.

  6. Diagnostics of MCF plasmas using Lyman-α fluorescence excited by one or two photons

    International Nuclear Information System (INIS)

    Voslamber, D.

    1998-11-01

    Laser-induced Lyman-α fluorescence of the hydrogen isotopes is investigated with regard to diagnostic applications in magnetically confined fusion plasmas. A formal analysis is presented for two excitation schemes: one-photon and Doppler-free two-photon excitation. The analysis includes estimates of the expected experimental errors arising from the photon noise and from the sensitivity of the observed fluorescence signals to variations of the plasma and laser parameters. Both excitation schemes are suitable primarily for application in the plasma edge, but even in the plasma bulk of large machines they can still be applied in combination with a diagnostic neutral beam. The two-photon excitation scheme is particularly attractive because it involves absorption spectra that are resolved within the Doppler width. This implies a large diagnostic potential and in particular offers a way to measure the deuterium-tritium fuel mix in fusion reactors. (author)

  7. The effect of asymmetric solar wind on the Lyman α sky background

    International Nuclear Information System (INIS)

    Joselyn, J.A.; Holzer, T.E.

    1975-01-01

    The Lyman α (Ly α) sky background arises from the scattering of solar Ly α from a spatial distribution of neutral hydrogen in interplanetary space. This distribution is partially determined by the solar wind proton flux, which provides the principal mechanism of loss by charge exchange of the neutral hydrogen. By generating isophotal maps of scattered Ly α for several choices of interstellar wind direction and solar wind proton flux distributions, the results show that latitudinal variations of the solar wind proton flux can have a significant effect on the observed location and shape of the Ly α intensity maximum. This fact should aid in the interpretation of Ly α maps and also indicates a possible method for inferring values for the average solar wind proton flux out of the ecliptic plane

  8. A Lyman Break Galaxy in the Epoch of Reionization from Hubble Space Telescope (HST) Grism Spectroscopy

    Science.gov (United States)

    Rhoads, James E.; Malhotra, Sangeeta; Stern, Daniel K.; Gardner, Jonathan P.; Dickinson, Mark; Pirzkal, Norbert; Spinrad, Hyron; Reddy, Naveen; Dey, Arjun; Hathi, Nimish; hide

    2013-01-01

    Slitless grism spectroscopy from space offers dramatic advantages for studying high redshift galaxies: high spatial resolution to match the compact sizes of the targets, a dark and uniform sky background, and simultaneous observation over fields ranging from five square arcminutes (HST) to over 1000 square arcminutes (Euclid). Here we present observations of a galaxy at z = 6.57 the end of the reioinization epoch identified using slitless HST grism spectra from the PEARS survey (Probing Evolution And Reionization Spectroscopically) and reconfirmed with Keck + DEIMOS. This high redshift identification is enabled by the depth of the PEARS survey. Substantially higher redshifts are precluded for PEARS data by the declining sensitivity of the ACS grism at greater than lambda 0.95 micrometers. Spectra of Lyman breaks at yet higher redshifts will be possible using comparably deep observations with IR-sensitive grisms.

  9. Lyman Break Galaxies in the Hubble Ultra Deep Field through Deep U-Band Imaging

    Science.gov (United States)

    Rafelski, Marc; Wolfe, A. M.; Cooke, J.; Chen, H. W.; Armandroff, T. E.; Wirth, G. D.

    2009-12-01

    We introduce an extremely deep U-band image taken of the Hubble Ultra Deep Field (HUDF), with a one sigma depth of 30.7 mag arcsec-2 and a detection limiting magnitude of 28 mag arcsec-2. The observations were carried out on the Keck I telescope using the LRIS-B detector. The U-band image substantially improves the accuracy of photometric redshift measurements of faint galaxies in the HUDF at z=[2.5,3.5]. The U-band for these galaxies is attenuated by lyman limit absorption, allowing for more reliable selections of candidate Lyman Break Galaxies (LBGs) than from photometric redshifts without U-band. We present a reliable sample of 300 LBGs at z=[2.5,3.5] in the HUDF. Accurate redshifts of faint galaxies at z=[2.5,3.5] are needed to obtain empirical constraints on the star formation efficiency of neutral gas at high redshift. Wolfe & Chen (2006) showed that the star formation rate (SFR) density in damped Ly-alpha absorption systems (DLAs) at z=[2.5,3.5] is significantly lower than predicted by the Kennicutt-Schmidt law for nearby galaxies. One caveat to this result that we wish to test is whether LBGs are embedded in DLAs. If in-situ star formation is occurring in DLAs, we would see it as extended low surface brightness emission around LBGs. We shall use the more accurate photometric redshifts to create a sample of LBGs around which we will look for extended emission in the more sensitive and higher resolution HUDF images. The absence of extended emission would put limits on the SFR density of DLAs associated with LBGs at high redshift. On the other hand, detection of faint emission on scales large compared to the bright LBG cores would indicate the presence of in situ star formation in those DLAs. Such gas would presumably fuel the higher star formation rates present in the LBG cores.

  10. First Constraints on Fuzzy Dark Matter from Lyman-α Forest Data and Hydrodynamical Simulations.

    Science.gov (United States)

    Iršič, Vid; Viel, Matteo; Haehnelt, Martin G; Bolton, James S; Becker, George D

    2017-07-21

    We present constraints on the masses of extremely light bosons dubbed fuzzy dark matter (FDM) from Lyman-α forest data. Extremely light bosons with a de Broglie wavelength of ∼1  kpc have been suggested as dark matter candidates that may resolve some of the current small scale problems of the cold dark matter model. For the first time, we use hydrodynamical simulations to model the Lyman-α flux power spectrum in these models and compare it to the observed flux power spectrum from two different data sets: the XQ-100 and HIRES/MIKE quasar spectra samples. After marginalization over nuisance and physical parameters and with conservative assumptions for the thermal history of the intergalactic medium (IGM) that allow for jumps in the temperature of up to 5000 K, XQ-100 provides a lower limit of 7.1×10^{-22}  eV, HIRES/MIKE returns a stronger limit of 14.3×10^{-22}  eV, while the combination of both data sets results in a limit of 20×10^{-22}  eV (2σ C.L.). The limits for the analysis of the combined data sets increases to 37.5×10^{-22}  eV (2σ C.L.) when a smoother thermal history is assumed where the temperature of the IGM evolves as a power law in redshift. Light boson masses in the range 1-10×10^{-22}  eV are ruled out at high significance by our analysis, casting strong doubts that FDM helps solve the "small scale crisis" of the cold dark matter models.

  11. Study of interplanetary hydrogen from Lyman alpha emission and absorption determination

    International Nuclear Information System (INIS)

    Cazes, Serge.

    1979-09-01

    The purpose of the work submitted in this paper is to contribute to the study of interplanetary hydrogen from Lyman alpha emission and absorption measurements, carried out on board the D2A, OSO-8 and Copernicus satellites. This study, which was undertaken from the D2A satellite, moved us to study the interplanetary environment as from observations made from the following experiments placed on board the OSO-8 and Copernicus satellites. The experiment set up on board the OSO-8 satellite made it possible to obtain the profile of the solar alpha Lyman emission. An absorption profile was observed for the first time on these profiles and this made it possible to attribute them to interplanetary hydrogen and enabled us to make a direct and local determination of the solar ionization rate. - The spectrometer set up on board Copernicus made it possible to obtain the emission spectrum of the interplanetary environment at the same time as the geocorona. The overall velocity of the interplanetary environment was deduced from the Doppler shift between the two spectra. In the first part, the principle of the REA and POLAR experiments is recalled but only the REA experiment is described in detail, particularly the problems arising from the construction and calibration of the cell. In the second part, a study of the interplanetary environment made from the D2A determinations is presented in synthesized form. On the other hand, the study to which theses initial results led us is presented in detail. Finally, in the third part, the results obtained by means of the OSO-8 and Copernicus satellites are given [fr

  12. Wandering in the Lyman-alpha forest: a study of dark matter-dark radiation interactions

    Energy Technology Data Exchange (ETDEWEB)

    Krall, Rebecca; Cyr-Racine, Francis-Yan; Dvorkin, Cora, E-mail: rkrall@physics.harvard.edu, E-mail: fcyrraci@physics.harvard.edu, E-mail: dvorkin@physics.harvard.edu [Harvard University, Department of Physics, Cambridge, MA 02138 (United States)

    2017-09-01

    The amplitude of large-scale matter fluctuations inferred from the observed Sunyaev-Zeldovich (SZ) cluster mass function and from weak gravitational lensing studies, when taken at face value, is in tension with measurements of the cosmic microwave background (CMB) and baryon acoustic oscillation (BAO). In this work, we revisit whether this possible discrepancy can be attributed to new interactions in the dark matter sector. Focusing on a cosmological model where dark matter interacts with a dark radiation species until the epoch of matter-radiation equality, we find that measurements of the Lyman-alpha flux power spectrum from the Sloan Digital Sky Survey provide no support to the hypothesis that new dark matter interactions can resolve the possible tension between CMB and large-scale structure (LSS). Indeed, while the addition of dark matter-dark radiation interactions leads to an improvement of 2ΔlnL=12 with respect to the standard Λ cold dark matter (ΛCDM) model when only CMB, BAO, and LSS data are considered, the inclusion of Lyman-alpha data reduces the improvement of the fit to 2ΔlnL=6 relative to ΛCDM . We thus conclude that the statistical evidence for new dark matter interactions (largely driven by the Planck SZ dataset) is marginal at best, and likely caused by systematics in the data. We also perform a Fisher forecast analysis for the reach of a future dataset composed of a CMB-S4 experiment combined with the Large Synoptic Survey Telescope galaxy survey. We find that the constraint on the effective number of fluid-like dark radiation species, Δ N {sub fluid}, will be improved by an order of magnitude compared to current bounds.

  13. Wandering in the Lyman-alpha forest: a study of dark matter-dark radiation interactions

    International Nuclear Information System (INIS)

    Krall, Rebecca; Cyr-Racine, Francis-Yan; Dvorkin, Cora

    2017-01-01

    The amplitude of large-scale matter fluctuations inferred from the observed Sunyaev-Zeldovich (SZ) cluster mass function and from weak gravitational lensing studies, when taken at face value, is in tension with measurements of the cosmic microwave background (CMB) and baryon acoustic oscillation (BAO). In this work, we revisit whether this possible discrepancy can be attributed to new interactions in the dark matter sector. Focusing on a cosmological model where dark matter interacts with a dark radiation species until the epoch of matter-radiation equality, we find that measurements of the Lyman-alpha flux power spectrum from the Sloan Digital Sky Survey provide no support to the hypothesis that new dark matter interactions can resolve the possible tension between CMB and large-scale structure (LSS). Indeed, while the addition of dark matter-dark radiation interactions leads to an improvement of 2ΔlnL=12 with respect to the standard Λ cold dark matter (ΛCDM) model when only CMB, BAO, and LSS data are considered, the inclusion of Lyman-alpha data reduces the improvement of the fit to 2ΔlnL=6 relative to ΛCDM . We thus conclude that the statistical evidence for new dark matter interactions (largely driven by the Planck SZ dataset) is marginal at best, and likely caused by systematics in the data. We also perform a Fisher forecast analysis for the reach of a future dataset composed of a CMB-S4 experiment combined with the Large Synoptic Survey Telescope galaxy survey. We find that the constraint on the effective number of fluid-like dark radiation species, Δ N fluid , will be improved by an order of magnitude compared to current bounds.

  14. Direct Detection of The Lyman Continuum of Star-forming Galaxies at z~3

    Science.gov (United States)

    Vasei, Kaveh; Siana, Brian; Shapley, Alice; Alavi, Anahita; Rafelski, Marc

    2018-01-01

    Star-forming galaxies are widely believed to be responsible for the reionization of the Universe and much of the ionizing background at z>3. Therefore, there has been much interest in quantifying the escape fraction of the Lyman continuum (LyC) radiation of the star-forming galaxies. Yet direct detection of LyC has proven to be exceptionally challenging. Despite numerous efforts only 7 galaxies at z2 have been robustly confirmed as LyC leakers. To avoid these challenges many studies use indirect methods to infer the LyC escape fraction. We tested these indirect methods by attempting to detect escaping LyC with a 10-orbit Hubble near-UV (F275W) image that is just below the Lyman limit at the redshift of the Cosmic Horseshoe (a lensed galaxy at z=2.4). We concluded that the measured escape fraction is lower, by more than a factor of five, than the expected escape fraction based on the indirect methods. This emphasizes that indirect determinations should only be interpreted as upper-limits. We also investigated the deepest near-UV Hubble images of the SSA22 field to detect LyC leakage from a large sample of candidate star-forming galaxies at z~3.1, whose redshift was obtained by deep Keck/LRIS spectroscopy and for which Keck narrow-band imaging was showing possible LyC leakage. The high spatial resolution of Hubble images is crucial to confirm our detections are clean from foreground contaminating galaxies, and also to ascertain the escape fraction of our final candidates. We identify five clean LyC emitting star-forming galaxies. The follow up investigation of these galaxies will significantly increase our knowledge of the LyC escape fraction and the mechanisms allowing for LyC escape.

  15. The large-scale cross-correlation of Damped Lyman alpha systems with the Lyman alpha forest: first measurements from BOSS

    Energy Technology Data Exchange (ETDEWEB)

    Font-Ribera, Andreu [Institute of Theoretical Physics, University of Zurich, 8057 Zurich (Switzerland); Miralda-Escudé, Jordi [Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia (Spain); Arnau, Eduard [Institut de Ciències del Cosmos (IEEC/UB), Barcelona, Catalonia (Spain); Carithers, Bill; Ross, Nicholas P.; White, Martin [Lawrence Berkeley National Laboratory, University of California Berkeley, Berkeley, California 94720 (United States); Lee, Khee-Gan [Max-Planck-Institut für Astronomie, Königstuhl 17, D-69117, Heidelberg (Germany); Noterdaeme, Pasquier; Pâris, Isabelle; Petitjean, Patrick; Rollinde, Emmanuel [Institut d' Astrophysique de Paris, Université Paris 6 et CNRS, 98bis blvd. Arago, 75014 Paris (France); Rich, James [CEA, Centre de Saclay, IRFU, 91191 Gif-sur-Yvette (France); Schneider, Donald P. [Department of Astronomy and Astrophysics, The Pennsylvania State University, University Park, PA 16802 (United States); York, Donald G., E-mail: font@physik.uzh.ch, E-mail: miralda@icc.ub.edu [Department of Astronomy and Astrophysics and The Fermi Institute, Chicago University, 5640 So. Ellis Ave., Chicago, IL 60637 (United States)

    2012-11-01

    We present the first measurement of the large-scale cross-correlation of Lyα forest absorption and Damped Lyman α systems (DLA), using the 9th Data Release of the Baryon Oscillation Spectroscopic Survey (BOSS). The cross-correlation is clearly detected on scales up to 40h{sup −1}Mpc and is well fitted by the linear theory prediction of the standard Cold Dark Matter model of structure formation with the expected redshift distortions, confirming its origin in the gravitational evolution of structure. The amplitude of the DLA-Lyα cross-correlation depends on only one free parameter, the bias factor of the DLA systems, once the Lyα forest bias factors are known from independent Lyα forest correlation measurements. We measure the DLA bias factor to be b{sub D} = (2.17±0.20)β{sub F}{sup 0.22}, where the Lyα forest redshift distortion parameter β{sub F} is expected to be above unity. This bias factor implies a typical host halo mass for DLAs that is much larger than expected in present DLA models, and is reproduced if the DLA cross section scales with halo mass as M{sub h}{sup α}, with α = 1.1±0.1 for β{sub F} = 1. Matching the observed DLA bias factor and rate of incidence requires that atomic gas remains extended in massive halos over larger areas than predicted in present simulations of galaxy formation, with typical DLA proper sizes larger than 20 kpc in host halos of masses ∼ 10{sup 12}M{sub ☉}. We infer that typical galaxies at z ≅ 2 to 3 are surrounded by systems of atomic clouds that are much more extended than the luminous parts of galaxies and contain ∼ 10% of the baryons in the host halo.

  16. The application of the linear-quadratic model to fractionated radiotherapy when there is incomplete normal tissue recovery between fractions, and possible implications for treatments involving multiple fractions per day

    International Nuclear Information System (INIS)

    Dale, R.G.

    1986-01-01

    By extending a previously developed mathematical model based on the linear-quadratic dose-effect relationship, it is possible to examine the consequences of performing fractionated treatments for which there is insufficient time between fractions to allow complete damage repair. Equations are derived which give the relative effectiveness of such treatments in terms of tissue-repair constants (μ values) and α/β ratios, and these are then applied to some examples of treatments involving multiple fractions per day. The interplay of the various mechanisms involved (including repopulation effects) and their possible influence on treatments involving closely spaced fractions are examined. If current indications of the differences in recovery rates between early- and late-reacting normal tissues are representative, then it is shown that such differences may limit the clinical potential of accelerated fractionation regimes, where several fractions per day are given in a relatively short overall time. (author)

  17. Dark energy and curvature from a future baryonic acoustic oscillation survey using the Lyman-α forest

    International Nuclear Information System (INIS)

    McDonald, Patrick; Eisenstein, Daniel J.

    2007-01-01

    We explore the requirements for a Lyman-α forest survey designed to measure the angular diameter distance and Hubble parameter at 2 or approx. 250 spectrograph is sufficient to measure both the radial and transverse oscillation scales to 1.4% from the Lyα forest (or better, if fainter magnitudes and possibly Lyman-break galaxies can be used). At fixed integration time and in the sky-noise-dominated limit, a wider, noisier survey is generally more efficient; the only fundamental upper limit on noise being the need to identify a quasar and find a redshift. Because the Lyα forest is much closer to linear and generally better understood than galaxies, systematic errors are even less likely to be a problem

  18. Lenses in the forest: cross correlation of the Lyman-alpha flux with cosmic microwave background lensing.

    Science.gov (United States)

    Vallinotto, Alberto; Das, Sudeep; Spergel, David N; Viel, Matteo

    2009-08-28

    We present a theoretical estimate for a new observable: the cross correlation between the Lyman-alpha flux fluctuations in quasar spectra and the convergence of the cosmic microwave background as measured along the same line of sight. As a first step toward the assessment of its detectability, we estimate the signal-to-noise ratio using linear theory. Although the signal-to-noise is small for a single line of sight and peaks at somewhat smaller redshifts than those probed by the Lyman-alpha forest, we estimate a total signal-to-noise of 9 for cross correlating quasar spectra of SDSS-III with Planck and 20 for cross correlating with a future polarization based cosmic microwave background experiment. The detection of this effect would be a direct measure of the neutral hydrogen-matter cross correlation and could provide important information on the growth of structures at large scales in a redshift range which is still poorly probed.

  19. Optimization of the dose level for a given treatment plan to maximize the complication-free tumor cure

    International Nuclear Information System (INIS)

    Lind, B.K.; Mavroidis, P.; Hyoedynmaa, S.; Kappas, C.

    1999-01-01

    During the past decade, tumor and normal tissue reactions after radiotherapy have been increasingly quantified in radiobiological terms. For this purpose, response models describing the dependence of tumor and normal tissue reactions on the irradiated volume, heterogeneity of the delivered dose distribution and cell sensitivity variations can be taken into account. The probability of achieving a good treatment outcome can be increased by using an objective function such as P + , the probability of complication-free tumor control. A new procedure is presented, which quantifies P + from the dose delivery on 2D surfaces and 3D volumes and helps the user of any treatment planning system (TPS) to select the best beam orientations, the best beam modalities and the most suitable beam energies. The final step of selecting the prescribed dose level is made by a renormalization of the entire dose plan until the value of P + is maximized. The index P + makes use of clinically established dose-response parameters, for tumors and normal tissues of interest, in order to improve its clinical relevance. The results, using P + , are compared against the assessments of experienced medical physicists and radiation oncologists for two clinical cases. It is observed that when the absorbed dose level for a given treatment plan is increased, the treatment outcome first improves rapidly. As the dose approaches the tolerance of normal tissues the complication-free curve begins to drop. The optimal dose level is often just below this point and it depends on the geometry of each patient and target volume. Furthermore, a more conformal dose delivery to the target results in a higher control rate for the same complication level. This effect can be quantified by the increased value of the P + parameter. (orig.)

  20. Flu Symptoms & Complications

    Science.gov (United States)

    ... Influenza Types Seasonal Avian Swine Variant Pandemic Other Flu Symptoms & Complications Language: English (US) Español Recommend on ... not everyone with flu will have a fever. Flu Complications Most people who get influenza will recover ...

  1. Pregnancy Complications: Shoulder Dystocia

    Science.gov (United States)

    ... Home > Complications & Loss > Pregnancy complications > Shoulder dystocia Shoulder dystocia Now playing: E-mail to a friend Please ... women more likely than others to have shoulder dystocia? A pregnant woman may be at risk for ...

  2. Complications and Deaths - State

    Data.gov (United States)

    U.S. Department of Health & Human Services — Complications and deaths - state data. This data set includes state-level data for the hip/knee complication measure, the Agency for Healthcare Research and Quality...

  3. Complications and Deaths - State

    Data.gov (United States)

    U.S. Department of Health & Human Services — Complications and deaths - state data. This data set includes state-level data for the hip/knee complication measure, the CMS Patient Safety Indicators, and 30-day...

  4. Skin Complications of IBD

    Science.gov (United States)

    ... Home > Resources > Skin Complications of IBD Go Back Skin Complications of IBD Email Print + Share After arthritis, ... about 5% of people with inflammatory bowel disease. SKIN DISORDERS COMMONLY SEEN IN IBD ERHTHEMA NODOSUM The ...

  5. Pregnancy Complications: Preeclampsia

    Science.gov (United States)

    ... online community Home > Complications & Loss > Pregnancy complications > Preeclampsia Preeclampsia E-mail to a friend Please fill in ... even if you’re feeling fine. What is preeclampsia? Preeclampsia is a serious blood pressure condition that ...

  6. Pregnancy Complications: Anemia

    Science.gov (United States)

    ... online community Home > Complications & Loss > Pregnancy complications > Anemia Anemia E-mail to a friend Please fill in ... anemia at a prenatal care visit . What causes anemia? Usually, a woman becomes anemic (has anemia) because ...

  7. Complications and Deaths - Hospital

    Data.gov (United States)

    U.S. Department of Health & Human Services — Complications and deaths - provider data. This data set includes provider data for the hip/knee complication measure, CMS Patient Safety Indicators of serious...

  8. Complications and Deaths - National

    Data.gov (United States)

    U.S. Department of Health & Human Services — Complications and deaths - national data. This data set includes national-level data for the hip/knee complication measure, the CMS Patient Safety Indicators, and...

  9. Performance Characterization of UV Science Cameras Developed for the Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP)

    Science.gov (United States)

    Champey, Patrick; Kobayashi, Ken; Winebarger, Amy; Cirtin, Jonathan; Hyde, David; Robertson, Bryan; Beabout, Brent; Beabout, Dyana; Stewart, Mike

    2014-01-01

    The NASA Marshall Space Flight Center (MSFC) has developed a science camera suitable for sub-orbital missions for observations in the UV, EUV and soft X-ray. Six cameras will be built and tested for flight with the Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP), a joint National Astronomical Observatory of Japan (NAOJ) and MSFC sounding rocket mission. The goal of the CLASP mission is to observe the scattering polarization in Lyman-alpha and to detect the Hanle effect in the line core. Due to the nature of Lyman-alpha polarization in the chromosphere, strict measurement sensitivity requirements are imposed on the CLASP polarimeter and spectrograph systems; science requirements for polarization measurements of Q/I and U/I are 0.1% in the line core. CLASP is a dual-beam spectro-polarimeter, which uses a continuously rotating waveplate as a polarization modulator, while the waveplate motor driver outputs trigger pulses to synchronize the exposures. The CCDs are operated in frame-transfer mode; the trigger pulse initiates the frame transfer, effectively ending the ongoing exposure and starting the next. The strict requirement of 0.1% polarization accuracy is met by using frame-transfer cameras to maximize the duty cycle in order to minimize photon noise. Coating the e2v CCD57-10 512x512 detectors with Lumogen-E coating allows for a relatively high (30%) quantum efficiency at the Lyman-$\\alpha$ line. The CLASP cameras were designed to operate with =10 e- /pixel/second dark current, = 25 e- read noise, a gain of 2.0 and =0.1% residual non-linearity. We present the results of the performance characterization study performed on the CLASP prototype camera; dark current, read noise, camera gain and residual non-linearity.

  10. Diagnosing the reionization of the universe - The absorption spectrum of the intergalactic medium and Lyman alpha clouds

    Science.gov (United States)

    Giroux, Mark L.; Shapiro, Paul R.

    1991-01-01

    The thermal and ionization evolution of a uniform intergalactic medium composed of H and He and undergoing reionization is studied. The diagnosis of the metagalactic ionizing radiation background at z of about three using metal line ratios for Lyman limit quasar absorption line systems is addressed. The use of the He II Gunn-Peterson effect to diagnose the reionization source and/or nature of the Hy-alpha forest clouds is considered.

  11. Late effects on normal tissues: oesophagus

    International Nuclear Information System (INIS)

    Pavy, J.J.; Bosset, J.F.

    1997-01-01

    Radiation-induced late effects of oesophagus are observed after treatment of various cancers. Acute reactions, mainly oesophagitis, are well known and accurately described; late effects share, for most of these, a common consequence: alteration of the main oesophageal function, namely to conduct the food bolus; clinically they are impaired in terms of mobility and stenosis. More rarely, ulcerations and pseudodiverticulae can be observed. Chemotherapy further increases the risk of late effects, especially in case of concomitant chemo-radiotherapy. All numbers and statistical data on oesophagus late effects should be regarded with caution due to recent changes in the therapeutic attitudes (more and more combined chemotherapy-radiotherapy) and some progress in given cancer locations. A common scale like the LENT-SOMA should enable the clinician to better know these late effects on oesophagus which is required to initiate effective prevention measures and adapted treatments. (authors)

  12. Detection of 3-Minute Oscillations in Full-Disk Lyman-alpha Emission During A Solar Flare

    Science.gov (United States)

    Milligan, R. O.; Ireland, J.; Fleck, B.; Hudson, H. S.; Fletcher, L.; Dennis, B. R.

    2017-12-01

    We report the detection of chromospheric 3-minute oscillations in disk-integrated EUV irradiance observations during a solar flare. A wavelet analysis of detrended Lyman-alpha (from GOES/EUVS) and Lyman continuum (from SDO/EVE) emission from the 2011 February 15 X-class flare revealed a 3-minute period present during the flare's main phase. The formation temperature of this emission locates this radiation to the flare's chromospheric footpoints, and similar behaviour is found in the SDO/AIA 1600A and 1700A channels, which are dominated by chromospheric continuum. The implication is that the chromosphere responds dynamically at its acoustic cutoff frequency to an impulsive injection of energy. Since the 3-minute period was not found at hard X-ray energies (50-100 keV) in RHESSI data we can state that this 3-minute oscillation does not depend on the rate of energization of, or energy deposition by, non-thermal electrons. However, a second period of 120 s found in both hard X-ray and chromospheric emission is consistent with episodic electron energization on 2-minute timescales. Our finding on the 3-minute oscillation suggests that chromospheric mechanical energy should be included in the flare energy budget, and the fluctuations in the Lyman-alpha line may influence the composition and dynamics of planetary atmospheres during periods of high activity.

  13. Complicated Horseshoe Kidney

    Energy Technology Data Exchange (ETDEWEB)

    Kim, K. S.; Kim, S. R.; Cha, K. S.; Park, S. S. [Chung Ang University College of Medicine, Seoul (Korea, Republic of)

    2010-05-15

    Horseshoe kidney is an important urological anomaly when it is complicated or accompanied by other diseases. Recently we have experienced four cases of horseshoe kidney which were complicated with hydronephrosis, renal stone and adrenal pheochromocytoma. With review of literatures, we emphasize the importance of detection of these complications.

  14. Complicated Horseshoe Kidney

    International Nuclear Information System (INIS)

    Kim, K. S.; Kim, S. R.; Cha, K. S.; Park, S. S.

    2010-01-01

    Horseshoe kidney is an important urological anomaly when it is complicated or accompanied by other diseases. Recently we have experienced four cases of horseshoe kidney which were complicated with hydronephrosis, renal stone and adrenal pheochromocytoma. With review of literatures, we emphasize the importance of detection of these complications.

  15. Evidence for Black Hole Growth in Local Analogs to Lyman Break Galaxies

    Science.gov (United States)

    Jia, Jianjun; Ptak, Andrew; Heckman, Timothy M.; Overzier, Roderik A.; Hornschemeier, Ann; LaMassa, Stephanie M.

    2011-01-01

    We have used XMM-Newton to observe six Lyman break analogs (LBAs): members of the rare population of local galaxies that have properties that are very similar to distant Lyman break galaxies. Our six targets were specifically selected because they have optical emission-line properties that are intermediate between starbursts and Type 2 (obscured) active galactic nuclei (AGNs). Our new X-ray data provide an important diagnostic of the presence of an AGN. We find X-ray luminosities of order 10(sup 42) erg per second and ratios of X-ray to far-IR lummositles that are higher than values in pure starburst galaxies by factors ranging from approximately 3 to 30. This strongly suggests the presence of an AGN in at least some of the galaxies. The ratios of the luminosities of the hard (2-10 keV) X-ray to [O III] emission line are low by about an order of magnitude compared with Type 1 AGN, but are consistent with the broad range seen in Type 2 AGN. Either the AGN hard X-rays are significantly obscured or the [O III] emission is dominated by the starburst. We searched for an iron emission line at approximately 6.4 ke V, which is a key feature of obscured AGNs, but only detected emission at the approximately 2sigma level. Finally, we find that the ratios of the mid-infrared (24 micrometer) continuum to [O III]lambda 5007 luminosities in these LBAs are higher than the values for Type 2 AGN by an average of 0.8 dex. Combining all these clues, we conclude that an AGN is likely to be present, but that the bolometric luminosity is produced primarily by an intense starburst. If these black holes are radiating at the Eddington limit, their masses would lie in the range of 10(sup 5) - 10(sup 6) solar mass. These objects may offer ideal local laboratories to investigate the processes by which black holes grew in the early universe.

  16. The escape of Lyman photons from a young starburst: the case of Haro11†

    Science.gov (United States)

    Hayes, Matthew; Östlin, Göran; Atek, Hakim; Kunth, Daniel; Mas-Hesse, J. Miguel; Leitherer, Claus; Jiménez-Bailón, Elena; Adamo, Angela

    2007-12-01

    Lyman α (Lyα) is one of the dominant tools used to probe the star-forming galaxy population at high redshift (z). However, astrophysical interpretations of data drawn from Lyα alone hinge on the Lyα escape fraction which, due to the complex radiative transport, may vary greatly. Here, we map the Lyα emission from the local luminous blue compact galaxy Haro11, a known emitter of Lyα and the only known candidate for low-z Lyman continuum emission. To aid in the interpretation, we perform a detailed ultraviolet and optical multiwavelength analysis and model the stellar population, dust distribution, ionizing photon budget, and star-cluster population. We use archival X-ray observations to further constrain properties of the starburst and estimate the neutral hydrogen column density. The Lyα morphology is found to be largely symmetric around a single young star-forming knot and is strongly decoupled from other wavelengths. From general surface photometry, only very slight correlation is found between Lyα and Hα, E(B - V), and the age of the stellar population. Only around the central Lyα bright cluster do we find the Lyα/Hα ratio at values predicted by the recombination theory. The total Lyα escape fraction is found to be just 3 per cent. We compute that ~90 per cent of the Lyα photons that escape do so after undergoing multiple resonance scattering events, masking their point of origin. This leads to a largely symmetric distribution and, by increasing the distance that photons must travel to escape, decreases the escape probability significantly. While dust must ultimately be responsible for the destruction of Lyα, it plays a little role in governing the observed morphology, which is regulated more by interstellar medium kinematics and geometry. We find tentative evidence for local Lyα equivalent width in the immediate vicinity of star clusters being a function of cluster age, consistent with hydrodynamic studies. We estimate the intrinsic production

  17. Metabolic complications in oncology

    International Nuclear Information System (INIS)

    Sycova-Mila, Z.

    2012-01-01

    Currently, a lot of space and time is devoted to the therapy of oncologic diseases itself. To reach the good therapy results, complex care of the oncologic patient is needed. Management of complications linked with the disease itself and management of complications emerged after administration of chemotherapy, radiotherapy or targeted therapy, plays a significant role. In addition to infectious, hematological, neurological, cardiac or other complications, metabolic complications are relatively extensive and serious. One of the most frequent metabolic complications in oncology is tumor lysis syndrome, hyperuricemia, hypercalcaemia and syndrome of inappropriate secretion of antidiuretic hormone. (author)

  18. Complications of wrist arthroscopy.

    Science.gov (United States)

    Ahsan, Zahab S; Yao, Jeffrey

    2012-06-01

    The purpose of this systematic review was to address the incidence of complications associated with wrist arthroscopy. Given the paucity of information published on this topic, an all-inclusive review of published wrist arthroscopy complications was sought. Two independent reviewers performed a literature search using PubMed, Google Scholar, EBSCO, and Academic Megasearch using the terms "wrist arthroscopy complications," "complications of wrist arthroscopy," "wrist arthroscopy injury," and "wrist arthroscopy." Inclusion criteria were (1) Levels I to V evidence, (2) "complication" defined as an adverse outcome directly related to the operative procedure, and (3) explicit description of operative complications in the study. Eleven multiple-patient studies addressing complications of wrist arthroscopy from 1994 to 2010 were identified, with 42 complications reported from 895 wrist arthroscopy procedures, a 4.7% complication rate. Four case reports were also found, identifying injury to the dorsal sensory branch of the ulnar nerve, injury to the posterior interosseous nerve, and extensor tendon sheath fistula formation. This systematic review suggests that the previously documented rate of wrist arthroscopy complications may be underestimating the true incidence. The report of various complications provides insight to surgeons for improving future surgical techniques. Level IV, systematic review of Levels I-V studies. Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  19. Discovery of Ubiquitous Fast-Propagating Intensity Disturbances by the Chromospheric Lyman Alpha Spectropolarimeter (CLASP)

    Science.gov (United States)

    Kubo, M.; Katsukawa, Y.; Suematsu, Y.; Kano, R.; Bando, T.; Narukage, N.; Ishikawa, R.; Hara, H.; Giono, G.; Tsuneta, S.; Ishikawa, S.; Shimizu, T.; Sakao, T.; Winebarger, A.; Kobayashi, K.; Cirtain, J.; Champey, P.; Auchère, F.; Trujillo Bueno, J.; Asensio Ramos, A.; Štěpán, J.; Belluzzi, L.; Manso Sainz, R.; De Pontieu, B.; Ichimoto, K.; Carlsson, M.; Casini, R.; Goto, M.

    2016-12-01

    High-cadence observations by the slit-jaw (SJ) optics system of the sounding rocket experiment known as the Chromospheric Lyman Alpha Spectropolarimeter (CLASP) reveal ubiquitous intensity disturbances that recurrently propagate in either the chromosphere or the transition region or both at a speed much higher than the speed of sound. The CLASP/SJ instrument provides a time series of two-dimensional images taken with broadband filters centered on the Lyα line at a 0.6 s cadence. The multiple fast-propagating intensity disturbances appear in the quiet Sun and in an active region, and they are clearly detected in at least 20 areas in a field of view of 527″ × 527″ during the 5 minute observing time. The apparent speeds of the intensity disturbances range from 150 to 350 km s-1, and they are comparable to the local Alfvén speed in the transition region. The intensity disturbances tend to propagate along bright elongated structures away from areas with strong photospheric magnetic fields. This suggests that the observed fast-propagating intensity disturbances are related to the magnetic canopy structures. The maximum distance traveled by the intensity disturbances is about 10″, and the widths are a few arcseconds, which are almost determined by a pixel size of 1.″03. The timescale of each intensity pulse is shorter than 30 s. One possible explanation for the fast-propagating intensity disturbances observed by CLASP is magnetohydrodynamic fast-mode waves.

  20. Central powering of the largest Lyman-α nebula is revealed by polarized radiation.

    Science.gov (United States)

    Hayes, Matthew; Scarlata, Claudia; Siana, Brian

    2011-08-17

    High-redshift Lyman-α (Lyα) blobs are extended, luminous but rare structures that seem to be associated with the highest peaks in the matter density of the Universe. Their energy output and morphology are similar to those of powerful radio galaxies, but the source of the luminosity is unclear. Some blobs are associated with ultraviolet or infrared bright galaxies, suggesting an extreme starburst event or accretion onto a central black hole. Another possibility is gas that is shock-excited by supernovae. But not all blobs are associated with galaxies, and these ones may instead be heated by gas falling into a dark-matter halo. The polarization of the Lyα emission can in principle distinguish between these options, but a previous attempt to detect this signature returned a null detection. Here we report observations of polarized Lyα from the blob LAB1 (ref. 2). Although the central region shows no measurable polarization, the polarized fraction (P) increases to ∼20 per cent at a radius of 45 kiloparsecs, forming an almost complete polarized ring. The detection of polarized radiation is inconsistent with the in situ production of Lyα photons, and we conclude that they must have been produced in the galaxies hosted within the nebula, and re-scattered by neutral hydrogen.

  1. New evidence from the Lyman-alpha forest concerning the formation of galaxies

    Energy Technology Data Exchange (ETDEWEB)

    Wolfe, A M

    1986-12-17

    A new type of survey for galaxies with z > 2 is described. The idea is to search for the spectroscopic imprint that the H1 disc of a foreground galaxy leaves on radiation emitted by a background QSO; namely, a Lyman-..cap alpha.. absorption line broadened by radiation damping. A continuing survey has revealed the presence of 15 damped L..cap alpha.. lines with redshifts between 1.8 and 2.8 in the spectra of 68 QSOs. In comparison, no more than three discs with the properties of nearby galaxies should have been detected. Furthermore, the mean column density of the 15 absorbers, = 1.4 x 10/sup 21/cm/sup -2/, is much larger than expected for the outskirts of H1 discs. The statistical and physical evidence accumulated suggests that the damped L..cap alpha.. systems are a distinct population of absorbers with properties reminiscent of H1 discs. It is concluded that the progenitors of the baryon content of nearby galaxies have been detected. The implications for theories of galaxy formations of the discovery of this damped population of absorbers are explained.

  2. Constraining the Intergalactic and Circumgalactic Media with Lyman-Alpha Absorption

    Science.gov (United States)

    Sorini, Daniele; Onorbe, Jose; Hennawi, Joseph F.; Lukic, Zarija

    2018-01-01

    Lyman-alpha (Ly-a) absorption features detected in quasar spectra in the redshift range 02Mpc, the simulations asymptotically match the observations, because the ΛCDM model successfully describes the ambient IGM. This represents a critical advantage of studying the mean absorption profile. However, significant differences between the simulations, and between simulations and observations are present on scales 20kpc-2Mpc, illustrating the challenges of accurately modeling and resolving galaxy formation physics. It is noteworthy that these differences are observed as far out as ~2Mpc, indicating that the `sphere-of-influence' of galaxies could extend to approximately ~20 times the halo virial radius (~100kpc). Current observations are very precise on these scales and can thus strongly discriminate between different galaxy formation models. I demonstrate that the Ly-a absorption profile is primarily sensitive to the underlying temperature-density relationship of diffuse gas around galaxies, and argue that it thus provides a fundamental test of galaxy formation models. With near-future high-precision observations of Ly-a absorption, the tools developed in my thesis set the stage for even stronger constraints on models of galaxy formation and cosmology.

  3. Investigating the physics and environment of Lyman limit systems in cosmological simulations

    Science.gov (United States)

    Erkal, Denis

    2015-07-01

    In this work, I investigate the properties of Lyman limit systems (LLSs) using state-of-the-art zoom-in cosmological galaxy formation simulations with on the fly radiative transfer, which includes both the cosmic UV background (UVB) and local stellar sources. I compare the simulation results to observations of the incidence frequency of LLSs and the H I column density distribution function over the redshift range z = 2-5 and find good agreement. I explore the connection between LLSs and their host haloes and find that LLSs reside in haloes with a wide range of halo masses with a nearly constant covering fraction within a virial radius. Over the range z = 2-5, I find that more than half of the LLSs reside in haloes with M test a simple model which encapsulates many of their properties. I confirm that LLSs have a characteristic absorption length given by the Jeans length and that they are in photoionization equilibrium at low column densities. Finally, I investigate the self-shielding of LLSs to the UVB and explore how the non-sphericity of LLSs affects the photoionization rate at a given N_{H I}. I find that at z ≈ 3, LLSs have an optical depth of unity at a column density of ˜1018 cm-2 and that this is the column density which characterizes the onset of self-shielding.

  4. Non-LTE effects on the strength of the Lyman edge in quasar accretion disks

    Science.gov (United States)

    Stoerzer, H.; Hauschildt, P. H.; Allard, F.

    1994-01-01

    We have calculated UV/EUV (300 A which is less than or equal to lambda which is less than or equal to 1500 A) continuous energy distributions of accretion disks in the centers of active galactic nuclei (AGNs) for disk luminosities in the range 0.1 L(sub Edd) less than or equal to L(sub acc) less than 1.0 L(sub Edd) and central masses ranging from 10(exp 8) solar mass to 10(exp 9) solar mass. The vertical gas pressure structure of the disk and the disk height are obtained analytically; the temperature stratification and the resulting continuum radiation fields are calculated numerically. We have included non-Local Thermodynamic Equilibrium (LTE) effects of both the ionization equilibrium and the level populations of hydrogen and helium. We show that these non-LTE effects reduce the strength of the Lyman edge when comapred to the LTE case. In non-LTE we find that the edge can be weakly in emission or absorption for disks seen face-on, depending on the disk parameters.

  5. Eight per cent leakage of Lyman continuum photons from a compact, star-forming dwarf galaxy.

    Science.gov (United States)

    Izotov, Y I; Orlitová, I; Schaerer, D; Thuan, T X; Verhamme, A; Guseva, N G; Worseck, G

    2016-01-14

    One of the key questions in observational cosmology is the identification of the sources responsible for ionization of the Universe after the cosmic 'Dark Ages', when the baryonic matter was neutral. The currently identified distant galaxies are insufficient to fully reionize the Universe by redshift z ≈ 6 (refs 1-3), but low-mass, star-forming galaxies are thought to be responsible for the bulk of the ionizing radiation. As direct observations at high redshift are difficult for a variety of reasons, one solution is to identify local proxies of this galaxy population. Starburst galaxies at low redshifts, however, generally are opaque to Lyman continuum photons. Small escape fractions of about 1 to 3 per cent, insufficient to ionize much surrounding gas, have been detected only in three low-redshift galaxies. Here we report far-ultraviolet observations of the nearby low-mass star-forming galaxy J0925+1403. The galaxy is leaking ionizing radiation with an escape fraction of about 8 per cent. The total number of photons emitted during the starburst phase is sufficient to ionize intergalactic medium material that is about 40 times as massive as the stellar mass of the galaxy.

  6. The environment and host haloes of the brightest z ˜ 6 Lyman-break galaxies

    Science.gov (United States)

    Hatfield, P. W.; Bowler, R. A. A.; Jarvis, M. J.; Hale, C. L.

    2018-04-01

    By studying the large-scale structure of the bright high-redshift Lyman-break galaxy (LBG) population it is possible to gain an insight into the role of environment in galaxy formation physics in the early Universe. We measure the clustering of a sample of bright (-22.7 model to measure their typical halo masses. We find that the clustering amplitude and corresponding HOD fits suggests that these sources are highly biased (b ˜ 8) objects in the densest regions of the high-redshift Universe. Coupled with the observed rapid evolution of the number density of these objects, our results suggest that the shape of high luminosity end of the luminosity function is related to feedback processes or dust obscuration in the early Universe - as opposed to a scenario where these sources are predominantly rare instances of the much more numerous MUV ˜ -19 population of galaxies caught in a particularly vigorous period of star formation. There is a slight tension between the number densities and clustering measurements, which we interpret this as a signal that a refinement of the model halo bias relation at high redshifts or the incorporation of quasi-linear effects may be needed for future attempts at modelling the clustering and number counts. Finally, the difference in number density between the fields (UltraVISTA has a surface density˜1.8 times greater than UDS) is shown to be consistent with the cosmic variance implied by the clustering measurements.

  7. Emission of Lyman α radiation in H2 + H*(2s) collisions at thermal energies

    International Nuclear Information System (INIS)

    Stern, B.

    1991-01-01

    A previously-published study of the thermal-energy collision between H 2 and metastable H*(2s), which could lead to the emission of Lyman α radiation, is reconsidered to take into account possible polarization effects. The total was function of the system is expanded in terms of the molecular states of the intermediate complex H 2 * , which constitute the minimal basis of the four adiabatic states dissociating into H 2 + H*(n=2) where they are normally degenerate in energy. The results of the calculation show the existence, between three of those states, of average values of the separation distance R (R ≅ 10 atomic units) of long range (ΔR ≅ 2 au) electronic interactions which depend on the geometric form of the H 2 * molecule. From the molecular data the hypothesis of no longer considering H 2 with H*(2s) as a rigid rotator is postulated and justified, after a purely quantum mechanical treatment of the radial equations. The mean ratio of the (oscillating) polarization angular differential cross sections tot he elastic ones is found important (> ∼ 1/10). The inelastic phenomena are anticipated to be more marked in the ortho than in the para hydrogen at a low collision energy (75 meV). (15 refs., 2 tabs., 9 figs.)

  8. Low-redshift Lyman continuum leaking galaxies with high [O III]/[O II] ratios

    Science.gov (United States)

    Izotov, Y. I.; Worseck, G.; Schaerer, D.; Guseva, N. G.; Thuan, T. X.; Fricke, K. J.; Verhamme, A.; Orlitová, I.

    2018-05-01

    We present observations with the Cosmic Origins Spectrograph onboard the Hubble Space Telescope of five star-forming galaxies at redshifts z in the range 0.2993 - 0.4317 and with high emission-line flux ratios O32 = [O III]λ5007/[O II]λ3727 ˜ 8 - 27 aiming to detect the Lyman continuum (LyC) emission. We detect LyC emission in all galaxies with the escape fractions fesc(LyC) in a range of 2 - 72 per cent. A narrow Lyα emission line with two peaks in four galaxies and with three peaks in one object is seen in medium-resolution COS spectra with a velocity separation between the peaks Vsep varying from ˜153 km s-1 to ˜ 345 km s-1. We find a general increase of the LyC escape fraction with increasing O32 and decreasing stellar mass M⋆, but with a large scatter of fesc(LyC). A tight anti-correlation is found between fesc(LyC) and Vsep making Vsep a good parameter for the indirect determination of the LyC escape fraction. We argue that one possible source driving the escape of ionizing radiation is stellar winds and radiation from hot massive stars.

  9. A Search for Lyman Break Galaxies at z>8 in the NICMOS Parallel Imaging Survey

    Science.gov (United States)

    Henry, Alaina L.; Malkan, Matthew A.; Colbert, James W.; Siana, Brian; Teplitz, Harry I.; McCarthy, Patrick; Yan, Lin

    2007-02-01

    We have selected 14 J-dropout Lyman break galaxy (LBG) candidates with J110-H160>=2.5 from the NICMOS Parallel Imaging Survey. This survey consists of 135 arcmin2 of imaging in 228 independent sight lines, reaching average 5 σ sensitivities of J110=25.8 and H160=25.6 (AB). Distinguishing these candidates from dust-reddened star-forming galaxies at z~2-3 is difficult and will require longer wavelength observations. We consider the likelihood that any J-dropout LBGs exist in this survey and find that if L*z=9.5 is significantly brighter than L*z=6 (a factor of 4), then a few J-dropout LBGs are likely. A similar increase in luminosity has been suggested by Eyles et al. and Yan et al., but the magnitude of this increase is uncertain. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained from the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555. These observations are associated with proposals 9484, 9865, and 10226.

  10. Optimizing BAO measurements with non-linear transformations of the Lyman-α forest

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xinkang; Font-Ribera, Andreu; Seljak, Uroš, E-mail: xinkang.wang@berkeley.edu, E-mail: afont@lbl.gov, E-mail: useljak@berkeley.edu [Department of Physics, University of California, South Hall Rd, Berkeley (United States)

    2015-04-01

    We explore the effect of applying a non-linear transformation to the Lyman-α forest transmitted flux F=e{sup −τ} and the ability of analytic models to predict the resulting clustering amplitude. Both the large-scale bias of the transformed field (signal) and the amplitude of small scale fluctuations (noise) can be arbitrarily modified, but we were unable to find a transformation that increases significantly the signal-to-noise ratio on large scales using Taylor expansion up to the third order. In particular, however, we achieve a 33% improvement in signal to noise for Gaussianized field in transverse direction. On the other hand, we explore an analytic model for the large-scale biasing of the Lyα forest, and present an extension of this model to describe the biasing of the transformed fields. Using hydrodynamic simulations we show that the model works best to describe the biasing with respect to velocity gradients, but is less successful in predicting the biasing with respect to large-scale density fluctuations, especially for very nonlinear transformations.

  11. Characterizing the Lyman-alpha forest flux probability distribution function using Legendre polynomials

    Science.gov (United States)

    Cieplak, Agnieszka; Slosar, Anze

    2018-01-01

    The Lyman-alpha forest has become a powerful cosmological probe at intermediate redshift. It is a highly non-linear field with much information present beyond the power spectrum. The flux probability flux distribution (PDF) in particular has been a successful probe of small scale physics. However, it is also sensitive to pixel noise, spectrum resolution, and continuum fitting, all of which lead to possible biased estimators. Here we argue that measuring the coefficients of the Legendre polynomial expansion of the PDF offers several advantages over measuring the binned values as is commonly done. Since the n-th Legendre coefficient can be expressed as a linear combination of the first n moments of the field, this allows for the coefficients to be measured in the presence of noise and allows for a clear route towards marginalization over the mean flux. Additionally, in the presence of noise, a finite number of these coefficients are well measured with a very sharp transition into noise dominance. This compresses the information into a small amount of well-measured quantities. Finally, we find that measuring fewer quasars with high signal-to-noise produces a higher amount of recoverable information.

  12. THE BIVARIATE SIZE-LUMINOSITY RELATIONS FOR LYMAN BREAK GALAXIES AT z {approx} 4-5

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Kuang-Han; Su, Jian [Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218 (United States); Ferguson, Henry C. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Ravindranath, Swara, E-mail: kuanghan@pha.jhu.edu [The Inter-University Center for Astronomy and Astrophysics, Pune University Campus, Pune 411007, Maharashtra (India)

    2013-03-01

    We study the bivariate size-luminosity distribution of Lyman break galaxies (LBGs) selected at redshifts around 4 and 5 in GOODS and the HUDF fields. We model the size-luminosity distribution as a combination of log-normal distribution (in size) and Schechter function (in luminosity), therefore it enables a more detailed study of the selection effects. We perform extensive simulations to quantify the dropout-selection completenesses and measurement biases and uncertainties in two-dimensional size and magnitude bins, and transform the theoretical size-luminosity distribution to the expected distribution for the observed data. Using maximum-likelihood estimator, we find that the Schechter function parameters for B {sub 435}-dropouts and are consistent with the values in the literature, but the size distributions are wider than expected from the angular momentum distribution of the underlying dark matter halos. The slope of the size-luminosity (RL) relation is similar to those found for local disk galaxies, but considerably shallower than local early-type galaxies.

  13. SPECTROSCOPIC CONFIRMATION OF FAINT LYMAN BREAK GALAXIES NEAR REDSHIFT FIVE IN THE HUBBLE ULTRA DEEP FIELD

    International Nuclear Information System (INIS)

    Rhoads, James E.; Malhotra, Sangeeta; Cohen, Seth; Grogin, Norman; Hathi, Nimish; Ryan, Russell; Straughn, Amber; Windhorst, Rogier A.; Pirzkal, Norbert; Xu Chun; Koekemoer, Anton; Panagia, Nino; Dickinson, Mark; Ferreras, Ignacio; Gronwall, Caryl; Kuemmel, Martin; Walsh, Jeremy; Meurer, Gerhardt; Pasquali, Anna; Yan, H.-J.

    2009-01-01

    We present the faintest spectroscopically confirmed sample of z ∼ 5 Lyman break galaxies (LBGs) to date. The sample is based on slitless grism spectra of the Hubble Ultra Deep Field region from the Grism ACS Program for Extragalactic Science (GRAPES) and Probing Evolution and Reionization Spectroscopically (PEARS) projects, using the G800L grism on the Hubble Space Telescope Advanced Camera for Surveys. We report here confirmations of 39 galaxies, preselected as candidate LBGs using photometric selection criteria. We compare a 'traditional' V-dropout selection, based on the work of Giavalisco et al., to a more liberal one (with V - i > 0.9), and find that the traditional criteria are about 64% complete and 81% reliable. We also study the Lyα emission properties of our sample. We find that Lyα emission is detected in ∼1/4 of the sample, and that the liberal V-dropout color selection includes ∼55% of previously published line-selected Lyα sources. Finally, we examine our stacked two-dimensional spectra. We demonstrate that strong, spatially extended (∼1'') Lyα emission is not a generic property of these LBGs, but that a modest extension of the Lyα photosphere (compared to the starlight) may be present in those galaxies with prominent Lyα emission.

  14. THE BIVARIATE SIZE-LUMINOSITY RELATIONS FOR LYMAN BREAK GALAXIES AT z ∼ 4-5

    International Nuclear Information System (INIS)

    Huang, Kuang-Han; Su, Jian; Ferguson, Henry C.; Ravindranath, Swara

    2013-01-01

    We study the bivariate size-luminosity distribution of Lyman break galaxies (LBGs) selected at redshifts around 4 and 5 in GOODS and the HUDF fields. We model the size-luminosity distribution as a combination of log-normal distribution (in size) and Schechter function (in luminosity), therefore it enables a more detailed study of the selection effects. We perform extensive simulations to quantify the dropout-selection completenesses and measurement biases and uncertainties in two-dimensional size and magnitude bins, and transform the theoretical size-luminosity distribution to the expected distribution for the observed data. Using maximum-likelihood estimator, we find that the Schechter function parameters for B 435 -dropouts and are consistent with the values in the literature, but the size distributions are wider than expected from the angular momentum distribution of the underlying dark matter halos. The slope of the size-luminosity (RL) relation is similar to those found for local disk galaxies, but considerably shallower than local early-type galaxies.

  15. Detection of baryon acoustic oscillations in the Lyman-α forests of BOSS quasar spectra

    International Nuclear Information System (INIS)

    Delubac, Timothee

    2013-01-01

    Baryon acoustic oscillations (BAO) form a standard ruler that can be used to constrain different cosmological models. This thesis reports the first measurement of the BAO feature in the correlation function of the transmitted flux fraction in the Lyman-α forests of high redshift quasars. This detection uses 89322 quasar spectra measured by the Baryon Oscillation Spectroscopic Survey (BOSS) of the third generation of the Sloan Digital Sky Survey (SDSS-III). Redshift of used quasars belong to the range 2.1≤z≤3.5. A peak in the correlation function is seen at 1.043"+"0"."0"2"1_-_0_._0_2_0 times the expected BAO peak position for a concordance ΛCDM model. In addition this thesis presents a new method of quasar selection through their variability. This method is applied to the Stripe 82 region where an important number of multi-epoch photometric data is available. On this region it achieves a quasar density of 30 deg"-"2 to be compared with the 18 deg"-"2 of usual color selections. (author) [fr

  16. Low-redshift Lyman limit systems as diagnostics of cosmological inflows and outflows

    Science.gov (United States)

    Hafen, Zachary; Faucher-Giguère, Claude-André; Anglés-Alcázar, Daniel; Kereš, Dušan; Feldmann, Robert; Chan, T. K.; Quataert, Eliot; Murray, Norman; Hopkins, Philip F.

    2017-08-01

    We use cosmological hydrodynamic simulations with stellar feedback from the FIRE (Feedback In Realistic Environments) project to study the physical nature of Lyman limit systems (LLSs) at z ≤ 1. At these low redshifts, LLSs are closely associated with dense gas structures surrounding galaxies, such as galactic winds, dwarf satellites and cool inflows from the intergalactic medium. Our analysis is based on 14 zoom-in simulations covering the halo mass range Mh ≈ 109-1013 M⊙ at z = 0, which we convolve with the dark matter halo mass function to produce cosmological statistics. We find that the majority of cosmologically selected LLSs are associated with haloes in the mass range 1010 ≲ Mh ≲ 1012 M⊙. The incidence and H I column density distribution of simulated absorbers with columns in the range 10^{16.2} ≤ N_{H I} ≤ 2× 10^{20} cm-2 are consistent with observations. High-velocity outflows (with radial velocity exceeding the halo circular velocity by a factor of ≳ 2) tend to have higher metallicities ([X/H] ˜ -0.5) while very low metallicity ([X/H] standard deviation) [X/H] = -0.9 (0.4) and does not show significant evidence for bimodality, in contrast to recent observational studies, but consistent with LLSs arising from haloes with a broad range of masses and metallicities.

  17. How to estimate the 3D power spectrum of the Lyman-α forest

    Science.gov (United States)

    Font-Ribera, Andreu; McDonald, Patrick; Slosar, Anže

    2018-01-01

    We derive and numerically implement an algorithm for estimating the 3D power spectrum of the Lyman-α (Lyα) forest flux fluctuations. The algorithm exploits the unique geometry of Lyα forest data to efficiently measure the cross-spectrum between lines of sight as a function of parallel wavenumber, transverse separation and redshift. We start by approximating the global covariance matrix as block-diagonal, where only pixels from the same spectrum are correlated. We then compute the eigenvectors of the derivative of the signal covariance with respect to cross-spectrum parameters, and project the inverse-covariance-weighted spectra onto them. This acts much like a radial Fourier transform over redshift windows. The resulting cross-spectrum inference is then converted into our final product, an approximation of the likelihood for the 3D power spectrum expressed as second order Taylor expansion around a fiducial model. We demonstrate the accuracy and scalability of the algorithm and comment on possible extensions. Our algorithm will allow efficient analysis of the upcoming Dark Energy Spectroscopic Instrument dataset.

  18. Ultraviolet photometry from the orbiting astronomical observatory. XVI - The stellar Lyman-alpha absorption line

    Science.gov (United States)

    Savage, B. D.; Panek, R. J.

    1974-01-01

    The stellar Lyman-alpha line at 1216 A was observed in 29 lightly reddened stars of spectral type B2.5 to B9 by a far-UV spectrophotometer on OAO-2. The equivalent widths obtained range from 15 A at type B2.5 to 65 A at type B8; in the late-B stars, the L-alpha line removes 2 to 3% of the total stellar flux. In this sampling, the strength of the L-alpha line correlates well with measures of the Balmer discontinuity and Balmer line strengths; luminosity classification does not seem to affect the line strength. The observed line widths also agree with the predictions of Mihala's grid of non-LTE model atmospheres. In some cases, the L-alpha line influences the interstellar column densities reported in the interstellar OAO-2 L-alpha survey. Hence, these data toward lightly reddened B2 and B1.5 stars should be regarded as upper limits only.

  19. An intensity monitor for solar hydrogen Lyman-alpha radiation (TAIYO SXU)

    International Nuclear Information System (INIS)

    Oshio, Takanori; Masuoka, Toshio; Higashino, Ichiro; Watanabe, Norihiko.

    1975-01-01

    The absolute intensity of hydrogen Lyman-alpha (1216A) from the total solar disk is currently monitored by an ion chamber as a part of the satellite mission of TAIYO. The apparatus consists of an ion chamber with a special input control mask and associated electronics. The ion chamber with an MgF 2 window and filled with NO gas is sensitive to a narrow spectral band including the Lα. The special mask serves to keep the angular response of the detector constant at the elevation angle of the sun relative to the plane perpendicular to the spinning axis of the satellite within an error of the order of one percent, when the angle is within +-30 0 . A flux reducer attenuates the incident radiation upon the detector by a factor of 20 to lengthen the life of detector. The associated electronics measures the output current of the ion chamber, holds the maximum value of the output every four-second period and sends it to the telemeter. From the currently observed data, the absolute intensity of the solar Lα is 3.2 x 10 11 photons/cm 2 sec and constant within +-4.2% during the period from 24 February to 31 May, 1975. (auth.)

  20. Dose-volume complication analysis for visual pathway structures of patients with advanced paranasal sinus tumors

    International Nuclear Information System (INIS)

    Martel, Mary Kaye; Sandler, Howard M.; Cornblath, Wayne T.; Marsh, Lon H.; Hazuka, Mark B.; Roa, Wilson H.; Fraass, Benedict A.; Lichter, Allen S.

    1997-01-01

    Purpose: The purpose of the present work was to relate dose and volume information to complication data for visual pathway structures in patients with advanced paranasal sinus tumors. Methods and Materials: Three-dimensional (3D) dose distributions for chiasm, optic nerve, and retina were calculated and analyzed for 20 patients with advanced paranasal sinus malignant tumors. 3D treatment planning with beam's eye view capability was used to design beam and block arrangements, striving to spare the contralateral orbit (to lessen the chance of unilateral blindness) and frequently the ipsilateral orbit (to help prevent bilateral blindness). Point doses, dose-volume histogram analysis, and normal tissue complication probability (NTCP) calculations were performed. Published tolerance doses that indicate significant risk of complications were used as guidelines for analysis of the 3D dose distributions. Results: Point doses, percent volume exceeding a specified published tolerance dose, and NTCP calculations are given in detail for patients with complications versus patients without complications. Two optic nerves receiving maximum doses below the published tolerance dose sustained damage (mild vision loss). Three patients (of 13) without optic nerve sparing and/or chiasm sparing had moderate or severe vision loss. Complication data, including individual patient analysis to estimate overall risk for loss of vision, are given. Conclusion: 3D treatment planning techniques were used successfully to provide bilateral sparing of the globe for most patients. It was more difficult to spare the optic nerves, especially on the ipsilateral side, when prescription dose exceeded the normal tissue tolerance doses. NTCP calculations may be useful in assessing complication risk better than point dose tolerance criteria for the chiasm, optic nerve, and retina. It is important to assess the overall risk of blindness for the patient in addition to the risk for individual visual pathway

  1. SU-C-BRC-01: A Monte Carlo Study of Out-Of-Field Doses From Cobalt-60 Teletherapy Units Intended for Historical Correlations of Dose to Normal Tissue

    Energy Technology Data Exchange (ETDEWEB)

    Petroccia, H [University of Florida, Gainesville, FL (United States); Olguin, E [Gainesville, FL (United States); Culberson, W [University of Wisconsin Madison, Madison, WI (United States); Bednarz, B [University of Wisconsin, Madison, WI (United States); Mendenhall, N [UF Health Proton Therapy Institute, Jacksonville, FL (United States); Bolch, W [University Florida, Gainesville, FL (United States)

    2016-06-15

    Purpose: Innovations in radiotherapy treatments, such as dynamic IMRT, VMAT, and SBRT/SRS, result in larger proportions of low-dose regions where normal tissues are exposed to low doses levels. Low doses of radiation have been linked to secondary cancers and cardiac toxicities. The AAPM TG Committee No.158 entitled, ‘Measurements and Calculations of Doses outside the Treatment Volume from External-Beam Radiation Therapy’, has been formed to review the dosimetry of non-target and out-of-field exposures using experimental and computational approaches. Studies on historical patients can provide comprehensive information about secondary effects from out-of-field doses when combined with long-term patient follow-up, thus providing significant insight into projecting future outcomes of patients undergoing modern-day treatments. Methods: We present a Monte Carlo model of a Theratron-1000 cobalt-60 teletherapy unit, which historically treated patients at the University of Florida, as a means of determining doses located outside the primary beam. Experimental data for a similar Theratron-1000 was obtained at the University of Wisconsin’s ADCL to benchmark the model for out-of-field dosimetry. An Exradin A12 ion chamber and TLD100 chips were used to measure doses in an extended water phantom to 60 cm outside the primary field at 5 and 10 cm depths. Results: Comparison between simulated and experimental measurements of PDDs and lateral profiles show good agreement for in-field and out-of-field doses. At 10 cm away from the edge of a 6×6, 10×10, and 20×20 cm2 field, relative out-of-field doses were measured in the range of 0.5% to 3% of the dose measured at 5 cm depth along the CAX. Conclusion: Out-of-field doses can be as high as 90 to 180 cGy assuming historical prescription doses of 30 to 60 Gy and should be considered when correlating late effects with normal tissue dose.

  2. Cardiovascular complications of cirrhosis

    DEFF Research Database (Denmark)

    Møller, S; Henriksen, Jens Henrik Sahl

    2008-01-01

    Cardiovascular complications of cirrhosis include cardiac dysfunction and abnormalities in the central, splanchnic and peripheral circulation, and haemodynamic changes caused by humoral and nervous dysregulation. Cirrhotic cardiomyopathy implies systolic and diastolic dysfunction and electrophysi......Cardiovascular complications of cirrhosis include cardiac dysfunction and abnormalities in the central, splanchnic and peripheral circulation, and haemodynamic changes caused by humoral and nervous dysregulation. Cirrhotic cardiomyopathy implies systolic and diastolic dysfunction....... The clinical significance of cardiovascular complications and cirrhotic cardiomyopathy is an important topic for future research, and the initiation of new randomised studies of potential treatments for these complications is needed....

  3. Complications of mechanical ventilation

    Directory of Open Access Journals (Sweden)

    Drašković Biljana

    2011-01-01

    Full Text Available Mechanical ventilation of the lungs, as an important therapeutic measure, cannot be avoided in critically ill patients. However, when machines take over some of vital functions there is always a risk of complications and accidents. Complications associated with mechanical ventilation can be divided into: 1 airway-associated complications; 2 complications in the response of patients to mechanical ventilation; and 3 complications related to the patient’s response to the device for mechanical ventilation. Complications of artificial airway may be related to intubation and extubation or the endotracheal tube. Complications of mechanical ventilation, which arise because of the patient’s response to mechanical ventilation, may primarily cause significant side effects to the lungs. During the last two decades it was concluded that mechanical ventilation can worsen or cause acute lung injury. Mechanical ventilation may increase the alveolar/capillary permeability by overdistension of the lungs (volutrauma, it can exacerbate lung damage due to the recruitment/derecruitment of collapsed alveoli (atelectrauma and may cause subtle damages due to the activation of inflammatory processes (biotrauma. Complications caused by mechanical ventilation, beside those involving the lungs, can also have significant effects on other organs and organic systems, and can be a significant factor contributing to the increase of morbidity and mortality in critically ill of mechanically ventilated patients. Complications are fortunately rare and do not occur in every patient, but due to their seriousness and severity they require extensive knowledge, experience and responsibility by health-care workers.

  4. Sinogenic intracranial complications

    DEFF Research Database (Denmark)

    Kofoed, Mikkel Seremet; Fisker, Niels; Christensen, Anne Estmann

    2018-01-01

    We present two 11-year-old girls with chronic recurrent multifocal osteomyelitis, treated with adalimumab. Both developed severe intracranial complications to sinusitis. Patient 1 had been treated with adalimumab for 15 months when she developed acute sinusitis complicated by an orbital abscess, ...

  5. [Complications in pediatric anesthesia].

    Science.gov (United States)

    Becke, K

    2014-07-01

    As in adult anesthesia, morbidity and mortality could be significantly reduced in pediatric anesthesia in recent decades. This fact cannot conceal the fact that the incidence of anesthetic complications in children is still much more common than in adults and sometimes with a severe outcome. Newborns and infants in particular but also children with emergency interventions and severe comorbidities are at increased risk of potential complications. Typical complications in pediatric anesthesia are respiratory problems, medication errors, difficulties with the intravenous puncture and pulmonal aspiration. In the postoperative setting, nausea and vomiting, pain, and emergence delirium can be mentioned as typical complications. In addition to the systematic prevention of complications in pediatric anesthesia, it is important to quickly recognize disturbances of homeostasis and treat them promptly and appropriately. In addition to the expertise of the performing anesthesia team, the institutional structure in particular can improve quality and safety in pediatric anesthesia.

  6. Lyman Alpha Camera for Io's SO2 atmosphere and Europa's water plumes

    Science.gov (United States)

    McEwen, Alfred S.; Sandel, Bill; Schneider, Nick

    2014-05-01

    The Student Lyman-Alpha Mapper (SLAM) was conceived for the Io Volcano Observer (IVO) mission proposal (McEwen et al., 2014) to determine the spatial and temporal variations in Io's SO2 atmosphere by recording the H Ly-α reflection over the disk (Feldman et al., 2000; Feaga et al., 2009). SO2 absorbs at H Ly-α, thereby modulating the brightness of sunlight reflected by the surface, and measures the density of the SO2 atmosphere and its variability with volcanic activity and time of day. Recently, enhancements at the Ly-α wavelength (121.57 nm) were seen near the limb of Europa and interpreted as active water plumes ~200 km high (Roth et al., 2014). We have a preliminary design for a very simple camera to image in a single bandpass at Ly-α, analogous to a simplified version of IMAGE EUV (Sandel et al. 2000). Our goal is at least 50 resolution elements across Io and/or Europa (~75 km/pixel), ~3x better than HST STIS, to be acquired at a range where the radiation noise is below 1E-4 hits/pixel/s. This goal is achieved with a Cassegrain-like telescope with a 10-cm aperture. The wavelength selection is achieved using a simple self-filtering mirror in combination with a solar-blind photocathode. A photon-counting detector based on a sealed image intensifier preserves the poisson statistics of the incoming photon flux. The intensifier window is coated with a solar-blind photocathode material (CsI). The location of each photon event is recorded by a position-sensitive anode based on crossed delay-line or wedge-and-strip technology. The sensitivity is 0.01 counts/pixel/sec/R, sufficient to estimate SO2 column abundances ranging from 1E15 to 1E17 per cm2 in a 5 min (300 sec) exposure. Sensitivity requirements to search for and image Europa plumes may be similar. Io's Ly-α brightness of ~3 kR exceeds the 0.8 kR brightness of Europa's plume reported by Roth et al. (2014), but the plume brightness is a direct measurement rather than inferring column abundance from

  7. DISCOVERY OF UBIQUITOUS FAST-PROPAGATING INTENSITY DISTURBANCES BY THE CHROMOSPHERIC LYMAN ALPHA SPECTROPOLARIMETER (CLASP)

    International Nuclear Information System (INIS)

    Kubo, M.; Katsukawa, Y.; Suematsu, Y.; Kano, R.; Bando, T.; Narukage, N.; Ishikawa, R.; Hara, H.; Giono, G.; Tsuneta, S.; Ishikawa, S.; Shimizu, T.; Sakao, T.; Winebarger, A.; Kobayashi, K.; Cirtain, J.; Champey, P.; Auchère, F.; Bueno, J. Trujillo; Ramos, A. Asensio

    2016-01-01

    High-cadence observations by the slit-jaw (SJ) optics system of the sounding rocket experiment known as the Chromospheric Lyman Alpha Spectropolarimeter (CLASP) reveal ubiquitous intensity disturbances that recurrently propagate in either the chromosphere or the transition region or both at a speed much higher than the speed of sound. The CLASP/SJ instrument provides a time series of two-dimensional images taken with broadband filters centered on the Ly α line at a 0.6 s cadence. The multiple fast-propagating intensity disturbances appear in the quiet Sun and in an active region, and they are clearly detected in at least 20 areas in a field of view of 527″ × 527″ during the 5 minute observing time. The apparent speeds of the intensity disturbances range from 150 to 350 km s −1 , and they are comparable to the local Alfvén speed in the transition region. The intensity disturbances tend to propagate along bright elongated structures away from areas with strong photospheric magnetic fields. This suggests that the observed fast-propagating intensity disturbances are related to the magnetic canopy structures. The maximum distance traveled by the intensity disturbances is about 10″, and the widths are a few arcseconds, which are almost determined by a pixel size of 1.″03. The timescale of each intensity pulse is shorter than 30 s. One possible explanation for the fast-propagating intensity disturbances observed by CLASP is magnetohydrodynamic fast-mode waves.

  8. The high-ion content and kinematics of low-redshift Lyman limit systems

    International Nuclear Information System (INIS)

    Fox, Andrew J.; Tumlinson, Jason; Bordoloi, Rongmon; Lehner, Nicolas; Howk, J. Christopher; Tripp, Todd M.; Katz, Neal; Prochaska, J. Xavier; Werk, Jessica K.; O'Meara, John M.; Oppenheimer, Benjamin D.; Davé, Romeel

    2013-01-01

    We study the high-ion content and kinematics of the circumgalactic medium around low-redshift galaxies using a sample of 23 Lyman limit systems (LLSs) at 0.08 < z < 0.93 observed with the Cosmic Origins Spectrograph on board the Hubble Space Telescope. In Lehner et al., we recently showed that low-z LLSs have a bimodal metallicity distribution. Here we extend that analysis to search for differences between the high-ion and kinematic properties of the metal-poor and metal-rich branches. We find that metal-rich LLSs tend to show higher O VI columns and broader O VI profiles than metal-poor LLSs. The total H I line width (Δv 90 statistic) in LLSs is not correlated with metallicity, indicating that the H I kinematics alone cannot be used to distinguish inflow from outflow and gas recycling. Among the 17 LLSs with O VI detections, all but two show evidence of kinematic sub-structure, in the form of O VI-H I centroid offsets, multiple components, or both. Using various scenarios for how the metallicities in the high-ion and low-ion phases of each LLS compare, we constrain the ionized hydrogen column in the O VI phase to lie in the range log N(H II) ∼ 17.6-20. The O VI phase of LLSs is a substantial baryon reservoir, with M(high-ion) ∼ 10 8.5-10.9 (r/150 kpc) 2 M ☉ , similar to the mass in the low-ion phase. Accounting for the O VI phase approximately doubles the contribution of low-z LLSs to the cosmic baryon budget.

  9. The high-ion content and kinematics of low-redshift Lyman limit systems

    Energy Technology Data Exchange (ETDEWEB)

    Fox, Andrew J.; Tumlinson, Jason; Bordoloi, Rongmon [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Lehner, Nicolas; Howk, J. Christopher [Department of Physics, University of Notre Dame, 225 Nieuwland Science Hall, Notre Dame, IN 46556 (United States); Tripp, Todd M.; Katz, Neal [Department of Astronomy, University of Massachusetts, Amherst, MA 01003 (United States); Prochaska, J. Xavier; Werk, Jessica K. [UCO/Lick Observatory, University of California, Santa Cruz, CA 95064 (United States); O' Meara, John M. [Department of Physics, Saint Michael' s College, One Winooski Park, Colchester, VT 05439 (United States); Oppenheimer, Benjamin D. [Leiden Observatory, Leiden University, NL-2300 RA Leiden (Netherlands); Davé, Romeel, E-mail: afox@stsci.edu [University of the Western Cape, Robert Sobukwe Road, Bellville 7535 (South Africa)

    2013-12-01

    We study the high-ion content and kinematics of the circumgalactic medium around low-redshift galaxies using a sample of 23 Lyman limit systems (LLSs) at 0.08 < z < 0.93 observed with the Cosmic Origins Spectrograph on board the Hubble Space Telescope. In Lehner et al., we recently showed that low-z LLSs have a bimodal metallicity distribution. Here we extend that analysis to search for differences between the high-ion and kinematic properties of the metal-poor and metal-rich branches. We find that metal-rich LLSs tend to show higher O VI columns and broader O VI profiles than metal-poor LLSs. The total H I line width (Δv {sub 90} statistic) in LLSs is not correlated with metallicity, indicating that the H I kinematics alone cannot be used to distinguish inflow from outflow and gas recycling. Among the 17 LLSs with O VI detections, all but two show evidence of kinematic sub-structure, in the form of O VI-H I centroid offsets, multiple components, or both. Using various scenarios for how the metallicities in the high-ion and low-ion phases of each LLS compare, we constrain the ionized hydrogen column in the O VI phase to lie in the range log N(H II) ∼ 17.6-20. The O VI phase of LLSs is a substantial baryon reservoir, with M(high-ion) ∼ 10{sup 8.5-10.9} (r/150 kpc){sup 2} M {sub ☉}, similar to the mass in the low-ion phase. Accounting for the O VI phase approximately doubles the contribution of low-z LLSs to the cosmic baryon budget.

  10. STAR FORMATION FROM DLA GAS IN THE OUTSKIRTS OF LYMAN BREAK GALAXIES AT z ∼ 3

    International Nuclear Information System (INIS)

    Rafelski, Marc; Wolfe, Arthur M.; Chen, Hsiao-Wen

    2011-01-01

    We present evidence for spatially extended low surface brightness emission around Lyman break galaxies (LBGs) in the V-band image of the Hubble Ultra Deep Field, corresponding to the z ∼ 3 rest-frame far-UV (FUV) light, which is a sensitive measure of star formation rates (SFRs). We find that the covering fraction of molecular gas at z ∼ 3 is not adequate to explain the emission in the outskirts of LBGs, while the covering fraction of neutral atomic-dominated hydrogen gas at high redshift is sufficient. We develop a theoretical framework to connect this emission around LBGs to the expected emission from neutral H I gas, i.e., damped Lyα systems (DLAs), using the Kennicutt-Schmidt (KS) relation. Working under the hypothesis that the observed FUV emission in the outskirts of LBGs is from in situ star formation in atomic-dominated hydrogen gas, the results suggest that the SFR efficiency in such gas at z ∼ 3 is between factors of 10 and 50 lower than predictions based on the local KS relation. The total SFR density in atomic-dominated gas at z ∼ 3 is constrained to be ∼10% of that observed from the inner regions of LBGs. In addition, the metals produced by in situ star formation in the outskirts of LBGs yield metallicities comparable to those of DLAs, which is a possible solution to the 'Missing Metals' problem for DLAs. Finally, the atomic-dominated gas in the outskirts of galaxies at both high and low redshifts has similar reduced SFR efficiencies and is consistent with the same power law.

  11. Absorber Model: the Halo-like model for the Lyman-α forest

    Science.gov (United States)

    Iršič, Vid; McQuinn, Matthew

    2018-04-01

    We present a semi-analytic model for the Lyman-α forest that is inspired by the Halo Model. This model is built on the absorption line decomposition of the forest. Flux correlations are decomposed into those within each absorption line (the 1-absorber term) and those between separate lines (the 2-absorber term), treating the lines as biased tracers of the underlying matter fluctuations. While the nonlinear exponential mapping between optical depth and flux requires an infinite series of moments to calculate any statistic, we show that this series can be re-summed (truncating at the desired order in the linear matter overdensity). We focus on the z=2–3 line-of-sight power spectrum. Our model finds that 1-absorber term dominates the power on all scales, with most of its contribution coming from H I columns of 1014–1015 cm‑2, while the smaller 2-absorber contribution comes from lower columns that trace overdensities of a few. The prominence of the 1-absorber correlations indicates that the line-of-sight power spectrum is shaped principally by the lines' number densities and their absorption profiles, with correlations between lines contributing to a lesser extent. We present intuitive formulae for the effective optical depth as well as the large-scale limits of 1-absorber and 2-absorber terms, which simplify to integrals over the H I column density distribution with different equivalent-width weightings. With minimalist models for the bias of absorption systems and their peculiar velocity broadening, our model predicts values for the density bias and velocity gradient bias that are consistent with those found in simulations.

  12. Neutral ISM, Ly α , and Lyman-continuum in the Nearby Starburst Haro 11

    Energy Technology Data Exchange (ETDEWEB)

    Rivera-Thorsen, T. Emil; Östlin, Göran; Hayes, Matthew; Puschnig, Johannes, E-mail: trive@astro.su.se [Department of Astronomy, Stockholm University, AlbaNova University Centre, SE-106 91 Stockholm (Sweden)

    2017-03-01

    Star-forming galaxies are believed to be a major source of Lyman continuum (LyC) radiation responsible for reionizing the early universe. Direct observations of escaping ionizing radiation have however been sparse and with low escape fractions. In the local universe, only 10 emitters have been observed, with typical escape fractions of a few percent. The mechanisms regulating this escape need to be strongly evolving with redshift in order to account for the epoch of reionization. Gas content and star formation feedback are among the main suspects, known to both regulate neutral gas coverage and evolve with cosmic time. In this paper, we reanalyze Hubble Space Telescope ( HST )-Cosmic Origins Spectrograph (COS) spectrocopy of the first detected local LyC leaker, Haro 11. We examine the connection between LyC leakage and Ly α line shape, and feedback-influenced neutral interstellar medium (ISM) properties like kinematics and gas distribution. We discuss the two extremes of an optically thin, density bounded ISM and a riddled, optically thick, ionization bounded ISM, and how Haro 11 fits into theoretical predictions. We find that the most likely ISM model is a clumpy neutral medium embedded in a highly ionized medium with a combined covering fraction of unity and a residual neutral gas column density in the ionized medium high enough to be optically thick to Ly α , but low enough to be at least partly transparent to LyC and undetected in Si ii. This suggests that star formation feedback and galaxy-scale interaction events play a major role in opening passageways for ionizing radiation through the neutral medium.

  13. THE Lyα LINE PROFILES OF ULTRALUMINOUS INFRARED GALAXIES: FAST WINDS AND LYMAN CONTINUUM LEAKAGE

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Crystal L.; Wong, Joseph [Department of Physics, University of California, Santa Barbara, CA, 93106 (United States); Dijkstra, Mark [Institute of Theoretical Astrophysics, University of Oslo, Postboks 1029, 0858 Oslo (Norway); Henry, Alaina [Astrophysics Science Division, Goddard Space Flight Center, Code 665, Greenbelt, MD 20771 (United States); Soto, Kurt T. [Institute for Astronomy, Department of Physics, ETH Zurich, CH-8093 Zurich (Switzerland); Danforth, Charles W., E-mail: cmartin@physics.ucsb.edu [CASA, Department of Astrophysical and Planetary Sciences, University of Colorado, 389-UCB, Boulder, CO, 80309 (United States)

    2015-04-10

    We present new Hubble Space Telescope Cosmic Origins Spectrograph far-ultraviolet (far-UV) spectroscopy and Keck Echellete optical spectroscopy of 11 ultraluminous infrared galaxies (ULIRGs), a rare population of local galaxies experiencing massive gas inflows, extreme starbursts, and prominent outflows. We detect Lyα emission from eight ULIRGs and the companion to IRAS09583+4714. In contrast to the P Cygni profiles often seen in galaxy spectra, the Lyα profiles exhibit prominent, blueshifted emission out to Doppler shifts exceeding −1000 km s{sup −1} in three H ii-dominated and two AGN-dominated ULIRGs. To better understand the role of resonance scattering in shaping the Lyα line profiles, we directly compare them to non-resonant emission lines in optical spectra. We find that the line wings are already present in the intrinsic nebular spectra, and scattering merely enhances the wings relative to the line core. The Lyα attenuation (as measured in the COS aperture) ranges from that of the far-UV continuum to over 100 times more. A simple radiative transfer model suggests the Lyα photons escape through cavities which have low column densities of neutral hydrogen and become optically thin to the Lyman continuum in the most advanced mergers. We show that the properties of the highly blueshifted line wings on the Lyα and optical emission-line profiles are consistent with emission from clumps of gas condensing out of a fast, hot wind. The luminosity of the Lyα emission increases nonlinearly with the ULIRG bolometric luminosity and represents about 0.1–1% of the radiative cooling from the hot winds in the H ii-dominated ULIRGs.

  14. The Lyman alpha reference sample. II. Hubble space telescope imaging results, integrated properties, and trends

    Energy Technology Data Exchange (ETDEWEB)

    Hayes, Matthew; Östlin, Göran; Duval, Florent; Sandberg, Andreas; Guaita, Lucia; Melinder, Jens; Rivera-Thorsen, Thøger [Department of Astronomy, Oskar Klein Centre, Stockholm University, AlbaNova University Centre, SE-106 91 Stockholm (Sweden); Adamo, Angela [Max Planck Institute for Astronomy, Königstuhl 17, D-69117 Heidelberg (Germany); Schaerer, Daniel [Université de Toulouse, UPS-OMP, IRAP, F-31000 Toulouse (France); Verhamme, Anne; Orlitová, Ivana [Geneva Observatory, University of Geneva, 51 Chemin des Maillettes, CH-1290 Versoix (Switzerland); Mas-Hesse, J. Miguel; Otí-Floranes, Héctor [Centro de Astrobiología (CSIC-INTA), Departamento de Astrofísica, P.O. Box 78, E-28691 Villanueva de la Cañada (Spain); Cannon, John M.; Pardy, Stephen [Department of Physics and Astronomy, Macalester College, 1600 Grand Avenue, Saint Paul, MN 55105 (United States); Atek, Hakim [Laboratoire dAstrophysique, École Polytechnique Fédérale de Lausanne (EPFL), Observatoire, CH-1290 Sauverny (Switzerland); Kunth, Daniel [Institut d' Astrophysique de Paris, UMR 7095, CNRS and UPMC, 98 bis Bd Arago, F-75014 Paris (France); Laursen, Peter [Dark Cosmology Centre, Niels Bohr Institute, University of Copenhagen, Juliane Maries Vej 30, DK-2100 Copenhagen (Denmark); Herenz, E. Christian, E-mail: matthew@astro.su.se [Leibniz-Institut für Astrophysik (AIP), An der Sternwarte 16, D-14482 Potsdam (Germany)

    2014-02-10

    We report new results regarding the Lyα output of galaxies, derived from the Lyman Alpha Reference Sample, and focused on Hubble Space Telescope imaging. For 14 galaxies we present intensity images in Lyα, Hα, and UV, and maps of Hα/Hβ, Lyα equivalent width (EW), and Lyα/Hα. We present Lyα and UV radial light profiles and show they are well-fitted by Sérsic profiles, but Lyα profiles show indices systematically lower than those of the UV (n ≈ 1-2 instead of ≳ 4). This reveals a general lack of the central concentration in Lyα that is ubiquitous in the UV. Photometric growth curves increase more slowly for Lyα than the far ultraviolet, showing that small apertures may underestimate the EW. For most galaxies, however, flux and EW curves flatten by radii ≈10 kpc, suggesting that if placed at high-z only a few of our galaxies would suffer from large flux losses. We compute global properties of the sample in large apertures, and show total Lyα luminosities to be independent of all other quantities. Normalized Lyα throughput, however, shows significant correlations: escape is found to be higher in galaxies of lower star formation rate, dust content, mass, and nebular quantities that suggest harder ionizing continuum and lower metallicity. Six galaxies would be selected as high-z Lyα emitters, based upon their luminosity and EW. We discuss the results in the context of high-z Lyα and UV samples. A few galaxies have EWs above 50 Å, and one shows f{sub esc}{sup Lyα} of 80%; such objects have not previously been reported at low-z.

  15. TWO LENSED z ≅ 3 LYMAN BREAK GALAXIES DISCOVERED IN THE SDSS GIANT ARCS SURVEY

    International Nuclear Information System (INIS)

    Koester, Benjamin P.; Gladders, Michael D.; Sharon, Keren; Wuyts, Eva; Bayliss, Matthew B.; Hennawi, Joseph F.; Rigby, J. R.; Dahle, Hakon

    2010-01-01

    We report the discovery of two strongly lensed z ∼ 3 Lyman break galaxies (LBGs) discovered as u-band dropouts as part of the SDSS Giant Arcs Survey (SGAS). The first, SGAS J122651.3+215220 at z = 2.9233, is lensed by one of several sub-clusters, SDSS J1226+2152, in a complex massive cluster at z = 0.43. Its (g, r, i) magnitudes are (21.14, 20.60, 20.51) which translate to surface brightnesses, μ g,r,i , of (23.78, 23.11, 22.81). The second, SGAS J152745.1+065219, is an LBG at z = 2.7593 lensed by the foreground SDSS J1527+0652 at z = 0.39, with (g, r, z) = (20.90, 20.52, 20.58) and μ g,r,z = (25.15, 24.52, 24.12). Moderate resolution spectroscopy confirms the redshifts suggested by photometric breaks and shows both absorption and emission features typical of LBGs. Lens mass models derived from combined imaging and spectroscopy reveal that SGAS J122651.3+215220 is a highly magnified source (M ≅ 40), while SGAS J152745.1+065219 is magnified by no more than M ≅ 15. Compared with LBG survey results, the luminosities and lensing-corrected magnitudes suggest that SGAS J122651.3+215220 is among the faintest ≅20% of LBGs in that sample. SGAS J152745.1+065219, on the other hand, has an unlensed r-band apparent magnitude similar to that of the 'Cosmic Eye', which places it near the mean of LBG survey results over similar redshifts.

  16. The non-linear power spectrum of the Lyman alpha forest

    International Nuclear Information System (INIS)

    Arinyo-i-Prats, Andreu; Miralda-Escudé, Jordi; Viel, Matteo; Cen, Renyue

    2015-01-01

    The Lyman alpha forest power spectrum has been measured on large scales by the BOSS survey in SDSS-III at z∼ 2.3, has been shown to agree well with linear theory predictions, and has provided the first measurement of Baryon Acoustic Oscillations at this redshift. However, the power at small scales, affected by non-linearities, has not been well examined so far. We present results from a variety of hydrodynamic simulations to predict the redshift space non-linear power spectrum of the Lyα transmission for several models, testing the dependence on resolution and box size. A new fitting formula is introduced to facilitate the comparison of our simulation results with observations and other simulations. The non-linear power spectrum has a generic shape determined by a transition scale from linear to non-linear anisotropy, and a Jeans scale below which the power drops rapidly. In addition, we predict the two linear bias factors of the Lyα forest and provide a better physical interpretation of their values and redshift evolution. The dependence of these bias factors and the non-linear power on the amplitude and slope of the primordial fluctuations power spectrum, the temperature-density relation of the intergalactic medium, and the mean Lyα transmission, as well as the redshift evolution, is investigated and discussed in detail. A preliminary comparison to the observations shows that the predicted redshift distortion parameter is in good agreement with the recent determination of Blomqvist et al., but the density bias factor is lower than observed. We make all our results publicly available in the form of tables of the non-linear power spectrum that is directly obtained from all our simulations, and parameters of our fitting formula

  17. Impact of Lyman alpha pressure on metal-poor dwarf galaxies

    Science.gov (United States)

    Kimm, Taysun; Haehnelt, Martin; Blaizot, Jérémy; Katz, Harley; Michel-Dansac, Léo; Garel, Thibault; Rosdahl, Joakim; Teyssier, Romain

    2018-04-01

    Understanding the origin of strong galactic outflows and the suppression of star formation in dwarf galaxies is a key problem in galaxy formation. Using a set of radiation-hydrodynamic simulations of an isolated dwarf galaxy embedded in a 1010 M⊙ halo, we show that the momentum transferred from resonantly scattered Lyman-α (Lyα) photons is an important source of stellar feedback which can shape the evolution of galaxies. We find that Lyα feedback suppresses star formation by a factor of two in metal-poor galaxies by regulating the dynamics of star-forming clouds before the onset of supernova explosions (SNe). This is possible because each Lyα photon resonantly scatters and imparts ˜10-300 times greater momentum than in the single scattering limit. Consequently, the number of star clusters predicted in the simulations is reduced by a factor of ˜5, compared to the model without the early feedback. More importantly, we find that galactic outflows become weaker in the presence of strong Lyα radiation feedback, as star formation and associated SNe become less bursty. We also examine a model in which radiation field is arbitrarily enhanced by a factor of up to 10, and reach the same conclusion. The typical mass-loading factors in our metal-poor dwarf system are estimated to be ˜5-10 near the mid-plane, while it is reduced to ˜1 at larger radii. Finally, we find that the escape of ionizing radiation and hence the reionization history of the Universe is unlikely to be strongly affected by Lyα feedback.

  18. DISCOVERY OF UBIQUITOUS FAST-PROPAGATING INTENSITY DISTURBANCES BY THE CHROMOSPHERIC LYMAN ALPHA SPECTROPOLARIMETER (CLASP)

    Energy Technology Data Exchange (ETDEWEB)

    Kubo, M.; Katsukawa, Y.; Suematsu, Y.; Kano, R.; Bando, T.; Narukage, N.; Ishikawa, R.; Hara, H.; Giono, G. [National Astronomical Observatory of Japan, National Institutes of Natural Sciences, 2-21-1 Osawa, Mitaka, Tokyo 181-8588 (Japan); Tsuneta, S.; Ishikawa, S.; Shimizu, T.; Sakao, T. [Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency, 3-1-1 Yoshinodai, Chuo-ku, Sagamihara, Kanagawa 252-5210 (Japan); Winebarger, A.; Kobayashi, K.; Cirtain, J. [NASA Marshall Space Flight Center, ZP 13, Huntsville, AL 35812 (United States); Champey, P. [University of Alabama in Huntsville, 301 Sparkman Drive, Huntsville, AL 35899 (United States); Auchère, F. [Institut d’Astrophysique Spatiale, CNRS/Univ. Paris-Sud 11, Bâtiment 121, F-91405 Orsay (France); Bueno, J. Trujillo; Ramos, A. Asensio, E-mail: masahito.kubo@nao.ac.jp [Instituto de Astrofísica de Canarias, E-38205 La Laguna, Tenerife (Spain); and others

    2016-12-01

    High-cadence observations by the slit-jaw (SJ) optics system of the sounding rocket experiment known as the Chromospheric Lyman Alpha Spectropolarimeter (CLASP) reveal ubiquitous intensity disturbances that recurrently propagate in either the chromosphere or the transition region or both at a speed much higher than the speed of sound. The CLASP/SJ instrument provides a time series of two-dimensional images taken with broadband filters centered on the Ly α line at a 0.6 s cadence. The multiple fast-propagating intensity disturbances appear in the quiet Sun and in an active region, and they are clearly detected in at least 20 areas in a field of view of 527″ × 527″ during the 5 minute observing time. The apparent speeds of the intensity disturbances range from 150 to 350 km s{sup −1}, and they are comparable to the local Alfvén speed in the transition region. The intensity disturbances tend to propagate along bright elongated structures away from areas with strong photospheric magnetic fields. This suggests that the observed fast-propagating intensity disturbances are related to the magnetic canopy structures. The maximum distance traveled by the intensity disturbances is about 10″, and the widths are a few arcseconds, which are almost determined by a pixel size of 1.″03. The timescale of each intensity pulse is shorter than 30 s. One possible explanation for the fast-propagating intensity disturbances observed by CLASP is magnetohydrodynamic fast-mode waves.

  19. A RESOLVED MAP OF THE INFRARED EXCESS IN A LYMAN BREAK GALAXY AT z = 3

    Energy Technology Data Exchange (ETDEWEB)

    Koprowski, M. P.; Coppin, K. E. K.; Geach, J. E.; Hine, N. K.; Smith, D. J. B.; Violino, G. [Centre for Astrophysics Research, University of Hertfordshire, College Lane, Hatfield AL10 9AB (United Kingdom); Bremer, M. [H.H. Wills Physics Laboratory, University of Bristol, Tyndall Avenue, Bristol BS8 1TL (United Kingdom); Chapman, S. [Department of Physics and Atmospheric Science, Dalhousie University, Halifax, NS B3H 4R2 (Canada); Davies, L. J. M. [ICRAR, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009 (Australia); Hayashino, T. [Research Center for Neutrino Science, Graduate School of Science, Tohoku University, Sendai, Miyagi 980-8578 (Japan); Knudsen, K. K. [Department of Earth and Space Sciences, Chalmers University of Technology, Onsala Space Observatory, SE-43992 Onsala (Sweden); Kubo, M.; Matsuda, Y. [National Astronomical Observatory of Japan, Osawa 2-21-1, Mitaka, Tokyo 181-8588 (Japan); Lehmer, B. D. [Department of Physics, University of Arkansas, 226 Physics Building, 835 West Dickson Street, Fayetteville, AR 72701 (United States); Van der Werf, P. P. [Leiden Observatory, Leiden University, P.O. Box 9513, NL-2300 RA Leiden (Netherlands); Yamada, T. [Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency, 3-1-1 Yoshinodai, 252-5210 Sagamihara, Kanagawa 252-5210 (Japan)

    2016-09-10

    We have observed the dust continuum of 10 z = 3.1 Lyman break galaxies with the Atacama Large Millimeter/submillimeter Array at ∼450 mas resolution in Band 7. We detect and resolve the 870 μ m emission in one of the targets with a flux density of S {sub 870} = 192 ± 57 μ Jy, and measure a stacked 3 σ signal of S {sub 870} = 67 ± 23 μ Jy for the remaining nine. The total infrared luminosities are L {sub 8–1000} = (8.4 ± 2.3) × 10{sup 10} L {sub ⊙} for the detection and L {sub 8–1000} = (2.9 ± 0.9) × 10{sup 10} L {sub ⊙} for the stack. With Hubble Space Telescope Advanced Camera for Surveys I -band imaging we map the rest-frame UV emission on the same scale as the dust, effectively resolving the “infrared excess” (IRX = L {sub FIR}/ L {sub UV}) in a normal galaxy at z = 3. Integrated over the galaxy we measure IRX = 0.56 ± 0.15, and the galaxy-averaged UV slope is β = −1.25 ± 0.03. This puts the galaxy a factor of ∼10 below the IRX– β relation for local starburst nuclei of Meurer et al. However, IRX varies by more than a factor of 3 across the galaxy, and we conclude that the complex relative morphology of the dust relative to UV emission is largely responsible for the scatter in the IRX– β relation at high- z . A naive application of a Meurer-like dust correction based on the UV slope would dramatically overestimate the total star formation rate, and our results support growing evidence that when integrated over the galaxy, the typical conditions in high- z star-forming galaxies are not analogous to those in the local starburst nuclei used to establish the Meurer relation.

  20. Neutral ISM, Ly α , and Lyman-continuum in the Nearby Starburst Haro 11

    International Nuclear Information System (INIS)

    Rivera-Thorsen, T. Emil; Östlin, Göran; Hayes, Matthew; Puschnig, Johannes

    2017-01-01

    Star-forming galaxies are believed to be a major source of Lyman continuum (LyC) radiation responsible for reionizing the early universe. Direct observations of escaping ionizing radiation have however been sparse and with low escape fractions. In the local universe, only 10 emitters have been observed, with typical escape fractions of a few percent. The mechanisms regulating this escape need to be strongly evolving with redshift in order to account for the epoch of reionization. Gas content and star formation feedback are among the main suspects, known to both regulate neutral gas coverage and evolve with cosmic time. In this paper, we reanalyze Hubble Space Telescope ( HST )-Cosmic Origins Spectrograph (COS) spectrocopy of the first detected local LyC leaker, Haro 11. We examine the connection between LyC leakage and Ly α line shape, and feedback-influenced neutral interstellar medium (ISM) properties like kinematics and gas distribution. We discuss the two extremes of an optically thin, density bounded ISM and a riddled, optically thick, ionization bounded ISM, and how Haro 11 fits into theoretical predictions. We find that the most likely ISM model is a clumpy neutral medium embedded in a highly ionized medium with a combined covering fraction of unity and a residual neutral gas column density in the ionized medium high enough to be optically thick to Ly α , but low enough to be at least partly transparent to LyC and undetected in Si ii. This suggests that star formation feedback and galaxy-scale interaction events play a major role in opening passageways for ionizing radiation through the neutral medium.

  1. The Lyman alpha reference sample. II. Hubble space telescope imaging results, integrated properties, and trends

    International Nuclear Information System (INIS)

    Hayes, Matthew; Östlin, Göran; Duval, Florent; Sandberg, Andreas; Guaita, Lucia; Melinder, Jens; Rivera-Thorsen, Thøger; Adamo, Angela; Schaerer, Daniel; Verhamme, Anne; Orlitová, Ivana; Mas-Hesse, J. Miguel; Otí-Floranes, Héctor; Cannon, John M.; Pardy, Stephen; Atek, Hakim; Kunth, Daniel; Laursen, Peter; Herenz, E. Christian

    2014-01-01

    We report new results regarding the Lyα output of galaxies, derived from the Lyman Alpha Reference Sample, and focused on Hubble Space Telescope imaging. For 14 galaxies we present intensity images in Lyα, Hα, and UV, and maps of Hα/Hβ, Lyα equivalent width (EW), and Lyα/Hα. We present Lyα and UV radial light profiles and show they are well-fitted by Sérsic profiles, but Lyα profiles show indices systematically lower than those of the UV (n ≈ 1-2 instead of ≳ 4). This reveals a general lack of the central concentration in Lyα that is ubiquitous in the UV. Photometric growth curves increase more slowly for Lyα than the far ultraviolet, showing that small apertures may underestimate the EW. For most galaxies, however, flux and EW curves flatten by radii ≈10 kpc, suggesting that if placed at high-z only a few of our galaxies would suffer from large flux losses. We compute global properties of the sample in large apertures, and show total Lyα luminosities to be independent of all other quantities. Normalized Lyα throughput, however, shows significant correlations: escape is found to be higher in galaxies of lower star formation rate, dust content, mass, and nebular quantities that suggest harder ionizing continuum and lower metallicity. Six galaxies would be selected as high-z Lyα emitters, based upon their luminosity and EW. We discuss the results in the context of high-z Lyα and UV samples. A few galaxies have EWs above 50 Å, and one shows f esc Lyα of 80%; such objects have not previously been reported at low-z.

  2. [O III] EMISSION AND GAS KINEMATICS IN A LYMAN-ALPHA BLOB AT z {approx} 3.1

    Energy Technology Data Exchange (ETDEWEB)

    McLinden, Emily M. [McDonald Observatory, University of Texas at Austin, Austin, TX 78712 (United States); Malhotra, Sangeeta; Rhoads, James E. [School of Earth and Space Exploration, Arizona State University, Tempe, AZ 85287 (United States); Hibon, Pascale [Gemini Observatory, La Serena (Chile); Weijmans, Anne-Marie [Dunlap Institute for Astronomy and Astrophysics, University of Toronto, 50 St. George Street, Toronto, ON M5S 3H4 (Canada); Tilvi, Vithal [George P. and Cynthia Woods Mitchell Institute for Fundamental Physics and Astronomy, and Department of Physics and Astronomy, Texas A and M University, College Station, TX 77843 (United States)

    2013-04-10

    We present spectroscopic measurements of the [O III] emission line from two subregions of strong Ly{alpha} emission in a radio-quiet Lyman-alpha blob (LAB). The blob under study is LAB1 at z {approx} 3.1, and the [O III] detections are from the two Lyman break galaxies (LBGs) embedded in the blob halo. The [O III] measurements were made with LUCIFER on the 8.4 m Large Binocular Telescope and NIRSPEC on 10 m Keck Telescope. Comparing the redshift of the [O III] measurements to Ly{alpha} redshifts from SAURON allows us to take a step toward understanding the kinematics of the gas in the blob. Using both LUCIFER and NIRSPEC we find velocity offsets between the [O III] and Ly{alpha} redshifts that are modestly negative or consistent with 0 km s{sup -1} in both subregions studied (ranging from -72 {+-} 42- + 6 {+-} 33 km s{sup -1}). A negative offset means Ly{alpha} is blueshifted with respect to [O III] a positive offset then implies Ly{alpha} is redshifted with respect to [O III]. These results may imply that outflows are not primarily responsible for Lyman alpha escape in this LAB, since outflows are generally expected to produce a positive velocity offset. In addition, we present an [O III] line flux upper limit on a third region of LAB1, a region that is unassociated with any underlying galaxy. We find that the [O III] upper limit from the galaxy-unassociated region of the blob is at least 1.4-2.5 times fainter than the [O III] flux from one of the LBG-associated regions and has an [O III] to Ly{alpha} ratio measured at least 1.9-3.4 times smaller than the same ratio measured from one of the LBGs.

  3. Constraints on Neutral Hydrogen Outflow from the Warm Rocky Planet GJ1132b using Lyman-alpha Transit Observations

    Science.gov (United States)

    Waalkes, William; Berta-Thompson, Zachory; Charbonneau, David; Irwin, Jonathan; Newton, Elisabeth; Dittmann, Jason; Bourrier, Vincent; Ehrenreich, David; Kempton, Eliza

    2018-01-01

    GJ1132b is one of the few known Earth-sized planets, and at 12 pc away it is also one of the closest known transiting planets. With an equilibrium temperature of 500 K, this planet is too hot to be habitable but we can use it to learn about the presence and volatile content of rocky planet atmospheres around M dwarf stars. Using Hubble STIS spectra during primary transit, we explore the potential for UV transit detections of GJ1132b. If we were to observe a deep Lyman-α transit, that would indicate the presence of a neutral hydrogen envelope flowing from GJ1132b. On the other hand, ruling out deep absorption from neutral hydrogen may indicate that this planet has either retained its volatiles or lost them very early in the star’s life. We carry out this analysis by extracting 1D spectra from the STIS pipeline, splitting the time-tagged spectra into higher resolution samples, and producing light curves of the red and blue wings of the Lyman-α line. We fit for the baseline stellar flux and transit depths in order to constrain the characteristics of the cloud of neutral hydrogen gas that may surround the planet. Our work extends beyond the transit study into an analysis of the stellar variability and Lyman-α spectrum of GJ1132, a slowly-rotating 0.18 MSun M dwarf with previously uncharacterized UV activity. Understanding the role that UV variability plays in planetary atmospheres and volatile retention is crucial to assess atmospheric evolution and the habitability of cooler rocky planets.

  4. Performance characterization of UV science cameras developed for the Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP)

    Science.gov (United States)

    Champey, P.; Kobayashi, K.; Winebarger, A.; Cirtain, J.; Hyde, D.; Robertson, B.; Beabout, D.; Beabout, B.; Stewart, M.

    2014-07-01

    The NASA Marshall Space Flight Center (MSFC) has developed a science camera suitable for sub-orbital missions for observations in the UV, EUV and soft X-ray. Six cameras will be built and tested for flight with the Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP), a joint National Astronomical Observatory of Japan (NAOJ) and MSFC sounding rocket mission. The goal of the CLASP mission is to observe the scattering polarization in Lyman-α and to detect the Hanle effect in the line core. Due to the nature of Lyman-α polarizationin the chromosphere, strict measurement sensitivity requirements are imposed on the CLASP polarimeter and spectrograph systems; science requirements for polarization measurements of Q/I and U/I are 0.1% in the line core. CLASP is a dual-beam spectro-polarimeter, which uses a continuously rotating waveplate as a polarization modulator, while the waveplate motor driver outputs trigger pulses to synchronize the exposures. The CCDs are operated in frame-transfer mode; the trigger pulse initiates the frame transfer, effectively ending the ongoing exposure and starting the next. The strict requirement of 0.1% polarization accuracy is met by using frame-transfer cameras to maximize the duty cycle in order to minimize photon noise. The CLASP cameras were designed to operate with ≤ 10 e-/pixel/second dark current, ≤ 25 e- read noise, a gain of 2.0 +- 0.5 and ≤ 1.0% residual non-linearity. We present the results of the performance characterization study performed on the CLASP prototype camera; dark current, read noise, camera gain and residual non-linearity.

  5. Solar minimum Lyman alpha sky background observations from Pioneer Venus orbiter ultraviolet spectrometer - Solar wind latitude variation

    Science.gov (United States)

    Ajello, J. M.

    1990-01-01

    Measurements of interplanetary H I Lyman alpha over a large portion of the celestial sphere were made at the recent solar minimum by the Pioneer Venus orbiter ultraviolet spectrometer. These measurements were performed during a series of spacecraft maneuvers conducted to observe Halley's comet in early 1986. Analysis of these data using a model of the passage of interstellar wind hydrogen through the solar system shows that the rate of charge exchange with solar wind protons is 30 percent less over the solar poles than in the ecliptic. This result is in agreement with a similar experiment performed with Mariner 10 at the previous solar minimum.

  6. Clasp/SJ Observation of Time Variations of Lyman-Alpha Emissions in a Solar Active Region

    Science.gov (United States)

    Ishikawa, S.; Kubo, M.; Katsukawa, Y.; Kano, R.; Narukage, N.; Ishikawa, R.; Bando, T.; Winebarger, A.; Kobayashi, K.; Trujillo Bueno, J.; hide

    2016-01-01

    The Chromospheric Lyman-alpha SpectroPolarimeter (CLASP) is a sounding rocket experiment launched on September 3, 2015 to investigate the solar chromosphere, and the slit-jaw (SJ) optical system took Lya images with the high time cadence of 0.6 s. By the CLASP/SJ observation, many time variations in the solar chromosphere with the time scale of region and investigated the short (regions. As the result, we found the regions. On the other hand, the <30 s time variations had no dependency on the temperature of the loop.

  7. The solar ionisation rate deduced from Ulysses measurements and its implications to interplanetary Lyman alpha-intensity

    Science.gov (United States)

    Summanen, T.; Kyroelae, E.

    1995-01-01

    We have developed a computer code which can be used to study 3-dimensional and time-dependent effects of the solar cycle on the interplanetary (IP) hydrogen distribution. The code is based on the inverted Monte Carlo simulation. In this work we have modelled the temporal behaviour of the solar ionisation rate. We have assumed that during the most of the time of the solar cycle there is an anisotopic latitudinal structure but right at the solar maximum the anisotropy disappears. The effects of this behaviour will be discussed both in regard to the IP hydrogen distribution and IP Lyman a a-intensity.

  8. [Surgical complications of colostomies].

    Science.gov (United States)

    Ben Ameur, Hazem; Affes, Nejmeddine; Rejab, Haitham; Abid, Bassem; Boujelbene, Salah; Mzali, Rafik; Beyrouti, Mohamed Issam

    2014-07-01

    The colostomy may be terminal or lateral, temporary or permanent. It may have psychological, medical or surgical complications. reporting the incidence of surgical complications of colostomies, their therapeutic management and trying to identify risk factors for their occurrence. A retrospective study for a period of 5 years in general surgery department, Habib Bourguiba hospital, Sfax, including all patients operated with confection of a colostomy. Were then studied patients reoperated for stoma complication. Among the 268 patients who have had a colostomy, 19 patients (7%) developed surgical stoma complications. They had a mean age of 59 years, a sex ratio of 5.3 and a 1-ASA score in 42% of cases. It was a prolapse in 9 cases (reconfection of the colostomy: 6 cases, restoration of digestive continuity: 3 cases), a necrosis in 5 cases (reconfection of the colostomy), a plicature in 2 cases (reconfection of the colostomy) a peristomal abscess in 2 cases (reconfection of the colostomy: 1 case, restoration of digestive continuity: 1 case) and a strangulated parastomal hernia in 1 case (herniorrhaphy). The elective incision and the perineal disease were risk factors for the occurrence of prolapse stomial. Surgical complications of colostomies remain a rare event. Prolapse is the most common complication, and it is mainly related to elective approach. Reoperation is often required especially in cases of early complications, with usually uneventful postoperative course.

  9. Imaging of osteochondroma complications

    International Nuclear Information System (INIS)

    Gomes, Fernando Santos Emerich; Lewin, Fabio; Mariotti, Guilherme Cayres; Capasso Filho, Mauro; Yamaguchi, Claudia Kazue; Cruz, Rafael O.; Baptista, Pedro Pericles Ribeiro; Yonamine, Eduardo Sadao; Prospero, Jose Donato

    2007-01-01

    Osteochondroma is the most common entity beyond all the known osseous tumors. It is a lesion with a high enlargement capacity and a continuous growing in some cases, and it may determine complications, mainly due to mass effect. It may be present in a solitary or multiple forms, and the last one is related with a higher tendency to sarcomatous transformation, which is the most frightening complication. The purpose of the present study is to demonstrate, through an iconographic assay, the most common complications caused by the osteochondromas, making the correlation of its clinical and radiological aspects. (author)

  10. Relative Contribution of the Hydrogen 2 s Two-Photon Decay and Lyman- α Escape Channels during the Epoch of Cosmological Recombination

    Science.gov (United States)

    Rubiño-Martin, J. A.; Sunyaev, R. A.

    2018-01-01

    We discuss the evolution of the ratio in number of recombinations due to 2 s two photon escape and due to the escape of Lyman- α photons from the resonance during the epoch of cosmological recombination, within the width of the last scattering surface and near its boundaries. We discuss how this ratio evolves in time, and how it defines the profile of the Lyman- α line in the spectrum of CMB. One of the key reasons for explaining its time dependence is the strong overpopulation of the 2 p level relative to the 2 s level at redshifts z ≲ 750.

  11. The effect of Lyman α self-absorption on population inversions between quantum states 2 and 3 of hydrogen-like ions in recombining plasmas

    International Nuclear Information System (INIS)

    Tallents, G.J.

    1978-01-01

    The effect in recombining plasmas of Lyman α self-absorption on quasi-steady-state population inversions between quantum states n = 2 and 3 of hydrogen-like ions is theoretically investigated. It is shown how the electron density range over which population inversion is possible diminishes as Lyman α self-absorption increases. The highest degree of absorption which can be tolerated and still achieve an inversion is shown to occur when the thermal limit corresponds to n approximately equal to 4. The results of the computations are related to the conditions to be found in the expansion plume of laser-produced plasmas. (author)

  12. The dynamic DNA methylation landscape of the mutL homolog 1 shore is altered by MLH1-93G>A polymorphism in normal tissues and colorectal cancer.

    Science.gov (United States)

    Savio, Andrea J; Mrkonjic, Miralem; Lemire, Mathieu; Gallinger, Steven; Knight, Julia A; Bapat, Bharat

    2017-01-01

    Colorectal cancers (CRCs) undergo distinct genetic and epigenetic alterations. Expression of mutL homolog 1 ( MLH1 ), a mismatch repair gene that corrects DNA replication errors, is lost in up to 15% of sporadic tumours due to mutation or, more commonly, due to DNA methylation of its promoter CpG island. A single nucleotide polymorphism (SNP) in the CpG island of MLH1 ( MLH1 -93G>A or rs1800734) is associated with CpG island hypermethylation and decreased MLH1 expression in CRC tumours. Further, in peripheral blood mononuclear cell (PBMC) DNA of both CRC cases and non-cancer controls, the variant allele of rs1800734 is associated with hypomethylation at the MLH1 shore, a region upstream of its CpG island that is less dense in CpG sites . To determine whether this genotype-epigenotype association is present in other tissue types, including colorectal tumours, we assessed DNA methylation in matched normal colorectal tissue, tumour, and PBMC DNA from 349 population-based CRC cases recruited from the Ontario Familial Colorectal Cancer Registry. Using the semi-quantitative real-time PCR-based MethyLight assay, MLH1 shore methylation was significantly higher in tumour tissue than normal colon or PBMCs ( P  MLH1 was not associated with MSI status or promoter CpG island hypermethylation, regardless of genotype. To confirm these results, bisulfite sequencing was performed in matched tumour and normal colorectal specimens from six CRC cases, including two cases per genotype (wildtype, heterozygous, and homozygous variant). Bisulfite sequencing results corroborated the methylation patterns found by MethyLight, with significant hypomethylation in normal colorectal tissue of variant SNP allele carriers. These results indicate that the normal tissue types tested (colorectum and PBMC) experience dynamic genotype-associated epigenetic alterations at the MLH1 shore, whereas tumour DNA incurs aberrant hypermethylation compared to normal DNA.

  13. Significant reduction of normal tissue dose by proton radiotherapy compared with three-dimensional conformal or intensity-modulated radiation therapy in Stage I or Stage III non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Chang, Joe Y.; Zhang Xiaodong; Wang Xiaochun; Kang Yixiu; Riley, Beverly C.; Bilton, Stephen C.; Mohan, Radhe; Komaki, Ritsuko; Cox, James D.

    2006-01-01

    Purpose: To compare dose-volume histograms (DVH) in patients with non-small-cell lung cancer (NSCLC) treated by photon or proton radiotherapy. Methods and Materials: Dose-volume histograms were compared between photon, including three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and proton plans at doses of 66 Gy, 87.5 Gy in Stage I (n = 10) and 60-63 Gy, and 74 Gy in Stage III (n 15). Results: For Stage I, the mean total lung V5, V10, and V20 were 31.8%, 24.6%, and 15.8%, respectively, for photon 3D-CRT with 66 Gy, whereas they were 13.4%, 12.3%, and 10.9%, respectively, with proton with dose escalation to 87.5 cobalt Gray equivalents (CGE) (p = 0.002). For Stage III, the mean total lung V5, V10, and V20 were 54.1%, 46.9%, and 34.8%, respectively, for photon 3D-CRT with 63 Gy, whereas they were 39.7%, 36.6%, and 31.6%, respectively, for proton with dose escalation to 74 CGE (p = 0.002). In all cases, the doses to lung, spinal cord, heart, esophagus, and integral dose were lower with proton therapy even compared with IMRT. Conclusions: Proton treatment appears to reduce dose to normal tissues significantly, even with dose escalation, compared with standard-dose photon therapy, either 3D-CRT or IMRT

  14. Postoperative rectal anastomotic complications

    Czech Academy of Sciences Publication Activity Database

    Polanecký, O.; Adámek, S.; Šedý, Jiří; Skořepa, J.; Hladík, P.; Šmejkal, M.; Pafko, P.; Lischke, R.

    2014-01-01

    Roč. 115, č. 12 (2014), s. 781-785 ISSN 0006-9248 Institutional support: RVO:67985823 Keywords : human * complication * anastomosis * rectum Subject RIV: FJ - Surgery incl. Transplants Impact factor: 0.439, year: 2014

  15. Complications of Circumcision

    Directory of Open Access Journals (Sweden)

    Aaron J. Krill

    2011-01-01

    Full Text Available In the United States, circumcision is a commonly performed procedure. It is a relatively safe procedure with a low overall complication rate. Most complications are minor and can be managed easily. Though uncommon, complications of circumcision do represent a significant percentage of cases seen by pediatric urologists. Often they require surgical correction that results in a significant cost to the health care system. Severe complications are quite rare, but death has been reported as a result in some cases. A thorough and complete preoperative evaluation, focusing on bleeding history and birth history, is imperative. Proper selection of patients based on age and anatomic considerations as well as proper sterile surgical technique are critical to prevent future circumcision-related adverse events.

  16. Complications of shoulder dystocia.

    Science.gov (United States)

    Dajani, Nafisa K; Magann, Everett F

    2014-06-01

    Complications of shoulder dystocia are divided into fetal and maternal. Fetal brachial plexus injury (BPI) is the most common fetal complication occurring in 4-40% of cases. BPI has also been reported in abdominal deliveries and in deliveries not complicated by shoulder dystocia. Fractures of the fetal humerus and clavicle occur in about 10.6% of cases of shoulder dystocia and usually heal with no sequel. Hypoxic ischemic brain injury is reported in 0.5-23% of cases of shoulder dystocia. The risk correlates with the duration of head-to-body delivery and is especially increased when the duration is >5 min. Fetal death is rare and is reported in 0.4% of cases. Maternal complications of shoulder dystocia include post-partum hemorrhage, vaginal lacerations, anal tears, and uterine rupture. The psychological stress impact of shoulder dystocia is under-recognized and deserves counseling prior to home discharge. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Pertussis (Whooping Cough) Complications

    Science.gov (United States)

    ... of Search Controls Search Form Controls Cancel Submit Pertussis (Whooping Cough) Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Pertussis Home About Pertussis Causes & Transmission Signs & Symptoms Complications ...

  18. Neurologic complications in oncology

    Directory of Open Access Journals (Sweden)

    Andrea Pace

    2010-06-01

    Full Text Available Neurologic side effects related to cancer therapy are a common problem in oncology practice. These complications can negatively affect the management of the patient, because they can inhibit treatment and diminish quality of life. Therefore specific skills are required to recognise symptoms and clinical manifestations. This review focuses on the most common neurologic complications to improve physician’s familiarity in determining the aetiology of these symptoms.

  19. Neurologic complications of vaccinations.

    Science.gov (United States)

    Miravalle, Augusto A; Schreiner, Teri

    2014-01-01

    This chapter reviews the most common neurologic disorders associated with common vaccines, evaluates the data linking the disorder with the vaccine, and discusses the potential mechanism of disease. A literature search was conducted in PubMed using a combination of the following terms: vaccines, vaccination, immunization, and neurologic complications. Data were also gathered from publications of the American Academy of Pediatrics Committee on Infectious Diseases, the World Health Organization, the US Centers for Disease Control and Prevention, and the Vaccine Adverse Event Reporting System. Neurologic complications of vaccination are rare. Many associations have been asserted without objective data to support a causal relationship. Rarely, patients with a neurologic complication will have a poor outcome. However, most patients recover fully from the neurologic complication. Vaccinations have altered the landscape of infectious disease. However, perception of risk associated with vaccinations has limited the success of disease eradication measures. Neurologic complications can be severe, and can provoke fear in potential vaccines. Evaluating whether there is causal link between neurologic disorders and vaccinations, not just temporal association, is critical to addressing public misperception of risk of vaccination. Among the vaccines available today, the cost-benefit analysis of vaccinations and complications strongly argues in favor of vaccination. © 2014 Elsevier B.V. All rights reserved.

  20. Complications in Hip Arthroscopy

    Science.gov (United States)

    Nakano, Naoki; Khanduja, Vikas

    2016-01-01

    Summary Background Recent developments in hip arthroscopic techniques and technology have made it possible in many cases to avoid open surgical dislocation for treating a variety of pathology in the hip. Although early reports suggest favourable results’ using hip arthroscopy and it has been shown to be a relatively safe procedure, complications do exist and can sometimes lead to significant morbidity. Methods This is a review article. The aim of this manuscript is to present the most frequent and/or serious complications that could occur at or following hip arthroscopy and some guidelines to avoid these complications. Conclusion Most complications of hip arthroscopy are minor or transient but serious complications can occur as well. A lot of complication e.g. acetabular labral puncture go unreported. Appropriate education and training, precise and meticulous surgical technique with correct instrumentation, the right indication in the right patient and adherence to advice from mentors and experienced colleagues are all essential factors for a successful outcome. Level of evidence: V. PMID:28066747

  1. On complicity theory.

    Science.gov (United States)

    Kline, A David

    2006-04-01

    The received account of whistleblowing, developed over the last quarter century, is identified with the work of Norman Bowie and Richard DeGeorge. Michael Davis has detailed three anomalies for the received view: the paradoxes of burden, missing harm and failure. In addition, he has proposed an alternative account of whistleblowing, viz., the Complicity Theory. This paper examines the Complicity Theory. The supposed anomalies rest on misunderstandings of the received view or misreadings of model cases of whistleblowing, for example, the Challenger disaster and the Ford Pinto. Nevertheless, the Complicity Theory is important for as in science the contrast with alternative competing accounts often helps us better understand the received view. Several aspects of the received view are reviewed and strengthened through comparison with Complicity Theory, including why whistleblowing needs moral justification. Complicity Theory is also critiqued. The fundamental failure of Complicity Theory is its failure to explain why government and the public encourage and protect whistleblowers despite the possibility of considerable harm to the relevant company in reputation, lost jobs, and lost shareholder value.

  2. The Canada-France deep fields survey-II: Lyman-break galaxies and galaxy clustering at z ~ 3

    Science.gov (United States)

    Foucaud, S.; McCracken, H. J.; Le Fèvre, O.; Arnouts, S.; Brodwin, M.; Lilly, S. J.; Crampton, D.; Mellier, Y.

    2003-10-01

    We present a large sample of z ~ 3 U-band dropout galaxies extracted from the Canada-France deep fields survey (CFDF). Our catalogue covers an effective area of ~ 1700 arcmin2 divided between three large, contiguous fields separated widely on the sky. To IAB=24.5, the survey contains 1294 Lyman-break candidates, in agreement with previous measurements by other authors, after appropriate incompleteness corrections have been applied to our data. Based on comparisons with spectroscopic observations and simulations, we estimate that our sample of Lyman-break galaxies is contaminated by stars and interlopers (lower-redshift galaxies) at no more than { ~ } 30%. We find that omega (theta ) is well fitted by a power-law of fixed slope, gamma =1.8, even at small (theta University of Hawaii, and at the Cerro Tololo Inter-American Observatory and Mayall 4-meter Telescopes, divisions of the National Optical Astronomy Observatories, which are operated by the Association of Universities for Research in Astronomy, Inc. under cooperative agreement with the National Science Foundation.

  3. A cosmic web filament revealed in Lyman-α emission around a luminous high-redshift quasar.

    Science.gov (United States)

    Cantalupo, Sebastiano; Arrigoni-Battaia, Fabrizio; Prochaska, J Xavier; Hennawi, Joseph F; Madau, Piero